Topics

• The quote in the title of this lecture is from Gertrude Stein (1874 - 1946) ( see, for example Gertrude Stein, 'A rose is a rose … ' Several Times Over ). Of course, besides waxing poetic about roses, one could also say, more prosaically "a tomato is a tomato is a tomato" or "corn is corn is corn." Until quite recently, these would have been rhetorical or poetic statements. Sure, there are many varieties of tomato, and of corn, and so on, but each one of these organisms was well defined and distinguishable from other varieties of the same species. Now, genetic engineering has changed all that. The purpose of this lecture is not to review genetic engineering at large, but only insofar as it relates to the phenomenon now known as genetically modified plants for food use and human health, or GMOs.

   

  

  Natural Biodiversity: Corn

   

  Good starting points for our investigation are two reports, the first issued in September 1998 and the second in February 2002, by the Royal Society in the UK. The reason for choosing them from among the vast literature on the subject, is that they are the work of a group of independent and eminent scientists, they are quite comprehensive, and they are largely written in relatively plain language. The reports are available as pdf files:   Genetically Modified Plants for Food Use and Human Health  and   Genetically Modified Plants for Food Use and Human Health: An Update.
  Another important resource is an article by Richard Lewontin,   Genes in the Food!", which first appeared in The New York Review of Books of June 21, 2001, and has been reprinted in his book It Ain't Necessarily So: The Dream of the Human Genome and Other Illusions, New York Review Books, NY, 2000, 2001. Second Edition. This article too is written in plain language, but it does something that few other reports, article and books do. It looks at genetic engineering in agriculture in the context of the history of agriculture in the last hundred years, which has been "a history of the increasing dominance of industrial capital over farming [ … ] The consequence of the growing dominance of industrial capital in agriculture for the classical 'family farm' has been the progressive conversion of the independent farmer into an industrial employee [ … ] The creation and adoption of genetically modified organisms are the latest steps in this long historical development of capital-intensive industrial agriculture. Roundup Ready herbicide-resistant soybeans have been created by Monsanto so that farmers will be able to use its powerful herbicide, Roundup, while at the same time buying Monsanto seed."
  For more resources I suggest you check the links provided by DMOZ, the Open Directory Project. In particular, the section on Genetically Modified Food. Notice that, since the whole GMO issue is a contentious one, just like, say, global warming, you must be careful in evaluating the resources found, and try to spot the vested interests, the political motivations, etc., which often distort scientific findings to a very considerable extent.
  A very recent report by FAO (the UN's Food and Agriculture Organization), entitled The State of Food and Agriculture, 2003-2004. Agricultural Biotechnology: Meeting the Needs of the Poor? presents a thorough re-evaluation of the issues. Read in particular 9. Conclusions: Meeting the Needs of the Poor. Meanwhile, the European Union has lifted a ban on genetically modified crops. Read for example EU Approves Three GM Maize Lines: "The ruling follows the ending of the six-year moratorium on genetically modified products by the EU in May 2004. The decisions on these products bring the total number of genetically modified strains approved under the EU to nine. All three types of maize must only be used in line with EU labelling and traceability rules, so that any product containing them will have to clearly state that is contains genetically modified ingredients."
• What are Genetically Modified Organisms (GMOs)? A GMO is an organism, such as for instance a corn plant or a mouse, the genome of which has been altered, for example by adding one or more transgenes, i.e. genes taken from another organism, in the hope that the host plant will display certain characteristics of the donor. Notice that this technology goes well beyond hybridization: in other words, the transfer can be made between two species which can not be bred naturally, say a fish and a tomato. Here is an example.

  "Agrobacterium tumefaciens causes crown gall disease of a wide range of dicotyledonous (broad-leaved) plants, especially members of the rose family such as apple, pear, peach, cherry, almond, raspberry and roses. A separate strain, termed biovar 3, causes crown gall of grapevine.

  The disease gains its name from the large tumour-like swellings (galls) that typically occur at the crown of the plant, just above soil level. Although it reduces the marketability of nursery stock, it usually does not cause serious damage to older plants. Nevertheless, this disease is one of the most widely known, because of its remarkable biology. Basically, the bacterium transfers part of its DNA to the plant, and this DNA integrates into the plant’s genome, causing the production of tumours and associated changes in plant metabolism.

  The unique mode of action of A. tumefaciens has enabled this bacterium to be used as a tool in plant breeding. Any desired genes, such as insecticidal toxin genes (see Bacillus thuringiensis) or herbicide-resistance genes, can be engineered into the bacterial DNA and thereby inserted into the plant genome. The use of Agrobacterium not only shortens the conventional plant breeding process, but also allows entirely new (non-plant) genes to be engineered into crops. [ from Biology and Control of Crown Gall ].

  B. thuringiensis (commonly known as 'Bt') is an insecticidal bacterium, marketed worldwide for control of many important plant pests—mainly caterpillars of the Lepidoptera (butterflies and moths) but also mosquito larvae, and simuliid blackflies that vector river blindness in Africa. Bt products represent about 1% of the total ‘agrochemical’ market (fungicides, herbicides and insecticides) across the world. The commercial Bt products are powders containing a mixture of dried spores and toxin crystals. They are applied to leaves or other environments where the insect larvae feed. The toxin genes have also been genetically engineered into several crop plants (see Agrobacterium)." [ from Bacillus Thuringiensis ]

  Using techniques like those described above, companies such as Monsanto, have developed certain crops (e.g. canola), called Roundup Ready, which are resistant to weed killers and other herbicides and insecticides (Roundup is one such product, also developed by Monsanto). Other transgenes can confer different properties to the crops so engineered, such as a greater resistance to low temperature, a shape better suited for packaging, etc. Here is an excellent resource: The Science Behind GMOs.

   

  

  How to Make a Cold-Resistant Tomato

   

• Let's now return to the Royal Society's reports, specifically to (a slightly abridged version of) the summary of the more recent document:
  1. "In 1998 the Royal Society published a report, Genetically modified plants for food use, which concluded that the use of genetically modified (GM) plants had the potential to offer benefits in agricultural practice, food quality, nutrition and health, but that there were several aspects of GM technology that required further consideration. The Royal Society appointed a group of experts to update this report based on research since 1998. This update focuses on the effects that GM foods might have on human health and the use of the principle of substantial equivalence in GM food safety testing.
  2. Few, if any, GM food products are currently available to buy in Europe and the UK. Commercial varieties produced elsewhere, in the USA and Canada for example, are designed to confer resistance to pests and to produce tolerance to specific herbicides. Over the next decade biotechnology will be aimed at improving many qualities of crops, including nutrition and agronomic performance. We support the continuation of research in this area as valuable in itself and as the only way to assess the true potential of GM plants.
  3. We endorse the conclusions of the 21st report of the Royal Commission on Environmental Pollution (1998) that scientific assessments must inform policy decisions but cannot pre-empt them, and that public opinion must be taken into account throughout. We believe that the public debate about GM food must take account of wider issues than the science alone. We also wish to stress the importance of informing debate with sound science.
  4. We have some concerns about the regulatory processes governing the development and use of GM plants. We agree with the FAO/WHO 2000 report that the criteria for safety assessments should be made explicit and objective …
  5. In the future safety assessments of GM and non-GM foods could make use of various new profiling techniques. Long-term research is required before these techniques can be applied. We recommend that research should continue to develop such technologies and thereby define the 'normal' compositions of conventional plants …
  6. One potential application of GM technology is to improve the nutritional quality of crops. It is possible that GM technology could lead to unpredicted harmful changes in the nutritional status of foods (MRC, 2000). Such alterations might also occur in the course of conventional breeding. Nutritional assessments are made as part of the safety assessment of GM crops, but more detailed guidelines would be beneficial. Vulnerable groups such as infants need special guidelines. To date no GM food for use in infant products has been submitted for approval. Detailed guidelines and legislation already exist for infant formulas and follow-on foods but it is not clear how they interact with GM food regulations …
  7. There is at present no evidence that GM foods cause allergic reactions. The allergenic risks posed by GM plants are in principle no greater than those posed by conventionally derived crops or by plants introduced from other areas of the world. One shortcoming in current screening methods, which applies to both conventional and GM foods, is that there is no formal assessment of the allergenic risks posed by inhalation of pollen and dusts. We therefore recommend that current decision trees be expanded to encompass inhalant as well as food allergies.
  8. Plant viral DNA sequences are commonly used in the construction of the genes inserted into GM plants, and concern has been expressed about this. Having reviewed the scientific evidence we conclude that the risks to human health associated with the use of specific viral DNA sequences in GM plants are negligible.
  9. One concern associated with GM foods is the possibility that genes introduced into GM plants might become incorporated into the consumer's genetic make-up. Since the Royal Society's 1998 report various papers have been published on this topic. The results need to be viewed in the context of a normal diet, which for humans and animals comprises large amounts of DNA. This DNA is derived not only from the cells of food sources, but also from any contaminating microbes and viruses. Given the very long history of DNA consumption from a wide variety of sources, we conclude that such consumption poses no significant risk to human health, and that additional ingestion of GM DNA has no effect."
  I must warn you that not everybody has accepted the conclusions summarized here, particularly items 7. and 8. I also want to point out a few important items which were included in the original report, but not in the update:
  1. "The uptake of genes via the food chain is not a new issue because genes (ie DNA) are normal constituents of the human diet. Many products from GM plants, such as sugar prepared from GM sugar beet, are absolutely identical to conventional products. Others such as GM tomato paste are so similar that they are regarded as 'substantially equivalent.' Others, for example flour from GM soya, may contain a new gene or its product, although many of the purification processes involved in food production will destroy any DNA present in the raw material.
  2. Some GM foods have been produced using an antibiotic resistance 'marker' gene, which is a laboratory device designed to identify genetically transformed plants. The Society is concerned about the use of such genes in food products and we support the Government’s advisory committees which concluded that any further increase in the use of such markers in the human or animal food chain would be undesirable.
  3. GM crop plants have been produced to improve insect tolerance and virus resistance, and to include herbicide tolerance, so that other plants such as weeds may be eradicated without harming the crop species. To ensure that unwanted side-effects are not transferred to non-target species of plants and that the development of resistance by target pests is minimised, the regulatory authorities must be assured that (i) any negative effects would be no greater than those resulting from conventional procedures; (ii) any long-term effects on the environment and ecology would be closely monitored, with statutory restrictions in place to control marketing; and (iii) best practice advice was adopted by growers."
  For a taste of the controversy, read the GMOs Q & A, published by the University of Illinois; Genetic Modification and Food, issued by the Institute of Food Science & Technology; GMOs and BSE : The Europeans’ View ;  Europe to Demand Strict Molecular Characterisation for GMOs? (where you can find other interesting articles). These documents span much of the spectrum of opinions concerning GMOs.
• Let us now examine the major questions that GMO technology raises. As the Royal Society, among others, points out in all its reports, "the public debate about GM food must take account of wider issues than the science alone." [ item 3 in the summary of the update ].
  One consideration which should be paramount, yet is seldom explictly mentioned, is that genes are not like loose marbles in a bag. The genome is a complex piece of machinery, the components of which interact with and regulate each other in ways which are still incompletely known. Therefore we do take potentially huge risks when we simply transfer one gene from one organism to another, since the 'genetic environment' of this gene will be generally different in the two organisms. Such differences may show up only in later generations of the modified organism. They may also show up in ways we are not looking for. Their effects may not be immediate, but cumulative, etc.

  "If we had the complete DNA sequence of an organism and unlimited computational power, we could not compute the organism, because the organism does not compute itself from its genes [ … ] There exists, and has existed for a long time, a large body of evidence that demonstrates that the ontogeny of an organism is the consequence of a unique interaction between the genes it carries, the temporal sequence of external environments through which it passes during its life, and random events of molecular interactions within individual cells. It is these interactions that must be incorporated into any proper account of how an organism is formed." [ from Richard C Lewontin, The Triple Helix: Gene, Organism, and Environment. Harvard UP, 2000. ]

  In other words, an organism is not put together as in a Lego set.
  A second consideration is that the modified organisms are usually grown in areas adjacent to or not far from other crops as well as wild areas. We know the role played by the elements (wind, rain, etc.) and by other species in dispersing seeds, spores, pollen, etc. over vast areas. Even if a genetically modified crop could be shown to be perfectly safe for human consumption, its impact on the ecosystem within which it is grown is rather unpredictable, and we know how sometimes even seemingly insignificant alterations of an ecosystem can bring about, usually not immediately, drastic changes, which may or may not be beneficial.

  "The likelihood of gene transfer to wild relatives therefore depends on the species of crop and the location in which the crop will be grown. For example, relatives of oilseed rape can be found growing near crops in the UK, whereas cereal relatives are rare. It may therefore be necessary to take special measures with the former.

  If gene transfer is judged to be likely, then it is important to assess what the consequences will be. This will depend on whether the inserted genes are likely to have a deleterious or advantageous effect as a result of expression in the plant to which they are transferred, if expressed in the wild species." [ from update ]

  For some ominous news, read GM Crops Created Superweed, Say Scientists.
  A third consideration:

  "Inserted genes may have potentially harmful effects if transferred to other crop plants. For example, genes for production of vaccines or pharmaceutical products in food plants should be prevented from entering the general food chain, by molecular methods (such as prevention of pollen formation) or by growing the crop at an isolation distance that minimises pollen transfer. This is normal practice for plant breeders and farmers who must enforce strict isolation distances when producing certified seed for sale. Also, for example, oilseed rape is grown for human consumption with low levels of erucic acid. Industrial oilseed rape produces high levels of erucic acid, which is toxic to humans. High erucic acid oilseed rape is therefore grown at suitable isolation distances from edible rape varieties." [ from update ]

  A related and fundamental concern is the issue of antibiotic resistance genes in GM foods:

  "When researchers wish to insert a new gene into a plant, for example to express a protein that will make the plant resistant to a specific insect pest, it is often linked to another gene known as a 'marker gene.' During the late 1980s, genes for resistance to a range of antibiotics were introduced as markers for selection. The marker genes are used to make it easier to select in the laboratory the cells, and subsequently the plants, in which the genes have been successfully inserted. Plants that contain a gene for resistance to an antibiotic will grow on material that contains that antibiotic, whereas if the genes have not been successfully inserted the plants will not grow. Because the 'marker gene' is linked to the other gene, those plants that have grown on the antibiotic will also contain the gene for resistance to the insect pest. The most commonly used antibiotic resistance marker genes in GM plants confer resistance for such purposes to kanamycin or hygromycin. In GM bacteria, ampicillin resistance marker genes are more often used.

  The use of antibiotic resistance as a marker for selection in GM plants for human or animal consumption has resulted in the fear that these genes may be transferred into the bacteria present in the stomach of the consumer. If this were to happen then the genes might be transferred from these bacteria into bacteria that cause disease in humans, making them resistant to the antibiotics that are usually prescribed. It is likely that if transfer occurs, it would only occur following consumption of the unprocessed GM plant, since processing of food causes DNA present in the food to be degraded. Further research is necessary to determine whether such gene transfer could occur, and to what extent."
  [ from from update ]

  In this regard, techniques have been developed which reduce the risk of unintended gene transfer. For example extra genes are inserted in the GMOs which turn off pollen production, effectively rendering the crop sterile. This can also be achieved by means of the so-called terminator technology. See for example The Terminator. A Seedy Venture: 'It Won't Be Back'. Particularly in developing countries, farmers have voiced strong opposition to such technology, which forces them to buy new (terminator) seeds every year, violating one of the most fundamental principles of agriculture. See, for example, the various discussions at the International Institute for Environment and Development.
  The list of concerns is quite long, and I will mention here just the headlines, referring you to the resources cited for further details: can GMOs alter our genetic makeup via the food chain? can GMOs create serious dangers for people suffering from allergies? will GM crops harm the environment and/or affect other plants and animals? will GMOs further reduce biodiversity, already damaged by our bad environmental practices?
  The last question is very important. See for example Biological Diversity in Food and Agriculture, or Values of Biodiversity (chapter 7 of an excellent hypertext book by Peter J Bryant, Biodiversity and Conservation). One of the problems with commercial crops in general, and GMOs in particular, is that they force farmers to replace the varieties they have slowly adapted to their local environment over many generations with a very limited number of commercial varieties, which are supposed to be suitable for a broad range of environmental conditions. This has happened for example with potatoes in Peru and other countries, with wheat in Europe, and so on. The result has been far from impressive, and in several places farmers have returned to their traditional varieties (if they were lucky enough to have kept samples).
  More generally, here is one of the final points emphasized in the Royal Society reports:

  "There are concerns amongst some consumers about the addition of GM crop plants to food, because ingredients derived from GM crops are beginning to be used in food manufacture. However, the difficulty in guaranteeing segregation of GM and non-GM commodity crops, such as soya and maize, due to long distribution lines between growers and consumers and differing regulations between producer countries, is causing severe problems with attempts to offer consumer choice through clear labelling. It is important for companies to recognise the widespread desire on the part of the consumers to have appropriate labelling of foods."
  [ from from update ]

 
Readings, Resources and Questions

• Read the latest news on the unintended side effect of GM crops in GM Maize Growing 'Needs Review', which reports on the work of Bruce Tabashnik, University of Arizona, and An Interview with Bruce Tabashnik, somewhat older, but quite interesting and relevant.
• A very informative report is the Nuffield Council on Bioethics's Genetically Modified Crops: The Ethical and Social Issues You should also explore the comprehensive Seeds of Conflict, a PBS website with Bill Moyers, which includes links to the Transgenic Crops: An Introduction and Resource Guide and the The National Health Museum Graphics Gallery ("a series of labeled diagrams with explanations representing the important processes of biotechnology").
• One of the unintended side effects of GMOs is on organically grown crops. As the Royal Society original report points out, "If the award of organic certification depends on the grower being able to guarantee that no inserted genes are present, then problems will arise if the crop has been grown in fields adjacent to a GM crop."