GENETIC MODIFICATION AND FOOD

The Institute of Food Science & Technology, through its Public Affairs and Technical & Legislative Committees, has authorised the following Information Statement, dated 27 July 2004, replacing the Statement of September 1999 and any previous version.

SUMMARY

Genetic modification (GM) has the potential to offer very significant improvements in the quantity, quality and acceptability of the world's food supply.

Food scientists and technologists can support the responsible introduction of GM techniques provided that issues of product safety, environmental concerns, information and ethics are satisfactorily addressed. IFST considers that they are being addressed, and need even more intensively to continue to be so addressed. Only in this way may the benefits that this technology can confer become available, not least to help feed the world's escalating population in the coming decades.

Introduction and definitions

Food biotechnology is the application of biological techniques to food crops, animals and micro-organisms to improve the quality, quantity, safety, ease of processing and production economics of food. It thus includes the traditional food manufacturing processes used for bread, beer, cheese and various fermented milk products.

A relatively more recent (i.e. starting about 25 years ago) application of biotechnology to food is genetic modification (GM), also known as genetic engineering, genetic manipulation, gene technology and/or recombinant DNA technology. The collective term "Genetically Modified Organisms" or GMOs is used frequently in regulatory documents and in the scientific literature to describe plants, animals and micro-organisms which have had DNA introduced into them by means other than by combination of an egg and a sperm or by natural bacterial conjugation.

Random genetic variation occurs naturally in all living things and is the basis of evolution of new species through natural selection. Even before its scientific basis was understood, mankind took advantage of this natural variation by selectively breeding wild plants and animals and even micro-organisms such as yogurt cultures and yeasts, to produce domesticated variants better suited to the needs of humans. Such selective breeding involves the transfer of unknown numbers and kinds of genes between individuals of the same species. Before the advent of GM technology, however, so-called "traditional" or "conventional" breeding technology involved far more than the foregoing. Over the past half-century it also included techniques involving polyploidisation and mutagenesis via x-rays, which are far more disruptive of the original plant genes than any GM modification. For example barley seeds (Golden Promise) were treated with x-rays in the Winfrith reactor in 1956 to yield the UK's favourite variety for brewing -- and this variety is also used in the production of organic beer.

Many changes to food materials brought about by gene technology are no different in essence from those which can take place in nature or by selective breeding, except that the gene technologist transfers a carefully targeted selected few specific genes, thus drastically reducing both their random nature and the time taken to produce an improvement.

Thus, within-species GM involves few fundamentally new issues. However, gene technology also makes it possible to move genes between different species. This property makes the technique revolutionary in terms of the potential benefits that it may bring but it has also caused concern regarding issues of safety, ethics, environmental impact and consumer choice.

Techniques of genetic modification

How is GM technology carried out? In simple terms, the gene technologist uses a "cutting-copying-pasting" approach to transfer genes from one organism to another. For this, bacterial enzymes are used that recognise, cut and join DNA at specific locations acting as molecular "scissors-and-tape". However, the selected gene is copied billions-fold, with the result that the amount of original genetic material in the modified organism is immeasurably small. Since DNA does not always readily move from one organism to another, "vehicles" such as plasmids (small rings of bacterial DNA) may be used; alternatively, some plant cells may be transformed by "shooting" small particles coated with the new DNA into the target cell using a special type of gun, the "Gene Gun". The modified cell can then be used to regenerate a new organism.

However, by currently available methods only small numbers of cells subjected to a genetic modification procedure are successfully modified. Furthermore, the regeneration of whole plants or animals from culture cells may take months or years. Consequently, it is necessary to identify the modified cells in a culture mix using "marker genes" closely linked to the genetic material to be transferred. Antibiotic resistance has often been used to "tag" genes so that they can be detected easily and rapidly at the cellular level in the laboratory, providing a basis for selection. The use of antibiotic resistance marker genes (ARMG) has, however, been a source of concern.

Although the transfer of antibiotic resistance from a marker gene contained in a GM plant to a microorganism normally present in the human gut has not been demonstrated experimentally, it has been suggested that the potential risk, however small, of spreading resistance to therapeutic antibiotics could have serious health consequences and therefore should be avoided. In the absence of reliable data, the UK Advisory Committee on Novel Foods and Processes (ACNFP) erred on the side of caution and recommended some years ago against the use of antibiotic resistance marker genes.

However, on 4 February 2004 a Working Party of the British Society for Antimicrobial Chemotherapy http://www.bsac.org.uk/ stated

"There are no objective scientific grounds to believe that bacterial antibiotic resistance genes will migrate to bacteria to create new clinical problems."

They looked at various routes "but are unable to identify a credible scenario whereby new drug-resistant bacteria would be created". However they point out  that the theoretical possibility of transfer by novel mechanisms cannot be entirely ruled out, and so consider whether transfer of the three drug resistance genes that have been used would pose a threat to antibiotic use in medical treatment. These 3 genes are common in bacteria, and found on mobile elements that move between DNA molecules and bacterial cells, and this gene mobility has already compromised clinical use of the antibiotics.

"The argument that occasional transfer of these particular resistance genes from GM plants to bacteria would pose an unacceptable risk to human or animal health has little substance. We conclude that the risk of transfer of AR genes from GM plants to bacteria is remote, and that the hazard arising from any such gene transfer is, at worst, slight."

The Working Party goes on to ask "Can a blanket ban on cultivation of GM plants carrying bacterial drug resistance genes be justified, even in part, because of extremely improbable, unquantifiable concerns?". They argue that a precautionary principle approach that argued that such a negligible risk must prevent the use of plants containing such genes, must be set against a pragmatic approach that takes account of the size of the risk and hazard and also the potential benefits of GM plants, such as reduced pesticide use. While the Working Party believes that the evidence means that most bacterial AR genes would be safe, they "consider it extremely undesirable and unnecessary to extend the list of AR genes approved for GM plant development. In particular, the use of any AR gene that if disseminated widely among bacteria would be likely to compromise use of a front-line or currently widely used antibiotic should be strongly discouraged, if not banned." They note that plant biotechnologists chose not to uses AR genes in this category. And conclude "The moratorium should continue, particularly as alternatives to AR genes are being developed".

On 16 April 2004 the European Food Safety Authority (EFSA) issued a scientific opinion http://www.efsa.eu.int/press_room/press_release/386_en.html   on the subject, classifying those evaluated into 3 groups based on their biological distribution and taking into account the current importance of the antibiotics concerned to human and veterinary medicine ... The EFSA GMO Panel has proposed the following classification for ARMGs:

·     Group 1 ARMGs contains antibiotic resistance genes which (a) are widely distributed among soil and enteric bacteria and (b) confer resistance to antibiotics which have no or only minor therapeutic relevance in human medicine and have only restricted use in defined areas of veterinary medicine. This refers to the antibiotic resistance genes nptII conferring resistance to the antibiotics kanamycin and neomycin with a 13-year history of safe use in food crops and the hph gene which encodes for a protein that inactivates hygromycin, an antibiotic that is not utilised in human clinical medicine. No restrictions are required with this class of marker genes either for field experimentation or for placing on the market ...

·     Group 2 ARMGs contains antibiotic resistance genes which (a) are widely distributed in micro-organisms in the environment and (b) confer resistance to antibiotics which are used for therapy in defined areas of human and veterinary medicine. This group includes genes which confer resistance to chloramphenicol (CmR gene), ampicillin (ampr gene) and streptomycin and spectinomycyn (aadA gene). The use of these genes should be restricted to field trial purposes and not be present in GM plants placed on the market ...

·     Group 3 ARMGs contains antibiotic resistance genes which confer resistance to antibiotics highly relevant for human therapy like the nptIII gene conferring resistance to amikacin and the tetA gene conferring resistance to tetracyclines. Irrespective of considerations about the realistic importance of the health threat, these genes should be avoided in the genome of transgenic plants to ensure the highest standard of preventive health care. Therefore these ARMGs should not be present in GM plants placed on the market or in plants used for experimental field trials.

However, other methods are becoming available. In a development, reported in Science in May 1999, researchers at University of Hawaii demonstrated the use of sperm to transport "foreign" DNA into an egg. It has a relatively high rate of success, is technically simple to carry out, has potential for transferring larger pieces of DNA and is applicable to animals.

Advantages and potential benefits of genetic modification

For the development of improved food materials, GM has the following advantages over traditional selective breeding:

• Allows a much wider selection of traits for improvement: e.g. not only pest, disease and herbicide resistance (as achieved to date in plants) but also potentially drought resistance, improved nutritional content and improved sensory properties
• It is faster and lower in cost
• Desired change can be achieved in very few generations
• Allows greater precision in selecting characteristics
• Reduces risk of random occurrence of undesirable traits.

These advantages could, in turn, lead to a number of potential benefits, especially in the longer-term, for the consumer, industry, agriculture and the environment:

• Improved agricultural performance (yields) with less labour input and less cost input
• Benefits to the soil of “no-till” farming practice
• Reduced usage of pesticides and herbicides
• Ability to grow crops in previously inhospitable environments (e.g. via increased ability of plants to grow in conditions of drought, soil salinity, extremes of temperature, consequences of global warming, etc.) leading to improved ability to feed an increasing world population at a reduced environmental cost
• Improved sensory attributes of food (e.g. flavour, texture, etc.)
• Removal of allergens or toxic components, such as the research in USA to produce a non-allergenic GM peanut (University of Arkansas) and a non-allergenic GM prawn (Tulane University) ; and in Japan, to produce a GM non-allergenic rice.
• Improved nutritional attributes such as:
  • Ingo Potrykus's EU research project jointly funded by the Rockefeller Foundation, resulting in increased Vitamin A content in rice, which will help to prevent blindness among children in Southeast Asia;
  • the announcement in September 2003 by Edgar Cahoon and his team at the Donald Danforth Plant Science Center in Missouri that by inserting a gene extracted from barley into a common type of field corn, they have created a strain that grows with six times the usual amount of vitamin E, a powerful antioxidant.
• Improved processing characteristics leading to reduced waste and lower food costs to the consumer.
• Prevention of loss of species to endemic disease (e.g. the Cavendish dessert banana which is subject to two fungal diseases that have struck Africa, South America and Asia, but could be reprieved by GM development of a disease-resistant version).

GM has huge potential for mankind in medicine, agriculture and food. In food, the real benefits are not the early instances that have been appearing so far, but its longer-term benefit to the world - and especially the developing countries - its potential for developing crops of improved nutritional quality, and crops that will grow under previously inhospitable conditions (see above), thereby contributing to alleviating hunger and malnutrition, while helping to prevent the otherwise inevitable future pressure to encroach on natural resources. Even today, there are 840 million people. 800 million of them in the developing countries and 200 million of them children, who regularly do not receive enough food to alleviate hunger, still less provide adequate nutrition. 24,000 people die of malnutrition-related causes daily. That situation will be greatly worsened as a result of the world's escalating population over the coming decades.

There are those who allege that “scientists claim that GM will solve the problem of world hunger”. This is a familiar "straw man". It is frequently argued by some that there is more than enough food to feed the world and all that is needed is "fairer distribution" (which so far mankind has signally failed to achieve) – or a variant of that, "the real problem is not shortage of food, it is poverty". Whatever may be done by way of improved yields through conventional methods, attempted population control and more effective distribution would, however, be inadequate for the future. There are probably enough cereals to feed the present world population (if only they could be distributed to the right places at the right times and could be afforded). But there will be substantial shortfalls in cereals in the next two decades. Moreover, "world hunger" is a complex not only of inadequate quantity where it is needed but of inadequate quality i.e. for vast numbers of people the lack of foods with the necessary micronutrients and of clean water, for reasonable nutrition and health.

However, In decades to come, with the expected substantial increase in the world population, mostly in the poorest, least developed countries, the demand for increased agricultural land and for water will greatly increase. The important point is not only how to feed the world now but addressing and trying to solve the problem of "How shall mankind feed the world in a few decades from now?". Of course the problem that has huge political and economic dimensions will not be solved by GM alone, or even by science alone -- but will certainly not be solved without the contribution of science, including GM.

Food scientists and technologists can support the responsible introduction of GM techniques provided that issues of product safety, environmental concerns, ethics and information are satisfactorily addressed. so that the benefits that this technology can confer become available both to improve the quality of the food supply and to help feed the world's escalating population in the coming decades.

Current GM foods and food ingredients

The "first generation" of GM food materials were those that were relatively easy to do, chosen for their likelihood of rapid commercial success by providing traits that would commend themselves to farmers. Consequently, most of the 80+ crops that have been modified and the 25,000+ field trials that have taken place world-wide to date have involved crops engineered for agronomic traits. The first food plants to be grown on a commercial scale and put on the market were the GM maize resistant to the European corn-borer, a serious agricultural pest, and the soyabean genetically-modified to be tolerant of the herbicide glyphosate. The latter involves one or two applications of a less toxic, more rapidly broken down herbicide than the spraying regime that it replaces, that of several applications of different herbicides.

However, these GM products did not offer consumers a readily perceivable benefit “at the point of purchase”; and with intensified campaigns and media amplification in the early part of 1999 and thereafter highlighting problems and uncertainties (some real, some pure speculation, some spin-doctored and some urban myths), the UK public became turned against GM. Reacting to their customers' views, major retailers and manufacturers decided to exclude GM foods and ingredients.

An incidental victim was the canned tomato puree, prominently labelled "Produced from genetically modified tomatoes", on sale in stores of two major supermarket groups in competition with non-GM tomato puree. The GM tomato puree was of better flavour and consistency, cheaper, and consistently outsold the non-GM puree. It is now no longer available

Chymosin, produced by GM micro-organisms, was developed to replace rennet, the milk-clotting enzyme used extensively in cheese-making, due to the severe shortage of the traditional source of the enzyme (i.e. calf stomachs). The GM enzyme, defined as a processing aid rather than a food additive in regulatory terms, has been in use since the late 1980s in the USA and in some European countries, including the UK. It is not clear whether it will survive in the current climate.

What are the concerns about GM?

Increasingly at the heart of the "concerns" debate about GM, is the fundamental matter of the role of science and society in relation to "new" science-based developments such as GM.

There are two ways of dealing with new developments with associated problems and uncertainties. One is to reject or ban the developments. The other is to address and solve the problems, and to accept that there are no certainties in any aspect of life. Fortunately in the long run mankind has generally adopted the second course, otherwise we would still be living in the Stone Age. Looking at more recent times, there would be no electricity; the first passenger flight would not have taken place, so there would be no air travel; the first surgical operation would never have been carried out so there would be no surgery; the first anaesthesia would never have been used, so there would be no anaesthetics (it is worth recalling that the medical profession of the day prevented Queen Victoria from having anaesthesia with the difficult births of her first seven children ("not natural, not proved safe, not sufficient testing, what about the long term effects?") -- the list could be endlessly extended.. Exactly the same arguments were used in the early decades of the 20th century to try to prevent the legalisation of milk pasteurisation. Fortunately it was eventually legalised and over the last seven decades has saved untold numbers of lives that would otherwise have continued to be lost to milk-borne tuberculosis -- second only to clean water as the most important public health measure ever adopted.

Science depends on gaining knowledge, organising it into a coherent structure, hence improving understanding, and applying it. It is society's tool and method for doing so. However, we can never know everything there is to know about a topic. The one certain thing about life is that nothing in life is certain. Science cannot prove that anything is "safe" (i.e. absence of harm) because "absence of evidence" is not "evidence of absence". So any policy purportedly based on requiring science to prove safety is unrealistic.

In real life, decision and action by society to meet its needs has to be based, not on certainty but on using the best knowledge available at the time, and on skilful selection of areas for urgently needed research. In the absence of certainty it has to involve the combination of risk analysis and the precautionary principle, which are two inseparable sides of the same coin. These lie at the very crux of any discussion on the application of GM.

Risk analysis (RA) consists of

         i.  risk assessment. a task for scientists who are experts both in the topic and in the methodology of risk assessment. Risk assessment should take account of the likelihood of a risk occurring and its seriousness if it does occur, and should be applied not only to a potential course of action, but also to failure to take that action and to alternative courses of action;

       ii.   risk communication, a multi-directional interchange of information between legislators, the scientific community and the rest of society, which should be an ongoing process; and

      iii.   risk management, for legislators to carry out on behalf of society in the light of i and ii.

The relationship involving these three activities in not a linear one but one of dynamic and ongoing interplay.

The precautionary principle (PP) is a concept familiar to, and used by, food scientists and technologists. It is at the heart of the Hazard Analysis Critical Control Point (HACCP) preventive food safety system.

However, various concepts and interpretations of PP abound, and a widely quoted concept regards PP as a preferred alternative to RA and its components. It is important to understand that in real life PP and RA are inextricably linked and need to be pursued hand-in-hand.

A commonly expressed (but unrealistic) approach demands that PP must be invoked

• where the scientific evidence for safety is insufficient, inconclusive or uncertain, or
• where preliminary scientific evaluation suggests that effects on the environment, health or safety may be unacceptable and/or inconsistent with the chosen level of protection;

and PP may be applied without waiting for the reality and seriousness of those risks to become fully apparent.

This fails to recognise that science can never produce conclusive results and cannot deal in certainty, Moreover, experience teaches that the situation envisaged is most likely to arise in areas (such as biotechnology) where there are strong ideological agendas, in pursuit of which some individuals, including, unfortunately, some scientists, present unsubstantiated speculation, assumptions and guesswork as though they were "preliminary objective scientific evaluation". This sometimes takes the form of published purported "research papers" which on scrutiny turn out to be merely the authors' speculations and opinions, complete with references to similar papers by like-minded individuals.

If that sort of presentation is considered enough to bring a development to a halt, and, as we have seen, scientific evidence is always insufficient and science cannot prove anything to be safe, it can then be argued in perpetuity both by its ideological opponents and by scientists who see further research as a funding opportunity, that the development should not be resumed "until we know more".

Purported "preliminary objective scientific evaluation" should, therefore, always be very carefully scrutinised to ensure that there is a broad scientific consensus that it is based on some hard scientific evidence.

On 2 February 2000, the EU Commission issued a "Communication on the Precautionary Principle" It is on-line at http://europa.eu.int/comm/dgs/health_consumer/library/pub/pub07_en.pdf

It is an oft-repeated environmental truism that we hold the world in trust for future generations. It would be a betrayal of that trust and an abdication of responsibility by the present generation if science were to limit itself to collecting and providing information about current biotechnology applications, or if society were to limit itself to arriving at verdicts about them. We (society and scientists as part of society) must not behave as disinterested spectators standing on the sidelines and observing problems that may stand in the way of providing future generations with the potential benefits that GM can offer. We have a duty to address and solve such problems. Science is society’s tool for doing that.

"As for the future, your task is not to foresee it, but to enable it."

[Antoine de Saint-Exupery, The Wisdom of the Sands (1948)]

Thus, the real questions to be answered are not "Is it safe? Is it environmentally friendly?" but "What do we have to do to make it safe? What do we have to do to make it environmentally friendly? " Recognition of that is the touchstone of sincerity and objectivity.

A joint report on "Transgenic Plants and World Agriculture" was published in July 2000 jointly by the Brazilian Academy of Sciences, the Chinese Academy of Sciences, The Indian National Science Academy, the Mexican Academy of Sciences, the National Academy of Sciences of the USA, The Royal Society (UK) and the Third World Academy of Sciences. It is available in printed form, published by The Royal Society, and it may be accessed on-line as a pdf file at http://www.royalsoc.ac.uk/policy/rep_fr.htm

The US organization, the Center for Science in the Public Interest (CSPI), which is no friend of corporations or of US regulatory agencies, issued a report in November 2001, primarily from a US perspective, entitled "Genetically Engineered Foods: Are They Safe?" but which also included environmental considerations. It mainly took the form of Questions and Answers by the co-directors of the Biotechnology Project at CSPI. The full text can be accessed on-line at https://cspinet.safeserver.com/nah/11_01/index.html

However, their "bottom line" conclusions were as follows:

1.       The genetically engineered foods that are currently on the market are safe. By increasing yields and reducing the use of pesticides, they benefit farmers and the environment.

2.       To ensure that new genetically engineered plants and animals are safe for humans and the environment, Congress should institute a mandatory government approval process that is open to public participation and review.

3.       The Environmental Protection Agency (EPA) should monitor the environmental impact of genetically engineered crops. It should require more field testing, enforce insect refuges for Bt crops, and adopt other environmental safeguards.

4.       The U.S. government should fund more research on genetic engineering, especially on fruits, vegetables, and other crops that are not of great commercial interest to the biotechnology companies.

5.       To enable developing nations to benefit from biotechnology, the U.S. government should:

o        fund research and the training of scientists,

o        help countries develop regulations to ensure the safe use of genetic engineering to produce food, and

o        press biotech companies to donate technologies and allow free access to patents that are used to produce genetically engineered seeds and animals.

On 21 February 2002, the US National Academy of Science (NAS) issued its report Environmental Effects of Transgenic Plants. The report, which was commissioned in January 2000 by USDA’s Animal and Plant Health Inspection Service (APHIS), reviewed the scope and adequacy of the APHIS component of the Federal regulatory framework for biotechnology. As requested, the report evaluates the evolution of APHIS’ regulatory program, assessed the effectiveness of changes that APHIS had made to improve the program over the years, and made recommendations for further refinements, particularly involving three processes: notification, permitting and petitioning for non-regulated status. On 2 August 2002, USDA's Animal and Plant Health Inspection Service (APHIS) announced the creation of the new "Biotechnology Regulatory Services" (BRS) Unit within APHIS "to focus on USDA's key role in regulating and facilitating biotechnology".

The full news release is at http://www.aphis.usda.gov/lpa/press/2002/08/bioreorg_brs.html

The World Health Organization has issued "20 Questions on Genetically Modified (GM) Foods". These questions and answers have been prepared by WHO in response to questions and concerns by a number of WHO Member State Governments with regard to the nature and safety of genetically modified food.

Safety considerations

When introducing any new technology, including gene technology, into the food chain, there is a need to adopt appropriate safeguards to protect human health. Most countries in the Western hemisphere started developing regulatory controls well before any GM foods reached the market. These controls were put in place not because safety problems had been identified but because of a lack of familiarity with GMOs. Although many of the early concerns regarding the safety of GM foods have not materialised, the precautionary approach has continued as it remains important to ensure that no new hazards are created.

When considering safety in relation to GM, generalisations cannot validly be made. Instances have to be considered and studied in a case-by-case approach, and each case should be assessed in relation to the food involved, as ready for consumption, whether by man or by animals.

Regulations in most countries, including the UK, include the concept of substantial equivalence. This concept was developed in the late 1980s by several national regulators and refined and given international recognition by the Organisation for Economic Co-operation and Development (OECD) in 1993 and further developed by the FAO/WHO Consultation in 1996 with particular reference to foods produced by modern biotechnology (fully detailed on the Web sites of FAO and the UK Advisory Committee on Novel Foods and Processes (ACNFP)).  The concept is based on the idea that existing organisms used as food or food sources can serve as a basis for comparison when assessing the safety for humans of modified foods or ingredients. If a new food or component is considered to be substantially equivalent to an existing food or component the theory is that it can be treated in the same manner with respect to its safety and nutritional assessments.

Acceptability or non-acceptability is established by determining whether a novel food is substantially equivalent to an analogous conventional food in terms of composition, nutritional properties, toxin and allergen content, the amount consumed, the type of processing (industrial or domestic) that the food might undergo and consumption by vulnerable groups of people (e.g. infants and the elderly). Foods are assigned to three categories:

1.       Products that are shown to be substantially equivalent to existing foods or food components

2.       Products that are substantially equivalent to existing foods or food components except for defined differences

3.       Products that are not substantially equivalent to existing foods or food components

Where differences are identified, extensive animal feeding and toxicological trials are required. The establishment of substantial equivalence is an analytical exercise which has to be approached carefully. The comparison may be a simple task, or very lengthy, depending upon the nature and experience with the foods or components being compared. It must also contain a dynamic element to take into account that the continuing modification of a food will require that the most recent novel food is compared with an appropriate former novel food and not necessarily with the original and traditional counterpart.

An understanding of substantial equivalence is key to understanding the basis of GM regulatory controls. This brief outline may be supplemented by studying the text of the Report of the Joint FAO/WHO Consultation on Biotechnology and Food Safety http://www.fao.org/es/ESN/food/pdf/biotechnology.pdf

The question of antibiotic resistance marker genes (ARMGs) has been addressed above.

There are no inherent grounds for assuming that GM foods are more - or less - allergenic than traditional foods. However, when developing any novel foods, including GM foods, care must be taken that allergenicity is not inadvertently introduced into the diet. This requires assessment of the allergenicity of a new protein by predictive methods, experimental testing and a post-marketing surveillance based on traceability.

The testing of GM products for suspected allergens can be done by an IgE test with serum from sensitive individuals [e.g. Herian et al (1990)]. However, there is also a need to test products where genes have been inserted from sources not known to be allergenic. Astwood et al (1996) have developed a method. Stability of a protein or protein fragments to digestion in simulated gastric fluid (SGF) may be used to assess the potential allergenicity of a protein.

The British Medical Association (BMA) in its earlier (1999)  "interim statement" on GM had been hostile to GM and called for an open-ended moratorium on all commercial planting of GM crops until more was known about their effects on human health. Indeed that had been one of the factors influencing the visiting party of Zambian scientists to return to Zambia with recommendations against GM.  "Doubts over the safety of genetically modified foods voiced by the British Medical Association were the main reason behind Zambia's decision to reject food aid in 2002, says a Zambian scientist who visited Europe this week. Famine still threatens 2.4 million people in Zambia today". New Scientist, 29 January 2003. http://www.newscientist.com/news/news.jsp?id=ns99993317 

However in March 2004  the BMA issued a new statement  http://www.bma.org.uk/ap.nsf/Content/GMFoods/$file/GM.pdf

 Announcing it they said 

"The BMA produced an interim report in 1999 on the health implications of  GM food crops. In accordance with our intention to keep the public informed, we held a round table meeting of experts in June 2003 and have recently reviewed the emerging evidence. In producing an update of our 1999 report, the BMA seeks to support balanced debate. As an organisation of doctors, we are not experts in agricultural techniques and crop science, but we are concerned with all issues of public health. The environment in which we live, the air we breathe, the water we drink and the food we eat, all have an impact on our health as individuals. It is this context that the statement has been prepared. The BMA shares the view of the Royal Society that that there is no robust evidence to prove that GM foods are unsafe. However, we endorse the call for further research and surveillance to provide convincing evidence of safety and benefit."

Numerous perceived concerns regarding the safety of GM foods have been aired, many of them speculative and without any scientific evidence, but three substantial concerns which have been most widely discussed are in fact urban myths. These are the L-tryptophan story, the brazil nut allergen story and the events surrounding Arpad Pusztai and his potato experiment.

The L-tryptophan story

A frequently repeated account  alleges GM as the cause of the disease that caused 1500 illnesses and 37 deaths in USA in 1989. The story refers to the so-called Eosinophilia-Myalgia Syndrome (EMS syndrome) associated with some dietary supplements containing the amino acid L-tryptophan.

The illnesses and death did occur, but the rest of the story is untrue. In reality, extensive investigation traced the cause to an impurity in L-tryptophan made by just one of its several chemical manufacturers, all in Japan. The culprit was Showa Denko KK of Tokyo (the fourth largest chemical manufacturer in Japan, but which had some 80% of the market for L-tryptophan). There has been successful litigation by three plaintiffs against SD KK. The GM issue was not raised seriously by the plaintiffs because there was such overwhelming evidence against it being a factor.

The manufacture of L-tryptophan is by a fermentation which also results in the formation of a number of secondary substances. To produce L-tryptophan of a purity necessary for human ingestion, the fermentation product mixture has to go through purification processes to remove the impurities, by-products and cellular debris, including treatment with activated carbon and reverse osmosis. Investigation of the records of Showa Denko KK showed that in the critical period (December 1988 to June 1989) they made a number of simultaneous changes to the manufacturing protocols . One of these was the use of the fermentation organism Bacillus amyloliquefaciens that had been genetically altered to increase the production of L-tryptophan. But this was accompanied by the partial bypassing of the reverse osmosis purification procedure, and a halving of the amount of activated carbon used (both stupid and irresponsible things to have done), thus failing to carry out the purification effectively. Subsequent research showed that in consequence the procedure left behind some sixty impurities; and also found significant correlation between the development of EMS and the reduction of the activated charcoal.

There have been several attempts to explain the precise mechanism by which the syndrome occurred. One involves a residual impurity 1,1 '- ethylidenebis-[tryptophan] (EBT), which then broke down to give 1-methyl-l,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (MTCA), a substance that was thought to have been involved in the EMS syndrome. Another suggests that it was the result of a reaction between two (or more) impurities. Like so many food poisoning outbreaks investigated after the event, the exact mechanism is unlikely now to be conclusively proved, but it was nothing to do with GM. Thus the "tryptophan" story was not a consequence of GM, nor of tryptophan itself, but an impurity or impurities left in as a result of irresponsible short-cutting by a particular chemical manufacturer.

The brazil nut allergen story

With the currently much greater recognition of food allergens as a food safety issue, the possible introduction of allergenicity by genetic modification is a concern; and the apocryphal story of "people made sick by a brazil nut gene transferred into soya" has become a widely believed urban myth.

In fact, such a product never came on the market, and nobody ever ate any such product. Soya protein is deficient in methionine, and a seed company, Pioneer Hi-Bred, wanted to investigate the possibility of producing a soyabean with increased methionine content (thereby improving the nutritional quality of soya protein), by transferring a brazil nut gene to soya. With any research involving any gene transfer, it is routine standard procedure to investigate whether any allergenicity could be thereby transferred. In this instance, many people are allergic (some very seriously so) to soya itself; but it was important to investigate whether such a transfer would make the resulting soya allergenic also to people who were allergic to brazil nuts. The research was carried out at the University of Nebraska, the leading centre for allergenicity research. Perhaps not surprisingly, the researchers found that brazil nut allergenicity was transferred to the experimental material. Pioneer Hi-Bred announced that the research project was discontinued, and the results were published in a peer-reviewed journal [Nordlee et al, (1995)].

The Pusztai potato experiment

This has received considerable publicity. It relates to the purported adverse effects on rats of GM potatoes in which lectins had been inserted, and the associated TV programme and media interviews given by Dr Pusztai. Lectins, which are complex plant proteins, appear to act as pest deterrents in plants and lectin insertion into a crop plant by GM has been investigated as a means of enhancing pest resistance.

The story has been greatly confused by contradictory reports as to exactly what happened, and as to the supposed ill-treatment of the researcher concerned – mostly culled from the media and claims by Pusztai himself and activists keen to exploit the situation. Fortunately there is now a first-hand history available. In March/April 1999 the House of Commons Parliamentary Select Committee on Science and Technology investigated GM, and on Monday 8 March 1999 they held a Hearing at which Dr Pusztai and his friend Dr Stanley Ewen, and Professor Philip James, Director and Dr Andrew Chesson, Head of the Nutritional Chemistry Unit, both of the Rowett Research Institute (RRI), all appeared and were examined.

The written statement submitted by the RRI, which, incidentally, is considerably sympathetic to Pusztai, gives a first-hand historical account (and, incidentally, disposes of the various myths that have been put around about Pusztai and his treatment). For a verbatim account of all the evidence submitted by RRI and by Pusztai himself, and for the Select Committee's conclusions, see UK House of Commons, Select Committee on Science and Technology,
http://www.publications.parliament.uk/pa/cm199899/cmselect/cmsctech/286/9030801.htm
and
http://www.publications.parliament.uk/pa/cm199899/cmselect/cmsctech/286/28602.htm

The study which caused the controversy has since been reviewed twice by the Audit Committee, by the Royal Society; by ACNFP; by the Committee on Toxicity; and by the Nuffield Council on Bioethics. All have found the experiment flawed, poorly designed, and incapable of leading to meaningful conclusions.. There is, however, agreement that adequate in vivo tests need to be developed before a new GM crop with a lectin insert is released for either human or animal consumption.

As the RRI Audit Committee stated

"The research was preliminary and not part of the process of testing specifically genetically modified crops destined for commercial use."

"However, the purpose of the research remains valid. It was part of a larger programme designed to identify possible candidate genes, and their implications, for possible future use in the genetic modification of crops to enhance the crops' resistance to pests."

Whilst investigations into this case have shown that the problems were not directly related to the genetic modification as originally claimed (and still perpetuated by some) they emphasise that a greater awareness of the possible areas of concern is needed when assessing the safety of GM foods.

Environmental considerations

Early regulatory controls over the release of GM crops had, of necessity, been developed on an ad hoc basis due to the virtual absence in the 1980s of quantitative data on the ability of GM organisms to survive in the environment. However, in recent years evidence has accumulated so that regulations and guidelines can now be developed on a more rational basis; but there is a continuing need for studies on the possible risks of GM crops to the agricultural environment In the last few years, the UK Government has responded to this need by funding over 20 projects in this area at a cost of over £6 million. Clearly, regulations will need continuous revision and updating as new data become available.

In the EU Member States, any release of GMOs into the environment is governed by national regulations implementing EU Directive 90/220/EEC (now superseded by Directive 2001/18/EC) (implemented in the UK as part of the Environment Protection Act). In the UK, at present there are no GM crops being commercially grown. An experimental release, such as a field trial of a food crop, requires consent from the Government. Applications for consent must include a considerable volume of data and a detailed assessment of the risk of harm to human health and the environment. If a risk is identified or there is some uncertainty about the level of risk, the applicant may propose measures to manage or eliminate the risk. The applications are scrutinised by the Advisory Committee on Releases into the Environment (ACRE), a group of independent experts who advise the Government on whether consent should be given and whether extra conditions should be imposed prior to giving consent. All releases are advertised locally and details are made available via a Public Register. Release sites are subject to inspection by the Health and Safety Inspectorate and those making the release are required to report any incidents that may occur during and after the completion of the trials. On the one hand this openness and transparency is admirable, but on the other hand the public information has been seized on by organised gangs of terrorist activists who invade and destroy the trials.

The EU objective has been to protect health and the environment when

• carrying out the deliberate release into the environment of GMOs for any purposes other than placing on the market within the European Community
• placing on the market GMOs as, or in, products within the European Community

Data required other than for higher plants:

1.       Information relating to the GMO characteristics of donor, recipient (or where appropriate parental) organisms characteristics of vector characteristics of modified organism

2.       Information relating to the conditions of release and receiving environment information on the release information on the environment

3.       Information relating to the interactions between the GMO and the environment characteristics affecting survival, multiplication and dispersal interactions with the environment

4.       Information on monitoring, control, waste treatment and emergency response plans.

Data required for GM higher plants:

1.       Information relating to recipient and / or parental plant

2.       Information relating to the genetic modification

3.       Information relating to the GM plant

4.       Information relating to the site of release

5.       Information relating to the release

6.       Information on control, monitoring, post-release and waste treatment plans

Since 1987, more than 25,000 field trials of GM plants have been carried out in 45 countries without adverse environmental consequences. Furthermore, the rate of field-testing has increased rapidly especially in the USA where the number of trials has doubled each year since 1987. In terms of field releases, the European Union lags well behind North America. More than 70% of field trials were conducted in the USA and Canada followed in descending order by Europe, Latin America and Asia, with very few trials conducted in Africa. These trials represent considerable accumulated evidence in support of a favourable safety and environmental record for the new gene technology.

However, the relevance of environmental data obtained from small field trials to large-scale sowing on several million acres of land has been questioned. More than 80 GM variants of several food crops including maize, rapeseed and soyabean have received regulatory approval in the USA and Canada for large-scale sowing and use in foods. From data collected by James (1998-2001) and summarized by Thompson (2003) the estimated global area of GM crops for 2001 was 52.6 million hectares grown by 5.5 million farmers in 13 countries. The increase in area between 2000 and 2001 was 19%, almost twice the corresponding increase between 1999 and 2000. The largest acreage of land planted with GM crops has been in USA and Argentina, although plantings in China and Canada have also been significant. More than one quarter of the GM crop area in 2001 was grown in six developing countries. The number of farmers that grew GM crops increased from 3.5 million in 2000 to 5.5 million in 2001. More than three-quarters of these farmers were resource-poor planting Bt cotton (i.e. crops with effective insect resistance owing to the introduction of the Bacillus thuringiensis (Bt) gene encoding an insect-specific toxin), mainly in China, but also in South Africa.

Past experience with introductions of new species to environments where they are not naturally present has shown that potential problems may take several generations to manifest themselves. Possible cross-pollination from GM crops to non-GM crops is of concern to organic farmers, who fear that, if it occurs, their produce could no longer be said to be "organic", and to those who wish to have the right to choose non-GM foods. There is also concern that traits such as herbicide resistance may spread to wild "relative" weeds (at present the only GM crops that have wild "relatives" are canola and squash) and that the problem of insect resistance may be aggravated. It has been suggested that the adoption of insect-resistant crops by farmers worldwide may lead to the extinction of certain insect species (e.g. Lepidoptera) thereby reducing the biodiversity of the planet. Environmental regulation is difficult to enforce when there are no clear standards against which the performance of a product can be measured (e.g. how many birds, butterflies and wild flowers should there be on a farm and to what extent can their numbers be affected before the environment is harmed?).

Concern has been expressed about the potential risk of GM crops hybridizing (i.e. sharing their genes) with wild closely related species and thereby creating herbicide resistant weeds. This has certainly happened with conventional crops but there is no evidence of it having occurred with GM crops. According to Rick Roush, director of the University of California Statewide Integrated Pest Management Program, reviewing the book "Dangerous Liaisons: When Cultivated Plants Mate with their Wild Relatives" by Norman C. Ellstrand Nature (Book Review) 427, 395 - 396; Jan. 29 2004) :

"Ellstrand provides an introductory section for readers who are not population geneticists, before detailing hybridization between domesticated plants and their wild relatives, and then presenting his interpretation of these observations. Despite his effort to provide this broad context for hybridization between crops and wild plants, and its consequences, I suspect that most readers will focus on chapter 7, where Ellstrand contrasts his views with an opening quote from the Israeli plant scientist Jonny Gressel: "Most crops have no interbreeding relatives in most of the world." Ellstrand reviewed the data for the world's 25 most widely planted crops, summarized their interbreeding with wild plants in a single table, and showed that 22 of them do hybridize with wild relatives somewhere in the world. I suspect that this table will be the most widely referenced in the book, and wish that a few of the distributions were more precisely stated. For example, cotton, beans and potatoes are listed with a "multicontinental" distribution of hybridization; more precisely this refers to Latin America (and, for cotton, some islands in the Caribbean and Pacific). But what about Gressel's proposition, especially in the context of GM crops? Using statistics from the database of the Food and Agriculture Organization of the United Nations, cited by Ellstrand http://fao.apps.org, I checked on the dominant GM crops. At least 87% of the world's soybean crop, and 95% of the world's maize and cotton, are grown in countries for which Ellstrand lists no hybridization — and even for those countries with hybridization, such as China for soybeans, wild relatives are found in only some areas. Many of the other crops are complicated to tabulate, but Gressel seems to be correct that most crops are not interbreeding locally with wild relatives. This still leaves the possibility that serious problems could arise in the few areas of the world where hybridization can occur. This currently seems possible for GM canola in Canada and the United States, and for transgenic maize that is probably growing illegally in Mexico (but has apparently escaped documentation in the refereed literature). But even after reading this book, I haven't seen any evidence of harm to human health or to the environment (including weediness) from such hybridization. Where are the super-weeds that were predicted to occur from the exchange of transgenes with wild relatives? In contrast to the lack of evidence for deleterious effects of gene flow from GM crops, there is evidence that conventional agriculture has adversely affected wild plants through genetic swamping of their populations, and that wild plants have generated weediness in crop--weed hybrids. As noted by Ellstrand, "problems associated with hybridization between conventional crops and their wild relatives received scant attention until potential gene-flow problems were described for transgenic crops". For example, hybridization with cultivated rice has been implicated in the near-extinction of an endemic Taiwanese wild rice. Hybridization of maize with its ancestor teosinte may be contributing to the extinction of teosinte populations. Indigenous cotton in the Galapagos Islands could be at risk of extinction or replacement as a result of hybridization with cultivated cotton. Ellstrand cites similar evidence for at least another nine species. He also documents in great detail the history of sugar beets in Europe, where hybrids between cultivated beets and their progenitors, the sea beets, have caused major weed problems."

However, the problem of gene flow, whether from GM to non-GM (or vive versa) or from hybridization of conventional crops with wild relatives may well be solved by -- genetic modification! The February 2004 issue of The Scientist http://www.the-scientist.com/yr2004/feb/tech_040216.html contains a report by Ivan Oransky as follows (courtesy of Henry Daniell):

Self-Containment for GM Plants

Genetically engineered plants pose several major environmental concerns, according to Henry Daniell, a professor of molecular biology and microbiology at the University of Central Florida. When foreign genes are introduced into the nuclear genome, they end up in pollen, posing the risk of transfer to other species. And sometimes, expression levels are low.

Daniell and colleagues have come up with what he says is a solution: chloroplast genetic engineering. The method--the recipient of several patents, most recently US #6,680,426--offers two benefits, says Daniell. First, like mitochondria, chloroplast genes are maternal and therefore not passed through pollen. And because each cell has 10,000 copies of the chloroplast genome, expression levels are generally high. "This is absolutely a beautiful system," he says.

The transgene construct is designed to minimize disruption of the chloroplast genome. The gene to be inserted is put under the control of chloroplast regulatory signals so that errant transgenes won't express in the nucleus, Daniell says. Those that do hit their mark in the chloroplasts integrate via homologous recombination into a non-coding spacer region, where, Daniell says, "they won't disrupt anything else." Gene delivery is achieved via a biolisitic "gene gun."

From there, it's typical transgenic manipulation--selection of cells that have modified chloroplasts, followed by testing the construct's maternal inheritance. Daniell has founded a company, Chlorogen, to license the method.

-The US National Academies of Science, National Research Council on January 20 2004 issued a report about a study of methods of preventing GM plants from mating or spreading novel genes to other species, entitled "Biological Confinement of Genetically Engineered Organisms". The report " ... will look at how biological techniques such as sterilization can be used to keep transgenic plants and animals from mating or competing with wild relatives, or from spreading novel genes to other species ..." The study is sponsored by USDA. and is expected to be completed around mid-2005.

In the UK, English Nature (the Government's statutory adviser on wildlife and natural features) monitors developments which may affect wildlife and advises on how any damaging effects might be avoided. Its environmental concerns about GM crops were among those which led the UK Government to approve the holding of the UK Farm Scale Evaluations (FSEs) of GM crops and to delay commercial introduction of genetically modified herbicide tolerant (GMHT) and insect resistant (IR) crops until research was completed and the results assimilated.

On 17 January 2002, the UK Government responded to a Report issued by the UK Agriculture and Environment Biotechnology Commission (AEBC), entitled: "Crops on Trial," dealing with the FSEs, which was issued on 10 September 2001.

AEBC includes a range of interests from all sides of the GM debate and has heard evidence from the public, politicians, farming and industry groups, non-governmental organisations and technical experts. Its report comprised a detailed analysis of the context in which the FSEs were being conducted as well as a thorough consideration of the issues raised by the intense interest in the evaluations, resulting in a list of recommendations regarding future decision-making. Its report is accessible on-line at http://www.aebc.gov.uk/aebc/reports.html

In its response the UK Government undertook a public debate on Agricultural Biotechnology before commercialization of GM crops will be allowed, and asked the AEBC to provide further advice how and when to promote an effective public debate on possible commercialisation of the FSE crops, and how to make best use of the results of such a debate. The advice should also cover how to determine the public acceptability of GM crops, in particular, cross-pollination thresholds and GM presence in organic crops. This AEBC report was issued on 26 April 2002 http://www.aebc.gov.uk/aebc/public_attitudes_advice.html
The Statement of the UK Prime Minister on the AEBC report is available on-line at: http://www.number-10.gov.uk/output/Page5763.asp.

The response of the UK Government involved three components. These were: a public debate; a review of the scientific issues relating to GM; and a study into the overall costs and benefits of GM crops to be carried out by the Prime Minister's strategy Unit. The UK Government accepted the AEBC's recommendation for a steering board, independent of Government, to oversee the debate, and invited Professor Malcolm Grant, the chairman of the AEBC, to head this board and to appoint other members, including others from the NGO community, the biotechnology industry, the health professions, consumer organisations, as well as individuals involved in the scientific and economic research.

The GM Science Review - the Science Review panel's first report was published on 21 July 2003 and is available at www.gmsciencedebate.org.uk/report/default.htm. The panel met during October 2003 to look at any relevant issues arising from the public debate report and also the first set of results from the Farm Scale Evaluations (see below). On January 22 2004 it released its second and final report, completing " ... the independent review of current scientific knowledge on GM crops and foods ..." In releasing the report, the panel noted that:

" ... The second phase of the expert panel's work has considered the report of the public debate, new scientific developments since the first report including the Farm Scale Evaluation (FSE) results, and feedback on the first report. Today's report has clarified a number of points and explores some issues in more detail but has not altered the first report's original findings. The first report found no scientific case for ruling out all GM crops and their products, but nor did it give blanket approval. It addressed the general characteristics of GM, but emphasised that GM is not a single homogeneous technology and its applications should be considered on a case-by-case basis. The second phase of the GM Science Review found that: none of the new research published since the first Report significantly altered the earlier conclusions; the FSEs were of high scientific calibre. The panel found that if GM herbicide tolerant crops are managed as in the FSEs, a significant reduction would be expected in weeds with GMHT beet and spring oilseed rape, whereas the opposite would be found with maize. These effects arise from the herbicides and are not a direct consequence of the GM process. The different findings for different GM crops reinforced the conclusion of the first Science Review that GM crops must be assessed on a case-by-case basis; and the first report covered the issues raised by the Public Debate Report: 'GM Nation?' and the foundation discussion workshops provided a useful framework for the Science Review. The Science Review Panel's conclusions on FSEs were released in advance of the second report so they could be submitted to the Advisory Committee on Releases to the Environment (ACRE) for consideration before they put their advice to Government ... The GM Science Review was requested by the Secretary of State for Environment Food and Rural Affairs with the agreement of Ministers in the devolved administrations. The Public Debate "GM Nation?" and the Strategy Unit report on the costs and benefits of GM crops have been the other strands in the GM dialogue aimed at engaging the public and assisting the Government with future GM policy decisions ... "

The full Science Review (including the first and second report), full list of panel members and more information is available at http://www.gmsciencedebate.org.uk The 22 January 2004 panel news release is available at http://www.gmsciencedebate.org.uk/background/pn220104.htm

Costs and Benefits Review - The study by the UK Government's Strategy Unit looking into the overall costs and benefits of GM crops. The report 'Fieldwork; weighing up the costs and benefits of GM crops' was published on 11 July 2003 and can be accessed at www.number-10.gov.uk/su/gm/index.htm.

The Public Debate - As a contribution towards the public debate, and as a result of consumer research carried out, a report was issued the UK Food Standards Agency on UK Consumer Attitudes toward GM was issued. A key finding was summed up as

"most consumers do not have entrenched views (either pro or anti) on GM food, but there is a suspicion of GM, and there is a lack of readily understood information".

The full report is at http://www.foodstandards.gov.uk/multimedia/pdfs/gm_rep.pdf

The remainder of the public debate involved some DEFRA-organised public meetings in several centres, plus many meetings organised by local groups, and an official Website http://www.gmnation.org.uk/. On 24 September 2003 the Report on the results of the public debate were announced. The Executive Summary can be accessed at http://www.gmnation.org.uk/ut_09/ut_9_6.htm#summary and the full Report can be accessed at http://www.gmnation.org.uk/docs/GMNation_FinalReport.pdf. It was not the purpose of the Report to say whether the public were right or wrong about any GM issue, even on matters of fact, but merely to report on public attitudes revealed. It identified seven key messages about public attitudes:

• people are generally uneasy about GM;
• the more people engage in GM issues, the harder their attitudes and more intense their concerns;
• there is little support for early commercialisation;
• there is widespread mistrust of Government and multi-national companies;
• there is a broad desire to know more and for further research to be done;
• developing countries have special interests;
• the debate was welcomed and valued.

Although a large number of people took part (some 37,000 including attenders at some 600 meetings, people completing questionnaires and senders of e-mail and text messages etc), they were entirely self-selected. The four years of intensive anti-GM indoctrination to which the UK public had been subjected was ongoing during the public debate; responses were heavily orchestrated by activist groups, and open meetings in the public debate were either organised by, or subjected to campaigning tactics by, anti-GM activists, leading to complaints from other members of the public that discussions have been compromised. Reported in The Guardian newspaper on 25 September 2003,

One leading British expatriate scientist said antipathy to GM science in Britain was so bad he would not consider coming home. Having left Royal Holloway University in London in 1988, Richard Dixon is now the director of plant biology at the Noble Foundation in Oklahoma. "There is far more suspicion of scientists in the UK. I can give a talk at a town hall meeting here and talk about how we want to genetically modify crops and get a really warm response. But when I went to a GM town hall meeting in York a couple of months ago, I nearly got lynched," he said.'

With all that, and a self-selected group of respondents, it was entirely predictable that the findings would be far more hostile to GM than those of the consumer research carried out by the Food Standards Agency. Thus the public debate Report found that more than half of all participants said they were opposed to the growing of GM crops under any circumstances. The vast majority (86%) of participants said they did not want to eat GM food, while only 2% said they would be happy to eat it.

The UK Government was also waiting for two further key inputs to help inform its policy-making on GM:, namely

      Farm Scale Evaluations (FSE) of herbicide-tolerant crops,  three of the four FSEs of GM crops. In 1998, four genetically modified crops had cleared most of the regulatory hurdles before commercial growing could be allowed in the UK. While these crops had been assessed as safe in terms of human health and direct impacts upon the environment, there had been insufficient research to determine whether there might be any significant effects on farmland wildlife resulting from the way that the crops would be managed. The FSEs of these GMHT crops were established to bridge this important gap in our knowledge.  The results for the three spring-sown crops were due to be published on 16 October 2003 and would then be considered by the Advisory Committee on Releases to the Environment (ACRE), would will provide independent advice to Ministers; and

A Report from the Agriculture and Environment Biotechnology Commission (AEBC) on the coexistence of GM and non-GM crops., involving ideas for possible co-existence measures, such as crop separation distances, and also looking at questions of liability. An overriding consideration is that decisions on whether individual GM crops can be grown commercially are subject to collective European Union agreement.

The results of three FSEs were issued on 16 October 2003. The presentations, by the authors, of the eight rigorously peer-reviewed research papers on the three spring-sown FSEs, between them constituting a huge, rigorously designed, rigorously conducted, epoch-making GM research project costing nearly six million pounds sterling. In their presentations the authors were at pains to point out that their findings did not relate to the fact that the GM herbicide tolerant (GMHT) crops were GM, but to the differing herbicides and herbicide management systems that accompanied the GM crops and the conventional crop controls respectively.

The eight research papers present the FSE findings for those spring sown crops (namely beet, maize and spring oilseed rape). The winter oilseed rape FSE will not be reported until later in 2004. They analyse the effect of each crops and accompanying herbicide and herbicide management system on the plants and animals living in the vicinity. About 60 fields in different parts of the UK where these crops were normally grown, each were sown with beet, maize and spring oilseed rape. Each field was split, one half being sown with a conventional variety managed according to the farmer's normal practice, the other half being sown with a GMHT variety, with weeds controlled by a broad-spectrum herbicide (glufosinate-ammonium in maize and spring oilseed rape, and glyphosate in beet). There was stringent auditing of the farmers' adherence to the protocols. Comparisons in biodiversity were made by looking at the levels of weeds and invertebrates, such as beetles, butterflies and bees, in both the fields and the field margins immediately surrounding them. The results, which until 16 October have been a closely guarded secret, will be studied by scientists, farmers, food companies and governments around the world. and they reveal significant differences in the effect on biodiversity when managing GMHT crops as compared to conventional varieties.

Predictably, activists of one sort or another, and the media, have been interpreting the results to fit in with their respective preconceived positions. For the scientist, the outcomes point to the importance of weeds and of soil seed-banks in sustaining farmland wild life. It has been axiomatic that with the present generation of GMHT crops that the purpose was to get rid of weeds as thoroughly and effectively as possible with the minimum of labour and tillage and with minimum application (in quantity and frequency) of a relatively environmentally-friendly broad-spectrum herbicide. Purely from a farmland wild live aspect, it could be argued that in two of the three crops (beet and spring oilseed rape) the herbicides performed their function too well. These results seem to suggest that there is a case for organizing the provision of sufficient weeds to maintain the farmland wild life.

Put another way, a rational society wishing to take advantage of the agricultural benefits that each of these GMHT crop systems can provide would recognize the need for a trade-off, to establish for each crop and herbicide management system a point of equilibrium where the benefits can accrue alongside the sustaining of the farmland "natural communities".

Whilst the findings cannot answer all the questions resulting from the intense public interest and debate on the future of genetic modification in agriculture in the UK, they do provide a valuable model for the assessment of technological change. The FSEs also demonstrate that it is possible to design experiments at an adequate scale to help forecast the potential environmental impacts of new technologies and practices in agriculture - something that has never been done before.

On 13 January 2004 ACRE gave its verdict on the FSEs. The Committee noted that in the cases of beet and spring-sown oilseed rape FSEs, evidence showed that insect species and weeds declined in the trial areas, endangering birds that fed on them. However, it supported the growing of GM maize, saying it was better for the environment than conventional farming. It also suggested the other crops might be grown in future if measures were taken to protect wildlife.

Although the UK Government subsequently approved  in principle the growing of the GM maize for animal feed, the approval was heavily hedged around with onerous conditions (including a four years repeat of the FSE trial but with a non-atrazine control). The company concerned (Bayer CropScience) regarded it as totally impracticable and “economically non-viable and withdrew.

On 1 July 2004 it was announced that Syngenta, the last big biotechnology company working on GM crops in Britain, is to close its research facility in the UK and transfer its efforts to the United States.

Socio-economic aspects

Much of the vocal antagonism to GM expressed by its opponents appears to consist of ideological antipathy to large companies engaged in GM and to the socio-economic system which allows large companies to exist and thrive. This is, however, not specific to GM, for similar antipathy by the same groups is expressed about large companies engaged in other products and activities. A great deal has been said and written to the effect that the existence of GM seeds somehow denies the farmer the ability to practice in the traditional way -- as though farmers cannot choose whether to use GM seed or stick with non-GM.

One manifestation of this concern has been about the potential for misuse of the so-called terminator genes which prevent seeds from germinating. Although patents exist for terminator technology, it is not available commercially. There are fears that large corporations might use such genes in all their GM crops to prevent farmers from storing seed and that plants that produce barren seed could make life more difficult for poor farmers in the developing world. However, farmers would only buy these seeds if they found an overall advantage in doing so; otherwise they could continue to grow conventional cultivars and save the seed in the traditional way. Furthermore, some fear that if cross-pollination occurs, GM plants with terminator genes could transfer their sterility to other plants grown nearby. However, on the positive side, terminator technology could ensure that GM plants do not themselves become weeds.

Concerns have been expressed  over the supposed problem of patents held by biotechnology companies preventing the use of beneficial GM crops in developing countries. Leaving aside the strange contradiction that these concerns are expressed  in many cases by the same people who deny that there are GM benefits and leaving aside too that many of the original patents are already expiring, the fact is that today, over  five million resource-poor farmers in South Africa, China, India, the Philippines and elsewhere already happily grow nearly one-third of the world’s total GM hectarage because they have higher yields, require fewer inputs and raise income.

The classic case is GM vitamin A rich golden rice developed by Ingo Potrykus (referred to earlier) and his colleague Peter Beyer . Here the research has involved the use of over 70 patents owned by biotechnology companies. from whom they had to obtain permission before they could begin testing the golden rice in field trials. What the critics fail to mention, however, is that those patent holders granted Potrykus and Beyer exemptions for Golden Rice; and moreover have agreed to provide free licences for use by poor farmers in developing countries.

At the 12th World Congress of Food Science and Technology in Chicago in July 2003, Potrykus stated, in the course of a comprehensive presentation, that obtaining those exemptions was time-consuming, but the main reason why golden rice and other GM nutrient-enhanced crops have not yet begun to help resource-poor farmers is not patents but "regulatory obstacles based on undue paranoia."  He has even argued that "those who oppose GM technologies for political advantage or self-interest [should be] held responsible for the unnecessary suffering of millions of people with vitamin A deficiency," which golden rice could help address.  His most up-to-date presentation (April 2004) is at  http://www.agbioworld.org/biotech_info/articles/potrykus.html

A wider matter, however, involves the general question of patents in relation to GM, and, more particularly whether genes can or should be patentable. By analogy with computer language, the procedure of inserting a gene into an organism is not just "cut-and-paste" but "cut- copy (billions of times over)-and-paste". The laboratory-generated copies by that procedure are in every way exact copies of the copied original, but are not the original. Precise details of patent law vary from country to country, but in principle, patents are intended to protect inventions and give the inventor monopoly for a limited time to benefit from the invention. Whether it is the original gene or DNA fragment, or a lab-generated exact copy, these are not "inventions" and ought not to be patentable. A gene is a pre-existing thing, and identification of a gene and its function is a "discovery" rather than an "invention". However, an invention is often a novel combination of pre-existing things, and it is not those things but the combination of them which may be accepted as an invention and therefore patentable. Generally, patent law requires novelty and also that the novelty and its claimed benefits would not be obvious to those "skilled in the art". If these principles are valid, then someone inventing a novel combination involving a gene can patent the combination, but cannot use patent law to prevent someone else from using that gene for other purposes (or even patenting a different combination involving that gene).

Ethical considerations

The officially appointed UK Committee on the Ethics of Genetic Modification and Food Use, chaired by the Rev. John Polkinghorne, carried out a wide public consultation and issued a report in September 1993 on all of the moral and ethical issues involved. This was accepted by the UK Government and welcomed by the Institute of Food Science & Technology. The Committee found that the concerns were misconceptions rather than of real substance, arising from lack of knowledge, outside the scientific community, of just what was involved.

The Committee pointed out that because any gene extracted from one species for copying into another, is not itself inserted but is copied in the laboratory and diluted millions of times before a single gene is transferred, the chance that the original gene would be found are much less than the chance of recovering a particular drop of water from all the oceans of the world. If this were widely understood fears of cannibalism or of contravening religious food taboos would be seen to be unwarranted. Unfortunately, this fact does not make good media copy, whereas sensational stories do.

The Polkinghorne Committee's conclusions were:

      genetic modification of food and medicines is here to stay. It is not something to be stopped, and it would not be ethically right or necessary that it should be;

      there is no reason for any ban on the use of copy genes of human origin or from animals subject to dietary restrictions, but scientists working in this field should be discouraged from using such genes where alternatives would be equally effective;

      products containing such copy genes should be labelled to enabled consumers to make informed choices;

      government and industry should look for ways of explaining genetic modification to the general public.

Because what is transferred to the "host" is not the DNA direct from the donor but a laboratory copy of it (in familiar terms, it is cut-copy (billions of times over)-and-paste rather than cut-and-paste) the perceived concerns are mistaken, but no less real for that.

As a matter of interest that not many people realise, we are in fact all cannibals - everyone is continuously shedding skin cells, which of course contain their DNA. We are all ingesting the DNA of people around us, or who, for example, have previously been in the same room or public transport.

It is noticeable that when "ethical aspects" of GM are raised it is mostly in terms of ethical objections. However, two major reports have included addressing the ethical and social imperatives involved in making the potential benefits of GM available to improve the present and future food supply, especially in developing countries.

A most thorough and balanced study of the ethics, environmental impacts and social aspects of GM was carried out in 1998 under the auspices of the Nuffield Foundation. The Nuffield Council on Bioethics carried out a widespread public consultation using a questionnaire posing the ethical, environmental and social issues and issued a comprehensive report on its conclusions and recommendations, "Genetically modified crops: the ethical and social issues".
http://www.nuffield.org/fileLibrary/pdf/gmcrop.pdf

In June 2003 the Nuffield Council on Bioethics issued for public consultation a  Discussion Paper on the use of GM in developing countries. This evoked a supportive response from IFST. Following the consultation, on 28 December 2003 the Nuffield Council on Bioethics issued its  Report (described as a "Follow-up Discussion Paper") on "The use of genetically modified crops in developing countries". http://www.nuffieldbioethics.org/filelibrary/pdf/gm_crops_paper_final.pdf

Information  aspects

Information (and particularly label information) about the GM status of foods or ingredients is a topic with polarised views that do not lend themselves to an intermediate position. On the one hand, it is argued that if a food or ingredient has been approved as "safe", the method of production is irrelevant and need not be stated.. On the other hand, it is argued that provision of that information is necessary for informed consumer choice, including the consumer who wishes to choose GM, and the consumer who wishes to avoid GM for whatever reason – even an irrational reason or whim. The EU Commission adopts the latter position (which is supported by IFST) while the US FDA adopts the former. 

Factors affecting EU approach to regulating GM

In the EU, the general legislative approach throughout its existence has been that if anything can conceivably be regulated, regulate it. So it had built a comprehensive system and machinery for considering and approving (or otherwise) applications for approval of specific lines of GMOs, and for controlling the release of GMOs into the environment. Likewise, it adopted from the outset the principle of informed consumer choice, which has led to increasingly comprehensive measures, initially voluntary and then by more and more stringent legislation, to provide distinctive labelling of GM foods. In this, as in other aspects, the nature and extent of the regulatory provisions has been influenced by the governments of the Member States, reflecting a public opinion in turn influenced by activist campaigning.

Differences from the US regulatory approach

In contrast, in the USA the Food and Drug Administration (FDA) has, despite increasing pressure, refused to require distinctive labelling of GM materials, on the grounds that it has determined that they are substantially equivalent to the non-GM versions; and that being so, their method of production is irrelevant. The most comprehensive analysis of the approach and reasoning underlying the US position is given in the Expert Panel Report on the Biotechnology of Foods issued by the Institute of Food Technologists (IFT). The full text is available at http://www.ift.org/govtrelations/biotech/

The absence of distinctive labelling in USA has had a consequence that most US consumers have not had the presence of GM foods or ingredients drawn to their attention (although over the past few years this situation has been gradually changing). Most of those that have been aware of it, have evidently been reassured by approval on the part of both FDA and EPA. This has in turn has been one of the factors making US consumers much less susceptible (so far) than European consumers to the kind of activist campaign that has dramatically affected public opinion in the EU and especially in the UK.

However, a Public Opinion Poll was recently conducted in New York State for the Cornell Cooperative Extension's Genetically Engineered Organisms Public Issues Education (GEO-PIE) Project - The poll " ... found that New York State residents are divided on the use of biotechnology in food production, with the public almost evenly split between those who oppose its use, those who favor it, and those who are undecided ..." Telephone data collection commenced on March 10, 2003 and was completed July 2, 2003. Details are at <http://www.comm.cornell.edu/msrg/research_news.html

A recent survey by the Pew Initiative on biotechnology and GM foods revealed that Americans’ knowledge of GM foods remains low and their opinions about its safety is just as divided as it was two years ago. The survey also shows that knowing FDA reviewed and approved a GM product can increase public confidence and that public support for GM products decreases as uses of the technology shift from plants to animals.

Using data from a similar survey released by the Pew Initiative in March 2001, the survey was able to compare awareness levels over a two-year period and draw two major conclusions: Americans’ knowledge about GM foods remains low, even as GM technology is increasingly applied to agriculture; and opposition to GM foods has softened somewhat in the last two years but opinions about safety remain split.

The survey also probed topics rarely explored in widely-available opinion polls about agricultural biotechnology, including how Americans feel about the way GM products are regulated in the US and the application of genetic engineering technology to animals. Key findings indicate that Americans oppose a ban on GM foods, but are strongly supportive of a regulatory process that directly involves the FDA. It was also determined that Americans are far more comfortable with genetic modifications to plants than animals, and are particularly supportive of genetic modifications that improve health.

The nationwide survey, conducted August 5-10, 2003 by The Mellman Group and Public Opinion Strategies, consisted of telephone interviews of 1,000 American consumers. The margin of error for this survey is +/- 3.1%. The margin of error is higher for subgroups. Data from a similar survey, released by the Pew Initiative in March 2001, was used for tracking purposes.

The full report is at http://pewagbiotech.org/research/2003update/

Another major difference is that, in the definition of substantial equivalence, still used in many countries including the USA and Canada, the presence of degraded novel DNA or protein does not preclude a GM food from being considered substantially equivalent to a conventional food. However, in the EU, the concept of substantial equivalence was redefined in December 1997. Only highly processed foods derived from GM crops, such as highly refined oil, white sugar and starch hydrolysates, are considered substantially equivalent to their conventional counterparts on the grounds that neither DNA nor protein would be expected to be present following the processing that these foods receive. All other ingredients derived from GM crops, such as flour and protein extracts, require a full safety evaluation as they may contain novel DNA and/or protein, in either intact or degraded form. Thus, lecithin from GM soyabean, used extensively as an emulsifier in many processed foods, would be considered substantially equivalent to conventional lecithin in North America but not in the UK and the rest of the EU..

Detection and analysis of GM materials

Effective regulatory control over GMOs is crucially dependent on the existence of reliable analytical methodology for detection and identification of specific genes, and for quantification where, for example, a threshold limit is set. Until the mid-1990s, in the absence of reliable analytical methods it was impossible to determine whether a food or food ingredient had been genetically modified. More recently, however, new methods have been developed based on the polymerase chain reaction (PCR) – a method for several-million-fold amplification in vitro of specific DNA sequences known as nucleotides or "primers". Compared with the millions of bases in the DNA in an organism, and 100 bases in an average gene, it has been discovered that primers as short as 21-24 bases in length can act as a unique "fingerprint" for a gene.

PCR-based assays involve the following three basic steps:

1.       DNA extraction and purification

2.       PCR amplification of DNA

3.       Gel electrophoretic analysis of PCR reaction products

Within the framework of the development of EU legislation on GMOs in food and food ingredients, the Health and Consumer Protection Directorate General of the European Commission in December 1998 commissioned two studies on the development of qualitative as well as quantitative methods for the detection of GMOs in food, after an open call for tender procedure (Official Journal S 122 of 27 June 1998, p.34) to two leading institutions in the field of analytical methods:

4.   The German Federal Institute for Health Protection of Consumers and Veterinary Medicine (BgVV – Bundesinstitut für gesundheitlichen Verbraucherschutz und Veterinärmedizin) and;

5.    The Institute for Health and Consumer Protection (IHCP) of the Joint Research Centre of the European Commission in Ispra.

The studies were completed in October 2000 and executive summaries can be accessed at
http://europa.eu.int/comm/food/food/biotechnology/gmfood/biotech04_en.pdf
and
http://europa.eu.int/comm/food/food/biotechnology/gmfood/biotech05_en.pdf

Meanwhile, the World Health Organization on 1 August 2003 announced the availability of a guidance manual which is " ... used in the training courses organized jointly by the Joint Research Centre (JRC) of the European Commission and WHO/Europe, [which] provides the theoretical and practical information on methodologies and protocols followed during the courses. It covers a wide variety of techniques for GMOs detection, identification, characterization and quantification, and includes key background theoretical information for working in the field of GMO detection ..." Details are available at <http://www.euro.who.int/foodsafety/Assistance/20030728_1

The course is intended to teach molecular detection techniques to laboratory personnel with a good level of analytical knowledge, but with no or little expertise in this specific domain. The Course Manual entitled "The analysis of food samples for the presence of genetically modified organisms", edited by M. Querci, M. Jermini and G. Van Den Eede, has now been made available on-line at http://gmotraining.jrc.it/

In March 2004  the European Committee for Standardization (CEN) issued European Standard EN ISO 21572 :2004 “Methods for detection of Genetically modified organisms and derived products – Protein based methods”.

EU Directives and Regulations concerning GM

Relevant regulatory information has been given under various headings in the foregoing text, but for convenience is collected under this heading, and presented in a way which shows the historical development of the legislation.

Regulations on Novel Foods and Novel Food Ingredients

The principal legislation is EU Regulation No. 258/97 of the European Parliament and of the Council of  27 January 1997 concerning novel foods and novel food ingredients. [OJ L43, 14.2.97, pp 1-7]. In the UK the enforcement and execution of certain provisions of the EU Regulation and set fees for assessment procedures in the UK are provided by:

      The Novel Foods and Novel Food Ingredients Regulations 1997 (SI 1997/1335)

      The Novel Foods and Novel Food Ingredients (Fees) Regulations 1997 (SI 1997/1336)

The Novel Foods Regulation applies to the placing on the market within the EU of foods and food ingredients which have not previously been used for human consumption to a significant degree and which fall into the following categories:

      foods and food ingredients containing or consisting of GMOs within the meaning of Directive 90/220/EEC (see below)

      foods and food ingredients produced from, but not containing, GMOs foods and food ingredients with a new or intentionally modified primary molecular structure

      foods and food ingredients consisting or isolated from micro-organisms, fungi or algae

      foods and food ingredients consisting of or isolated from plants and food ingredients isolated from animals, except for foods and food ingredients obtained by traditional propagating or breeding practices and having a history of safe food use

      foods and food ingredients to which has been applied a production process not currently used, where that process gives rise to significant changes in the composition or structure of the foods or food ingredients which affect their nutritional value, metabolism or level of undesirable substances.

The novel foods and food ingredients must not present a danger for the consumer, mislead the consumer or differ from the foods or food ingredients which they are intended to replace to such an extent that their normal consumption would be nutritionally disadvantageous for the consumer. Derogations are available for foods and food ingredients which according to expert scientific opinion are substantially equivalent to existing foods in respect of their composition, nutritional value, metabolism intended use and level of undesirable substances contained therein.

These particular regulations do not apply to GM-derived food additives, flavourings and extractions solvents. On this basis soya lecithin derived from GM soya would not have required an indication that it is derived from GM sources (but see later).

The EU Novel Foods Regulation also specifies the assessment procedures which must be carried out before a novel food can be placed on the market, and makes for provision for objections to be raised by interested parties. A procedure for re-assessment of novel foods is included if they subsequently appear to be endangering human health and for a review of the regulations within 5 years from implementation in any case.

The Novel Foods Regulation has been in force for around seven years. There have been relatively few applications for full approval of GM food sources or ingredients, some of them by the 'substantial equivalence' notification route.

The European Food Safety Authority is now the central body controlling assessment of novel foods and novel food ingredients. Applications can be made to a national authority (in the UK, the Advisory Committee on Novel Foods and Processes (ACNFP)). The findings of a national body, which must be stated within 90 days, are circulated to those of the other Member States, which have 60 days in which to disagree, failing which approval is ratified. ACNFP carries out this task in consultation with the Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (COT), the Scientific Advisory Committee on Nutrition (SACN) (formerly known as the Committee on Medical Aspects of Food and Nutrition Policy (COMA)) and the Food Advisory Committee. The ACNFP has the option to assess food ingredients on a "fast track" route on the grounds of "substantial equivalence" to existing products or subject them to a full safety assessment. So far the Committee has concluded that highly processed, refined foods derived from GM crops such as hot pressed oil, white sugar and starch would be substantially equivalent on the grounds that neither DNA nor any proteins would be expected to be present. However, other ingredients like flours and protein extracts require a full safety evaluation because they may contain novel DNA intact or in a degraded form and protein products denatured to varying extents.

Releases into the Environment

Council Directive 90/220/EEC of 23 April 1990 on the deliberate release into the environment of genetically modified organisms [OJ L 117, 8 May 1990, p 15; amended by Commission Directive 94/15/EC (OJ L103, 2214/94, p.20) and Commission Directive 97/35/EC (OJ L169, 27/6/97, p 72)]. This Directive. is administered in the UK by the Department of the Environment and implemented in the UK by the following Regulations

      The Genetically Modified Organisms (Deliberate Release) Regulations 1992 (SI 1992/3280) and

      The Genetically Modified Organisms (Deliberate Release) Regulations 1995 (SI 1995/304)

      The Genetically Modified Organisms (Deliberate Release and Risk Assessment - Amendment) Regulations 1997 (SI 1997/1900).

Under this Directive, a manufacturer or importer must submit a notification to the national competent body of a Member State where the product is to be first placed on the market, before undertaking a deliberate release into the environment of a GMO, or placing it on the market.

The notification should contain a technical dossier of information including a full risk assessment. The Member State that received the notification examines the dossier and in the case of a negative evaluation the notification is rejected.

In the case of a favourable opinion, the dossier is forwarded to the European Commission and all the competent authorities of the other Member States who have the right to raise objections. If there are no objections, the competent authority that carried out the original evaluation grants the consent for the placing on the market of the product, which may then be placed on the market throughout the European Union.

In case of objections, a decision has to be taken at Community level. The Commission seeks the opinion of the European Food Safety Authority before drafting a Decision which is put forward to the Regulatory Committee composed of representatives of Member States for favourable opinion. Otherwise a proposal is put forward to the Council, which decides by qualified majority. If no Council decision is taken within 3 months the Commission takes the decision. In any case, in accordance with Directive 90/220/EEC, the Commission is ultimately obliged to adopt measures to authorise a GMO, if the application fulfils current EU legislation and if it is not rejected by unanimity in the Council, or if the Council fails to act within the fixed deadline.

GMOs have to undergo a scientific assessment of risks to human health and the environment before receiving Community authorisation. Risk assessments are performed on a case by case basis.

The safety assessment takes into account of the following:

      How the GM was developed - including the source of the genes to be introduced and detailed molecular analysis of the modified plant and organism. The process can be likened to that of 'cutting' and 'pasting' where pieces of DNA are cut out of the donor organism, copied and pasted into a recipient organism. It is necessary to establish which genes are incorporated and where in the recipient genome.

      Risk associated with the gene products in the plant, mainly proteins. It is necessary to know that the gene does not encode for a protein that is toxic to humans or does not produce an allergic response. It must also be established that the inserted gene(s) does not result in unexpected effects.

      Investigation of the possibility that the inserted gene may be transferred to bacteria. This has particular relevance to the possible transfer of antibiotic resistance genes.

Up to 29 October 2001, under the procedure foreseen in Directive 90/220/EEC and using the current risk assessment methodology, 18 GMOs had been authorised in the EU. Two genetically modified plants, a variety of soya and a variety of maize were authorised for use in food. From October 1998 until the present no further authorisations were granted under Directive 90/220/EEC and as of 29 October 2001, 12 applications for authorisation were pending. The moratorium continues at this time but (unless blocked by some Member States) is on track to be lifted following the adoption of the new Directives.

Council Directive 90/220/EEC has now been superseded by Directive 2001/18/EC providing for deliberate release of GMOs into the environment.

Containment

EU Council Directive 90/219/EEC on the contained use of genetically modified micro-organisms [OJ L117, 8 May 1990, pp 1-14], as amended by Council Directive 98/8 1 1EC of 26/10/98 (OJ L330, 5 December 1998, p13). This Directive, which provides the circumstances and conditions under which GMOs (including fermentation organisms) require consent for contained use, is implemented in the UK by:

     The Environmental Protection Act 1990, Part VI, Genetically Modified Organisms, Sections 106-127. Section 106 states that this Part (i.e. Part VI) has effect for preventing or minimising any damage to the environment which may arise from the escape or release from human control or genetically modified organisms.

     The Genetically Modified Organisms (Risk Assessment) (Records and Exemptions) Regulations 1996 (SI 1996/1106) restrict the import and acquisition of GMOs under Section 108 (l)(a) of this Act.

     The Genetically Modified Organisms (Contained Use) Regulations 1992 (SI 1992/32 17)

      [The Genetically Modified Organisms (Contained Use) Regulations 1993 - now revoked]

     The Genetically Modified Organisms (Contained Use) (Amendment) Regulations 1996 (SI 1996/967)

     The Genetically Modified Organisms (Contained Use) (Amendment) Regulations 1996 (SI 1998/1548)

Labelling

Prior to May 1997, labelling of GM foods in many countries, including the UK, was not explicitly mandatory. Nevertheless, some food manufacturers and retailers labelled GM foods on a voluntary basis (e.g. the Co-op's vegetarian cheese prepared using GM chymosin and Sainsbury's and Safeway's GM tomato puree) to allow consumers to exercise choice and to gain consumer confidence. Labelling guidelines developed by a number of bodies including the independent Food Advisory Committee in 1993 (revised in 1996) and the Institute of Grocery Distribution in 1997. These guidelines took into account the need for labelling of novel foods which contain material (e.g. allergens) which may have implications for the health of some sections of the population (e.g. infants or the elderly) as well as those which contain "ethically sensitive genes". The latter include foods that contain copy genes originally derived from humans or from animals which are the subject of religious dietary restrictions (e.g. pig genes for Muslims) or any animal genes for vegetarians. Much of the provision on ethically sensitive genes has been based on the findings of the UK Polkinghorne Committee, which reported on the ethics of genetic modification in 1993.

On 15 May 1997, the EU Novel Foods Regulation (258/97) were made, controlling the placing on the market and the labelling of GM foods or foods obtained from GMOs mandatory in the European Union if, on the basis of a scientific assessment, they were judged not to be substantially equivalent to an existing food (for a definition of substantial equivalence, see section above on "Safety and regulation of GM foods"). Article 8 of the Novel Foods Regulation requires foods and food ingredients containing or consisting of GMOs and foods and food ingredients produced from (but not containing) GMOs to be labelled so as to inform consumers of any characteristic or property that makes the food or food ingredient different from an equivalent, existing food or food ingredient. Not only must the modified characteristic or property be identified, the method by which it was obtained must be indicated. The regulation allowed voluntary labelling to indicate the absence of any genetic material.

However, specific lines of GM soya and GM maize approved under the Deliberate Release Directive 90/220, and consumed to a significant degree before the Novel Foods Regulation came into effect on 15 May 97, were, therefore, outside the scope of that Regulation.

To deal with that situation, on 1 November 1997 a Commission Regulation 1813/97 was adopted which made food ingredients from those crops subject to the same distinctive labelling provisions as those contained in the Novel Foods Regulation. This regulation also stated that detailed Community Rules on labelling would be adopted as soon as possible in accordance with the requirements of Article 8 of Regulation 258/97. In line with this provision, Council Regulation No 1139/98 [OJ L 159, 3/6/98, p4] came into effect on 1 October 1998. As later amended by Regulation 49/2000, it requires that where a food consists of more than one ingredient, the words "produced from genetically modified soya" or "produced from genetically modified maize", as appropriate, shall appear in the list of ingredients. This wording can be shortened to "genetically modified" where an ingredient is already listed as being produced from soya or maize; or where it is used as a footnote, linked by asterisk to "soya*" or "maize*". This regulation applies to foods delivered as such to the final consumer.

EU Regulation 50/2000 applies similar requirements to the labelling of GM derived additives and flavourings, but extends beyond GM soya or maize to any GM source.

In the UK, this requirement was taken one step further in early 1999 by the announcement that labelling of GM soya and maize will be required not only for manufactured products but also in restaurants, cafes, delicatessens and sandwich shops. Since it is not always practically possible for catering establishments to provide labelling at the point of sale, the Food Labelling (Amendment) Regulations 1999. S.I. 1999/747 (UK) allow such establishments to inform customers about GM foods via their staff. The availability of this information must also be indicated on the menu or on a prominent notice. In addition, information must also be made available to customers who place telephone orders for take-away food. The Regulations allowed for a 6-month lead-in time (i.e. to September 1999) to enable reprinting of menus and staff training. The selling of foods containing GM material where this has not been properly declared can now be prosecuted and fined up to £5,000.

Regulation 1139/98 also requires that validated testing methods be established so that the presence or absence of GM materials can be scientifically determined. To deal with adventitious contamination of foods or food ingredients with GM materials, a threshold for detection of genetically modified DNA would be set at or below which foods would not need to be labelled. Provision for a negative list of processed foods in which any genetically modified DNA or protein present would have been destroyed was also to be drawn up under the Regulation. Foods may only be exempted from distinctive labelling if they contain less than an agreed threshold level of GM material.

Regulation 49/2000 of 11 January 2000 set the threshold at 1% of a single ingredient food or, in a multi-ingredient food, 1% of each ingredient considered separately; but only if the manufacturer can demonstrate that the ingredient has been obtained from a non-GM source (but note that this only permits exemption from distinctive labelling for food or ingredients below the threshold; it does not permit such foods to be designated as "GM-free" – however, the EU Commission's program of future work foreshadowed the development of a Regulation for the labelling of GM foods). Of course, effective regulatory control in relation to a threshold limit is crucially dependent on the existence of a validated reliable analytical method for detection, identification and quantification of specific genes.

The original expectation was that the food components compared should be key nutrients and toxicants rather than tiny fragments of degraded DNA and associated proteins. The Regulation recognised that in some cases it would not be possible to segregate foods which contain genetically modified and conventional produce (e.g. soyabeans imported from the USA). In such circumstances, the Regulation recognised that providing other information for the consumer (e.g. point-of-sale leaflets) identifying that GMOs may be present fulfilled the labelling obligation.

Enforcement of these measures has been carried out by Member States' authorities.

From July 2000 discussions and work proceeded in the Commission, the Council of Ministers and the European Parliament, to provide a new comprehensive and stringent regulatory regime, replacing the previous piecemeal measures covered in the various pieces of legislation. This would cover traceability of GMOs throughout the chain from farm to table, and labelling of GMOs and products produced from GMOs and regulating GM food and feed.

'Traceability' here means the ability to trace and follow a food, feed, food-producing animal or substance, through all stages from rearing or growing of primary products, through production, manufacture and distribution up to and including its sale or supply to the final consumer; and in the case of a food containing a GMO, or a food, food ingredient, additive, or flavouring derived from a GMO, an unique code identifier following it from "farm to fork", and provision to the authorities of information facilitating the detection and identification of a particular GM product including lodging of a sample of the GMO or its genetic material.

Of course traceability is highly important for all aspects of product food safety. But for any scheme that needs an effective system for authorization of specific GMOs, and labelling distinction between GM and non-GM products, not only analysis but also traceability is a must. However, this was the first time that a proposal had been made to establish mandatory traceability measures. Moreover, it would seem that the new approach placed emphasis on traceability of heritage rather than relying solely on analysis.

On 27 July 2001 the Commission published the two Proposals for two Regulations of the European Parliament and of the Council

      on genetically modified food and feed http://europa.eu.int/comm/food/fs/biotech/biotech08_en.pdf

      concerning traceability and labelling of genetically modified organisms and traceability of food and feed products produced from genetically modified organisms http://europa.eu.int/comm/food/fs/biotech/biotech09_en.pdf

On 1 July 2003, the EU Commission issued an updated Questions-and-Answers fact sheet on the regulation of GMOs in the EU, divided into two sections; Part A covers legislation in force; Part B covered the new legislative proposals on traceability and labelling. It can be found at
http://europa.eu.int/comm/dgs/health_consumer/library/press/press298_en.pdf

On 29 September 2003 the EU Commission issued "Questions and Answers about GMOs in seeds," which provides answers to the following questions: What is the EU seeds legislation? Is there separate legislation on GM seeds? Why is there a need to set thresholds for GM-impurities in conventional seeds? What thresholds for GM-presence in conventional seeds will the Commission propose? What is the aim of such thresholds, what is the relationship between the seed thresholds and the labelling thresholds for food and feed products? What kind of GMOs will benefit from the thresholds proposed? and Will these thresholds be important for the co-existence of genetically modified crops with conventional and organic farming? It can be found at
http://europa.eu.int/rapid/start/cgi/guesten.ksh?p_action.gettxt=gt&doc=MEMO/03/186|0|RAPID&lg=EN

As mentioned earlier, the Commission's proposal placed the European Food Safety Authority (EFSA), rather than individual Member States, at the centre of the approval process. The EFSA would be responsible for undertaking a risk assessment covering both environmental risk and the risk to human and animal health when assessing a GM food or feed ingredient. In practice, the safety assessment would be carried out by Member States, on a rota basis, on behalf of the EFSA. For GM products likely to be used as either food or feed, authorisation would be recommended for either or both uses or none at all. On the basis of the opinion of the EFSA, the Commission will be responsible for drafting a proposal granting or refusing authorisation. The proposal will then be put to Member States for final approval.

The scope of application for the labelling of GMOs would not include products derived from animals fed with GM feed (eggs, milk and meat).

The proposals went through a long period of gestation and debate, but finally emerged from their second reading in the European Parliament in June 2003. The new legislation was given final approval by the Council of Ministers on 22 July 2003, published in the Official Journal of the European Union on 22 September 2003 and designated

      Regulation (EC) 1829/2003 of the European Parliament and of the Council of 22 September 2003 on genetically modified food and feed;
http://europa.eu.int/eur-lex/pri/en/oj/dat/2003/l_268/l_26820031018en00010023.pdf
and

      Regulation (EC) 1830/2003 of the European Parliament and of the Council of 22 September 2003 concerning the traceability and labelling of genetically modified organisms and the traceability of food and feed products produced from genetically modified organisms and amending Directive 2001/18/EC .
 http://europa.eu.int/eur-lex/pri/en/oj/dat/2003/l_268/l_26820031018en00240028.pdf

These mean that GM crops have to be kept separate from conventional crops and put strict limits on the accidental mixing of the two. The rules allow for no more than 0.9% accidental mixing of GM in non-GM shipments to the EU. All products containing more than 0.9% GMOs  have to be distinctively labelled as genetically modified. Genetically modified material will also have to be traced at all stages of production.

Several countries in the EU had said they would keep the unofficial moratorium in place until the new legislation regarding labelling and traceability was introduced. Member States were divided in several votes since December 2003, which under EU rules sent the decision ultimately to the EU Commission.

On 12 May 2004  the Commission decided to lift the 6-year-old unofficial moratorium by approving imports of an insect-resistant Bt11 strain of sweet corn for human consumption from Swiss-based Syngenta. This GM corn would only be imported and not grown in the EU, although an application for cultivation is pending. Any sold – whether canned or fresh - would have to be labelled in accordance with the new Directives. This development has not, however, stopped the US from going ahead with its WTO case against the EU. Although favouring a lifting of the moratorium, the US considers such stringent labelling laws unworkable and in practice as trade barriers.

David Byrne, EU Commissioner for Health and Consumer Protection, said the GM corn was approved after "the most rigorous pre-marketing assessment in the world”.

"It has been scientifically assessed as being as safe as any conventional maize. Food safety is therefore not an issue, it is a question of consumer choice. Labelling provides consumers with the information they need to make up their own mind. They are therefore free to choose what they want to buy."

The question arises, however, whether, in the present engendered climate of European consumer fears, importers and retailers in the EU Member States will consider it too commercially risky to offer consumers that choice.

In the UK, the Food Standards Agency has carried out a consultation on the enforcement and penalties in the UK  of these two EU Regulations, and on draft Guidance Notes http://www.food.gov.uk/multimedia/pdfs/gmconsultnotes.pdf
although, as FSA points out, this is draft informal guidance for application of both Regulations in the UK and cannot modify the Regulations themselves.

In the UK DEFRA is carrying out a consultation on proposals
http://www.defra.gov.uk/corporate/consult/gm-transboundary/index.htm
for administering and enforcing Regulation (EC) No 1946/2003 of the European Parliament and of the Council on transboundary movements of GMOs
http://europa.eu.int/eur-lex/pri/en/oj/dat/2003/l_287/l_28720031105en00010010.pdf
coming into force in November 2004

The laws also allow EU Member States to take “appropriate measures” to ensure GM crops planted in the EU do not cross-pollinate with conventional crops. However, on 26 January 2004,  EU Agriculture Commissioner Franz Fischler warned delegates at a conference on organic farming that food which is completely free of GMOs is a thing of the past. When it comes to setting acceptable thresholds for the levels of GMOs in organic and conventional products, the Commissioner said that Europe must take guidance from scientists, rather than politicians.  'We have been banished from paradise. The idea of a zero per cent threshold was no doubt possible in the Garden of Eden, but not in the real world,' said Dr Fischler.  Then on  23 February 2004 a report was issued by the (US) Union of Concerned Scientists entitled "Gone to Seed: Transgenic Contaminants in the Traditional Seed Supply". It described tests carried out in USA on supposedly unmodified corn, soy and canola seeds, all purchased commercially. Of 18 seed varieties tested, 16 seemed to contain some GM elements.

On 27 February 2004 the 87 member states of the Cartagena Protocol on Biosafety, which entered into force in September 2003,  adopted documentation requirements and other procedures for promoting the safety of international trade in GMOs http://www.biodiv.org/doc/press/2004/pr-2004-02-27-bs-en.pdf

Conclusions

The exercise of informed choice by consumers requires that they have accurate and unbiased information. The reverse is currently the case. The provision of such information will be a key factor in the acceptance of food applications of gene technology.

IFST fully supports the notion that academic and industrial scientists, professional bodies, learned societies, food retailers, governments and consumer organisations must all play an active role in communicating both the benefits of, and concerns about, GM foods to the public. The realisation of the potential benefits of gene technology will depend both on the further work of scientists in addressing and solving the above-mentioned potential problems and on effective communication between scientists and the rest of society, including the lay public.

Food scientists and technologists can support the responsible introduction of GM techniques provided that issues of product safety, environmental concerns, information and ethics are satisfactorily addressed. IFST considers that they are being addressed, and need even more intensively to continue to be so addressed. Only in this way may the benefits that this technology can confer become available, not least to help feed the world's escalating population in the coming decades.

On-line References

In addition to Web addresses given in the text of this Information Statement, the following are useful references:

Advisory Committee on Novel Foods and Processes (ACNFP) (UK) Annual Reports 1989-2001, http://www.food.gov.uk/science/ouradvisors/novelfood/acnfpannual

Animal & Plant Health Inspection Service of USDA, Biotechnology Regulatory Services, http://www.aphis.usda.gov/brs

Bennett, P M et al, "An assessment of the risks associated with the use of antibiotic resistance genes in genetically modified plants”: report of the Working Party of the British Society for Antimicrobial Chemotherapy

http://www.agbiotechnet.com/news/Database/jac.oupjournals.org/ 

Biotechnology at Work Web site of the Department of Trade and Industry (UK) http://www..dti.gov.uk/biowise

Department of Health (UK) "Health Implications of Genetically Modified Foods" http://www.doh.gov.uk/gmfood.htm

Department of Food, Environment and Rural Affairs (UK)
http://www.defra.gov.uk

Center for Science in the Public Interest: “Genetically Engineered Foods: Are They Safe?” https://cspinet.safeserver.com/nah/11_01/index.html

European Food Safety Authority (EFSA) Scientific advice on the use of antibiotic resistance marker genes in genetically modified plants

http://www.efsa.eu.int/press_room/press_release/386_en.html

European Union DG Consumer Policy and Consumer Health Protection ("Sanco") Web site http://europa.eu.int/comm/food/index_en.html

Question and Answers on the regulation of GMOs in the

European Union : http://europa.eu.int/comm/food/index_en.html

European Union: Consultation on "Life Sciences and Biotechnology: A Strategic Vision"
http://europa.eu.int/comm/dgs/health_consumer/library/press/press298_en.pdf

European Union: Questions and Answers on the European Food Safety Authority
http://europa.eu.int/comm/dgs/health_consumer/library/press/press135_en.pdf

European Union: European Food Safety Authority Website http://www.efsa.eu.int

Foodfuture: Food and Biotechnology, Food and Drink Federation (UK)
http://www.foodfuture.org.uk

Food and Agriculture Organisation (FAO). Report of Joint FAO/WHO Consultation on Biotechnology and Food Safety http://www.fao.org/es/ESN/food/pdf/biotechnology.pdf

Food and Agriculture Organisation (FAO). Annual Report, "The State of Food and Agriculture 2003-04" ftp://ftp.fao.org/docrep/fao/006/Y5160e/y5160e00.pdf

IFIS: Review of some some GM-relevant Websites

Institute of Food Science & Technology (IFST)
http://www.ifst.org

Nuffield Council on Bioethics (1999). Report "Genetically modified crops: the ethical and social issues".
http://www.nuffield.org/fileLibrary/pdf/gmcrop.pdf

Nuffield Council on Bioethics (2003). Follow-up Discussion Paper “The use of genetically modified crops in developing countries”

http://www.nuffieldbioethics.org/filelibrary/pdf/gm_crops_paper_final.pdf

The Royal Society
http://www.royalsoc.ac.uk

Royal Society Statements:

Feb 1998: Genetically Modified Plants for Food Use;

March 1999: The Regulation of Biotechnology in the UK;

April 1999: Scientific Advice on GM Foods: A Response to the inquiry by the House of Commons Science and Technology Committee;

April 1999: GMOs and the Environment: A Response to the inquiry by the House of Commons Environmental Audit Committee.

Links at http://www.royalsoc.ac.uk/policy/rep_fr.htm

UK House of Commons, Select Committee on Science and Technology http://www.publications.parliament.uk/pa/cm199899/cmselect/cmsctech/286/9030801.htm http://www.parliament.the-stationery-office.co.uk/pa/cm199899/cmselect/cmsctech/286/9030801.htm; and

http://www.publications.parliament.uk/pa/cm199899/cmselect/cmsctech/286/28602.htm

World Health Organisation (WHO): 20 Questions On Genetically Modified (GM) Foods http://www.who.int/fsf/Documents/20_Questions/q&a.pdf

The Canadian Food Inspection Agency 's Food Safety Enhancement Program Web page of links at http://www.cfia-acia.agr.ca/english/ppc/haccp/haccp.html

Further Printed Information

Advisory Committee on Novel Foods and Processes (ACNFP). 1989-2001. Annual Reports. Available from ACNFP Secretariat, Food Standards Agency, Aviation House, 125 Kingsway, London WC2B 6NH, UK. (See also On-line References)

Advisory Committee on Releases into the Environment (ACRE). 1993-present. Annual Reports. Available from DEFRA, Nobel House, 17 Smith Square, London SW1P 3JR, UK (See also On-line References)

Astwood, J.D. et al. 1996. Stability of food allergens to digestion in vitro. Nature Biotechnology 14, 1269-1273.

Committee on the Ethics of Genetic Modification and Food Use (The "Polkinghorne Committee"). 1993. Report. Available from HMSO, P.O. Box 276, London SW8 5DT.

European Committee for Standardization (CEN): European Standard EN ISO 21572 :2004 “Methods for detection of Genetically modified organisms and derived products – Protein based methods”

Food Advisory Committee (FAC). 1990-present. Annual Reports and Guidelines for the Labelling of Foods Produced using Genetic Modification. 1994. Available from FAC Secretariat, Food Standards Agency, Aviation House, 125 Kingsway, London WC2B 6NH, UK. (See also On-line References)

Food Labelling (Amendment) Regulations 1999. S.I. 1999/747 (UK)

Foodsense. Genetic Modification and Food. Leaflet available from DEFRA, London SE99 7TT.

Food and Drink Federation. 1995, 1997. Food for our Future and Modern Biotechnology - Towards Greater Understanding. Colour brochures available from the FDF, 6 Catherine Street, London WC2B 5JJ.

Herian, A.M. et al. 1990. Identification of soybean allergens by immunoblotting in sera from soy-allergic adults. International Archives of Allergy Applications and Immunology 92, 193-198.

Institute of Food Science and Technology (IFST). 1996. Guide to Food Biotechnology. Available from IFST, 5 Cambridge Court, 210 Shepherd's Bush Road, London W6 7NJ, UK.

Institute of Grocery Distribution. 1996, 1997. Biotechnology Factfile. Available from IGD, Grange Lane, Letchmore Heath, Watford, Herts., WD2 8DQ.

James, C. (2001) Global Status of Transgenic Crops in 2001. ISAAA Brief No. 24. ISAAA, Ithaca, New York.. 30 pp.

Novel Foods and Novel Food Ingredients Regulations 1997. S.I. 1997/1335 (UK).

Nordlee, J.A. et al. 1995. Identification of Brazil-nut allergen in transgenic soybeans. New England Journal of Medicine 334, 688-692.

Nuffield Foundation on Bioethics (1999). Report "Genetically modified crops: the ethical and social issues" (also available on http://www.nuffieldbioethics.org/filelibrary/pdf/gmcrop.pdf ).

Regulation (EC) No. 258/97 of the European Parliament and the Council of 25 January 1997 concerning Novel Foods and Novel Food Ingredients, Official Journal of the European Communities No L 43, 14 February 1997.

Thompson, J (2003) Chapter 3 in Report on "Genetically Modified Foods for Human Health and Nutrition: The Scientific Basis for Benefit/Risk Assessment"; a Monograph resulting from an ICSU sponsored workshop in 2002 (in press).

UK National Consensus Conference on Plant Biotechnology. 1994. Final Report. Available from The Science Museum, London SW7 2DD, UK.

The Codex Alimentarius Commission revised 3 basic texts on food hygiene in 1997; officially published in Volume 1B of the Codex Alimentarius and have been republished in a compact format: 15 x 21 cm, 58 pages, ISBN 92-5-104021-4 Contents:
May be obtained through the worldwide Sales Agents, see http://www.fao.org/ or Publication-sales@fao.org(cost around $7).

The Institute of Food Science & Technology (IFST) is the independent professional qualifying body for food scientists and technologists. It is totally independent of government, of industry, and of any lobbying groups or special interest groups. Its professional members are elected by virtue of their academic qualifications and their relevant experience, and their signed undertaking to comply with the Institute's ethical Code of Professional Conduct. They are elected solely in their personal capacities and in no way representing organisations where they may be employed. They work in a variety of areas, including universities and other centres of higher education, research institutions, food and related industries, consultancy, food law enforcement authorities, and in government departments and agencies. The nature of the Institute and the mixture of these backgrounds on the working groups drafting IFST Information Statements, and on the two Committees responsible for finalising and approving them, ensure that the contents are entirely objective.

IFST recognises that research is constantly bringing new knowledge. However, collectively the profession is the repository of existing knowledge in its field. It includes researchers expanding the boundaries of knowledge and experts seeking to apply it for the public benefit.

Its purposes are:
(1) to serve the public interest by furthering the application of science and technology to all aspects of the supply of safe, wholesome, nutritious and attractive food, nationally and internationally;
(2) to advance the standing of food science and technology, both as a subject and as a profession;
(3) to assist members in their career and personal development within the profession;
(4) to uphold professional standards of competence and integrity.