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Genetically Modified Crops: Demystifying the Science

Given to the RSA -- Royal Society for the encouragement of Arts, Manufactures and Commerce -- in the UK

By Professor Derek Burke
Cambridge, UK

1. Introduction

1.1. Let me first tell you what biotechnology is. I shall define it as "the application of biology to human use" and then distinguish, in this broad definition, "old" from "new" biotechnology. By "old biotechnology", I mean a series of technologies that have been in use since we ceased to be hunter-gatherers. These include:

  • Fermentation, for the production of fermented drinks, such as beer and wine, and foods, such as bread, sauerkraut and such delicacies as Swedish fermented herrings!
  • Plant breeding, extending from the dawn of agriculture, in the breeding of corn for example, right up to the present day, in the production of modern high-yielding wheat strains, for example, the short-stalked varieties.
  • The use of enzymes in food processing, for example the use of an extract of the calf's stomach (containing the enzyme chymosin) in cheese processing. Then there are a number of 20th Century developments, such as:
  • A fermentation process for the production of acetone, for use in explosives, developed during the first World War.
  • Another fermentation process, using deep vat fermentation, that was developed for the production of penicillin in the Second World War.
1.2. But "new" biotechnology derives from techniques discovered only in the last 20 years. Briefly they are:
  • The ability to cut and stitch DNA.
  • The ability to move DNA and genes from one organism to another and moreover the ability to persuade the new gene in this new organism, that is to make new proteins.
  • The ability to modify proteins by a process termed "protein engineering".
1.3. DNA is first cut up by the use of a class of specialist enzymes, called restriction enzymes, which cut DNA into gene-sized pieces. The mixture of pieces is then forced into bacteria, at an average of one piece per bacterium, and then these so-called 'transformed bacteria' are grown up, on ordinary agar plates, so that each single bacterium grows to form a single colony. Each bacterium in the colony will be the same as all the others, that is the colony is a clone - like a very large number of identical twins! Most of the clone will contain a single one of the gene-sized pieces, although some will contain none and some two or three. There may be several million of them and somewhere in there is a bacterium with the gene you are hunting for! Or maybe only part of it, because the restriction enzymes can cut in the middle of a gene. But this process has achieved three things:
  • It has broken the DNA down into gene-sized pieces,
  • It has separated them from each other, and
  • It has turned one molecule into millions, and given the scientist enough to work with.
1.4. The next part is the hardest: finding the right gene. It is just like trying to find a needle in the haystack and it is hard unglamorous work! It is called 'screening' and involves testing the DNA extracted from individual clones, or more commonly, from pools of clones, for the gene you are searching for. Once you have the gene cloned, then the precise sequence of the DNA can be determined by a mixture of chemical and biochemical techniques. Finally it is possible to reinsert any of these pieces into another organism, which does not have to be a bacterium, but maybe a plant or animal cell. So genes can be isolated, their structure determined, transferred to other organisms and, crucially, made to work there. This is possible because, rather broadly, the way genes work is universal, from bacteria to man. These two techniques are what is called "genetic engineering" or "genetic modification".

1.5. Over the last twenty years, we have learned how to isolate any gene from any living organism, introduce the new gene into another organism, and get it to work there, and because genes work in almost the same way in all living organisms; it is incorrect to speak of a human gene, or a fish gene etc. The gene is a human gene because it is functioning in a human cell, not because there is anything about its structure or its chemistry that is basically different; an important point that lies behind some of the current confusion. Indeed genes from different organisms may be very similar to each other; the insulin genes, for example, only differ marginally between fish and humans.

1.6. So genes can be isolated, and their precise structure can be determined. A typical gene consist of about 1000 units strung end-to-end in a precise sequence, with one of four possible building blocks at each position. This part of the gene is called the coding sequence because it determines the sequence of the product - the protein. So we have the central dogma of molecular biology: 'DNA makes RNA and RNA makes protein'. Genes also have switch signals at either end, to switch the gene on and off. The 'on' switch is called a promoter and they do differ, not only between organisms but within an organism. For example, plants have specific promoters, so that starch is made in the tubers we call potatoes and not in the leaves, although the genes to make the starch are present in every cell of the plant.

1.7. Once the structure is known, the gene can then be made synthetically - that is put together in the correct sequence from the building blocks. And variants of the gene can be made too; these will make different proteins which may be more suitable for what we want to use them for. So, for example, the enzyme that breaks down grease in biological washing powders can be modified to make it more stable at higher temperatures, so it will still work in a hot wash. This process of 'improvement' is called protein engineering.

2. Applications in medicine

2.1. The first applications of this new technology were for human medicine, and that involved the isolation, characterisation and utilisation of human genes. That was not easy; there are 70-100,000 genes in the human cell, and the process is literally like finding the needle in the haystack. However, the process of isolation of a human gene, introducing it into a bacteria and getting it to work there is now straightforward. That is not to say that it is easy; what is called 'gene cloning' in the trade is now much easier than it was, but is still difficult. I led a team that isolated the genes for human interferon in the early 80's and it was very, very hard, and we weren't first anyway. I don't think I have ever worked so hard in such a repetitive fashion in my life! But the difficulties have been solved, and we can make now make human proteins such as insulin, growth hormone or interferon in bacteria. These are high value/low volume products and were initial targets not only because they were needed for human medicine but also because they were the obvious first targets for commercial development. So what is sometimes called 'red biotechnology', as opposed to 'green biotechnology' was born, and the implications for the pharmaceutical industry have been profound.

2.2. To state the obvious; the old species barriers have gone. Any product from any source can now be made in any host, and although all the first generation of products were made, for technical reasons, in bacteria, now insect, yeast or animal cells can all be used - grown in lots of tens of thousands of litres in huge fermenters for an ever expanding market. But there is another implication; products that once were rare can now be made in gram amounts. So there was a profound effect on the interferon trials - whether against cancer or viruses - which had always been limited by the amount available. In principle, any of the hundreds of products made by the body - often in minute amounts, so, for example, the group of substances called the lymphokines, which act like hormones for the immune system, can now be cloned and produced in large amounts.

2.3. The products, after some initial hesitation - over insulin in particular, have been totally accepted; and the only problem for the consumer, or more precisely, the patient, is the price and you may be familiar with the problems in the UK over the costs, and hence the rationing, of interferon-b for treatment of MS.

2.4. What about the risks of these processes?

Risk assessment involves identifying all the possible hazards and then ascribing a probability to each one of them. Both the nature of the hazard and its probability can be difficult to determine, and this is certainly true for new products, especially those from genetic modification, where the technology is so new and the risks unknown. And the hazards? The first question is whether the product is safe, and here highly developed drug safety procedures swing into action. There have been no problems with the drugs, although there was a problem with the food additive tryptophan, an amino acid which is taken in gram amounts by some. Such products are assessed by the drug safety procedure in the UK, but not in the US, and there, a serious illness developed in several hundred users, due, it was claimed by the green lobby groups, to the fact that the product was made by genetic engineering. It is almost certain that the damage is due to a minor contaminant in the product, which was there because the tryptophan purification process had been changed. But it is must have been a very expensive mistake.

2.5. But what about possible health risks for the scientists and technical people involved in the production of these new products? And what about the risks to the environment? There are very tough rules in place, which are the responsibility of the Health and Safety Executive in the UK. Experiments are categorised as to potential risk and this risk then determines the level of isolation of the laboratory worker, the production plant and the way in which the waste products are disposed of. I know of no problem in the UK, and I was a member of the relevant regulatory committee for nine years.

3. The development of genetically modified plants

3.1. We can also modify both plants, and animals, in exactly the same way, and it is now possible to transform any crop plant efficiently with single genes, and techniques for transformation with gene clusters are coming. This new technology will lead to many new crop products, of several general types:

  • Modifications of the genetic material of plants to switch off a particular gene or genes. This has been used to extend the shelf life of tomatoes, by switching off the gene that causes breakdown of the plant cell wall,
  • Introduction of new genes, or enhancement of the activity of existing genes, to improve starch or oil yield, or to produce modified oils or starches, to enhance fruit flavour, colour or nutrition,
  • Modification of the genetic material of plants to produce novel parental lines for the production of new hybrids, for example rape, with enhance yields,
  • Modification of the genetic material of plants to introduce resistance to herbicides or pests, for example, soya, potatoes, cotton and corn, and, in the longer term:
  • Introduction of whole new genetic systems into the plant to increase, say, yields from photosynthesis or to enable crops such as wheat to fix nitrogen. This is proving to be very difficult.
3.2. It is very difficult to predict exactly when these new developments will become available, but it is possible to arrange them in an approximate time sequence:
  • Continued development of rapid genetic typing methods to speed conventional plant breeding,
  • Continued development of plants resistant to herbicides and a wide variety of pathogens,
  • Continued development of novel fertility systems for F1 hybrids with increased yields,
  • Continued development of fruits and vegetables with longer shelf-lives,
  • Modification of crops to produce oils with properties more suitable for industrial use, fats more suitable for the human diet and starches for either dietary or industrial use,
  • Isolation of genes that control flower shape and colour for the horticultural industry,
  • Modification of fruits and vegetables to improve flavour and nutritional content,
  • Elimination of genes for toxic or allergic substances,
  • Isolation and utilisation of the complex systems that control salt tolerance and drought resistance,
  • Isolation and modification of genes that control plant development and differentiation, for example, the genes responsible for short-stalked wheat or the genes responsible for control of the response to day length. In this way, crops such as rape could be grown further north in Canada or Sweden,
  • Modification of trees for pest and disease resistance,
  • Production of drugs and vaccines in plants,
  • Introduction of new genetic systems to increase plant yield, for example, modifying photosynthesis or enabling crops such as wheat to fix nitrogen,
  • Applications to crops such as cassava, important for the developing world.
3.3. To take a specific example, genetic modification of potatoes could:
  • Increase the availability of UK varieties by extending the growing season,
  • Improve flavour and mash texture through modification of starch and sugar content,
  • Reduce the water content and alter cell-wall composition to limit the fat retained in crisps and chips,
  • Extend shelf-life by suppressing sprouting and reducing rot,
  • Reduce chemical residues by introducing herbicide tolerance, disease- and pest-resistance traits.
3.4. An indication of the spread of transgenic crops can be gained from some recently published figures. The global area (excluding China) of transgenic crops was 1.7 million hectares in 1996, 11.0 million hectares in 1997 and 27.8 million hectares in 1998, a 15 fold increase in three years. These are very high adoption rates for new technologies by agricultural standards. The five principal transgenic crops grown in 1998 were, in descending order of area, soya, maize, cotton, rape, and potato; with soya and cotton accounting for 52% and 30% of the global area. The principal benefits reported include more flexibility in crop management, decreased dependency on conventional insecticides and herbicides, higher yields and cleaner and higher grade of end product. In the US in 1997, the economic benefit to growers was estimated at $81 million for Bt cotton, $119 million for Bt corn and $109 million for soya, with a collective total of $315 million, up from $92 million in 1996.

3.5. So what else is driving the genetic modification of plants?

Primarily, many say, the need to feed a growing world population. Global population is increasing by 87 million per year, and is estimated to reach 8 billion by 2020 from its present 5.9 billion. In addition, loss of land to urbanisation means that the amount of cultivated land supporting food production has fallen from 0.44 ha per person in 1961 to 0.26 ha per person now, and is projected to fall to 0.15 ha per person by 2050. The need for irrigation is increasing, the climate is changing and as people become more prosperous, they replace plant foods with animal foods-which are less efficient in trapping solar energy. So about one-half of the grain produced in Europe, North America and Russia is already used as feed. How are we going to feed all these people? Surely new approaches will be needed in addition to the continued improvement of existing methods?

3.6. On the other hand, others say that genetic modification is not needed to produce more food. They argue that the planet's food problems are due to economic and political problems, not because we can't grow enough, and that poverty in particular, makes it impossible for people to buy food even when it is available. There's truth in that; for if the world's food supply in 1994 had been evenly distributed, it would have provided an adequate diet of about 2350 calories per day for 6.4 billion people, more than the world population. But distributing it evenly will not be easy, even if the world's population was not increasing. There are many other problems in the future which will not be solved by redistribution; for example, by 2020 half the worlds population will not have enough water available to grow their own food, and they will have to depend on food imports.

My own view is that of course we should try to change some of the practices that limit food supply, and of course biotechnology is only part of the answer, but it seems perverse, even immoral, to me to walk away from a potential increase in the world's food supply. I believe that it is not only possible, but essential, to introduce genetically modified crops for the developing world although we shall need care, and political will, to avoid undue disruption of social systems. Previous new technologies, for example universal vaccination, have been controversial in their time, but where would we be without them?

3.7. Let me briefly mention three examples of ways in which biotechnology could help the developing world. First, the introduction of rice modified by increased levels of beta-carotene would help deal with the problems due to the lack of vitamin A. In developing countries and in Asia particularly, one hundred and eighty million children suffer from Vitamin A deficiency and each year two million die from diseases linked to Vitamin A deficiency. This is a particularly serious problem for many poor children in Asia who are weaned on rice gruel and little else. Similar introduction of rice with an over threefold increase in available iron would help deal with the chronic problem of anaemia in women in SE Asia. Third, scientists in Mexico have added genes to rice and maize that help plants tolerate high concentrations of aluminium, a soil toxicity problem that constrains cereal production over vast areas of the tropics. Finally, the recent isolation of the gene that is responsible for the dwarfing of wheat, a change that we are all familiar with, has the advantage of concentrating energy on grain production rather than on straw biomass.

The isolation of this gene, which turns out to be very similar in many plants, means that this gene, which was so important in the massive increase in yield in the 'green revolution' can now be transferred to other crops such as basmati rice (Peng et al., Nature, Vol. 400, p.256, 15 July 1999). Here is a situation where genetic modification offers a clear advantage over plant breeding; for in plant breeding two different sets of 25.000 genes are brought together and the product is selected for a particular new property. In doing so, many of the qualities which make a particular variety particularly suitable for a particular ecosystem are lost.

In contrast, with GM, the gene to produce dwarfing is introduced into that variety which is most suitable for the environment. GM, despite the greatly exaggerated claims of the Green groups, can bring clear environmental advantages. It is highly significant that seven academies of science (not companies, note!) from developed and developing countries - Brazil, China, India, Mexico, the UK, the US, and the Third World Academy of Sciences have recently agreed to develop "an authoritative joint statement" on genetic modification in world agriculture, making clear that it expects to agree that the technology is needed to feed future populations, and that we need to think through - now - the implications.

3.8. It is possible to modify animals in much the same way; and specifically by injecting the cloned gene into the fertilised egg of a sheep or a goat - the animals that have been worked with most so far. The immediate objective here is to use such 'transgenic' animals to produce the same sort of high value/low volume products that I described earlier - pharmaceuticals. By attaching a tissue-specific promoter to the gene, it is possible to arrange for the product to be made only in a certain tissue, say the mammary gland, and then the product is secreted into the milk. In this way the animals can produce large amounts of the product, and in a form which is exactly the same as is found in the human; specifically having the right sugar molecules attached, and that doesn't always happen with bacteria. These systems are just coming through into commercial development. It is also possible, in theory, to modify animals so that they produce less fat for example, and although this is little more than an extension of traditional breeding techniques, it is likely to meet such consumer resistance that such developments are, in my view, years away.

4. Uses of genetic modification in the food industry

4.1. Genetically modified foods have entered British supermarkets over this last year. The outcome has been mixed; for some were accepted without hesitation-for example, the puree made from genetically modified tomatoes. But the flour from genetically modified soya beans has caused a huge amount of controversy, and food manufacturers have now ceased to use this product in the UK, although not in the US. Why is this? If it's OK to use genetic modification for medicine then why not for food? Is GM soya unsafe, and will these crops damage the environment? What are the risks?

4.2. The first two products-the tomato paste and 'vegetarian cheese' offered the consumer both advantage and choice. For example, both Safeway and Sainsbury sold 170 g of the modified tomato paste at the same price as 142g of the conventional product-because there is so much less loss in transporting the tomatoes from the field to the processing plant, and furthermore, it tastes better. Not surprisingly, the GM puree outsells the conventional product-for they are offered side by side on the shelf.

4.3. In contrast, the flour from the herbicide-resistant soya, from Monsanto in the US, offers no obvious advantage to the consumer, but rather to the producer, and the consumer has not been offered choice. Of course, the increased yields from this crop should stabilise or possibly even lower the price of the product, and some recent figures I have seen for maize suggest that roughly 25% of the increased value goes to the company, 50% to the farmer and 25% to the consumer. I don't have the figures for soya, but the consumer cost advantage will be very hard to see when soya makes up such a small amount of many products. So although all the evidence - including the fact that 300 million Americans have been eating it for several years without mishap - is that GM soya is as safe as normal soya, it offers the consumer no advantage, and the scare stories might just be true. So avoiding it is a perfectly understandable reaction, but this is interpreted by the Green groups as evidence that a large majority of the British public are against GM as such. I doubt whether that is true.

4.4. So, is this new soya safe?

Herbicide resistant soya was genetically modified by the introduction of a gene from a soil bacterium to make the plant resistant to the herbicide glyphosate. Before it can be sold in Britain, it needs Government approval and Ministers take the advice of the Advisory Committee on Novel Foods and Processes, which I chaired for nine years. Now we do not eat soya beans but the flour made by grinding and defatting the beans. Both the added gene and the new enzyme are degraded by this treatment, and they then will be quickly broken down in the gut. The Committee, which includes a consumer representative and an ethical advisor, considered this new soya to be as safe as conventional soya, and so advised the Minister.

4.5. But trust in the regulatory process has been eroded, especially by the BSE outbreak, and this Government is working hard to re-establish trust in the regulatory system by opening up the approval procedure. Agenda and summaries of decisions by the Novel Foods Committee have been published for years, and now Minutes are being published, the Internet is being used for rapid, widespread communication, and consideration is being given to increasing the number of consumer representatives, and meeting in public. Such changes will be essential to restore public confidence, but may not be sufficient, and in my judgement, the approval process will have to continue to be opened up.

4.6. What about the effect on the environment?

The public have been very concerned about the possibility of such effects. Will these crops lead to an increase in the use of herbicides? Will the modified genes escape into the environment to fill our fields with resistant rape, or will the genes spread to other species? A number of environmental groups have been very concerned about risks in this area, and political pressures have focused on a call for a 'moratorium' on the planting of all genetically modified crops in Britain, even though such a moratorium would be illegal under EU rules. For example, English Nature is concerned about the environmental effects of such plantings and want a period of three to five years to plan and carry out appropriate research. They point out that the English countryside, especially, is very different from that in North America where farm land and natural land-for example in their splendid National Parks-are far apart, whereas in England especially they are cheek by jowl. The Soil Association is chiefly concerned with the promotion of organic farming, and so wants to prevent contamination of organic produce by pollen from GM crops, which they regard as unnatural; so they want either a ban or possibly a total separation of land used for organic farming from that used for GM crops. Greenpeace want a long term ban of all genetically modified crops.

4.7. These pressures have led Government to announce an agreement with the plant breeders to delay the introduction of commercial planting of such crops, and in the meantime, to conduct a series of farm scale evaluations of the risks associated with the growth of GM crops in the UK. These are now under way; although it is deplorable that Greenpeace have taken the law into their own hands and have destroyed several of these trials. I do not believe that we can resolve issues in an advanced democracy like ours in this way. My judgement is that GM crops are no more likely to spread their pollen than the crops that we have been growing for years, and certified seed is already grown under conditions that produce 99.9% pure seed. But if organic farmers want to ensure that the rape that they grow has absolutely no 'contamination' at all from GM rape, and if by 'no' they mean zero, then we have a very difficult problem to solve.

5. So why are consumers so concerned?

5.1. If GM soya is as safe as unmodified soya, and we can control adverse effects on the environment, do consumers want to eat it? Certainly, some do not. Why are consumers so concerned? There have been a number of thoughtful articles on this topic; for example a publication from the Dept. of Health, which points out that: "Risks are generally more worrying if perceived:

  • to be involuntary (e.g. exposure to pollution) rather than voluntary (e.g. smoking),
  • as inequitably distributed,
  • as inescapable by taking personal precautions,
  • to arise from an unfamiliar or novel source,
  • to arise from man-made rather than natural sources,
  • to cause hidden and irreversible damage,
  • to pose some particular danger to future generations,
  • to threaten a form of death or illness/injury arousing particular dread,
  • to damage identifiable rather than anonymous victims,
  • to be poorly understood by science,
  • as subject to contradictory statements from responsible sources."
GM soya scores ten out of eleven from the Department of Health fear-factors. No wonder there has been trouble!

5.2. We are getting very sensitive to talk of risk, particularly as other threats to our safety recede. We live in a 'blame culture' where somebody is responsible, and culpable, for everything that goes wrong. Anthony Giddens, this year's Reith Lecturer, has made the distinction between 'natural risks', such as earthquakes etc., and 'manufactured risk', which is due to our activity. I think that it is more complicated than this, and I would want to make a further distinction between those risks we choose to take, and those that are thrust upon us, and yet a further one between risks linked to medicine and those linked to food. Risk issues are not simple. There is another difficulty - science can only ever say that there is no evidence of risk, while the public now asks for evidence of no risk. That can never be supplied - with GM foods, mobile phones, or any other new technology.

5.3. So for reasons such as these, consumers want to make their own decisions, rather than trust the experts. And what are the reasons for this loss of consumer confidence? Let me suggest several:

  • First, scientists, and the expert approval processes, are no longer trusted as they once were. The BSE epidemic has of course been disastrous for confidence.
  • Second, I think the public is largely unaware of the development of careful scientific methods of assessing risk, such as the use of hazard analysis, to come much closer to an 'objective' evaluation of risk. But it is also true that we find great difficulty in explaining, and the public in understanding, what is meant by different degrees of risk. Our National Lottery-with its slogan of "It could be you" does not help either-the message is clear: even what is very unlikely may happen. So even if the risk from a new product is very low, maybe it will be me!
  • Third, the public finds it difficult to know how seriously to take the points put by the many single-issue pressure groups.
  • Fourth, risks are assessed differently according to the context. We will accept quite high risks when we are seriously ill, but will not tolerate much risk at all with food.
5.4. One explanation for such conflicting views is that scientists and the public work from different value systems. Scientists and technologists see novel applications of new discoveries as logical and reasonable-and characterise all opposition as unreasonable. "If only they understood what we are doing" they say "the public would agree with us." Experience tells that this is not always true. Scientists and technologists are used to an uncertain world, where knowledge is always flawed, can handle risk judgements more easily, and are impatient of those who differ from them. The public's reaction is quite different, and it can be described as:
  • Outrage - "how dare they do this to us?" - the way the public now regards Monsanto.
  • Dread - the way we would regard a nuclear power station explosion.
  • Stigma - the way the public regard food irradiation.
5.5. The net effect of this is that it is not possible to predict the way in which the public will react to a new risk by consulting just scientists and technologists, and perception of risk is now much more important than any technical assessment of risk in the introduction of new technology.

5.6. So all these issues are raised by GM foods, but are they intrinsic to the technology?

Rather, I believe that GM foods have become a lightning rod for many modern concerns; scepticism about the regulatory process, gusts of anxiety about our food, growing hostility to high intensity agriculture, and concern about the way in which the agrifood business has consolidated into about six companies world-wide. So decisions about the future of our food are being taken in the US or in Switzerland. Consumers feel they have lost control and blame the technology, and some wish to ban it altogether. I do not believe that that is a sensible way ahead. I believe that should respond by regulating this coming change, which I believe is already with us, so that it is the least harmful and the most helpful to us all.

6. But what about the future?

6.1. My view is that genetic modification of crops for food use is here to stay, certainly in North and parts of South America and Asia, and inevitably in Europe. Although the future is now less certain because of Monsanto's clumsy introduction of modified soya, it is worth stressing that herbicide resistant and insect resistant crops are first generation products. Second generation crops which will tackle more sophisticated problems are in development-herbicide resistance is early 80's technology. These new targets must have consumer benefits - and taste and nutritional value are high priorities here. We must also deliver benefits for the farmer and for the developing world. At the political and regulatory level, we must ensure that the consumer is able to exert choice, knows what is in the product, and crucially, has regained confidence in the regulatory process.

Professor Burke was Chairman of the Advisory Committee on Novel Foods and Processes from 1989-1997, and Vice-Chancellor of the University of East Anglia from 1987-1995.