ISIS Report 26/05/04
Pharm Crop Products In US Market
Prof. Joe Cummins discovers that
dangerous GM pharmaceutical crops have been produced and marketed in the United
States for at least two years, unbeknownst to the public, via a gaping loophole
in the regulatory process.
A fully referenced version of this article is posted on ISIS
members website. Details here.
There has been a great deal of public opposition recently to the testing
of rice genetically modified to produce the human proteins lysozyme and
lactoferrin in the United States. So far, those tests have been stalled (see
But, Sigma-Aldrich, a US chemical company, has been marketing the
biopharmaceutical products trypsin, avidin and beta-glucuronidase (GUS)
processed from transgenic maize, for at least two years. Meanwhile, Prodigene
Corporation and Sigma-Aldrich are marketing aprotinin (AproliZean) from maize
and from a transgenic tobacco.
Trypsin is a digestive enzyme used extensively in research, to treat
disease and in food processing. The product TrypZean is marketed as an animal
free product, and is produced jointly by Sigma-Aldrich and Prodigene (the
company fined for contaminating food crops with biopharmaceuticals in the
United States last year).
The development of genetically modified (GM) food crops generally
follows a certain pattern in the United States: First, controlled field tests
are undertaken for a number of seasons. Then, the proponent applies for
deregulation of the GM crop following reviews by the Animal Plant Health
Service (APHIS) of the Department of Agriculture (USDA), the Food and Drug
Administration (FDA) and by the Environmental Protection Agency (EPA) if the GM
crop includes a plant incorporated bio-pesticide. Upon completion of the
process, the GM crop is deemed to be deregulated and can be grown without
However, none of the biopharmaceutical-producing GM crops appears to
have gone through the usual regulatory process. Instead they appeared to have
progressed from field-testing to marketing without the benefit of final
regulatory approval, with apparently full cooperation of the FDA and USDA (the
agriculture department has proprietary interest in some of the
biopharmaceuticals). The biopharmaceuticals have proceeded to the market via
the backdoor, thanks to a loophole in the regulation of field tests.
According to the Pew Initiative on Food and Biotechnology, "current
APHIS regulations do allow the commercialization of a GE [genetically
engineered] crop without a prior affirmative approval by the agency and without
public notice. Developers are not required to file a petition for non-regulated
status before they produce a plant commercially. It is possible for developers
to grow plants at a commercial scale under notification or field trial permits,
even if the plants might pose some identifiable environmental or human health
Crop production facilities are permitted as "field tests", but locations
of such facilities are designated "confidential business information" and are
not disclosed to people living nearby, even though the genes and products of
such sites can easily contaminate crops, ground water and surface water. There
seems to be no direct way to find out where the production facilities are,
except via producers and government regulators.
The US government seems committed to going ahead with a procedure that
bypasses public input and scrutiny, and which if, when disclosed, will threaten
the marketability of US food exports. In contrast, the Canadian Food Inspection
Service maintains that "plant products of test sites cannot be marketed", even
though numerous plant biopharmaceutical products have been tested.
The regulation of plant-derived biopharmaceuticals was reviewed by the
FDA in 2000; and by the Pew Initiative in 2004. Only the Pew report came to
grips with the practice of marketing virtually untested products commercialized
without public input.
As indicated earlier, test plot permits for crops producing
biopharmaceutical proteins are usually designated confidential business
information so that the nature of the products is hidden from the public as
well as the location of the test sites. APHIS does, however, record the crop
and the state in which the modified crop is tested. Between 2003 and 2004,
Prodigene had test plots in Nebraska, Texas, Iowa and Missouri.
Production of the commercial biopharmaceuticals was, for the most part,
achieved using maize, even though it is a food crop of fundamental importance
and should not have been used to produce biopharmaceuticals, especially when
the products are by no means benign for humans and animals exposed to them.
Trypsin is an enzyme produced in the pancreas to digest proteins. It is
extensively used in laboratory applications, in wound treatment and to treat
diabetes. It is also used in food processing and often put into infant
formulations to aid in digestion. The plant-produced product is desirable
because it is free of prions and animal viruses.
According to the safety data sheets provided by trypsin manufacturers,
the product is capable of causing allergy it is a skin, eye and
respiratory irritant and may be a mutagen.
Avidin is a protein found in birds eggs. It functions to bind the
vitamin biotin, which is required for many insect pests. The pests are
inactivated by the absence of the necessary vitamin. Transgenic maize modified
for avidin production is resistant to storage insect pests.
A case study done by the Friends of the Earth turned up substantial
evidence that the protein avidin caused dangerous biotin deficiency in humans
and animals, leading to immune deficiency and growth retardation. Even marginal
biotin deficiency is linked to birth defects in mice and in humans.
Aprotinin is a protease inhibitor normally prepared from the pancreas
and lung of cows. Recombinant aprotinin produced in plants is currently
marketed. Bill Freese of Friends of the Earth reviewed the problem of allergy
and pancreatic disease associated with this product.
Aprotinin is also listed as a reproductive hazard. There is serious
danger to those exposed to aprotinin after having had a previous exposure. For
example, a two-year old child suffered severe anaphylactic shock (a
life-threatening allergic reaction characterized by swelling of body tissues
including the throat, difficulty in breathing, and a sudden fall in blood
pressure) after a test dose of aprotinin. Fatal anaphylaxis followed aprotinin
exposure in a local application of fibrin glue. A similar application led to an
immediate skin reaction following re-exposure to fibrin sealant.
Secret field testing of plant-based recombinant aprotinin could
result in severe or fatal anaphylaxis, either in a brief exposure in the maize
field of someone previously treated during surgery, or exposure of someone
exposed to the maize field followed by treatment during surgery.
The final commercial recombinant protein in maize is
beta-glucuronidiase (GUS). The gene is used in a wide range of experimental
situations but does not appear to have therapeutic importance. It has been
observed that formula milk for infants had a low content of GUS while
mothers milk had elevated GUS.
Elevated GUS has been implicated in bilirubinaemia (jaundice) of
breast-fed infants and breast-fed infants of diabetic mothers. GUS is used
extensively as a marker, believed to have little effect on the phenotype of the
test organism. However, GUS was found to enhance the feeding activity in the
peach aphid, suggesting that the marker may not be entirely without effect on
In conclusion, the secretive production of dangerous pharmaceuticals in
food crops is a truly disturbing development. The sale of such products without
transparent public approval is adding insult on injury, reinforcing the public
perception that the regulatory authorities are putting corporate profit far
above public safety.