GENETICALLY MODIFIED PEAS CAUSED DANGEROUS IMMUNE RESPONSE
PART 1 of 2

 

 

 

By Jeffrey Smith
January 14, 2006
NewsWithViews.com

SUMMARY:
Genetically modified (GM) peas under development created immune responses in mice, suggesting that they may also create serious allergic reactions in people. The peas had been inserted with a gene from kidney beans, which creates a protein that acts as a pesticide. When this protein is produced naturally in beans, it does not elicit a response from mice. When produced in the GM peas, however, it did cause a reaction. Using sensitive testing methods, scientists discovered subtle differences between the bean and the GM proteins�the added sugar chains were slightly different. They speculate that this difference caused the immune reactions. Based on the results of the study, the Australian developers abandoned their 10-year, $2 million project.

This study reveals serious and potentially deadly flaws in the regulations and assessments used to approve GM foods. GM crops on the market, like corn and soybeans, were never tested for immune responses using animals and never subjected to a similar analysis of their proteins. Thus, the transgenic proteins in GM foods may have subtle undetected differences that are causing health problems. It is sobering to note that if the GM peas were tested with only the methods used on soy and corn, it likely would have been approved as well.

The approvals of genetically modified (GM) food are largely based on four pillars. The first is the reliance on a long list of assumptions about food safety. Unfortunately, these assumptions are principally based on what was known about genetics 40 years ago, and many have been overturned.

The second pillar is that safety research on GM foods is primarily controlled by industry. Much of it is secret, and the few studies that have been made public are largely superficial�designed not to contradict the assumptions.

The third pillar is an ineffective regulatory system, often hijacked by people with close ties to industry. They accept unscientific assumptions and poor research, and ignore adverse findings.

The fourth pillar is spin�merciless, relentless, in-your-face spin�that magically flips facts to proclaim their opposite. Examples are forthcoming.

On November 17, those pillars took a considerable beating. GM peas under development were evaluated by tests normally applied to medicine�not to GM food.[1] The peas created a dangerous immune response in mice which, if found in humans, might be life threatening. The 10-year pea project, costing over $2 million dollars (US), was abandoned. If those same peas had been evaluated with tests used for other GM crops, however, they could have sailed through the approval process anywhere in the world.

The peas were developed by Australian scientists at the Commonwealth Scientific and Industrial Research Organization (CSIRO) to assist the country�s $100 million pea harvest. They targeted the pea weevil, a pest that takes a hefty bite�up to 30%�out of yields. But if weevil larvae were to bite a GM pea plant, they would starve to death.

That�s because the pea contains a protein called alpha-amylase inhibitor, an anti-nutrient that interferes with the bugs� digestion. That protein is produced from a gene normally found in �common� (kidney) beans and when fully cooked is safe for humans. Scientists spliced the gene into peas, figuring it would be safe there as well.

Safety Assessment

Researchers checked the sequence of the kidney bean gene after it was inserted into the pea�s DNA. It hadn�t changed during the insertion process, but this is not always the case. Genes inserted into soybeans and corn, for example, were mutated, fragmented or truncated, and several appeared to rearrange over time. Remarkably, safety assessments don�t always require that the transgene�s sequence is determined. In the US, for example, gene sequencing is not part of the approval process.

If a gene�s sequence changes, it might create proteins with the wrong amino acids. But analyzing the sequence of amino acids is also not required. According to Bill Freese, a research analyst at Friends of the Earth, �At present, the standard practice is to sequence just 5 to 25 amino acids,� even if the protein has more than 600 in total. They assume that the rest are fine. Most of GM foods on the market have never had their novel proteins sequenced. The GM peas, however, were checked. The protein produced in the peas did have the same amino acid sequence as the original in the beans.

Scientists at the John Curtin School of Medical Research inCanberra tested the peas on mice, to see if they elicited an immune or allergic response. Groups of mice were fed a commercial diet and also given GM peas, non-GM peas or beans, twice a week for four weeks. After the feeding period, the mice were tested with a battery of immune response tests. Reactions were elicited only in mice that were fed GM peas. Specifically, injections of the GM protein into the footpad resulted in significant swelling; when introduced into the trachea, it caused mild lung damage and tissue inflammation (similar to asthma in humans). Lymph nodes also responded to the presence of GM protein. The researchers did not check for allergies, per se, but used tests that they say are predictive of allergenic sensitivity.

Simon Hogan, the lead researcher for the study, said, �The study is fairly conclusive.� He added, �These types of assays are commonly used in medical research.� They have not, however, been used in safety assessments for GM foods on the market. Even though experts with the Food and Agriculture Organization and the World Health Organization (FAO-WHO) recommend using animal studies to test for allergies, no government actually requires it, and it is almost never done.

According to immunologist Ricki Helms, who has served on several expert panels examining the potential allergenicity of GM foods, �Animal models can contribute to the evaluation of allergenicity but cannot offer absolute certainty.� This lack of certainty is a common justification by industry scientists for why they don�t use animal allergy studies as part of their assessments. The two methods that they prefer, however, also lack certainty.

In the first method, the transgenic proteins are put into test tubes with digestive enzymes and acid to measure how quickly they are broken down. This test is based on the fact that allergenic proteins often�but not always�break down slowly in the stomach and intestines. The problem is that test tube studies do not accurately predict what happens inside humans. And even if they did, a protein that is broken down quickly may still cause allergies. Thus, potentially harmful allergenic proteins can pass this test.

In the other method, researchers search databases to see if the amino acid sequences of the transgenic protein are similar to known allergens. This method also offers no guarantees�not all allergenic sequences have been identified and allergenic proteins can certainly pass this test as well. In spite of the shortcomings of these two methods, the FAO-WHO recommends them as part of the assessment and offers specific criteria for each. Regulators can ignore those recommendations. The GM soy, corn, and papaya on the market, for example, fail the FAO-WHO criteria. GM pea developer TJ Higgins told me that when his peas were evaluated for protein stability and amino acid similarity, they were �borderline.�

In addition to creating an immune response in mice, GM peas also increased their immune system�s sensitivity to other substances. For example, mice fed the non-GM peas showed no response to egg albumin. The GM-fed mice did have an immune reaction to the albumin, as well as to three other substances tested. The ability of one food to increase the sensitivity to other foods is called an �adjuvant� response. It suggests that humans fed GM peas might develop allergic or immune responses to a wide range of other foods. According to Judy Carman, an epidemiologist and the director of The Institute of Health and Environmental Research in Australia, �If a GM food was introduced onto supermarket shelves and caused an immune reaction, it would be very difficult to find the culprit, particularly if it caused reactions to other, different foods, as this GM pea was found to do.� As you probably guessed, adjuvant testing is not part of any normal GM food approval process.

Independent researchers did test a GM product both for immune and adjuvant responses using mice.[2] They tested one type of Bt-toxin (Cry1Ac) found in GM cotton, which is similar to Bt toxins produced in several varieties of GM corn (Cry1Ab). Like the alpha-amylase inhibitor in peas, Bt toxins kill pests. Not only did the Cry1Ac produce a significant immune response, it elicited an adjuvant response as well. Another study showed that Bt toxins in spray form caused antibody responses and allergic symptoms in farm workers and others.[3] Taken together, these studies overturned several safety assumptions. In spite of claims to the contrary, Bt is not fully destroyed during digestion, it is bioactive in mammals (including humans), and current safety assessments are inadequate. By the time this research was done, Bt crops were already planted on millions of acres. Withdrawing them will apparently require more evidence of human harm.

Another assumption used often by the biotech industry is that cooking their GM crop will destroy its potential to create allergies. Cooking can change the protein�s structure, or �denature� it. Proponents have claimed that when Bt is denatured, it is no longer effective as a pesticide and will therefore no longer be allergenic. The GM peas were boiled for 20 minutes. After cooking, the alpha-amylase inhibitor was denatured and was no longer effective in protecting against weevils. Industry assumptions notwithstanding, the cooked pea protein still caused an immune response in mice.

Tracking Down the Cause

What was it about the transgenic protein in the GM peas that caused it to affect the mice, when the �same� protein in its natural form in kidney beans did not? This question intrigued Hogan and his team. He said their �scientific, inquisitive nature� led them to look for subtle differences in the protein structure. Although the amino acid sequences of the GM and non-GM proteins were identical, that doesn�t tell the whole story. Amino acids are the building blocks, and according to Carman, �If you knock down a house and then study the pile of bricks, it won�t describe the house. Similarly, the amino acids don�t reveal the structure, shape and unique characteristics of the protein.�

David Schubert of The Salk Institute for Biological Studies points out that in higher organisms such as plants and animals, �each cell type expresses a unique repertoire of enzymes capable of modifying protein structure.� Depending on where they are, a protein may have added molecular chains, �such as phosphate, sulfate, sugars, or lipids,�[4] which alter their function. In a 2002 article in Nature Biotechnology, Schubert argues, �With our current state of knowledge, however, there is no way of predicting either the modifications or their biological effects.�[5]

We can, however, detect such modifications. For instance, when sugar chains are added to proteins, this process, known as glycosylation, can influence allergic responses. Hogan�s team used the sensitive MALDI-TOF mass spectrometry technique, and confirmed that the GM and non-GM proteins had slightly different glycosylation patterns. They believe that these subtle differences may be the cause of the immune responses.

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Here again is more bad news. The MALDI-TOF method is not required and has rarely been used for the safety assessments of GM food already on the market. According to Doug Gurian-Sherman, a senior scientist at the Center for Food Safety and formerly at the US Environmental Protection Agency, the differences in glycosylation between the GM pea protein and the non-GM counterpart in kidney beans �would not be detected by the tests that are currently required by US regulatory agencies.� If companies do assess differences in protein, it is typically by �gel� tests, which won�t reveal the subtle differences in glycosylation that may have caused the immune response. In fact, TJ Higgins looked at gel tests in the 1990s and did not see any difference between the GM and non-GM proteins.

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Footnotes:

1, V. E. Prescott, et al, Transgenic Expression of Bean r-Amylase Inhibitor in Peas Results in Altered Structure and Immunogenicity, J. Agric. Food Chem. 2005, 53
2, Cry1Ac protoxin is a systemic and mucosal adjuvant (Vazquez-Padron et al, 2000b)
3, Bernstein, et al., (1999). Immune responses in farm workers after exposure to Bacillus thuringiensis pesticides. Environmental Health Perspectives 107(7), 575-582
4, David Schubert, "A different perspective on GM food," Nature Biotechnology vol. 20, 2002, p. 969
5, David Schubert, "A different perspective on GM food," Nature Biotechnology vol. 20, 2002, p. 969

� 2006 Jeffrey M. Smith- All Rights Reserved

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