Eating Growth Factors? No Thanks

Eating Growth Factors? No Thanks
Stanley Ewen
Consultant Histopathologist, Grampian University Hospitals Trust
(Presentation made at the launch of the Independent Science Panel, 10 May 2003, London)

Stanley Ewen extended Arpad Pusztai’s talk, discussing the effect of GM potatoes on rat guts. He said that the GM potato used in the research does have growth factor effects. (Growth factors are proteins that promote cell growth and multiplication that, if uncontrolled, result in cancer.) While stressing that he did not believe that GM potatoes are fully carcinogenic or capable of causing cancer, he cautioned that we need to be careful about what we are eating, as there could be indirect effects.

Ewen reported that the feeding of rats with GM potatoes for 10 days produced elongation (or thickening) of the small bowel mucosa (the lining of the small bowel). This effect has also been observed by other independent workers – Fares et al. fed mice raw GM potatoes and recorded similar findings (Fares NH and El-Sayed AK. Fine structural changes in the ileum of mice fed on endotoxin-treated potatotes and transgenic potatoes. Natural Toxins, 1998, 6, 219-33).

He compared the two pieces of research: Fares et al. in 1998 used 4 week-old male mice, and fed them for 14 days. The inserted gene was Bt, and they examined the mucosa of the mouse ileum by planimetry. Their results showed 21.7% increase in the size of the ileal cells after feeding with GM potatoes. Ewen and Pusztai in 1999 used 6-week old male rats, and fed them for 10 days. The GM potatoes had the snowdrop gene, and they looked at the jejunal crypt by image analysis. They recorded an increased length in the crypt of 57.8%.

Ewen then showed slides of the rat jejunum, the first part of the bowel, after feeding with raw GM potatoes and raw parent line (non-GM) potatoes. When the villi – the finger-like projections in the gut involved in absorbing and secreting – were examined, there was clear elongation of the crypts, in rats fed GM potatoes (see Slide 1). (The villi also showed slight elongation.) Something has clearly caused this, and the only difference they knew about was that one had the inserted GM construct, and the other was an ordinary potato from off the shelf.

They observed similar effects in the ileum, at the lower end of small bowel (See Slide 2). Clearly, this is something that affects the whole length of the small bowel. The rats fed GM potatoes had very elongated ileal crypts, compared to those fed with the parent line potatoes.

Ewen then described additional unpublished observations of their research. (In a sense, these additional findings have now been published in the new review: Pusztai A, Bardocz S and Ewen SWB. ‘Genetically Modified Foods: Potential Human Health Effects’, Chapter 16 in Food Safety: Contaminants and Toxicants. JPF D’Mello, ed. 2003. CABI Publishing. See the ISP website for the link to the paper.)

They found that that number of cells in the crypt and the mitotic rate (i.e. the number of cells actually dividing) had increased in the small bowel of young rats fed GM potatoes.

Ewen said that the increased cell length, the increased number of cells and the increased mitotic rate, are in his opinion, changes that indicate that GM potatoes have acted as a growth factor leading to hyperplasia of the lining. (Hyperplasia is enlargement of an organ or tissue due to increased reproduction rate of its cells, often as an initial stage in the development of cancer).

The crypt cell count had gone up by about 25% and the number of dividing cells had also increased. These were highly significant differences.

In addition, the number of lymphocytes within the epithelium also increased significantly, in rats fed GM potatoes, when compared to rats fed parent line potatoes. In the jejunum, this statistically significant difference was found in rats fed raw GM potato. With rats fed boiled GM potato, the process of which was expected to inactivate whatever in the construct that was causing the effect, significant difference was also found.

Ewen then went on to ask, what about the colon? If effects were observed in the small bowel, then changes could be expected in the colon as well. Indeed, microscopic changes are certainly present in the rat colon. Could active GM material reach the colon and not be digested in the small bowel? Harry Gilbert and colleagues have shown that GM DNA from soya reaches the colon in human ileostomy patients. However, as the clinical history and details are not known, it is an imperfect experiment. Nonetheless, it is reasonable to suggest that GM soya products do reach the end of the ileum, and hence are capable of being presented to the colon.

He then showed slides of the rat colon, when fed with cooked GM potatoes compared to raw GM potatoes. With the rats fed raw GM potatoes, their colon cells showed elongation and thickening (see Slide 3). There is a change in the colon, and the cells appear bigger in the crypt.

He also showed a slide that confirmed Gilbert’s observation, showing a specimen from a surgeon who had conducted a colectomy. There was vegetable material the size of a small pea still present in the terminal ileum, and which contained DNA. When faecal material in the colon is examined, it also has a great deal of DNA still present in the vegetable material. Such DNA might act as a source of whatever is present in the GM potatoes that causes the effects they observed.

Ewen went on to explain the significance of growth factors getting into human colon. Disease of the colon is common and is either inflammatory or neoplastic. (Neoplasia is the presence or formation of new, abnormal growth of tissue, especially as a characteristic of cancer. This is illustrated by the polyp-cancer sequence; see later.)

He stressed that he was not saying that GM food directly causes cancer of the colon. He only wished to raise the possibility of growth factors and the possible effect in the human colon.

He asked, “How safe is exposure of the diseased colonic mucosa to growth factors present in GM food?” Food manufacturers assume that everyone has normal stomachs and normal colons, but that is far from the truth. Would diseases of the stomach enable GM food to be abnormally digested?

He explained that colon cancer is the biggest killer in non-smoking males in Scotland. In Northeast Scotland, Ewen has showed that the population there has a very high incidence of colonic polyps. Some polyps (about 30%), but not all, will become invasive cancer.

Ewen then described the polyp-cancer sequence. At the present time, the cause of colon cancer is not known. Experts assume that if the faecal content of the colon is imbalanced in some way, then polyp formation can occur on the surface of the colon. Step by step, the polyp increases in size, aided by growth factors in the faeces, eventually resulting in malignancy. This process is assumed to take several years.

At different stages of the process, extraneous growth factors, such as GM food, could contribute to this process. Ewen further asked if adding extra growth factors could speed things up.

Screening for polyps is important, as assuming that the polyp-cancer sequence takes several years, mortality can be reduced if these effects are picked up. Such screening is already happening in Eastern Scotland.

Ewen was concerned that food growth factors could accelerate the polyp-cancer sequence, particularly if there is going to be more and more GM food, especially GM fruit that is eaten raw. If this were to happen, the screening interval would have to be more frequent.

Ewen concluded that raw GM potato growth factors could reach the human colon. They could act on the colon of those predisposed to develop polyps. This may accelerate the polyp-cancer sequence. Expensive screening programmes may then have to be revised by reducing the screening interval.

During the Question and Answer session, Ewen pointed out that as far as he was aware, nobody has conducted studies to see if these growth factor effects have accelerated cancer sequences in animals, which was something they (Ewen and Pusztai) would have done, if the project hadn’t been shut down due to the ensuing controversy.

When asked if this growth factor effect is a general feature of genetic modification, Ewen pointed to the Fares research, which showed a similar effect. He also mentioned that the Flavr Savr tomatoes did cause problems in the stomach, i.e. ulceration, which was however something they had not observed in their research.

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