GE foods are unsafe!
Physicians and Scientists for Responsible Application
of Science and Technology (PSRAST)

1. General conclusion
Based on both scientific theory and experimental data, it can be concluded beyond any doubt that genetic engineering of plants and animals may potentially cause them to unexpectedly contain substances harmful to people who eat them. Scientists cannot however estimate the probability that harmful substances will be created in any specific case, because not enough is known about the new field of genetic engineering.Some of the harmful substances which are known to be possible in genetically engineered foods could cause allergies or toxic reactions. But, because the knowledge of DNA is incomplete, genetic engineering of food plants and animals may produce other problems which scientists have not yet anticipated.

So GE foods are inherently unsafe and we neither have enough knowledge to estimate the risk for harmful effects nor fully reliable testing methods.

2. Reasons why GE may cause the appearance of unexpected substances
Molecular biologists have shown in the laboratory that the insertion of a gene may induce unexpected metabolic changes that in the worst case may result in harmful substances for the following reasons: With presently used techniques, it is impossible to guide the insertion of a gene. Therefore, it will occur haphazardly in the midst of the ordered code sequence of DNA. This will perturb the normal close control of DNA over metabolic processes resulting in unpredictable effects on the metabolism. This is especially so as, to be successful, the inserted gene has to be inserted in a region of DNA that is active (most of DNA is inactive, and genes inserted there will not have any effect).

“The so called promoter that is always included in gene insertion packages, may cause metabolic disturbances (the most commonly used promoter comes from the Cauliflower Mosaic Virus “CaMV”). The promoter is added because it is an absolute requirement to ensure the inserted gene is “read”; i.e. copied into RNA and translated into the protein for which it codes. In addition, other regulatory sequences called enhancers are often included as they strongly stimulate gene expression. However, the socalled enhancers also stimulate the activity of surrounding native genes with potentially deleterious consequences. The metabolism of the cell may become disturbed in unpredictable ways. The enhancers may also activate genes that should normally bee inactive. For example a toxic protein that normally is only expressed in the leaves of a food plant, may become active in the fruit or seeds used. Moreover, normally, the activity of genes is the result of a refined regulation of their expression, so no gene is active longer than needed. The artificially inserted strongly stimulating promoter-enhancer complex without any coupling to inherent regulatory mechanisms eliminates this delicate demand/supply regulation. This may have unpredictable effects on cellular functioning.”

Genetic engineering means in most cases the insertion of a gene coding for a protein foreign to the species. There is no way of knowing what the presence of a foreign protein will have on the metabolism and functioning of an organism. It may have unexpected effects in addition to its desired effect including the possibility that it may cause the generation of a harmful substance.
The effect of a gene is context dependent. In a foreign environment, it may have unpredictable effects. These effects may be difficult to detect but might in the worst case generate harmful substances. See “The new understanding of genes”. Most of the foreign proteins that are used in genetic engineering have never existed in food. There is no way of knowing beforehand, without extensive food safety assessment, if it is safe to eat food containing such proteins.

Regulatory genes may inadverently be included in the inserted gene, causing unpredictable complications (however, with the kinds of genes presently used, this risk is considered unlikely). The knowledge of regulatory genes is incomplete so there is a risk that an inserted DNA sequence may possess unanticipated regulatory activities. These genes regulate the activity of other genes. This might disrupt any of the cellular processes in which DNA or RNA participate which might result in many kinds of unexpected effects including the production of harmful substances, (for more details, see The underlying mechanism involved in the “reading” of regulatory information... [AL]; (part of an article by John Fagan).) If so called fusion proteins are generated through GE, they may cause unexpected allergies that may be more allergenic than proteins produced by the original DNA sequences. Fusion proteins are created by linking pieces of DNA sequences from two or more sources. The regions where two proteins are joined can assume conformations very different from those of either of the original proteins.

Furthermore, the likelihood of generating allergenicity in fusion proteins is increased by the fact that the junctions at which two proteins are fused often assume configurations that are not common in natural proteins, and are, therefore, more likely to be allergenic. There are also other reasons why genetic engineering might caused increased problems with allergens, see Allergens generated in recombinant foods [AL]; by John Fagan.

A special class of hazards might be unexpected effects of known substances. Obvious candidates are GMOs modified to produce pesticides, substances designed to be toxic. An example of this is the demonstration of long term toxicity of a strain of GMO potato by Arpad Pusztai (Lancet 1999 Oct 16;354(9187):1353-4). Conclusion There are several known ways in which the artificial insertion of a gene may cause unexpected complications of a kind that never occurs in conventional breeding. Some unexpected effects have been experimentally verified, see Examples of unexpected effects of genetic engineering. In addition, because the knowledge about DNA is very incomplete, there may be effects that cannot be even imagined presently, see “Incomplete knowledge about DNA”

It took almost 50 years after the introduction of nuclear technology and synthetic pesticides to appreciate the health and environmental hazards they present. Because recombinant DNA technology (genetic engineering) is even more complex, and because we have almost no experience with it, it is reasonable to expect future surprises. The U.S. FDA and the European Union have been denying any hazards with GE foods. It is satisfying to find that evidence have been unearthed indicating that this has been the result of suppression of truth, see footnote.

3. Is it possible today to estimate the risk for appearance of harmful substances due to genetic engineering?

Risk is the probability that some adverse effect (hazard) will occur in the future. Of course, no one can predict the future with perfect certainty. The degree of accuracy of a risk assessment is dependent on how much relevant information is available, the quality of that information and how well that information is interpreted. Thus, some risk assessments are more reliable than others.
For example, because insurance companies have many years worth of information about automobile accidents, they can predict rather well the characteristics of drivers (using data on age, sex, type of car, and accident history) is most likely to be involved in an accident. On the other hand, because the physics of only a few major earthquakes have been monitored with sophisticated seismic equipment, and because there are debates about what physical signals are important indicators, it is not yet possible to predict the likelihood of a major occurrence.Specifically, it is not possible to assess the risk of harm from eating GE food with a high degree of accuracy because:

Genetic control of cell function is not well understood (see footnote ·Incomplete knowledge of DNA). Not even the DNA sequence of presently marketed genetically engineered plants is fully known.In order to understand what can go wrong with a system and to evaluate its potential to go wrong, it is first necessary to understand how the system works. A cardiologist must understand anatomy, physiology, biochemistry and pharmacology to diagnose heart disease, predict outcome and prescribe appropriate remedies.

Since the genetic control of cell function is an extraordinarily complex system which is only poorly understood, our comprehension of all that can go wrong when foreign genes are added to foods, our ability to predict the outcome of eating such foods, and our ability to design safe GE foods is highly limited.

Furthermore, as anyone who uses a computer knows, the opportunity for malfunction is increased as systems become more complex and as the manipulation of complex systems becomes more random and uncontrolled.·Laboratory experiments with GE have been very limited. For some (but not all) GE foods, some short-term studies have been conducted on experimental animals. But there are almost no long-term toxicological, neurological, metabolic, endocrinological, developmental or reproductive studies of these foods. Such studies are necessary to evaluate the effects of substances which are slow-acting, have cumulative or reproductive effects. For details see ·”The approval of Roundup Ready GE-Soy - based on incomplete evidence” and for a suggested procedure, see ·”Testing the safety of genetically engineered foods” by professor John Fagan.

Human experience with GE foods has been very limited. GE foods have been on the market for only about five years, so there obviously has been no experience with long-term exposure to these novel foods. Few controlled short-term human studies have been conducted on these new foods.

Moreover, since GE foods have not been labeled, there has been no way for scientists to compare the health of people who have and have not been eating them. In contrast, humans have had thousands of years of experience with naturally occurring foods, and the conditions under which they pose hazards (e.g., eating solanine in green potatoes) are well-known. The problems of risk assessment per se have been further aggravated by the way regulatory agencies have been handling the GE food issue, see footnote: Unsatisfactory handling by regulatory agencies.

Conclusion
There is no scientific knowledge at all that makes it possible to estimate how likely it is for harmful substances to be generated in GE foods. But we can definitely say today that there is no scientific basis for maintaining that harmful substances may not appear or are very unlikely.

Problems with food safety testing Safety testing of GE foods is problematic because genetic engineering may give rise to unexpected and unpredictable substances. It is illuminative to compare with a closely related field, the testing of medical drugs,especially as there is an extensive experience of the reliability of such testing.·On the basis of knowledge about the chemical properties of a medical drug, it is possible to predict, to a quite large extent, what kind of harmful effects might occur.

In the case of GE foods, there is no clue to decide if an unexpected substance may be toxic, allergenic, carcinogenic, mutagenic or otherwise harmful.·In medical drug testing, it is possible to expose test objects to several times higher doses than used clinically. This helps to get an idea of the harmfulness of a drug.

For foods, such a procedure is impossible because it would give rise to nutritional mbalances. For these reasons, it is considerably easier to detect harmful effects of a medical drug than of a GE food. Still about 3 percent of drugs released on to the market have been withdrawn because of unexpected harmful effects that were not revealed until the drug had been used at a large scale. And about 10 percent have had so serious side effects that their use has been considerably restricted.

Yet the drug companies have been using the best available methods in the world. Laboratory animal and human testing has been used as well as long term clinical studies. They have been applying the tests very rigorously and carefully. This is because the development of a new drug is very expensive, so a forced withdrawal from the market means a loss of billions of dollars.

The greatest problem in toxicological testing is to reveal long term harmful effects. Against the experiential backgound from medical drug testing, it can be confidently predicted that even most rigorous safety testing of GE foods is likely to fail to detect long term harmful effects to a considerable extent.

The only way of minimizing the risk of not detecting unexpected harmful effects of harmful substances is to use long-term testing. As animals are not fully reliable predictors of food safety for humans, it is necessary to use Physicians and Scientists for Responsible Application of Science and Technology (PSRAST) long term humhttp://www.psrast.org/defknfood.htman studies.Strategies for long term testing of GE foods have been suggested by professor Arpad Pusztai, see “The need for rigorous biological risk assessment” and professor John Fagan, see Testing the safety of genetically engineered foods.

As experimental long term testing is not sufficient to ensure safety, Fagan has suggested a monitored premarketing test on a population of about 2.000.000-3.000.000 people during 2-3 years with close surveillance of its health status. Even with that test included, he concludes that there will remain a “residual risk” for unexpected long term damage.These testing schemes are fundamentally different from the superficial testing that has been presently been accepted for approval of GE foods, see “Substantial equivalence versus scientific food safety assessment”

Footnotes
Incomplete knowledge about DNA Suppression of truth turning untenable Unsatisfactory handling by regulatory agencies Published in May 1999. The present version is the result of an ongoing and not yet completed revision through the contribution from new co-authors.Latest update: May 12, 2000.
All the authors of this document have, along with several other scientists, signed an Open Letter demanding that GE foods that have not been tested properly should be withdrawn from the market (in practice this means all GE foods).

Authors:

Dr Michael Antoniou M.D., Senior Lecturer in Molecular Genetics, GKT School of Medicine, King’s College, London, UK

Dr Joseph Cummins PhD, Professor Emeritus in Genetics, University of Western Ontario London, Ontario, Canada

Dr Edwin E. Daniel Ph.D. FRSC, Professor Emeritus Health Science, Faculty of Health Sciences, McMaster University, Hamilton, Ontario Canada

Dr Samuel S. Epstein M.D., D.Path., D.T.M&H, Professor of Environmental and Occupational Medicine at the School of Public Health, University of Illinois Medical Center Chicago, USA

Dr C. Vyvyan Howard MB. ChB. PhD. FRCPath. Senior Lecturer, Toxico-Pathologist, University of Liverpool, UK

Dr Bob Orskov DSc, OBE, FRSE, Honorary professor in Animal Nutrition of Aberdeen University, Macauley Land Use research Institute, Aberdeen, UK

Dr Arpad Pusztai FRSE, Biochemistry&physiology. Retired, formerly at Rowett Institute, Aberdeen, UK.

Dr N. Raghuram Ph.D., (Plant Molecular Biology) Lecturer, Department of Life Sciences, University of Mumbai, (formerly Bombay), India.

Dr Gilles-Eric Seralini PhD, Hab.Dir.Rech., Professor in Molecular biology, University of Caen, France

Dr Suzanne Wuerthele Ph.D., Toxicologist and risk assessor, Denver, Colorado, ISA Editor: Dr Jaan Suurkula, M.D. Chairman of PSRAST

“Genetically Engineered Food - Safety Problems” Published by PSRAST www.psrast.org/defknfood.htm

Jaan Suurkula psrast@swipnet.se , info@psrast.org