Full Speech

THURSDAY, JANUARY 20, 2000

MORNING SESSION: "THE SCIENCE OF BIOTECHNOLOGY"

Ambassador Cynthia P. Schneider , U.S. Ambassador
to the Netherlands

"Introduction"

It is a great pleasure to welcome you today to "Biotechnology: the Science and the Impact". I hope that together we will learn from each other, exchange ideas, and help to set the tenor for a positive dialogue on this subject.

I suspect that all of you know why you are here, but many of you may be wondering why I am here. The question I have been asked most frequently in my work on this conference has been "Why is an American Embassy organizing such a conference?" The answer is that this conference reflects core functions of American Embassies abroad: to communicate and promote understanding of American ideas and to advocate American products. The realization of these goals through a conference has more to do with my personal background. From my academic training, I have acquired the habit of going to the experts, if possible in person, to study an unfamiliar subject. To an academic, the best method of all is to organize a conference or symposium in which multiple viewpoints are represented. Hopefully, through the exchange of ideas and opinions, a hitherto unfocused image sharpens and clarifies.

But, then, why biotechnology? The choice of subject, I can assure you, has nothing to do with my background. I come to this subject unburdened by any scientific knowledge! No one can deny, though, that it is a critical issue today in the relationship between Europe and America and between the developed and the developing worlds. Just this week one front-page story and several others in the International Herald Tribune focused on biotechnology.

Time magazine has declared the twentieth century to be to be "the century of science and technology"; Business Week proclaimed that the next will be "the biotech century", but at the same time there are others willing to march in the streets in opposition to biotechnology. Some claim that biotechnology holds the key to solving problems of hunger and disease, while others are afraid to eat genetically modified foods. Clearly, there is a need for communication of information and constructive dialogue on biotechnology. Hopefully, this conference will provide both.

It will address the following current issues: the benefits and potential risks of biotechnology in agriculture and pharmaceuticals; benefit/risk assessment by public officials; the use of genetic modification in animals for the development of medicines; the sequencing of the human genome and its applications; the potential value of biotechnology as a tool for solving problems of hunger and disease in the developing world; the relative importance of biotechnology to regional and national economic growth; and the regulatory climate for biotechnology in Europe and America. Other issues undoubtedly will arise. I hope that we will be able to address them all openly, with respect for differences in opinion.

In order to facilitate dialogue and maximize participation, the audience will be invited to pose questions after each speaker. At the end of each session, the speakers will re-assemble on stage to answer questions from the audience and each other.

I would like to extend my thanks to the many people who have helped to make this conference possible. You are too numerous to name, but I would like to make a few specific acknowledgements. First of all, I would like to thank the Foreign Commercial Service of the U.S. Embassy in The Hague for so ably handling the organization of this conference. If you feel satisfied - as I hope you do - with the registration process and all the organizational details, FCS deserves the credit. In particular, I would like to mention Larry Eisenberg and Alan Ras. Our consultations with many different people involved with biotechnology in The Netherlands and in Europe were tremendously helpful as we planned the program. I hope you will agree that we listened to your good advice. From America we received assistance from many organizations and individuals as well. In particular, The Institute of Genomic Research deserves special mention. Finally, I am grateful to the Dutch Ministries who have cooperated with us --Health, Economic Affairs, and Agriculture. Their help with this conference is just one example of the myriad ways in which our two countries work together productively. We are honored to have three Dutch Ministers speaking at the conference.

The Ministers illustrate three of the multiple aspects of biotechnology that will come under discussion during the conference. We have brought together speakers who represent not only different viewpoints, but also the different functions of biotechnology in today's world. Thus, you will hear from scientists making discoveries at the frontiers of knowledge, politicians grappling with the implementation of those discoveries, and ethicists and public interest groups who question their value. Hopefully, a productive exchange will lead to a better understanding of the potential impact of biotechnology on society.

Let us begin in the spirit of Louis Pasteur, who urged scientists to "worship the spirit of criticism. If reduced to itself, it is not an awakener of ideas or a stimulant to great things, but, without it, everything is fallible; it always has the last word." It remains to be seen who will have the last word by tomorrow afternoon, but let us hope that it is reached through a positive, fruitful exchange of ideas. Thank you very much for coming.

I will now turn the podium and the session over to Professor Marc van Montagu of the Genetics Department of the University of Gent.

 

Professor Marc van Montagu, University of Gent
"Chair's introduction"

Morning, welcome. First place let me thank Ambassador Schneider and here team for bringing us together today. I think it's an important issue, even people standing outside remind us, how important for Europe and globally this issue is. The morning session will be mostly about the science. What has been done? Can we at the moment say that there is no danger for man and animals with this genetically engineered organisms. Are there problems for the environment, what has been reached and what are the socio-economical issues and the political issues that are behind all the stress that we see here at the moment in Europe.

So I will remind you that for the talks we should really try to stick to the schedule, so the speakers should really please pay attention to that. After each talk, there will be some questions for which there are microphones in the aisle. We are linked via internet to cybercast. They can bring in their questions immediately. Nevertheless, I think it will be better to keep the cybercast questions for the general discussion at the end. So now I want to immediately ask George Poste, who was with SmithKline, to tell us as an introduction "what is biotechnology".

George Poste, Health Technology Networks
"What is Biotechnology"

Ambassador Schneider, ladies and gentlemen, good morning. Ambassador Schneider has given me the unenviable task of attempting to offer a perspective as to the broad reach of biotechnology. Many of the points I make I am sure will be obvious to this audience, but biotechnology in its most fundamental form is really understanding the processes of biology and the processes of the organization of all forms of live on the planet. Anyhow, by understanding the biological processes that underpin live, how far can we harness those for the productive expansion of the human endeavor for the benefit of medicine, agriculture and the other areas which are shown on that slide.

There is no such thing as biotechnology itself. It's a composite of many disciplines. And even genetics is an oversimplification. You can almost put biology in a circle as opposed to genetics, but what I hope will become apparent through my talk is the fact that we are dealing with multiple disciplines, but also the convergence of disciplines which has previously been separate. If you like, biology computing and advanced miniaturization engineering. But the process of understanding the analysis of biological processes whether it be simple organisms or complex organisms, such as mammals and ourselves, is the genetic dictionary.

What is the genome, so in short the total coding potential of genetics, to give rise to the proteins, which are expressed by those genes, that then give rise to structure function and reticular pathways. So in biological specificity it is how does that program account for 18 trillion cells in our body, which then exist in 312 different cell types. Some of which are completely static, some of which are reproducing themselves in terms of billions per day and this is the question of the progressive higher order assembly from the gene all the way through to a complex organism through tissues, organs and the creation of the whole organism. In half we refer to it as physiology and obviously when something goes wrong that the processes are aberrantly disregulated it gives rise to disease namely physiology becomes pathology. But the other element which is now beginning to be sensed is the fact that predisposition by understanding what is actually embedded in the genetic code, we can in fact define predisposition to pathology.

Another way of saying that is the fact that biology is about understanding the basic building blocks by which all live forms on the planet are assembled. There is a remarkable economy of biological design. All live forms on the planet use the same coding material out of DNA, which codes for proteins. And we have essentially got a molecular Lego set, whereby nature has put together all these building blocks in different forms, so that we call it everything from a bacterium to a human being. So those processes become higher order assemblies and that constitutes biological diversity and in the process of evolution the origin of species and within species, what is the genetic basis of individuality and the relentless imposition of selection forces represent fitness.

Now for the first time transgenesis, the ability to build on these basic processes to actually then start altering the genome in terms of enhancement or eugenics, is possible. And now even more extreme the question of so called directed evolution, whereby one fundamentally alters genetic programs and creates genetic programs which have never existed before in the natural evolutionary process. And of course that is a very complex agenda. In short there are many who would argue that that should be forbidden knowledge and that is very much the nature of this debate today.

When I was first invited, I was asked to speak in an area that is my principle area of expertise, which is medicine, so I'm focusing most of my remarks in medicine. We are moving as a consequence of understanding the human genome in moving medicine from simply being a descriptive empirical discipline to one in which merely describing things we now actually elucidate mechanism. So biology is joining chemistry and physics in terms of being mechanistic as opposed to merely descriptive. By understanding the molecular basis of biological processes and what's going wrong in disease, that is creating for industry the ability to dissect disease processes to identify new targets for diagnostics, therapeutics and vaccines in a much more rational way. But the other element that is becoming clear is that diseases that we thought were previously uniform are in fact heterogeneous. Such that the molecular heterogeneity of disease means that while it may have common symptoms there may be different types of genetic pathology underlying that. So that means that we have to now no longer think about one drug for a disease but the right drug for the right disease, in short the right subtype of disease.

And then superimposed upon the heterogeneity of disease is the issue, which we see by looking around this room. Unless you have an identical monozygotic twin, each one of us is unique. And that uniqueness not only reflects the way we respond to environmental stimuli, it reflects the way we respond to drugs. And in the longer term it relates to the question of disease predispostions. So the impact of individual genetic variation is the field of pharmaco-genetics, is the right drug for the right patient, but increasingly and certainly more controversial is the issue of mapping predispostions to disease, giving rise to prophylactic diagnostics and prophylactic therapeutics. So in the future, pharmaceuticals for example still play a major role in human health, but the utilization of that drug will be much more tailored against the genetic background of the patient. The diagnostics to do that profiling will grow in importance and the importance of information whether it be carried as a smart card or a subcutaneous implantable chip with the medical record in it, is in fact the vista that we will now explore.

There will be others in this meeting who will focus upon the ravages of the large demands of the developing world in terms of tropical diseases and infectious diseases as epitomized by mosquito-born diseases. There will be dramatic advances in whole body imaging and then probably the next frontier is this one. How do we actually not just understand genes in disease but actually regulate them and reprogram them. So the next two decades will be dominated not just by understanding the genome as a sequence of information, but what are the controls that switch genes on and off.

In short, how do we inactivate genes that are abnormally expressed or reactivate genes that have been switched off? How do we repair damaged genes?

On the longer term this gives rise to the field of regenerative medicine. And the significance of Dolly is not in terms of extremes with regard to the hysteria about cloning human beings. The significance of Dolly is, it reveals the fact of what was known for some time that now demonstrated in mammals is the fact that every single cell in our body contains the same genetic instructions. And those genetic instructions, even in adults such as ourselves, have not been programmed (a liver cell has one program versus a brain cell and so forth). But the ability to reprogram that genetic repertoire means that you can in fact contemplate therapeutic engineering. So in short, the significance of Dolly is at the level of DNA here, what are the controls that switch the genes on and off, so that one can move to an era of regenerative medicine. We have interest in repair processes. Our bodies are able to exhibit highly capable repair functions, but compare to certain lower organisms, which have complete regenerative capacity. Cut such an organism in half and it will completely regrow. Take the limb off of a salamander or a newt it will regenerate. We have lost many of those traits. But the purpose of therapeutic engineering is how far can we take cells in this case such as spinal neurons for the repair of paralysis of the kind shown their effect in the actor Christopher Reeve. But the real trend I would submit is harnessing molecular medicine towards making care increasingly targeted and customized.
In short the trend will be to move medicine form being reactive (namely, a disease exists), to the modification of disease in a proactive way (in short, which disease does this person have and diagnosing treatment of existing disease, to which person is at risk of having this disease). This can be easily stated, but it will be a long and difficult journey.

So this is where we are today, medicine is largely reactive. The next trend in reactive medicine is the right drug for the right disease and the right drug for the right patient. But longer term, as we begin to correlate more and more genes with particular diseases, that defines my risk profile and your risk profile. And then how do we mitigate that risk, either by lifestyle modification or by therapeutic intervention. In short proactive medicine and moving medicine to disease prediction and prevention. And all this is dependent upon the ability to assemble large amounts of information. But with risk identification there are some increasing parallel trends.
First is the fact that we have improved monitoring of existing disease. Micro devices that you either ware in or on your body, or being able to put your hand up to a sensor mechanism in your home to be able to diagnose health status, I think will become an increasingly important element. And certainly as disease risk predisposition profiling comes about, these will all be linked.
So if I have a predisposition to a particular disease my weekly health check in my home will be to actually monitory health status relative to that particular risk. And I think this will become increasingly important as a social responsibility also.

In the future the challenge for all the G7 nations is the economics of health care delivery. Namely infinite demand set against finite resource and in how far should society reasonably suspect individuals to take responsibility for there own wellness. And so the dimension of being able to monitor health status through small remote devices with wireless transmission into centralized monitoring systems, I think, will become increasingly commonplace.

So it is this union between medicine and computing that will become a dominant theme. So in short the research level we are describing is understanding the informational content and the principles of biological design. Genes giving rise to proteins, to assemble the whole body and what goes wrong in disease. In clinical medicine the need to assemble large scale population databases whereby we correlate particular genes with disease, genes with treatment outcome and the question of my risk and your risk. But it will be more than that. Cybermedicine will be this interface in terms of monitoring devices that monitor health status.
At the same time behavioral disorders, I think, we will see a new pattern of therapy. In stead of taking pills it may well be that interactive software may be a much more effective way of treating certain mental illnesses than therapeutics and doctors will have to become much more used to using the term physician decision software to optimize clinical status.
But the next dimension and again likely to be highly controversial is the carbon silicon interface, namely how do we breach computing directly into neural circuitry. We're seeing the first examples of that now, where micro implants are being used to augment or replace damaged functions. This can be bionic prosthesis or individuals having micro implants to compensate for motor or sensory deficits. But I think the more controversial one will be as we progress over the next two or three decades is to how far intrinsic cognitive and intellectual capacities can in fact be modulated by direct insertion and tapping into those neural circuits. How far then does that move us towards a cyborgian dimension of hybrid intelligence with direct porting of information, whether digital or chemical directly into neural circuitry and of course with that the inevitable controversy in terms of actually having a mind print. Someone said, could you actually monitor someone with criminal or terrorist intent when they walk through instead of just a security barrier today to pick up metal, could you in fact pick up certain form of pattern in terms of neural circuitry? So that to some extent paraphrases the dimension of what we're about, namely, the icon of the 21st century, the helix of DNA, is indeed double edged. It is a controversial subject.

And indeed this is a very complex terrain of ethical, legal and social issues that demand legitimate public scrutiny. The privacy in confidentiality of genetic information in the context of the risk of that information being used to discriminate against individuals for insurability, education and employment. Extending that into the intra uterine environment, prenatal diagnostics and then the decision for elective abortion certainly more likely to be controversial in the United States then Europe. But intimately linked to that is, the question of procreative freedom. Another controversial area will be if I can profile a given disease' risk, yet there is no treatment available for that disease, what level of social and medical contribution is that making. And certainly in the area of behavioral genetics, what is the balance in the nature nurture equation and how far is neuro gegenic predeterminisme a critical issue in certain social traits such as violence and criminality.
And at the same time, coming back to the issue of Dolly, embryonic stem cells and regenerative medicine, not only will this inflame the debate about the embryo and the fetus, we then have, and I have not talked about it, the question of genetic modification of human beings. Whether it be in a non inherited way in terms of modifying the somatic cells of the body or by direct modification of sperm or eggs for transmission of that plus an inherited characteristic. And of course, superimposed on this, as Ambassador Schneider has already said, is the fact that this is the ugly and unacceptable face of corporatism in the global agenda.

But there are also growing national security implications in the context of biowarfare and bioterrorism, were the targets be people, plants or animals.
So in short, the issue that we're all wrestling with, is does the genomic era really represent an opportunity unprecedented for improving the human condition on the global scale and augment personal autonomy, or is this some grotesk technological distopia which is about to be visited upon society. And it is by definition a very complex equation. Society is polarized, the pace of change even for those of us who work closely with it, is dramatic. It is dizzying.
Unlike many elements of high technology, genetics has a great resonance with the public. If you talk with people about the superconducting supercollider they don't care. There eyes glaze over because it's abstract. But everyone has a recognition of the importance of health in their lives. There is this issue of playing God. Are we guilty of Promethean excess and is science practicing ubristic and arrogant behavior? Genetic determinism, free will and individuality, people' s sense of isolation and remoteness in terms of loss of control and autonomy and with that filled by fear and ambiguity. And as society becomes increasingly precooned from risk, even our chairman asked a moment ago, is there no risk associated with this technology, and the answer is unequivocally: No! Because we can never define the fact that there is no risk. And the minute we allow society become sufficiently delusional to believe that there is never any risk, then we're doing something profoundly wrong at the intellectual level. Because the equation is one of growing complexity and uncertainty associated with technology versus a society in which either society is cocooned or politicians want simple answers to complex problems. I remind you of H.L. Menkins comment: "of course there are simple answers to complex problems, but they are invariably wrong." That is the dimension of what we have to wrestle with. And many highly creative and well funded anti technology lobbies have in fact seized in a very creative way, and that is used in an applauding term, the inherent ambiguities in the risk benefit equation. And the technical community including, whether it be academic or industrial, has failed to engage adequately in the public debate.

And I believe that we have got two principals at work here. One is the polarizing principle, namely for the media controversy sells, it's much easier to portrait conspiracy and conflict versus cooperation and consensus. Single issue activism is alive and well, the slick simplistic Sandbites and the media are very reluctant to challenge the hypocrisy of many of those positions. They have already referred to societies delusional believe that zero risk is attainable and at the same time, whether it be corporations or the scientists involved, we have been very inapt in communicating the challenges involved.
At the same time the populist principle, namely it is very difficult for politicians to remain in a centrist position and satisfy issues at any given time and increasing distrust of traditional sources of expert knowledge is now rampant.

In the intellectual salons we see now science portrait as a social construct, in short an expert's opinion is no different from that of anyone else's. And politicians everywhere across the G7 are succumbing to opinion poll politics and expedient spin versus reverting to the much more difficult pathway of evidence based regulation and succumbing to the zero risk lobby. And then you have the pervasive growth and insidious growth and particular in Europe of the application of the precautionary principle, which has in legitimate intellectual origins the elements the environmental movement.

But in short, if a theoretical risk exists then the proponents of that technology must produce contrary evidence that that risk is illusory. On the other hand you create an intellectual teratology, because you cannot in fact conduct the work that you need to do, to show that there is no risk at all. And one thing that we all got to remind ourselves of is, all complex multi parameter systems, it will never be possible to fully define an inventory, the full range of risk or benefits at the beginning. But I would submit that we can not continue with our blind pursuit of the precautionary principle. If we took a poll of everyone in this room, and said, what do you think of the top ten impacts of technology for good in the last century or the millennium. There will be probably a significant overlap between most of us, but I would argue that none of those advances would ever pass the precautionary principle as we intent to apply it now.

So in closing, I think we are alive in one of the most remarkable epochs of the expansion of the human intellectual endeavor. I think that contemporary biology and computing offer the prospect of remarkable advances, not only in medicine, agriculture and the environmental sciences. As I tried to portrait in brief in medicine, the trend will be to shift medicine, from its current emphasis on the diagnosis and treatment of existing disease to the prediction and prevention of disease, in short the shift from illness to wellness. Each of us as predisposition risk become defined will have to take responsibility for avoiding those risks. Profound technological discontinuity is not only an evident now, those will accelerate, they will increase. Biotechnology will also become increasingly important on the international security front. And that daunting array of ethical, legal and social issues should evoke legitimate public scrutiny and new regulatory and legislative frameworks and again Ambassador Schneider, my compliments to you and to your staff for assembling this quite unique assembly of people to examine this complex subject.

Thank you very much indeed.

Professor Marc van Montague
"Chair's Introduction of Chris Somerville, Stanford University"

Thank you very much for this brilliant start. I think that we all have a good look in the future now and we realize that with the more than six billion people we count and 95% of the population living in developing countries, where they have an income of some dollars a month, for many billions of them, and the challenge for our society and global equilibrium, are really immense.

Now I call upon Chris Somerville, from Stanford University. Chris Somerville has been working over the year in the field of Plant Gene Engineering, metabolic pathways and he will tell us how the science has progressed in the plant field and what we can expect there in the upcoming years.

 

Chris Somerville, Stanford University
"The Genetic Engineering of Plants"

My task is to give an overview of some of the applications of genetic engineering to plant improvement and I thought I'd begin with a slide showing the accomplishments of traditional plant breeding. What this shows is something very remarkable. In 1950, we grew worldwide about six hundred million hectares of cereal, about 5.5 percent of the earth's surface. If we were growing the same type of cereal today, we would be using about 1.4 billion hectares of land, or actually most of the arable land on earth, because of the demands of population growth. Because of the improvements brought by plant breeders using traditional technology we're still only using about six hundred million hectares of land worldwide. So I want to make a point that first of all there is, obviously, increased demand for plant productivity. And secondly, when it comes to environmental issues, the greatest environmentalists of all time are the plant breeders who saved 800 million hectares of land from agriculture. In fact agriculture is the greatest threat to biodiversity. And I think that much of the debate about the environmental consequences, are somewhat displaced from reality. Now the problem is that those increases were effected or at least began during a time of substantial annual productivity gains. This slide shows the rolling average of the annual rate of increase of cereal productivity due to breeding. And you can see that in the 60s or the late 50s the annual rate of increase was about 4 percent per year. However today that increase has dropped to about 1 percent a year in spite of the best efforts of the breeding community. What this implies to many people is the necessity for new technologies to maintain the increase in productivity that we need in order to prevent the expansion of agriculture onto currently non utilized land. So from my view, plant biotechnology is fundamentally nothing more then the application of knowledge to this process.

Plant breeding by itself, traditional plant breeding technology, is a process-oriented technology, rather than a knowledge rich technology. The traditional tools of plant breeders are to make crosses within species to try and bring in variation that exists within nature, within the species, and then select useful variation. In limited cases, interspecific processes have been used and I don't know if it's widely understood that many of the wheat cult used are no longer truly wheat but actually contain genes from other species that were brought in through laboratory means. To create variation, using irradiation and chemical mutagenesis, anything that can create variation, has been used traditionally. One way to think about the goals of biotechnology is to acknowledge that these technologies have not raised alarm, in spite of the fact that they do create a lot of variation in plant species. By contrast, what biotechnology or genetic engineering brings to the table is that it is now possible to introduce genes from any species and to control where and when they are expressed. This fundamental issue should be seen as a mechanism of increasing the variability that plant breeders have to deal with. That is, instead of the limitations to crosses that can be made and propagated by laboratory techniques, it is now possible to take a very directed approach. The directed modification of endogenous genes is the other possibility that it is not all genetic engineering involves bringing a gene from another species. Some of it involves productively modifying genes that are already present in a species by changing the amount of expression or altering the function of an endogenous gene or altering where and when the gene is expressed. These basically are the tools of agricultural biotechnology. They are rather simple and in fact, the technology for producing transgenic plants is also simple and natural. Typically, it exploits a natural process in which a species of bacterium has evolved. The ability to transfer genes into plants. In nature, that capability is used by bacteria to colonize plants and to transfer genes into plants from the bacterium so that they produce nutrients that support the growth of the bacteria. The revolution in plant biotechnology, that was actually partly created by Marc van Montague and Jeff S____ and colleagues, was to learn to tame this bacterium so that we could add a gene of interest to us. Typically what is done is leaf discs, for example, are dipped in a bacteria that contains a gene of interest and the cells resulting from that gene transfer can then be regenerated into plants. It is a fairly low-tech approach. The knowledge that comes into this is actually not through the process, but through the identification and understanding of the genes that are added to the plant or modified in the plant through the use of this very simple and rather natural technology.

I think the question that arises and typically is, "How predictable is this process, to what extent do we know what we're doing". I think, perhaps we could have a discussion about this later, but from my view, we do have a lot of certainty about what is introduced. There is no questions, when we make a transgenic plant, typically we know exactly what we put in and we know where it's gone and that's very understandable. The manipulation of a plant by any method, that is the introduction of a gene or traditional technology, traditional breeding, can create alterations in the genome of the plant. But the technology of making transgenic plants doesn't actually in that respect does not do anything that is not already possible by other technologies. I think that's a very important point. Even though none of the scientists involved in this would claim total predictability of what a transgenic plant may perform, I think everybody would agree that the performance of a transgenic plant does not (except for the properties introduced by the specific gene or genes) the rest of the variation is within the natural range that could be created by any other traditional technology such as mutagenesis or out-crossing. Concern about creating plants with unknown properties, I think, is largely unfounded a scientific perspective.

Much of the debate about plant biotechnology seems to focus on a, from my perspective, very narrow range of applications. The BT gene certainly seems to dominate and I thought rather than discuss things that have wide discussion already, I'd focus on a few opportunities. From my perspective and I think from that of my colleagues, we see a number of opportunities in different areas. There are certainly many opportunities to alter the nutritional qualities of plants, to increase the feed efficiency that is the use for feeding animals (and I'll come to that in a moment), to decrease the losses to pests and pathogens. To put that into perspective, I need to tell you that in Asia and Africa, as much as forty percent of all plant productivity is lost to pest and pathogens. So one of the most productive possibilities for increasing the world food supply is to actually deal with this problem. To increase the stress tolerance of plants, one of the major limitations to plant productivity is stress, (and I'll give you an example later) eventually as we understand plants in more detail, we believe it's going to be possible to generate intrinsic yield increases by modifying processes, such as photosynthesis. We can certainly adapt plant to agricultural practices. You need to bear in mind that plant were not created for our purposes and there are still many changes that would be useful in plants that would allow us to farm them or use farming practices in a better way. It is certainly possible to make novel products, and if time permits, I will mention this. Particularly technical products, non-food products that have useful environmental consequences. This latter refers to idea of actually expanding the range of plants that we can use. There is, as you probably know, a movement to move towards a more diversified agriculture and I think it's true that no plant has been domesticated in this century because of the difficulty of actually domesticating a wild plant. There are 250,000 plant species out there, many of which have useful properties. I think the tools we now have available will allow us to actually bring some of those plants to use.

Among food improvements, I thought I would briefly talk about some possibilities in nutritional values or food improvement. I'm going to briefly refer to some improvements, pending and existing in the case of altering the fatty acids, anti-oxidants and vitamins. There are many other improvements that can be made in the flavor, color, fiber contents, the elimination of toxic substances and the inclusion of health promoting substances. These were not included in the first generation of products for historical reasons, but these kind of improvements compose a great deal of the research on the emerging products. I think it's inappropriate to consider where the technology is going without understanding that there is a lot of innovation in the pipeline. As a first example, I want to describe briefly a result that was published last week in "Science". It refers to the fact that a quarter of the world's people are dependent on rice as a primary staple. Of those, 400 million are deficient in vitamin A and according to reports I've seen, as many as a million children a year die because rice is a poor source of vitamin A (in fact, it has almost zero). In addition, at least 800 million people are iron deficient for the same reason and I'll refer to the mechanistic basis of that. A paper in science by the lab. of Ingo Patrikas, Zurich, reported the creation of a rice variety with high vitamin A. This was done by introducing several genes, several of which came from daffodils and one came from a harmless bacterium. Basically, what it did was it converted a compound which is present in rice into Beta Carotene or pro-vitamin A.

The introduction of these genes brings the level of that compound to a level such that now, 300 grams of rice (which is a low daily ration) will provide the necessary amount of Beta Carotene to meet people's daily requirements. A nice aspect of this work, and something I think also gets lost in the debate, I think that many people tend to think of plant biotechnology as something done by big companies. This is absolutely not true of coarse. Patrikas managed to do this work in a way that he has given it to the international rice research institute, which will in the next several years, release it to subsistence farmers at no cost and no strings attached. I think it's a very nice example of the potential of the technology. This was supported, fortunately by the Rockefeller Institute. It took eight years to do and it will take three years to reach the fields. Since the time this work started until it ends, another billion people will be born. It is very important to remember the time frame for many of these innovations is long and the consequence of not doing them is high.

Another problem with rice is that eating rice decreased the available iron in your diet because rice, like so many other cereals has a high content of this compound (it is a sugar with six phosphates on it). That compound reacts with iron and makes it unavailable. Patrikas has also made an innovation that hasn't been released yet, but has expressed an enzyme called phytes in the rice, so that the phytes will withstand boiling. When the rice is cooked, the phytes comes in contact with the phytic acid and removed the phosphate groups and makes the iron available in the diet. I think this will also be a useful innovation in treating that limitation.

As with many aspects of plant biotechnology, typically there are many uses for these innovations, and I thought I'd take this example to show another use. I think one of the best ways to increase productivity is to increase the efficiency with which we use things. There is a concept called "feed efficiency". It turns out that in most of the animals we use as foods, what determines the ratio of useful to not useful product is one or several limitations. So in the case of, for example many of our animals, it is the amount of phosphate in the foodstuff that limits the ratio of useful to not useful. It's been shown that by simply increasing or adding the enzyme phytes to foodstuff of several animals, like chicken, you can strongly increase the ration and decrease wasteful bi-product. I think that innovation was actually created in here in the Netherlands by a little company called Mogen some years ago. I think it's another nice example that illustrates the many opportunities.

I want to talk about one more food application that's highly relevant to everybody in this room. It turns out that about a third of the calories in our diet come from vegetable oil or fats. About 80 percent of that comes from vegetable oil. Plant vegetable oils are typically not ideally suited for our needs. In particular, the presence of three double bonds in the fatty acids makes them susceptible to oxidation. This was dealt with by bubbling hydrogen through the oil to remove the double bond. Unfortunately, that process not only removes double bonds, but it changes the stereo-chemistry of the remaining double bond. Instead of having all-sys configurations about 40 percent of the remaining fatty acids have what is called a trans-configuration. Everybody in this room is now carrying these trans-fatty acids in their body from our diet. These are actually worse for you than saturated fatty acids. The FDA currently has an advisory on this and is looking into labelling needs. That's existing technology and I believe there are reasons to be concerned about it. Until recently, we had no alternative to that. However, during the last decade, the genes that are involved in making the double bonds have been identified and indeed these genes can be used to eliminate or prevent the insertion of the double bonds in the first place. In fact, this means it will become possible to produce plants that have ideal compositions of fatty acids with respect to human nutrition by simply using endogenous genes to turn off or regulate the expression of the endogenous genes. So taking a gene out of a plant and putting it back in in such a way that it suppresses the endogenous gene expression.

I think it's a nice example of a health benefit that is going to touch everybody and it's just one of many that's coming along. While I'm on the subject of fatty acids, I would like to state that my personal interest in this technology stems mostly from what I consider to be the positive environmental consequences. Since the mid-80's, salmon farming, in which salmon are held in pens offshore, has grown to be a very large industry. However, it is ecologically not very attractive because to grow salmon in salmon farms, each pound of salmon requires four pounds of other fish. So basically, we're going out, we're catching other fish, grinding them up, feeding them to salmon. You might ask, "Why are we doing that and not feeding them soybeans?" It is because the fatty acid composition of plants will not support the growth of salmon. However, the same genes or related genes to the ones I described that could be used to alter the composition of soybean oil, can also be used to create modified soybeans that can be used to feed these salmon and eliminate the need of such a feeding.

I'd like to conclude by conveying that there are a large number of opportunities. Many of these opportunities have benefits for consumers, many have benefits in the environment, and many have benefits for farmers. Not everything that we do, in my opinion, it seems unrealistic to expect that all applications of the technology only benefit consumers. Furthermore, I would say that this technology does arise from a very deep knowledge of the underlying processes in plants. And indeed, the plant community is currently engaged now in using genomic technology to determine the sequence of all the genes in several important plants, including rice. During the next decade (in the United States, Europe and Japan at least) there will be a coordinated effort to understand the function of all plant genes. I just participated in a group that worked out a plan to complete this process so we're entering an ere in which we will have complete knowledge of what's required to make a higher plant and we also have tools (that I also don't have time to talk about at the moment) that will allow us to interrogate every plant as to what each of the genes is doing in that plant at any given time. Perhaps I will end on that note, which is to basically say, "There is a lot of opportunity and there are no limitations in my opinion to our ability to use that knowledge to improve agriculture in different ways. Thank you."

 

Professor Marc van Montagu
"Chair taking a question"

Thank you very much for your beautiful introduction and showing the importance of plant engineering. Maybe we could rapidly have one question if somebody wants to challenge or ask for more explanation? Yes, please Ambassador Schneider.

 

Ambassador Schneider
"Ambassador Schneider asking a question"

On the connection between the history of selective breeding and current plant biotechnology techniques, one hears that current techniques are more scary, more unknown, more threatening. Are they more exact? How would you compare what is used now with the tradition of hundreds of years of selective breeding.

Chris Somerville
"Chris Somerville's response to Ambassador Schneider's question"

Traditional breeding is process-oriented. If you gave ten plant breeders the same starting materials, they would produce ten different varieties as an end result. It doesn't depend on a deep knowledge of the underlying biology and it's rather unpredictable. By contract, biotechnology is totally knowledge-driven and very predictable. The result from genetic engineering is hundreds of times or thousands of times more predictable than the results of traditional breeding

 

Professor Marc van Montagu
"Chair's introduction of Jonathan Eisen"

I am afraid we have to move on. Now I will ask Jonathan Eisen from TIGR to talk about the genomics aspects. As Chris has already introduced, there is an enormous progress we see now in plant sciences and it depends on the enormous progress that food human genome programs, all organisms are making. We will hear more now about micro-organisms and plants.

 

Jonathan Eisen, The Institute for Genomic Research (TIGR)
"Microbial and Plant Genomics"

I want to thank the Ambassador and her staff for organizing a really amazing meeting. This is a collection of different interests, different backgrounds. For those of you who didn't notice or realize, I am not Claire Fraser, who was originally scheduled to speak from TIGR. She was unable to attend.

I am going to speak mostly about genome projects and genome information done at the Institute for Genomic Research, where the first complete genome was determined. However, I want to make a note that there are genome projects going on all around the world now. An enormous number of them, both micro-organisms of plants of various eukaryotic pathogens and of humans and other things. I am going to focus on the ones we are doing at TIGR.

I am going to give a little background on microbial genomes and talk about some aspects of that. Then, I am going to focus on three particular applications of genomics: Using genomics to better develop vaccines, or at least to start develop vaccines; Using genomics related to bio-remediation, and then; Using genomics to better understand the evolution of species. In particular what that says about gene transfer that occur naturally in the field. Microbiology had it's beginnings right around here in Delft. Van Leeuwehoek, I probably pronounced that incorrectly, was the first to document the existence of these microbes. What we now realize, is that microbes pretty much dominate this planet. They're the major causes of pathogenic diseases and still the major cause of death around the world. In terms of evolutionary diversity, this is an evolutionary tree of life and highlighted in the big box are all of the micro-organisms. Only at the tip of the eukaryotic evolutionary branch do we see large collections of larger organisms so the rest of everything: the bacteria; this strange group of organisms called the 'arkea' or 'arke bacteria' and even most of the eukaryots are micro-organisms. Micro-organisms play major roles in global energy and nutrient cycles as I said in pathogenesis. They are also responsible for a lot of features of non-micro/macro-organisms through symbiosis with those organisms. They count for a large portion of the bio-mass on the planet and they also count for pretty much the majority of biochemical and physiological diversity.

In 1995, before I got to TIGR, the first complete genome was determined of the bacteria "hymofelous" influenza. I'm not going to spend time talking about the method by which the genome sequences are determined but I'm happy to talk to people about that afterwards. Since that genome was completed and published just 5 years ago there has been an incredibly accelerating rate of publication and release of genome sequences. In addition there are many being done by private corporations and entities that are not really releasing them. This is a time line showing some of the different genomes: in red are the ones that have been done at the Institute for Genomic Research and yellow are the ones done at other institutions. The different colors show different types of organisms so all the white ones here are bacterial genomes that continue to be sequenced. The ones in sort of pink color are arke-bacterial genomes and the ones in green are eukaryotic genomes or chromosomes and they are many more like yeast and plasmodiam chromosomes and soon we will have the complete genomes of many eukaryots as well. Just another prospective on this just showing that the determination of complete genome sequences rapidly increasing and we are going see an even probably more exponential increase in the next few years. There are literally hundreds of bacterial genome projects going on around the world.

Now I just want to spend a minute or two talking about why we actually want the complete genome sequence, rather than just most of the genome sequence. When you have the complete genome sequence through a variety of techniques you can determine not just the presence of particular genes that you might have a hard time determining through other methods, but also what is very important in some organisms is the absence of particular genes. For some pathogenic organisms, in particular pathogenic bacteria, they are missing key genes that for example regulate the mutation rates. Many pathogens have high mutation rates and that in some cases is due to the absence of genes that limit the mutation rates in other organisms and you can determine that from a complete genome sequence. In addition, having the complete genome sequence really allows you to get a firm grip on a lot of genome features that having incomplete genomes just doesn't allow you to do, such as large genome duplications, the order of genes can be important for understanding the function of some of those genes, where the genome might originate its' replication can also be very important for certain biotech applications. Even when you are missing a small amounts of the sequence you can be missing very important things, for example, TIGR just finished sequencing chromosome II of the plant "Arabadopsis Thaliana" and through a sort of "curculian" effort of sequencing technologies we went into sequencing some of the hard to sequence regions in the centrum area of the genome and discovered that there were some very interesting features there. So in many cases people are avoiding sequencing some of these hard to sequence regions in genomes, but it turns out that there will be things of interest there and it is worth pursuing that if at all possible.

Completed genomes have provided an enormous resource to scientists as well as to people applying the genomes to particular studies. For example, when you identify all of the genes in the genome we run a variety of prediction programs to try and guess what the function of those genes are. Through doing that we can identify in some organisms novel metabolic pathways that may not have been expected in those species. Novel regulatory elements or just in general characterizing the regulatory elements. You can identify genes which are relatively unique to that organism or which have no predictable function which may be worth pursuing as novel candidates for interesting biochemistry or physiology, you can identify pathogenesis features, "envirolence" features and I'm going to talk a little bit about using this to identify vaccine candidates. You can also apply the complete genome sequences to a better understanding of both species diversity through "compara-genomics" as well as through characterization of uncultureable organisms by say "hyberdization" to arrays of genomes from soil samples you can identify what species are out there in the soil and what there properties might be. I'm going to talk a little bit about insight into evolution of genes and species. But the real key for genome projects is that they are the beginning of a lot of biological research. They allow you to do things that may have been limited before by not having that sequence information. And most of what we do from the complete genome sequence requires further experiments to follow up the guesses we make from the complete genome sequence or the predictions that we can make. And so it really is a nice starting point for characterization of particular species now, to have its complete genome sequence.

For example, I've just highlighted a few genomes done at TIGR, done a search of med-line database and plotted the number of publications about that particular organism over time. And you see in this the "mycoplasm genetalium" as soon as the genome was published the number of other publications about this species increased exponentially and it is increasing even further now. The same things happens with other microbial genomes. The genome sequencing really does stimulate a lot of research.

I'm just going to spend a couple of minutes talking about vaccine development. When you have a complete genome sequence, it allows a targeted approach to vaccine development that was difficult or not possible with standard methods of vaccine development. So, one thing you can do is, by sequence comparisons, identify genes in your genome of interest that are similar to genes that are known to be antigens in other species. And so now, you can use those as targets for developing vaccines for that particular species. Through predictions of the structure of the genes in a genome, you can also identify candidates that might be on the surface of the organism that might, therefore, be antigenic peptides. You can use the sequence to make the DNA-based vaccines, which are being developed in some places. Another thing you can do is, in a lot of organisms, the genes that are antigenic are also genes that are under strong selective pressures in that species to vary. And many organisms have developed means to create this variation. And one of those means is by having phase-variable genes, such that the mutation rate in these genes in that organism is very, very high. And it allows that organism to evolve responses to the immune system rapidly. You can identify candidate variable genes from the genome sequence pretty well, based on the sequence features.

This is an example of some of the methods that are being used, based on some of the sequence coming out of the malaria organism, "plasmodium phosyperum". We're in the process, an international organization of which TIGR is part of, to sequence the genome of this organism. We take that genome and we make whatever predictions we can make, based on the gene sequence and identify candidate antigens. And these antigens can then can be fed into a variety of systems to test vaccines, based on those antigens. It requires some ways of doing experiments in that species or using those antigens. But, again, the genome sequence is the starting point for identifying any of these candidate antigens.

We've just recently completed the sequence of the bacteria "Aneasyria Menengititus", which is one of the causative agents of meningitis. From this genome, it's known from previous biological work, by people like Richard M______, that phase variation, the thing I described just a minute ago is very important in determining the pathogenesity of this organism. Prior to having the genome sequence, around fifteen to sixteen phase variables genes were known in this organism. From the genome sequence, we can identify at least fifty new phase variable genes, or likely phase variable genes from this species. Therefore, that increases the possibility of vaccines, based on these genes.

Now I'm going to talk very briefly about another application of genome sequencing. In this case to understanding organisms that survive in extreme environments and the potential application of that. In this case, TIGR has just finished sequencing the genome of the bacteria "Dynacoccus Radiodurands", which is most radiation-resistant bacteria known. It can survive doses of gamma radiation that will start to melt the test-tubes that you're growing it in and it really doesn't care too much that it's getting that dose of radiation. These are doses a thousand times greater than, let's say, the bacteria E-coli can survive. It's also extremely resistant to desiccation, to mutagenesis, to UV radiation, to just about anything you can throw at it.

This is just a map of the genome sequence. From the genome sequence, we went through and tried to identify likely genes involved in some of these resistant processes. In particular, we focused on looking at genes that might be involved in protecting the organism and the genome from this damage. For example, you can scavenge oxygen radicals. There are various mechanisms that will allow an organism to tolerate the damage, even when it occurs. In particular, what we were most interested in is genes that were involved in actually repairing the damage. In particular, repairing the damage to the DNA of the genome.

This is a list of the DNA repair genes, putative DNA repair genes in the genome that we have identified, based on comparison to other species. What this allows you to do, is to take that list of DNA repair genes and either go in because some genetics is available in the species and target disruptions in those genes and see if they really do account for the extreme resistance of this organism or you can transfer those genes into other organisms to see if they make those other organisms equally radiation resistant. So far that has not been the case for the genes that have been transferred into other organisms.

What Dynacoccus is actually being used for more is to take pathways from organisms that can degrade toxins, for example, and transfer them into Dynacoccus Radiodurands. Because Dynacoccus can survive extremely high doses of radiation and for long periods of time, the hope is that in mixed contamination waste sites you can introduce toxin degrading pathways into Dynacoccus, release Dynacoccus in that environment where it will be able to survive the radiation and at the same time degrade the other toxins that are in this environment. It's not clear whether this is going to work. In particular, I think it has a potential not to work because Dynacoccus Radiodurands is not the most competitive known. The only way that people have really been able to isolate it, is be irradiating the heck out of a sample and it's the only thing that's left. Before you irradiate it, it's very difficult to isolate it. It's present in very small levels and it doesn't out-compete the other organisms that are there. It has potential to be used as such a bio-remediation device, but we really don't know whether or not it's going to be efficient at such a process.

The last topic I'm going to talk about with complete genomes is, using genomes to study evolution. In particular to learn about gene transfer among organisms through evolutionary comparisons. The general model for evolution of organisms that was around for a long period of time was a model of vertical inheritance. That is, you start it with some individual organism or a small population of organisms. These are split into different lineages and those lineages evolve separately into different species at the end. It's been known for a long time, that among populations, there is a reasonable amount of gene flow within a species, but there is some gene flow between closely related species (hyberdization in nature). But there was little information on gene transfer between organisms. There were specific cases that were well documented, for example, exchange of plasmids. In this case just a model of say some green species of bacteria and a red species of bacteria next door and there are many well documented cases where small pieces of circular DNA, called plasmids can be exchanged from one organism to the other. If the green feature is due to the genes on this plasmid, then this organism would essentially become green.

There have been many other examples of gene transfer in the environment involving things, such as viruses, transposable elements, the agro-bacterium plasmid that we've heard about already. This bacteria transfers some of its genes to plants, in order to cause the plants to produce compounds that are useful to that bacteria. The general amount of this gene transfer is considered relatively minimal compared to the total size of genomes. Specific cases of gene transference involving large amounts of DNA were well documented with transfer genes from organelles to the nucleus; from the mitochondrion chloroplast to the nucleus of organisms. Mitochondrion chloroplasts were originally living bacteria. They are now a symbiosis with eukaryots and they've transferred many of their genes to the nucleus. From "Arabadopsis" chromosome two sequence, we find many more cases of this organelle to nuclear gene transfer then we previously expected, including a 275 kilobase section of the mitochondrial genome inserted, very recently, into the centromere of Arabadopsis chromosome. And many other cases on Arabadopsis. From all the genome sequences that have been coming out, we find that gene transfer appears to be more of a rule than an exception. Studies of the deep-branching, early-evolving bacteria "Thermatogo Maritima" clearly show that there have been enormous amounts of gene transfer between thermophillic bacteria Anarchia, as I mentioned in Arabadopsis Thaliana. In Dynacoccus, we actually believe that some of the smaller chromosomal elements will actually be referred to as the chromosome two and the mega-plasmid may actually have come from other sources. Again, this appears to be the rule in organisms rather than the exception - enormous amounts of transfer involving huge chunks of the genome either at one time or over long periods of time.

And so this is what the tree of life actually really looks like. It's not a tree of life, it's a web of life or a network of life where gene transfers are occurring constantly between organisms. What this means is not just that the tree of life is really a web of life, but, related to this conference, that genetic engineering is actually going on in microbes quite a bit. They're transferring genes and sampling diversity of processes by soaking up DNA from other organisms and thereby possible evolving new pathways or new resistances to things. So this gene transferring is occurring all the time. It can actually be extremely precise in nature, in that single genes inserted into very particular regions of the genome through regulated processes, very similar to targeted genetic modifications being done in labs now. However, what this also means - it is a double edge sword - it also means that it is likely that when we make genetically modified organisms some of those genes could be transferred to other organisms and should be considered a potential process either through viruses or bacteria or recombination or hyberdization. All sorts of mechanisms allow this. What appears to be the most important thing, at least from the evolutionary analysis to determine or not whether these gene transfers occur. Not the possibilities of the genes being exchanged. That appears to be very easy. But whether or not, the gene that is exchanged can be maintained in the new organism. First you have to have a strong selection to keep it there. In addition it has to have the right features to fit into that organism's replication and genome processes.

So just to end…The genome sequences are the starting point for a lot of more detailed research. They have provided a lot of insight into things like lateral gene transfer. They also allow people to do genome-wide experimental studies, which we will probably hear more about later, such as genome micro arrays and things like that. Things that have not yet been done, but we'll continue to do in the future are comparisons of closely related species, such as human and mouse or very closely related bacteria. And that provides a very different type of information than the comparison of distantly related organisms.

 

Professor Marc van Montagu

Thank you very much for taking us into the world of micro-organisms. If we think how many endorphines, animals, we ourselves, and plants are carrying that have never been studied. If we realize that in the micro-organism, maybe ten percent can be isolated and studied. Now we can proceed with that, which is a really important activity for society, that is now developing thanks to the sequencing. I think also that evolution is complicated and that the spreading of genes is complicated. Until now, society has never discussed it and has not been informed and you give us the cues to do it.

Is there an urgent question please? Then, in order to stay on time, we will keep it for the general discussions. Now I call on Steve Tanksley, from Cornell University. The title is very clear, "There is No Such Thing as a 'Natural' Red Tomato". We will now see what is at the heart of the discussions on genetically modified organisms.

 

Steven Tanksley, Cornell University
"There is No Such Thing as a 'Natural' Red Tomato"

Thank you very much for the opportunity to speak. What I would like to talk about is one aspect of biotechnology and genomic research which is not often thought about. That is the role of this technology in utilizing natural diversity in plants for improvement in plants. First, I want to dispel the title of my talk, which is "There is No Such Thing as a 'Natural' Red Tomato". You have all seen them in the supermarket and grown them in your gardens. There are nice luscious tomatoes. Whether these are natural is a matter of perspective.

I think to put everything in perspective, we have to remember that even though there are tens of thousands of plants that grow on this planet, only a very small number sustain humans. On the order of thirty plants species account for almost all the fruit and fiber produced in this world. In terms of human evolution, the existence of these crop plants is a very recent phenomenon. More than ten thousand years ago there were not such things as crop plants. Humans did not exist in a settled agricultural situation, but were hunter gathers, taking what was available in the wild. In these times, these plants they were using are very different to what we have today.

For example, if we look at tomato and imagine what we have here in the supermarket and actually go back to the wild where tomatoes came from in South America, along the western coast, you find that tomatoes look more like this. The first thing you will notice is that these are very small berries. They are very full of seed. They do not have nearly as much flesh as would one of these cultivated types here. The second thing is that, even though some of these are red, the most common form of wild tomatoes is green. They do not produce this nice red lycopene that we associate with tomatoes. The last thing is that most of these wild types have compounds that are toxic to humans or would at least make you ill. That is in part a defense mechanism because these plants have to defend themselves against insects and herbivores. The reason these berries are so small is that one of the mechanisms for survival in the wild is dispersal. You have to reproduce yourself and the progeny has to spread over some distance for the species to survive. These wild tomatoes are very small and full of seed because they are harvested by small rodents and birds, which can pick them up and carry them some distance to spread the species. These cultivated types have much exaggerated fruit. In fact, the change in size between these wild types and cultivated types is up to a thousand-fold difference. This change in size is quite striking. If you were to put it into perspective with a human body, imagine that magnifying your body a thousand fold could be quite absurd or obscene. The point of this is that these plants now produce something useful for humans at the determinant of the plant. These cultivated tomatoes no longer could survive in the wild. They put, first, far too much energy into the fruit itself, to the detriment of the plant and, second, these fruit could not be dispersed easily, except perhaps by a very large eagle. This is not a unique situation.

If you look at other plants that feed the human population, the same thing has occurred. This is on the western tip of the Fertile Crescent, which is in Northern Israel. This is Dr. Nivo from Haifa University. He is a plant ecologist and evolutionist. He is here out along the roadside, holding up a piece of grass, which if you look more closely is actually a close ancestor of cultivated wheat. If you are familiar with cultivated wheat, you would immediately notice that this is a much smaller spike than you would see in a cultivated type. The cultivated type would be up to ten times larger and bear many more seed and much larger seed. The second difference is that these seed drop off before harvest, which is a natural dispersal mechanism. If we were to look at these ancestors of wheat, which is what our ancestors actually began cultivating, their productivity is very low from a human perspective, but very adapted from the plant perspective. The reason they drop off the seed, which is good for the plant, is dispersal, but for humans you could not harvest them because of the shattering. Humans have modified a few plants so dramatically that these plants can not survive on their own. In fact, they owe their existence to us and we owe our existence to them. If it were not for this first revolution in genetics, there would be no civilization.

One of the side products of this process, in addition to producing these very abnormal plants which we associate with agriculture, is that it put plants through a bottleneck which we call a genetic bottleneck. Humans did not domesticate all wheat, tomatoes or rice. They domesticated a few selected types that were more to their liking and from those they selected additional ones which had new mutations and accumulated a sufficient number of mutations desirable from the human perspective, not from the plant perspective, to produce these cultivars which were the early domesticated which gave rise to settled civilization. In the last hundred years, there has been a remarkable application of the knowledge of genetics of breeding to further reduce genetic variation, while producing higher yields and productivity. The end of this process is plants highly adapted to human use, but also much lower genetic variation than was present in the wild. We have realized, for some time, that this variation that was the source for these crop plants in the beginning, is the same variation with which we have to make progress in the future.

Without genetic variation, even naturally induced, there is no improvement of crop plants. Starting at the early part of the century, there was a directed collection of plants, wild and related species of crop plants to put into gene banks, with the knowledge that we would need these for future improvements. One of the dilemmas of this whole situation is that we have collected large amounts of genetic material hoping to improve crop plants, but if we actually look at how well it has been utilized, it has been fairly minimally utilized. If we look at, for example, rice and we look at all of the collections of rice that make up gene banks, only a small proportion of those variants have made their way into cultivated types that are used around the world. Tomatoes are even more severe. If you look at all the tomatoes you see in the supermarket from cherry tomatoes to the very large beefsteak tomatoes, their amount of variation is less than 5% of what is available in nature. The reason it has been difficult to utilize this natural variation is because plants have some thirty thousand or more genes. To go into these plants and specifically identify the genes you would like to transfer, which are beneficial against the background of these many other genes, many of which are not beneficial, has been problematic for plant breeders. The processes of plant breeding are not conducive to transferring a few genes or identifying a few genes.

Crop plants, this fairly small number of species we depend on for agriculture, have been highly modified to the point that they really are unique and dependent upon humans and us on them. Domestication itself reduced genetic variation, on which we depend for further improvement of plants. The dilemma we face for the future, and Chris Sommerville already made this point, is that the world's population is continuing to grow and to meet those demands we have to continue our agricultural production. The first green revolution which took place in the late 50s and 60s, was a combination of genetics and technology, the genetics being breeding and the technology being the application and availability of petroleum based pesticides and fertilizers, and to develop crops that are compatible with those. This resulted in a huge increase in production, and was quite successful. The second green revolution, most likely, can not depend on a further input from petroleum based products; first, because there are limited supplies and second, because of the damage that is caused by the applications of these in terms of contamination of the environment and also, in some cases, the food supply. Our next green revolution, if we are going to keep up with food production and also provide for a sustainable quality of the environment, will have to be almost entirely genetic.

The dilemma is that the variation we have to deal with has not increased. In fact it has decreased and without variation we can not make progress. This just shows results from rice. This is looking at the production of rice under optimal conditions and look at the varieties that are available. This is post green revolution. This is after some of the semi-dwarf varieties of rice came out. We see that while the varieties under substandard conditions may be more productive, if we optimize conditions, the genetic potential has not changed greatly. It has been a fairly flat curve. Unless we can turn that curve up, we have some significant problems ahead.

One of the applications I mentioned for the genomic research and biotechnology is actually going back to the ancestors of our crop plants and bringing back variation for selected genes in a manner that can help produce better crops. One of the goals in my own lab has been to look into processes of this. We have been using the entire tomato genus, which only has one cultivating species and many wild forms, and looking through these genomes for genes that could increase productivity. The tools we have done this with are a combination of genetic tools and molecular biology. It allows one to go in and identify the position of the genes controlling any number of agronomic characters and to selectively pick out sections of the genome from these wild plants that have potential for increasing productivity. As a result of this, we have been able to identify many of the key points or mutations that allowed tomatoes to become domesticated to produce these large edible fruit. With this knowledge, we are now able to isolate the genes involved in this domestication process. The implications are that, first, if one has the genes available which are the key set of genes involved in the key changes for humans, one can look more directly for natural variation, or second, one could actually create a set of novel variants in the laboratory, which could help increase productivity. The second point is that, as we learn what the steps are or what the switches are that converted wild plants to domesticated types to produce products humans like, like large fruit, we can imagine in the future that we may be able to add a second wave of accelerated domestication, so we do not depend on only thirty plant species and grow these at the exclusion of other plants. Perhaps we can modify existing natural plants adapted to environments to produce the products that we desire.

I want to show a slide that shows some of the surprises that come through search wild plants for genes of agricultural value. We have been screening through the wild tomato germ plasma with these molecular mapping and probing techniques, looking for genes for value. One of the traits we have looked at is increased production of lycopene, which is the red pigment that we all value so much in tomato and in tomato products. We have been successful in finding quite a few mutations or novel variants in wild types that increase the production of lycopene. Here is an original variety we started with and here is one modified by adding a gene from of these wild species. The surprise comes in that the gene that we isolated, or in this case we transferred a small piece of chromosome, actually came from a plant that does not produce lycopene at all. This is Lycopersic Eeurpseudum. It produces no lycopene at all. Nonetheless, it has at least one gene that has a form, when transferred over here, that can increase color production. There is much hidden potential in wild germ plasma flowers. As we move into the future and we have to go into the second green revolution using genetics and genomic technologies, we will have to depend on finding variation like this, both from wild tomatoes and also other plants from which we can bring in novel genes.

I want to end with this collage that shows a number of crop plants. Again, these are very highly modified forms that have been useful for human success and that is something humans have created. We have to continue modifying these in a form that can benefit humans, not at the expense of the environment. When it comes to making a judgement about which technologies we use to create the variation to improve plants, I think we should not make a judgement about the technology, but we should make a judgement about what the goals are of the technology and if the goals are justified, there is no reason why one should accept plant breeding as a "natural process" and transgenic plants as a non-natural process. In the large scheme of this, it is all a non-natural process, in that we have modified plants for human benefit that can no longer survive in the wild. But if we look at in the scheme of co-evolution, we are co-evolving with these plants and we have to use the technologies available to do the benefit to both us and the environment.

With that I'll close. Thank you very much

 

Professor Marc van Montagu

Thank you Steve and Ambassador Schneider says, we will not take questions now. We'll keep the questions later when all the presentations have been done.

Now we will switch to animal production and animal production for developing countries. With Steve, we've already seen how important biotechnological contributions can be to improve this agriculture. So I call on Tony Irvin, from ILRI, to speak on what biotechnology can bring and how is the situation of animal production in the third world.

 

Tony Irvin, International Livestock Research Institute
"Genomics and Livestock: Changing the Face of Animal Agriculture in the Third World"

Over 1 billion people live in absolute poverty, attempting to survive on less than US$1 per day and nearly 800 million (more than the combined populations of N. America and Europe combined) do not have enough to eat. Over 95% of these people live in developing countries. At the 1996 World Food Summit, the leaders of the 186 nations represented pledged to halve the number of people living in absolute poverty by the year 2015. Within a longer-term horizon, the world population is estimated to reach 10 billion by the year 2050 - a doubling in 55 years. Some 90% of this increase will be in developing countries. A doubling of world population will require a greater than doubling of food production if we are to meet new demands and make up existing deficiencies, particularly of livestock-derived products (milk, meat and eggs). Achieving these targets will place enormous pressures on food production, agricultural land and world economies. To meet the world's needs, it is estimated that food production in the next 25 years must equal that of the last 10,000years. Currently the world cultivates some 15 million square kilometres of land (about the land mass of South America). If we continue to rely on conventional farming techniques this area would need to increase to some 40 million square kilometres (equivalent to the whole of North and South America). Simply increasing land area is not enough. Already, most of the world's fertile lands are intensively cultivated and much over-exploited land is losing its fertility or, worse still, reverting to a severely impoverished state which can no longer support economically viable agriculture. If future food production is to be conducted in sustainable ways that will not destroy the environment nor deplete natural resources but, at the same time, meet the increased demands, there must be:
· Improved efficiency of food production
· Reduction in wastage of food products
· Introduction of new technologies.

Food production made a major advance in the developing world in the 1970s as a result of applying new technologies in plant genetics - this led to what became known as the Green Revolution. This initiative, coordinated by the Consultative Group on International Agricultural Research (CGIAR), resulted in development of improved varieties of wheat, rice and other cereals that were particularly suited to growth in small-holder farming systems in developing countries. This led to an enormous upturn in grain production bringing food security to millions of people in many countries. Current levels of grain production are now, in very broad terms, sufficient to meet global needs. Problems arise, however, due to difficulties of distribution between the developed and developing world and lack of purchasing power of poor people. Continued advances are, of course, still needed in crop production to meet the needs of growing populations but, over the next decades, there will be a disproportionate increase in the demand for livestock products as compared with crop products in order to meet the changing demands of peoples' diets (particularly driven by increasing urbanisation and rises in per capita income), and to address dietary deficiencies, particularly of women and children through provision of vital nutritional ingredients and micro-nutrients from animal sources.

Table 1 compares the expected changes in annual demand for meat (from cattle, pigs, sheep and poultry) and milk between developed and developing countries over a 20-year period to 2013. The implications, opportunities and challenges represented by these demands of the developing world are considered by some to be as great as those that accompanied the Green Revolution of the 1970s.

Table 1

	1993 (annual demand - metric tonnes)	2013 (annual demand - metric tonnes)	% increase
Developed countries
Meat	100	115	15
Milk	245	263	7
Developing countries
Meat	88	189	114
Milk	168	391	133

Source: Delgado et al (1999) "Livestock to 2020. The next Food Revolution". IFPRI/FAO/ILRI. Food agriculture and the environment. Discussion paper 28.

Over 90% of the livestock in developing countries are owned by small-holder farmers and, quite apart from their role as producers of food, livestock play critical roles in other ways which contribute to sustainable farming systems and to human welfare. They produce fibre (wool) and skins (leather); they provide draught power for tillage and carting; they convert poor quality feeds and crop residues into high value food products, and produce manure for fertilizer and nutrient cycling; they are a form of capital investment (particularly for landless people); and have important social values in many different societies. Livestock thus play a critical role in both the sustainability and intensification of crop production systems within small-holder systems, and without livestock to provide draught power and manure for fertiliser, crop production, in many such systems would be severely compromised. However, within these small-holder systems, livestock productivity and productive potential are seriously constrained by 3 main factors:
· Diseases which kill or debilitate animals
· Low genetic potential in terms of productivity
· Poor quality and/or inadequate supply of feeds

While major improvements to livestock productivity in developing countries can be achieved through more effective application of existing knowledge, biotechnology has the potential to provide new opportunities and options in terms of:
· Improved animal health (better vaccines, drugs and diagnostics) · Animal genetic improvement
· Improved nutrition through improved feeds

Livestock diseases kill millions of animals every year in the developing world, and millions more suffer from the debilitating effects of chronic disease. These are losses which the poor small-holder farmer can ill afford. The death of a dairy cow on a small-holder farm, for example, can mean the difference between subsistence survival or poverty and famine. Although the major pandemic diseases of livestock (e.g. rinderpest, foot and mouth disease, Newcastle disease) can be effectively controlled by vaccines in developed countries, their control is not always effective in developing countries where distribution channels, cold chains and vaccine affordability pose serious problems. Furthermore, there are a number of tropical diseases for which effective vaccines are still lacking. Examples are trypanosomosis, theileriosis and contagious bovine and caprine pleuropneumonias. Genomic techniques can be applied to identify and isolate highly specific antigens for development of improved vaccines against specific diseases. It can provide the means of making these vaccines strain-specific against target organisms, heat-stable for use in tropical climates, and it offers the prospect of these vaccines being more readily affordable by poor people. In the longer term, multi-valent vaccines will be developed that allow concurrent vaccination against several diseases. Gene sequencing may identify novel biochemical pathways within pathogenic organisms that can be targeted by specific customised drugs, or such pathways may be amenable to immunological attack through new vaccines. These highly targeted and specific approaches are in contrast, for example, to the use of chemicals to control disease vectors, such as ticks or tsetse flies, where the indiscriminate use of pesticides (particularly in the hands of unskilled and possibly illiterate farmers) can have serious environmental consequences.

Specific antigens, identified through gene sequencing and other approaches, are improving the accuracy of disease diagnosis, without which effective disease control and animal health improvement programmes are seriously compromised.

Long-term adaptation of indigenous livestock in developing countries to local climatic conditions and diseases has allowed the evolution of local breeds and strains of animals which are highly resistant to the endemic diseases, tolerant of local environmental conditions of heat and drought, and well adapted to survive on poor quality feeds. Adaptation to these conditions is as a result of genetic selection that is inherited by the offspring. Although livestock in these environments often appear, through Western eyes, to be malnourished and stunted and they may lack the genes for high milk or meat production, they are nonetheless exquisitely adapted through natural selection to survive and be productive in the absence of management intervention. Characterisation and identification of the markers linked to the unique genes present in such populations is now possible through the biotechnological approaches of molecular genetics and other techniques. For example, genetic markers associated with tolerance to bovine trypanosomosis have been identified in Ndama cattle from West Africa, and markers linked to resistance to haemonchosis (gastro-intestinal parasitism) have been identified in Red Maasai sheep in East Africa. Marker-assisted selection (MAS) programmes are now being applied to introgress these genetic traits into breeds with higher production potential. The application of MAS and other advanced genetic techniques, in order to combine the resistance genes of livestock from developing countries with the production genes of developed country livestock, could provide the optimal animals for both tropical and temperate environments. The alternative approach is to take the adapted livestock of the tropics and introgress into them the higher production genes that have been selected in temperate breeds. Genetic improvement approaches, however, presuppose that the management levels under which these livestock will be reared allow for optimal expression of improved traits.

While it is likely to be some time before specific genes linked to genetic markers can be identified in livestock, and the genetic manipulations currently applied to micro-organisms and plants can be applied in a practical way in animals at the farm level, genetic analysis and gene sequencing of the major domestic species will allow identification of molecular and biochemical mechanisms and pathways which are responsible for specific physiological traits or disease resistance. This understanding will allow us, for example, to understand disease resistance mechanisms and develop new vaccines and drugs to control specific diseases. Selection of animals on the basis of genotypic rather than phenotypic markers will allow improved cross-breeding programmes to be undertaken and genetic improvement to advance more rapidly.

It is vital that the unique genetic pool of indigenous livestock breeds (and of wildlife) that exists in many developing countries is conserved and utilised as appropriate, so that valuable genetic material is not lost through injudicious cross breeding or simply through neglect. A major international programme through the International Livestock Research Institute (ILRI), the Food and Agriculture Organisation (FAO) and similar organisations is seeking to identify and conserve key populations and breeds, and preserve this rich bio-diversity for future generations, both for the benefit of the countries concerned and of mankind as a whole.

While health and genetic constraints are major impediments to improving livestock productivity in developing countries, nutritional constraints (in terms of feed quantity and quality) are probably the most important of all. Most small-holder farmers cannot afford, or do not have access to, quality feeds to allow animals to achieve their full production potential. In such cases livestock have evolved to subsist on poor quality grazing or crop residues and wastes. Such feeds are often deficient in energy and key nutrients. Thus animals are being required to be productive on diets that would not even allow survival of Western breeds let alone additional output in terms of production. Biotechnology can be applied, however, to enhance the feed quality of plant residues on which many livestock are fed. The genetic manipulation of factors such as leaf/stem ratio and "stay-green" traits can greatly enhance the nutritional value, for livestock, of crops such as maize, sorghum and millet, the residues of which form a major component of the diet of cattle and small ruminants in many small-holder systems. In the longer term, there are good prospects of manipulating the rumen micro-flora, which are responsible for metabolising feed in ruminant species, to break down anti-nutritive factors or degrade fibre and lignin, thus increasing the nutritive value of poor quality feeds such as straws or potentially toxic feeds such as certain legumes (high in protein). Furthermore, it is likely that there are genes amongst the rumen micro-flora which control novel biochemical pathways that could have potential bio-medical or commercial value.

The international community is already aware of the potential value for human medicine of tropical plants, and bio-prospecting for novel pharmaceutical and biological agents is increasing rapidly. On the livestock side, considerable efforts are now going into exploring the rumen micro-flora and into identifying the factors in blood-sucking arthropods, such as ticks, to identify those which can suppress or activate normal host responses and allow the ticks to continue feeding. Good progress is being made towards identifying some such factors that can suppress allergic responses and could have a role in treating human conditions such as asthma.

ILRI is the only institute with a global mandate for livestock research. It is applying modern molecular and genetic techniques in animal health, genetics and nutrition to address livestock problems in developing countries and, in this capacity, is uniquely placed to provide the link between the Advanced Research Institutes of the developed world and the National Agricultural Research Services of the developing world, responsible for introducing and implementing the new technologies that will enhance food production. ILRI also has an important role in transfer of technologies and in training, so that the new technologies can be made available to, and applied by, scientists in developing countries. Current livestock production methods are unlikely to be able to meet the increased demands for food production, and new technologies are required to provide new options and innovative ways of increasing both crop and livestock production. The enormous progress made in recent years in biotechnological research now offers us the tools to tackle these challenges. The international community, through the CGIAR and similar organisations, can once again take the lead in applying science towards a revolutionary solution to the problem of food production in the developing world. The potential to develop and apply the tools of modern biotechnology and take these from the world's advanced research laboratories into the farms of the small-holder farmers in poor countries, heralds the start of a Gene Revolution which could massively increase food production and address the problems of food security faced by millions of impoverished people.

 

Susan Mayer, Genewatch UK
"How Safe is Safe: Biotechnology and Risk Assessment"

Thanks very much for inviting me to speak today.

I think there can be little doubt among any of us that there is a dispute going on about the safety of genetically modified crops and food. And the reassurances that come from industry and regulators, that the GM foods and crops that we are growing and eating now is safe and those in the future will be because of the regulations we have in place. These arguments simply aren't accepted by large sectors of society, both the U.K. and the rest of Europe and increasingly, I think, in the rest of the world. At the bottom of this lies a dispute, a controversy really over what a safety assessment involves, on what it's scope and what its focus should be. And that's what I want to look at this morning. Because unless we understand this dispute, this controversy, we're going to remain locked in a very unproductive situation, a highly polarized fight, if you like, over genetically modified foods and crops.

I'm going to look at each one of those in turn. First of all, we'll look at precision and predictability. I am going to compare two statements as we look at this. If we look at the first one of those, which comes from Monsanto, who emphasize and say, "This more precise science allows plant breeders to develop crops with specific beneficial traits and without undesirable traits…" If we compare that with an alternative view from a geneticist, who emphasizes the unpredictability in the long term…"With genetic manipulation, there's a huge new evolutionary risk and what's been proved safe today may change into something different tomorrow."

But secondly, there's a controversy over the quality of information available to regulate us. So on the one hand, we have commentators saying things like, "Nothing has escaped, got out of control and done harm. This technology comes to us tested and regulated as none before." But on the other hand, we have other, such as Erik Millstone and Tim Lang questioning that evidence…"The value of that [safety] assurance is, however, undermined by the poverty of evidence on which it is based."

And even thirdly, with its potential benefits on whether this will improve our quality of life. On the one hand, we'd have a view -this is from Jack Cunningham, who is a U.K. politician - the "Genetics of science can give us potentially huge gains for our well being. We can make peoples''lives better, improve their health, stop pesticides." But on the other hand, we have a different view. This is from Andrew Simms, "We feel that instead of improving lives, GM foods could strengthen the very market forces that leave the poor poorer and make the rich richer."

But it's the fourth area, the boundaries of the risk assessment, the boundaries of safety, where I think things have kind of come to a head, where all these things come together. And it's that which I am going to focus in on now - the boundaries of the risk assessment - for the rest of my talk. And the official focus of risk assessment that comes out in a regulatory framework, is on the technical dimensions - the genetic modification itself. But, not only the technical issues will actually affect what the final outcome will be. Whether the technology will prove to be safe or harmful in the long-run. Because there are two other things, agricultural and socio-economic issues that will impinge on the outcome. I'm going to go through each of these areas in turn: The technical, the agricultural and the socio-economic and show why a more rigorous approach to risk assessment, a more scientific approach to risk assessment has to actually encompass these dimensions. When they're discounted, as they are at the moment in official versions of safety, that simply isn't safe enough and it is not broadly accepted as being so.

So, first of all, I'm going to examine the technical dimensions to it and emphasize some of the technical issues, which means there are some questions to answer about safety in the long term or what the effects might be.

The first of these is obviously that genes are being transferred between unrelated species. But also that, although we've heard that this is a precise technology, that you can choose the type of characteristics you're going to investigate, the actual process in one of random integration with an unpredictable number of genes being integrated and often being reversed in the actual process. In addition to that, we have a situation where over very short periods of time, selected organisms, those best performing organisms in a laboratory are tested on a small scale before being released on a potentially enormous scale. This is a very compressed time period, if you like, in terms of environmental health testing. Of coarse there are pressures in time, from getting financial rewards from the investments in the technology. But parallel with this, we've got to remember that these aren't trivial changes that are being made to organisms. They're quite dramatic changes to how the organism will behave. So we make a crop resist a chemical, which would have killed it previously. We make it toxic to an insect that would have eaten it without harm before or we make it resistant to a disease, which would have previously killed it. And also we see, hidden below here, another dimension. That is, the same genetic modification is being used not only in one species, but across a whole variety of different species. So, in oils, maize, cotton, soybeans, so on and so forth, the same changes are being made. But you may say, okay, these are differences. We can perhaps agree on those. Are they relevant? Are they really important? Do they matter? And isn't it the case that we have experience with natural and other systems to be competent. Well, I just want to carry on now and just say - staying with the technical issues - why these things are relevant and important.

First of all, to turn to natural gene transfer between species, which I think is different. It take over much long time periods and organisms taken out of context and multiplied up. When I talk about natural gene transfer, I'm referring to both agro-bacterium, perhaps mediated methods in the natural environment, but also the increasing evidence we're seeing from studies of genomics that we have evidence, even in ourselves and lots of higher organisms have genetic material, which probably came from other species, like viruses for example. So it is different, but also, traditional breeding can't hope to replicate the scope and form of change that is offered by genetic modification. These things, together with the changes, mean that we can quite logically expect there to be effects, ecologically, bio-chemically and physiologically that have to be addressed. Furthermore, what is going to be worryingly hidden by the bottom of the podium is perhaps one of the most important messages, is that we have limited experience with this new technology. Our knowledge is actually limited. It isn't complete. Neither about the technology itself nor the organisms it's going to be used in. And so, predictions are going to be uncertain. These technical issues I've referred to are, to more or less extent, with lesser and greater rigor, addressed in quite a lot of environmental and food safety assessments. But I want to go on now and just outline the dimensions that aren't really covered even though they will influence the effects on the environment and on food safety.

Firstly, I'm going to move on to agricultural issues. Some of the relevant things there include, firstly, patenting. Alongside and parallel to the introduction of genetic modification, we now have patents on crops, which is forcing changing relationships between farmers and seed companies, and it may also in the long run, through the privatization of genetic material, obstruct plant breeding in the public interest. We're also seeing seed production being dominated by fewer and fewer companies, raising questions about food security in the long run. Thirdly, seeing the potential for changes to bio-diversity, through altered agricultural practices, changing patents on pesticide use, changing patents on land use. And again, we have this situation where we're relying on the same gene across many species, which may make crop vulnerable to failure in the long run. And that's not just on a local scale. It's on a regional, national, global scale because the same kind of changes are not being used in just one country. They're being used globally.

And finally, another area agricultural issue, which will affect the outcome is that although safety measures are going to be put into place and farmers are going to be asked to follow the rules, they may be unable or unwilling to follow them. Not out of badness, but simply because the practicalities of farming make life quite difficult sometimes. So, having isolation distances to reduce gene flow may be difficult. Cleaning your vehicles out. They're important things which may mean that safety rules aren't being followed. But by and large, with the exception of efforts now in Europe, very welcomed to start to address some of the biodiversity issues of altered agricultural practices, these areas are discounted really in the risks assessements.

But now, let's move on to the other area of socio-economic issues, where we're also seeing situations that are being ignored. I'm going to look at four here, and the first of those is that there are alternatives. Alternative options exist in terms of producing food and growing crops, which aren't being explored. There's no comparative safety evaluation. Because of coarse, we don't have absolute safety. There's no zero risk. But we can make comparative evaluations and that isn't taking place. Could we grow crops more sustainably by developing organic and IPM more. When we look at things like rice with vitamin A and iron, although I think those kinds of developments are very welcome and seem to have a real benefit, it's also not the case that it's the rice which is at fault for not having enough vitamin A and iron, it's simply because people don't have enough money to buy fruit and vegetables. So there are alternative, which we must weight up, compare and contrast. But also, as a part of neglecting alternative is that we don't rigorously look and examine the actual benefits. What are the benefits? Are they real? We should critically evaluate them. I think that is partly, what also doesn't take place in the risk assessment, is a look at the justification for taking risks. It's not openly addressed. I really think that what has happened is in the evolution of the regulatory framework, this being taken for granted assumption, a very unscientific, uncritical assumption, that GM crops, GM foods will bring benefit. That they will be beneficial. I don't think that that is a very rigorous way of looking and trying to find the best option in the long run. Perhaps where the most obvious, the most great omission has taken place is that there has not been the allowing of choice and influence in the marketplace. And that's because, labeling, where it exists has been restricted to situations where there's altered chemistry. Where there's altered DNA or protein in the final food, meaning that many derivatives from many GM crops simply go unlabelled, like the oil from GM soybeans. Unfortunately, this isn't, in a plural society, where there's a new technology, which raises ethical issues, questions about environmental safety, equity, it's not an acceptable basis for allowing choice. I think you can see that by thinking about - if I held up two eggs now, one of which was a free range egg and the other came from an intensively farmed chicken - and said to you that you can't have these labeled. These are chemically the same. There's no proven health reason why one is better or worse, so they can't be labeled. That would not be perceived, that would not be accepted as an acceptable situation. People want to make choices for other reason than on the final chemistry of the product.

I think we can see now that the narrowing of the boundaries of the risk assessment that's taken place - this lack of comprehensiveness of risk assessment - has had some extremely serious consequences. Not only do people quite rightly consider that relevant parameters haven't been included and therefore the pronouncements of safety remain disputable. Also what happened is that democratic traditions have come under threat. We live in a market place. Yet people haven't been allowed the right to work out and make choice as citizens inside that marketplace. That's not necessarily a safe society to encourage developing in the future.

But also there's the situation where other options are being developed in the interest of a particular industry. There are other business opportunities and other fields, which are being potentially neglected because of the narrowing of the boundaries of the risk assessment. And also, we're seeing that by characterize as much as possible, we see in the rhetoric that GM is really very little different from traditional breeding in technical terms. By narrowing the boundaries, what we're tending to do is rather than encouraging scientific inquiry, ironically we're trying to, or tending to, suppress scientific inquiry by not admitting that these other issues are relevant and will affect the outcome. We're not looking into them.

As a result of the narrowing the boundaries of the risk assessment, and looking at the results of what has taken place as a result of that, we've actually seen the first evidence of direct harm from GM crops and foods. And that really is that the biotechnology industry has come to the verge of collapse. Certainly, it is the agricultural biotechnology industry, certainly in the UK and Europe and it looks very wobbly elsewhere. An interestingly, that's the industry developing them. And yet I believe, that if these risks had been evaluated, that was a consequence that never was never incorporated in the risk assessment. And yet, of coarse it's extremely relevant, looking at those industries, the people that work for them and so on and so forth.

Finally, where do we go from here. How can we take some lessons forward from what's gone on; The controversy, which has taken place here and is growing elsewhere. Can we come to some agreement on what would be an acceptable definition of 'safe'. I think there are three things that we need to do. Three pre-requisites if you like. Firstly, we need quite urgently to have a public involvement in a debate about the future of agriculture and food. To have an agreement on what would fulfil our aspirations, in environmental and health terms, in sustainable agricultural terms in the future. Secondly, we also need to recognize that if we're going to have a rigorous approach, we also going to need a broader base to the risk assessment of GM crops. And finally and perhaps crucially, the one thing I don't think that GM foods will go anywhere, unless it's accepted, is that unless there is the recognition of the right of people to choose, based on the method of production, this will be seen as an imposition and will be fought. I would predict, tooth and nail, whatever innovations tend to come along and that may be a very, very damaging state of affairs. Thank you.

 

Professor Marc van Montagu

Thank you very much for summarizing your perceptions on risk. Now we go on again with animal biotechnology and ask George Hershbach from Pharma to talk on new biopharmaceuticals.

 

George Hersbach, Pharming Netherlands
"Animal Biotechnology: New Biopharmaceutical for Critital Diseases"

I am very honored to have the opportunity to speak to you today and I would like to change the application of biotechnology by focusing on human health care. In particular, I would like to present to you the power of what I believe is a very promising and strong technology, which is animal biotechnology and the power of developing new biopharmaceuticals for diseases that today can not yet be treated. Let me go a little wider and look at the opportunities for health care and biotechnology. There are more than 100 products from biotechnology on the market, treating diseases that 20-25 years ago could not be treated yet. The in-depth research of the Human Genome Project has helped us tremendously. 20-30 years ago, pharmaceuticals were simple chemical entities, not easy to make at all, but certainly not human elements. The Human Genome Project brought us to understanding the genetic make-up of the human body. We far better understand the causes of diseases, particularly when certain people develop a disease as a result of a genetic disorder. It can be as simple as a human body that is hampered when trying to produce the correct amount of a certain essential factor, as a result of which the human being gets diseased. There are, based on all that knowledge, more than 700 of these novel biopharmaceuticals, that I have been able to find, currently in clinical trials for various clinical diseases.

What are the challenges in the heath care arena? First, if you want to treat complicated diseases it is very unlikely that you can do that with simple products. Biotechnology has become an essential tool to try and address those diseases. Furthermore, the requirements for purity, in particular, by using a biopharmaceutical perentirally as an injection has become more stringent. Last but not least, traditional production methods are not sufficient anymore. We need advance technologies to make those pharmaceuticals for those critical diseases.

Here is where I believe animal biotechnology comes in-- making biopharmaceuticals in milk. Why in milk? It is renewable. You can milk an animal for a long time. The potential here, when compared to traditional biotechnology, fermentation from microorganisms, or from natural sources, such as human blood, are that, first and foremost, it has a broad applicability. It can make complex products to treat those critical diseases. We have experience that the safety of products coming from milk is significantly higher as opposed to, for instance, human blood. Using human blood as a source for making pharmaceuticals for treating critical diseases, you run the risk of contamination of viruses such as HIV or Hepatitis. Milk does not have that problem. Large animals have a large production capacity for these types of products. Last but not least, especially for cow's milk, you are talking about a production system with relatively low costs. You do not need a multi-million dollar investment. This job can be done with a relatively simple, though up-graded, and very clean farm facility.

What we aim for here is addressing a mathematical need-- that so far has not been met-- true production of these very advanced biopharmaceuticals in milk. What I would like to do is explain a little more about the technology and give you clear examples of products that are being developed to treat critical diseases. To generate animals capable of producing very valuable biopharmaceuticals in their milk, it all starts with the genetic information that controls the production of the biopharmaceutical of choice. Together with an element that directs the production specifically to the mammary glands, that genetic information is inserted into the one cellular stadium, an egg, of the animal of choice. That egg is cultured in the laboratory to an embryo and the embryo is transferred to a recipient mother animal. After the gestation period, you have the birth of a genetically modified animal, a small animal that has been taught to make the biopharmaceutical in her milk. Obviously, by doing it in rabbits, the process is quicker, but they make less milk. Our choice is to let the market determine the species of choice. If it is a large market, with a large amount of biopharmaceutical required, we choose cow's milk. If it is a small market, we go to smaller animals such as rabbits. As soon as you have such an animal you can generate a colony. A large number of female animals, and we have specific manners to do that, that are able to produce those biopharmaceuticals. Those animals you can milk on an ongoing basis for quite a long time. You can process the milk, purify the products and you end up with the active ingredient basis for the ultimate medicine. It can either be oral, which is easy for milk, or it can be a topical product or a perentiral product. The two examples I will give are perentiral, which means that they are administered to human beings as an injection.

There are clear timeline differences. I already told you that rabbits are a lot quicker than cows. However, we have taken a novel technology into use by generating cows capable of generating those biopharmaceuticals. This is the technology of nuclear transfer, often loosely referred to as animal cloning. That is not to make a bunch of identical animals. That is not the purpose. The purpose is to shorten timelines-- to reduce time to market. To make those critical and valuable pharmaceuticals available to the patients who are in desperate need. Let me move to some products. I will present the medical needs that have been identified. First and foremost, genetic disorders-a great opportunity for animal biotechnology. Infectious diseases, tissue and bone damage, cardiovascular disease, and surgical procedures. As you can see, in each of these areas there are one or more indications already under development. I would like to focus today on two critical diseases-Pompas and hereditary endudema. The latter is an uncontrolled immunoreaction. People suffering from this genetic disorder miss an essential element in their human blood and through outside influences, like hitting your body, burning or a bee-sting, these people develop huge swellings. If you have a bee-sting on your neck you might actually suffocate and die. The only thing these people miss is an element called Human C-1 ascurase inhibitor, a complex compound that today comes from human blood. There are more patients in the Western world than we can collect for from human blood, let alone the problems associated with human blood that I have already referred to. For that reason, animal milk is an ideal basis for making these products and this product in particular. You may not be surprised that we are working with the Netherlands Red Cross in Amsterdam to develop this.

We are currently in a pre-clinical stage. Later this year, we will start the first human clinical trials. We are very confident since we know what the product is like and because there is already a limited product available from human blood. We have received from the U.S. FDA orphan drug destinations for this product and this application. That gives us protection for seven years market exclusivity in the U.S. I am very happy that there is a similar law under development here in Europe. We can get similar protection. This investment in these limited markets can only be justified if you have the opportunity to get a return. Otherwise, we would not be able to find investors interested in these types of indications.

The next product is one of the leading products of my company. It is targeted at the treatment of Pompas's disease-- another critical genetic disorder. It is lethal, hereditary and muscle related. People suffering from this disease miss the compound human alpha glucosidase. They do not have enough or they have none at all, a result of which is that they store the carbohydrates that they eat. They do not convert it all to energy, but they store it in their muscle cells. This results in the muscles disfunctioning and the patient ends up in a wheelchair, with respiratory and heart problems. More often than not, they die from respiratory failure. For this disease, there is no product available. Infants that are diagnosed with the disease normally die three or four months after diagnosis. They have a mean survival rate of two or three months after diagnosis. I am happy to say that in our clinical developments, we have a number of infants and actually all of the infants that have entered are still alive. They have been living since their inclusion a year ago. This is a significant increase in survival rates. We can also see that these children develop the milestones, muscles and develop better than normal Pompas patients, but not like normal children. They do survive and they do relatively well. We are also currently treating elderly patients between the ages of 10-25. We hope to continue to do that. We have just initiated a multi-center trial. Here you can see that a compound that no one has been able to make in the last 15-20 years, since we know what causes Pompas's disease. Animal biotechnology, making these products in milk, has a significant potential. Again, an orphan drug destination has been given to us by the U.S. FDA and we hope to be able to file for registration later this year.

There are many more products under development. I have given a simple overview. But I do want to point out to you that there is an exclusive relationship between my company Pharming and the American Red Cross. Why is that? I have already mentioned the safety issues associated with making biopharmaceuticals from human blood to treat, for instance, hemophilia. The problems with that are clear and the U.S. Red Cross has developed over the last 15 years. The only alternative that they could find to make these compounds was to make them in animal milk. Once they were successful, they decided that they could not do this on their own, but they needed to go to a specialist in the area to make sure that the time to market would be as short as possible. Needless to say, we are proud that we have been selected as the American Red Cross partner in this area.

It is important in any biotechnology, but also in this area, to be able to patent the technology and products. We have been able to do that throughout the world, as you can see. In most of the jurisdictions where I believe we need them. Let me say a few words about the company and the commercial side. We are a biotech biopharmaceutical company that started as a spin-off of the Netherlands' oldest university, Leiden University, about 11 years ago. We grew nationally and internationally, acquiring a small company in Finland and establishing subsidiaries in Belgium and the U.S. That is where we currently are - in nine locations in these four countries. We employ 190 people, who all work very hard to make these biopharmaceuticals and bring them to the market in the shortest possible time. We have been financed over the years through grants from governments, as well as equity. We are now a stock quoted company on both the ESDAQ, the European NASDAQ equivalent, as well as in Amsterdam.

Let me draw some conclusions. First and foremost, animal biotechnology-- making biopharmaceuticals in milk-- offers the opportunity to produce products with improved properties and clearly, if you compare it to human blood, with improved availability. Large quantities can be made. Therefore all the patients suffering from diseases can be treated. We have already shown that we can produce products with an effectiveness that otherwise could not be made. The safety is there as well. That can not be said for all blood products. The timelines for these developments, if I just point out to you that we started with Pompas' disease in 1995 and we will most likely have it on the market next year, are significantly reduced. The normal timeline of ten years to market, we can most likely reduce to 5-6 years. There are very competitive manufacturing costs, needless to say, if you make things in milk. Particularly cow's milk is relatively inexpensive as compared to other technologies. Last but not least, reduced capital investments. Let me finish with a quote from Art Levinson, "In the next quarter of a century, we will see a quantum leap in medical research. There is a distinct possibility that even within the next ten years there will be cure's for Parkinson's disease, hemophilia, AIDS and cancer." I believe that producing biopharmaceuticals in milk using animal biotechnology will be an extremely important tool to develop these biopharmaceuticals to develop therapies to treat diseases that currently can not be treated.

 

Professor Marc van Montagu

Thank you very much. We're exactly on time. I would like to ask the speakers to come to the table now, so that we can start the discussion part, in which I hope you will actively participate. Who would like to start while the participant are moving into place? Remember, we're also on internet, so that people from outside can follow this.

 

Question and Answer Session
with a Panel of Morning Speakers

Question for Steve Tanksley: In the process of providing solutions for societal problems, environmental problems, I think the time factor is very important and I also think that it is the success factor. Related to this, I have two questions: 1) Can you estimate the acceleration factor of the domestication with biotechnological aids as compared to one without, and 2) What is the absolute requirement in time spans for domestication, using biotechnology aids?

Answer from Steve Tanksley: I'll try to answer your question. I think both the answers will be theoretical because we don't even now know how long the domestication process took originally, since that was thousands of years ago. I have to answer it, understanding that we don't know what the original time was. Also to point out that the idea of accelerated domestication is something that's also theoretical. But taking a best case scenario, one could identify the set of genes required, to have say produce a large edible fruit and simultaneously remove any toxic compounds, one could theoretically transform a plant and that's a really short period of time. I guess the answer is it would probably be much faster that the original domestication, but until one actually did the experiment, we wouldn't actually know how many genes would be required nor how long it would actually take.

Question continues: Is it years or ten years or fifty years? Can you roughly estimate?

Answer from Steve Tanksley: Well, if we had the genes in hands to transform a plant from a non-edible type to an edible type, the transformation experiment itself is quite short. We're talking about a matter of a few years. Some transformation technologies are already developed. In that narrow context, it would be a very short period of time.

Next question: I have a question for Mr. Hersbach. In the animal biotechnology that Pharming is doing, I believe there is a rather large portion of DNA, human DNA, that is inserted into each cell of the recipient organism. My question is, In this portion of DNA, there are remnants of virus infections that the human donor has had?

Answer from George Hersback: Indeed you're right. We insert human DNA, or I should say copied human DNA, into the single cell, into the egg of the animal. You have to understand that this is really synthetic, or if you will, artificial DNA. It's copied from the human sequence. So the likelihood that there are viruses in there is absolutely nil because it's made in the laboratory.

Question continues: I don't mean actual virus, but pro-virus material, which are remnants that are incorporated in the DNA portion. I have inquired into this and I've heard that this is a possibility. Furthermore, it is a possibility that is small, but nonetheless existent that this pro-virus material recombines with animal viruses, which is able to infect human beings.

Answer from George Hersbach: That is assuming that pro-virus is inserted or present in the construct. I don't think it is and I think we have a significantly proved that it isn't there because it is really copied DNA. It is made in a laboratory.

Question continues: If you copy DNA, you copy the pro-virus material as well. I think that if you produce in this way a solution for sick people that are in the amount of 5,000 or 10,000 in the whole world, and introducing a risk like this, which is small but nonetheless existent, for the whole world population. I believe it's a rather big risk to take.

Answer from George Hersbach: I understand your concern and I respect your concern, but you have to understand that we are producing a product that we believe cannot be produced in any other way for treating these critical diseases. Indeed, we're focused, at least today, on those diseases that are caused by genetic disorders. These people could otherwise not be treated. I think the whole process of generating the animals, purifying the product, releasing the product and formulating the product, is done with the utmost care and quality control and insurance, which is normal for the pharmaceutical industry. It is certainly very normal for the pharmaceutical production done by biotechnological means. I believe that the risk associated, that you're alluding to in this type of technology, is not any different then any technology andcertainly not any biotech. means. I, nevertheless, think that given the level of quality control, given the type of tests that we are doing in every single step that we minimize that risk, in my opinion, that may be in existence.

Question continues: Do actually check for the presence of this pro-virus material?

Answer from George Hersbach: I wouldn't be able to tell you because I don't have a molecular biology background, but I would be more than happy to look into that.

Question from the cybercast audience: Is it true that genetically modified corn is not grown in developing countries?

Answer from Steve Tanksley: I'm not sure I have any better answer than you do (referring to Marc van Montague's comment on the definition of a developing country). I don't know the extent to which transgenic maize is grown in developing countries. Certainly, it is growing in Argentina and probably being grown in other parts of the world, but I don't know the specifics. It's not an area that I…..

Supporting answer from Marc van Montague: It's grown in China, but I don't know on what scale. (Prompted by Ismail Serageldin, he responds with) Fourteen percent of the transgenic acreage in Argentina. One to two percent for the rest of the developing counties.

Next question from the audience: I have a question for Mr. Eisen. You said in your speech that we are now slowly finding out what the web of life really looks like now when it comes to horizontal gene transfer. You also said that engineering in nature can be extremely precise. I think it is one of the critiques towards genetic engineering, that we lack a lot of knowledge still in the understanding of how this web of life and horizontal gene transfer is happening there. Also, seeing that it can be so extremely precise, we first need to know how this web of life works in life. How do the genomes work and why is it so exact. Our applications, these transgenic plants are really interfering with something we don't know enough about and we don't know what we're doing there. I would like you comment on that and I also have a question for Mr. Tanksley. What do you see as an option to guarantee to farmers that don't want to use GM plants. How do they keep that possibility. The problem of contamination is a severe problem for many people and it's associated with the treat to democracy, as it is perceived by many people. I would like to know if you have a view on how to solve that problem.

Answer from Jonathan Eisen: I think in terms of gene transfer, we definitely don't know an enormous amount about how it occurs and how often it occurs and exactly where it occurs in nature. We know that it is very common among certain organisms, in particular among organisms that grow near each other. In some cases, it looks like organisms can take up DNA from the soil or from the water so that they don't actually have to be in proximity to the organism that is the donor. It' correct that we don't know an enormous amount about exactly what's going on with gene transfer in nature. I would probably disagree that that necessarily means that we can't assess the safety and related issues of genetically modified organisms. Nevertheless, without having that complete knowledge of gene transfer in the wild. I think that because we have documented, it is generally agreed that gene transfer has been very common. That closely related species certainly are exchanging genes all the time, as well as distantly related species that genetic modification per say of organisms is not a totally new thing. It is not a fundamentally paradigm shift. And so that the individual organisms that are being modified, are the things you have to consider whether or not they are safe rather than the concept of modifying organisms. I don't know whether you would like to address that?

Answer from Steve Tanksley: Yes, I guess the one questions is about how does one assure that non-GMOs would be availble in a market where GMOs are sold and produced. I think the answer to that is one that is also the answer to the how do seed companies currently keep varieties separate, since different varieties have different out-crossing rates and varieties can cross-contaminate each other. Seed companies already have requirements on isolation differences between varieties when they're being produced for seed production. I think the applications of those same regulations would be the same for GMOs and non-GMOs to maintain purity, so people can buy non-GMOs if they wish.

Question continues: If I may add another question. The complaints that are coming from farmers now is that companies may do that, but in the field, contamination is happening. And the complaints from farmers now is that they want to work GMO free. This is impossible in the way this is going now. In a few years time, everything will be contaminated.

Rebuttal: I think that's only true if the farmer is propagating their own seed - collecting their own seed and replanting each year. I think the majority of the production taking place, is from seed which is obtained from normal seed outlets.

Question from the audience: I have a question for Susan Mayer. I understand I have to look for a new job as soon as possible if I follow your recommendations. I understand your questions, but I'm not sure whether I understand your recommendations and answers you give. You're putting forth the right questions, but I'm not sure whether I understood the answers. For example, you say, 'Can we come to some agreement on the safety?' and you gave three answers to that. And the first answer was, 'We need a public involvement about the future of agriculture and food'. The second is, 'We need to recognize the broad base of genetic engineering' and the answer you gave was, 'You have to recognize the right to choose'. Could you clarify to me how this relates to your question of 'Can we come to some agreement on safety?'

Answer from Susan Mayer: Yes. The first one to do with the debate on where we want agriculture to go is that when we come to evaluate safety, what we do is we normally make comparisons. So we say, for example, in the evaluation of environmental safety of GM crops that this GM crop, if we compare it to conventional agriculture, that's what happens in the UK at the moment, that it is as safe. It is no more dangerous. I think that yardstick, as a yardstick for safety, needs some discussion. A lot of people would argue that conventional agriculture, in terms of environmental protection, is not a very rigorous yardstick. So, that's what I mean. We need to debate what we want. What the goals are. What the yardstick should be for safety in the sense of weighing things up. If conventional agriculture is seen to be damaging and things don't weigh up in relation to other options, of coarse safety takes a different perspective.

To go on to the second one, the broadening of the base, what I was trying to describe there is that things, issues that will bare on final safety aren't actually being systematically addressed. So, let's take one of these issues that came up earlier about separation. Whether farmers can physically and will practically follow the rules. There might be refuges to reduce the likelihood of insect resistance. There isn't anywhere that I see any rigorous sensitivity analysis, for example, in terms of the risks over following or not in different ways. That's just one example, but in lots of ways, what are the issues around having seed market control by a few companies.

The last one, which you may find most puzzling, "What has choice got to do with safety?" I think we need to look at the world and safety is not just about whether I drink this glass of water and I don't drop down dead. Safety also has to do with a kind of security and our respect for other people - the kind of cohesion for our society, how our society operates in is sustainable. One of the thing we feel at the moment, and we live in a very plural society - you know, the different religions, the different races, the mixing - and we have to have respect for people's different wishes. We have to try to find ways to accommodate that because that will be the most sustainable way forward for society. We don't want to create unnecessary divisions. I think the only way that we will do that with GM foods at the moment is if we allow that element of choice. So we allow people to exercise their extremely deeply held convictions and ethics about the concerns of gene transfer. That they can al least have some influence in their own personal behavior, even if it doesn't affect anything else. That they can keep their own integrity. That's a dimension of social safety that we need to address, as well as these little technical dimensions that we are perhaps more familiar with thinking about.

Next question: My question is to several of the panelists. I've heard so many interesting new aspects of biotechnology that I would like to hear from several of you, with respect to the third world, what are the benefits of biotechnology in the near future; near, medium-term and long-term future. Specifically, it was brought up that 80 percent of farming is in the hands of small farm holders and I would like to know how, biotechnology is applied by the small farm holder in the developing world.

Answer from Chris Somerville: I think that the rice example that I cited this morning, in which a new rice variety with a high pro-vitamin A content is going to be distributed by the international rice institute free of charge. One of the attractive things about the technology is that in contrast to the first green revolution which required input, the input in this era is knowledge input. Once that investment has been made, it doesn't impose additional cost. So in fact, I think it's very beneficial to subsistence farmers in the developing world.

Supporting answer from Marc van Montague: I think this morning's session has also pointed out how all the genetic tools can now bring in new crops in circulation that in this century, until now by breeding, no new plant has been introduced as a food crop. At the moment, with all the rapid sequencing and the databank available, genetic maps will be done from a lot of plants that are typically poor farmers' crops. The crops of the subsistence farmers about which until now, no scientist could be interested because he would never have received the ground because the task was so immense. You could never convince a panel that you could achieve something there. Now we have the tools so that we can do it. And quite some universities and organizations are planning it. I think it will be taken up very rapidly. I think we'll see a lot of success there.

Question from the audience: I have a question to the plant speakers of this morning. If we're discussing risk, we need to balance the risk of one strategy against the risk of another strategy. I think, there is now, ample experience in the United States with insect resistance or herbicide resistance in plants. Is it possible to draw any conclusion on the impact of the use of these plants on reduction of insecticides or herbicides?

Answer from Chris Somerville: Last year, the use of BT cotton resulted in the elimination of the use of 200 million pounds of insecticides.

Comment from the audience: It is just a brief intervention, more than a question. As a biotechnologist, I want respond to the first person that made comments about DNA sequence copying and so on. I can imagine that before copying a sequence of DNA and inserting it into a cell, the company or scientist in question would have entirely sequenced the fragment of DNA and found out what each individual gene does, and what it is and whether there are any pro-viruses. I can imagine that before any DNA fragment is introduced, it will have undergone complete sequencing beforehand.

Question from the audience: Are you aware of the sequencing of the genome of the major pro-plant. You said also that the sequencing and the information about DNA sequencing is essential in the characterization of a certain species. How is this information controlled? Who owns this information? How will small plant breeders be able to use this information? Is there a danger that big seed companies have control over this information and how is sequencing information going to influence the future of molecular breeding.

Answer from Jonathan Eisen: If I said otherwise, I didn't mean to imply that most microbial genomes have been done. A couple have been done. If you look at diversity of microbes, than we have in fact very poorly sampled the diversity of microbes. In terms of plant genomes, there are a large number of plant genome projects underway, including the genetic model plant "Arabadopsis Thaliana", which is not a crop plant, but it is considered a model for a lot of experimental work in plants and that should be completed within a year - the complete genome of Arabadopsis. As for crop plant, there are genome sequencing projects for rice, for corn, for a lot of other crops, as well as expresses sequence tag projects for a lot of crop genomes. As to sharing the data, places like TIGR are funded by government grants and we're required to release all of our data at a certain point to the world. Than we publish papers on the genome and prior to that, release most of the data and then eventually release all of the data to make it publicly available. There are plenty of projects being done at private corporations that don't always release all of the data. So, if you're interested in a particular organism, you can't really rely on the private corporations to release that data. We need a public effort for getting access to that data. There are patent issues where certain companies make patents on genes and gene information for some of those crops that they hope to use for various biotech. and related issues, and that's a very separate issue. I think, in the long run, those have been very beneficial to research and development of products related to those organisms. So I think it prevents use of those genes by other companies for profit. But in the long run, most of that data is also released, to be used by scientists and other people.

Chris Somerville: I misspoke when I was asked earlier about the reduction of pesticide use. The total amount of insecticide used on field crops last years was 200 million pounds. I don't have the actual numbers for what the reduction was, but about 65 percent of that was used on cotton and between 50 and 60 percent of the cotton was transgenic. So you can get a rough estimate of the decrease in use.

George Hersbach: (Rebuttal to the comment/intervention from the audience) Yes, if I may, it was based on the first question about these pro-viruses and the audience person added some information to that. Another piece of information that may be of importance is that by assessing risk, if any, is the fact that the production is actually done in the milk as you know. And, there is no transfer of viruses known to milk. Milk, in that respect, is very, very safe. Even if a mother animal - in our case that isn't the case, but - even if the mother animal is infected or has some kind of disease that is not transmitted to the offspring through the milk. In that respect, it's another argument in favor of the safety of milk and producing biopharmaceuticals in milk.

Marc van Montague: Coming back to problem on the question of patents, we turn to a question posed by the cybercast.

Cybercast question: Is it true that biotechnology inventions can be patented?

Marc van Montague: That means that public opinion can be very sensitive to what can be patented and not. If someone from the panel, who has experience with industry, would like to answer that.

Answer from George Poste: The answer, simply put is, yes. Why diversity, inventions, biotechnology are subject to patent protection, whether it be a gene, a product from that gene or a process for making that particular protein. So you can apply patents at multiple levels. I think there's a lot of misinformation that is circulating about what intellectual property provisions constitute. In biotechnology, this word ownership get contaminated in the debate. There's no such thing as ownership of a gene. The only thing that intellectual property confers is the right to utilize that commercially in a particular setting. If you have a patent on a human gene, then you don't own the human gene in any individual. You have a commercial opportunity to utilize that gene whether as a diagnostic, as a therapeutic or as a vaccine. I think, where there is legitimate ground for concern in the patenting arena, and it often happens when the technology is new, the patent office itself, whether it be in Europe or North America, may not be familiar with that technology and therefore grant overly broad patents. I think we've seen several examples of that in biotechnology where we are actually seeing overly broad patent granted, which I think can be legitimately criticized as restraining research in the arena. But I think where patents are very carefully drawn, that they actually prescribe a specific utility. Than I think time has taught us that that is in fact the only commercial incentive that provides protection for the investor, who invest in these daunting levels of 600 million U.S. dollars that is now needed to produce a new pharmaceutical. And without a measure of intellectual property protection no one in the investment community is going to step up to make that level of investment.

Question from the audience: My question is for Tony Irvin. It relates to the biosafety discussions that we have here in Europe and the freedom of choice discussion we have here in Europe. Also seeing of coarse, the social safety issue occurring. My question to you is, 'Do you think that this discussion, and the way it's going on here in Europe, helps the freedom of choice in developing countries?'

Answer from Tony Irvin: I think the important thing is that the developing countries are sufficiently informed. I think we don't perhaps have sufficient representation here today from the developing world. There are very significant developments in the field of biotechnology in many, many developing countries. Increasingly emphasizing the training, the importance and needs. One of the difficulties across developing countries is that they don't have the financial backing that is present in the developed world to pursue these technologies and in many cases, they have to rely on the knowledge that is being passes down to them. I think it's extremely important to give those people empowerment through training, through involvement in the technologies. Not just to attract people out of developing countries to work in the States and Europe. But for those people, to give them the empowerment to apply this technology in their own countries while addressing some of the problems that are faced in those countries. I simply do not believe that by improving management or applying existing knowledge is going to be sufficient to meet the enormous demand of food that the increase in population is demanding.

Marc van Montague: Since the reaction in Europe is mostly political, it has an enormous impact on developing countries. We also take decisions at the political base. Even in Mexico, the nice results that are obtained there for aluminum tolerant plant cannot be applied because the government say that Europe says that it's dangerous and we're too close to the United States to believe what the United States said. So we don't allow you to use your own invention because of what Europe is doing. We see that same at the moment in Thailand they are questioning and even in China they are very sensitive to what Europe says because sometimes in a political situation this could be used. So indeed, the decisions that we are making and the education that still has to come in Europe has an enormous influence on the applications in developing counties. I think at the moment that that is even more important than science.

Question from the audience: I have a question for Mr. Hersbach on your earlier remark about the safety of milk as a medium with respect to viruses. Am I right in believing that aids can in fact be transmitted from mother to child through the mother milk?

Answer from George Hersbach: I don't know to be honest with you, but I don't think so.

Remark from the audience (from upcoming chairperson, Eric Claassen): I have to remarks about this discussion. One is that we're not talking about normal viruses here. We're talking about retro-viruses like aids. And the essence of retro-viruses is that they integrate into the mammalian DNA. Therefore, essentially although viruses per say have difficulties being transmitted into the milk, of coarse retro-viruses have not because they integrate into the mammalian DNA, and as we all know, the farmers are paid also on the cell count of the level. Meaning that in all the milk we consume, mammalian cells are present, albeit to a low level, but the are present. Therefore, by definition, pro-viruses and retro-viruses might be present in those mammalian cells. Now this doesn't say anything about the issues discussed before about decreased safety. It's a well-known fact that if you synthesize C-DNA for insertion into a transgenic animal, than the sequences are always synthetic, thereby, matched with existing databases, also matched for all known retro-viral sequences. That is an essential and applied safety step, which is now in place. So we have two discussions here: One is non-retroviral viruses, and therefore, you can say that milk is safe, and the other one is retro-viral sequences and therefore all science I know and all publications I know have sequenced, synthetic DNA and have matched against universally available Washington database, where all these sequences are available and updated on a weekly basis.

 

LUNCH SESSION

Koos N.M. Richelle,
Director General International Cooperation
Ministry of Foreign Affairs, Government of the Netherlands
Chairperson

Chair: Let me first introduce myself - my name is Koos Rochelle and I'm director general of international cooperation of the Netherlands. I think the reason that the ambassador of the U.S. has asked me to chair this luncheon meeting, is that from our line of duty, in the ministry of foreign affairs and development cooperation, we have strong ties with the speaker of today, Mr. Ismail Serageldin - not only personally, although we meet him in very many instances - he's a very important man - he knows about everything, you could say. But also because we support him on a number of issues that he is really carrying forward in the world bank or in specific functions attached to that. Also in the field of biotechnology, we are supportive of some of the activities around the world, and in this case I might mention the consultative group for international agricultural research that Mr. Serageldin chairs. For us its not only a matter of technology, we of course, feel a certain responsibility toward developing countries not that we want to take their place in terms of ownership of processes, we have to acknowledge that institutional capacity in many developing countries in all fields, but certainly in the fields of biotechnology, is limited. It's not only a question of using developing countries as experimental fields for development of biotechnology, but also making sure that they profit in very responsible way, from all the benefits that biotechnology can offer. In our opinion, biotechnology might be a solution, for instance, for having food security all over the world. Also in developing countries. But apart from technical aspects, we in the Netherlands of course are very much interested in the ethical norms and value aspects connected to biotechnology. From our side, the Netherlands, more than one ministry is interested in biotechnology. As far as development cooperation is concerned, we are supporting out of a budget of 7 and a half billion guilders, not more than 10 or 15 on biotechnology. So it is relatively a small part of the business, but nevertheless one that is very important - has a very great political attention because non-governmental organizations are very interested, and make it a political question. A heated debate, a debate that sometimes shows irrationality. One of the good things of this meeting until now at least, is that we have seen a very responsible kind of debate on a very high level and I think I must commend the American ambassador, Cynthia Schneider, for her personal initiative to do this. The debate between the United States and Europe is sometimes heated too in these kinds of issues, so it calls for some audacity to organize this event here, and I think you did the right thing and you timed it very well, in this timeframe.

Let me now focus on the introduction of Ismail Serageldin. I suppose I do not really have to introduce the man - I only have to give some kind of a laudation to him and that is one in a long row. He is paid by the World Bank as a vice president, but he does a lot of other things in that time. He publishes a lot - hundreds of articles. I've been told that when you hit "Serageldin" on Internet, you get 1103 hits so that's something. He has 12 honorary degrees and doctorates from various universities all over the world. I think one of the relations to this conference is his work as the chair of the consultative group of the international agricultural research. Mr. Serageldin will speak to us for about 25 minutes. The room will be darkened a little bit, so I hope that you can find your plate and your food, but he will grab your attention immediately. Afterwards, I think there's about 15 minutes question and answer time. I now invite Ismail Serageldin to take the floor and to speak to us.

 

Ismail Serageldin, World Bank
"Biotechnology in the Service of the Poor: Challenges and Prospects"

Thank you very much Koos, for this very kind introduction. Ambassador Schneider, ladies and gentlemen, it's a privilege to be with you here today and to discuss a little bit about biotechnology and the developing world and in particular, something about the challenges and the prospects. I've chosen to use slides because I want to cover a lot of material, and I think it will come alive a lot more by using slides. And fundamentally, I think we have to start off with an appreciation of the current context for the developing world. Simply stated, we have a huge population expansion, even though it is slowing down, we still expect at least 2 billion people more on the planet, almost all of them in the developing countries. And we have to be concerned about the provision of food security which means adequate amounts of food at adequate prices and accessible to all people at all times. And we have to do it in a way that doesn't destroy the environment in the manner in which it has been done in the past. Now this therefore implies clearly that it is not a matter of producing less than we are now producing, but to produce differently and rethinking resource use in terms of how we are going to meet that food security challenge.

Let me dismiss one particular statement which is the idea that somehow exports from the north can feed the south - that is not going to work and we can discuss why, fundamentally, the only way we're going to deal with the triple problem of reducing poverty, dealing with food security, and protecting the environment, is by reaching to the smallholder farmer in the developing world and successfully transforming and increasing the productivity and profitability of the smallholder farm. Now, as it stands today, even though global production of food may be in balance, we still have 840 million people, mostly women and children who are chronically malnourished and approximately 40,000 people who die from hunger-related causes, not to mention the hidden hunger of iron deficiency, iodine deficiency, and of course vitamin A deficiency which affects 125 million schoolchildren and produces irreversible eye damage in some 14 million children, hence the argument about vitamin A rice being so important, which we'll come to later on.

Now, we know that production by itself is not enough, that despite the availability of food, frequently we find people going hungry. This is therefore a very big challenge and food security is not only about production. In fact, there is a complexity to the issue. It is not just the production but the access by the poor to that production. It is not just the amount of output but the process by which it is produced and whether that process is sustainable. If it is being produced by eroding the soils and cutting the forests, then it is not sustainable. And it is not just the availability to technology but also the policy that encourages its use for example in the case of water and irrigation if you give water for free, people are not going to use ? techniques, the policy has to be put in a particular place to make the adoption technology possible. And regardless of the global issues, we know that the problems are really hid in a national context, whether it be Northern Korea or Somalia, these are really national contexts and not just global balance that are there. And at the national level, it is not just national level, it is also at the household level, because there is even hunger in rich countries. And finally I will be talking mostly rural, but there is an increasingly an urban underclass that needs to be reached. However, dealing with the problem of urban poverty is best done by transforming the rural production system in developing countries because the urban poor by definition purchase their food and is a significant amount of their consumption basket and therefore reducing the cost of food to them is a direct way without adminstering a program of actually giving them greater income. And finally it is not the amount of food but also the nutritional content of the food that is important.

Now as a result of the complexity of the issue has lead people to say, it is not just about production but it is true and (name?), who won the Nobel prize for talking about famine but he pointed out, you can have famine with production, but as he rightly pointed out, he says, 'I am being misquoted. I said, Production is not sufficient but I never said it was not necessary'. So production is still going to be necessary. But on the short term, medium term and long term and if you look at household, national, and global, in the short term horizon for household it is access in a traditional content, for global level in the long term it is a sustainable production system and a fair trading system at the global level. In between that, you have a lot of other things that come in, in particular I would like to focus on the production side which I think is essential. Fundamentally we are going to have to reach out to very poor people in what are known as resource poor environments in the rural areas. Why? Not only because the rural people the ones that produce the food, but because even in absolute terms, they are going to remain the majority in the developing world at least for another ten to fifteen years. In terms of poverty, they represent about seventy percent of total poverty that is available right now and many of those in the rural poor tend to be in the less favored areas, meaning in other words, landscapes, such as this one, which is incredibly difficult to increase productivity of agriculture in that type of context. That is where we have to reach in order to be able to deal with the poverty side and to deal with the production side.

So meeting the production challenge, how serious is it? Well let me give you a few statistics. We are going to need forty percent more grain in 2020. Almost all of it will have to come from yield increases because the amount of land and water that can be brought under agriculture is pretty much the same. The bulk will be in developing countries and the demand for cereals and livestock fields will double in developing countries, and that cereal imports by developing countries will almost double to fill the gap between production and demand. So yes, there will be an increase, but it will be a fraction of the total amount required and increasing imports will be a fraction of the amount required. Now these cereals are going to be essential to be reaching a very large number of people and although the developed countries are the ones that are really controlling debate about biotechnology, different technologies trade regimes, they account for about fifteen percent of the total net increase in cereal demand. Eighty-five percent is going to be in the developing world and therefore the voices of the developing world have got to be heard. If voices of the small holder farmer, especially the women who are the ones who produce about eighty percent of the food in places like Africa have to be heard. Now in terms of increases for meat products again it is going to be the developing world, that is going to be the majority of increase, 15.4, 15.9 percent in the developed countries, in the OECD countries, and about eight-five percent in the developing countries. Fundamentally the agricultural production challenge is going to be in a developing country challenge, not so much in the industrialized country challenge , and in terms of livestock in dealing with these kinds of herders and pastoralists as Tony Irvin was talking about earlier today.

Now meeting the production challenge would require increasing biological yields, improving the nutrient content of the food, intensifying the agricultural systems, and managing the agricultural systems sustainably. And that brings me to revisiting the last time we did this, which was in the Green Revolution, the so-called Green Revolution, which has been much maligned in some environmental circles, I am an environmentalist myself and I think it is inappropriately maligned because not only do it really deal with the food crisis of the (place?) in the 1960s, please recall (place?) Asian drama fighting famine of 1975, in the late 1960s there was an expectation of famine in South Asia , that did not happen because of the green revolution. But more importantly, it saved them and is still spreading. But it left a huge institutional reform agenda that is still unfinished and I want to show you what these miracle rice, miracle wheat varieties, as they were called (name?36) in particular and what they produced. This is in India for all cereals, but you could have globally the same figures produced that if you want to produce the same amount of food by 1990, with the yields that you had in the 1960s, you would have had to bring this additional area under cultivation. This green area, this green triangle of land here is the land that has been spared from being brought under cultivation because of the increases in yields. Now this area is not insignificant. This is incidentally a very conservative estimate because it assumes the same yields per hectare for the green and the red area although we know we are going towards less productive lands as you increase land you go to more marginal land, therefore the yields will be less therefore the triangle should be even bigger. But even this triangle, it is 300 million hectares of land that was spared. That is an area the total size of India, it is more than the total agricultural land of Canada, U.S. and Brazil combined. Therefore think if we did not have the green revolution, how many more forests would have been chopped down, how many more habitats would have been lost, how many more species would have been irreversibly lost.

Now we are trying for a doubly green revolution. One which will redress the imbalance of the first one by going for genetically diverse new crop varieties, minimize chemical use who integrated task management, reduce the input as Chris Somerville was talking earlier today, and improve on-farm water efficiency and nutrient management. These three cornerstones, diversity of the genetic base of the new plants, the reduction of chemical inputs and the integrated soil, nutrient and water management on the on-farm basis are the three pillars of this doubly green revolution.

But we are also working on the nutritional content. This is an interesting slide, it is not about pigs, it about high protein maze. These pigs are twins; one was feed with regular maze and one was fed with high protein maze. And I think you can see the difference in the quality of the nutritional content of the same maze that can be done in this fashion. Increasingly we are looking at how to reduce post harvest losses, which are extremely important, because in many countries, about 20-30 percent of the harvest are lost after harvesting, and thus reducing the habit is a way of increasing the production challenge as well. The emerging issues are the enormous pressures on land, water to produce food in developing countries. Take a country like Bangladesh, it has a 120 million people in an area the size of the State of Wisconsin or the State of Arkansas which has 2.5 million people. It is going to have 200 million people there less than .8 of hectare acre per person today. Now this means agricultural intensification will be required that will come from biological yields, greater synergies between different types of farming inputs and better resource management. And we therefore need all the scientific tools, and biotechnology is one of those promising scientific tools.

Now today in the agricultural research to achieve this doubly green revolution we have a double shift in the research paradigm. The first of this is the contextualization of crop research. Where in the past green revolution we are pushing the yield from tier IV? rice or from wheat or from maze just a crop specific research, we are now contextualizing it and the second one is the genetic imperative. What do I mean by contextualization? It means the integration of the crop specific research into its regional and sustainability issues, geographically in terms of local regional ecology, thematically in terms of that fact that smallholder farmers never do one thing only, they are not monoculture producers. And therefore we need to develop the synergies between livestock, forestry, agricultural farming etc., and to recognize the socio-economic issues, which are the farming systems of the smallholder level with a special emphasis on the gender dimension. Now it does make a difference whether you are producing plants to grow in an environment like this or in an environment like that one. And thus the regional ecology is extremely important we have heard about the importance of livestock but the integration, the synergies that have come from corralling livestock so that the manure can be effectively used does produce dramatic results. Here is a test in West Africa, semi-arid West Africa, in promilet yields, and as you can see a huge increase with the proper corralling of livestock at the time of planting this is the control field. So whatever you could do on the yield alone, even if you doubled it, it would only reach so high, on the other hand you can see the huge increase from synergies. So I want to capture the synergies of these farming systems, and the way to do that also involves participation of the farmers themselves, in setting priorities for research agenda. This is an actual priority setting exercise for one of the CGIR centers with illiterate farmers in the MesoAmerica area.

Now the second shift, which concerns us here in the seminar, is the one of the molecular genetics. And that is to link cutting edge work in genetic mapping, molecular markers in biotechnology to breeding with a special focus on issues for the poor and the environment. Now this is very important because a lot of the discussion has been biased by the fact that a lot of biotechnology is for commercial cash crops in the industrialized countries. But the technology itself is inherently usable for these other purposes as well. And the genetic markers are already widely used and they are not considered problematic, but the potential power that technique is coming to the fore, and I was very moved by Steven Tanksley visit to me a few years ago, I had read in draft form that he and Susan McKush? wrote, that showed in fact that you could really look at quantitative trait? and molecular mapping as a way of improving very complex characteristics. And earlier today Steve showed the issues of tomatoes, I have a picture of that too as well. But the fact that we discovered that there is a lot greater similarity between dipods and the monopods among themselves which means you can actually find similarities in work being done on different plants around the world. Plus the communication technology that exists today unleashes a much greater potential for participation and collaboration among scientists around the world, were it not for intellectual property rights. But we will come to that in a moment.

The real issue I think in the revolution and aspects related to that, is that the paradigm needs to shift away from selecting parents? on the basis of phenotype, which means the way a plant looks, the way it feels in the field, towards evaluating directly for the presence of useful genes. And the tools that make such analysis possible are molecular maps and the integrative power of OTL? analysis. Now, traditional farmers have always selected plants based on phenotype, this is how they look in the field, how they behave, their yield characteristics and so on, and that was not just the traditional farmers, that was in fact scientists did the same thing in conventional breeding programs. Now complex characteristics require a number of ? located on the genome, to be active. High yielding cultivar?, a high yielding variety, let's say for example its shields are effective by seven such sites, may have five that are well expressed but maybe missing number six and number seven. And that you may have a wild relative that does not appear to be a high yielding variety but does have number six or number seven that is well expressed and therefore crossing them produces these results. Now in the absence of doing that has lead to the fact that going from wild species towards the early domesticits towards modern varieties, we have been gradually reducing the gene pool on which we are working and therefore the constant breeding of the high elite cultivars? Is working on a narrower and narrower gene base.

Now a new molecular mapping, enables us, in fact to discover things in the non-used plants, so in tomatoes for example, it is a very small fraction that is cultivated tomato and the rest is exotics, and for rice it is a bit more that is cultivated but still three quarters of the rice that are available in terms of wild rice are not used for cultivation. We got to them for pest resistance or stress resistance but now we are discovering they can also turn very valuable for yields and it is this combination of molecular knowledge, molecular genetic knowledge with the traditional knowledge that enables us to unleash this new potential. And these are some of the pictures from name? Article, which shows the increasing human pigmentation by using the wild relative, you saw better slides of that this morning. This one I like very much because this is the wild relative and that's the elite cultivar and crossing those two produces eleven percent larger food, which you wouldn't obviously thinking of having a cultivar like that and crossing it with a plant like that in order to increase its yield but it does. And this is where the new knowledge of molecular genetics enables us to see things that can not be seen from the phenotype alone.

Now biotechnology promises obstacles in doing this kind of work faster and doing the transfers more accurately than we have ever done before. But it does raise other sets of issues. Now regretfully, ever since Dolly the sheep made her appearance on the 22 of February 1997, on the magazines of the world and the media, it has been very difficult to have a sort of calm discussion of the issues. It has been a very heated discussion, it has been fed by the media by sensationalists. But I think there are very real issues in this discussion and I was very pleased by Sue Mayer earlier today raised some of those. There are issues of ethics. And we will be hearing from Neolle Lenoir more than one later on these issues. And there are issues of intellectual property rights, and there are issues of safety. And they are different issues. I don't think we should constantly mix them up. If we want to have a really productive discussion, we should disentangle these issues from each other. Now the intellectual property rights, about which I have some reservations, I want to say, yes they are important in the sense that they mobilize an enormous amount of private sector money for research which otherwise could not be available but they are also potentially obstructing research in different ways. Now what is a gene? A gene is a protein making part in our DNA as you all know but it has sequences that come before it and after it that tell it the timing, the place, the quantity, the entry point, the start, then the part that is tryptic?, the protein, then the part that stops the frequency by which it should do this and so it shouldn't continue indefinitely producing itself. This construct, which we all call a gene, in fact, intellectual property rights have been taken not just entire gene, but on selection genes on quality trade genes, on promoter sequences, each one of those intellectual property has been taken on different bits and pieces of that, including gene transfer technology and enabling technology. A lot of that intellectual property is now under the control of multinationals and this raises an issue for a number of people about the concentration of power in the hands of a few multinationals.

OK, that is a topic worthy of discussion. But let's not confuse that with whether it is safe or unsafe. The issue of concentration of power patenting controls, is a worthy topic of discussion but it is not the same as whether it is safe or unsafe. But the fact is, speaking from a developing country perspective is that while this race is going on to patent, in the labs of the industrialized countries, here is a compelling picture. This is a rice farmer in China two thousand years ago and this is a rice farmer in China today. Two thousand years ago, and today. This is the reality we are talking about and this is the climb? that we have to reach if we are going to meet the triple challenge of reducing poverty, increasing food security and protecting the environment. And thus the extent to which the availability of these technologies is restricted will lead us in this century towards a form of scientific upperkite? For those who have and control the knowledge may make it inaccessible to the others. That is a very serious question which we need to address and there are ways of addressing it and I have suggestions. But biotechnology itself as a technology is not the issue here. That is a separate issue. That is the issue of property rights, one can respect contract law, the U.S. today Department of Justice is taking Microsoft to court for monopolizing power, so it has nothing to do with software per se, but it has to do with economic concentration. And the same issues are here, because the biotechnology that we identify with bulgar cotton for example, is also the biotechnology that gave us vitamin A rice. As a technology, as a scientific approach, and I would venture to say that given the magnitude of the challenge that we have in the developing countries, we absolutely need to use all this technology. Now where is it going to take us if we go beyond 2000, look somewhere into the future, some people are thinking that we may in fact assembling entire genomes like legal sets and who knows? Maybe we will producing giant crops like that? (reference to slide). In fact in the CGIR and other centers, we are looking towards more mundane, but more compelling and challenging issues. For example, rather than irrigated rice, what if we had upland rice or rain-fed rice that is perennial that has a one hundred and fifty grains per pentacle, that has sturdy stems, deep roots, is nitrogen fixing, that can withstand pests and diseases, and that can last from 3-5 years in the field. Now that is changing the architecture and the characteristics of the plant. Now I don't think we can do it without biotechnology; if we succeeded in doing that we will reach some of the very poor people in the remote environments that I showed you pictures of before and we can do the same for lots of other crops. And a lot of that can not be done with conventional breeding programs. But there is a lot of potential there, if only we can capture it.

So biotechnology can help us in improving nutrition, we talked about Vitamin A rice, but we could also have edible vaccines, we could improve desirable traits such as nitrogen fixation and better plant architecture; we could tackle biotechnology and other stresses, we could deal with animal health and nutrition, and we could solve feed problems, because animal feed problems are going to become a very big issue in the future. And we could do so much more. Now to make this work, we are going to need new types of partnerships. We are going to have to get beyond the adversarial relationships and into partnerships. Back in 1996, in Washington, the first meeting of the Global Forum for Agricultural Research that pulled together the advanced research institutions of the north, the private sector companies, the international centers, and the national development country research systems and the NGOS and farmers' associations got together. And it is not just getting together in the board rooms, but it is getting together also in the fields that is equally important, because everybody has a contribution to make. I think it is extremely important that we think of ways by which this technology, which incidentally, unlike mechanization, for example, is not inherently against the smallholder farmer, mechanization is not scale neutral. Technology that passes in the seed is scale neutral and can reach the smallholder farmer because that is what would enable this little girl to find food in her bowl when she grows up, and it would enable us also function as true stewards of the earth. Thank you.

Chair: Well as I announced, ladies and gentleman, first of all let me thank Ismail Seregaldin for his comprehensive and very quick presentation of the huge developments. There is a possibility to shout some questions to the speaker. We will repeat it from here, not more than 3 or 4 questions because you should be back in the meeting hall on time. Who would like to ask the first question? Yes please.

Question from the audience: How could biotechnology help solve the problem of animal feed, which was eluded to by Chris Somerville this morning, which is a big problem, and where would the money come from to do research of that kind when universities and others are not focusing on it?

I think it is a very important point. Let me point out, India today has twenty percent of the world's livestock; only 1.5 percent of the range land. As a result, India today uses 400 million tons annually of crop residues as animal feed. Now because we want high yielding varieties, and want to prevent the plants from falling over when the have a lot of seeds and cereals and then they rot on the ground, we stiffen them. That is one of the things conventional breeding has done, we stiffen them and therefore this increase the lignant? content in the plants. The result of that is it makes the crop residue not very digestible. Now to break the lignant? link in the cells of the plant, is a very complex problem that can not be done by conventional breeding and would probably require some biotechnology inputs. If we could do that, you could feed the same amount of livestock, or even an increased amount of livestock, for less crop residues. Which would therefore release more of the biomass of the existing plants for cereals for human beings. So the same amount of land, the same amount of water would produce more food for people by in fact ensuring that less go to crop residues is these are more digestible. So I think this a very important way and may turn out to be as important as directly trying to increase the yields of plants because you have to take into account that the farmers actually use crop residues. And I hope that the donors who are concerned about development would fund the research and many are present here. I think it wasn't wasted on them.

Yes, please.

Question from the audience: Many development practitioners recommend using low tech approaches and believe that a combination of better management and organic farming will produce all that is required.

I think myself, that it is not an either or proposition. The challenges that are put before you are so enormous to increase food production by forty percent within, a global food production by forty percent by 2020, to catch up with reductions in the stock of malnourished people, to improve the nutritional content of the food, to manage this at the level of the smallholder farmer you need all the tools that you can get. And in fact, I showed you an example of the synergies between livestock and promilet? So I am not ignoring that side. There are gains to be made there but there are also types of problems, like the animal feed problem, that can not be easily dealt with in any other way. Other problems, such as bananas, which are extremely difficult to breed, because of particular problems that are there, and are susceptible to diseases, we know that if we can solve that by biotechnology and there is some lab work on that, we could also benefit plaintans? because it is the same ? genome. And these plantans are a primary food product for our people. Now, casaba was mentioned earlier this morning. Now I hate to say this, but it is very sad for me, coming from the south as I do, to know that despite the fact that casaba Is an essential food for 300 million human beings, nobody would invest in sequencing the casaba Genome or improving it, because they are very poor people in remote areas. On the other hand, if casaba turns out to be a good feedstock for hogs, for pig farming, in the U.S., then it would be done, because it is a commercially viable production system. So it would be looked at if it is for feedstock for hogs in the U.S. but it would not be looked at if it is a primary staple for 300 million poor human beings around the planet. This is why we need the priorities of the research to be more than governed exclusively by commercial considerations and we need public goods research to address these kinds of issues. And that public goods research would look at IPM? Would look at synergies, but would also use benign biotechnology that is publicly available to everybody. So I think we need all the tools we can get to meet the challenge which we have but clean up the backlog of hungry and malnourished people and to meet the future demand as well.

Question from the audience: What can we do to improve the public debate on biotechnology and GMO's specifically?

I think personally what needs to be done is to disentangle the issues and be clear whether you are talking about ethical issues, the 'oughts', because science has very little to say about ethical issues. It is a cultural, political, social set of questions that has to be answered. Just to put it in perspective, if somebody says I am opposed to surrogate motherhood because there is danger to the mother or the fetus, the question of danger to the mother or the fetus is a question that technical and scientific research can address. But if somebody says I am opposed to it on a matter of ethics, regardless whether it is safe or unsafe, than science has nothing to say to that. Now, if we recognize that there are ethical issues and discuss those as ethical issues, there are safety issues and we discuss those. What I personally believe is that we need a proper food regulatory regime because if you look at what is happening in the U.S., I guess there is about 100 million food poisoning incidents a year, not one of those is related to GMO's, whether it is saminela or raspberries from Guatemala or whatever it is. People in Europe talk about BSE, they talked about dioxin chicken, they talked about Coca-Cola contamination. None of that has anything to do with GMO's. What you are looking at there is a question about the regulatory regime. The third thing we can do is improve knowledge by labeling, so people have information and they can choose what they want to do. Behavior changes are up to people to decide about what they want to do. And the last part which we need to address is the intellectual property rights issues and there are suggestions there about how to keep some parts of that so you don't block the processes that could be used for other things from being used, but these are technical questions and I really don't think we can get into them. So dividing the issues, clarifying them, clarifying therefore the terms of the debate, which clarify when we are talking about science and evidence and when we are talking about political judgements and cultural and ethical issues we feel strongly about.

Chair: Well, unfortunately time is running out and we can not prolong this discussion. On behalf of all of us, I would like to thank you for this very thorough lecture you gave us and the time you took to answer the questions.

 

AFTERNOON SESSION: "IMPLICATIONS FOR SOCIETY"

Eric Claassen, ID-DLO Netherlands
Juan Enriquez, Harvard University

Introduction by Eric Claasen: Part of the goals of this conference is the continuous education of all of us. The scientists should be educated to communicate in a proper way and to challenge viewpoints, but also, of course scientists have the responsibility to engage in the public debate and to educate the public. It is our great pleasure to welcome today our first speaker, Neysa Call, who is standing in for Rita Colwell, who is of course, the Director of the National Science Foundation and who will tell us more about biotechnology and the future of scientific research.

 

Neysa Call for Rita Colwell, National Science Foundation "Biotechnology and the Future of Scientific Research"

For those of you who know Rita Colwell well, you will know that she is quite a petite woman, but for such a petite woman, she has left me huge shoes to fill here today. It is a tremendous honor to step in for her today on behalf of the National Science Foundation. The topic of our discussion today is what motivated me in my career path. I went the extra mile in my graduate education program to combine science and policy. If you know graduate education systems in science they do not even like to use the words "science" and "public policy" in the same sentence. From there, I went immediately to the U.S. Congress and now I am at the National Science Foundation, working specifically on iotechnology issues to help shape policy.

I want to start first by offering Dr. Colwell's apology for her absence today. At the last minute, her schedule was changed so she could accompany President Clinton to California. Some of you might have heard the news snippets about President Clinton's budget proposal for 2001. Most of those rumors are true. He will be highlighting a significant budget increase for the National Science Foundation and other R and D programs. I am going to deliver a message that is similar to Dr. Colwell's on behalf of the foundation. An added bonus is that you get the perspective of two generations of scientists. Her talk was entitled "Biotechnology and the Future of Scientific Research". I find it appropriate, as did she, to broaden that theme and talk about biotechnology in the broader scope of science. It was Dr. Colwell's hope to identify different parts of the scientific landscape where we could find common ground. I will do this by touching on three topics. First, the history: how we got to where we are. Second biotechnology's role in the future of research generally. Finally, the paramount importance of fostering a broad base public discussion on the full range of issues, from the scientific, to the economic, to the moral and ethical.

I would like to begin with a brief survey of how we got here. This science timeline helps frame how biotechnology and its public perception developed. We have come a long way since Mendel taught us the laws of heredity, which begins our timeline in the upper left-hand corner. This issue began to take hold of the public psyche some eight years later, when we learned that DNA governed heredity in cells. You see that benchmark in the middle of our timeline. We knew it was time to step back and take stock of the situation in the early seventies. That is when we first mastered modern gene splicing techniques. This technique left scientists and the public intrigued and concerned. This inspired the 1975 Assilimar Conference in California, which ends the timeline. Scientists called for a moratorium on recombinant DNA research until we better understood the implications of this powerful capability. In many respects, Assilimar outlined the framework that allowed work in this area to forge ahead. The conference in California was convened for two purposes:

1. Confronting concerns about the safety of this line of research. 2. For recommending actions.

Over two decades ago, scientists suggested the guidelines for safe conduct on the new DNA experiments. During the two decades since Assilimar, the science has continued to progress. You can see that the adoption, views and impact have progressed even faster, especially in recent years. This timeline shows some of those highlights. Products of biotechnology have moved out of petridishes and into the marketplace. Today, it is clear that we are at a juncture similar to the one that brought scientists to Assilimar twenty years ago. On the scientific side, we are ready to say full steam ahead. On the societal side, we are saying let's make sure we know where we are headed. All of this makes our gathering here especially timely and appropriate. Like many emerging sectors of the global economy, biotechnology owes much of its advance to public investment in basic research. For this reason, it is important to consider research funding in a larger context when we consider the future of biotechnology. We find ourselves in a paradoxical situation. I will illustrate with the trends of U.S. R and D funding. The two major sources of financial support for research and development in the U.S. are industry and federal Government. You see them here as the yellow and red areas on the chart. It is easy to see that together they provide 95% of all the funds spent on R and D performed in the U.S. In 1980, industry surpassed the federal Government as the leading supplier of R and D dollars. Since then, industry's share of the national R and D performance has been rising steadily, from two-thirds of the total in the 1970s, to nearly three-fourths in the late 1990s. More than ever, public investments are decline as a share of the total investment and at the same time, industry is increasingly dependent of public funded research at the frontier.

You may be familiar with a now famous study by Dr. Francis Neran and his colleagues at Kie Research. Since 1968, Kie Research has pioneered the developments of science and technology citation analysis. This study demonstrates the linkage between patents granted in the U.S. system and frontier research published in archival journals. Nearly two-thirds of the papers on patents were published by organizations primarily supported by public funding. This tells us that the knowledge that drives innovation comes predominantly from publicly funded research. Even more important is the rate that this link is increasing. The latest data shows that over 100,000 citations on U.S. patents issued in 1998, referred to scientific and technological articles. Granted that some of this increase is due to our new capabilities to search on-line with computers, but that does not explain the entire trend. We see a ten-fold increase since 1998 and a doubling in just the past two years. Just as pay-offs have blossomed, we have let publicly funded research investments whither. This situation makes President Clinton's imminent announcement even more exciting.

We at NSF are very aware of this funding trend. We recently unveiled our poster to launch our celebration of NSF 50, the fiftieth anniversary of the Science Foundation. We choose the theme "Where Discoveries Begin." We are marking the occasion with a campaign to spread the word about how investments in fundamental research and education spawn discoveries and advances that benefit everyone.

Even today's sophisticated tools of biotechnology can be traced to earlier investments in basic research by NSF, such as the case of PCR the polyimerate chain reaction. This technique was pioneered in the private sector in the 1980s, but only after heat resistant DNA polimeraze was discovered. A NSF supported research found the source of bacteria in the hot springs at Yellowstone National Park. Fundamental research like that searching for the bacterium was traditionally focused on understanding the tiny components of nature, but lately we are watching discrete disciplines fuse. We see places where information technology merges with biotechnology, like the recent advent of DNA on a computer chip. This is a microarray, a long strand of DNA spread out on a chip. With this technique, the genetic code of any organism can be probed and key genes located, like the genes that predispose us to cancer. It is easy to see that the links between all aspects of science and engineering at all levels are strengthening with each passing day. This takes the future of science in a new direction. At NSF we call it biocomplexity. Biocomplexity refers to phenomenon that arise as a result of dynamic interactions that occur in living systems and between systems and their physical environments. These systems range from microscopic to global in scale and they exhibit properties that depend not only on the individual interactions of the components, but also on the interactions of these components. The time is right for this approach to biological systems. We have a very solid understanding of many of the system components. That gives us the intellectual platform to address how these components interact in complex systems. Biotechnology will be key to understanding the complexity of life on our planet.

Let us use some research snapshots to briefly survey some of the tools and discoveries providing insights into this complex world. You see here a simulation of a DNA fragment in water. You are not only able to read this three-dimensional structure, but we can see its behavior when we manipulate it. This research has broad applications. On the left, you see a plant and on the right a fruit fly. Scientists funded by the NSF reprogrammed the DNA of this plant in sync with its Arcadian rhythm. It is appropriately called the clock gene. The plant glows as its sense of daylight, literally shedding light on the molecular mechanism of its Arcadian rhythm. On the right, you see the same technique applied to the fruit fly. As we move to an even larger scale, biotechnology offers solutions to environmental problems, like those posed by landfills. Non-degradable plastics are a prominent feature. A NSF grant for exploratory research marked the beginning of biodegradable polymers in plants. Here is the core plast of a transgenic Arabidoxis plant, filled with a naturally produced biodegradable plastic. Here we see biotechnology as a force to protect our environment; a primary component of any global sustainable development. In terms of potential, we have only just begun to reap the benefits of biotechnology. As scientists, we understand that technology is the easy part of the equation. The more complex element concerns our societal goals, ethics and values. No area of science calls for more public outreach and discussion as much as biotechnology. This is the bare substance of life itself. We must approach it with both respect and with perspective.

A number of recent surveys make clear that, as a society, we are both impressed by the science and concerned for a moral standpoint. These results from a 1997 cross-national survey of Canadians, Americans and Europeans tell us that over 70% of the public think that the insertion of human genes in bacteria to produce medicines is useful, moral acceptable and should be encouraged. We are more divided when it come to the food we eat. Two-thirds of Canadians and Americans think bio-engineered foods are useful and morally acceptable. A majority of Europeans agree, but only half find it morally acceptable. We all agree that these technologies are potentially the most powerful and revolutionary in recorded history. They will literally touch every part of our lives, from our kitchens, to our closets, to our medicine cabinets. I would argue that all of us, scientists, educators, the media, public officials and experts from all sectors, have an absolutely critical role to play in these issues. We must foster a broad-based discussion that includes public comment and interest. Many of my friends in research often say, if the public only understood the science, they would accept it. Reality is much more complicated than that. Our goal for science education should not be to have everyone nod in agreement. It is to provide a foundation for a fully informed and inclusive discussion. In that way we can help society gauge tough, but critical concepts of life. Another survey from the NSF's science and engineering indictors illustrates with a case in point. It tells us that only one in five Americans can provide a minimally acceptable definition of DNA. Granted Deoxyribonucleic acid is a mouth full for anyone, but grasping the concept of this technology is even tougher, especially without pertinent background information. Only with an appropriate grounding can policymakers, parents and the public make informed choices about new technologies. I assure you that, during the next century, the public will have to come to grips with more advances than just biotechnology. We have E-commerce, digital divides, at home healthcare, educational technologies and much more. Just last month, Science published one of a series of essays on visions of the future. It talked of virtual intelligence, synthetic genetics, metabolic pathway redesign, artificial cell design and multi-universe cosmology. We need to be ready for the next generation of scientific breakthroughs.

As we expand our understanding of the world and all its complexity, no longer can science be a mysterious ritual for a single class of professionals. Public involvement and informed discussion are essential to set priorities for science and engineering. In turn, scientific progress is meaningless without strong public support. To forge ahead with discovery, we must come to a common understanding. Only with open discussions like this today will we find common ground. Finding common ground will require combined abilities. It will require work across governments, civics groups and communities. It will require an extraordinary level of compromise and cooperation. Dr. Colwell would say that we need to extend the frontiers of science and open its doors to society at the same time. She and all of us at the NSF look forward to moving ahead thoughtfully, with a measured sense of both the potential and perspective. We agree that the capabilities before us can help us conquer society's most persistent challenges. NSF looks forward to its part in realizing its promise for all of science and society. Thank you.

Eric Claasen: I like your statement about public involvement. I still feel we should also talk about the scientific commitment because by definition the public is involved, but by definition we as scientists are not always committed to this dialogue. The second speaker is Isi Siddiqui of the U.S. Department of Agriculture. We have already heard about the necessity of biotechnology for the Third World, but I am sure it is also necessary for the developed world.

 

Isi Siddiqui, U.S. Department of Agriculture
"Biotechnology and Agriculture"

Thank you very much for that kind introduction, and for the opportunity that you have given me to offer my thoughts on this defining issue for the new century.

It's my hope that this conference and others like it are the beginning of a more intellectual and productive dialogue on genetic engineering, one where we move toward consensus rather than further isolating ourselves in rigid ideological camps.

Let me begin by saying that (Agriculture) Secretary (Dan) Glickman and I are believers in the life sciences and their ability to alleviate human suffering and enhance the productivity and sustainability of agriculture around the world. But we also believe that technological progress must never come at the expense of environmental degradation or human safety ... that government has a responsibility to protect the people where they are largely powerless to protect themselves.

People always want us to choose sides in this debate, but I don't think it is government's job either to actively promote or thwart biotechnology. Rather, our role is as impartial judge. We evaluate prospective biotechnology products, ensuring that they meet our rigorous human safety and environmental standards.

To do this, we have a regulatory process that is tight, comprehensive and grounded in the most demanding, scrupulous science. There are many strict checkpoints through which a GM product must pass on the road from petri dish to grocery store shelf.

Those checkpoints are manned by three different federal agencies working in sync with one another. At the Department of Agriculture, we guard against potential risks to plants and animals. The Food and Drug Administration is the watchdog for a GM product's impact on food safety. And the Environmental Protection Agency examines products that can be classified as pesticides. Regulators at all three agencies are scientists who work full-time on review of new products. They are not beholden to any political party or movement, nor to any entity that stands to profit from biotech commercialization.

In addition to being scientifically rigorous, the process is open and inclusive. We hold public meetings with scientific advisory panels. For each product, information is regularly posted on the Internet. Americans can believe in the integrity of the process because they have the opportunity to watch it happen and participate in it themselves.

This system has worked. In 13 years, not a single product that has made it to market has been proven environmentally hazardous or unsafe for human consumption. Thirteen different GMO applications have been withdrawn voluntarily because of possible risks that our regulators would have caught. For example, a soybean variety that had been infused with a Brazilian nut gene was withdrawn because of the possibility that those allergic to the nut would have a similar reaction to the soybean.

In the next few minutes, I would like to focus specifically on the Agriculture Department's role in the approval process for transgenic crops.

The Department's Animal and Plant Health Inspection Service -- or APHIS, as we call it -- is the federal government's lead agency in regulating the safe development and release of biotechnology-derived, new plant varieties into the environment. Since 1987, we have overseen field testing at more than 22,000 sites and granted determinations of non-regulated status for 50 new crop varieties, thus allowing them to come to market. These products have already become a huge presence in the commercial marketplace. In 1998, 43 percent of the total U.S. cotton crop, 44 percent of the soybean crop, and 36 percent of the corn crop were genetically engineered. This year's figures will likely surpass those benchmarks.

Our authorities, under the Federal Plant Pest Act and the Plant Quarantine Act, require scientific researchers to obtain authorization prior to introducing genetically engineered organisms that are, or could possibly be, derived from plant pests.

Thus, when any entity -- a company, an academic research institution, a non-profit organization, or a government scientist -- wishes to field test a biotechnology-derived plant, they must first contact USDA for permission.

The field testing can proceed in one of two ways. The first involves obtaining a permit from us before testing, to ensure that the test is conducted in accordance with all regulatory requirements. USDA issues field testing permits annually, and each permit requires specific information from the tester about the plant, including all new genes and gene products, their origin, the purpose of the test, how the test will be conducted, and specific precautions that will be taken to prevent the escape of pollen, plants, or plant parts from the field test site.

Before authorizing a field test, we review the permit application for possible effects on the environment, endangered or threatened species, non-target species, and the potential for any gene transfer to cultivated wild or weedy species.

We also have a streamlined permit process, which most applicants can now use. The applicant provides a notification of the intent to field test, which USDA has 30 days to review and approve. Although these simplifications have shortened the overall permitting process, these field tests are still required to meet all the same safety standards as required under the original procedure. And no matter which permit process you pursue, even when the permit is approved, USDA officials and their state counterparts may inspect the field test site before, during, or after a test to ensure that it is conducted and managed safely. After several years of laboratory and field testing, a developer may decide to commercialize the genetically engineered variety and petition USDA to be released from regulatory oversight. In other words, the developer will submit a petition for "determination of non-regulated status."

Upon receipt of a petition, USDA thoroughly evaluates the scientific information provided. Specifically, we examine the biology and genetics of the plant; the nature and origin of the genetic material used; possible effects on other agricultural products and organisms in the environment; and all field test reports. Depending upon the particular plant line, we evaluates a variety of potential effects such as:

1. the potential for creating plant pest risk;
2. disease and pest susceptibilities;
3. the expression of gene products, new enzymes, or changes to plant metabolism;
4. weediness, and impact on sexually compatible plants;
5. agricultural or cultivation practices;
6. effects on non-target organisms, including humans;
7. effects on other agricultural products; and
8. the potential for gene transfer to other types of organisms.

USDA also completes an environmental assessment of the new variety to ensure the plant poses no significant risk to the environment, other plants or non-target species, including humans. Our agency evaluates all available scientific information, including the information provided by the developer in the petition. We then work to ensure that the new transgenic plant:

1. exhibits no plant pathogenic properties;
2. is no more likely to become a weed than the non-engineered plant;
3. is not likely to increase the weediness of any other plant with which it is sexually compatible;
4. will not cause damage to processed agricultural commodities; and
5. is not likely to harm other organisms that are beneficial to agriculture.

We then either approve or reject the petition for technical completeness. If rejected, the developer may choose to either amend and resubmit the petition or withdraw it. We publish both the petition and the environmental assessment in the Federal Register for public comment, and we consider public comments before publishing the final environmental assessment and before deciding that the transgenic plant is no longer regulated. Copies of these our decision documents are available to the public.

If it is determined that the new plant poses no significant risk to other plants in the environment and is as safe to use as more traditional varieties, USDA finalizes the environmental assessment and writes a determination of non-regulated status. This determination enables the new plant to be cultivated, tested, or used for traditional crop breeding without any additional action on our part. In essence, this determination allows the plant to be widely grown and commercialized.

As you can see, our biotech approval process is thorough, demanding and transparent. As confident as we are in it, we are working diligently to make it better, more airtight, more accessible and more responsive to the accelerating pace of technology.

At USDA, we asked the National Academy of Sciences to conduct an outside review of the approval process, and they came back with 89 suggestions. And soon we will announce the men and women who will serve on a committee that will advise Secretary Glickman on biotechnology issues. To ensure that the Secretary receives balanced advice, the committee will bring together a broad cross-section of opinions and expertise. Farmers and private sector representatives will sit on the panel, but so too will consumer advocates and representatives from environmental groups.

It is this kind of oversight, this kind of system of checks and balances, that is lacking in the EU. And that, I believe, is the source of consumer skepticism about GMOs among Europeans. Given the mad cow scare and the discovery of dioxin-tainted chicken, the skepticism is less a reaction to or a judgment about biotechnology itself ... than a lack of faith in their government to protect them from unsafe foods.

There have been some encouraging signs. During his visit to the United States in October, European Commission President Prodi signaled his commitment to establishing an independent European regulatory authority modeled on the United States' FDA. And just last week, the Commission issued a white paper that calls for the establishment of an independent, transparent, science-based food safety regime.

President Prodi also has said that he understands that risk can never be eliminated altogether, that we have to make decisions about new technologies based on the science that is currently available. This would appear to be at least a slight retreat on the "precautionary principle," which has been the basis of European GMO policy. President Prodi is setting the right tone, and I believe a dialogue has at least begun that will help us resolve these issues.

But any such resolution will be a long time coming. And in the meantime, we're still in the middle of a divisive conflict on biotechnology, one that's creating serious transatlantic tension and a polarization that is counterproductive at best and destructive at worst.

All of us have a role to play in toning down the debate and building common ground. While the anti-GMO forces have been responsible for most of the outrageous rhetoric, even the biotech industry is not without blame.

In focusing their research and development on technologies that would help farmers -- those who grow the food -- industry overlooked the concerns of those who have to eat the food - consumers. Few current GMO products have the better taste, freshness and nutrition that consumers would expect from enhanced food. New genetically engineered rice fortified with Vitamin A and iron, developed by the Swiss Research Institute in Zurich, is a perfect example of the next generation of bioengineered crops from which consumers can accrue direct benefits.

The good news is that industry has begun to recognize some of its mistakes and adjust its strategy. At the same time that they have improved their marketing efforts and better explaining the benefits of biotechnology, they are also extending something of an olive branch to consumer groups and environmentalists, in an attempt to launch a more reasoned dialogue.

Further belligerence benefits nobody, certainly not farmers, many of whom rightly feel they've been sold a bill of goods on biotechnology. Already battered by low prices, they are now caught in the middle of what is literally and figuratively a food fight. They embraced GMOs at the behest of the seed companies. But when it turned out that the companies had miscalculated the market for GMOs, farmers were asked by those very same companies to perform the logistical and financial impossibility of segregating their GMO seeds from traditional varieties.

The United States stands by its biotechnology approval process. It is not simply a routine rubber-stamp. It is an exacting system that never begins with the assumption that the product is safe. The burden of proof is always on the product and its purveyors to prove safety, not on the consumer or on government to prove hazards. And we believe that, to increase the flow of agricultural trade, the EU and other nations need to adopt a similar system.

But we also remain open-minded. We hear the doubts and concerns about biotechnology expressed by people on both sides of the Atlantic and around the world, and we respect their concerns. Let's work together, so that we can allow for scientific progress without in any way compromising human or environmental safety.

Thank you very much.

Chair: This morning we talked about animal production and actual production of medicines by farming, described by Dr. Hersbach and now we have Dr. John Pierce of Dupont who will tell us something about the realization of all the promises considering plant and microbiobial biotechnology.

 

John Pierce, DuPont Agricultural Enterprise
"Realizing the Promise of Plant and Microbial Biotechnology"

First slide: This slide is just to remind us that for this entire past century, there have been issues facing global agriculture that seem almost timeless - to feed an increasing world population, to protect the environment, to keep a safe and healthful food supply, which is becoming ever safer and ever more healthful, to provide renewable resources and to do so in a way that is economically viable. We've had help along the way, and the help comes from our neighbors on this planet, the plants and the microbes, and we turn we plants and crops for food and feed and shelter. And microbes are our friends in making all types of food, beers wines and breads and cheeses and medicines and materials. so this type of biotechnology in conversion ultimately of the sun's energy into carbohydrates, and then ultimately, into somewhat more interesting materials has been going on for some time. As we heard this morning from the speakers on both the plant and the microbial side, developments in biotechnology are providing additional opportunities to utilize plants and microbes to produce improved products and materials, ultimately stemming from agriculture. So the impacts that we've had and are having are summarized in this slide. I'll give some examples of the current products on the market that provide for increased crop yields, improved environmental aspects of agriculture and economics for people participating in the production of crops. And in the second part of my talk, I'll talk about the so-called second wave of products - products that provide improved quality of harvested yield with benefits for food safety and nutrition. And then finally, I would like to give an example of some of the uses of microbial technology in renewable production of materials. Now in many ways, and as we have just heard, some of the issues have to do with the folks on the other side of the Atlantic importing something over here, while we're busy over there, dealing with an import from Europe, too, and that's the European corn worm. It's a insect that is present in most all fields of corn in the U.S., it burrows into the plant where it becomes unavailable to insecticide treatments and causes losses and a variety of other damages. The so-called BT corn, the ECB protected corn is one arrow in the quiver to try to control this billion dollar a year pest, it's been rapidly adopted in the U.S. because it provides improved pest control. Another thing that has been found is that the insect serves as a vector for fungal contaminants and fungal contaminants produce micro-toxins these highly toxic material from fungi in the corn and the majority of the plant in the ECB corn has a much reduced amount of micro-toxin in them as an add-on effect to the control of this insect. But perhaps an even larger insect pest in the U.S. is the corn root worm. These pictures show the adults but the most of the damage comes from the larvae who feed on the roots and current control methods require the use organelle phosphates insecticides, soil fumigation and rather certain uneconomical cooperation practices. There is another follow on generation of BP products coming. There a number of companies working on them. This just gives an idea of some root systems of corn, controlled corn plant that has not been treated but the roots have been hurt by the corn root worm, an insecticide treated control and the genetically enhanced product that shows even better control than insecticide treatment, so we're hoping this will be a second addition to enhancing the sustainable yield of corn production that we heard about this morning.

Now going further, there is a whole area of the quality of what is produced in agriculture. These major crops constitute some 80% of calories consumed in the world: corn, soy, wheat and rice are used in processed into a variety of value added ingredients that people consume. I'd like to focus here on soy beans, a major crop in the United States. Soy beans are grown primarily for 2 reasons: for oil and for protein. Oil products that can be obtained from soy beans these days, to the use of biotechnology include soy bean oil with high amounts of mono insaturated fatty acids that was discussed a bit this morning, I'll show you a little more: increased flavor stability and decreased amounts of anti-nutritional components. Many plants that have to live in the environment and take whatever the environment throws the, fill themselves up with compounds that make them unpalatable to organisms that want to eat them. Soy beans are the same way and they cause problems with digestion and we have ways to deal with them. And also there a protein products and I will talk about that.

But soy beans contain a number of bioactive components like soflavones, phytic acid, amino acid constituents and after a long series of clinical studies in the U.S., it was shown that a diet containing soy produced a substantial decrease in total cholesterol and low density lippro proteins in humans. So this is a good thing, people take medicines to try control their tryglyceride levels and recently, last year, FDA allowed for a health claim to be provided on soy products indicating the beneficial affects of an increased soy diet on cardio-vascular health. Now one of the problems with soy beans is getting it widely adopted and used in those parts of the world that have cardio-vascular issues, that is to say the western world. Many people don't like the taste of soy beans and the soy beans indeed have, I personally find them bitter, and they have anti-nutritional components in them. But through breeding, we've been able to develop soy beans that are very low in these anti-nutritional carbohydrates called golacticides and instead have a high concentration of sucrose. So now these soy beans are very low in anti-nutritional components and very high in sucrose, so you have a sweet bean that is digestible and now you can take these soy beans and use them in a variety of products; in soy milks, in cereals in any number of let's say main stream products where normal consumers can consume normal products and get the benefits that are inherent in a soy diet.

You can make them even better by modifying the oil content. Soy beans have a certain amount of oil in them, a large amount, and I believe that 80% of the oil consumed in the U.S. is soy bean oil and some 30% world wide, so this a very major source of calories in this world and to biotechnology we have been able to modify the types of oils that are produced in soy beans. We can make very high mono-insaturated oils, very stable oils for frying and other uses. Very low polyone saturates, very high saturates, very low saturates, some of these are made by GMO techniques, some of them are made by breeding techniques. One in particular, the hiolaic soy bean oil has 85% of hiolaic acid, this is mono-insaturated fatty acid that is found, that predominates in olive oil. It's very stable and as a result you can use this oil in a variety of applications where normally you'd have to hydrogenate and produce trans-fatty acids. Trans-fatty acids have been implicated again in cardio-vascular diseases and we are thinking that adoption of this oil will provide for improved nutritional use of soy beans. This is an interesting case where this is a GMO. We had studied a non-GMO version of this, but we found that the non-GMO version was unstable in various environmental conditions, so if you grew it in the South it had hiolaic, if you grew it in the North it didn't and the hiolaic acid content varied all over the place and that's because it was hiolaic in all parts of the planet and they responded to the environment differently. This plant is hiolaic only in the seed and so it provides a stable production of hiolaic acid. And we again are anticipated by the FDA who in November proposed a new rule for labeling in the U.S. for trans-fatty acids, after some year or whatever, the FDA's process is if it works out there will be labels in the U.S. indicating the amount of the trans-fatty acids in foods. These labels can be reduced by the use of this material. And if you couple the high sucrose bean with the hiolaic you get a very tasty soy bean that is very stable and has all types of new foods uses. So what we hope is this lowly soy bean comes from China, grows in the U.S. will be able to have even further utility in the food supply to take advantage of its inherent qualities.

Now just for the last couple of moments, I would like to turn to biotechnology materials. It hasn't been discussed much today, but you know agriculture and petroleum are both huge huge sources of raw materials. I mean we forget about it's the sheer magnitude of material 'carbon' that is produced in agriculture or dug out of the ground. In fact they are marginally equivalent in size and they cost about the same. They cost about $0.06 a pound to produce corn or petroleum. And now biotechnology as we have heard this morning enhances the use of microbes for further utilizing let's say products such as sucrose or glucose from agriculture to produce value added materials. I would like to give one example of that: polyester. So there is some polyester in the room I am sure. Normal polyester is called 2GT, it's made by alternating molecules of 2 carbon molecules and an A carbon molecule. It's been known for about 50 years that if you make polyester with a 3 carbon molecule so-called propane diol, that you get a polyester that has improved stretch recovery and softness better dye binding capacity, basically a better polyester. The problem is to make it from petroleum you couldn't make it cheap enough to be able to sell it into the market required so it wasn't made and we all have 2GT around. It turns out that there are some bugs, microbes, that can convert glycerol to propane diol and there are microbes that can convert glucose to glycerol. So we were able to study the enzymes involved in this transformation, isolate the genes associated with these transformations and have them incorporated into one microbe, with a result that we now have fermentation process that will now take glucose from corn and make propane diol. So the question then is: Can you make it cheap enough? And in fact, this shows our progress in creating, let's say high concentrated fermentation's to produce propane diol. At present our current process has a greater efficiency than the process used to make ethanol today. Now the ethanol process of course is something that has been done for some time and studied forever and we are just knocking on the door, we are not quite ready to pull the trigger but we certainly are ready to make development investments because we believe we are on the track to success here. We hope in the very near future to make very large quantities of a very nice polyester from a renewable resource deriving from agriculture. So again this is the type of capabilities that will become more and more common in the future. So I'd just like to close again these few examples of actual developments, actual commercializations. First generation crops with improved yields and environmental performance continuing the history of agriculture in adopting the latest technologies to improve productivity. Second generation crops just knocking on the door now with improved nutritional components and health aspects and just coming out of the starting gates but destined to become an important component of biotechnology is the development of new materials from renewable sources that have high value. Finally whilst all of this is going on, and as we've heard this morning, the computational techniques, genomic techniques are adding daily to our understanding of the common processes underlying this web of life and so we can look forward to an ever increasing ability to accurately specify desirable uses of plants and microbes.

Thank-you.

Chair: Thank you very much. The Ambassador reminded me of the fact that in the Netherlands we make cars from potato proteins at ATO in Wageningen, people are here in the audience actually so if you have missing car parts you should talk to Peter Symons, he'll only charge you a bag of potatoes! No GMO's involved, lots of biotechnology .

 

Benedikt Haerlin, Greenpeace
"Genetic Engineering vs. Biotechnology: An Organic Vision of Sustainable Agriculture"

The Dawn of the Biotech Age.

There seems to be little doubt that this brand-new century will be the beginning of the Biotech Age. Biological processes and their proper understanding and use by human ingenuity will replace today's predominately mechanical and chemical production of the industrial age. This will include subsequent replacement of pyrotechnical energy and transformation systems by organic, phyto-technical and biotechnological systems, In combination with the ongoing, revolution of information technologies biology will be the lead science base of technological innovation and transformation of our production system. We all know that today's industrial system is about to destroy and exhaust this planets life support systems and will be unable to sustain future generations. But let's not fool ourselves, there is no automatism or guarantee that the bio-technological revolution will be more sustainable.The only difference is that it has the potential to be sustainable.

What is Biotechnology?

Biotechnology is probably nearly as old as humankind and can be defined very generally as the use of biological processes or organisms for human purposes. Plant breeding and animal husbandry, beer brewing and yoghurt fermentation as well as more advanced technologies of using micro-organisms, phyto-pharmacology, vaccination or the use of biomass for energy production - All these technologies are forms of biotechnology. Progress in all areas of biology, but especially in molecular biology and biochemistry have added powerful additional tools to biotechnology over recent decades.

What is Genetic Engineering?

There is also the remarkably diffuse term of "modern Biotechnology" which some PR guys have coined to avoid calling genetic engineering genetic engineering. However there is a precise definition for genetic engineering, which is the direct intervention on the genetic makeup of an organisms usually by introducing foreign DNA into it's gene pool by means that would not occur naturally. This very specific subset of biotechnology enables humans since less than three decades to create artificial organisms, which are no longer the result of the natural rneans of evolutionary development.

What is GPs position on Genetic Engineering?

Greenpeace is not fundamentally opposing or condemning genetic engineering technologies. Given the still very limited experience with this technology as well as the even more limited understanding of it's overall impacts however we advocate utmost precaution in using this technology, especially on a large scale. However we appreciate the biomolecular insights this type of manipulations have provided over the past years and we believe that genetically engineered organisms can play an important role in the production of new pharmaceutical substances as well as in the conversion of other chemical production methods. The only limit we suggest to this use of GMOs is that they should be kept in hermetic containment and not enter the biosphere.

Why are we opposed to releases of GMOs into the environment?

The fundamental disagreement we have with some genetic engineers and their employers is whether or not such genetically engineered organisms should be releases into the environment. At this point we principally reject the release of GMOs into the environment and the reasons for this fundamental position are probably well known to most of you. So I will repeat then here only in a nutshell:

1. Genetic engineering of organisms creates unprecedented and qualitatively new transgenic lifeforms that have not occurred in nature before.

2. The present scientific knowledge about the functionality of DNA but even more about the dynamics of interaction between organisms are completely insufficient to assess the possible impacts of the release of such new lifeforms the environment. Only a portion of all existing organisms is even known today. And our understanding of their interactions is in its infancy. There are no valid concepts nor is there substantial experience to especially assess long term evolutionary effects of transgenic organisms. While we do not know too much about the possible direct, indirect, cumulative and synergistic effects of GMOs in the environment, we do know that organisms reproduce and adapt to their environments. They are neither stable in their genetic composition nor in their behavior, location and interaction with the environment. Once released into the environment however we have to assume that GMOs cannot be recalled.

This leads us to the conclusion that the only responsible way to handle this technology in the foreseeable future is to prevent tile release of GMOs into the environment. We derive this conclusion primarily from our assessment of what is not known and want cannot be known and to a much lesser extend from what is and can known about the possible impacts of GMOs on the environment. The combination of massive uncertainties about possible detrimental effects of GMOs in the environment and the global and long time potential of such possible effects leads us to demand the strictest possible application of the precautionary principle to refrain from releasing GMOs into the environment.

What are the challenges of Agriculture in the new century?

We certainly all agree that agriculture and food production faces tough challenges and choices, which are determined by environmental and demoscopic imperatives. It has:
· To supply access to sufficient food and a balanced diet for an estimated world population around 8 to 9 billion people in 2030,
· To drastically reduce its emission of climate gases and persistent organic polluters from inputs, production, transport and food processing,
· To stop and reverse soil erosion,
· To stop contamination of water and adapt to the regional levels of sustainable water supply,
· To reduce its destructive impact on habitats and biological diversity,
· To and it will finally have to adapt to highly probable but still unpredictable effects of climate change over the next century. In addition rural production and distribution structures will be decisive for the question of employment and social security of the majority of citizens of this planet. It will determine the speed of emergence and growth of entirely unsustainable mega-cities all over the world. And it will shape the development of global consumption patterns. The total challenge to agriculture in this context is therefore to provide for an increasing number of rural jobs and livelihoods.

To put it a bit simplistic, the challenge is to replace toxic, energy intensive and otherwise detrimental inputs by smart and qualified intensive labor using the state of the art of biotechnology.

Over the past decades, during which we have realized these imperatives, little consequences have been drawn.
· Food production and distribution related energy consumption and climate gas emissions are still steeply growing
· Water consumption is not reduced and increasingly relies on non renewable resources
· Toxic emissions are still unacceptably high and accumulating · Soil erosion continues in most regions of tile world
· All we know about man made extinction rates indicates they are still increasing
· The number of rural livelihoods is decreasing dramatically in most parts of the world, especially in relative terms to the growth of populations.

Further rationalization by increasing industrial input and emissions leads to further extermination of rural livelihoods and employment as well as invaluable so called traditional know-how about the land, the weather and the habitats. The proportional share of industrial inputs, transport, processing and distribution in food production is continuously increasing. The diversity of crops and varieties used in agriculture Is still decreasing and so is the pool of germplasm these varieties are based upon. And last not least the inequality in access to food as well as total per capita use of arable land has rather increased than decreased and is still one of the ftindarriental shames of this world, which leaves hundreds of millions of people hungry and malnourished at a stage of substantial overproduction of food.

Why do we cafi our vision organic?

Over the two decades of Greenpeace campaigns against the emission of persistent toxic substances into the environment and especially during the last years of campaigning against the release of GMOs into the environment, we have come to distrust more and more any short term technical fixes offered by industry in this area. Our conclusion today is that there are fundamental contradictions between industrial agro-chemical production, including genetic engineering and sustainability.

Let me name a few of these contradictions and opposing visions:
· the pursuit of principally unlimited growth and accumulation as opposed to the search for appropriate and sustainable equilibria
· the tendency to speed up and optimize processes to the achievable limit as opposed to adaptation to natural life cycles
· the tendency to optimize single aspects of the production at the expense of it's broader context, resulting in technical solutions frequently creating more problems than they solve
· the tendency to fully exploit economies of scale at the expense of the best small scale solution
· the tendency to standardize processes, products and knowledge at the expense of optimal adaptation to varying local and regional needs and conditions of biological and cultural diversity
· the need to cut costs irrespective of their nature, which leads to destructive exploitation and enforces neglect of unprized or underprized common goods
· the exclusive search for commercially viable products, which progressively include science, know-how and information and the inability to develop, provide and share free access to science, know-how and common goods
· a tendency for short term technical fixes as opposed to longer term integrated and systemic solutions
· the tendency to develop high tech and high risk systems requiring continuous control and elimination of errors as opposed to decentralized small scale and diverse, error-friendly and error-utilizing systems

Organic farming today

Derived from these structural contradictions we have come to learn that the movement and concept of organic farming is by far the closest to address these problems and provide an integrated and forward looking vision of future agriculture.

Let me name some of their basic principles as codified in IFOAM organic standards:
· To produce food of high quality in sufficient quantity
· To interact in a constructive and life-enhancing way with natural systems and cycles
· To consider the wider social and ecological impact of the organic production and processing system
· To encourage and enhance biological cycles within the farming system, involving microorganisms, soil flora and fauna, plants and animals
· To develop a valuable and sustainable aquatic ecosystem
· To maintain and increase long term fertility of soils
· To maintain the genetic diversity of the production system and its surroundings, including the protection of plant and wildlife habitats
. To promote the healthy use and proper care of water, water resources and all life therein
· To use, as far as possible, renewable resources in locally organized production systems,
· To create a harmonious balance between crop production and animal husbandry
· To give all livestock conditions of life with due consideration for the basic aspects of their innate behavior
· To minimize all forms of pollution
· To process organic products using renewable resources
· To produce fully biodegradable organic products
· To produce textiles which are long lasting and of good quality
· To allow everyone involved in organic production and processing a quality of life which meets their basic needs and allows an adequate return and satisfaction from their work, including a safe working environment
· To progress toward an entire production, processing and distribution chain which is both socially just and ecologically responsible.

We know that organic agriculture is still a niche economy, just like solar energy is today in the field of energy production. Despite the fact that it is actually one of the fastest growing businesses in many developed and less developed countries, organic farming is still in its infancy. Not only regarding the scale of the operation, but also regarding it's technological and scientific development.

Organic farming at its present stage of development is not and does not claim to be a drop in solution for all problems in food production today. In order to meet the global challenges outlined above, organic agriculture needs a boost of scientific and technological input and development. In 1998 according to FAOS agricultural committee 0,01% of USDAs research budget is directed to organic farming. EU figures may not look much better.

The ecological, but also socioeconomic successes of organic ventures are striking and by far outpace anything we have heart from genetic engineering which has absorbed billions of R&D investments and public spending.

Still the organic vision will require the collaboration and concerted efforts of governments, business and civil society in order to make it happen over the next one or two generations. While it is a widespread myth that it could not provide comparable and sufficient yields over the long run, organic conversion does require the investment of reduced yields over a period of transition. And we are about to run short of time: With progressing depletion of farm land, water resources and diversity and increasing numbers of people on this planet it is actually conceivable that there will be a time where short term and unsustainable yield increases may appear as the only option left. This would be obviously shortly before we face real and massive catastrophic consequences of the present farming system. The political and moral strength needed for change by then might go beyond our capabilities.

If there is one lesson we have learned from closer and closer collaboration with the organic movement, but also with more thoughtful scientists and experts in the field, than it is that there are no quick fixes and there is no such thing as a free lunch, as Americans would say. To pursue this organic vision requires substantial investments and the ability to wait for their return sometimes a little longer than the next shareholder meeting or the next election.

This appears to be one of the most challenging aspects to the conversion from unsustainable, destructive agricultural practices to more and more sustainable and ultimately organic solutions.

The whole concept does not lean to the short term perspectives of corporate and political decision makers and it appears to contradict the business concepts of major companies in the field. How could Monsanto, however it will be called by then, DuPont, .Aventis, Syngenta actually become organic players? Where is the profit for them? What kind of products could be organic blockbusters? Certainly not pesticides, certainly not monocultural wonderseeds, and probably not even copyrighted or patented software packages. There is most likely no "Agricultural Windows 98" or "Farm Office 2000" that could effectively serve the world- wide diverse need for appropriate information, training, exchange and interaction (however truly effective you might deem Microsoft's products in reality

We have started to talk to more open minded representatives of Life Science companies, to scientists, farmers, politicians about this. We are committed to pursue this discussion further and one of the messages I am trying to get across to you today is that we would like to invite all of you to participate in trying to solve that riddle. However Our preliminary conclusion at this point is that an organic future also requires, if I may say so, more organic business structures and that size as Well as the type of customer-relation required may not match with present company structures.

This is no good news from our perspective. Because from a Greenpeace campaign point of view telling a company to simply get lost, is the least promising of all proposals you can make to them. We certainly love confrontation as a special form of public dialogue, but we do not seek to make real enemies. Whatever action we do - it is always an invitation to cooperate. So we are still -working hard oil this problem.Yet maybe the reason we have not found fully satisfying solutions also has to with the fact, that industrial agriculture as it works today, is an open invitation to a majority of farmers and their communities to get lost. And from what I have said so far, YOU Will Understand that Greenpeace would obviously never subscribe to such a concept of food production.

So where will we be in 10 to 20 years time from now and where might the "battle royal" as Dan Glickman dubbed the great global debate about the use of GMOs in agriculture have taken us by then?

You will not be surprised to hear that I do not see any future for GMOs in agriculture and that my prediction is that we may be smiling about a few arguments we are exchanging now. There are two reasons for this prediction. The first is the presently unfolding global rejection of GMOs in food, which has already significant repercussions in the very few countries that have embraced this technology so far.
We are hearing of reduced GMO planting in the USA in the range of 10 to 30 percent. And we expect similar developments in Canada as well as Argentina. We also realize that major commodity traders are preparing for full segregation of GMO and non-GMO products. We also realize that the great expectations on the future of so called functional foods seem to work pretty well without food producers embracing any GMO inputs. We also realize that major players in the Life Science business are planning to spin off their ag-biotech departments as they are seriously concerned about their future and do not want them to hurt their pharmaceutical business. And we read about consumer attitudes in North America coining closer and closer to those in Europe.

But there is a second reason, which leads me to that prediction the more we will understand about the functionality of genes and the genetic composition of organisms the more likely we %\,-III develop much more elegant and less intrusive and brutal methods of achieving our goals in plant breeding. The better we will be able to combine classical methods of breeding and selection with genomic information and understanding, the smarter and easier we will be able to achieve and use certain traits of plants without shooting foreign DNA at random places of their genome or infecting them with genetically manipulated viruses to incorporate bits and pieces of entirely unrelated genetic information from other species. Genetic engineering as we know it today will soon be seen as an extremely primitive and ignorant way to interfere with the filigreed and complex genetic makeup of individual organisms as well as the web of life.

When we look at the really breathtaking progress of plant, animal and human genomics, we can see how the genetic information of organisms is revealed faster and faster. And we can foresee thousands of books. Of life to unfold literally within months. Of course it will take more than high throughput screening to make sense of this wealth of new information. It actually will take hundreds Of thousands of scientist-years to sit down and read this information carefully in order to better and better understand it I wonder how well trained today's young scientists really are in order to do that job. I am quite certain that young farmers and agricultural advisors are by no means prepared for this. And then again it may well take even longer to put this information and understanding into an ecological context and to analyze and understand exchange, communication and general interactions between all these organisms. That will, by the way, include the discovery of hundreds of thousands of new organisms we are presently not even aware of. There will be plenty of most exiting work for generations of taxonomists and ecologists and molecular biologists and farmers. They will work with devices that will probably compare to today's sequencing equipment just like the latest palmtops to mainframe computers of the early 60ies. And genetic information only the biggest and richest companies can gain and compile today will most likely be as cheap as today's throwaway chips. Probably we will ultimately see still within our lifetime paradigmatic changes in our present concept of information as such, which will be derived from advanced computer, biological and neuro-science All these developments are extremely exiting and hold enormous promises for the biotech age. Certainly this technology will also entail massive risks and probably unprecedented destructive potentials, They may put options in front of societies as well as the international community, which are far beyond our present Imagination. For certain this unfolding knowledge will require the development of ethical and cultural principles and societal adaptation that goes far beyond such simple questions as whether or not we should release GMOs into the environment today.

I personally perceive this global debate about the release of GMOs as a starting point of a much broader and complex challenge we all have to prepare for. And I see certain elements within this debate that I suspect to survive the present dispute:

· The question whether we are able to abstain from the immediate use of something that can be done, but probably should not be done

· A vastly extended realm of scientific uncertainty we will have to deal with in a responsible, which means precautionary manner

· The ability of the scientific community as well as the media and many other institutions to bring together information and knowledge from very different disciplines in a way that enables informed judgement of and democratic decision making of laypersons (who we all realize to be to a higher or lower degree at this time of knowledge and information explosion)

· The question whether governments role Is simply to regulate and adapt to corporate driving forces and structures or whether they are able to organize democratic decision making about technological options

· And finally there is the obvious and actually quite dramatic need for global ethical principles in dealing with decisions of global impact

The organic vision I have tried to sketch out and Greenpeace is pursuing is one contribution to this challenge. And so is our principal rejection of releasing GMOs into the environment. We will be happy to share our visions with other visions and to refine them together with you.

BIOSAFETY NOW!

Last not least let me put these thoughts in context with the most pressing challenge of our political agenda today. I will be flying to Montreal the day after tomorrow, where negotiations of a global Biosafety Protocol have just started and I look forward to meet quite a few of you there again. The establishment of minimal global rules and of an international body to further develop safety standards, is the most obvious prerequisite for any further discussions on this issue.

You all know that negotiations for this Biosafety Protocol, which aims to set at least minimal standards for the transboundary movement of GMOs, have collapsed nearly a year ago because the position of six nations that represent nearly 100 % of today's GMO exports appeared to be incompatible with the position of the rest of the 130 nations represented. And you may also know that the United States of America have been the most important and powerful opponent to tile adoption of that Biosafety Protocol. Negotiations basically collapsed because there was no common ground on these questions:

· Should all GMOs be regulated under this agreement or should more than 95% of all traded GMOs, which are declared as "commodities" be exempted?

· Should the Precautionary Principle guide decisions or only proven detrimental effects of GMOs allow nations to reject their import?

· Should there be a liability scheme holding GMO exporting companies responsible for possible damage or not?

· Should a clear system or traceability of GMOs be introduced or not?

· Should this agreement be guiding trading rules under the WTO or should WTO regulations override the Biosafety Protocols provisions?

Greenpeace has been following closely these negotiations ever since they have been started under the Biodiversity Convention 5 years ago. The majority consensus on this agreement by no means reflects what we would consider advisable and necessary. We never pretended that our demand to stop the release of GMOs could be imposed on the participating sovereign nations. But we equally believe that the international community must not and cannot accept that this urgently needed first international agreement on Biosafety is prevented by a single nation, however powerful it may be. The arrogance of the United States Senate's decision not to sign the Comprehensive Test Ban Treaty of nuclear weapons last year would actually to some respect be dwarfed by the achievement of the United States administration to wreck this Biosafety Protocol.

If short term commercial interests of presently three GMO exporting nations can prevent the establishment of minimum safety rules on this issue, than any further discussions about common ground and perspectives must appear the government simply futile. Another failure of the negotiations in Montreal next week would not only be the most embarrassing declaration of bankruptcy of the worlds governments democratically establish international law under the long shadow of the WTO. It would also withdraw any reasonable common ground for further discussions about the use of genetic engineering in agriculture. And hundreds of congresses like this could never make up for the fundamental loss of credibility of a nation, whose government has chosen to be the most vociferous advocate of GMOs worldwide. It can be in nobody's interest to enter the age of Biotechnology by frivolously missing the chance to establish an international framework of Biosafety.

 

Els Borst, Minister of Health, Welfare and Sports and Deputy Prime Minister, Government of the Netherlands
"Biotechnology and Health"

Madame Ambassador, ladies and gentlemen,

We have just embarked upon a new century. It will no doubt become known as the era of two important technologies: Information and Communications Technology - ICT and biotechnology. It is certain that both will have a dramatic impact on our lives, but there is a major difference. The two technologies are perceived in very different Ways. ICT gives rise to far less anxiety and suspicion than biotechnology. I have never heard anyone ask 'should people really to go that far?' in connection with the Internet. Yet biotechnology constantly gives rise to this question, probably because people regard it as a development which seeks to tamper with life itself.

Government policy with regard to any new technology cannot be based on scientific facts alone. When devising policy, a minister must also take public opinion into account. How do people view the new technological possibilities, their benefits and their risks? The Dutch writer Harry Mulisch, in his novel "The Discovery of Heaven" recounts a discussion between two gods in heaven about us humans here on Earth.

I quote: With each new invention people have stolen a piece of our omnipotence. With their rockets they are already traveling faster than the wind, sound even, and one day they will approach the speed of light. They can see in the dark, they can look into the insides of a human being without opening him up- (.,) If they want, they can even destroy the Earth. Excuse my saying so, but that power really was our prerogative. In the foreseeable future they will have mastered our absolute privilege: the creation of life. End of quote.

There are differences in the level of acceptance of the various applications of biotechnology. There is, for example, a greater degree of social resistance in the case of food than there is in the field of medicine. Haernophilia patients are on the whole much happier with clotting agents produced with biotechnology than with those isolated from donor blood. With the natural product, the chance that this may be contaminated with HIV hepatitis B virus, or some virus we haven't even discovered yet, is always at the back of their minds. Their wish for safety seems to overrule any negative feelings about biotechnology procedures. I now turn to my main theme: What contribution can biotechnology make to healthcare? I have no doubt that biotechnology will provide us with new knowledge which will lead to many improvements in prevention and therapy. Yet it can also provide us with knowledge which may lead to increased suffering.

Let me first give you some examples of the medical advancements of biotechnology. To begin with, better vaccines. Many vaccines produced by traditional methods have drawbacks, such as allergic reactions to vaccines cultured on chicken protein. Biotechnological techniques circumvent such problems. This development has already been put into practice.

Then there is the development of better, safer drugs. I have already mentioned Factor Vill for the treatment of haernophilia. Another example is insulin for the treatment of diabetes. A completely new field is that of pharmaco-genomics: the development of never drugs by the application of our knowledge of DNA sequences. This approach will lead to more effective and more specific drugs. Currently, around thirty per cent of patients using some form of medication derive no benefit from it at all. By targeting the drug to the

And it is this last application which brings me to the other side of the biotechnological coin, the side that can lead to increased suffering. Unfortunately, the opportunities for diagnosing genetic abnormalities are developing faster than the therapeutic possibilities. One of the most harrowing examples of this is Huntington's Disease. Here, a genetic defect inevitably leads to a condition which reveals itself in early adulthood and then steadily progresses to result in death within ten to twenty years. By 'inevitably', I mean just that: one hundred per cent certainty. In the final stages of the disease, the patient develops dementia. We now have excellent means of prognosis, but absolutely no means of prevention or treatment. In a situation like this, it is essential that people receive the very fullest information, so that they can decide for themselves whether they wish to know their fate or not. Everyone has the 'right not to know'. This is a fundamental and inviolable right which we must conscientiously uphold.

Knowing that biotechnology can bring many improvements to health care, what should be the government's role in the development and introduction of medical biotechnology?

The Dutch government has a positive attitude towards medical biotechnology. It is essential that the government is seen by the general public to be both trustworthy and credible. People's confidence in science and scientific methods can no longer be taken as read. However, people are prepared to place their confidence in careful and conscientious procedures, by which I mean procedures in which various parties examine a development or product from various perspectives. The government must ensure that this is what happens. The policy I advocate is one which is open, careful and pro-active.

We therefore apply a number of measures to ensure that the patient's interests are foremost. First, all health risks are identified and assessed. The moral issues are raised and discussed both in a public debate and in parliament The benefits of the new applications are examined and weighed against the risks. A Central Committee must be trained in providing proper guidance to patients to help them in dealing with the new knowledge which predictive medicine provides.

We shall lose a great deal if we don't move forward with biotechnology in healthcare, but many questions remain to be addressed. These questions are not primarily the concern of doctors and geneticists, but that of the social scientists, behavioral scientists, ethicists and public administration experts. My request to the medical biotechonologists is therefore: be open to cooperation and interaction with these disciplines. Your work and its products will not automatically be accepted by society. You are dealing with extremely complex matters with far-reaching consequences. They require a process of continuous communication. Or, if Harry Mulisch will allow me to paraphrase the title of his book, "Only together can we discover heaven."

 

Annemarie Jorritsma, Minister of Economic Affairs and Deputy Prime Minister, Government of the Netherlands
"Biotechnology and Economic Development"

Madam Ambassador, Ladies and Gentlemen,

On the one hand, I feel sorry for you. If I have counted correctly, I am the 18th speaker who you are expected to listen to today. On the other hand, I also envy you. Because today and tomorrow, you will be faced by a large number of people who can tell you everything there is to know about biotechnology, and its significance to society. People from the world of science, industry, politics and the environmental protection movement. I would therefore like to compliment the American embassy for its choice of speakers, because both supporters and opponents have been invited to tell their side of the story.

In me you will find a proponent, for the simple reason that I anticipate that this new millennium will be the era of IT and biotechnology. Both IT and biotechnology will expand to become important and high-quality economic clusters. And, as minister of Economic Affairs, I therefore believe that the Netherlands should do everything in its power to take advantage of the potential inherent in these fields.

We are already quite successful in the field of IT. According to a recent study conducted by the American International Data Corporation on the subject of IT applications and developments, the Netherlands ranks 7th in a group of 55 countries. We are now counted amongst the leaders, the 'information elite', together with the US, Singapore and the Scandinavian countries.
With respect to biotechnology, we don't rise above average, despite growing investments and an increase in the number of biotech companies. Currently, there are about 50 young Life Sciences companies active in the Netherlands, and almost 300 somewhat older companies involved in research and the quest for new product applications in this field. As such, these figures are no reason for us as a country to hang our heads in shame, but I want more. I am not satisfied with a place in the pack. I want to be amongst the leaders, like we are when it comes to IT. Don't misunderstand me, I don't mean the world top - that would be too ambitious - but I do want to aim for the European top, the European 'biotech elite'. Surely that must be possible. The Netherlands has an excellent level of scientific knowledge, and cooperation between industry and science is good.

The Netherlands therefore has everything Life Sciences companies could wish for - at least, that's what I thought. But there's one thing the Netherlands lacks, or has too little of: I am referring to starting Life Sciences companies.

Studies have shown that the Netherlands comes tenth in Europe with regard to the number of starting biotech companies. This is an alarming figure, because it is precisely these start-up companies that are so important. Not only to commercialise scientific knowledge, but also to expand those industries that are already so vital to the Netherlands: the chemical, food and pharmaceutical industries.

Using the benchmark method, where we compared our own situation to a number of successful regions in the field of biotech, we discovered why there is such a shortage of start-up companies. The Netherlands is lagging behind considerably when it comes to a number of important issues:

Keeping these facts in mind, I called a meeting with experts and people from the field. Together, we drew up an action plan aimed at two things: to catch up with the lags I have described, and to ensure that the Netherlands attracts more starting Life Sciences companies as soon as possible. Put in more concrete terms: currently, we welcome about 5 biotech starters each year. We must boost that number to at least 15.
Ladies and Gentlemen,

I won't bore you with all the details of this plan, but I would like to describe a number of measures to you. In summary, as far as the government is concerned, this relates to funding and the establishment of a platform. We don't wish to involve ourselves any further, because I believe that the primary responsibility lies with the parties involved.

As far as funding is concerned, I will make a total of 100 million guilders available over the next 5 years. This money will be used in various ways. First of all, to stimulate enterprising researchers to set up their own company, based on their findings. Also, to set up office space and lab facilities and to purchase research equipment. Finally, I want to use part of that money to supplement the available venture capital by introducing a start-up participation fund to the market. This fund is designed to support new companies with start-capital.

In addition, following the example of the US, Germany and Canada, I want to establish a Life Sciences Platform. This platform, where scientists, industry, investors and governments will be represented, must assure the progress of the action plan. Furthermore, the Platform will be involved in all kinds of important activities, such as creating and expanding networks, providing courses on entrepreneurship to researchers and promoting the Dutch Life Sciences cluster, both at home and abroad. This platform is due to commence no later that June this year. In early February, at the opening of the European headquarters of Genzyme, I will go into further details.

Ladies and Gentlemen,

That's the action plan to date, and that's my story almost told. A story that puts strong emphasis on the economic opportunities of Life Sciences and biotechnology - and a story about the measures designed to enhance these opportunities enormously. In particular, because our neighbours are more active than we are in stimulating this cluster. As a consequence, companies may prefer to base themselves in these countries, rather than in the Netherlands.

Apart from this threatened loss of employment opportunities, another factor to consider is that the Life Sciences cluster is an ideal knowledge cluster. A saying we also have here in the Netherlands says it all: knowledge is power. Companies, universities and knowledge institutes know that they must develop increasingly more sophisticated products and production processes if they are to survive. And this knowledge is also very important to Dutch industry, because it should help us to overcome a number of boundaries, a number of barriers. For example, space-restricting boundaries, barriers to mobility and environmental barriers. Biotechnology in particular has served us very well in this area already. For example, technologies used for soil decontamination and water purification, and applications in the chemical industry that have led to reduced emissions.

Therefore, we are very keen to have and to keep the knowledge that will generate a strong Life Sciences cluster within the Netherlands. Does that mean biotechnology at all costs? No, of course not. Nevertheless, I have great confidence in science and technology. And I have great confidence in the way new products must undergo thorough controls by industry. I also trust the public and the environmental movements, because any excesses will be severely punished, and rightly so.

Finally, the public has the assurance that the Dutch government will also keep a close scrutiny on new developments. Together with my colleagues, minister Els Borst who also spoke here today, Laurens Jan Brinkhorst, who will speak here tomorrow and Jan Pronk, we are drafting a policy document that will indicate exactly under which scientific, social and commercial preconditions these technological applications will be accepted. I anticipate that this policy document will be published shortly.

All these, to my mind rock-solid certainties mean that I must conclude, in unison with my colleague Els Borst: 'We lose a great deal if we don't move forward.'

José Sarukhán, Instituto de Ecología, Mexico
"Biotechnology and the Environment"

The agricultural revolution has been, arguably, the most fundamental innovation in the history of the cultural and socio-economic development of humankind. This was, from the beginning, a revolution with a definite environmental impact on Biodiversity through the complete removal of natural ecosystems. Contrastingly, it also increased biological diversity through the creation of new, formerly non-existent domesticated plants and animals. This was achieved through a process of selection under domestication and germplasm management. Due to the expansion of the agricultural frontier through the centuries to provide food and goods for an ever-increasing human population, it has been repeatedly mentioned that agriculture has been a human activity intrinsically destructive of biological diversity (1). It is not surprising that this argument has been used to palliate statements concerning the possible negative effects of the use of GMO's on the biological diversity of a region. This is particularly true when agriculture is practiced in a resource-inefficient way, or when it uses technologies not adapted to the environmental characteristics (soils, slopes or climatic regimes) of an area. But it is not acceptable as a "blanket statement" to justify risks imposed by GMO's. Small holding, poor quality and highly pervasive agricultural systems in developing countries, as well as resource-and-energy inefficient, high-input, "monetarily-productive" agriculture in great extensions in developed countries, are both equally destructive of biological diversity.

In my presentation today, I will analyze the environmental effects of the release of genetically modified organisms (GMO's) into the environment, mostly regarding the conservation and sustainable use of biological diversity (Fig. 1). Besides referring to the effects of agriculture in general and GMO's in particular, I will deal with aspects of risk assessment and monitoring as well. However you will see, by the examples I will be using, that much of what I will say about the potential environmental risks or impacts of the use of transgenic technologies, is equally applicable to present day conventional agricultural practices the world over.

SELECTED EXAMPLES OF THE ENVIRONMENTAL EFFECTS OF AGRICULTURAL ACTIVITIES

By far, the most important global cause of Biodiversity loss, habitat fragmentation, soil degradation, reduction on aquifer replenishment, etc., is the loss of natural habitats by their conversion into agricultural and grazing land (Fig. 2). It is also the second most important emitter of green house gasses. Virtually all of the territorial extension of Europe was thoroughly transformed due to agriculture since the last few thousand years. 85% of the old growth forests in the US disappeared due to the extension of the agricultural frontier since European colonization. The present high rates of deforestation in the world's tropics result from habitat loss to agriculture. One-fifth of the world's forest has been lost to agriculture in the last 300 years.

Human activities, fundamentally agriculture, have at least doubled the equivalent of N fixed by plants and made it available in the environment (31). This has exacerbated acidification of soils and water bodies, changing species composition of ecosystems, raising nitrate levels beyond acceptable levels in drinking water and causing eutrophication of lakes and the sea. The most dramatic example (Fig. 3) of the latter is the "marine dead-zone" created in front of the delta of the Mississippi in the Gulf of Mexico. Global fertilizer use soared from less than 14 million tons in 1950 to 145 million in 1988, falling back to 135 in 1996 (Fig. 4).

In 1995, world pesticide consumption reached 2.2 million metric tons of active ingredients. Pesticide use causes 3.5 to 5 million cases of acute poisoning a year. Developed countries use 70% of the world total pesticides in about 26% of the Earth's total landmass, while developing countries use the rest in roughly 72% of that landmass.

Agriculture accounts for some 70% of water consumption worldwide and the UN forecasts an increase of 50-100% in irrigation water in 25 years. However, agriculture is the single biggest and often most inefficient user of surface and groundwater worldwide.

HOW MUCH DO WE KNOW ABOUT ENVIRONMENTAL EFFECTS OF GMO USE

GMO's have been released into the environment relatively recently and their geographical expanse and ecological conditions are so far relatively constrained. Consequently, solid information about their actual effects on the environment and on biological diversity is still very sparse, and there is not yet an agreed measurement of the seriousness of their environmental harm.

Most of the released GMO's have traits that fall into the following four categories (Fig. 5): 1) Herbicide resistance, allowing the use of broad spectrum, short lived herbicides, to which the GMO is resistant; 2) Resistance to viral, bacterial and fungal infections, mostly through the introduction in the plant of genetic material of the viruses, in a technique similar to vaccination in humans; 3) Resistance to insect attacks, mostly through the introduction of the Bt gene from Bacillus thuringiensis, a bacterium toxic to many insect species, specially moths and butterflies, and 4) Resistance to conditions of high salinity or toxic concentrations of certain metals such as aluminum in degraded tropical soils. These are traits difficult to obtain since numerous genes regulate them. Undoubtedly, to each beneficial aspect it is possible to also define a possible harmful effect. There will always be risks inherent in any technological intervention with nature.

The British Nuffield Council of Bioethics' report on Genetically modified crops (3) concludes that, regarding damage to the environment by GMO technology, they believe there is no evidence of harm to justify calls for bans or moratoria on GMO plantings in Britain (2). Basically a similar conclusion was reached by the Bern conference sponsored by Swiss Governmental agencies last year, when over a 100 worldwide specialist from different disciplines met. In both the Nuffield report and the conclusions of the Bern conference it was concluded that risk assessment activities should be based on scientific grounds and results validated case by case, and step by step, before they are accepted by regulatory bodies.

A few instances of specific environmental harm related to GMO's have been reported in the literature. A well-known and publicized example is the one referring to the effect of pollen of Bt maize on larvae of Monarch butterflies. John E. Losey and collaborators reported (15) that caterpillars of the butterfly fed with milkweed leaves dusted with Bt engineered maize pollen, showed 46 % mortality. However, the authors point out that caterpillars normally avoid eating leaves that contain normal pollen of any species, probably due to behavioral traits. They conclude- very wisely in my opinion- that given the projected increase of acreage of Bt maize in the U.S., "it is imperative to gather data necessary to evaluate the risks associated with this new agrotechnology and to compare these risks with those posed by pesticides and other pest-control tactics".

I think it convenient to make a reference also to potential positive influences that GMO's might have towards the environment, some of which may also take place in areas different from agricultural fields. The genetic changes that have made possible the domestication of agricultural crops have not been possible for trees, since hundreds of generations are required to achieve some degree of selection of a trait. Now genetic engineering provides the opportunity to achieve such changes in a few years. Scientists at the Forestry Department of the North Carolina State University are developing a gene that reduces the accumulation of woody tissue (lignin) in the trunk increasing the amount of cellulose, and stimulates the growth of aspen used for the production of cellulose for paper. Fast growth is an attractive economic trait and the reduction of lignin from the cell walls helps solving the most energy intensive and environmentally harmful step in the industrial process of pulp and paper production.

An additional potential beneficial application of genetic engineering of use at a global scale may be the future development of different non-crop plants adapted to grow in highly stressful conditions with the purpose of ecologically restoring severely deteriorated soils.

APPLYING THE PRECAUTIONARY PRINCIPLE.

The paucity of reliable data on the effects of GMO's on Biodiversity, does not make acceptable the argument stating that "the lack of evidence of harmful effects is evidence of lack of harmful effects". Adopting a precautionary approach when releasing a GMO into the environment, is clearly and scientifically sustained by the theoretical and empirical knowledge provided by evolutionary ecology. It is extremely dangerous to generalize about the ecological properties of a species. There is no meaningful way in which a study made of one sample from a species can be said to represent that species, until the range of variation within and between its populations can be established (3).

However, to be consistent in applying the precautionary principle for the protection of the environment from the risks of GMO technologies, we should also consider in all fairness its application to current agricultural practices, whose severe environmental effects at the local and global level we have briefly seen. However, arguments have been advanced by eager GMO promoters saying that: a) there is no reason to apply such principle now, because it was never applied before in deciding which agricultural technologies are acceptable in relation to their effects to the environment or, b): the principle constitutes a hindrance to further research and development of new technologies.

These arguments make little sense. The precautionary principle should be interpreted as a vigorous promoter of more research to understand better the possible implications of these new agricultural technologies for the environment, and not as an obstacle to innovative research.

ENVIRONMENTAL RISK EVALUATION.

The range of ecological variation affecting a given GMO crop is dependent on the biology of a species and its geographic and environmental ranges. Therefore, a case-by-case risk evaluation must always be practiced, based on a descriptive "equation" of risks (Fig. 6):

Characteristics of the GMO + Its intended use + Environmental characteristics = RISK ASSESSMENT

The information necessary to properly carry out risk assessments is not simple to obtain, if it exists at all. Basic data are needed for such environmental assessments. To begin, full information of the biological aspects of the living organism before it is genetically modified is needed including, among other elements, its ecology, reproductive systems, taxonomic and phylogenetic information, dispersal and distribution mechanisms. Concerning the innovative traits the living modified organism has acquired (e.g. herbicide or insect resistance), we need to know about the methods of expression of the trait, new genotypic or phenotypic attributes, characteristics of the host or parental organism, and interactions of the GMO with the target environment (27).

To determine the possible risk scenarios it is essential to define the uses a GMO is intended for, since this is an important part of risk assessment (2, 8,15, 27, 28). This is to say the planned extensions and volumes of production, the objectives of the release and the human-health risk assessments. Relevant ecological data about the intended sites of release needs to be collected at local and regional scales. Examples are temperature, precipitation, surrounding vegetation types, presence of taxa phylogenetically related to the GMO (potential recipients of a GMO's gene flow), and relevant invertebrate fauna (particularly pollinators and herbivores). The possible effects on populations of wild species (e.g. birds) need to be assessed as thoroughly as practicable, in order to reassure the public of the exact effects of the release of GMO's on those populations (4). It must be shown that the various impacts of the GMO technology have been carefully considered and that they are at least neutral or innocuous (5, 16, 17).

MONITORING THE ENVIRONMENTAL EFFECTS OF GMO'S.

Finally, when all these data are available at an adequate level, a decision can be made to release a GMO into the environment (2, 6,19, 29, 30). The need for risk management and monitoring commences at this point. Monitoring of the possible effects of GMO's on the environment, particularly on the biological diversity of a site or region, is essential if one wants to evaluate the impact of these new agricultural technologies and learn more about how to use them efficiently. The methods needed to evaluate and monitor biological diversity in both natural or man-managed ecosystems are essentially similar: one needs base-line information on the original biological diversity at the species and genetic levels, population sizes of key species, characterization of guilds of species, etc.

Countries or regions which are centers of origin of crops, possessing many relatives of domesticated or semi-domesticated species, should receive specially careful consideration about possible impacts of the release into the environment of transgenic crops of which they are centers of origin or diversification (6, 7, 8).

Experiences regarding genetic or DNA flux from GMO´s into wild relatives of cultivars and into the cultivars themselves are concentrated on species of economic importance in European agriculture. A virtual absence, particularly in highly susceptible species like maize, impose the need to carefully and continuously monitor the effects of GMO´s, on an individual basis, in the field (9, 10,).

Some of the environmental questions that in my opinion deserve research and observation in a monitoring effort are (Fig. 7):

a) Is the escalation of the "co-evolutionary war" between GMO plants and their pests equal or greater than that occurring by the use of the traditional agricultural techniques? (11, 12,13)

b) If genetic traits of stress tolerance were passed into wild taxa, is there an expansion on the niche of these species that may result in the suppression of biological diversity in the surrounding areas affected by the GMO cultivation?

c) Would the adoption of stress tolerant GMO's (e.g. adaptation to severe soil deficiencies), promote a considerable extension of the agricultural frontier, further reducing extensions of natural ecosystems where formally no agriculture could be practiced?

d) Do high diversity communities (e.g. in the tropics) have greater resilience and therefore are less prone to potential risks represented by GMO's?

e) Is the greater pollinator specificity found in general in tropical species a barrier to pollen flow from GMO's?

Finally, there is need to monitor the cumulative effects of modified crops, since it is this impact what may become unacceptable, rather than the individual cases.

SOME FURTHER CONSIDERATIONS.

The aptitude to evaluate and manage the potential risks of GMO´s is directly related to the capacity to produce and/or use them in a safe and efficient manner. This is an important issue. Both the potential benefits and risks of releasing GMO's into the environment are site, region and country dependent. This implies that national, regional and local aptitudes are key components not only to make decisions regarding the environmental release of GMO's, but also defining the economic success and the environmental safety with which transgenic organisms can be utilized in agriculture. These aptitudes involve not only a country's scientific and technical skills; they are also related to regional or national agricultural policies, as well as socio-economic and cultural traits, which should also play an important role in a country's decision to adopt GMO technologies.

Such traits and skills are fundamental in determining whether the use of the new GMO technologies may be a true alleviator of environmental stresses posed by present day agriculture (14), or if they will become one more deleterious addition to already existing conventional technologies which negatively impact the biological diversity of the world. Both poverty and structural change in rural areas have historically resulted in severe environmental deterioration. The adoption of modern biotechnologies should not generate these processes or make them advance further.

CONCLUSIONS

Three premises must be observed in order to reduce the negative impacts of agricultural systems on the environment, whether using GMO's or not (Fig. 8). The first one is that we have a limited knowledge on how ecological systems operate and react to different impacts of human activities; consequently, particular care should be taken in the assessment of the environmental effects of GMO's on impact assessments by establishing truly efficient and long-running monitoring mechanisms. The second is that, globally speaking, no single agricultural technology is the answer to an ecologically sustainable and economically successful agriculture. If we want to preserve as much as possible the biodiversity of an area, we must adopt diversified agricultural systems that maximize such diversity, developing multi-strategy technologies, based in the best available agricultural practices that are environmentally "friendly". These may include anything from the so-called "traditional or indigenous agricultural practices" to the use of GMO's. A good model to study in detail are the biologically diverse agricultural systems practiced in many parts of the world, particularly in biodiversity-rich, developing countries (17, 18, 19). Here, the biological diversity of the agricultural system is maximized at the genetic, species and community level. This is achieved by simultaneously cultivating several genotypes (or land races) of a crop; mixing the main crop with other, secondary crops and maintaining a highly diversified floristic community, which is both a source of useful plants for the farmer and is host to many biological controls of pests. And finally, the third is that it is technically feasible to design GMO crops which avoid the potential risks that some of the present generation of GMO's have. An example would be avoiding the expression of Bt genes in pollen. Also, the development of genetically engineered organisms with bioremediation and ecological restoration purposes should be encouraged and made available at very low costs for utilization the world-over.

In order to achieve in the following decades the enormous potential that genetic engineering has for securing food production and their possible role for ecological restoration, the development, introduction and adoption of GMO's cannot be based in regarding the environmental damage as an externality in the economic considerations of both genetic engineering companies and Nations alike.

A final conclusion is that Science must be at the center of any discussions or controversies about the potential benefits or harms of GMO' on the environment. And the well-being of mankind should be the aim of those discussions, considering humans as a species totally dependent on the ecological systems which contain the world's biological diversity and provide the ecological services essential for sustaining life on Earth as we now know it.

 

Jim Murray, The European Consumer's Organization (BEUC) "Biotechnology and the Consumer"

Consumer concerns about biotechnology in Europe, in terms of environment, health and other issues have tended to focus on foodstuffs. The use of biotechnology in other sectors is less apparent and tends to present a different risk/benefit aspect. The introduction of GM food and food ingredients in Europe has been disastrous for everybody: producers, industry and consumers.

BEUC does not oppose the development and introduction of GM food and food ingredients; nor do we think that there is any inherent general risk to human health in the use of these products (although we do oppose some specific products). We believe that there must be a good authorisation system for such products (which we do not have at present), that certain potential health issues must be addressed and above all that consumers must be able to choose to cat or not to eat products derived from genetic modification.

GM products did not come on the market one by one for consumers to accept or reject. They came through derivatives of commodities, particularly soya, which potentially may be found in 60-70 % of packaged or processed foods. As a result, we launched our Campaign for Consumer Choice two years ago. The attached slides give a "flavour" of our demands, which were two-fold: that consumers should continue to have a choice between GM and non-GM products and that they should have the necessary information to exercise that choice. In other words, we wanted availability (of non-GM products) and labelling of products derived from GM organisms.

At the beginning we saw little hope of persuading the Commission or other public authorities to take action in the form of new regulations and our initial objective therefore was to try to change conditions in the market, which would then be followed by the appropriate regulatory response.

The new labeling regulations announced by the European Commission last week will not meet consumer demands. On our analysis of the text, it seems that it will not be necessary in practice to label food containing highly processed soy oil derived, from GM soya. It will be easy to avoid having to label modified starch and GM maize/corn derivatives such as maltodextrin, fructose syrup, glucose syrup, or additives such as sorbitol and mannitol.

The exact effect of the regulations is not yet known, because we do not yet know the scope of the proposed "negative list". It seems clear, however, that the labeling requirement can be avoided for many ingredients, by way of extra processing (to remove DNA or protein) and/or by putting such products on the negative list.

If our interpretation is correct, there will be many food products on the market containing ingredients derived from GM plants which will not have to be labeled, even when the producer and manufacturer (but not consumers) know very well that the ingredient comes from a GM plant. This is not consumer choice. I call on the Commission to bring forward new measures to close the loopholes opened up by the use of so-called "principle of equivalence" and the negative list", and to ensure that food and food ingredients derived from GM organisms are labeled accordingly.

 

Juan Enriquez, Harvard University
"Conclusion"

I want to talk to you today about systems. I want to talk to you about how systems are changing and how quickly they are changing. In 1700, the difference between the richest country in the world and poorest was about four to one. The reason for that was that in an agricultural society or in a system based on mining, it was very hard for one human being to be leveraged to the extent that if he got up an hour earlier, he worked a little bit more or he got a better plot of land, that region or that society could generate a much greater differential with other societies. What happened with the industrial revolution was that all of a sudden a machine did the work of 1000 people and so the people who had access to those machines and who were able to build those machines all of a sudden started generating very much more product, in terms of the economic output, then other societies. One of the effects of that is that last year, the difference between the richest nation in this world and the poorest nation in this world was about 245 to 1. So you go from a 4 to 1 ration to a 245 to 1 ration.

Now I would like to just show you what has been happening as of the 1930s and 40s. Most of the nations in this world, including the Netherlands, were following pretty much a parallel track even after the industrial revolution. You had a system where the Netherlands, Japan and Germany were basically on the same track. After World War II, one of the things that happened with the computer revolution was that some people became computer literate and IT literate. Communications, information technology and electronics have been a driver along with a series of other technologies that have continued to separate nations that develop technologies and that do not. You can see this change in who are the largest corporations. If you look at the U.S. the names in 1900 of which companies were large companies were cotton, oil steel, sugar, refining tobacco, electric, lead, mail and gas. Not one of those is in the list of the largest companies in 1998. What you are going to see with the IT and biotechnology revolutions going forward is that the companies that you are going to see on this list in fifty years are going to be very different companies that you see on the list now. Meanwhile, the rest of the world, Latin America, Africa, parts of Asia, are still such in a commodity economy. If you look at the largest companies in Latin America, you find that they are oil, gas, cars, tabacco, utilities and one telecom. That differential, the ability to produce and use knowledge, has incredible consequences for the life styles and the ability of people to survive. It is incredible how quickly this is happening. Even if you assume that there is a Wall Street bubble, which there probably is, even if you assume that the Internet economy is overvalued, which it is, the speed of change in this economic structure is absolutely staggering, because you have established firms in almost every field; media, finance, transport, even in the auction business, that have been around for 100 years, that have relatively large market capitizations. A company like Yahoo, which was founded in 1994, all of a sudden has twice the market capitalization of a company that has been around for 100 years. That becomes consistent. You see it in places like Sears, that has been around since 1893 and Amazon.com is now valued at twice what Sears is. Then you look at employment. Sears is working with 325,000 people and Amazon is working with 2100. That has implications. What this is telling me is that you can create an awful lot of value. You do not need factories. That value can move. You do not have to depreciate a factor over ten years and if you lose the people who are able to generate a knowledge economy in your society. You are going to lose a lot of value and it can happen very quickly.

Let me give you a sense of how quickly this is happening in the biotech revolution. The ability to sequence genes is like a new alphabet. If you think in terms of what the digital revolution did, the digital revolution took an alphabet that was 26 letter and it said that everybody in the world, instead of speaking in 26 letters, is going to speak in two letters, in ones in zeros. A common language started driving businesses that were completely separate together. All of a sudden the guys who were doing photography, music, cable, pagers and phones, were speaking the same language as the guys doing newspapers. You started getting industrial combinations like Time Warner, CNN/AOL, MSNBC, and ABC Disney. Disney is not buying ABC because it wants to advertise Mickey Mouse. It is buying this company because the language that both of these companies are speaking is interchangeable. Now think of a base four alphabet. Think of what it means to be able to describe all forms of life as long strings of ATCG. Think of what happens when you have a basic computer code. If you rewrite the computer code the screen looks different. That is the source code. If you get the source code for life, you can start rewriting, and directly and deliberately influencing the course of evolution. That is an absolutely mind bending task, because it puts enormous power not in the hands of nations, but in the hands of individuals. It is individuals who are driving the world economy today. Let me give you a sense of how quickly that id happening. The cost of sequencing a gene in 1974 was about $150 million. Today it is about $150. This is not a slow revolution.

I am not going to go into why it is happening, because previous speakers have said it. What I do want to say is there are reasons why this goes way beyond biotech. Biotech was very quickly cutting, splicing and shooting. What you have today is an absolutely extraordinary explosion of an ability to build on a molecular level. Think of it as being able to build with bricks, but on a molecular level. It is driven by a whole series of technologies that are additional to and complementary to biotech. What it is doing is that it is having the same effect as the digital revolution did. The digital revolution led to five of the largest mergers in this world over the past decade. The life science revolution by bring together chemical, pharmaceutical, energy, cosmetic companies and others, all of these companies are going to start speaking the same language. The implication of them speaking the same language is that their scientists are going to start interchanging information and if you see anywhere near the effects that you saw in the IT revolution, this is going to drive a series of mergers that are going to be very large. In fact, the Glaxo SmithKline merger creates an entity that is larger than about 150 countries in this world in terms of market capital and GNP.

There is a poor guy sitting in the patent office in the U.S. In 1991, someone shows up with 4,000 requests for patents. The other guy is overwhelmed. What is he going to do with 4,000 requested patents? Four years go by, and as he is processing these things, he gets 22,000 applications. One more year goes by and 500,000 applications arrive. What this is telling you is that this stuff is happening faster than Moore's Law. The amount of data being deposited in Gendaq is about fifty percent faster than the speed at which computers double their power and halve their price. This is a revolution of an absolutely unprecedented order of magnitude and speed. It takes basic industries like agriculture and because seeds are packets of DNA that you can reprogram, it raises the value of seed companies and it does so very quickly whether you company is old, relatively new or very new. All of a sudden, a company goes from a stock price of $1.67 for a boring old seed company producing corn every year, to about $ 3. When you start seeing returns like that, one of the things that happens is systems start driving even faster. Your price earnings were issued on the stock. What people are expecting seeds to produce, how quickly they are expecting it to produce, you can see by the PE ratio. How much am I willing to pay for a stock? How much is it earning? How much is it expected to earn? These go from ten, to fourteen, to thirty-two. In the case of something like Delta Pineland, which produces most of the cotton in the world, they have a PE ratio of about 494. These are expectations. Maybe they will become reality or not.

One of the things that happens is that the approval of GM foods goes very quickly. It is not just the products, but the products derived from these products that very quickly hit the supermarket shelf. There are a lot of people in Europe upset about this. They are trying to stop this. One of the things that people should be think is: what are the potential consequences in a system that is moving this quickly, of getting into a debate like that. The labeling debate requires segmenting a commodity system. That is a very interesting thing to do because it decommoditizes what has so far been a commodity system. Let us assume for a second that bad, old Montsanto has to decommoditize and actually create a traceability system from seed through shelf. Right now, in the supermarket, there is GM corn and non-GM corn. You are probably going to buy the non-GM corn. If you start seeing rice with beta-carotene, or a series of nutriceuticals, and these products actually come to market, one of the consequences of separating these commodity systems is that there is going to be one system with the ability to trace farm to shelf. The other system, the European system, will remain commoditized. Guess where you make more money? Guess who is going to be more competitive? The second thing that people might want to think about is differentials in productivity. Agriculture is big business in Europe. Agriculture uses 50% of the EU budget. Agriculture has very low margins. What happens in this system if one part of the system becomes a lot more productive a lot quicker? The third thing that you might want to think about is how quickly can you generate a lot of capital, a lot of brainpower and a lot of investment. The second largest super computer in the world has been built in the last nine months. It was built by a company that did not exist in Europe. You will hear from the founder of that company tomorrow. Let us take a look at the subsidy system. If you are using 50% of the EU budget right now to sustain agriculture and the reason is you want to sustain a lifestyle, you want to sustain a structure and the stuff has a three to five percent margin. If you find a way to make farmers in the rest of the world more productive by three percent a year through biotechnology, in the first year it eats up all the profits that exist in the European system so far. Every year there after, to maintain the same lifestyle farmers, the Europeans will spend $1-1.5 additional in the EU budget to stay on the same treadmill. I wonder if that is a sustainable system. Particularly at a time when the real value of commodities is about one-fifth of what it was in 1945. You are paying a lot of money to produce something that the world is getting very good at producing and is producing at a lower price. This is not unprecedented change. Agriculture, precisely because it has low margins, is a system that changes very quickly. Framers that fall behind go out of business very quickly and you see a series of examples, when you started using grain elevators, the cost of moving a bag of grain in the 1850s went from about 5 cents to about one-tenth as much and very quickly. You saw the same thing with horses and self-propelled combines, where over the course of a decade you go from $1.75 an acre to 25 cents an acre. In 1809, nine out of ten Americans lived on a farm. By 1884, 50% and by 1998, 2% living on a farm. In systems that have low margins, you do not have a lot of margin for error and you do not have a lot of time to change if your neighbor changes.

Churchill said, "the great empires of the future will be the empires of the mind." He said in 1953. The empires of the mind today are in Silicon Valley and in Massachusetts. That is where the IT and biotech companies are and the amount of wealth being generated by these companies is staggering. They are not generating it in the same way. Massachusetts started out because of Harvard and MIT having an enormous advantage over Silicon Valley in the 1950s. If you look at the founding date and the employment rate of these companies, in 1959, Massachusetts was about five to one over Silicon Valley. Massachusetts followed a series of policies that frittered the stuff away. Within twenty years you saw the employment in Silicon Valley about three times the employment in Massachusetts. One of the windows to what is going to happen are patent trends. The patent trends and who is patenting in a global economy is important, because it tells you, over the next twenty years, who is going to dominate technology. If you look at the bottom line on this, the amount of people it takes, in the Netherlands, to produce one U.S. patent, is about 11,360 people. In Japan, it takes about 4,000 people and in Taiwan, it takes about half the people it takes in the Netherlands. The other thing that is important to realize about this chart is that the rate of growth of patents in the Netherlands between 1985-98 increased 66%. Patents in Taiwan went up about 137%, about twice that rate and in Taiwan, 1812 and Korea 1600. You can argue those rates of growth are not sustainable, but it tells you that on the ramp of knowledge and what is going to happen over the next twenty years, there are countries that are getting a lot better producing knowledge and protecting knowledge. By the way, they are on a much faster growth curve. When you think of who is going to be generating the wealth and having lifestyles, these are important points.

I want to finish by telling you a cautionary tale. Think here is one more American haranguing us. I come from Mexico. I watched this happen in my country. We have a lot of oil and we thought we were going to get rich on basis of oil, while keeping our culture and we were a strong culture and society, and therefore, we keep things going the same way as they were. We did not have to invest in people, education and small businesses and so on. As a result, in 1985, the number of patents being produced in Korea and the number in Mexico, Brazil and Argentina were basically comparable. One of the things that happened from 1985-98, is that South Korea got better at becoming a knowledge economy and Latin America did not. Latin America basically doubled the amount of patents it was producing per country. This is what South Korea did. Let me close by telling you what the impact of that was. In terms of productivity and real wages of one society versus the others, wages in Korea went up 950%. From 1960-1990. Wages in Mexico today are, in real terms, are below what they were in 1960. That is what happens if you try and maintain a commodity economy. Productivity and income are the same story. That is why it is important to understand that in this debate there are a lot of precautions you should take, but you do not want to create a society that is not on board changes in technology that are occurring very quickly.

 

Question and Answer Session
with a panel of afternoon speakers

Question from the audience: This question is for anyone, particularly Jim Murray and Dr. Mayer. This whole question about consumer choice and what is it about GMOs that is so intrinsically different that consumers have to be informed. We have products on the selves that were made with plants that were hybrids using x-ray mutation and other very high-tech methods, but no one is demanding labeling of those products. Who decides which technologies are so fundamentally different that products must be labeled because of the production process? US regulations on labeling talk about health, nutrition and other characteristics. They do not talk about labeling based on process. The other consumer right, consumers do have a right to know, but consumers do have a right to low prices, it seems to me. If you did a survey of consumers in several countries and asked them if they would purchase a product if it were less expensive, you would probably have a much higher rate of agreement than you did on buying GMOs. This question of choice and why GMOs have to labeled, when all our other industrialized products, many of which are very different than what our grandparents ate or even our parents ate, where do you draw the line on labeling?

Answer given by Jim Murray: To answer first your question on who decides on labeling, you will be glad to know that I do not. We are here to make an argument about that and at the end of the day the decision will be made partly by people in the market, as it has been, in response to consumer demand and by government regulators and so on. As to what should be labeled, the consumer organization did not even lead this charge. We were following consumer concern. Consumers are more concerned about this than other issues which could well be labeled, for example, the question of labor and social issues, animal rights and so on and so forth. There seems to be a strong political imperative for labeling. As it happens, I also believe, that is for you to disagree with, that it is now probably the way in which we can win public, citizen and consumer acceptance for this new technology on the supermarket shelves. I do not have the slightest problem with presenting consumers with two products of differential prices, provided that those prices are not rigged, and letting consumers choose between them, assuming the basic regulatory issues are dealt with. As a consumer organization we would be perfectly happy to see that. I believe in the longer term, if it happens, the consumers are presented with GM products by reputable companies and reputable retailers in particular, and particularly if they see an advantage in it, they will grow to accept it over time. That is unless they have reason to believe there is something bad happening in the other areas where there is environmental or health, or something like that. We certainly do not decide. We argue. We are in a free market for ideas on this and arguing that this is something, which should be labeled. It is an argument which, two years ago, we were told we had no hope of winning which now I feel more hopeful about.

Question from the audience: This question is for Jim Murray. It is nearly the same question, formulated in a sharper way. The way you presented your talk, you were happy about the evolution. You were enjoying that it took this road. My question is whether you are puzzled by the fact that you announce that you agree there are no health hazards with the genetically engineered food that is produced now. Your colleague from the Dutch consumer association said that everyone has been saying today that there are so many questions and so many dangers around it. Indeed, if you would ask any consumer why they are against, he would also say that it is because it is dangerous. Actually, what is happening is an enormous level of scientifically incorrect situations that have enormous implications at the moment, that all the science for the developing countries is not going on and other things are stopped. Are you not worried about the kinds of successes you are having?

Answer given by Jim Murray: Yes, I think you misunderstand me if you feel that I rejoice in all the things that have happened. I tried to describe some of them as a matter of fact. Of course, there are bad aspects about it as well, including the fact that there is an awful lot of nonsense talked about GM food. There is an awful amount of misinformation talked about GM technology. That, I have to say, does not come from my organization or from our members. Just for the record, while I have the highest respect for the "Alternatieve Consumenten Bond" (a consumers interests organization), who you described as my colleague, they are not in fact members of my organization. I should say that. They may indeed wish me to say that. Some of the things that have happened have not been good. Demonizing of GM food for whatever reasons has not been good. We happily concede that point. Demonizing goes on in many different ways. Sometimes it goes on for marketing reasons. Somebody says our product does not contain GM or our product contains no this or that. This is a process that can be driven for marketing reasons too. Sometimes it can be driven by the media. Of course, it can be driven by NGOs. I find it hard to worry about that. If you take Brussels, there are according to the Wall Street Journal, somewhere between ten and fifteen thousand lobbyists in Brussels, who I assume are not stupid and do not lack resources. There are at best a few hundred NGOs and public interest groups. The only thing we have going for us is words. I have no economic power. I can not tell consumers to vote this way or that way. We are there making an argument. Within that argument it is certainly open to people, because it is a free society, to be wrong, to be stupid, to make wrong arguments. That is the first amendment right in the US, though it is not quite so entrenched in Europe, but nonetheless it is there and it is a free market of ideas. That means that what we say should also be open to attack. I have no problem with that and trying to defend it. I do believe that some of the nonsense that is written in the media and other nonsense written by people, we should simply attack it and say this is nonsense and have a more robust debate about it. But there are serious points here, reflecting serious concerns and they must also be addressed.

Question from the audience: Mr. Pierce, do you feel that the safety of GM products, on an ecological level are adequately tested in the US and do you have experience with contradictory market entrance requirements from the FDA on several different products? Is it a homogeneous playing field?

Answer given by John Pierce: In terms of the first question, there are series of tiered tests regarding the release of GM crops and these are analyzed on a product by product basis. There are tests regarding allergenicities, effects on non-target organisms, and durability in the environment. When they have reached the types on analyses that take a few years and the package is prepared and judgement is made as to their safety, and then approval is given. Yes, my belief is that they have been safe and are as safe as other crops. Current history with them and observations suggest that that is the case. For the second question, the regulations are on a tiered system. There are a number of questions that are asked and they start off depending on the type of product you would be thinking about commercializing. Depending on whether this is protein, a history of food use, does it look like an allergen, is it in fact an allergen? There is a series of tiered questions. Depending on the answers you go through ever more stringent analyses or if you can not answer them in a satisfactory fashion, then you have a different burden of proof. In fact, different products have different regulatory hurdles. That is rightly so.

Question from the audience to Jim Murray: If the reactions of a number of big retailers to stop selling GM food continue then the future will be that genetically improved foods can not be bought anymore by me or other consumers. That does not fit with the philosophy of freedom of choice, which I think should be possible. That could be a real risk, missing out on potentially interesting products. Are you or your organization actively persuading retailers to sell labeled GM foods?

Answer given by Jim Murray: The strict answer to your last question is no. But I agree with everything else you said. We do not want a ban on GM foods. We do not want them to be taken off the market. We do not want consumers to be denied the possible benefits. That is not to say that I believe in specific claims about specific benefits. We do not want that to happen. I think you are, with respect, putting on to my poor shoulders everything that every NGO says everywhere about GM products. I am not responsible for all of them. Benedikt Haerlin from Greenpeace is a good friend of mine, but I am not responsible for anything he says and he is not responsible for anything I say. He does not wish to be. Our own points are quite clear. The points by our members are quite clear, that we are not against them and we want choice. We do not see any point in demonizing. As it happens, to some degree, some choice has come about by the fact that at the moment, and this is a slight improvement but not an ideal one, that if you want to avoid GM you have the possibility of shopping in one place rather than another. That is an improvement. It is not the ideal solution, but it is definitely an improvement of some kind. It means that the juggernaut is stopping and people have to rethink it. I hope this is only a temporary situation and as I said in my speech, we do not have the slightest problem with the idea of properly identified GM and non-GM products existing side by side on the supermarket shelves and let consumers choose.

Question from the audience: This is a question for Juan Enriquez. I was fascinated by your presentation and I want my question to be answered by you and any other panelists who have comments on this. I think that your charts were telling us that the rate at which innovation is taking place in different parts of the world is quite varied. What I gather from this is that the Asian economies are moving forward rapidly, based on this increased number of patents. Moving then from a commodity based economy to a knowledge economy, which should be a priority for all of us, is something that is happening at very different paces. Europe lags far behind. The Netherlands seems to lag far behind, despite the fact that it is relatively advanced in terms of ICT in Europe. Could you comment on the impediments to innovation? What you did not have a chance to say was what was causing the Asian countries to go ahead. Is it the regulatory environment? Is the black box here, government policy making is more complex, less user friendly to innovations or to firms? Do you have any thoughts to this and how it can be changed?

Answer given by Juan Enriquez: The traditional answer that you get is let us upgrade the educational system. That seems to be an overall fix it. That is an essential, but not sufficient component to this. The cautionary tale that I offer is India. India has an extraordinary system of six Indian institutes of technology that graduate some of the best mathematicians, physicists and scientists in the world. The problem is that most of them get up and leave. The problem is that right now 40% of the businesses founded in Silicon Valley are founded by Indians. You have this phenomenon where they contracting labor back home in Bangelore and creating a software city in Bangelore which has become the second largest software producer in the world after the US. The precautionary tale on this is that much of the value of the intellectual capital stays in the US. Last year India registered one patent in the UK. Given the ties between India and the UK that is not a good number. Part of what this tells us is that you do not only need a good educational system and smart people, but you also need a system of support that has a tremendous incentive for those smart people to stay in your place and not get on KLM and fly. In ten hours that person can be in Silicon Valley. Believe me, the US will give them an H1V- visa and the venture capitals will show up and say, here is five billion dollars. It will be easy to incorporate the business and there will be people in favor of that business. That does not mean that every country has to accept that. Not every country has to be a biotechnology power, but as this debate goes forward and positions polarize, it is very important this not become an anti-science debate. If you try and stay in the same place you are going to lose. The world is moving too fast.

Comment from a panel member: The last point that Juan made is very important. The distinction between both East Asia and other parts of the developing world is that they have had both a relatively stable micro economy and much greater openness to foreign capital for many years. Therefore, they were able to invest. The models are very different. Taiwan has a lot of little companies. Korea has five huge conglomerates that account for 60% of exports. The top sixty companies in Taiwan account for five percent of the exports. It is really a reverse model. It is not the East Asia model. The other thing that is different between Europe and the US is the enormous difficulty in getting venture capital in Europe. The fact that in Silicon Valley someone can go bankrupt once or twice and still go back to the top again and get funded. Because there is this knock down, get up again and try again, this is extremely important in a situation where you have a lot of start-ups in new technologies which are coming. People are willing to put money and expect that they will lose in six or seven out of every ten ventures, but that they will hit in two or three of those and that those will become the big ones. That kind of thing is not yet sufficiently found on the European stock markets or capital markets. That is a difference. In developing countries, of course, with the exception of East Asia, the markets are quite small in most developing countries.

Question from the audience: A point that was raised several times throughout the day was the soundness of the science that is at the basis of the practice of recombinant DNA technology. Indeed, if that science is sound and we get on board with these rapid evolutions then certainly, as humanity, we will go to a bright world where we will all be healthier, happier and affluent. But this science is developing very rapidly. We are not in the same place as yesterday. A few years ago a biophysicist named Rolands told us that we interpret DNA as children in the first year of primary school read words. We have very little understanding of the levels of organization of DNA which correspond to whole phrases, paragraphs and chapters, let alone the whole book. Since then a number of scientists have researched these higher levels of integration of the DNA and a few integrating principles which span bigger domains than a single genome or a few genomes. On the basis of these principles a number of experiments have been done with genetic manipulation which show that in each and every case recombinant DNA technology, this localized insertion of chimerical DNA into a whole genome, inevitably in each and every case, damages these higher levels of integration of the DNA thereby scientifically establishing that recombinant DNA technology is an inherently damaging and flawed technology. This information is largely ignored or even suppressed. My question is about intellectual candor. Are the scientists, who are in this business, willing to look at it and adapt their behavior, because this entails dropping the current level of biotechnology that is being produced, which has products on the market?

Answer: If you look at the scale of knowledge we have for the last 53 years, since Crick and Watson came up with DNA, we are talking about understanding the human genome, we are talking about the genome of corn and rice. I personally think saying that this information has been suppressed in an open society, US or Europe. I do not think any suppression of information is going on. With this predictable behavior of the recombined DNA I think it is really amazing that you have reached the conclusion that there is something inherently wrong with this technology. I think it is a different story when you talk about consumer choices. But as for the safety of these products, in nature there has been modification of genes going on. Through trial and error we then perfected the technology into hybrid seed. Now we are talking about precise insertion of genes. To me there is more predictability by doing what we are doing with gene splicing, then what we used to do 20-30 years ago. I have to disagree with you that this is inherently unpredictable technology. I think there is more predictability of what you are going to get in the product derived from biotechnology than from previously used techniques.

Comment from John H. Monyo: I would like to comment on what Mr. Haerlin from Greenpeace said. He said that we should concentrate on organic agriculture. Taking into account that we have some 800 hundred million people or more in developing countries hungry. Many of them can not use chemicals. They are therefore using organic methods that are not working. Therefore, we do need improved technologies to make things change. On the question of international regulation of food safety, as you are probably aware, the Codas Elementarius is a commission in FAO, shared with the WAO, there are one hundred and sixty member countries who participate in this commission to determine standards which are acceptable internationally for food. Food safety is a major theme. Recently, last year, at a meeting of the commission, they did create a task force on biotechnology, which is going to meet in Japan in March. The Question of labeling is going to be taken into account. I have a question for Mr. Siddiqui. You said, and I agree, that some science is very important. A transparency in the regulatory system and testing is very important. It seems like the US has done the job well and the public has been susified in many ways. Were you surprised by what happened in Seattle? A new survey shows that 56% of consumers in the US would like to be told if the food is GMO or not. Does this surprise you?

Additional answer given by Dr. Siddiqui: What happened in Seattle is like mixing apples and oranges. In a society as open as we are, everyone has the right to express. If you look at the reaction to what happened in Seattle, by and large, the American public was really puzzled and upset that the meeting of the WTO was essentially jeopardized and essentially disrupted by some people who broke the law and took the law into their own hands. As for us trying to put more meaning in to it, there are concerns. Environmental concerns, concerns of losing sovereignty, that WTO is dictating some things which some people do not like. I did not see that there was a connection there. Some people, who were also protesting against GMOs, in a population of close to 300 million people, I think that you see a few hundred or a thousand people demonstrating it is still a small fraction. There are still some people who do not like this technology. We have been saying is to me the same thing. There have been people for the last 30-40 years who do not like the use of pesticides and chemicals in their food. For that there is an emerging industry and that is organic food. They can prefer if they do not like pesticides in food more and more you can buy organic. For the same reason, I would like to see the labeling issue settled that where non-GM food is labeled where these who do not want GM contents can buy non-GM food.

Question from the audience: I do not think it was correct of Professor Montagu to dismiss consumer concerns as unscientific. I think Mrs. Mayer this morning and Mr. Haerlin this afternoon, and Mr. Sarukhán have given some of the scientific controversy about some of the risks concerned with genetically engineered food. Maybe you would like to illustrate some of that?

Answer given by Mr. Haerlin: Maybe I should point out that Greenpeace, maybe you have noticed as well in my presentation, is not predominantly concerned about the safety of GM food. We do see major gaps in the regulations. We believe that the concept of substantial equivalence, which is the basis of the risk assessment, is scientifically flawed. We do not see risks comparable to the type of environmental risks. We are really concerned about, that could not be handled. It is a different level of concern. We are not a consumer organization in the first place. Greenpeace, for instance, does not believe that the safety of the environment should be put to vote on the supermarket shelves in all cases. We do not believe that consumers put in front of different products at different prices are the best arbitrators about what is the best, environmentally most sound method of producing food necessarily. We are also not predominantly campaigning for choice. By the time there was freedom choice everything was OK. In other cases, you would certainly agree that freedom of choice can not be the only ground for democratic decision making. On the other hand, I think labeling is a prerequisite for any citizen to take his or her stand on this issue. My personal experience is that most people I have been talking to about this issue are not mainly concerned about immediate health impacts, such as allergic reactions to GMO food. My other experience is also that many people to whom I try to explain what our concerns are about GMOs would not listen very long to this, but much earlier say, well, this outrageous. You do not do this. I believe that many of you might want to consider that a large portion of the rejection of GMOs is not about food safety, and probably not even about environmental risks, such as the risks that have been described, such as to the Monarch butterfly that has been discussed, or rather risks that can be named and identified with existing GMOs at the moment. A lot of people say this is simply not right. It does not feel right. I think it is a big mistake not to take this into consideration. You say, but that is an emotional reaction. Emotion should have nothing to do with our decisions. I think emotion must have a lot to do with our decisions. The people I am really afraid of are those who try to exclude their emotions from decisions. One species who have developed this to a very high level is actually scientists, who are extremely emotional. I am sitting in these types of conferences often and getting purely emotional reactions from scientists. As I have trained myself to quite a few of these arguments over the past ten years looking at these issues. As I know a little bit about the scientific discussion, I can tell you scientists are perfect at abusing scientific facts for sheer emotional purposes. It is by no means true that in an open society information can not be suppressed. Information can very well be suppressed. Scientific communities can be extremely harsh and not based on scientific scrutiny, but on self-interest, like any other group in society. I have learned, hat is a comment on the question of sound science, to very much distrust the emotions of scientists in this field.

Comment from another panel member: With due respect to my colleague here, you said it is not an issue of safety or the environment. You said it just does not feel right. Given that choice, I feel sometimes about certain things as well, but I want to reverse the role. If I do not feel right about something, I do not want to deny you your rights. I think saying it just does not feel right so you want to deny this technology a chance to contribute to answering a number of problems, such as nutritional enhancement of products or reducing pesticides. Where you were using ten applications in cotton, now because of BT cotton you have to use one application. That is a ninety percent reduction in pesticide usage. I am addressing to you, that "it just does not feel right", if it were my case I would not use that product, but I would not want to deny other segments of society the right to use that product.

Mr. Haerlin: I probably said a little more today then "it does not feel right". What I was saying is that this is a frequent consumer reaction.

Question from the audience: The speeches this afternoon have underlined the importance of science and technology in the future. We see the excellent performance of South Korea, Japan and India in this respect. But, if I look around at the universities here we see that there is almost no sex appeal in engineering. We have few students in physics, mathematics and chemistry. How are we going to solve this if it is so important? What we do see are many students in business administration and management. The point is that they do not do the work, but we want to tell others how to do the work. It is the same in the US. American professors are surrounded by Chinese and Indians who they publish with. Afterwards when they start a company. The Americans are not interested. They say why should I become a scientist if it is easier to become his boss. It is easier to have a salary that is 3 to 4 times higher.

Answer given by Juan Enriquez: The trends you are talking about are exceedingly worrisome. In the US, 27% of the doctorates that are coming out of science and engineering are Asians. About 2% are African Americans. About 1% are Hispanics. If you want to address, in the long-term, income inequalities in the US you have to start addressing these trends, because the way in which you generate knowledge is through more and more technology and science enterprises. How do you go about creating more of a science in kids? One of the things that is important, science is a wonderful adventure. It is not a dirty thing that is simply involved in manipulating genes and scientists are only involved in creating Frankenstein monsters. Societies that go out of their way to portray scientists as liars or who go out of their way to portray scientists as different from us because they have less emotion, or go out of their way their way to portray science as something that they do that we do not do, are going to have trouble surviving in the long-term. I want to remind you in terms of national competitiveness, three quarters of the nation states in this world did not exist 50 years ago.

Comment from Professor Krol: I think we do a very bad job. If you look at the start of secondary school, there is no difference in talents between boys and girl. But if you look at science faculties, there are no women there. We have lost 50% of all talents to start with, not because they have less talent. We lose it for social reasons. Maybe it is not important. We do well economically. But you say that science and engineering are so important for the future.

Question from the audience: Mr. Serageldin was quoted by the chair this afternoon of having given us the vision of how GMOs could actually help the world or to be exact, help us feed the poorest people in the world. If I understand your talk during lunch right, you also say that the way we structure science, at the moment, as mainly driven by economic interests and also the way we handle patents, these benefits will not arrive at the poorest people. Is it not actually a very hollow, empty vision that has been quoted and what needs to be changed, given that GMOs are actually be beneficial, which I still question. What needs to be changed?

Answer given by Mr. Serageldin: This gives me a chance to clarify. If I gave that impression it is not quite correct. You are absolutely correct. I did say that a large part of the global problems we are facing which is with very poor communities, malnourished people, in remote areas, and I showed you pictures of those, are not going to be serviced by the private sector. Certainly, that problem is not going to be solved by excess production in the north that is shipped to the south. You can only deal with the problems of poverty reduction, food security and environmental protection on a global scale by improving the productivity of the small holder farmers. That is the premise. That will require the recognition of public goods research, which is research that is not going to be marketable for orphan crops. I gave the examples of cassava and that it is likely to be sequenced if it turns out to be an effective feed stock for hogs in the US, but the fact that 300 million Africans depend on it is not going to generate private sector response, because it is not a marketable one. We have seen this also in medicine.

My demand is the following. The contextualization of research is needed, so that crop research is fitted within an overall context. The context is ecological. I showed you examples of different ecologies. The context is, in terms of farming systems at the small holder level, for the synergies between livestock and manure of livestock, where the crops, cash crops and food crops. It is also socio-economic. The recognition of the agenda I mentioned. Food production tends to be most handled by women. Cash crops by men in many parts of Africa. The small holder farmer focus. The second part, which is enormously complimentary, is this gene revolution: the genetic imperative. This enables us to do things which Steve Tanksley and Chris Sommerville showed, which you can not see by the normal breeding practices where you screen by the appearance of the plant. It enables you to do things which you can not do otherwise, such as increasing the nutritional content. We talked about the example of vitamin A rice. We also talked about the examples of resolving the feed problem by increasing the feed problem. There is a piece of the equation that requires biotech research. That biotech research is not going to be done exclusively by the private sector, but we can not ignore that the private sector is the driving engine for that research today. Therefore, we have to find a way for a public/private partnership and I showed you a picture of how we are trying to get together to establish that partnership between north, south, farmer's associations, NGOs, private sector and public research institutions, and also in the field. I showed you pictures of the organization of farmer's on the ground. That is the vision. The recognition that we need all the pieces. The challenges are enormous. It is not an either/or, I can do it all with one way or not. Different parts of the world require different problems and we need to be able to mobilize the talents and abilities of everybody and not deny ourselves the potentialities of what could be very benign technologies. Unlike mechanization, for example, which is scale sensitive, biotechnology which is transferred through a seed, is not necessarily scale sensitive. Therefore, it could be useable for assisting the small holder farmer. Whereas, if you say, mechanization and high input capital would not be. These are the pieces that I saw and tried to sketch out as a vision of where we should be going and where in fact all the pieces really come together with the recognition that there is no single fix. There is no magic bullet. There is no single solution to all the problems.

 

FRIDAY, JANUARY 21, 2000
"THE CHALLENGES "

Chair- Sir Robert May,
Chief Scientific Advisor to the Prime Minister of Great Britain Introduction

A cartoon by the British cartoonist Gilray speaks to the fuss made two hundred years ago about the immunization that got rid of small pox. It captures some of the apprehensions and the riots in the streets of those days and you see, in full Frankenstein mode, the cows appearing out of people's arms. It was an intensely controversial subject. This is not, however, to suggest that such apprehensions in the past, that have beset so much novelty, are not to be thought about carefully. It is often said that when trains appeared, also two hundred years ago, there were many dire predictions that this would be the end of life as we know it. My own view is that there were contained within the sometimes exaggerated apprehensions, real concerns which had we taken notice of would have made for much less inconvenience and ill health brought by smog from trains in cities in the last century and early in this century.

My point in beginning this way is against the background of the discussion yesterday, which dwelt more on the underlying science and questions about it. To move to this morning, where we think about the challenges and how we manage consequences of innovation. The perspective I bring to it personally, in many ways reflecting the perspective the British Government brings to it, is in many ways one that says we have just come to the end of a century, which more than any other century in history has been a century of betterment of life, but often accompanied by unintended consequences.

One hundred years ago, the global population was one and a half billion. Today, it has doubled twice, to six billion. Fifty years ago, the average life expectancy at birth, on this planet, was forty-six. Today it is sixty-four years. Fifty years ago, the difference in life expectancy at birth, between the developed and the developing world was a shameful twenty-six years. Today it is twelve. The unintended consequences of that are, today, a still growing population and a human population that consumes between a quarter and a half of all the globe's primary productivity. All the plant material, from the tropical forests to the prairies, that grows on Earth each year, today, we consume. We are pressing limits. One clearly demonstrated consequence is that we do not know the rates of extinction of other creatures we share the globe with, because we do not know how many other species there are. We do know, with an almost physics like precision, that for birds and mammals, the rates of extinction over the past century have accelerated to one thousand times the average extinction rate in the background fossil record. They will surely accelerate another factor ten in the coming century, putting us squarely in the extinction rate regime that characterizes the big five episodes in the fossil record, such as that which ended the dinosaurs.

Just in the last thirty-five years, the human population has increased sixty percent, but as a result of the green revolution, we have doubled food production. We have doubled food production using what is sometimes called "natural" methods of crop breeding. However, before the advent of molecular genetics based methods, the so-called GM, the methods which created, particularly, the later stages of the green revolution, are as different as what went before in this long evolutionary history. The co-evolutionary history of humans and their plants and animals, that reaches back ten thousand years (what we did before GM; tissues, cell-based methods) are as different from what went 100 years ago as GM is from what we do today. In doubling food production, we are keeping pace with population growth. The problem with feeding the world today is about distribution, not food abundance. No simple problem is older than agriculture itself. In so doing, we have increased land under cultivation only about 20-30%, but other non-linearities, such as the increased input of fertilizers like nitrogen. It poisons many water supplies. If you want one headline figure to underline the singularity of our time, it is this, half the atoms of nitrogen and phosphorus incorporated in plant material around the world this year, are there as a result of fertilizer, not natural process. Against that background, I think it is very important that we think about unintended consequences as we move forward to take advantage of our increasing understanding of the molecular machinery of life, which we need to do, because we could not feed today's population with yesterday's agriculture. We can not feed tomorrow's population with today's agriculture.

As we embark on this next stage of a series of transformations that characterize our history, in the developed world and particular in the UK and Europe, we hear many opinions expressed. You will hear them expressed with a different balance on emphasis depending on the particular conference you are at. All of them, in my mind, have legitimacy. There is the voice of agri-business that sees the potential; the voice of science, that takes pleasure in its increasing understanding of how the world works and its ability to further improve human health and other aspects of our lives; the voice of government which seeks wide consultation in a world delightfully less respectful of authority, which sees itself as a referee, creating regulations and inviting the discourse that is the only way to go forward; environmental lobbies, English Nature, Royal Society for the Protection of Birds in Britain, with concern and worry for biological diversity in the countryside; ideological political groups, who are opposed to globalization, big business and raise, in my mind legitimate questions about unintended consequences, often raising that political agenda obliquely under the cloak of environmental concern; the public in general, informed by media whose agenda is a mixture of information and their own competitive advantage. The competitive commercial concerns of many newspapers will not necessarily be precisely congruent with dissemination of the most accurate facts in an unbalanced way, which is natural, not to be criticized, but is sometimes a problem for enlightened discourse.

In the UK, I would say that my own personal taxonomy of the worries and concerns are of three broad kinds. Human health, which will be the focus of an OECD meeting on the basic science at the end of February, where I see the real need to focus on safety aspects of all novel foods, but where I do not see GM foods as particularly different and in some ways less threatening than other kinds of novel foods. We need to think about consequences for cross-fertilization and pollen escaping. Again, this is not a new problem. The problem is actually, around the world, much more attached to the escape of things brought in as garden plants, which are much more robust than your average crop, which is pretty wimpy. The third category of worries, as I have already touched on, are worries that deal with the increasing and legitimate aspiration to intensify more competitive agriculture, which conflicts with the desire to have a countryside with creatures populating it other than us. Intensification means growing crops that no one eats but us. There is a tension there that needs to be more carefully exposed and discussed. To my mind, the increasing sophistication of the methods that you heard about yesterday, poses us interesting choices as to whether we use these tools primarily to realize benefits for agriculture itself. Or will we put the focus on using the techniques to bring benefits to the consumer and the environment. The sad paradox is that the ideals of the organic farming movement make them, in some sense, potentially the most important beneficiaries of GM techniques and yet, if you do not see it clearly, it does not look that way.

This is not something where differences between American and European approaches reflect deep cultural differences. If you actually ask people about different applications of advances of our understanding of our molecular machinery of life and what they see as the risks, benefits, and ethical concerns about medicines, GM food, and zynotransplantations, people in Europe or in the U.S. will say I see the risks and I see the benefits or I see no ethical dimension, I am in favor of it. For zynotransplantation, they will say they see a modest benefit. I see a risk. I worry about the ethical dimensions and I am unhappy about it. For GM foods, they say I see a risk, I see no benefit, I see no ethical dimensions. Let us avoid any potential worries until we see a benefit. In the 1970s, as this technology was born, following the Assilimar meeting on gene splicing, there was much apprehension and reservation in the U.S. The building of the molecular biology building at Princeton was delayed, which I at that time had responsibility of, by a year or more. There was no such apprehension in Europe. Today in the wake of BSE, it is very much the other way. It is not innate to the cultures. What do I see as the way forward? Procedures and discussion, as we increasingly have in Britain with our guidelines for science advising and policy making, that embrace wide consultation and open discussion.

Even more importantly, I see the need for products that benefit the consumer. It is not that I believe that an emphasis on agri-business is wrong, but it is not a good way to motivate people to engage in the debate. When I say products that benefit the consumer, in the developing world, I mean products that remedy vitamin deficiencies or many of the other potential benefits of detail, as well as the transcendent benefit of feeding tomorrow's world. In the developed world, they may be more the kinds of products that address a privileged elite on the globe, who have never had a problem with food. They will be things like nuts without allergies. Ultimately, there might be a GM apple that will make you thin. We will really have a product that will motivate people to engage.

 

Ambassador David L. Aaron
Under Secretary for International Trade,
U.S. Department of Commerce
"Making Biotechnology Safe"

Good morning. Thank you Sir Robert May for that introduction and thank you Ambassador Schneider for organizing this important conference on biotechnology. I hope it will contribute to a more informed and productive transatlantic dialogue.

Biotech foods have generated enormous real and potential benefits to mankind and the environment. But somehow, when we hear charges of "Franken Foods" and find biotech linked to unrelated food problems such as dioxins and mad cow disease, we're seeing prudent skepticism overcome by hysteria.

Hysteria over food is nothing new in Europe or the United States. Take the history of the tomato. It was once widely believed in the U.S. and Northern Europe that tomatoes were poisonous because of their relation to the nightshade family of plants. Tomatoes even had their own "Franken Food" title - the "Wolf's Peach."

In fact, the belief that tomatoes would bring sudden death was so strong that in 1820 the state of New York banned their consumption.
That was until 1830, in Salem New Jersey, when Colonel Robert Gibbon Johnson changed the image of tomatoes forever. In what was thought to be a suicidal act, Johnson announced that he would appear on the courthouse steps and eat an entire basket of these "Wolf's Peaches." With 2000 on lookers and a marching band playing a somber tune, Colonel Johnson recited this speech: "The time will come when this luscious, scarlet apple...will form the foundation of a great garden industry, and will be eaten, and enjoyed as an edible food...and to help speed that enlightened day, to prove that it will not strike you dead - I am going to eat one right now!"

Well, just by driving past the miles of hot houses dedicated to "wolf peaches" in Holland, you know how things turned out for the Colonel and the tomato. And I am certain things will turn out similarly for biotech foods, considering that today, instead of the Colonel, we in the U.S. have an extensive system to ensure our new foods are safe.

The question is, how can we work together to expand the benefits of biotechnology while ensuring the safety of our people and the environment.

To do this we must address regulatory issues, and consumer confidence. So I would like to discuss first, the U.S. approval process, second, some principle issues related to bioengineered foods, and third, the evolving EU system and the problems it may raise.

Thirteen years of experience with biotech products in the U.S. have shown us that biotech foods developed and used in the U.S. present no food safety risks beyond those of their "natural" counterparts -- not a single ailment has been attributed to biotech foods. Not one! Not a sneeze, not a rash, not a headache.

That is the fundamental fact about biotech foods. And it is the effectiveness of our regulatory system that has ensured this. The key to our regulatory system is that it is transparent, science -based, politically independent and responsive to new scientific evidence. As a result, our public has a high degree of confidence in the system and subsequently in their food - be it bioengineered or not. There is no great public anxiety despite the furor in the EU and the best efforts of some advocacy groups in the U.S..

U.S. law requires companies to ensure that any bioengineered foods they sell meet stringent safety standards. This means they must pass a rigorous approval process through three different agencies. If they don't, they don't go to market. It's that simple.

Today bioengineered agricultural products are subjected to five to seven years of regulatory review from the time that permission is requested to conduct crop field tests until a product is commercialized and marketed. With two crop yields per year, that means up to 14 generations or more of a bioengineered plant variety is reviewed before approval.

The fact is that in the United States, bioengineered foods go through more extensive and intensive food safety and environmental evaluation than any other food in human history.

Dr. Siddiqui has talked about the role of the USDA. I'll focus on FDA and EPA. The FDA has focused on the questions of allergenicity and antibiotic resistance on human health. If genes from foods known to create an allergic reaction, such as nuts or eggs, are transferred to non-allergenic foods, such as corn, the allergenicity could be transferred to the safe food.

The FDA advises companies on how to assess new genetically modified foods for potential allergenicity. If there is a suspicion of allergenicity in any foods, the FDA requires extensive testing of the food. Under U.S. law and the FDA's biotech food policy, companies must tell consumers on the food label when a product includes a gene from one of the common allergy-causing foods.

The second principal issue for the FDA is antibiotic resistance. Some believe that industry use of antibiotic resistance marker genes in product development will cause infectious germs to develop and adversely affect human health. The FDA has determined that this is highly unlikely.

The particular antibiotic being employed was approved by the FDA for industry because it has no medical significance and is not being used in human or veterinary medicine.

Nevertheless, to be on the safe side and respond to public concern, the FDA has advised GM food developers to avoid using any clinically important antibiotic as a marker and industry is increasingly turning to non antibiotic markers such as color.

On the environmental side, our regulators principally focus on gene transfer and pest impact. The concern with gene transfer is that genetically modified herbicide resistant plants might cross pollinate with their wild cousins creating super-weeds that cannot be controlled by herbicides.

For cross pollination to occur there has to be an indigenous species or a wild cousin growing in the same region. Not only must this wild cousin exist, but it must be a threat as a weed. For corn, and soybeans there are no cross cousins in the United States, nor as far as we know, in Europe.

In addition to the possibility of gene problems arising from transfer being very low, precautions are taken to prevent it. Cross pollination can be avoided through buffer zones planted around the fields, a practice developed, tested, and mandated by the EPA.

Another environmental concern has arisen from the use of genetic engineering to build inherent pest protection into plants. For example, the gene from a microbe called Bt is inserted into corn making it resistant to the European corn borer. Building in such pest protection is less dangerous and less polluting than insecticide sprays. In California Bt cotton needs only one application of insecticide per season instead of 13!

Bt is so safe it is commonly used by organic farmers. However, there is concern that its widespread use will lead to pests that are resistant to it. Resistance to an insecticide over time, particularly through improper use, is a potential problem for most chemical insecticides as well. That is why, pesticide use, including the use of bioengineered plants, is regulated and monitored for signs of pest resistance by the EPA and the USDA and regulated by the use of refuges.

The EPA consistently revises its regulations in response to evidence from the field and scientific research. For example, because of the success and the unexpectedly rapid increase in planting biotech pest resistant crops, the EPA has just increased its refuge requirements for most Bt corn varieties.

In summary I would like to stress that our regulatory structure has more than adequately addressed the real concerns about biotech foods and has provided specific safeguards. And we are constantly updating our testing procedures and precautions. For example, the National Academy of Sciences, an independent body, reviews the regulatory process of the FDA and the USDA, periodically in order to ensure that they are as safe as can be based on the best scientific knowledge available.

So what about the EU system? It's no secret that we are having problems with it. We share a common purpose, we all want to protect our people, we all want to protect the environment, and we all want to do so with credibility. In our experience, an effective system dealing with biotechnology and food safety must be transparent and rigorously based on science. It must confront the issues of:
1. Product Approvals,
2. Labeling, and
3. Testing.

So far, Europe's system is still under construction and so does not yet meet these tests. The EU's product approval system for agri-biotech goods, EU Regulation 90/220, has effectively broken-down. For over two years, no products have been approved. That amounts to an eternity when we consider how rapidly biotech products are developing.

In fact, there is no truly EU-wide approval system. Approvals are carried out by the Member States. This is a big part of the problem. The information required for product approval is not uniform throughout Europe. And this makes it difficult for all the Member States to accept with full confidence that all the necessary testing has been preformed.

We are intrigued by proposals for an EU food safety agency but disappointed so far that its scope would be limited to analysis not actually guiding EU-wide risk management decisions. The EU and the US began in 1999 to address this issue cooperatively, albeit from different perspectives -- the US concerned about science based decisions, the EU about public credibility. In December we had the first meeting of the US-EU high level group on biotech to address market access concerns. We also are forming a private sector eminent persons group on biotechnology to advise the US and EU on biotech matters -- including ethical and moral issues. Both groups will be reporting to the next US-EU Summit in June.

Labeling is also problematic. We think it is a mistake to stigmatize a technology that has had no demonstrable ill effects. Nonetheless, our companies are prepared to try to meet the one percent threshold for incidental contamination by genetically modified material. But be aware that this one percent threshold is on the ragged edge of scientific feasibility. It will lead to a lot of false positives. News stories that professor "so and so" or activist group "such and such" has found GM contamination in officially GM free food, could jeopardize the entire process.

So, unless Europe establishes strict testing protocols and licensed labs, labeling will actually undermine confidence in products, in government, and in the regulatory process. It will add to, not reduce, public concern.

The lack of public trust in Europe on biotech foods has a lot to do with people being confused about the issue. Observer after observer has noted that these reservations are not so much related to biotech foods per se, but a lack of trust in the EU system to regulate any foods. This has been exacerbated by a number of scares from mad cow to dioxins in chicken and even AIDS tainted blood. This confusion doesn't just hurt U.S. companies, Europe suffers too. In an October 1999 survey by the EU's Environment Directorate, genetically modified organisms ranked last in a list of European citizen's top environmental concerns.

The same survey found that chemicals and pesticides in food and drinking water were one of their top concerns. European farmers apply pesticides at two times the rate of U.S. farmers and biotechnology could significantly reduce the application of harmful pesticides, yet public and official confusion have curbed the availability of such products in Europe.

In my judgement, what we really need are vigorous efforts on both sides of the Atlantic to educate the public on the science, risks, and promise of biotechnology. We teach very little about this subject in schools on either continent. We can't leave our education to the tabloids.

Before I conclude, I also want to say a few words about the "Precautionary Principle." Precaution must of course be a central feature of any regulatory system. But I fear its elevation to a political principle could create a false public expectation that food risks can be cut to zero. The real issue is how much risk and uncertainty is acceptable and still considered safe. Should we wait until both are at absolute zero? That's infeasible. How many people here have cell phones? Some people claim they cause brain tumors. Can we be absolutely sure that's not true? No. Have we banned them or labeled them? No, we made a judgement about risk and uncertainty and got on with our lives.

The U.S. system is not perfect. It can't be. But when problems arise, public fears do not grow out of control because they trust that the authorities are doing the best and not covering up. That is because the system is open, reacts quickly and does not promise absolutely zero risk.

With biotech's great promise and over 13 years experience, our people as well as our government are persuaded that these products are safe. It is urgent for Europe too, to create a transparent, timely, and consistent system to assess risk and regulate of biotech foods. This is not just for the sake of our transatlantic relationship. It is crucial to restoring the trust of EU citizens in their governments' ability to regulate foods, and most importantly, to making sure that the EU does not exclude itself from the rapidly growing fruits of the biotech revolution. We want to help and we want to cooperate. As a first step I propose a truce. Americans have to stop accusing Europeans of being luddites for caring about their food, and politicians in Europe have to cease trying to recoup their credibility by attacking U.S. biotechnology.

When looking at its vast benefits, I think it is safe to say that the biotechnological revolution is here to stay. In my judgement, we can do much for the prosperity of our own peoples and of the rest of the world by working together to advance the development, scientific regulation of, and use of biotech foods.

Thank You.

 

J. Craig Venter, Celera Genomics
"The Human Genome"

I'm going to give an update on what's happening with the genomic revolution (refers to slide). So in 1995, we published a paper in this issue of Science, which described the first complete genome of a free living organism. This was "mopholis influenza" that causes meningitis in children, ear infections, it does not cause the flu, that's a virus.

Next slide. Since that time, and you might have heard this from Jonathan Eisen yesterday from TIGR, we've been in an exponential growth phase of new information in genomics, but it is really important to keep in mind that this field is barely 5 years old, yet the data is growing clearly at an exponential rate. We now have complete genomes of close to 30 micro-organisms most of these key pathogens that affect the human condition like tuberculoses and malaria. A cholera genome is just about finished at TIGR and will be published soon. In addition, just a couple of weeks ago in Nature, a combination of efforts from TIGR and a European consortium, published the first two plant chromosomes from 'Arabadobis', primarily under the leadership of what you heard yesterday from Chris Somerville. This new information is now changing our view of biology, taking us literally from the dark ages to where we actually have solid information to go on and make rational decisions. So there should be no excuse going forward for the irrational.

Next slide. In fact we had covered genomes with a wide variety of chemical content from very high GC contents with tuberculoses 'Dynacoccus Radiodurands', the extreme radiation resistant organism, down to the malaria genome which has mostly "A"s and "T"s in it. The concerns were that a lot of genomes were non-sequencable, the human genome for example was considered to be a multi-decade, multi-country, multi-billion dollar project.

Next slide. Well we had the opportunity and scientists don't get these opportunities very often, where I offered close the US$ 400 million and some new technology, to apply what we learned with genomics to sequence the human genome. That was the formation of Celera the former 'Percanome' corporation putting up the money based on a new technology, they developed the first automated DNA sequencer. This was also based on the whole genome shot gun method that we developed at TIGR with the first genomes.

Next slide. As is any field of science new instruments change what can be done, the telescope back in Galileo's day made a big difference, having an automated DNA sequencer totally changes what we can do and understanding the chemical constituents of all living species including ourselves. This was such powerful instrument and the first truly automated one (next slide) that we decided we would need several of these. We actually ended up getting 300 of these US$ 300,000 machines each and set up the world's largest sequencing factory in Rockville, MD, just outside of Washington, D.C.

Next slide. The amazing thing though is, because of this automation, all this work is done with only 50 people, but as a consequence we use a lot of electricity and our electric bill is about US$1 million a year, so the local utilities are very pleased with us.

Next slide. In fact the biggest challenge of all was not with the sequencing, but with the interpretation of the information. It's a great slide for this to crash on, this is talking about our new super computer (laughter). So we built the world's largest civilian super computer in collaboration with our partner Compaq Computers. The largest super computers are in the U.S. Department of Energy for simulating nuclear weapon blasts.

Next slide. Well what are we doing with this technology? We are sequencing multiple genomes. The first one we decided to undertake was the fruit fly genome. It may be disturbing to some of you to learn that your genome is very closely related to that of the fruit fly and not being insulting, mine is too, and it is the first organism actually with a central nervous system. Tremendous work has been done over the past one and half decades, both in England and in the U.S. The information from the fruit fly has led to more advances in our understanding of our own central nervous system than any other development. I'll give you an update that sequencing has been finished and that took only a few months. End of September we switched to the human genome, flashing over there on the far side are 2 key species: rice & Arabadopsis. Those are model organisms for maybe 250,000 different plant species including species representing over 50% of the world's food production.

Next slide. Well as soon as a human is finished, and that will be done we think in June of this year, we will switch to doing the mouse genome. What you might have heard yesterday from Jonathan Eisen is that field of comparative genomics is going to be one of the most important ones going forward. In other words we will only understand the human genome, our own genetic code, by comparing it to data from all other species. The mouse has been the key experimental model and is having a huge impact.

Next slide. In fact an example is, there is a gene called Pact 6, that in 'trasoffala', when you knock out this gene, it leads to an 'illospheno' type. In mice it leads to blindness and this has been demonstrated in 3 different mice now, it's an English fairytale about 3 blind mice and mutations in this gene cause 'anariddia', leading to blindness in children, so we can carry information forward we learn from one species to another.

Next slide. Well with the fruit fly genome we finished this in August. There were 2,500 genes known when we started, now there are 14,000 genes characterized.

Next slide. Just to put this is in context, when we sequence the genome of 'hymopholys' influenza, it took about 4 months with 24 people had to do 26,000 sequences. 'Drosophola', which is about 80 times bigger, we had to do about 3 million sequences but it only took 4 months and only about 40 people. So because of all the technology we can go up 80-fold with the similar number of people.

Next slide. I'll skip this one in terms of the algorithm for assembly which has been controversial but if you'll take my word on it, it clearly works and scientists have just underestimated the power of computing and the power of the uniqueness of each of our genomes. If it was not a single mathematical solution, none of us would be alive today.

Next slide. In fact one of the reasons we chose 'trasoffala', was we knew it would be well-validated as how well this new procedure worked. There were 22 million base pares that had been sequenced by our collaborators in Berkeley, CA and we found by comparing our data to the map there was only a tiny fraction of the data bits that didn't agree.

Next slide. In fact when we actually compared it to the sequence, there was one discrepancy. Jerry Ruben, our key collaborator said 'Before you say anything, let me go back and check in the lab' and he went back and checked and found they had sequenced a 'cimaric' clone which can happen with the standard cloning procedures that most labs use. Gene Meyers who developed the computer out rhythms said well of course we knew the error was theirs, there was only a single mathematical solution.

Next slide. It is impossible to read down at the bottom, but I think one of the most humbling parts of all of this, with every genome that we have sequenced, about half of the genes are new to biology. It has never been seen before, we don't know what they do. And its very key, tells us a lot about our state of knowledge and state of science.

Next slide. Well the same is true with 'trasoffala' in fact 48% of the genes and the 'trasoffala' genome are of unknown function. We expect the same percentage to carry forward into human. So half the genes we are discovering right now in the human genome are in this new unknown function category. It means discovery in analysis of genomes, understanding of our own physiology is going to be going on for this entire century and at the end of this century scientists will still be examining the genetic code we have determined in these few years and making major discoveries.

Next slide. Major new neuro-transmitter receptors - I think you will hear in the next talk about how some of this information affects drug development - these receptors have the key in terms of targeting drugs that change disease and also because 'trasoffala' is an insect in this case, to develop new insecticides that can may be help cure and eliminate diseases such as malaria in the world.

Next slide. What with the human genome, we now go up a little bit higher in scale, but it's only going to take us 10 months to finish the genome. And we've only increased from 40 to 50 scientists but the algorithm team - the mathematicians - we have we've to increase that group even more.

Next slide. As of this last week, we have close to 6 billion letters of human genetic code. The human genome for those of you who have been keeping track has around 3 billion letters in it, and this effort started only on September 8th, and we are adding around 2 billion letters of genetic code to this database every month.

Next slide. This just shows the tremendous acceleration. The human genome project started officially in 1990. It really started in 1985 but it was the stimulus for all the work that we and others are doing, but essentially we started in May and we will have the genome completed in June.

Next slide. We just announced last week that we now have 90% of the human genome in our database and that covers 97% of the human gene, but again about half of those are of unknown function. We expect to finish the sequencing phase in June and have the complete human genome sequence put together annotated and hopefully published in the scientific literature by the year's end. That is a considerable change in scale from 15 years to about 1 year.

Next slide. This is a cartoon of the human chromosomes. Next slide. People have been asking the difference between the methods we developed. The EST method versus the whole genome method, and it turns out that even though people have been claiming they've had all the genes with the "Arapadobis" chromosomes, it looks like at best half the genes were discovered by the EST method. With "trasoffola" only about 60% had EST matches, with the human genome these numbers are about the same. So tens of thousands of new genes have been discovered just in the last few months in Rockville.

Next slide. That's an interesting slide. This is talking about the impact of what starts to happen with science when having the complete genetic code. If we have 80,000 genes and that number is still looking very reasonable, each of us probably has close to 1 million different proteins circulating in our bodies. Some of those proteins like insulin have tremendous medical importance. What's happening going forward is that a new field called 'proteiomacs' is developing on a worldwide basis to finally look at these proteins and we can only do that for the first time on a reasonable level because we will have the complete genetic code.

Next slide. Now I think that the most important thing we are going to get out of sequencing the genome is better information about ourselves. If we were going to sequence any one of your genomes the chromosomes that you got from your mother and the set that you got from your father differ from each other in about 3 million letters out of 3 billion in the genetic code. For probably only 10 to 20 thousand of those lead to the substantial differences that you think you see when you're looking at the person sitting next to you. We are sequencing the genome of 5 different individuals. We've been concentrating on one for the early phases, that will give us 2-3 million of these 'polymorphic' variations. By the summer we will have tens of millions potentially of these 'polymorphic' variations in our database, being able to link these changes in the genetic code to key human traits. For example, in Africa it has been demonstrated that there is certain alleles associated with increased susceptibility to tuberculoses infections, increased susceptibility to malaria infections. Conversely, some of us carry alleles that allow us to be resistant to tuberculoses, resistant to malaria. Understanding the fundamental basis of our own generic code will allow us to understand and hopefully impact and change medicine throughout the world.

Next slide. This is going to lead us to what we think the era is coming starting in the next few years of personalized medicine. Most people don't realize that the drugs that are given affect at the most 50% of the population usually about only a third of the population due to the genetic differences. We have different structures in our receptors, different structures in our genes of these different proteins that these different drugs interact with by understanding what your unique genetic profile will be will determine which drugs you should get in the future to treat a disease you might have and which ones you shouldn't get. For example, a new class of Type II diabetes drugs are just phenomenally effective in treating Type II diabetes, except roughly 1 in 10,000 people either die or develop severe liver toxicity. If we can understand the genetic differences of those few people then we can do a prescreen to make sure only the effective benefit of the drug takes place and not the toxic affects. Our goal is to provide this information to individuals allowing them to interact with physicians and solution providers.

Next slide. Security of the information is very key. We feel very strongly that only you should be the controller over your own genetic code. It should not be in a government database, it should not be in a company database and so we are going to be providing genetic profiles for people but you will have your own CD-Rom or DBD disk with that information that you can work with physician or solution providers.

Next slide. The collective information is beginning to change the linkage of genes to disease, so the pharmaceutical industry knows what genes to target to try and block disease. Several years ago I was involved with Bert Bogalstein at John Hopkins University in finding genes linked to colon cancer and it is now with non-polyposis colon cancer we know all the genes that lead to a greatly increased susceptibility, greatly increased odds of you having colon cancer.

By you having that information earlier in your life, it gives you power over your own lives. Because instead of just waiting until symptoms appear, which by then it's usually too late and mortality rates are very high, if you know you have greatly increased chances of having colon cancer you can have increased physical exams at increased frequency. And if cancer is caught early it's virtually 100% treatable. So the goal is to empower individuals with this information and I think it's going to have a dramatic impact in changing the medical world.

The last slide is just a cautionary note in terms of this is a quote from a state senator in the U.S., it's an abortion of a Shakespeare quote "People used to think their destiny was in the stars, now we know it's in our genes, it's in our DNA". But I don't think you'll find too many reputable scientists in this field that believe in genetic determinism. In fact with identical twins, you might call them clones today that have the exact genetic code to one another, only have a 50/50 chance of developing some of the same diseases. So our genes determine a set of repertoire that of susceptibility interactions with the environment but they are not deterministic, in fact the only thing that's truly deterministic in genes is sexual determination and we can determine that pretty easily with 'x' and 'y' chromosomes. So I think this is going to have a big impact on the legal system, people are looking to absolve themselves of personal responsibility but I don't think they will find solace in the genetic code that allows them to do that.

Thank you very much.

 

Jean-François Mayaux, Aventis Pharma
"Functional Genomics: Impact on Drug Discovery"

What I am going to talk about today is a follow up to the previous conference, um, the previous presentation, What is the impact of the functional genomics on drug discovery? So I am responsible for biotechnology at Aventis Pharma, Aventis is the product of a merger between ("Rond Blank & Huegts"?) it has been, for a very limited period of time, number one in life science, worldwide. It has been for a very limited period of time because so many companies are merging these days so it is getting very difficult. Our goal is to remain among the ten first companies.

So the background is to tell you that we are facing a challenge in the pharmaceutical industry. Drug development is indeed becoming a long and risky process and I think this is something that should be clear to all of you and what is indicated here is some figures. Roughly the length and complexity of drug development has increased. As you can see, we need about twice as much time now to develop a drug than in the 1960s. Since 1980, the number of clinical trials needed has doubled. The number of patients, everything has doubled or tripled. The well-known figure is that the total average pre-tax cost for drug development worldwide is in the range of 500 million dollars and this is approximately a ten-fold increase in twenty years. What you should bear in mind is that only three out of ten drugs that are approved do recover the average R&D cost and fund the R&D process….
A few more figures just to tell you that spending in research-based is indeed increasing in a very significant way. For instance over the last twenty years the percent of U.S. domestic sales allocated to R&D has increased from 11 to 21 percent. And to give you an idea, all other industries is less than 4 percent so we are very much above the average and probably very close to the maximum (pro-rate?). So we are faced with pressure, and the pressure is of course due to the fact that the payers and regulatory agencies request more and more from us, which is fair enough and I guess we have no choice by the way, but the point is that we do have to find solutions to improve the process and what I am going to try to convince you about is that genomics part is only one key aspect of our response to that. Clearly not the only one so don't believe that genomics is going solve everything but clearly it is one key point. Other aspects I am not going to discuss are new technologies for screening drugs, -?chemistry, and non-strategic types of things such as the merger frenzy and other stuff.

A few words about biotechnology. Question is, Will biotechnology/genomics offer breakthrough treatments for the next centuries? As you can see, some of our leaders do believe it will be the case if the expectations have already been mentioned by the previous speaker. We want to prevent, cure and treat more diseases.We want to develop more precise and effective new medicines with fewer side effects. We want to anticipate and prevent disease rather than just react to disease symptoms as is most often the case currently. And the third aspect which is mentioned here and is pretty well known, we want to provide replacement human protein therapies without risks but this is already pretty much in place.

The message I would like to convey to you is that the revolution is still to come. Interestingly enough, we have talked about biotechnology already for twenty years. When I personally started in research a little more than 20 years ago, there were already articles in the media. So what happened recently, what happened during those 20 years? Recombinant proteins, recombinant DNAs, in the beginning of the 80's it was suppose to revolutionize the industry. In fact, there was a very significant evolution, we are using recombinant proteins, ?-transgenetic animals, models? organisms, we are using yeast organisms- as explained by Dr. Venter, but if we look at the products, the recombinant proteins remain rather a limited part of the business of the pharmaceuticals. Probably around five… less than 10 percent. So the impact has been limited so we should bear that in mind. Gene therapy, there has been a lot of excitement around gene therapy, and I am not going to talk about gene therapy today, although we have a rather significant effort at Aventis in gene therapy, but as you know it is not yet there. Our most advanced product is clinical trials in the U.S. and we should have some good or bad news in one or two years. So it is not yet there. The full impact on drug finding, which I am going to discuss in a little bit more, is still to come, so the age of biotechnology has just begun.

What is going to be the impact of genomics on drug discovery? Currently, you should know we have only about 500 distinct targets for the current drugs. Of course this is a very limited amount of potential targets. The number is expected to increase by 6 to 20 fold as we have been told, because we believe will have 3,000-10,000 possible targets. If you say the human genome is 80,000 it is very likely that not all the genes are targets, 10,000 is a little optimistic, but at least 3 to 5,000 is likely to be the number. As you know, we will have either from Celera, or from other parts, we should have a draft of the humane genome soon. We already have an already pretty extensive covering of ESTs and CDAs from humans and other organisms but especially humans. So this is going to be a very major change as already alluded to. So the key point is the efficient use of this information and most relevant technology platforms and expertise is going to provide a key competitive advantage. Dr. Venter said that he can sequence in 10 months, but I can tell you it is going to take years, tens of years to extract the information to derive drugs. So the challenge is to select the most relevant targets, translate that into effective, safe and rapid treatments, and devise new ways of carrying out high-throughput functional genomics methods in the chain of drug discovery to identify the best targets to pursue. So the goal is really to identify susceptibility genes for common diseases, translate those discoveries into target selection and apply genetic methods to the development of the right medicines for the right patients.

The expectations from the industry are pretty high. Those are numbers… I am not going to go into those numbers. This is from a real survey, so it is not my own fantasy and you have for 1996 the real numbers, the real statistics, and what is expected of the industry so you can see that the impact of genomics is believed to be very signicant, the discovery time is going to be much lower, the number of leads per year per employees is going to rise, rise very significantly, discovery spending per NCE (new chemical entities) is expected to be much lower etc. and so on and so forth.

It is interesting because despite that we have such a survey, it happens that very few pharmaceutical companies have effectively integrated genomics into the overall discovery process and most remain uncertain how, and how much they will invest in genomics capabilities. So the belief is functional genomics will be key in the near future.

Just to give you an example for that, this is a real survey, so 1-13 are major companies, I am not just talking of biotech start ups here. They have been asked what is the percentage of targets you are currently working on which is derived from genomics, and interestly one has answered 95 percent, but you see also that quite a few of them have 'no', so the impact of genomics is currently null and the average is around 20 percent for the major pharmaceutical companies. So what do you think, what do we think, will be future scheme for drug discovery, what will be the process for drug discovery in the genomic age. We will start more and more from sequence information. That is absolutely key so I can readily and happily confirm what has been said by the previous speaker on that, at least. Then we will have a filtering process and we will start classifying what are those genes of interest. Then we will have to "functionalize", which means ascertain the biochemical function and how it fits in a biochemical pathway. Then we will have to carry out some target validation, target validation means role in a disease model and therapeutic index, at least enough to convince us to move forward in a rather costly process and then only the drug discovery process per see can start, which means assay development & screening, identification, optimization and so on and so forth… to lead to a new drug. The new part of it is the beginning because that is not exactly the way we proceeding until now.

What happens in the so-called genomics companies? I am not going to talk about Celera but I am going to talk about the first, historically-speaking, genomics companies called human genome sciences, and this is of course from public claims/ information. They have started in 1983 and have claimed to have sequenced ESTs, covering 95 percent of human genes. They say that over 75 to 80 percent are fully functional and one of their major stratagies to isolate complete set of human genes capable of producing secreted or signaling proteins, the believe being that those secreted proteins are the most relevant ones for future development. They have identified 12,000 genes. They say that over 11,000 are not yet recorded in the scientific literature and they are busily involved in full length cDNA cloning and sequencing and not just getting a small piece of it, but the whole gene. They have 9000 genes and only a little more than 500 are closely related to known proteins. So as the previous speaker said, the conclusion for them and for us, is that the great majority of signaling molecules evolved recently and can not be discovered by homology searches based on the small universe of known proteins and based on bacterias and yeast and lower (bacarates?). What are they doing with that? They are carrying out some biological screening, gene mapping, they do expression profiling, and I will come back to that later on, then they expression/purification of recombinant proteins of interest to them, do some cellular screening, develop some tools, and what is the output? What is output for these companies for several years now? Patents. That is the key message. The output is patents. Primary output is patents. They have over 5000 patent applications and something like a 100 now applications allowed and about 70 issued in the US and in terms of products it is little less good. Of course, this is getting more and more complex, I would like that you understand the difference between getting genes and getting products.

So the products they are currently involved in are two recombinant proteins and one project is by the way a joint product in gene therapy. So as you see a real discrepancy between the huge amount of information and the real output as products.

So let me now give you very quickly a few examples how we can use this information. One has already been mentioned and this is what we call the target family approach. The principle is very simple with genomic based strategies you can now access many new members of a protein family, the pharmeceutical relevance of which is already well established. You can do that either through directed cloning approaches or electronic searches in databases which now are getting quite relevant to do that. This relevant target families approach can be defined on the basis of properties of known members their biological function and specificity, their operational advantages in the drug development process. The two examples I will give you, one of them has already been mentioned is orphan nuclear receptors and the other G Protein Coupled Receptors. So of course the challenge behind that is really target validation is how to make sure there is a disease relevance. So very quickly for instance orphan nucleur receptors which as you know are already a target for hormones and receptors for hormones, so we can now find many different receptors in this family and some of them have already been identified as being receptors for quite relevant (lygens?).

A key aspect of functional genomics is what we call gene profiling/ gene expression profiling. I will give you just one example for that, which is the so-called chip, for instance a (?)chip, which I think is one of the most advanced and utilized ways of doing that, so you can extract messager RNA from a given a biological sample and really understand what is the gene expression provide, what genes are expressed, what genes are down regulated, etc. It gives you a very precise map of any given organisms, or tissues or cell. What can we do with that? Of course, we can compare diseased states and normal states, cells which have been submitted to a drug for instance, and can derive very relevant information from that, either markers or even in some cases targets. We can not only do that with messager RNAs but you also can do that with proteins because as already mentioned, we now have access to technologies which really enable us to directly look that whole (protell?) of a given cell and really analyse those proteins of importance and this is not science fiction, we already have very nice examples of that.

So the very last point I would like to make is about the future impact of genetics, human genetics, this was also mentioned. The differences in gene function between individuals are indeed a major component of the differential drug responsiveness and differential susceptibility to common human diseases. One of the predominant variant sequence type is the so-called SNP and there are some very major scientific achievements that are going to occur in the next three years or so that should really revolutionize the impact of human genetics and drug discovery and development. We will get a complete human genome soon, how soon is still a matter of debate. We will have a high-density snip, map, of the human genome and Aventis is part of a Consortium that will help identify some 300,000 SNPs. And also very importantly we should have, in the next two years, very high-throughput genotyping platforms, that will deliver millions of genotypes per day or per week and this is very important of course to be able to really access and use this information. The future impact of human genetics is going to be on drug target discovery because of the high scale snipping and association studies that will be able to carry out on both diseased and normal populations and so we will be really able to identify disease susceptibility genes and new disease related pathways. This is going to be important for drug development and pharmengenomics. We will understand the human polymorphisms of a drug target, we will understand the variations in metapolizing enzyme coding genes and we will be able to incorporate this genetic susceptibility knowledge into clinical trial design and clinical practice and the final goal is to derive several individualized therapy or the right drug the first time, which I think is still a little bit of science fiction. So I think I will end my presentation here. Yes, biotechnology has a very significant importance for drug development for providing tools, for products it is not exactly yet there. We really believe the next stage, which is going to be genomics, functional genomics, is going to be one of the key assets we will have that can meet the challenge to provide you with more effective and safer drugs.

Thank you.

Chair: I thank the speaker particularly for the foresight for bringing backup material. I think we have time for one question.

Question from the audience: I just wonder, you mentioned, and Craig Venter also mentioned, personalized medicines, but does the pharmeceutical industry get enough benefits to produce personalized medicines, you can't produce them in bulk.

Mr. Mayaux: That is a very relevant point. I am not saying that we are already ready to cope with all the possible consequences of that. So I agree with you. Let me give you one example where we have decided not to step in. This is called cellular therapy, which is a little different from gene therapy. Cellular therapy means that we get your cells, we modify them in a therapeutically relevant way, and we re-inject them for you to get a potential benefit. It is difficult for the time being to envision genetic cellular therapy, so you have to do it in a very individualized way. We have been involved for at least two years in thinking about how it could be done and the conclusion was no, we are not going to get in that business and we have stopped all our activities in cellular therapy. So this is just to give you an example. To say that yes, it is a difficult question. I mean this individualized therapy is not something that we do readily grasp currently.

Chair: Thank you very much again.

 

Matthias Kummer,
Political and PR-Organization of Swiss Business
"Biotechnology and Public Communication"

transcript will soon be available

Noëlle Lenoir, French Constitutional Court
"The Ethics of Biotechnology"

The European Perspective.

In 1947, Canguilhem, a French epidemiologist, wrote that " the renewal of metaphysical and no longer just scientific interest in biological problems could have wide-ranging practical implications for our civilization... Quite an understatement, isn't it. Canguilhem hit the nail on the head. His observation is precisely what the ethics of biotechnology is all about. I mean that the ethics of biotechnology is based on the idea that there is no real separation between science and politics, contrary to what was postulated by Max Weber some decades ago. According to Weber, science is strictly separated from politics because it is not of the order of action, but seeks only the pursuit of knowledge. The responsibility of the scientist is thus limited to the faithfulness of the reflection and his fidelity to the search of the truth.

Nevertheless, this classical view of science is now difficult to maintain since science is narrowly linked to technology. This transformation is mostly important as regards the attitude of society towards scientists. Indeed, they are asked to participate in the same ethics of responsibility as is traditionally asked of public decision-makers.

Biotechnology in particular entails this ethics of responsibility. Indeed, everyone acknowledges that it is a source of profound change in our way of living - the food we eat and the medical treatments we have, for instance - and is even able to change the nature of all living species, the human species. Is this why biotechnology is subject to so many controversies? I think so.

And in my view, it is quite understandable that people raise questions about the long-term consequences of a technology which, of course, may help to wipe out' famine and eradicate many of the world's most feared diseases, but which, on the other hand, may go one step too far in manipulating life. For example, human reproductive cloning.

I'll see the ethics of biotechnology from the point of view of a European, of course. Indeed, I've had the good fortune to have been associated from the very beginning, as a member and then chairperson, with the EGE, an then be able to think about ethics at the EU level. I've observed the way ethical considerations have progressively been introduced in European Community law especially with regard to research, the environment, patents, animal welfare and medicine. Undoubtedly the setting up of "ethical standards", if I may say so, is closely linked to building of the EU, which is not only a single market, but is also more and more deemed to be a political community. That's to say that European ethical values, and especially those concerning science and technology, defined by law are intimately connected to Europe's cultural and political identity.

But the ethical debate is not limited to Europe. It also exists in the US, in Canada, in Japan and in more and more countries throughout all parts of the world. That's why I think it is essential to deal with the issue at the highest level, which cannot be but on the international level. In my opinion, there is an urgent need for a permanent body at the international level where views between the different cultures of the world can be exchanged and where there's access to experts whose legitimacy and accountability are universally recognized. Why not create a kind of true international Agency of the UN, , with advisory capacity, to act on contradictory expertise in particular in the field of safety ? Researching food safety, for instance, in cooperation with other organizations such as the FAO and the OECD. The agency would include an ethics department which is multidisciplinary and independent, and whose task would be to foster widespread consultation for all the parties involved (industries, scientists and NGOs, for example ). The Agency could be consulted, if necessary, at any country's request.

There are many different places where the ethics of biotechnology is discussed, but there lacks a well identified, independent and permanent body. Sooner or later, one must be established, and the sooner the better. Such an innovative initiative is not unrealistic, since the UN already showed its interest in bioethics in endorsing in late 1998 the "Declaration on the Human Genome and Human Rights", elaborated by UNESCO one year before. Keep in mind that the adoption of this Declaration was strongly supported by the US, which approved the balancing in the text between safeguarding respect for individual rights and ensuring freedom of research.

Worldwide dialogue is all the more essential as it is the only way to ease to lift misunderstanding and search for solutions to common problems. The world is our village, technology has no boarders. Dialogue is key and especially International dialogue. What about the situation in Europe. What strikes me is that, although Europe and the US share the same values, in Europe the ethical debate has much more influence on politics than anywhere else in the world.

The European background is indeed different from the American one in three ways:

1. Europe's concern with the ethical aspects of technological development is rooted in old juridical tradition. For example, as early as the nineteenth century, ethical considerations made their first appearance in European law on patents. Indeed the first European treaties on the subject stipulated that inventions could be denied a patent where they were "contrary to morality". And the same restriction is set up, in a more contemporary context, by the patenting life" Directive of 1998, which singles out as contrary to morality (and therefore unpatentable) human cloning, modification of the human germ-line, and inventions involving the use of human embryos for industrial and commercial purposes.

2. For many Europeans, and not only the older ones, biotech research also revives horrific memories of the medical experiments carried out by the Nazis. This explains why embryo research in particular is strictly forbidden by German law. This explains also why the Europeans, by and large, are much more pessimistic than Americans about science and progress. Biotechnological developments are more feared in Europe, in the food sector as well as in the medical field. Generally speaking, unlike in the US, the biotech industry is often suspect and its inventions eyed askance.

3. Recent history has only strengthened this distrust towards science. In the post mad cow era, anything which has to do with food technology is suspect. I suppose subconsciously the plagues are too. The radical changes in public opinion in the UK are striking. Before the discovery of the transmission of the mad cow disease to human beings, the Britains raises no objections to biotech developments of in the food sector. British consumers regularly bought for instance genetically modified tomato sauces. How things have completely changed now! Public opinion, in the UK, has become mostly skeptical about the benefits of GMO. And this skepticism is now shared by the rest of Europe. Result? No new GM crops have been authorized in the EU since April 1998. Obviously, public opinion is influencing more and more the European decision making process since the EU Parliament, whose deputies are ever sensitive to public concerns, now has extensive legislative powers.

This all points to the fact that European decision makers have striven to take into account public concerns in making biotech policy. This Policy has three characteristics.

1. First, the choice was made very early on to give the horizontal approach precedence over the vertical one based on a product by product regulation. That's to say that the main European Directives on biotech - on safety of deliberate release of GMOs as well as on life patenting, for instance concern all life-science applications. This approach has facilitated the ethical debate about the social and political implications of genetic engineering as such. "Ethics must never be subordinated to biology" said E.0 Wilson. This sums up the European approach. The debate on the patenting life Directive was so hot that its first version was rejected by the European Parliament on March 1995. It's illustrative to see that the reason why Parliament vetoed the text is due to its ambiguity with regard to the respect of the principle of non-commercialization of the human body, including the human genes. As everyone can see, the ongoing debate on the modification of the 1990. Directive on approving GM crops is much more political than strictly scientific.

2. The second choice was to open by creating in 1991 the first European ethics committee ( the EGE), whose task defined by the European Commission, at that time chaired by Jacques Delors, is to play an advisory role in policy making. This shows that without question ethics would be an essential part of the EU community law. Setting up an ethics committee was the more ambitious as, unlike other bodies of its kind, its remit was to deal with all the ethical aspects of biotech by and large, and not only biomedicine. It's interesting to note that among the fourteen opinions already made public by the EGE, more than half of them did not deal with human genetics, but with other applications of genetics:

· Bovine somatotrophin, GM food, patenting, cloning and genetic modifications on animals,...for instance. It's also very noticeable that the Group, which now can be consulted not just by the Commission of Brussels, but by the European Parliament and the Council of ministers too, has also become the interface between the Parliament and the Commission. Indeed, their approach is quite different, for the latter has to take into account commercial and industrial imperatives while Parliament sticks closer to public opinion and to the NGOs claims.

3. The third specificity of biotech ethics at the EU level is that "fundamental ethical principles" are enshrined in public law.
I don't use this term by chance. The concept has indeed become part of European community law. For instance, the decision made by the European Parliament and the Council of Ministers on December 1998 to refuse funding for research involving human reproductive cloning or the modification of the human germ line, provides that "the Union, in its research and technological activities, respect fundamental ethical principles". And it is not unusual for these ethical principles, such as in particular the right to privacy, the principle of non commercialization of the human body or the principle of human dignity, to be expressly referred to in different legislation.

This is the main difference which exists, in my view, between the American and the European approaches. Unlike Americans, we Europeans hold the view that public authorities must establish the principles according to which research must be conducted. What are these principles ? I've identified four main "Fundamental ethical principles" which express, in my view what is at the heart of the biotech ethics in Europe.

1. First, the principle of human dignity and the respect for human life seems stronger in Europe than the principle of unrestrained research. This explains, as I said before, why are banned at the European level reproductive cloning and on human germ line modification and why this ban remains unchallenged. Let's be clear. The principle of the respect for human life does not mean that one can cultivate morality simply by following nature. The idea that morality is located in the prolongation of biological nature is praised by a tiny minority in Europe. Respect for human life implies means considering that the genetic make up of human beings cannot be manipulated as if they were mere objects.

2. A second important principle has to do with animal welfare and the protection of animals against excessive and unnecessary suffering. This results in legal restrictions in Europe on the use of animals either for farm purposes or for experimental and other scientific purposes. Animals are now regarded as "feeling beings" and many European regulations are aimed at protecting them. One of the most illustrative regulations is the patenting life Directive which states that " processes for modifying the genetic identity of animals which are likely to cause them suffering without any substantial medical benefit to man or animal, and also animals resulting form such processes" are unpatentable.

3. The right to privacy with regard to genetic data is also considered a fundamental ethical principle since the principle of medical secrecy is deeply rooted in European culture. In this respect, it's illustrative to note that the Directive on data protection of 1995 is officially based on this principle. It thus strictly restricts the processing of data concerning health or sex life. Its preamble stresses that "the establishment and functioning of the free market in which the free movement of goods, persons, services and capital is ensured, require not only that personal data should be able to flow freely from one Member State to another, but also that fundamental rights of individuals should be safeguarded". Am I right when I assert that the ongoing debate in Congress about the protection of the confidentiality of medical data is being partially influenced by this European statement?

· (Indeed the Directive states that the transfer of personal data from Europe to a third country must be authorized only if the country in question "ensure an adequate level of protection").

4. The last important ethical principle, now expressly mentioned in the European Treaty, is called the "precautionary principle". This principle, in spite of its environmental origin, is deemed applicable to all kinds of biotechnological products and processes. Contrary to what is often thought, it does not imply a call for a moratorium each time there is no absolute proof that such products and processes are safe in the long term. First, such absolute proof is impossible in so far as all risk assessment evaluations are based on knowledge which by definition may be Subject to improvements in the long term. Second, the precautionary principle is essentially aimed at ensuring that the decision makers remain ever mindful of the possibility of detrimental eventualities. The European Commission is going to issue in a month or two a publication on the precautionary principle. There is also a pending case before the European Court of Justice which will lead to clarification of the concept. However, at the risk of being too personal, I'd like to just mention one principle which I believe is very useful in the present context, namely that irreversible damage is very possible unless strong emphasis is placed on safety and caution above economic interests. As a consequence, ethical evaluation and open public debate must come before research or before the marketing of new products in the most controversial areas. I admit that things are not so simple. One could indeed think that to underline possible risks, while these risks remain unknown, is unjustified and could even be dangerous. But one must also admit that our society is evolving. European citizens in particular aren't asking for absolute safety, but rather for a safety net to be safeguarded by public authorities. Of course, there are few real differences in the safety standards applied in the US and in Europe, but our mentalities differ considerably in the US, the FDA is trusted and its decisions are generally go unchallenged. In Europe, however, we don't and won't have such a federal type structure. Indeed the Food Safety Agency, whose creation was recently announced by President Prodi, will only have an advisory capacity. I bet that Europeans will in any case continue to doubt the benefits of GMOs, for there is a lack of trust in industries as well as in politicians. In addition, it's uncertain that the risk assessment evaluation process is really appropriate with regard to food safety contrary to what is the case in medicine. In other words, as is shown in surveys such as the "Eurobarometer", Europeans accept risks in using new medical treatments, but not in eating new foods which are thought as even less "genuine" than those now on the market. On another hand, the right to transparency, asserted by the Treaty of Amsterdam, is now seen as fundamental in order to ensure that the people regain confidence in public and private decision makers, including, of course, industries. That's why GM food labeling is now regarded in Europe as part of freedom of choice and something which must be guaranteed to consumers.

The ethics of biotechnology, whose emergence has led to the introduction to European community law of provisions directly inspired by ethical principles, is now part of the very fabric of European Union identity. Nevertheless, it does not reflect the extreme diversity of national cultures in Europe. Sometimes the ethical imperative is to respect this diversity by giving precedence to the so called "subsidiarity principle" which prohibits the legislation at the EU level, for example when it is not really necessary and when it would be more adequate to leave it up to each country to decide the appropriate regulation. Along these lines, the EGE stated regarding human embryo research, that " because of lack of consensus, it would be inappropriate to impose one exclusive moral code". But in case legislation is thought necessary either at the national or at the European level, then, unlike in the US, this regulation must be applicable to the public as well as to the public sector. I quote again the EGE which stressed in its opinion of 1998 on human embryo research that "it is crucial to place this research, in the countries where it is permitted, under strict public control, while ensuring maximum transparency, whether the research in question is carried out either by the public or by the private sector".

I'll wind up by asking what's ahead?

1. Since we are facing considerable scientific progress in the life-sciences, our democratic society requires very high awareness by all citizens regarding progress in view of ensuring that they fit with their needs and aspirations. The ethics of biotechnology, especially in Europe, corresponds to this democratic imperative.

2. I'm convinced that the ethical debate cannot be but enlarged in Countries other than Europe. It will oblige decision makers - in industry and politics to take into account the fears and claims of the citizens, some of which are expressed in the media by NGOs. The media are indeed a strong vector of ethics since they allow groups of interests to exert pressure on the decision making process, namely in the field of biotech.

3. In order for this debate to be conducted in an unbiased way, it's not Just reasonable but crucial to call for the creation of an international permanent Agency able to produce scientific evaluations as well as evaluations on ethics when needed by countries that need to consult it. This implies that the agency experts are not only top level, but enjoy a status which enables them to assume their task with sufficient means and total independence.

We're no longer the passive playthings of evolution. We are almost able to grow strawberries on grapevines or to change rocks to roses, it seems. That's why I believe that those who pretend that ethical concerns are not Justified are either insincere or don't know the huge responsibilities now confronting society as a whole.

 

Laurens Jan Brinkhorst,
Minister of Agriculture, Government of the Netherlands
"Biotechnology - Implications for Agriculture and Society"

In 1818 'Frankenstein, Or The Modern Prometheus´ was published, written by the twenty-year old Mary Shelley . The novel was made into a film many times. We are all familiar with Victor Frankenstein´s monster. He is the product of a technique, an artifact, the result of a scientific experiment that went badly wrong. Nowadays the monster stands for the horror scenario attendant on modern biotechnology. Thus there is talk of Frankenstein food and European Frankenfears. But this does no justice to Mary Shelley´s book nor to modern biotechnology. Mary Shelley was a product of the Age of Enlightenment. She did not intend to discredit science or technology. She wanted to show us how a creature of human mind could turn into a monster when left unattended. Mary Shelley´s book teaches us that we must never lose sight of the relations between science and technology or society and nature. The search for new answers is a continuous process, a process we must adopt to keep the spirit of the Enlightenment alive and realize the progress promised by science and technology.

This by way of introduction. I will first sketch what I believe are the implications of biotechnology for agribusiness and society.

After that I will talk about the challenges for the agrofood sector and the government. I will come back to Mary Shelley at the end.

Now let us look at the implications of biotechnology for agribusiness and society. The impact of modern biotechnology on the agrofood sector is enormous. It will drastically change the nature of production. It will blur the traditional boundaries with other sectors of production. Agricultural sciences are turning into life sciences. Factories will be replaced by plants. New product categories will come about, such as nutriceuticals, functional foods, drugs, novel proteins. The forces that link up information technology, biotechnology and transport technology will create an enormous impact. International production and marketing chains will change beyond recognition.

But the public support for the use of modern biotechnology in the agrofood sector will profoundly affect the relations between the links in the international production and marketing chain. Producers will get a thorough shake-up. An international market has emerged which is driven by consumer demand. The final links in the chain, the retailers and multinational food processors, are demanding a new position. They will force the chain to adapt and that is not infrequently done with strong-arm tactics. Just look at the actions of the European retailers. Consumer autonomy, freedom of choice, consumer concerns, flexibility and transparency of the production and marketing chain are the key words here. The large multinationals with their brand names are more vulnerable than ever.

The relationship between civil society and the industry is also undergoing change. In an international demand driven market the industry can no longer ignore the demands society makes. The post Brent Spar effect. Food producers will not only need a legal license but also a license to produce. The consumer organizations, single issue organizations and NGOs have become a force to be reckoned with. Globalization is not just restricted to the industry, single issue organizations and NGOs know their way around. The influence of NGOs has increased strongly, worldwide.

Now something about the impact of biotechnology on society. Biotechnology, in my view, is a key technology of the 21st century. It will have major consequences for our individual way of life. Dietary patterns will change but so will our agricultural landscape, which will be furnished with novel crops. Biotechnology will help us solve problems in our society. Problems in health care, the environment, food security, poverty. But this will only work if we know how to deal with this complex technology, how to keep it in check. We shall have to keep asking questions about our modern risk society. About or relationship with nature, our cultural identity, ethics, the risks involved for man and the environment and the fair distribution of wealth and natural resources. We shall have to keep asking ourselves whether something is ethically acceptable. For one thing is clear: with biotechnology, hitherto unknown applications come within our reach. We will have to find out again and again whether an application is still socially acceptable. With biotechnology we will break new grounds: it is even possible to cross the boundaries of species.

The questions raised here will certainly be similar to those raised by our transatlantic partners. And, given our global markets and common interests, we will have to make a joint effort to agree on how to formulate the answers. We can only do this if we accept the fundamental point that people in Western Europe and people in the US think differently about the acceptability of risks, the cultural role of food and the monitoring role of the government.

Now let us look at the challenges for the agrofood sector. The open society I talked about calls for new forms of governance in which the creation of trust and stakeholder value for the agrofood business should come first. In this way the agrofood business can obtain a licence to produce. I would therefore urge the business to come forward in the debate, rather than take a passive role and just respond to changes. The agrofood sector is my firm believe cannot do other than respect consumer autonomy. This requires transparency in the production and the marketing chain and clearly identifiable products. Market segmentation is on the increase.

* We now see a modest but growing market for organic products
* Alongside, we will see the segment for traditional agricultural products.

Within the latter we see a further division between guaranteed GMO-free products and products which can contain genetically modified organisms for which labeling is or is not yet compulsory. Freedom of choice is what the consumer wants. The right to make your own decision about what to eat and what not is deeply rooted in the European culture. It was a point overlooked when genetically modified maize and soy was introduced on a large scale. Meeting the demand for the right to chose is a major challenge for the entire food industry. I am well aware of how fundamental the changes will be and how complex the tasks ahead:
* of introducing a reliable, unequivocal labeling system;
* of ensuring that all the links in the chain guarantee the quality they claim to provide;
* of ensuring the separate production flows; and
* of reorganizing the trade in commodities where bulk handling will be replaced by the handling of smaller volumes for specific market segments.

The second challenge lies in communication. How do we communicate in a way that is open, honest and factual about how biotechnology can help us solve problems in our society. This is a rather crucial issue for the food industry. The recent food scares and the introduction of the first generation of GMO products have made the food industry extremely vulnerable. It was not exactly clear how the first generation of GMO products served consumer interests. Let alone the public interest as might have been the case in the pharmaceutical industry or medical technology. The claimed environmental benefits of these agricultural food products were questionable. Some even argued there weren't any. Therefore, when environmental claims are made for new transgenic crops or when transgenic animals are said to benefit public health, researchers and the industry are obliged to give full and factual information.

The industry has omitted to do so, so far. Which may have been one of the reasons why the public is hesitating on modern biotechnology. But I am convinced that the public sees reduced pesticide use in crop production as a benefit. This must however first be proved. It is therefore vital that public interest groups have full access to the dossiers that are being presented by companies to obtain a license. This has already been done in the Netherlands where the dossiers of transgenic animals and applications for field trials were open to inspection.

The industry should not only be clear about the envisaged benefits but also about the possible risks. Of course the risks involved are sometimes incalculable. Prudence is therefore of the essence and the latest scientific insights. I would therefore be in favor of a case-by-case approach. We are after all still learning. If we adopt Mary Shelley´s attitude and address the questions fair and square there is no need to resort to doom scenarios, to think in black-and-white or make the precautionary principle absolute, as some environmentalists seem to do. Such an attitude can call a halt to all technological developments. It is not necessary. Take the opposition against the antibiotics resistant marker gene that is used in plant production. The public debate helped to make the industry develop an alternative. I am very glad that the industry picked up this signal.

What are the challenges presented to the government? The government must prevent new trade barriers and harmonize existing regulations. We must seek compromises given that international forums such as WTO and Codex Alimentarius are always offering the latest findings new perspectives on progress and improvement. We must therefore make joint investments to develop new methods and technologies for technology assessment. The international forums active in this area will become increasingly important. We will have to make a major effort here. We must invest in the mutual adaptation of risk management systems and here too the law of the moving scientific insight applies. We can learn from one another. We could learn to make the decision-making process in Europe more efficient and transparent. Perhaps the US might learn something from the thoroughness of European risk analysis. In my view the government should also enable third world countries to profit from the new technology by for instance encouraging free technology transfer. We might for instance give third world countries access to our knowledge of the enrichment of local rice and cereal species with vitamins. Regarding Western societies, we must not forget that differences of view will continue to exist given the historical, philosophical and religious backgrounds of the various cultures in the western world. This insight however must not be used as a license to impose new trade barriers.

Let me conclude by returning once again to Mary Shelley. In her book Victor Frankenstein recoils from the sight of what he has created. This was not what he had had in mind. So he leaves his creation, alone and unattended. It is then that the monster turns on his creator and starts to kill all the things his master loves. In my introduction today I have tried to point out that that was 200 years ago and we have come a long way since. We have learned, albeit with ups and downs, to take the responsibility for what we have created. The responsibility for embracing the new must only be taken from the realization that uncertainty is inherent in all new technology. This is why I strongly believe in a transatlantic co-operation and a transatlantic public debate. I therefore very much appreciate the fact that Ms Schneider has organized her conference here in The Hague and encourages the debate in the media in Europe and in the Netherlands.

 

Mr David Byrne,
European Commissioner for Health and Consumer Affairs
"Biotechnology and the Public"

Ladies and Gentlemen,

I would like to begin by thanking Ambassador Schneider for the opportunity to speak at the end of this important conference organized, around the topic of the science and impact of biotechnology.

As European Commissioner for Health and Consumer Protection, I am particularly pleased to be here today and to give you my perspective on biotechnology and the public. In the past, the citizen in his capacity as consumer, has often been overlooked in discussions on biotechnology even though he or she is a legitimate stakeholder in the debate and the decisions taken on the utilization of this new technology. I , am also pleased that the aim of this conference is to discuss both advantages and disadvantages of biotechnology. The application of biotechnology has far- reaching consequences for society as it. has already been pointed out by many speakers before me - and apart from risks and benefits, ethical concerns are also important to-the public.

The only way forward to face the controversy surrounding biotechnology is to promote an open-minded and balanced dialogue between all stakeholders - scientists, industry, farmers and consumers and by ensuring full transparency in the risk/benefit assessment of biotech products. Furthermore, we have to accept and respect the consumers' right to have clear information in order to take informed decisions on which products they want to buy. I will return to this issue later, but let me first outline the recent European experience on food safety in general and the public concerns about biotechnology in particular.

Simply put, in the 'minds of, the European public, safety is the most important ingredient of their food. Other considerations - very important considerations - such as quality, value for money, choice, taste etc, come second. When the consumer chooses a product from the supermarket shelve, their first and over- riding presumption is that it should be safe.

The recent crises or scandals in Europe such as BSE or the more recent dioxin contamination have called into question the very safety of food. The fall-out from such events can have grave consequences for health as well as the economy. One clear lesson from the BSE and the dioxin crises is that there are no winners.

Compromising on food safety is not a way for a farm or a company to reduce costs. It is actually a very dangerous path, not only for, consumers, but also for the farm or company itself and for the whole sector involved. In an industry worth 600 billion euros annually in the European Union, that is about 15% of total manufacturing output, even a slight dip in confidence can have significant effects. Between the agro-food sector and the farming sector, there are about 10 million employees in Europe. High levels of confidence are necessary to boost job numbers and competitiveness. Confidence and Predictability are also essential elements to boost trade and you all know how important this is between the EU and the US who are each other's best trading partner.

I fully accept that in many respects food has never been safer. I am also fully aware that zero risk is not achievable, as in most other human activities. Nevertheless the public's demands and expectations have never been higher and confidence is very fragile. We have one of the best informed, discerning and sophisticated group of consumers in the world.

Each successive crisis undermines the public's trust in the capacity of the food industry, in its broadest sense, and in the public authorities, to ensure that their food is safe. You can, see from the press the extent of consumer unease about what they eat, you can read articles full of questions and analysis -right and wrong about genetically modified foods, the use of growth promoters, pesticide residues in food, salmonella, E-Coli, anti-microbial resistance to name only some. And, in addition to food safety, other legitimate factors play a significant role for many European consumers. Issues like animal welfare, environmental considerations, sustainable agriculture, consumers' expectations and fair information are being discussed more than ever Ethical questions concerning food production- have also entered into the political agenda all over Europe and needs to be addressed.

We all suffer from the fall-out from this loss of confidence. The crisis of confidence has had the unfortunate but inevitable effect of eroding the trust of consumers in systems and institutions at national and international level that should monitor and assure the highest standards of food safety. In saying all this, I would like to make it clear that Europe, nevertheless, has one of the best food industries in the world. And also one of the safest food control systems. The challenge is to make the systems even better.

In order to rebuild European citizens confidence that their food is safe "from the farm to the fork", the European Commission adopted last week THE WHITE PAPER ON FOOD SAFETY, on which I would like now to say a few words. I believe that, in the White paper, the Commission has put forward an ambitious, action plan to transform today's EU food policy. The actions planned are based on a comprehensive, integrated approach throughout the food chain - in other words from "farm to table" designed to make EU-legislation more coherent, understandable and flexible. The more than 80 separate actions proposed include proposals on GMOs as we are acutely aware of the need to have a coherent and predictable framework on GMO foods, animal feeds, and seeds, for example.

The White Paper provides that scientific assessment and advice must be based on independence, excellence and transparency. Public confidence can only be maintained in a system where scientific assessments are carried out by eminent scientists and independently of industrial and political interests. Scientific advice must be open to rigorous public scrutiny. The Commission has proposed the establishment of an independent European Food Authority with particular responsibilities for risk' assessment and risk communication. The Food Safety Authority should provide a single, highly visible, point of contact for all stakeholders. It would not only act as point of scientific excellence, but would also be available to consumers to provide advice and guidance. The Food Safety Authority will not be a European FDA, but -will work in close co- operation with national scientific agencies and institutions in charge of food safety. Unlike the FDA, and this is very important, it will not have regulatory powers. These are entrusted to the Commission, the European Parliament and the Council of Ministers. We wish to make a clear distinction between, on the one hand, risk-assessment which has to be based on sciencific excellence- and independence and, on the other hand, risk-management which is the responsibility of decision-makers, who are politically accountable to the citizens.

One very important element in the system is that the roles of all stakeholders must be clearly defined. This includes a clear understanding that feed manufacturers, farmers and food operators have the primary responsibility for food safety. In this new comprehensive approach to, food safety we are trying to meet some very specific consumer demands.

First of all, consumers have their right to make informed choices. I firmly believe in and support the consumers right to information and to take informed decisions about what products they want to purchase. Consumers want to be in a position to take informed choices. Information on production methods and labeling of products are key to this increased awareness and to the development of a civil responsibility .in this respect. I am of course not talking of products which are judged to be unsafe; clearly those should not be put on the market at all. The Amsterdam Treaty, our new I legal framework for European integration, has explicitly introduced the right to information for the consumers. European consumers have consistently demanded that GMO-food be labelled - not for reasons of safety, but in order to make an informed choice. A survey carried out in 1998 showed that 86% of the European consumers demand labelling of GMO food. I think that consumers in Europe have never been so united on any one issue as on the labeling of GMOs. Regulators and the food industry must ensure that this demand for information is met if GMOs are to win acceptance.

The Commission is currently working on improving the EU-legislation on labeling of "GMO-free" and on the legal framework for a "GMO-free" production line, to which producers can adhere on a voluntary -basis The objective is to provide consumers with clear information, and a choice between products. I believe that an appropriate labeling system of genetically modified food is one of the cornerstones in resolving the current controversy concerning the application of biotechnology to food. Without appropriate consumer information, mistrust about biotechnology and GMO food is bound to proliferate. I am therefore pleased to see that many other countries, such as Japan, Korea, Australia and New Zealand, are adopting a similar approach. In some cases they have already acted! This responds to the demands we have had from consumers in the Transatlantic Consumer Dialogue.

Information is of course very much linked to the issue of traceability. A successful food safety policy also demands traceability of feed and food. This obviously applies to GMOs Adequate procedures to facilitate traceability must be introduced. This includes the obligation for feed and food businesses to ensure that procedures are in place to withdraw feed and food from the market where it presents a risk to the consumer. It must be emphasized however that unambiguous tracing of feed and food is a complex issue and must take into account the specificity of different sectors and commodities.

Let me now turn to another element: control. European Consumers have repeatedly stressed the link between consumer acceptance of biotechnology and rigorous and transparent .control of GMOs. Biotechnology is a new area. Because of this I believe that it is fully Justified that authorizations should be reviewed and time-limited and that genetically modified organisms are carefully, monitored in the light of evolving science. Indeed, when important new scientific information on an authorized product becomes available, a new scientific assessment should be carried out. Another of the central elements in restoring consumer confidence is to make decisions concerning food safety which are based on science -that is a scientific assessment of potential risks. The Commission is determined to continue to use the best available science in developing its food safety measures. Under the current European legislation, genetically modified food can only be placed on the European market after it has been, scientifically evaluated and when, according to the latest scientific knowledge, it is considered to be safe for human health and the environment. This is a science-based approach. However, in cases where scientific evidence is insufficient, inconclusive or uncertain, and where possible risks to health or the environment are unacceptable, measures should be based on the precautionary principle. This is in line with the consumer demand for a precautionary approach not only in relation to GMOs but also -to a variety of food safety issues, where scientific data are sparse and scientific judgement is uncomfortably imprecise.

The Commission is currently working on a communication defining the precautionary principle and clarifying when and how it can be applied to protect the public while avoiding its use for trade protectionist purposes. The Commission also wants to clarify the conditions for the use of the precautionary principle, and develop multilaterally agreed guidelines for that purpose. To sum up, I think that the principles I have outlines are fundamental for a new framework on GMOs:
· first and foremost, GMOs must be safe
· there is a need for proper information
· the traceability of novel feed and food must be ensured
· authorizations must be time-limited and
· there must be careful monitoring

They are all contained in the Common Position recently adopted by Council on the revision of the EU-legislation on the deliberate release of GMOs into the environment, and I believe that this is the way forward. The debate on GMOs so far in Europe and elsewhere has been characterized by a great deal of emotion and insufficient reason. The EU is not against the application of biotechnology but I feel that the biotechnology industry has moved forward very quickly without taking sufficient account of the concerns of society and a parallel failure, to inform citizens sufficiently as to the merits of this technology. A recent Euro-barometer survey revealed that only every second European finds it morally acceptable to apply biotechnology to food. Opposition to, GMOs products has to date been largely, found in Europe, but, I am aware of growing concerns in the US as well.

I believe we all need to have a predictable and coherent framework in place, and I am determined to do my utmost in full collaboration with my other colleagues in the Commission, in particular the Commissioner in charge of the environment Ms Walstrom, listening, to all interested parties. Many consumers have questioned the benefits of biotechnology to the man in the street. In the public debate, there is a tendency to overlook many different aspects of biotechnology and sometimes to focus on negative effects. I am sympathetic to the fact that for some products, the benefit to man may not be so obvious. However, it has to be recognized that most of the GMOs currently on the market are not targeted to deliver clear benefits for the consumer, rather to provide benefits for producers. From a consumer point of view, this has given rise to skepticism, .independent from safety questions. The public attitude towards GMO food might change once products with clear benefit to consumers are marketed.

But it is also essential to point to some of the advantages of, biotechnology as many speakers have already done during this conference. Can we afford to ignore the potential offered by biotechnology to address many important medical, environmental and nutritional challenges? Taking the risk of repeating other speakers let me give you some examples. For instance, we can now treat children, who suffer from retarded growth, without risking contaminating them with Creutzfeldt-Jacobs Disease, as was the case when we had to rely on growth hormone extracted from cadavers. I need not remind you that the latter practice led to a number of tragic deaths of children.

We can also alleviate the sufferings of hemophiliacs with unlimited sources of coagulation factors free from the AIDS or Hepatitis C viruses, which have killed many patients. For that alone, I think we should be grateful to biotechnology. Take the situation on rare diseases. As most of them are caused by genetic disorders, the advances in gene technology will contribute very much to the understanding of the causes of these diseases and perhaps lead to a cure.

Gene therapy is currently the biggest hope for people suffering from. genetic diseases. Without biotechnology, the causes of such diseases could not have been tackled. However, even though science is an indispensable basis for decisions on food safety measures, we have to acknowledge the inescapable limitations on its role. Determining the, acceptable level of risk is a political exercise and cannot be confined to science. In some cases, there are demands - due for instance to ethical or environmental considerations to go further in the area of health. protection measures than the scientific evidence suggest is necessary.

Let me now conclude. Ladies and Gentlemen, I firmly believe that biotechnology and GMO-products can only produces in an environment where the consumer is fully recognized as a legitimate stakeholder the consumer is given a free choice, where risk/benefit assessments are fully transparent and where consumer concerns, including ethical questions, are addressed and taken into account.

Consumers not only want to understand, for instance the health and nutritional implications of their- choices, but, in many cases, they are interested in the environmental and ethical implications of the way the products are produced. Clarity and improvement are needed in this area in order to provide essential information to consumers. We do not solve problems by digging trenches. I have sometimes heard scientists and industrialists dismissing consumers' apprehensions as being groundless and irrational. I do not share this view. Consumers are entitled to clear information and a free choice of products. It is after all, the consumer who decides what products to buy and who pays. Only an open-minded, transparent and balanced dialogue between all stakeholders, including the consumer, can in the long-term help to de-mystify the application of biotechnology.

Thank you for your attention.

 

Question and Answer Session with a panel of Industry, Consumer, Academic and Government Representatives, including the morning speakers and:

- Alain Labergère, Confederation of the Food and Drink Industry of the European Union

- David Bowe, Member of the European Parliament Committee on the Environment, Public Health and Consumer Policy

- John H. Monyo, Food and Agriculture Organization of the United Nations

 

Introduction by Alain Labergère: I am chairman of the food and drink industry for Europe, which you can imagine, is an easy job. This gathers all the federations of Europe, plus a certain number of branch associations, plus the incoming countries. We are working on horizontal subjects as well as vertical, such as labeling, consumer protection, and nutrition, the same as international market competition. When Ambassador Schneider invited me very nicely two months ago, she told me again this morning that I could use my second minute to tell you what my key concerns are. I must say that we are proud to run the food industry. This is the biggest industry in Europe; bigger than automobile or chemical. We have done a fabulous job of improving the quality and the offer of our product, but today we have lost the consumer's confidence. Nobody has anymore, in Europe, the consumer's confidence; not politics or scientists… nobody. I think the thing which I heard in these two days, which I encapsulate in fifteen seconds, is that we should not forget that we did it all wrong for the GMO. We started with a commodity product which was widespread overnight. We have been taken by surprise. There was as, Sir Robert said, no consumer advantage. When we have asked the consumer if they want a choice they say, "sorry, it is too late. It is too complicated; forget about it". Last but not least, when he has asked scientific questions, there has been total confusion. In this world of media, anyone could talk, primetime, on any television, and everything and the contrary has been said by everybody. I think we should start with a clean sheet of paper. The food industry agrees that we have to go forward. The way forward is to go quietly, well organized and with a common communication, as Mr. Kummer was saying. A lot of things I heard here, including what Mr. Byrne said, are very encouraging.

Introduction by David Byrne: I am the European Parliament spokesperson on the Deliberate Release Directive. It is my report which will be coming back into focus in the next few months, as we do the second reading of the Deliberate Release Directive. Many of the issues you have heard being discussed today, we will deal with in the next few months in the Parliament; whether it is risk assessment, the liability regime, the need for an ethical committee to be consulted, or most important of all, the need to uphold the precautionary principle. They are the issues we will be talking about. They are the issues we will be answering questions about today. We need to go forward and get ourselves a good piece of legislation that we can put into practice, that develops public confidence in it, and is workable for the industry. Hopefully, if we achieve that, we will have achieved something in Europe from which will progress the biotechnology industry.

Introduction by John Monyo: Lately, I have been asked to be chair of an interdepartmental working group on biotechnology. This came on board because the membership of the FAO organization felt that they should be more pro-active in the ongoing debate on biotechnology. The most important thing is that FAO, as a food and agricultural organization, believes, supports and promotes the production of sustainable agricultural production. It advocates the right to food; that it should be accessible, adequate, nutritious and safe. We embrace developments and new technologies. That is necessary in particular for developing countries, where if we can help through biotechnological solutions, which are incorporated into the genotype, be it a plant or animal, to make the biotech stresses contained, to be better for them. I would just like to say, before I stop, that before I came to FAO, I lived on organic agriculture. Many of the 850 million people in developing countries and a big proportion of those who will come on board in the next twenty years, are forced to live on organic agriculture, which is inadequate, not because they want to, but because they can not afford the inputs required to produce more. But we are trying to produce more anyway and we believe that biotechnology can provide some help.

Question for David Bowe and John Manyo: The issue of contamination in the field just came up. Contamination of transgenic seeds in the West, mainly to organic farmers, but in Southern countries to most farmers who work with open pollinating varieties. Could you indicate how the revision of the Directive deals with this issue?

Answer given by John Manyo: I come from a plum green background, therefore it is very important that if you breed a crop, if you want the intended people to benefit, you must prevent as much as possible, contamination. FAO also has the commission for food and agriculture, where it is important to preserve biodiversity for the use of future generations. The most important thing to do, of course, is before a new development crop or process comes on to the market, there should be the sorts of things that are done for us by the FDA. What you need most is a good national regulatory system, which should be science based, but science is not going to be enough if you are to use it as a basis for policy to engage the public. We have heard that. You need to have the public to have confidence in the science and to understand the intentions. You can provide guidelines on how best to contain a given new variety. This happens not only with GMOs, but it would happen in conventional plant breeding, in which I was involved for many years.

David Bowe's response to the question: First of all, we will deal with the issue of farmers in non-EU countries, who may be using openly fertilized seeds. The Parliament itself has been very clear about this. We want to see controls on the exports of GM products to the EU. We want to see an authorization procedure and we want to have instituted, if you like, a prior informed consent procedure, where you will have the import consent of the importing country. That is not, unfortunately, very easily within our control. It is very much an issue that will be discussed next week at the Biosafety protocol meeting in Montreal. Nevertheless, we recognize that problem. That is what we would like to see. That is the current view of the Parliament. In terms of within the EU, we have looked very carefully at the risk assessment. We have added to the risk assessment, specifically issues related to gene transfer. We are particularly concerned to ensure that there is not a damage to biodiversity in some protected areas of the Union. That having been said, let me say one thing that we are very critical about, in terms of the organic farmers. There seems to be a considerable effort from the organic lobby to condemn gene, and specifically, pollen drift, as a major dangerous, damaging issue. I can not understand this because the organic lobby has been coping perfectly well with pesticide drifts for years. They never raised the same issues of concern. They simply set quietly, without telling very many people, a minimum percentage of contamination which is acceptable to remain an organic product. I do not see why you can not do the same for possible GMO contamination.

Comment from Chair: Nothing in nature is static. There are no closed systems. An earlier speaker spoke of solving problems of pesticide resistance. Anyone who understands evolution knows there will always be pesticide resistance. You put and you challenge and you get a response.

Question from the audience: What role could genetic engineering play in the development of biological weapons?

Answer given by Noëlle Lenoir: I am not a scientist, but nobody is perfect. I have no idea of the mechanism, but what I must say is that the declaration at international level on human genetics has been adopted by all member states of the UN, including the US, which states in a specific provision that human genetics must not be used in view of making weapons. Of course, it is a declaration with no binding effects, but it is a statement that is important to see that it has been introduced in this state, because there was concern from several groups of interest.

Answer given by Ambassador Aaron: We do have a biological/chemical weapons treaty in this area. I do not know about the feasibility of this. It strikes me that it would be quite feasible to develop specific biological weapons. That is why this convention is so important. That is why, for example, the case of trying to root out the biological weapons of certain countries, such as Iraq has been so terribly important to demonstrate that the international community will not tolerate that. I think that this is a worry and it puts a premium on making the biological weapons convention truly effective.

Answer given by Craig Venter: This is something that comes up a lot on the Internet, that there will be biological weapons targeted at specific races or ethnic groups. It is just bunk. Just like genetic determinism will not come out of the genetic code, neither will the ability to target weapons against certain individuals.

Answer given by Chair: To hold the view that you can produce race targeted biological weapons, you have to be profoundly ignorant of population genetics, because for all the occasional surface differences in a handful of genes that give us different skins and other superficial things, the variation within humanity hugely swamps the differences between any two groups. There is much more variation within any one group than there is among groups.

Question for Mattias Kummer: I want to ask you about the follow up since you engaged in this very intense debate in Switzerland. It seems to me that one of the purposes, even the main purpose of a meeting such as this is to establish a dialogue and some communication. In a meeting of this size, there are a few hundred of us here, and hopefully a few thousand connected on the Internet. It seems to me that in Switzerland you engaged in a debate of a few million people. Yesterday, we discussed that we need to start a debate that ultimately will involve billions of people. We also heard yesterday about the fast rate of change and complexity of what is going on. I was wondering, since your intense, large debate, how have you followed up on the debate? Have there been specific plans and actions taken to continue the debate and the education? If so, what kind of follow up has been planned and if not, why not?

Answer given by Mattias Kummer: I can, of course, only give you the Swiss view. The Swiss Government published a package, Genelex. Civil liabilities, ethics and all the things, we will deal with this. This is, of course, will produce quite a discussion in our country again. I think the most important thing for business is that we keep up our credibility. Credibility was a very important element during the whole campaign. We should never lose credibility. I think we have it now in Switzerland. It was three hard years of work, at least. Even with the media, for instance, who are commonly not very close to us, we have this credibility and we must keep it up. Otherwise we will really fall back to the middle ages concerning communications. We will deal with this package. We will, of course, keep up the discussion concerning food and agro in a climate that is not emotional. I told you about Internutrition, the organization that we founded to deal especially with these two issues. This is a long haul program.

Then if you are talking about communicating with millions of people, if I have learned one thing in my life concerning communications, it is that you have to concentrate on target groups. Do not think that overall communications is of great value. You have to define target groups and contact people where they are interested. I would not say that it is of much value now really to have a discussion all over the world or the globe on these themes. I think that every country, industry and industry sector has to do it properly concerning its own target groups. If we can help you, we have certain experiences. The situation in Switzerland, which is a very small country, direct democracy is perhaps not a typical case. Our people are forced to vote at least twenty times a year. They are used to dealing with things. They are not touchy. I could imagine that in other countries, this could be tremendously different.

Question to Craig Venter and John Manyo: The other sequencing consortium, namely the Sanger Center, supported with financial aid from the Wellcome Foundation, have a different view to companies such as HGS, that they regard the basic, primary sequences as owned by the public for the benefit of mankind. They also recognize, on the other hand, the interest of pharmaceutical companies in patents, but they are only going to support patents after functions of genes have been established. Can you comment on what your view on this matter is? What would be the preferred situation in your opinion?

Answer given by Craig Venter: I think US patent law and European patent law are coming together in this area in terms of that you have to know a function to even have a chance of getting a patent. That is what we are hearing from the pharmaceutical industry. They do not want to have happen what HGS has done and just patenting genes with no known function. Because of the expense that you heard for developing pharmaceuticals and the fact that I gave you that about half of the human genes have no known function at this point in time. Patents have a finite lifetime. The pharmaceutical industry does not want patents on those genes until they have a chance of having an impact on therapeutic development. The only genes that people want to have patented are those that are going to have a direct impact immediately on developing new treatments for disease that effect all of us. I think it is a greatly exaggerated problem because the press loves this issue.

Comment from Jean-Francoise Mayaux: Within the pharmaceutical industry, it happens that some industries have rather different attitudes to this problem. For instance, a company like SmithKline is going to become SmithKline Glaxo, is probably very aggressive in terms of patenting. It will be interesting because Glaxo is not as aggressive. They will have to change their strategy. What is definitely going to be requested and what the industry would like to see is patent applications based on utility, and real utility. It is easy to write a patent application for a person who is knowledgeable in the art, but, I think, real utility is going to be key. In some cases, the gene might have a direct utility and it will be adequate for a patent application. In some other cases, the gene is going to only be a first step to very significant further developments. Then, the importance of a patent for these particular cases is, I think, highly questionable.

Answer given by John Monyo: In principle, in line with the WTO, patenting is here to stay. The only thing I will say is that many developing countries, of course, are disadvantaged in this, because the race is already on and they have not started. There will be cases where a patent could be made available to those who would not make a difference to the type of profit you make, for example, something you use on maize, but could also be used on cassava, which is not going to change the market.

Comment made by Noëlle Lenoir: I am not an expert on patent law, but I think that there are very few difference between US legislation and the EU directive on patents, with regard to the difference between a discovery and an invention. One must recall that the patent law, which was invented in the US in 1780 and in France at the same time, was based on the social contracts between the inventor, who gave society the benefits of his intelligence and the industry. Now we have a lot of data. What of the new social contract with this data, because as we said, some industries open their data banks to the public or to the academics and researchers when the use is surely not commercial or industrial. Some other industries do not do that. They keep it secret. Is there an idea, because I think it is necessary and even urgent to have a clear view of the new social contract which has not to do only with invention and the prevision where absolutely needed because life sciences raise new issues concerning the differences between invention and discovery- different from the inert matter. What is the basis of the social contract concerning genetic data as such when their functions are known or unknown?

Additional comment from Craig Venter: This is one area where the EU is well ahead of the US law, because in Europe, you can copyright a database and have protection. That is what has been happening with genetic databases, DNA databases in Europe. Legislation is pending in the US and it is very uncertain which way it is going to go. I think Europe is very much ahead. It is the same social contract, but I want to make something very clear. Even though we are using private money to sequence the Drysophala genome and the human genome, we have already made one hundred percent of the Drysophala sequence available on the Internet, it is in Genebank, free to the public, even though we are using our own money. We will be doing the same later this year with the human genome. We will be on the Internet and through a DVD disk, giving it to scientists for free, because we do not see the value in the genetic code itself, but in the computational interpretation of this information. We had to build a hundred million dollar super computer to understand the information and that is what we are providing access to. It is the basic information itself, although it will be available even faster if we had laws in the US allowing us to do the same copyright we can do in Europe.

Comment from Chair: It is not simply the Sanger Center. The public money sequencing operation is roughly two-thirds US, one third UK (largely federal money, public money, NIH money in the US, charity money in the UK, with other contributions from other countries). Those other countries are united in a clarity of principal, that the basic sequenced information is the common property of humankind, and that basic sequencing information should no more be patentable than it should be possible to patent a newly discovered primate species in the Amazon, of which six have been discovered in the last ten years. Without any editorializing unduly, it may well be as Craig just said, between his and the others I just articulated, in practical terms really quite small. My personal opinion is that as issues of principle, there is a gulf and it is something we do not have time to discuss further. I am convinced that in practice the differences are much less than maybe in principle.

Question from the audience: I would like to come back to the question of labeling and consumer choice. I was very glad to hear many speakers speak out for consumer choice, particularly Commissioner Byrne. My question is: can we actually do it? Genetic pollution is inevitable and we also have slowly that a farmer can not guarantee that the crops are actually GM free. Would it not be more honest to tell the consumer that he will not have a choice in the long run if we release GMOs into the environment?

Answer given by David Byrne: The legislative structure that is in mind at the moment focuses first of all on the deliberate release instructive, that is 19-20. That is going through the amending procedure, as David mentioned a moment ago. It is hoped that that directive will be in amended form and enacted some time by sometime in mid-summer or autumn. That particular directive focuses on the issuing of labeling. So also will the novel food directive, which has been, up to February 1, the responsibility of my colleague, Commissioner Lickenen and DG Enterprise, and is about to be transferred to my DG from February 1. We will be looking at this with a view to also suggesting amendments to the Novel food directive to bring it in line with 19-20. We also have in place a draft novel seed directive and we are currently drafting the novel seed directive. In all of these we will be focusing on the issue of labeling. Somebody touched on it earlier, that in the event that there is accidental contamination to a threshold of 1%, in those circumstances there will not be as the law and as the thinking is at the moment, there will not be a requirement to label that product as being GMO derived. Nor will there be an entitlement to label it as being GMO free. During the process, before Parliament recently, my colleague Commissioner Lickenen was asked if would he reduce that threshold level to a lower level. I understand the position to be from him, and we will be looking at this ourselves in the near future, that the measurement mechanisms that are available to us can not measure to a threshold level below one percent. He gave an undertaking to Parliament in his presentation that if such mechanisms do become available that a lower threshold level would be put in place.

I realize that your question was focusing more on the practical consequences of that, rather than the legal aspects of it. That, I suppose, is more in the scientific realm of it than myself, but I have to say that our decisions in relation to these issues in the Commission, are going to be science based and time limited. We will be bringing forward our proposals on that basis. Obviously, we have to seek and get the very best scientific advice that is available to us and put it through the legislative process at that stage. My belief is that it is necessary to give the information to the consumer. In the vast majority of situations, the consumer is going to accurately informed of the situation. In the circumstances of accidental contamination, that situation will be identified earlier and the consumer will also be aware in those circumstances. It may well be that scientists can give a more accurate response to the technicalities of that, but that is how I see it from a legal point of view.

Comment: I do not claim to be a scientist, although I did do a science degree. I learned one thing from my science degree and that is there is no such thing as zero, certainly in terms of risk and certainly in terms of possibilities. When we talk about gene-transfer, of course there is a possibility, even in circumstances where you put similar species together that might cross-fertilize. I am not saying it would happen. What I am saying is that there is no natural assumption that there is going to be genetic pollution every where, because, quite frankly, take, for example, maize. If you grow maize as a fodder crop in the UK, there is no chance that there is going to be pollution from GM maize being grown as a fodder crop. One, it does not produce pollen and two, it as very little in the way of natural relatives to cross with. I do take exception to this continuous suggestion that there is going to be massive pollution. We have drawn up a very carefully worded directive because we realize that it is possible. We realize that the possibility of gene-transfer exists. We have taken necessary safeguards to guard against it. The idea that you can not have GM free food again is silly, because we are already getting GM free food. We are getting GM free food from GM free sources. Go look in the supermarket. The labeling regime that has been in since the beginning of the year as already got virtually no GM food on the supermarket shelves. To suggest that it is going to 100% free does not work. I have seen it with regard to admissions from incinerators, where people demand zero admissions from incinerators, but we can get down to three. I have seen this argument used fruitlessly so many times and in so many circumstances when we have been framing legislation. I think we should start living in the real world.

Question from the audience: There have been several comments on the benefits to GMOs for the Third World. My question is to Mr. Monyo and Ambassador Aaron. I would contend that it is hugely more important to Third World development, for the Third World farmer to have full and free access to First World markets than access to GMOs. Do you agree?

Answer given by Ambassador Aaron: I do think that for the economies of Third World countries there is nothing that we could do that would be better than to change the rather massively distorting set of constraints that are on agricultural trade. And in particular, though this will not be popular here to say, the massive distorting effects of the European agricultural system, in particular its export subsidies. If we get rid of that, that would be enormously helpful to these countries. I also believe that it is important, as we are going to need new kinds of crops. We are going have an enormous increase in population, some say by two billion. Some people say that by 2040, we will have almost a doubling of the population. I am not a demographer. Whatever it is they are not making anymore Earth. It is quite clear that we are going to have to use more marginal land. We are going to have to have plants that can grow in these circumstances. We are going to have to have plants that need less water and a number of things of that sort in order to feed that population. I think it can make an enormous contribution. It is essential and we have to see biotech go in that direction. I would encourage our industry to do that. It is another part of the social compact that was mentioned earlier, that this industry has got to respond to human needs of the developing world as well as the developed.

Comment: In the context of the WTO negotiations in Seattle recently, this issue arose and the negotiator on behalf of the EU made it public that the EU is receptive to this proposal and would agree to that proposal being put in place. There may have been one or two small caveats, but I think, we may have been alone in that. There were one or two others, some of the other large trading blocks were not involved as far as I am aware.

Answer given by John Monyo: We are not producing enough in the developing world. It is important to have low cost technologies which increase production. If you can increase production you will meet the subsistence needs and hopefully have a surplus for export.

Question for Ambassador Aaron: Can we expect next week the US to welcome commodity crops into the biosafety protocol and if not, how are we going to take that basic regulation forward? How would the US feel about Europe having that in their regulations and whether you would welcome that in the biosafety protocol as well?

Answer given by Ambassador Aaron: As you probably know, we are not actually direct participants in the biosafety protocol because we are not members of the over-arching agreement that goes with the protocol. I think you will find that we will be present and that we are working with the Miami group and we are not rejectionists in any way about this. We are prepared to be flexible, but we are also looking for flexibility from the EU. I must say that we deeply concerned about some aspects of trying to take the precautionary principle beyond the way it was described here this morning, which I think was very sensible and enshrine it as something that could be exploited by others as a trade barrier. On the specific question of labeling commodities, I think, we are going to be prepared to discuss that issue and whether or not there are ways that could be done that could be informative for people and not stigmatize the products.

Question from the audience: Many objections voiced during the conference may prove to be irrational, but what if people prefer to be irrational. Rational answers to their questions does not mean that have persuaded them.

Answer: I will repeat what I said. You are obliged to really drive your down your arguments till the end. It is a long-term job. The worst that can happen is that all these little accidents are terrible to build up confidence. You said it is emotion that leads the scene. When the consumer sees that there are benefits, it is a matter of time.

Answer: What we believe in the food industry is that if we can agree with the trade, the agriculture, commerce and the consumer on one product, which should be in a niche market with clear consumer benefit, with the same communication all over the place and start with a clean sheet of paper again, that would restore confidence. We are working on that.

 

Ambassador Cynthia P. Schneider
"The science and the Impact"
"Conclusion"

I would like to begin by thanking all the speakers. You did such a wonderful job. I asked the scientists to speak in terms that a layperson, such as myself, could understand. You did so just beautifully. And, in so doing, you have shown the value of scientists taking a more prominent role in the public debate over biotechnology, and I hope you will do so. I would also like to thank the audience. You have been wonderful in participating and asking so many good and interesting questions.

I would like to take a few minutes to review some of the ideas that have emerged from the conference.

A goal of this conference was to bridge some of the differences and to find common ground between the U.S. and Europe. We agreed on the mutual goal of bringing the very best product to the consumer, taking full advantage of the scientific advances that we are privileged to witness, and, at the same time, maintaining the highest standards of safety. Let us hope that we will be able to maintain the momentum of dialogue begun here, and move forward sensibly, prudently, and productively with biotechnology.

I would like to conclude with my own version of a quotation from Brave New World by Aldous Huxley. Toward the end of the book, the savage, who you will remember resists the "brave new world" where everything is controlled and where emotions or problems do not exist, insists on living in something comparable to the world we live in today. He says, explaining his position, "I am claiming to be unhappy. Not to mention the right to grow old and ugly and impotent. The right to have syphilis and cancer. The right to have too little to eat. The right to live in constant apprehension of what might happen tomorrow. The right to catch typhoid. The right to be tortured by unspeakable pains of every kind."

Over the past two days, we have heard about biotechnological medicines, which treat hitherto untreatable diseases, alleviating "unspeakable" pains. We have heard of innovations and plant biotechnology in agriculture that hold the promise of feeding the hungry so that they need never worry about "what will happen tomorrow". And we have heard about human genome sequencing that holds the promise one day of curing cancer.

I will conclude, then, by rephrasing Huxley in the hopes that in the coming biotechnological century perhaps the savage, who we will now call the citizen, will claim the right not to be unhappy; the right not to grow old and ugly and impotent; the right not to have syphilis and cancer; the right to have enough to eat; the right not to live in constant apprehension of what might happen tomorrow; the right not to catch typhoid; and the right not to be tortured by unspeakable pains of every kind.

Thank you very much.