Panel II
Using Biotechnology for the Benefit of Humanity

Advances in science and engineering are creating powerful tools for harnessing biological activity for human use, but these tools entail risks—some real and some perceived. This panel discusses the informed, responsible use of emerging biotechnologies to address global problems.



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Engineering and Environmental Challenges: Technical Symposium on Earth Systems Engineering Panel II Using Biotechnology for the Benefit of Humanity Advances in science and engineering are creating powerful tools for harnessing biological activity for human use, but these tools entail risks—some real and some perceived. This panel discusses the informed, responsible use of emerging biotechnologies to address global problems.

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Engineering and Environmental Challenges: Technical Symposium on Earth Systems Engineering Genetically Modified Organisms An Ancient Practice on the Cusp MAXINE F. SINGER Scientists and engineers are trained to adjust to change. During my own undergraduate and graduate studies about 50 years ago, eminent biologists were still choosing up sides as to whether proteins or nucleic acids carried genetic information in chromosomes. Look where we are now! But revolutionary change doesn’t go down easily outside of the technical community. As Paul Ehrlich, the distinguished environmentalist, recently pointed out, “A major contemporary human problem is that the rate of cultural evolution in science and technology has been extraordinarily high in contrast with the snail’s pace of change in the social attitudes and political institutions that might channel the uses of technology in more beneficial directions” (Ehrlich, 2000). The different rates of change is a setup for problems. Serious gaps can develop between engineers’ and scientists’ ideas about the natural world and those that are current in mainstream society. A case in point concerns genetically modified plants. For much of the nineteenth century a significant part of what we now call biology was called natural history. Tramping around the countryside looking for new species of beetles, fossils, or plants was considered a charming and harmless pursuit by the wealthy leisured class. Then, around the middle of the century, three great discoveries signaled a new kind of biology. One was the formulation of cell theory—the concept that all organisms are composed of one or more living cells. The second was Mendel’s elaboration of the laws of inheritance. The third was Darwin’s concept of evolution and the origin of species. Darwin, of course, opened a huge gap between science and the public that still haunts us. By the end of the twentieth century these three paths had converged into one biology—a science that is

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Engineering and Environmental Challenges: Technical Symposium on Earth Systems Engineering extraordinarily sophisticated and productive, although somewhat less charming and less acceptable to some. As originally conceived, genes, though real enough, were thought to have no substance; they were considered abstractions. Mendel showed that genes are discrete bits of information passed from parents to offspring. One gene dictated the color of peas, another one whether they were smooth or wrinkled, and so on. Every organism, he realized, had two genes for each discrete trait, such as pea color—one from its maternal parent and one from its paternal parent. Most important, Mendel learned that any particular gene—for example, the gene responsible for the color of a pea—could occur in different forms. Depending on the two forms that were present in an individual plant, the peas would be green or yellow. These different versions of genes are responsible for variations within a species, including the variation we see if we look around a room at different faces. Geneticists call the individual variants of a gene an “allele,” such as the green allele and the yellow allele for pea color. In most populations of organisms there are many alleles for a given gene, not just two. New alleles, known as mutations, can arise. Although the word mutant has a negative connotation, not every mutant allele is bad news. Some alleles give organisms an advantage over their cousins in a particular environment. The advantaged organisms reproduce more efficiently than their cousins, thus explaining Darwin’s idea of natural selection. Breeders of animals and plants practice unnatural selection, relying on human intervention to ensure the efficient reproduction of a selected organism. The earliest plant breeders, probably starting about 10,000 years ago, made use of allelic variations, although they were ignorant of the underlying mechanisms. They observed new, rare alleles in fields and, when they noticed a novel property that was advantageous, they bred it into standard varieties. Wild potatoes, for example, contain high levels of alkaloid toxins. At least 4,000 years ago central Andean populations began selecting and breeding potatoes, presumably with alleles that reduced the poison. Today, of course, we know that genes are made of segments of DNA. Alleles can differ from one another in the sequence of the four DNA bases that constitute their genetic code. Some alleles have more draconian changes—large segments of DNA or even most of a gene may be lost. Other alleles differ not in the gene coding sequence but in the surrounding DNA sequences that regulate the level at which the gene operates, or even whether it operates at all under particular conditions. This sort of modulation of gene activity, which biologists call gene expression, underlies one of the alleles that differentiates modern maize, or corn, from teosinte, corn’s wild ancestor of the same species (Zea mays), which is indigenous to central Mexico. Very few wild plants are closely related to corn, and none of them—not even teosinte—looks very much like the corn we know. Teosinte is a bushy plant with many tassels (the organ that produces pollen) and

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Engineering and Environmental Challenges: Technical Symposium on Earth Systems Engineering many seed-bearing stalks. The stalks are an inch or two long and have two rows of tiny seeds, each of which is covered with a very hard case. Unlike corn, these seed stalks have no green casing, or husk. The seeds eventually fall to the ground, sowing next year’s plants and providing food for birds, which also disperse the seeds. Corn could never have arisen or been propagated by natural processes because the seeds, or kernels, are tightly attached to the cob and cannot disperse. Corn plants cannot propagate themselves without human intervention. About 5,000 years ago, Central American plant breeders began selecting and growing teosinte variants because they were advantageous. The fundamental differences between teosinte and the corn we know are accounted for by variant alleles in five genes. At least one of those fundamental changes—the one that makes corn grow as a single straight stalk rather than a bush like teosinte—reflects a change in a regulation of gene activity rather than in a coding segment of a gene. This is an extraordinary case of human engineering of a natural system. Our modern diets are composed almost entirely of genetically modified organisms (GMOs). If that history were better understood, the current public debate about GMOs might have a different focus. Today, the term GMO is commonly used to refer to plants that have been modified by modern molecular techniques, and I will use it that way. Few people understand the continuum between ancient and modern methods. Modern molecular techniques emerged about 30 years ago when biologists learned how to manipulate genes precisely through techniques variously called recombinant DNA and cloning. These techniques enabled researchers to make direct changes in DNA structure to accomplish a predetermined purpose. Rather than waiting for the chance emergence of a desirable allele and then breeding it into a variety of plant, biologists can now design alleles to meet their needs. The methods used in plants are essentially the same as those used to understand and develop treatments for human diseases. All of them generally entail changing only a small number—from one to several thousand—of the billions of base pairs in an organism’s genome. The new methods can yield all of the allelic changes that occur spontaneously, and in much less time than the five to ten years normally associated with traditional methods. Biologists can also introduce new genes into plants as they have done with the interbreeding of two species (such as crossing a pomelo and an orange to produce a grapefruit). In traditional interbreeding, successes are rare, and there is a significant probability that traits undesirable in terms of the environment or food safety will remain. In contrast, the new techniques are rapid, because they allow biologists to introduce a single change to a single gene, and the probability of introducing undesirable properties is much lower. What kinds of genes or alleles are introduced? The possibilities include genes from varieties of the same species, genes from related species, and genes from totally unrelated species, including genes from bacteria and animals. This,

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Engineering and Environmental Challenges: Technical Symposium on Earth Systems Engineering of course, is very different from traditional breeding. The apparent strangeness of this idea, for example, putting a fish gene into a strawberry plant to protect the plant from frost, has elicited a great deal of discussion and misunderstanding. It’s important, therefore, to consider exactly what we mean when we say that we’re putting a bacterial gene or a fish gene into a plant. Biologists first identify the appropriate gene—a segment of DNA—and then isolate it from the rest of the DNA of the source organism using the technique known as cloning. Usually this means allowing bacteria to reproduce the DNA segment and then chemically isolating it. Sometimes biologists can introduce the isolated DNA directly into a plant, but often they modify it first to make it more suitable for its new location. For example, the DNA code words might be changed to enable the gene to work more efficiently in its new plant host. Biologists then introduce the gene into the new plant, sometimes by shooting it in and sometimes by transferring it on the DNA of a special bacterium that, in nature, transfers its own DNA into plants. The original gene may have come from a fish, but it has been modified and amplified in many different bacterial cells before it is inserted into the plant’s genome. At that point it is a pure, definite chemical structure, a piece of DNA. Is it still a fish gene? That, I believe, is a philosophical question, not a scientific one. Like all complicated problems, the question of whether genetically modified plants will be safe for human health and the environment has no simple yes or no answer. Even assuming they are safe, we can’t even say whether they are desirable. Opinions are sure to differ, depending on who is answering the question. However, the issues raised are no different from those posed by new plant varieties produced by traditional breeding. The questions aren’t focused on the process used to produce the plants but on the nature of the modified plant. Each type of modified plant must be assessed on its own merits in relation to its use and the environment in which it will be grown. To do this, we must focus on several different classes of concern. In the case of food, we’re interested in the safety of the engineered plants for human and animal consumption. The environmental effects of all modified plants, both positive and negative, must be weighed. The resolution of environmental issues depends on scientific information that may or may not be readily available. And some concerns are only partly answerable by science. These include economic and humanitarian concerns, such as the limited ability of poor people, largely in Africa and Asia, to gain access to new plant varieties. Consider, for example, Bt corn and Bt cotton, which have been engineered to resist certain insect pests by enabling the plants to produce an insecticidal protein within their own cells. Corn and cotton have also been bred for insect resistance through traditional breeding methods based on natural plant alleles that make plants resistant to some insects. Insects can also be controlled by chemical spraying of fields. So the question is one of balance: which method is preferable—spraying, traditional breeding, genetic engineering, or some combination? For

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Engineering and Environmental Challenges: Technical Symposium on Earth Systems Engineering genetically engineered and traditionally bred food plants alike, we must ask whether newly introduced changes yield a protein that’s allergenic or toxic to humans and animals. Has the amount of some toxic component in the normal plant been increased? If biologists used an antibiotic-resistant marker gene for convenient manipulation, as they often do, we might be concerned that the effectiveness of an important drug might be compromised. Five years ago U.S. farmers began planting Bt corn and cotton. These crops contain copies of genes coding for proteins that are toxic to a major corn pest, the European corn borer, and other pests that destroy cotton. The genes were copied from a bacterium called Bacillus thuringiensis, or Bt for short. As of summer 1999, more than 30 percent of the corn and 27 percent of the cotton planted in the United States contained Bt, a total of 30 million acres (Vorman, 1999). The underlying purpose is to reduce the 30 to 40 percent of the crop that is lost to pests each year worldwide. Organic farmers have used Bacillus thuringiensis itself by the ton for more than 40 years to control insect pests, so biologists had good reason to think that the Bt toxin would be harmless. A lot of the engineered corn is fed to animals or goes into products like corn oil that we’ve all eaten. Except for the possibility of allergies, which all corporate and academic researchers and government regulators are attentive to, there are no indications of untoward effects from eating foods from any of the currently harvested genetically modified plants. Nor are there are obvious reasons to worry about the health effects of foods and fibers in the pipeline. What about the balance between desirable and undesirable effects on the environment, including biodiversity, from insect-resistant GMOs? First, GMO crops require much less chemical insecticide than unmodified crops. According to the U.S. Department of Agriculture, with GMOs the use of noxious polluting chemical pesticides was reduced by one million gallons between 1996 and 1998 (Monsanto, 1999), with concomitant cost saving to farmers. Spraying chemicals indiscriminately eliminates all of the insects in a field, including species that are vital for pollination and biological control. Thus, GMOs can improve insect biodiversity. However, last year two scientific reports showed that milkweed leaves dusted with heavy concentrations of Bt corn pollen are toxic to monarch butterfly larvae in laboratory experiments (Hansen Jesse and Obrycki, 2000; Losey et al., 1999). This was not surprising, because biologists knew that the Bt toxins were toxic to lepidoptera in general. These findings attracted an enormous amount of public attention and concerns, which were amplified by the well-known fact that there has been an unexplained drop of about 70 percent in the population of monarchs wintering in Mexico since 1996 (Monsanto, 2000). Is there a relation between the use of Bt corn and the decline in the monarch population? Perhaps. But it’s also likely that the effect of Bt corn is relatively small compared with the known effects of habitat destruction in Mexico and the use of chemical insecticides in both Mexico and the United States. More recent

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Engineering and Environmental Challenges: Technical Symposium on Earth Systems Engineering experiments, some in the field, indicate that the lethal effect of Bt corn pollen depends on the particular variety of Bt corn—various Bt genes have been introduced—and the level of the toxin the plant produces, as well as the amount of pollen that spreads and how far. A few rows of regular corn between the Bt field and uncultivated surrounding areas can diminish the effects. Wise policy making will have to be based on the factors that effect monarch mortality (chemical insecticide, the spraying of tons of Bacillus thuringiensis bacteria, the use of genetically modified pollen) as well as crop yields, costs per acre, and local conditions, such as the abundance of monarchs and the timing of larval feeding compared with pollen production. Another environmental concern is that pest resistance might be spread through the dispersal of pollen to wild relatives of crop plants, which could lead to insect-resistant weeds. If no wild relatives are in the vicinity, there’s no problem. For example, there are no wild relatives of corn in the corn belt of the United States. But in Mexico teosinte grows around cornfields. One technique for minimizing this problem would be to plant a border of unmodified plants around a field of modified plants, the same technique that decreases the exposure of monarchs. Yet another concern is that insects and other pests might develop resistance to the antipest agent in the GMO. This is already a problem with chemical insecticides and with the alleles that provide spontaneous resistance introduced through traditional plant breeding. The development of resistance to all insecticides is a fact of life for farmers, just as resistance to antibiotics is a medical problem. That’s one reason farmers are constantly looking for new ways to control pests. Offsetting measures can and are being taken, such as requiring farmers to plant unmodified crops to inhibit—though not necessarily eliminate—the development of resistance in insects. Since January 2000, the Environmental Protection Agency has required farmers to plant 20 to 50 percent of their acreage in conventional corn (EPA, 2000). Discussions are continuing about whether this is necessary and, if so, what percent of acreage is sufficient, but the general principle is imbedded in the U.S. regulatory structure. As these examples show, we should not be acting on hunches or preliminary findings or irrational concerns but on thoughtful, informed analysis. In our country, the U.S. Department of Agriculture regulates meat and poultry products, the Food and Drug Administration regulates other foods, and the Environmental Protection Agency regulates pesticides. Approval of crops requires testing for both human and environmental toxicity. The regulatory process must be open, transparent, and vigorously enforced so that the public can judge for itself whether its interests are being served. Evidently this did not happen in the case of the corn flour that was used for making tacos, the story of which was on the front pages of all the newspapers. To address other issues, science can provide, at best, a modicum of useful information. For many people food is a personal and cultural issue, not a scientific

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Engineering and Environmental Challenges: Technical Symposium on Earth Systems Engineering one, and all of us want choices about what we eat. We can also find historical examples demonstrating the occasional folly of some traditional approaches. The French deprived themselves of the nutritious and delicious potato for 200 years after it was brought to Europe from the Andes in the sixteenth century because they believed that potatoes caused leprosy. Tomatoes, another sixteenth century New World contribution to global diets, suffered a similar fate. At first only the Italians were bold enough to challenge the widespread notion that tomatoes were poisonous, as indeed some of its relatives and its foliage are. Recently a new golden rice has been engineered to produce significant amounts of beta-carotene, the precursor of vitamin A. Scientists hope that, after some additional development, the widespread use of golden rice will reduce the number of people in Asia and Africa who are afflicted with blindness because of a dietary deficiency of vitamin A. Some argue that the golden rice will not be palatable to people accustomed to eating white rice. That’s a choice the affected populations must make for themselves. Personally, I find it hard to imagine that people would be willing to watch their children go blind rather than change their eating habits. The argument that GMOs should not be used because they are not natural is frustrating for scientists. What, after all, is natural in this context? Certainly not our standard diets, which are derived from centuries, even millennia, of careful, directed breeding. Some experts believe that the older breeding methods have achieved about as much as they can in terms of productivity of farmland and water. Thus, in many parts of the world more and more forests are being cleared and more and more land cultivated to feed growing populations. Yet most people agree that preserving forests is essential to preserving biological diversity and limiting global climate change. The new genetic engineering techniques could potentially increase the productivity of agricultural land and water and, perhaps, save forests. Other aspects of the vocal opposition to GMOs have little to do with science. One motivation for the anti-GMO campaign is antagonism to the practices of large agricultural industries. Some people worry that the commercialization of plant varieties means that they will be unavailable to developing countries, which is a legitimate concern, because about 80 percent of new plants have been developed by companies, though not, I should mention, golden rice. We must try to avoid injustices like those associated with the limited availability of drugs to fight AIDS. Opposition also comes from the organic food industry, which lobbied hard to include the absence of genetic modifications in the official U.S. definition of organic food, although, in fact, organic farming techniques could benefit greatly from the use of certain GMOs. Other critics of GMOs are people who are honestly concerned about their environmental implications. Some people opposed to GMOs have even become violent. For years, in Europe, they have engaged in the willful destruction of greenhouses, laboratories, and experimental fields; similar

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Engineering and Environmental Challenges: Technical Symposium on Earth Systems Engineering acts have occurred in the United States (Sydney Morning Herald, June 24, 2000; Montreal Gazette, August 10, 1999; Washington Post, October 26, 1999; Fumento, 2000). I do not mean to say that the promoters of GMOs are blameless. Several large corporations have invested heavily, and then promoted, the development and production of seeds of genetically modified plants. The concerned public is naturally suspicious of claims that these plants are harmless and valuable. Suspicions about these claims are reinforced by the fact that the crops have as yet had no direct, obvious advantage to consumers. Can the 6 billion people on Earth (or the 9–12 billion people expected to populate the Earth by 2050) be adequately, economically fed without the investments and products of large companies? American farmers, who are usually pragmatic, initially embraced engineered corn, soy, and cotton because they believe they will be economically advantageous. Thus far we’ve seen only the tip of the iceberg of GMOs. Promising research is under way in many areas. Researchers are working on incorporating vaccines—for example, against diarrhea-producing organisms—into edible, easy-to-ship, easy-to-store plants like potatoes and bananas; this could go a long way toward addressing distribution problems for vaccines in many countries. Someday plants may provide fuels and lubricating oils for automobiles, thereby saving fossil fuels and mitigating their damaging environmental effects while making direct use of the energy of the sun. Researchers are also engineering trees to reduce the amount of chemicals needed to produce paper. On balance, although GMOs can bring real advantages to agriculture, health, and the environment, the use of this new technology has been all but foreclosed, at least for now, in Europe and some other countries. Exaggerated arguments about potential problems—particularly the implication that GMOs are not safe to eat—could bring the United States to a similar position. If scientists can address and allay these concerns, we may all reap a good harvest. REFERENCES Ehrlich, P. 2000. The tangled skeins of nature and nurture in human evolution. Chronicle of Higher Education 47(4): B7–B11. Available online at <http://chronicle.com/free/v47/i04/04b00701.htm>. EPA (Environmental Protection Agency). 2000. Biopesticide Fact Sheet: Bacillus thuringiensis Cry1Ab Delta-Endotoxin and the Genetic Material Necessary for Its Production (Plasmid Vector pClB4431) in Corn [Event 176]. EPA 730-F-00-003. Available online at <http://www.epa.gov/pesticides/biopesticides/factsheets/fs006458t.htm>. Fumento, M. 2000. Crop buster. Reason Magazine 31(8): 44. Available online at <http://www.reason.com/0001/fe.mf.crop.html>. Hansen Jesse, L.C., and J.H. Obrycki. 2000. Field deposition of Bt transgenic corn pollen: lethal effects on the monarch butterfly. Oecologia 125(2): 241–248. Available online at <http://link.springer-ny.com/link/service/journals/00442/contents/tfirst.htm>. Losey, J.E., L.S. Rayor, and M.E. Carter. 1999. Transgenic pollen harms monarch larvae. Nature 399 (6733): 214.

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Engineering and Environmental Challenges: Technical Symposium on Earth Systems Engineering Monsanto. 1999. USDA Report Cites Pesticide Reductions and Yield Increases Associated with Biotech Crops. Biotech Knowledge Center, 1653, July 7, 1999. Available online at <http://biotechknowledge.com/showlibsp.php3?uid=1653>. Monsanto. 2000. Butterflies and Bt corn pollen, Lab Research and Field Realities. Biotech Knowledge Center, 3069, February 15, 2000. Available online at <http://biotechknowledge.com/showlibsp.php3?uid=3069>. Vorman, J. 1999. USDA issues first estimate of GM crops. Available online at <http://www.gene.ch/genet/1999/Oct/msg00028.html>.

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