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