| - The following are extracts from the submission prepared by the Institute for Health and Environmental Research Inc regarding the inadequate health testing undertaken by the Regulatory bodies for the approval of Bayer Cropscience's Invigor canola:
Placement of the genetic insert
The introduction of a gene into a plant cell using genetic engineering is a very hit-and-miss affair with many target cells not expressing the gene at all and some cells expressing multiple copies at various levels of expression depending on where the new gene or genes are incorporated into the host chromosomes. As the inserts are placed indiscriminately, some may be placed where they affect the expression of the plant’s genes. This may turn genes off, or on, affect the function of other genes, produce new toxins or allergens, or produce a ‘wild characteristic’ such as higher levels of toxins found in a wild ancestor.
Unfortunately, this may have occurred with these canolas. They provide evidence that line RF3 has one full copy and a partial copy of the genetic insert, while Topas 19/2 has one copy and an inverted copy of the inserted DNA. Because Bayer CropScience provided Southern blot analyses but not Northern blot analyses, it cannot be determined that the canola has not produced new substances as a result of this insertion. Furthermore, the OGTR believes that its document indicates that the genetic insert into RF3 has gone into a non-coding region of the canola DNA. However, as we do not know all of the genes in canola, this cannot be demonstrated to be the case. Even worse, the flanking regions of MS1, RF1 and RF2 clearly indicate that the genetic insert has gone into a coding region of the canola. But because the function of that region is not as yet known, the OGTR has assumed that the insert will not change the genetic expression of the canola and that no new substances will be produced. This is very dangerous ground, indeed.
Of additional concern, the OGTR relies on Bayer’s results from ELISA tests that various proteins that were genetically engineered to appear were not detected in various plant products. For example Bayer could not find PAT protein in canola oil nor NPTII protein in seed. However, the OGTR document (OGTR, 2003) then stated that the Canadian Food Inspection Agency had found the NPTII protein in seed and that Bayer had stated that the values found by the Agency were below the limit of detection of Bayer’s tests. This suggests that Bayer’s tests were insufficiently sensitive and that these proteins may be found with more sensitive tests. Yet the OGTR did not require the more sensitive tests to be undertaken in order to aid its decision.
Animal feeding studies
Because these were so badly summarised in the OGTR document, the IHER had had to refer to the FSANZ document on these feeding studies to gain further information.
Of the 7 canolas and the many potential hybrids that are being assessed, feeding studies are reported for only 1 canola (Topas 19/2 on chickens) and 2 hybrids (RF1xMS1 and RF3xMS8 on rabbits and canaries). In addition, the fraction that is fed to humans, the canola oil, was not fed to animals. Rather, canola seed was used, which humans do not eat. FSANZ has previously argued that studies feeding oils to animals may cause nutritional and biochemical imbalances and hence are inappropriate. However, a review of the nutritional literature shows that they are not only appropriate, but often conducted.
Furthermore, only one of these studies used significant numbers of animals (280 commercial strain broiler chickens), but these were only male chickens fed for 42 days and only body weight, feed intake, mortality, chilled carcass weight and deboned breast meat yield were measured. A study on rabbits (a low number of 10 rabbits per diet) were only measured over 4 days and faecal samples were taken and analysed to determine the digestibility of the seed and “zootechnical performance” of the canola seeds. Note that this limited rabbit study is the only one conducted on the hybrid expected to be grown immediately in Australia. Also note that there is a contradiction between the OGTR and FSANZ documents. The OGTR document mentions 2 feeding studies on rabbits, whereas the FSANZ document mentions only one (it does not mention the hybrid selected for widespread commercial production in Australia) and does not mention a feeding study on canaries at all. The OGTR document states that for the canary study, food consumption, behaviour or body weight were measured. No mention was made of the number of canaries per group or how long they were fed.
Chickens, rabbits and canaries are very unusual animal models for human health. Some of the measurements taken from these animals are also unusual measures of human health, such as chilled carcass weight, deboned breast meat yield and faecal composition. It can only be concluded that these tests have not been set-up to measure human health at all, but rather to reassure primary producers that GM feed will permit farm animals to grow sufficiently to get a reasonable price at market (rabbits are farmed overseas). However, in its safety assessment, the OGTR remarkably uses these kinds of experiments as evidence that these foods are safe for human consumption. What is even worse is that the only results that could be translated to humans from these experiments were death, food intake and body weight. These are profoundly crude measures of human health. On the basis of these kinds of tests, tobacco, alcohol, asbestos, thalidomide and chronic heavy metal exposure would all be regarded as safe. Important tests such as biochemistry, immunology, tissue pathology, and gut, liver and kidney function and microscopy results were not given, and were therefore probably not done. In addition, animals were not fed for long enough for cancer studies, or studies into the effect of offspring, to be done. Consequently, those experiments could be regarded as initial experiments in what should have been a long series, starting with several thorough animal experiments and finishing with several detailed human experiments, yet they remain the only ones done. On the basis of these tests, it is recklessly negligent of the OGTR to regard oil from these canolas as safe for human consumption.
Human safety testing
It is clear that InVigor® canolas have not passed human safety tests. In fact, they have never even been safety tested on humans. In particular, these canolas have not undergone the safety rigours of a clinical trial. Before a clinical trial is even begun, thorough animal testing is undertaken to determine adverse and therapeutic effects of the treatment in those animals. If the tests are passed, the four phases of the clinical trial begin. Phase I tests for adverse effects in a small number of healthy volunteers, Phase II tests for the therapeutic effect in a small number of volunteers, and Phase III is the randomised controlled trial (RCT). If the new treatment passes all these steps, it is then monitored in the community (Phase IV). As a result of the push towards ‘evidence-based medicine’ a further step is often undertaken, the meta-analysis. This process statistically sums the results of a number of randomised controlled trials to get a better picture. It is clear that InVigor® canolas have not even completed the pre-clinical trial animal testing stage of this process. No reasons are given for this lack of safety testing. It is of concern that in the face of this overwhelming lack of evidence of safety, the OGTR unwisely still regards these canolas as safe for humans.
However, even these studies cannot determine the long-term health effects of GM foods on humans. To do this, long-term cohort studies are required, where people’s current self-selected exposure to various GM foods are measured over future years and any diseases noted as they arise. In addition, specific surveillance systems would be required to pick-up any ill-health effects in the general population.
Instead, the OGTR relies on Bayer’s self-report that their employees did not show “changed allergic reactions in annual medical examinations”. No information is given as to whether baseline measurements were taken before employment, what measurements were taken at the examinations (allergies are rarely measured at medical examinations), if allergies were measured, how they were measured (specific measurements on blood would need to be undertaken), whether those who left before a yearly examination were chased-up for their reasons for leaving (were there medical reasons?), etc. Little mention is made of the fact that it is in the interests of employees to demonstrate their good health to an employer in order to continue their employment. In short, this is not a properly-conducted study. There is too much bias. Only a properly-conducted epidemiological study on a large number of people can determine the relationship between exposure to InVigor® canola and adverse health. This Bayer report is not it.
It is also clear that these canolas have not been designed for any benefit to humans. Consequently it would only require a small adverse effect on people for any harm to completely outweigh the (nil) benefit.
In the face of this profound lack of information, the IHER believes it is recklessly negligent to consider InVigor® sufficiently safe to permit 19 million Australians to be exposed to it, either directly in fields, via pollen or in food.
Human health monitoring and surveillance
One of the reasons that OGTR gives for finding this canola safe for humans is that there have been no reports of adverse effects on human health reported from this canola. However it is clear from the OGTR document that there may have been no system in place to report any adverse events. That is, there has been no proper attempt at surveillance and monitoring. It is also clear that there have not been any epidemiological studies into the effects of InVigor® canola on human health.
It is also of concern that the OGTR appears to be using the same argument as proponents of GM food and the FSANZ, that because no-one has found any documented cases of people who have gotten ill from eating GM food, then GM food must be safe. This is completely unrealistic. Unfortunately, there may be many cases of illness from exposure to GMOs that we are unaware of because we have inadequate general surveillance systems, no-one is being paid to look at those surveillance systems for cases and there is a complete lack of a specific surveillance system for GMOs. Furthermore, if exposure to a GMO causes a novel illness, then by definition, we do not have a surveillance system to pick it up. In addition, because of the lack of full animal testing, we don’t even know which diseases to look for in our general surveillance systems, such as hospital separations databases. Consequently, we may be sitting on a big problem that we are completely unaware-of. This happened with HIV/AIDS for decades, and even today, we still don’t know how many cases of this disease there are.
Finding cases of illness is however only the first step. Then a team of epidemiologists would need to prove that GM food was the cause by mounting an investigation, because surveillance only indicates there is a disease. It does not inform us of the cause. This would require an application for a considerable amount of money through the grant funding system, which takes years and has a very high failure rate. If funding is secured, various causes of the disease would be suggested and tested by different investigating teams. For an existing disease, existing hypotheses would likely be considered and tested before GM foods are considered. For example, an investigation into an increase in bowel cancer would likely concentrate on the fat and fibre content of the food. Furthermore, obtaining accurate recall from study subjects of foods that they may have eaten years ago is highly inaccurate. Consumption of GM food components are even harder to quantify, as many manufacturers still do not know whether they are using ingredients derived from GM sources, or they do not label the food as containing these. This makes it extremely difficult to determine the amount or types of GM foods eaten in a group of ill people. It therefore becomes almost impossible to prove that a GM food has caused a disease, even if there are thousands of cases. For these reasons, the OGTR’s assumption that absence of evidence of harm is the same as evidence of absence of harm is very dangerous.
Of additional concern is that the OGTR is proposing minimal oversight conditions on InVigor® canola that appear not to include any provisions for monitoring or surveillance of InVigor® canola on human health. This is remarkable, as on the one hand, the OGTR states that it will review the commercial release if there is evidence of harm to human health. However, it has then chosen a system of regulation that has excluded any conditions or provisions that would determine if this harm was occurring. The IHER regards this as negligent. An active surveillance system is required.
The barnase/barstar system
GM sterile crops use barnase, an enzyme which destroys RNA. RNA is the essential link between DNA and its functions in all living cells. Barnase is a non-specific poison, capable of killing any cell exposed to it. Obviously, every cell in the plant will contain the barnase gene, which will only be expressed in its reproductive organs. This means there will be billions of copies of the gene for barnase in even a small field of this canola. This new (plant) environment has provided the barnase gene with new opportunities for gene transfer to organisms that may not previously have occurred. The consequences of this could be absolutely awful.
The use of antibiotic marker genes
Genes coding for antibiotic resistance are used as selectable markers for transgenic plant production. This provides organisms, including humans to unnatural and unprecedented exposure to new sources of antibiotic resistance genes.
These GM canola plants confer resistance to aminoglycoside antibiotics such as antibiotics, kanamycin, gentamicin and neomycin. The OGTR has sated that neomycin and gentamicin are infrequently used. This is news indeed to several clinicians and hospital scientists that specialise in the area that were contacted by the IHER. Neomycin is used occasionally as a topical antibiotic in medicine. Gentamicin is not used for trivial infections because it is reserved for seriously ill hospitalised patients for serious conditions such as complicated urinary tract infections, septicaemia, burns, infected wounds, bone and soft tissue infections, including peritonitis. It is widely used in these applications, particularly for people who are risk of death due to septicaemia. Such is the concern about antibiotic resistance in the medical community, that some gentamicin-like antibiotics are kept in reserve, not to be used until last resort. Amikacin is one of these. The experts contacted were highly concerned that widespread use of the NPTII enzyme may place the use of these highly reserved antibiotics at risk as well. It should be remembered that the InVigor® canola meal will be fed to animals in intensive husbandry. In these conditions it is routine to constantly feed antibiotics to animals as both a growth promoter and as a preventative prophylaxis. These conditions have the highest potential to spread antibiotic genes to bacteria. From there is only a matter of time until antibiotic resistance is found in bacteria in people. The OGTR also stated that the NPTII enzyme is so non-specific that it can inactivate aminoglycoside and butirosin antibiotics but is somehow so specific that it can discern between different sub-types of one of these antibiotics, gentamicin. The OGTR provides no reference for such an interesting statement. The antibiotic resistance was put in the plant in order to be able to grow it in the presence of gentamicin as a selective marker. Unless Bayer has access to special, pure subtypes of gentamicin that specialist clinicians and hospital scientists have not heard of, it would have used “normal” gentamicin, which indicates that the NPTII enzyme can indeed inactivate clinically-used gentamicin. Moreover, cross-resistance has been demonstrated between different aminoglycoside antibiotics and even between different classes of antibiotics.
There is a considerable lack of understanding about antibiotic resistance, how it develops and how it is transferred between organisms. However, there is some evidence that once a bacterium has acquired one gene for antibiotic resistance it is more likely to be able to acquire others. The significance of this is that even using a gene for resistance to an obscure antibiotic may ultimately increase resistance to clinically significant antibiotics. For these reasons, the OGTR should take great care about allowing genes that confer resistance to antibiotics to be widely grown in a commercial release of GM plants.
Allergenicity
The OGTR quotes widely from papers and documents written by Bayer and Monsanto-paid scientists. Many have not even been published. If the OGTR had done a proper literature search and consulted a FAO document, they may have been better informed.
The sequence homology approach accepted by the OGTR to determine whether the GM food is allergenic is regarded by the FAO as only the first of several steps to indicate whether the GM food is allergenic (FAO, 2001). The other steps have not been undertaken for InVigor® canola. Moreover, the FAO points-out that the protein and gene databases used for homology testing are often not up to date and hence cannot be relied-upon. Furthermore, little is known about the actual proteins that cause allergy, even for peanut allergy, one of the most serious and well-documented food allergies. For example, there appear to be “less than ten” protein fractions that cause peanut allergy (Sampson et al 1998). Given this lack of understanding, it is inadequate to consider that a comparison of the sequence homology of new proteins in GM plants to sequences of known allergens will be sufficient to determine whether a new protein is allergenic.
Furthermore, one of the key reasons why the OGTR found that oils from InVigor® canola was safe for humans was that canola oil does not contain protein. This is completely untrue. It has long been recognised that oils contain proteins (McCance and Widdowson, various editions). In fact, different brands of oil in the USA contain between 2 and 62 μg/ml protein (Moneret-Vautrin et al, 1998), which is sufficient to cause an allergic reaction in sensitive people. In fact, in an oral provocation test, 22% of patients allergic to peanuts reacted to peanut oil (Moneret-Vautrin et al, 1998). Moreover, there is evidence that allergy to peanut oil may be the main cause of anaphylactic reactions in England.
It is also important to consider that if oils contain protein, they are also likely to contain small sections of DNA. Under these circumstances, horizontal gene transfer between InVigor® canola and humans needs to be considered. In the light of the evidence above that this event occurs with GM soy after only a single meal, the awful potential of a bacterium in the gut taking up the gene for barnase needs to be considered.
Pollen is known to cause hay fever, asthma and allergies due to specific proteins expressed in the pollen. When new proteins are introduced into plants through genetic engineering, it is essential to test whether these proteins occur in pollen and to assess their allergenicity when inhaled as pollen. For example, a protein which is found in soil bacteria may not cause an allergic response on hands but may cause an allergic response when inhaled. In addition, honey will become contaminated with GM pollen and the allergenicity of oral GM pollen should also have been assessed. Based on the tiny amount of protein required to elicit an allergic response from oil, the amount of GM proteins in pollen in honey may also cause an allergic reaction.
In addition, the OGTR states that that allergenicity is unlikely to GM plants because humans are frequently exposed to these novel proteins, because the proteins are derived from common bacteria in the environment. Unfortunately, the opposite is true. People develop allergies to certain proteins because they get exposed to those proteins. Moreover, the allergic reaction tends to get worse with continued exposure.
Source: http://www.iher.org.au/ |
