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Human genes and GM tomatoes as medicines (14/9/2004)

Here's a response from EPA toxicologist, Dr Suzanne Wuerthele, writing in a personal capaity, to a posting by Prof Joe Cummins on research on the "folate enhancement" of genetially engineered tomatoes using a synthetic copy of a human gene gene. As Dr Wuerthele notes, "The idea of genetically engineering foods to make medicines raises many issues" and Dr Wuerthele deals with many of these issues point by point.

The background to this particular research, as Prof Cummins had noted, is that "folic acid deficiency is a major factor in neural tube birth defects, such defects are very prevalent in modern society. The deficiency is also implicated in breast cancer and heart disease. The most simple procedure has been to add folate to bakery products. The publication below shows how tomatoes may be enhanced by genetic modification using a synthetic copy of a human gene."

The publication is:
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.040
Folate biofortification in tomatoes by engineering the pteridine branch of folate synthesis
Rocío Díaz de la Garza *, Eoin P. Quinlivan , Sebastian M. J. Klaus *, Gilles J. C. Basset *, Jesse F. Gregory III , and Andrew D. Hanson *
Departments of *Horticultural Sciences and Food Science and Human Nutrition, University of Florida, Gainesville, FL 32611
---

From <[email protected]>

The idea of genetically engineering foods to make medicines raises many issues, as we have seen with the infamous "golden rice". The GE folate tomato presents these and other issues, too:

1. Is this really necessary? Folate is readily available in supplements, and women who could get pregnant are advised to take folate supplements. This seems to be an effective solution, at least among people who can afford the supplements. Will poor women who cannot afford supplements be able to afford these high-tech tomatoes? Surely the University of Florida will at least want to patent the GE folate tomato so they can recoup what will likely be high development costs. They may also wish to make a profit from future sales.

2. Folate content in supplements can be carefully controlled, but it is not likely to be controlled in a perishable fruit which comes in different sizes, and which might produce different amounts of folate at different stages of ripeness or even under different agronomic conditions. Recently researchers who toyed with the idea of producing vaccines in tomatoes admitted that the fruit would have to be dried, pulverized, chemically analyzed and encapsulated so that dose could be controlled. What is the advantage of going through all this when we already have folate in supplement form?

3. We have learned that it would be necessary to eat many pounds of "golden rice" daily to prevent Vitamin A deficiency. How many GE folate tomatoes would a woman have to eat to ensure she will not have a child with neural tube defects?

4. Could GE folate tomatoes present a risk of excessive consumption? Even though oral folic acid is not directly toxic to humans, it may counteract the effect of antiepileptic drugs. FDA has recommended that oral tablets of folic acid be limited to 1 mg or less. How could people who need to avoid excess folate identify the GE folate tomatoes? Will FDA require folate tomatoes to be labeled with a warning? Who would be liable if someone with epilepsy had seizures as a result of eating folate tomatoes?

5. Genetically engineered organisms have produced unintended toxicants Genetically engineered yeast developed for the brewing industry produced the toxicant methyl glyoxal and had to be abandoned. High methionine soybeans containing a nut transgene had to be abandoned when it was learned that people allergic to nuts could react to the soybeans.

Roundup Ready (glyphsate-resistant) soybeans have a lower concentration of some phytoestrogens than normal soybeans. Will the GE folate tomato produce unintended toxicants, or allergens or have reduced nutritional properties? Will FDA require the manufacturers of the folate tomato to ensure its equivalency to normal tomatoes with real data? Or will it just assume it is "substantially equivalent" as it does with other GE crops?

6. Recently the University of California at Davis revealed that it had accidentally shipped genetically engineered tomato seeds to agronomic researchers all over the world, but had told the recipients that they were simply another non-GE cultivar. How will seeds from GE folate tomatoes be contained?

7. The main transgene of interest in "golden rice" comes from the daffodil. The GE folate tomatoes will receive a gene described by its creators as "a synthetic gene based on mammalian GTP cyclohydrolase I". Joe Cummins informs us that this actually is a synthetic copy of a human gene. Clearly, production of human proteins in food via transgenes derived directly from humans would present ethical or religious problems for many people. What about proteins derived from a synthetic form of a human gene?

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