GM Free Cymru

GMOs and Human Health

(Comment from GM-Free Cymru: This is one of the most thoughtful and well-informed assessments of the GMO-health issue that we have seen. It was first published in the year 2000, and it should be compulsory reading for our regulators who nowadays wave through GM applications without even bothering to read them.)

by Dr Stanley W.B. Ewen

Human health issues are difficult to quantify but will usually relate to the 6th decade upwards in a "Western - type" society. Food related changes may thus be extremely difficult to detect as degenerative changes become dominant and life style indiscretions, occurring 20 years previously, easily forgotten or overlooked. BSE may have little to do with human GMO ingestion but lessons can be learned from the catastrophe that has all but destroyed British farming.

The possibility of transmission of an apparent species specific pathogen to cattle or humans was completely ridiculed initially and television pictures of a government minister feeding his baby daughter a pie potentially containing tainted meat was dramatic although reprehensible. BSE is, as the name indicates, a spongiform condition of the brain that was rare in humans and always recognised in the elderly. It was only after neurologists and neuropathologists recognised that some young people developed a clinical syndrome closely analogous to Creuzfeld Jacob disease that a new disease was perceived (NVCJD). The unwillingness of government agencies to recognise the remote possibility of a new food related disease in young adults was incomprehensible. The lesson revealed by this disaster seems clear; a new disease will only be recognised when it has unusual pathology, occurs in an unusual age group and has overt recognisable clinical features. The demonstrated proclivity for food related disease to affect the young should not be understated. Several diseases seem to affect growing children rather than fully developed adults with static body parameters. It must also be stated that no current test considered to be sufficient evidence of safety would or could have detected NVCJD. It follows that all new foods, in particular GM food, must be tested in animals, especially young animals, as the human guinea pig approach seems to be global anathema.

With these factors in mind, the present oft reiterated banal statement by regulatory authorities that many billions have eaten GM food with no reported ill effect seems misleading. As I commented at the recent WHO/FAO expert consultation in Geneva, diseases with a biological history measured in decades, such as cancer, would not be observed to be significantly increasing in the elderly or occurring in the young until several years of careful analysis of records had been compared. The specific reason for highlighting cancer is based on my meticulous measurement of changes within the gut lining in young rats fed GM potatoes for 10 days (Lancet 354, 1353-1354 16th October 1999). Despite all manner of attack, the peer reviewed published histological observations are unassailable and reveal a clear growth factor effect visualised as microscopic lengthening of the proliferative compartment of the lining of stomach and intestines. This effect may not be permanently harmful and is probably reversible after a few days of GM withdrawal but increased chronic inflammatory cells were also evident consistent with involvement of the immune system. Proliferative effects have been previously recorded following GM food ingestion viz. proliferation of stomach lining following 'Flavr Savr' tomatoes and proliferation of small intestinal lining following ingestion of transgenic potatoes by mice (Nat. Toxins (1998) 6,219-233).

Unfortunately food scientists seem oblivious of the fact that the population is not all adult and that approximately half of all adults have disease of either stomach or large intestine. The stomach disease I refer to is H.pylori infection that has been shown to be closely associated with gastric cancer. H.pylori is a micro organism that causes chronic inflammation accompanied by proliferation of the lining of the stomach and is present in 40% of the population by age 40 years. It is reasonable to suggest that additional dietary growth factors in GM food could further increase proliferative effect hastening the development of gastric carcinoma; similarly polyps in the colon could be accelerated to become invasive cancer. After several years of chronic inflammation, the stomach will change its lining to resemble the small intestine and, later still, lose the ability to produce acid and enzymes if the infection is not eradicated by powerful triple antibiotic therapy.

Ewen and Pusztai's histological results clearly indicate that the growth factor effect is not caused by the newly expressed transgenic protein but appears to be due to the gene construct inserted into the recipient DNA. The construct includes, not only the transgene, but also marker genes and a powerful promoter. Endogenous plant promoters seem unable to cause transgene expression and most success can be expected by using a viral promoter to drive foreign gene expression for example, (-carotene was not expressed in rice using endogenous promoters and a viral promoter was required to produce "golden rice". The use of a viral promoter, the infectious part of the virus, seems to be alien to food safety as the usual viral promoter is almost identical to human hepatitis B virus. Hepatitis B is endemic in African and Far Eastern populations and any possibility of intact promoter reaching liver might have unexpected effects. The possibility of gene transfer, either to resident gut commensal micro organisms or gut lining cells, is considered all but impossible. Most molecular biologists do not accept the possibility and assess the chance at 1 in 1027 although many experts suggest that 1 in 1015-18 is the reality. On the other hand, the infectious part of a virus might not be degraded in the stomach and could gain access to gut bacteria or lining cells similar to sporadic viral infection of the stomach or intestines.

The essential problem hinges on complete degradation of food proteins during digestion. Current testing of completeness of digestion relies on recombinant proteins exposed to stomach enzymes (non human source) and acid in vitro. This artificial system demonstrates that simple recombinant proteins are indeed destroyed but I do not consider this approach to be representative. Recently, a sample sent to the Pathology Department, University of Aberdeen was submitted as a possible gall stone found at the end of the small intestine during an operation. Histology revealed that the object was recognisable as a seed despite having been exposed to gastric juices , pancreatic enzymes and small intestinal enzymes during transit. The undigested seed contained identifiable DNA (confirmed by specific tests) that could have leaked from the seed during passage along the small intestine. Thus the plant cell walls prevented digestion in the upper gastrointestinal tract and horizontal gene transfer was a possibility throughout stomach and small intestine at least. Our histological experiments, referred to above, do reveal that cooking reduces the growth factor effect of GM potatoes consistent with the observation that 950C or higher, is required to degrade DNA beyond the point of genetic information transmission (Chiter et al). It could be argued that the presently available heavily processed GM products may not be capable of genetic information transmission and oil from rape seed contains almost no GM DNA. I believe that the real problem that we face is with fruits and vegetables that are usually eaten raw (the normal diet contains about 30% raw plant produce whereas the vegetarian diet will be at least twice this amount). GM fruits and vegetables have not been released as yet but have certainly been successfully produced.

Unfortunately human food is not suitable for testing in a standard toxicological experiment. In a classical toxicological investigation a single substance of defined chemical composition can be administered in identical dose to a group of laboratory animals. Even a single foodstuff is considered to be too complex to dissect out a single undesirable effect that can be acceptable as unsafe. For this reason, GM food safety relies on simple identity, by chemical analysis (substantial equivalence), compared to the parent - nutritional and metabolic effects are not considered. Unfortunately, substantial equivalence is imprecise and the degree of acceptable variation has never been stated. Undoubtedly, adequate nutritional and metabolic GM evaluation would require laboratory animal testing that would greatly increase the approval costs of GM products.

Postscript; at the time of writing (19.10.00) the local press contains a report from Prof. R. Orskov (formerly of Rowett Research Institute) who states that he will not drink milk from cows fed with GM maize until further testing is performed.

Impressions of operation of Joint FAO/WHO Expert Consultation on foods derived from Biotechnology. I was asked to submit my curriculum vitae to WHO by Consumers International and, to my surprise, I was invited to attend the above consultation meeting in Geneva on May 29 this year. I was completely unfamiliar with proceedings but most of the others present were "old hands" and immediately subverted the meeting by proposing and seconding the chairman (Kuiper). Then Mariansky was proposed and seconded as reporter and, despite protestation, was accepted as the American influence was dominant. The WHO staff seemed powerless to prevent this take over despite trying to infuse transparency by inviting others, such as myself, new to the meeting. My enduring impression was that North American, English, Dutch and Scandinavian interests were well represented although other European, Asian, South American and African interests were not. The experts, apart from one nutritionist, one epidemiologist, one economist and one pathologist, were food scientists usually from national regulatory bodies. With amazing alacrity, they stamped their dominance on the meeting and comments from the minority groups were given rather short shrift and were not incorporated into the final version of the report. The meeting was unrepresentative and financial, industrial and government interests were not fully disclosed. Food safety was in the hands of plant molecular biologists with unknown allegiance and medical aspects were simply a nuisance that impeded dominance of big industrial companies.

One subject that did receive attention - Allergenicity of GM Foods - will be the main topic for discussion at the next meeting (Rome January 2001). Allergenicity is of concern because there is no animal model available and all testing has to be done in human volunteers, preferably allergic human subjects. Several GM foods express a bacterial toxin or lectin and these proteins are resistant to cooking and digestion and will bind to, and enter, the lining cells of the intestines (usually considered a prerequisite to allergenicity). The proposal, presented at the Geneva meeting, is to use post market surveillance to detect GM food allergy despite the fact that, for some, the allergy will be fatal.

Environmental matters

There can be little doubt that reduction of biodiversity is deprecable and once GM seeds are broadcast the ensuing contamination is permanent. Thus, should any adverse effect be traced to GM plants at some point in the future then eradication will be well nigh impossible. The difficulty is that many companies have persuaded the authorities to believe that genetic engineering resembles traditional plant breeding methods. This viewpoint negates the fact that foreign DNA has been inserted into the recipient plant in a way that is completely at odds with natural breeding. Once the foreign gene has been successfully inserted a powerful promoter, usually viral, is required and most people would prefer not to eat living virus. It is possible that the promoter may not be broken down in the mammalian gut and thus the environmental contamination would include all sea life. It does appear foolhardy to promote planetary pollution unless some other motive, such as patenting with exclusive rights and substantial profits, is at stake. Unfortunately many of those on government advisory committees have clandestine financial interests and thus plant molecular biologists determine policy best suited to profit rather than complete safety evaluation. The old refrain that GM technology is required to feed the burgeoning world population is promotion by guilt. The United Nations Food and Agriculture Organisation (FAO) recently concluded that the world could be fed without GM food (Agriculture: Towards 2015-30, FAO April 2000). In Europe, current non GM agriculture is so productive that 10% of cereal land has to be kept out of production and it appears that civil strife and corrupt government is responsible for malnourishment in the Third World. Deliberate environmental pollution, in the form of US food aid sent to cyclone victims in Orissa, India, occurred last October and consisted of GM soy beans and maize rejected by traditional markets in Europe and Japan. It is claimed that the US government used the opportunity to create a market entry for GM products. This type of approach pays little heed to traditional agriculture and will severely limit future biodiversity.

Stanley William Barclay Ewen, M.B.Ch.B., Ph.D., F.R.C. Path., Department of Pathology University of Aberdeen Foresterhill, Aberdeen AB25 2ZD Scotland

Soul and conscience witness statement by Stanley William Barclay Ewen M.B.Ch.B., Ph.D., ROYAL COMMISSION NZ