Talk presented at the Asilomar 25th Anniversary Meeting, Pacific Grove, CA, on February 16, 2000

Agricultural Biotechnology: Its Past and Future

Peggy G. Lemaux
Asilomar after 25 Years
February 16, 2000

At what point and in what ways did recombinant DNA develop in the agricultural field?

Difference between classical breeding and genetic engineering

With plants perhaps more than any other kingdom of organisms, humans have been involved in modifying their characteristics through the careful selection of the male and female plant that would participate in the sexual union to give rise to the next generation of plants. The parents were chosen based on their characteristics, plants with a greater yield or better disease resistance characteristics were chosen in order to generate progeny with both those characteristics. Progeny were screened to find those that had the desirable characteristics from both parents. It was a process like this that led over time to the conversion of an ancient ancestor of corn into the modern hybrid corn we see today.

What did this process look like at the genetic level? Most every cell in a plant, or in the human body for that matter, contains DNA. That DNA is made of chemical units and it is the arrangement of those units that determines what characteristics a plant has. If one were to represent each of those units by an alphabetic letter, it would take 1.7 million pages to contain all the information in a wheat plant, for example. If one were then to cross two wheat plants to get an improved variety, genetic rules state that we can't end up with 3.4 million pages, but 1.7 million pages. This means that there is random retention of certain volumes in the progeny from each parent. In addition volumes often get rearranged during the normal fertilization process of the egg and sperm, resulting in different portions of the volumes being juxtaposed in progeny. The breeder involved in this genetic exchange has no control over which volumes are kept or lost and can only observe and chose progeny with the desired characteristics.

How is this similar to or different from the process used with genetic engineering? In general similar enzymatic machinery is used in both cases, but in one case it occurs inside the cell and in the case of genetic engineering the DNA manipulations occur in the laboratory. The amount of DNA that is manipulated in the molecular approaches is relatively small, comparable to a half page of information in the analogy, but the "text" in that half page is known to the scientist, who can "read it" and understand its function. In contrast to the classical breeding approach, the source of the DNA need not be related as with sexual crosses. The DNA can be from the same plant, an unrelated plant, a bacterium or even a mammal. In addition with genetic engineering it is possible to control precisely in which tissues the linked gene is expressed. If one is looking to improve the nutrition of a grain, for example, it is possible to target expression of the new characteristic to a particular compartment of the grain, like the endosperm. It is very difficult to accomplish this through classical methods.

How is genetic engineering of plants accomplished?

Plant biotechnology had its beginnings with some fundamental discoveries that made the genetic engineering of plants possible. Most notably these included the finding that a naturally occurring bacterium, Agrobacterium, was capable of infecting plant cells, injecting some of its own DNA, which existed on a extrachromosomal element, and having that DNA become a heritable part of the plant cell's genome. Once recognized, plant biologists saw this as an opportunity to use a "natural" mechanism to put the genes of their choice into plants by simply substituting Agrobacterium sequences with their genes of choice.

Another hurdle in achieving a genetically engineered plant was how to get this introduced DNA to be passed on to progeny in the germline. This was a significant issue with mammalian engineering where the changes had to be made in germline cells, cells that participated in the sexual union that gave rise to the next generation. But plant cells have a unique property that made this process easier, a phenomenon called totipotency. This relates to the ability of somatic cells (non-sexual cells), like those in the leaves or stem, to be reoriented in their developmental pathway to reform an entire plant. This meant that, if you could introduce DNA into a single plant cell, any plant cell, then you could recreate a plant, all cells of which contained the new genetic information.

The ability to demonstrate totipotency in different plant species in large part determined the speed with which the new recombinant technologies could be applied. Some species, like tobacco and petunia, were easy to manipulate and success came in the mid-80's. This is because the cells of these species easily "remembered" how to reform a plant, while other plant species were more difficult, including many crop varieties, like cotton, sugarbeet and perhaps most notably, the cereals. Success with these species came in the early to mid-90's. Today nearly all major plant species can be manipulated in this manner.

What are the methods and objectives today?

Initial attempts at manipulating plant species made use of easily transformable varieties and easily identified genes, such as those for herbicide tolerance and certain types of pest resistance. The latter used an approach based on a naturally occuring toxin from a soil bacterium, Bacillus thuringiensis, which had been used by backyard gardeners for years. It was also determined early in the process that the expression of certain viral genes themselves, e.g., the coat protein, were capable of confering viral tolerance to the host. Plants are being grown commercially that utilize these approaches, for example the Roundup Ready soybean, BollGard cotton and viral resistant potato and papaya.

More recent modifications have made use of fundamental information gained through genetic, biochemical and genomic studies of the plant species themselves and their pathogens. These approaches are just being studied in laboratories and in some cases in limited field tests, but will be a part of the next generation of engineered plant species. These will include:

The latter category could include foods with lowered allergenicity, like wheat and peanut, and plants from which antinutritionals, like the glycoalkaloids in potato and cassava, are removed. They could also be foods that have better nutritional characteristics, like rice with higher iron and/or vitamin A content or oils with higher vitamin D. A step further would be to use foods to deliver medicines, such as edible vaccines for preventing cholera, rabies and even shows promise for certain types of cancer, like non-Hodgkin's lymphoma. There are also approaches to use foods for immunotolerance therapy for diseases like juvenile diabetes. Finally plants can be used to make alternatives for products that are currently being made from non-renewable resources, such as industrial oils, gasoline substitutes and plastics.

What controversies have arisen in this field?

Despite its potential for providing options to the farmer in the near- and long-term and to consumers in the long-term, a portion of the public is nervous about the products of biotechnology and who is developing them. Biotechnology is certainly not the first technology over which intense public discussion has arisen and, if constructive, such discussions can help shape responsible deployment and use of the technology. Furors have arisen in the past over, for example, the use of microwave ovens and the processes of vaccination, pasteurization and food irradiation.

The issues surrounding the use of biotechnology to improve foods have become increasingly contentious in the past year in the U.S. This follows some rather strong outcries by consumers in Europe. The reasons for these outcries are very complex. A major contributing factor is likely the fact that there were several food safety scares that made E.U. consumers fear that their regulatory system could not assure food safety. These included the mad cow disease crisis in the U.K. and the dioxin scare in Belgium. The decisions made by government officials during these controversies were perceived by many to be based on political expediency rather than on public safety concerns and this undermined consumers' confidence in the government to assure food safety with foods derived from biotechnology.

The issues surrounding the application of genetic engineering technologies to agricultural crops fall into several categories, which can broadly be grouped as food safety, environmental and ethical issues. It seems that the perceptions of these "risks" depends on who is making the assessment. For example in the food safety arena, there have been issues raised by consumer groups as to the possibility of creating new allergens through the process of genetic engineering. While this issue is being raised, scientists counter with their perspective that such technologies can and are being used to remove allergens from foods that cause problems for human consumers, like peanut and wheat. The same is true of the nutritional quality issue. While one group argues that genetic engineering might result in foods with decreased nutritional quality; scientists demonstrate that nutritional quality can be improved through genetic engineering as shown with the new golden rice varieties.

For the preceding reasons and also because of issues relating to food preferences by vegetarians and religious group, there has been a demand for extensive labeling of GMOs. Existing FDA policy only requires labeling when foods differ significantly from existing varieties in nutritional quality or the presence of antinutritionals or allergens. Because of what appears to be strong public sentiment in favor of a labeling policy, the FDA recently convened a series of meetings around the U.S. to solicit consumer opinion on the FDA policy. Bills are currently being introduced into state and federal legislatures demanding labeling, based in part on a consumer right-to-know issue.

In the area of environmental issues, there have been numerous issues raised regarding the safety and desirability of GM crops. Some of the issues have to do with unintended effects on insect or pest populations, like the now well-known example of effects of B.t. corn pollen on Monarch butterflies, published as a note in Nature by a scientist that had conducted a small study on the effects of pollen on monarch larval feeding. Other scientists have demonstrated a beneficial effect of B.t. canola on a beneficial wasp that infects a major canola pest; the diamondback moth; this likely resulted from the decreased use of pesticides. Other environmentalist concerns relate to the potential for GM crops to have detrimental effects on the environment, like the potential for increased herbicide usage or long-lived residues in the soil. These are countered by scientific studies showing some positive effects on beneficial insects and a sparing of pesticides on GM crops, particularly B.t. cotton. Other individuals have more generalized concerns about the impact of GM crops on biodiversity.

Much of the controversy between the two groups derives from the basis for comparison of impact. Some groups compare the impacts of GM crops to a zero risk paradigm in which agricultural practices have no impact on the environment; others compare GM strategies to the impact that modern production agriculture has on the environment. Having a different "denominator" in the equation often leads individuals to draw very different conclusions.

The last category of concern is related to ethical considerations and encompasses issues relating to intellectual property and control of germplasm.

Questions are raised as to the mechanisms for utilizing such technologies in developing countries and determining how to use these technologies to improve nutrition in developed countries. Perhaps the most universal concern is the issue of who will controls the food supply and the concern over the role of multinational corporations in developing and controlling the GM varieties.

How have the controversies shaped the field--in terms of who raised the concerns (scientists? environmentalists? farmers? government officials?) and what means were available to deal with them?

Of the concerns mentioned above, most have been raised by groups other than scientists or regulators. Environmentalists and other activist groups have been very vocal in opposing the application of biotechnology to agriculture. As they articulate their concerns, it is a fear of the unknown; we do not know enough about the technology to take a long-term view and know what issues need to be addressed. How can we predict the long-term consequences of consuming GM foods or growing GM crops in our fields. Many ascribe to the precautionary principle, which embraces the "guilty until proven innocent" paradigm, a situation that is opposite to the way in which food policies have been shaped in the U.S. in the past.

Farmers have begun to gain experience with these crops and in fact most of the improvements engineered to date have been focused on farmer's needs and making their jobs easier. For example, traits that improve processing, pest resistance, weed management were the first ones to be commercialized. In some cases, farmers have found the crops to improve their lot; in other cases, they have not. I believe that the environmental issues that are raised regarding GM crops are not significantly different from issues that farmers must address now with conventional crops and farmers believe that they can manage the environmental issues. As GM crop strategies become more sophisticated and the performance of the modified crops better, farmers are likely to embrace them if they deliver benefits.

The different government agencies have taken different approaches to the regulation of GM crops. The FDA does not consider process in assessing the safety issues related to GM foods; they focus on the scientific risks regardless of the means by which the new trait was introduced. The EPA and to a lesser extent the USDA do consider genetically engineered crops to have inherent differences that warrant separate regulatory structures and different risk assessments.

Public-sector scientists have stayed relatively quiet during the controversy, with a few exceptions. Scientists in Switzerland became very involved in explaining biotechnology to the public when a referendum was introduced that could have curtailed their activities. Increasingly scientists here in the U.S. are becoming more vocal as they attempt to address the scientific assessments of risks of the new GM foods. But scientists can only speak knowledgeably to scientific risk and not to safety, which is defined as an individual's acceptable level of risk. This is a matter of public definition and how this is determined in the international marketplace, where the array of cultural differences abound, is not clear at present.

The first products of the technology are crude; the Roundup Ready soybean is not the best that can be engineered in terms of an herbicide-tolerant crop. Many of the current products will not achieve the potential necessary for user or consumer acceptance. But the strategies will likely be improved and refined, just as the computer moved from a machine that took up city blocks to one that fits on your wrist. It is likely the case that some products of the technology will find favor with users and consumers; some will not. Some will be a commercial success; some will not.

How has "risk" been defined in this field? By whom?

Risk can be measured scientifically and in cases where our experience allows us to do this with GM crops, scientists either have done or are doing this. But scientific risk is not the same as perceived risk or acceptable risk, which is how "safe" an individual thinks something is. Most activities in which we engage carry some degree of personal risk, flying on an airplane, breathing in cigarette smoke, engaging in exercise programs or picking wild mushrooms. But in instances where we engage in these activities, we accept the risk because we believe the benefits outweigh the risks, as long as we voluntarily engage in the activity. Second-hand smoke, for example, has a different perception of safety than if one chooses to smoke.

In the case of GM foods, scientists for the most part have a different perspective than those not involved in the utilization of the technology. Scientists can see the potential for long-term benefit of the technology and therefore assess risk in a different way from the consumer who has yet to see tangible benefits in the products of the technology. Farmers also can see some tangible benefits if the technology lives up to expectations and are therefore willing to accept responsibility for managing environmental risks that the use of the crops might bring.

But farmers and producers are driven by consumer attitutudes and if there is a sense that GM foods are not going to be eaten or used, they will not want the liability of growing the foods and not being able to sell them at the end of the season. In the end the utility of the technology will be determined by the interplay of a variety of factors, only one of which reflects the scientific measurement of risk; the other factors will be market- and consumer-driven.

2000 Peggy G. Lemaux