01 June 2004

Myths about the Digestion of Proteins and DNA

Dr Catherine Clinch-Jones

May 2004

The Institute of Health and Environmental Research Inc. (IHER) is a not-for-profit research institute with a scientific interest in genetically modified (GM) organisms, particularly those destined for food. Its directors hold the following degrees: ordinary degrees in Medicine, Science and Agriculture, Honours Degrees in Agricultural Science and Organic Chemistry, a Master of Public Health, and PhDs in Plant Genetics and Medicine. The Directors have training and expertise in plant science, agriculture, medicine, chemistry, biochemistry, nutrition, epidemiology and biostatistics.

There is a myth held by many people that proteins in food are completely digested in the gut of animals or humans by being completely broken-down into their constituent amino acids and that therefore, ingested proteins cannot cause disease.

However, food allergies, such as those to peanuts, rely on the fact that many proteins are not fully digested. In some people, this allergic reaction can result in anaphylaxis and possible death. An associated myth is that oils are so thoroughly refined that they do not contain protein. It has been known for decades that oils contain small amounts of protein (Holland et al, 1991). The amount is sufficient to trigger an allergic response in some sensitive people (Moneret-Vautrin et al, 1998).

Of even greater concern is the example of Bovine Spongiform Encephalopathy (BSE), generally known as "mad cow disease". This disease is cased by a prion, which is a protein. It is clear that this protein survives digestion in both cows and humans. It causes variant Creutzfeldt-Jakob disease in humans. Cows who have eaten this protein may pass it on to other cows or humans that eat the carcass, thereby passing-on the disease. This example is not an isolated case. Kuru is a similar disease resulting from eating certain protein(s). There are concerns that, similar to Kuru, variant Creutzfeldt-Jakob disease may not become manifest in most people until decades after consumption of the protein. This is based on recent reports of results from tissue samples from UK patients undergoing surgery, indicating that many more thousands of people may be infected with the protein than currently have symptoms (The Australian, 2004).

Animal and human studies have also conclusively shown that macromolecules, including food proteins and allergens eaten by the mother can enter breast milk and the foetus (Dahl et al, 1984; Jakobsson, 1991). Egg producers should therefore be aware that it may be possible for ingested proteins to pass from the hen into its eggs.

Consequently, assertions that proteins are completely digested in the gut and hence cannot cause disease are simply wrong. Similar assertions that a protein in the diet cannot be passed on to others are similarly wrong.

There are additional concerns about the potential health effects of proteins produced in GM organisms, because of the way these organisms are made. GM plants are usually made by taking a section of DNA from an organism that expresses a desired characteristic, joining it with other sections of DNA such as viral promoters, and inserting the resultant gene cassette into the plant in imprecise ways. For example, one method takes gold or tungsten particles, coats them with the gene cassette and fires them into the plant. Partial copies may be inserted. As there is no way to guide the point of insertion, the inserts are placed where they may not be found in nature. They may therefore affect the expression of the plant’s genes by turning genes off or on, affect the function of other genes, produce new toxins, proteins or allergens, or produce characteristics, such as higher levels of toxins similar to those found in ancestral forms of the plant.

Ingesting products from a GM organism has already caused illness. The Showa Denko KK company produced the amino acid tryptophan as a dietary supplement from a GM bacterium that caused an epidemic of eosinophilia-myalgia syndrome in the US and Europe (Belongia et al, 1990). Although the product was 99.6% pure (Mayeno and Gleich, 1994), thirty seven people died within months and 1500 were permanently disabled before governments stopped counting (Anderson, 1999). The GM bacterium had produced several substances that were not fully removed during purification (Mayeno and Gleich, 1994). It is sobering to remember that GM products entering the marketplace are rarely purified, particularly to this extent, so any novel substances are likely to occur in much larger amounts in the final product.

There is also a myth that DNA would be quickly broken down in the gut and hence would pose no health risk. However, there is evidence that this is not the case and that instead, ingested DNA can be absorbed into the bodies of animals. In mice, ingested foreign DNA was found in white blood cells, spleen, liver and cells of the immune system. Some was bound to mouse DNA (Schubbert et al, 1997). Other work has demonstrated that short DNA fragments from plant chloroplasts can be found in the lymphocytes of cows, and possibly in their milk, while muscle, liver, spleen, and kidney tissues from chickens were found not only to contain, but to amplify, certain introduced gene fragments (Einspanier et al, 2001). Not only DNA, but whole cells can cross the placenta into the foetus (Dayton, 2003) and hence may be passed-on to future generations.

There is a particular concern that transgenic DNA may be more likely to do this than "natural" DNA because transgenic DNA is specifically designed to cross species barriers and to jump into other genomes (Ho, 2002). In fact, human simulations indicate that transgenes in GM food may survive in the human stomach and small bowel for up to four hours (Martin-Orue et al, 2002). Furthermore, an oral bacterium was found to take-up and express free exogenous DNA within a minute (Flint and Scott, 2002).

In addition, in the only GM food study that could be found on humans, seven people - who had previously had their lower intestine removed and consequently used colostomy bags -were fed a single meal of a burger and milkshake, both containing GM soy. It was found that "a relatively large proportion of genetically modified DNA survived the passage through the small bowel" (Netherwood et al, nd). There was also evidence of genes being transferred from the GM soy to intestinal microbes (Netherwood et al, nd). This is particularly worrying, as genes coding for antibiotic resistance, which are present in most GM foods, may be transferred to bacteria, thereby worsening our current problems with antibiotic resistant bacteria in humans and intensively-reared animals.

Some people believe that GM foods have been fully safety tested. This is not the case. First, almost all of the safety tests have been done by the companies that want to sell the crops, a clear conflict of interest. There has been almost no independent safety testing. In addition, the companies generally do not publish their results in scientific journals for others to look at. There have been no tests on offspring who were exposed to GM foods in utero, during lactation or early life, a concern given that digested substances can cross into breast milk and the foetus. There have been no human health safety tests, even though a billion people may be eating these foods. Some have not even been tested on animals. In contrast, a new pharmaceutical drug would require full animal testing followed by the four phases of a clinical trial on people before it could be deemed to be safe, even though it would be ingested by far fewer people than a GM crop.

Some people also believe that the federal government’s food standard’s agency, FSANZ, does its own safety testing of GM foods. It does not. It relies on information given to it by the applicant company. FSANZ’s policy is that GM foods are regarded as safe until they are proven to be harmful (FSANZ, 2000), the opposite of the precautionary approach.

Studies by the company to determine the digestibility of novel proteins are not done in animals but in vitro ("in glass") in a laboratory. Such experiments therefore cannot investigate possible effects on intestinal organisms (Heinemann, 2004). These studies have also been criticised for using conditions that breakdown the novel proteins in an unrealistically short time, such as using 2.5 million times the recommended concentration of a digestive enzyme (Heinemann, 2004).

Most of the animal tests undertaken by these companies involve placing a single oral dose of the protein(s) that the plant has been engineered to produce into a few rats and watching them for seven to fourteen days, basically to see if the animals die. This assumes the following myths: that the only new substance to appear in the plant will be the one genetically engineered to appear, that the GM plant-produced substance will act in the same manner as the tested substance that was usually obtained from a bacterium, and that the substance will create an obvious illness within a few days that will be able to be picked up without a full autopsy (Carman, 2004).

Very few GM foods are safety tested by feeding the whole food to animals. Even then, animals are generally only fed for 4 weeks. Unusual measures of human health may be used, such as de-boned breast meat yield and milk production. Full autopsies are rarely undertaken. The studies assume that any illness will become obvious within a few weeks and will be able to be picked-up without a full autopsy. Furthermore, the small numbers of animals in both types of animal experiments are profoundly inadequate to assess what may occur in the real world (Carman, 2004). Under these conditions, it would be very hard to find anything wrong with substances such as tobacco, asbestos or thalidomide.

Of even greater concern, when adverse effects were found in animal experiments, the experiments were not repeated or expanded to fully determine the incidence, nature and cause of the adverse effects. Rather, the company simply deemed that these results were not clinically significant or not due to the GM food, even when there was no other realistic explanation (Carman, 2004). It is unlikely that such conclusions would have been permitted if the substance had been a pharmaceutical drug.

There is a myth that because no-one has found any documented cases of people who have become ill from eating GM foods, GM food must be safe. Such a position either ignores the Showa Denko KK case or regards this case as not being due to a food produced from a GM organism, even though this company’s product was an amino acid used as a dietary supplement.

It is a common myth that any new illness, or any increase in an existing illness, would be immediately known and that the cause would be obvious. In reality, knowledge about most rates of illness relies on current surveillance systems. These systems are woefully inadequate to pick-up any ill-health effects due to GM foods (Carman, 2004). Furthermore, no person or agency is analysing the surveillance systems we do have. In addition, some diseases such as cancer may take decades to develop. As GM foods have only been eaten widely for a few years, such diseases may still be incubating.

Under these conditions, we are unlikely to be aware of any problem until there are so many cases of disease that the situation becomes overwhelmingly obvious. HIV/AIDS is an example of a disease found this way. It took decades to find and had by then infected thousands.

But even this just tells us there is a disease; it doesn’t tell us the cause. That requires detailed epidemiological and laboratory studies that may take years before the cause can be identified, by which time many thousands more people may be affected.

Consequently, the lack of identified cases of illness due to eating GM foods does not mean that GM foods do not, or will not, cause illness.

Furthermore, because almost everyone is exposed to GM foods, if these foods do cause illness, the public health implications could be enormous. Even a low rate of illness, such as one case per 1,000 exposed people, would eventually result in 20,000 cases in Australia alone.

• Proteins are not always broken-down in the gut and can cause disease. Proteins from GM plants are a particular concern.
• DNA is not always broken-down in the gut. Ingested DNA has been found in tissues of animals. DNA from GM organisms is a particular concern and has been found in intestinal microbes.
• The safety testing of GM foods is inadequate.
• The lack of identified cases of illness due to eating GM foods does not mean that GM foods do not, or will not, cause illness. Because of the numbers of people exposed, if these foods do cause illness, they may eventually cause a great deal of illness.