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Why Putting Human Genes in GE Tomatoes is a Bad Idea

9/11/04

GM WATCH daily
http://www.gmwatch.org

---
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 <Wuerthele.Suzanne@epamail.epa.gov>

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?

Origional post from SANET by Joe Cummins

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 use of synthetic copies of human
genes in food crops does deserve special attention and study.

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

Plants are the main source of folate in human diets, but many fruits,
tubers, and seeds are poor in this vitamin, and folate deficiency is a
worldwide problem. Plants synthesize folate from pteridine,
p-aminobenzoate (PABA), and glutamate moieties. Pteridine synthesis
capacity is known to drop in ripening tomato fruit; therefore, we
countered this decline by fruit-specific overexpression of GTP
cyclohydrolase I, the first enzyme of pteridine synthesis. We used a
synthetic gene based on mammalian GTP cyclohydrolase I, because this
enzyme is predicted to escape feedback control in planta. This
engineering maneuver raised fruit pteridine content by 3- to 140-fold
and fruit folate content by an average of 2-fold among 12 independent
transformants, relative to vector-alone controls. Most of the folate
increase was contributed by 5-methyltetrahydrofolate polyglutamates and
5,10-methenyltetrahydrofolate polyglutamates, which were also major
forms of folate in control fruit. The accumulated pteridines included
neopterin, monapterin, and hydroxymethylpterin; their reduced forms,
which are folate biosynthesis intermediates; and pteridine glycosides
not previously found in plants. Engineered fruit with intermediate
levels of pteridine overproduction attained the highest folate levels.
PABA pools were severely depleted in engineered fruit that were high in
folate, and supplying such fruit with PABA by means of the fruit stalk
increased their folate content by up to 10-fold. These results
demonstrate that engineering a moderate increase in pteridine production
can significantly enhance the folate content in food plants and that
boosting the PABA supply can produce further gains.

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This GMO news service is underwritten by a generous grant from the Newman's
Own Foundation and is a production of the Ecological Farming Association
www.eco-farm.org <http://www.eco-farm.org/>
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