The reasons why hazardous substances may be created because of genetic engineering

The hereditary substance consists of so called DNA molecules. These are long sequences of small molecules, tied together. There are four kinds of these molecules. The sequence of these molecules constitutes the genetic code which instructs what proteins should be synthesised by the cell. Some proteins act like signal substances, controlling the activities, others are enzymes, catalysing various cellular processes and still others become the material out of which the cell is built. And all this variety of substances is governed entirely by the activity in the DNA and the sequence of the DNA code. Only a small proportion of the whole DNA of a cell is active.

The text in point 1 and 2 below is mainly based on the article "Assessing the safety and nutritional quality of genetically engineered foods [ML] " (size 73K) by the molecular biologist John Fagan. Because of the length of this article, we have below, for Your convenience, linked to separate files with excerpts from this article.

Genetic engineering causes two drastic changes in the cell of the recipient organism:.
1) A new gene is introduced haphazardly into the genetic code of DNA. To be successful, the insertion has to be in the active regions of DNA.
2) The new gene will cause the creation of new proteins, most often alien to the species of the recipient.

Both changes may have unexpected consequences:

1. UNEXPECTED EFFECTS BECAUSE OF THE INTRODUCTION OF A NEW GENE

a) Effects because of the genetic change (mutation). There are no possibilities presently to direct the insertion of the new gene. It is a matter of pure chance where it becomes attached. The insertion may occur in the middle of a DNA-code sequence that instructs the creation of an important protein. This will change the properties of the protein so that it may in the worst case become toxic or allergenic. Or the presence of the protein may disturb the functioning in the cell so that harmful substances are created in the worst case. If the protein is an enzyme, important changes may occur in the cell metabolism. This may again result in the creation of new and in the worst case toxic or allergenic substances. The synthesis of important nutrients may be changed or stop. Furthermore, the fact that successful insertion has to be in an active region of DNA increases the disturbing effect of the inserted gene on the functioning of the neighbouring genes. The normally tight and precise control of cellular metabolism is therefore more or less perturbed by genetic engineering.

See also the section on mutations due to genetic engineering in John Fagan's article.

b) Effects because of the influence from an inserted promoter gene. The gene to be inserted is often combined with so a called promoter gene (from certain viruses). A promoter gene has the function of enhancing the activity of the genes associated with it. But the promoter gene may not promote only the activity of the inserted gene, but may influence the activity of other neighbouring genes. The effect may be especially strong if it happens to be inserted close to a so called regulator gene that regulates the activity of other genes. Then the creation of important substances, for example enzymes, may increase or decrease considerably which may have unexpected and in the worst case hazardous consequences. A promoter gene may also happen to be inserted close to a gene that governs the creation of toxins or allergens in an other part of the plant than the one used as food. Thereby it may stimulate the production of these substances in the part used as food.

2. UNEXPECTED EFFECTS BECAUSE OF THE CREATION OF NEW PROTEINS DUE TO GENETIC ENGINEERING

a) The new proteins often come from organisms that are very different from the recipient organism. For example genes from bacteria and fish have been inserted into plants. There is no experience at all whether these proteins are suitable to eat for human beings. The proteins may be allergenic, toxic, mutagenic or carcinogenic.

b) The new protein may influence the metabolism of the cell so that unexpectedly, new molecules are created that may be toxic, allergenic or deleterious in other ways.

See also the section on new proteins due to genetic engineering in John Fagans article.

Conclusion: It is inevitable that more or less pronounced disturbances of the functioning of the cell occur due to the insertion of a new gene into active regions of DNA. There are several different possibilities how this disturbance may cause unexpected creation of harmful substances of various kinds.

For a more thorough presentation, see the chapter "Molecular mechanisms..." in the above mentioned article by John Fagan.

Se also "The Safety of Genetically Engineered Foods. Reasons to expect hazards and the risk for their appearance." a scientiic paper that explains how hazardous substances can appear.

EXAMPLES OF CASES WITH UNEXPECTED EFFECTS

Below some experimental results are presented that verify that unexpected new substances that may be harmful, can appear because of genetic engineering

The research on genetic engineering and the development of new transgenic organisms has to a very great part been financed by the Biotechnological industry. The policy of the industry has been to exaggerate the benefits while downplaying or denying problems with genetic engineering. Therefore it is justified to suspect that cases of unexpected biochemical complications, are not likely to be reported.

Examples of suppression or witholding of facts

One example is the finding of damage to mouse intestines caused by the FlavrSavr Tomato. In this case it was US Food and Drug Administration (FDA) that suppressed the finding. FDA scientists noted a pattern of stomach lesions that raised a safety issue. Therefore they repeatedly requested more testing. Yet none was performed. Consequently, FDA experts concluded "... the data fall short of 'a demonstration of safety'" and said "... unresolved questions still remain." Yet, the FDA not only approved the tomato, it claimed that all relevant safety issues had been satisfactorily resolved - and that because the Flavr Savr did so well, it would be unnecessary for any subsequent GE food to go through the same rigorous testing." This was revealed when a lawyer, Steve Druker in a Lawsuit against FDA obtained confidential FDA documents (see http://www.psrast.org/fdalawstmore.htm)

An other example of suppression is the case of a bovine growth hormone that was maintained to be identical with its natural counterpart. But it was disclosed that the amino acid lysine in the hormone unexpectedly had been replaced by the amino acid epsilon-N-acetyllysine (Violand BN et al. Protein Science. 3:1089-97, 1994). Such a change of a protein may change its properties and effects.

Another way of suppressing the truth has been to make studies that give a misleading impression of safety, see the article "How It Happened That We Don't Regulate Biotech".

A few examples of published unexpected effects

1. Tobacco plants were genetically engineered to produce the Gamma-linoleic acid. In stead the plant unexpectedly mainly produced the toxic octadecatetraenic acid. This substance does not exist in the natural tobacco plant. (Reddy SA, Thomas TL. Nature Biotechnology, vol 14, sid 639-642, May 1996).
2. When a yeast was manipulated for increased fermentation there was an unexpected production of a metabolite (methyl-glyoxal) in toxic and mutagenic concentrations. (Inose, T. Murata, K. Int. J. Food Science Tech. 30: 141-146, 1995).
3. When a gene from the Brazil Nut was inserted into a Soy bean it appeared that it unexpectedly caused strong allergic reactions in people allergic to nuts who never had any problems formerly in eating soy products.(Nordlee, J.A. et al. The New England Journal of Medicine 14: 688-728; 1996).
4. Signs of damage to Mouse Intestines was caused by a potato engineered to contain a gene from Bacillus Thuringiensis (CryI gene var. kurstaki strain HD1). The authors concluded "Although mild changes are reported in the structural configuration of the ileum of mice fed on transgenic potatoes, nevertheless, thorough tests of these new types of genetically engineered crops must be made to avoid the risks before marketing." ( Nagui H. Fares, Adel K. El-Sayed. Natural Toxins Volume 6, Issue 6, 1998. Pages: 219-233).

Finally a very serious accident should be mentioned. Four genes were inserted into a bacterum to have it produce more of the amino acid tryptophan. In the tablets very small amounts of highly toxic molecules appeared. 37 persons died and 1500 contracted seriuous chronic neurolgocial and autoimmune disorders before the cause was detected.

The bacteria were unfortunately destroyed after the accident so it was impossible to directly investigate whether GE was the cause or not. But it has been ascertained that the tryptophan tablets were the cause of the injuries. (Mayeno, AN et al Tibtech 12:364, 1994). Other causes seem less likely according to the molecular biologist John Fagan, see "Tryptophan summary". See also The Showa Denko Tryptophan disaster - Genetic engineering most probable cause.

Conclusion:

There are good scientific grounds for the opinion that genetic engineering may cause the creation of unexpected substances that may, in the worst case, be toxic, allergenic or otherwise detrimental to health.

Only rigorous toxicological testing, including paid human volunteers would minimise the risk. But as even the best tests available are not foolproof (see addendum below), a residual risk remains as pointed out by Fagan.

CONSEQUENCES FOR SAFETY ASSESSMENT

Very extensive experience of safety assessment of chemical substances has been acquired in the development of medicines. It is disconcerting that the best available safety assessment methods have failed to detect harmful effects in altogether about 13 percent of the cases of new drugs.

In the case of genetically engineered foods, the situation is even more problematic, as in this case, it is not known at all what chemical substance may be harmful. This may increase the risk of failed detection of seriously harmful substances considerably above the level for drugs.

We find that too little is known about the safety of GE foods to justify an approval of their use. Therefore we demand a moratorium on their use. And if this takes time to implement, we demand labeling of GE foods. If there is no labeling of genetically engineered foods, early detection of a harmful food will be very difficult, if not impossible. This means that very large number of people may be affected before the cause is discovered.

For more details see the article: "No safety assement methods are fully reliable"

Against this background you may want to know if GE-foods presently developed are so valuable that it is worth taking the risk of jeopardizing the health of millions of people. If so, take a look at "Traits introduced in foods by genetic engineering". The major argument of biotech proponents that GE can contribute to a solution of the world hunger is an unsubstantiated assumption as you will find in "Can genetic engineering produce crops that increase food production?" and "It is a myth that world hunger is due to scarcity of food".