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Issues Surrounding Genetically Modified (GM) Products
About ten years ago, Dr. Acharan Narula and I tried to solve a problem for several patients by providing a protein supplement made from soybeans with added isoflavones. The basic situation was that some people were suffering from protein deficiency due to reduced appetite such as occurred in patients with cancer, HIV, and those with chronic digestive system disorders. Inadequate protein intake leads to reduced serum albumin levels, and this condition has been shown to be an indicator of decreased capability to heal. For example, hospital patients with low albumen have longer recovery time from surgery. Among the vegetable sources of protein, soy protein is one of the most complete. A useful method of evaluating the quality of a protein is the protein digestibility-corrected amino acid score (PDCAAS). This is a means of comparing the amino acid contents of a protein with human amino acid requirements and corrects for digestibility. Casein, the highly digestible protein component of milk, is given a score of 1.00 and then other proteins are rated against that standard. The human requirements are based on those of young children, because it is considered that a protein suitable for them will also be suitable for adults. Following is a table of these scores from the UCLA Center for Human Nutrition; soybean protein isolate scores barely below casein and egg white.
| Protein Digestibility-Corrected Amino Acid Score Values | |
| Casein | 1.00 |
| Egg White | 1.00 |
| Soybean isolate | 0.99 |
| Beef | 0.92 |
| Pea flour | 0.69 |
| Kidney beans | 0.68 |
| Garbanzo beans | 0.66 |
| Pinto beans | 0.63 |
| Rolled oats | 0.57 |
| Lentils | 0.52 |
| Peanut meal | 0.52 |
| Whole wheat | 0.40 |
Soy beans naturally contain substances called isoflavones, which are considered to be of special value to human health; the main ones are genistein (which has been the most intensively studied) and daidzein. These substances, present in the amount of about 150-200 mg per 100 grams of soy powder, can regulate inflammatory mediators (such as IL-8) to reduce inflammation, and influence other processes to help prevent disease and alleviate symptoms. According to a report by the College of Agriculture at the University of Illinois, the following are among the potential benefits:
The amount of soy protein or its isoflavones needed to accomplish these benefits is higher than is practical for most people (in Japan and China, high intake of soy-based products like tofu, may provide these benefits). Specifically, about 25-50 grams of soy protein isolate or soy flour per day would probably need to be consumed. The isoflavone intake from these sources is about 60-180 mg/day (estimates of East Asian dietary intake of the isoflavones is 20-80 mg/day). Other beans also contain isoflavones, but far less than soy beans, about 1% as much.
Thus, to make a useful supplement, additional isoflavones from soy were added to the soy protein so that one serving would supply 13 grams of protein but 60 mg of isoflavones. The resulting product is called "Narula-Soy" and it is described as a "genistein-enriched soy protein beverage powder."
No sooner was this supplement introduced, then questions about the sources of the soybeans were raised (e.g., are the soybeans non-GMO?). GMO (or simply GM) refers to "genetically modified organisms." At first, I was surprised that this was a concern, and thought that the soybean powder was probably from "ordinary" soybeans, which might include the GMO type. However, Dr. Narula had already encountered the concern and had obtained the "non-GMO" soy protein powder for the product (the label states: "100% certified non-GMO").
Why the high level of concern about this? Following is an analysis of the GMO situation, which will hopefully clarify the specific issues that are encountered. It should be noted that herbal medicines have not been the target of the type of genetic modification to be described, with one notable exception: ginseng. An effort has been made, for example, to develop ginseng that produces far higher levels of the desired active constituents, the ginsenosides, than are found in the ordinary roots. This is because ginseng is very difficult to grow (it is easily damaged by root rot and it takes many years to get a mature root) and then the content of ginsenosides in the collected roots is relatively low, so that it becomes a very expensive remedy. One of the solutions to this problem that has been pursued in China is to extract ginsenosides from other parts of the plant that are normally discarded, namely the leaves and fruits. In Russia, scientists have worked on genetically modified ginseng cell cultures to see if a higher ginsenoside content could be achieved.
For centuries, humans have altered plants and animals by selective reproduction (breeding, hybridizing). As a result, we have a wide range of domestic animals and plants grown for food and for a variety of non-food uses (such as for fibers and decorative purposes and as a source of fuel). These efforts to adjust the characteristics of organisms in nature do not involve direct genetic modification by humans, but involve human actions working with existing natural processes for selection of traits. These traits are in the genes, so there are some differences in the genes of the original and modified versions of the plants and animals.
Direct genetic modification is a relatively new process based on a set of technologies that alter the genetic makeup of living organisms, including animals, plants, bacteria, or fungi by inserting genes rather than using cross-breeding and selection techniques. The purpose of the modification of the genes is to derive certain benefits. Genetic modification is accomplished by inserting one or more genes from one organism into a different organism (for example, from bacteria into a plant or from one species of plant into another). Combining genes from different organisms is known as recombinant DNA technology ("gene splicing"), and the resulting organism is said to be "genetically modified," "genetically engineered," or "transgenic." The end product we use may be part of the genetically modified organism itself (e.g., the beans of the soy plant) or something produced by the modified organism (for example, a drug produced by fermentation using modified bacteria or fungi).
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The first reported recombination of genetic material was in 1973, so this technology is just over 30 years old. One of the first applications was the production of insulin by bacteria (insulin to be used for treating diabetics was previously derived from pig pancreas); the recombinant insulin product was approved by the FDA in 1982. The bacteria used for this purpose is a strain of E. coli, a common organism (it is a major bacteria in the human intestinal tract), into which the human insulin gene is inserted. The advantage of this technology is that the product matches human insulin exactly and it is cheaper to produce; the pig product is more likely to cause allergic reactions.
A few years later, in 1988, the first field tests of a genetically modified food plant were undertaken in Canada; this was for the canola plant that yields a very desirable vegetable oil (lowest in saturated fat; high in cholesterol-lowering mono-unsaturated fat; best large-scale plant source of omega-3 fatty acids). The genetic modification increased the yield and decreased the need for fertilizers, lowering the price. But, it wasn't until 10 years ago, in 1996, that commercial production of genetically modified (GM or GMO) crops was undertaken: these involved not only canola, but also corn, potatoes, and cotton.
The primary focus of the research on genetic modification involves locating genes that can produce the desired results-such as those conferring insect resistance, reducing sensitivity to herbicides, increasing the amount of desired nutrients, or preventing fruits from rotting as quickly as usual. This difficult process is becoming easier with technologies that permit rapid gene sequencing and with sophisticated computer programs that can match up genetic patterns with their protein products.
An example of genetic modification is the introduction of a gene from the soil bacterium Bacillus thurigiensis into the genes of a crop plant; the selected gene codes for a protein that is toxic to certain insects. The genetically modified plants then produce the protein, making them resistant to pests like the European Corn Borer or Cotton Boll Worm (the genes also protect potatoes and rice from destructive insects). By using this technology, the yield of plants is higher (since fewer are damaged by insects) and the use of insecticides against these pests can be reduced. Other pest-resistant GM crops on the market today have been engineered to contain genes that confer resistance to specific plant viruses.
Another example of genetic modification for food use is associated with the production of cheese. Traditionally, an enzyme preparation called rennet is added to milk. Rennet is isolated from the lining of calf stomachs; it contains the enzyme chymosin, which causes milk protein (casein) to clump together into a solid gel, making hard cheese, like cheddar cheese. By the 1960s, the amount of rennet was insufficient to meet the increasing world-wide demand for cheese. So, cheese manufacturers turned to getting the enzyme from the stomachs of other animals or obtaining a similar enzyme from certain fungal strains (used for "rennetless" cheese that vegetarians preferred). Genetic engineering is the solution that worked the best. Bacteria were modified by inserting a gene that codes for producing chymosin identical to the enzyme obtained from calf; it produces a better quality cheese than that produced using non-calf rennets. The technology was worked out in 1981 using bacteria, but relying instead on genetically modified food yeasts was soon found to be more productive. In 1988, chymosin was the first enzyme from a genetically-modified source to gain approval for use in food; compared to the calf chymosin, its activity is more predictable and it has fewer impurities. Also, vegetarians have approved of these cheese products.
One of the best known of the GM food crops is the "roundup ready" soybean, introduced into commerce in 1997. These were developed by Monsanto, the same company that had produced the GM canola and that manufactures the herbicide (weed killer) called "Roundup," a form of glyphosphate. This genetic modification allows soybean farmers to get rid of weeds with Roundup while the soybeans are not adversely affected by it. Otherwise, soybean crop yields would be lowered by the growth of weeds, or less desirable chemicals would need to be used to control competition by weeds (glyphosphate is not carcinogenic, does not affect reproduction and development of animals, does not accumulate in the body, and is not acutely toxic in its dilute form). Today, 85% of the soybeans grown in the U.S. are GM soybeans. As the graph (below) displays, starting with that 1997 introduction, GM crop production took off.
Other crops grown commercially or field-tested include a sweet potato resistant to a virus that could decimate most of the African harvest; rice with increased iron and vitamins that may alleviate chronic malnutrition in Asian countries; and a variety of plants able to survive weather extremes. There are over 100 species of plants in the testing phase for potential commercial use of their genetic modifications.
While these GM crops are becoming increasingly relied upon, they still represent only a small fraction of all farming activity. In 2003, about 167 million acres (67.7 million hectares) were devoted to transgenic crops; this is out of 1.5 billion total hectares, or about 4.5% of the world cropland. These crops were grown by about 7 million farmers in 18 countries, but mostly in the U.S., Argentina, Canada, Brazil, China, and South Africa. The main crops were the ones already mentioned, being herbicide-resistant and insect-resistant soybeans, corn, cotton, and canola.
In 2003, countries that grew 99% of the global transgenic crops were: the United States (63%), Argentina (21%), Canada (6%), Brazil (4%), and China (4%), and South Africa (1%); see the graph below, listing the acreage in millions for the countries indicated. Although growth of this enterprise will eventually plateau in industrialized countries, it will increase for decades in developing countries. It has been predicted that during the next few years we will see an exponential progress in GM product development as researchers gain access to genetic information and resources beyond the more limited scope of individual projects undertaken thus far.
Technologies for genetically modifying foods offer dramatic promise for meeting some areas of greatest challenge for the 21st century. Like all new technologies, they also pose some risks, both known and unknown. Controversies surrounding GM foods and crops commonly focus on human and environmental safety, labeling and consumer choice, intellectual property rights, ethics, food security, poverty reduction, and environmental conservation (see last page for a summary: "GM Foods: Benefits and Controversies").
The rapid introduction of these genetic engineering technologies has posed the serious question of whether we are rushing into an area of potential danger without giving it adequate thought. One can raise the "Jurassic Park" specter of messing with DNA and having the results come back to "bite you" just when you thought everything was going so well and that the few initial problems were resolved.
Some of the fears are generated by and kept active among groups who discuss the matter without having any significant training in biology and who may be relying on misconceptions and incorrect information. Science fiction writers and movie makers may help play into these fears as will authors of "non-fiction" works who sensationalize and misrepresent certain scientific concerns. Real problems with genetic engineering can then blend into the imagined scenarios, to make people become very agitated.
There have also been a number of technology scares that lead to a general concern about moving into new areas like genetic engineering. One can think of nuclear weapons and the threat of global destruction; nuclear power and the problems of Chernobyl and Three Mile Island; the excessive use of the pesticide DDT and the potentially devastating outcomes for animals and humans that was averted by banning it; the contamination of water supplies with mercury and contamination of the soil with lead; the possibility that continued global warming and serious adverse consequences due to human activities, and so on. In these instances, drastic actions have been considered-and sometimes utilized-in order to prevent catastrophes, sometimes after a wake-up call from a limited disaster. In addition, there have been worries about human activities even from the non-technological end, such as decimating forests. So, some people simply want humans to back off from altering nature and leave things alone to the extent possible; that includes not altering the DNA of organisms.
On the other hand, most people like the numerous benefits of technology and simply want it to be used sensibly. Instead of protesting against technological innovations, they want to be assured that reasonable safeguards are in place. Some of the genetic modifications have raised virtually no objections, such as the use of bacteria to make insulin and the use of yeasts to make enzymes for cheese. These technologies are unlikely to stir up much controversy because the genetically modified organisms stay inside the factory and no problems have yet been detected. Some of the fears about genetically modified foods are not consistent with our knowledge of biology and toxicology. For example, eating a food that includes a protein (such as the one serving as a natural insecticide or protecting against herbicides) doesn't appear to pose any threat to humans (that protein already existed in nature and was present in small quantities in some foods). The protein is not toxic to humans and is broken down, like other proteins, into amino acids that nourish the body. The gene is not going to change human genes. Nor is the gene within the food we eat going to mutate into a virus or other pathogen. Eating genetically modified soybeans will not have a direct adverse effect on the person eating them.
However, the underlying issue of worrying about eating genetically modified foods is not entirely without certain merits, in that certain genetic modifications might affect humans. A process was developed to make soybeans a richer source of nutrition by adding a gene from Brazil nuts. The purpose was to make the balance of amino acids in soybeans better for nourishing humans (something that was really not necessary). Soybean nutrition is compromised slightly by a relative deficiency in its methionine content; the Brazil nut gene for producing a methionine rich protein was introduced into the soybean genes. The problem is that some people are allergic to the protein produced by the gene from the Brazil nut (they are allergic to these nuts and this protein happens to be one of the allergenic substances). So, that GMO crop idea had to be abandoned (it had not been commercially introduced). Still, the fact that scientists went down this particular path of potential product development shows that the technology can get into areas of trouble.
Greater anxiety occurs when the organisms are out in nature. What will happen as these genetically modified organisms interact with other organisms? Already, there is a concern that crops resistant to weed killers will themselves become uncontrolled weeds in other fields. This can occur especially when the crop plant pollinates a related species that is a weed; then the weed can also be resistant to weed killers. Below is a table of some crops that have problematic weeds as relatives:
| Crop | Weedy Relative |
| oat (Avena sativa) | wild oat (Avena fatua) |
| canola (Brassica napus) | birdsrape mustard (Brassica rapa) |
| sunflower (Helianthus annus) | common sunflower (Helianthus annus) |
| rice (Oryza sativa) | red rice (Oryza sativa) variety |
| sorghum (Sorghum bicolor) | johnsongrass (Sorghum halepense) and shattercane (Sorghum bicolor) |
| wheat (Triticum astivum) | jointed goatgrass (Aegilops cylindrica) (wheat goatgrass hybrids are mostly sterile) |
Another question that is raised is the extent to which the genetic modification actually provides a benefit. As an example, studies have suggested that some of the pest-resistant GM crops do not actually result in a significantly lower amount of pesticides being used on them. Thus, any potential risks of using the technology might not be balanced by sufficient benefits. Also, nature can find a way around the genetic modifications. For example, with increasing sowing of the Roundup ready crops, this particular herbicide is being very extensively used; so weeds resistant to that pesticide are turning up.
Perhaps the biggest ethical problem is the one of the "slippery slope." Genetic engineering has definitely provided some benefits and also appears to have many more benefits to offer as the technology progresses. Companies and governments may rush into production one or more products of the new technologies that will turn out to be harmful, either to the environment or to humans directly. Consider, for example, a country where a large part of the population is starving (example: North Korea) and where researchers might find a way to vastly increase the yield of a crop or the nutritional benefits of a food. There would be a lot of pressure to move quickly to put this GM crop into commercial use, and to downplay any objections raised (as well as to consider that any problems that might arise could be resolved later). These genetically modified organisms are not always confined to the country where they are being used (particularly in the case where pollen is spread by the wind). Who knows what kind of ecological disaster might arise from failure to consider the unintended consequences. Similarly, when bacteria are used in batch cultures to produce proteins (as in the case of producing insulin), often the bacteria is one that is commonly found in nature (e.g., E. coli). If it escapes into the environment, could it then cause problems? Might these organisms be inadequately safe-guarded in some countries?
Objections that do not involve the biology of genetic alterations might still be mentioned here in passing, such as the consideration of economics and society. The leading technologies and the ability to make use of them on a large scale is often dominated by countries with the greatest wealth or companies with patent protections. There is some concern that the utilization of the technology and the economic benefits may not be equitably shared. This is not unique to genetic modification, but because of the diversity of genetic work that can be accomplished with the state of the art technology and production facilities, there is definitely a concentration of power in certain areas of the world.
Genetic modification has become a routine part of biotechnology, and it is being increasingly relied upon. In certain areas, such as producing drugs and food-modifying enzymes, the potential for serious problems to arise seems small, but when used in food crops, there are some evident dangers from the fact that these crops become so widespread in the world environment. The level of alarm felt by some people about risks from eating these food crops is most likely exaggerated. However, as the technology develops further, attention must be paid to possible rare adverse responses to foods, especially allergenic responses, before commercial production begins.
The apprehension about environmental problems, even disasters, is a valid issue that must be addressed carefully and is a matter of investigation for researchers in this field. The issue of the safety and value of GM crops has been especially expressed in Europe and parts of Asia with the result that it has slowed the process of regulatory approvals. One consequence of such actions is that it has led to segregating crops so that non-GM crops can be exported when necessary. This particular manifestation of GM-worries is not entirely based on biology, ethics, or true fear of the crops; sometimes this is a mechanism to control trade. For example, if France wanted to reduce its import of soybeans from the U.S. and rely more on its own farmers, its government can restrict the use of GM soybeans, in which case it is difficult for the U.S. (where 85% of the soy crop is GM) to ship any to them. So, when fears about GM products are expressed, one should examine some of the motivations behind them.
Even if there are some irrational fears or political considerations, this should not detract from our understanding that genetic modification is a new technology and there are specific problems that can already be observed. Considering the rapid advances in this field and the sudden emergence of GM organisms into commercial production, the chance for negative consequences becomes significant, especially when one takes into account the difficulty of carefully controlling the process of development in some parts of the world.
December 2005
It is important to become educated about the biology and technology behind genetic modification, and to make decisions appropriately. Among the decisions are consumer choices, supporting the activities of educational organizations, supporting or rejecting certain political actions on the subject, and becoming directly involved in the field.
The following outline of benefits and controversies concerning GM products was posted by the Human Genome Project Information site (illustrations added from other sources):
(http://www.ornl.gov/sci/techresources/Human_Genome/home.shtml)
Crops
Animals
Environment
Society
Safety
Access and Intellectual Property
Ethics
Labeling
Society
