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Australian researchers to discontinue GM trial

The production of genetically modified food is becoming more and more widespread on a global level. As the use of GM foods increases, scientists are debating the attendant benefits and risks. In Australia, researchers abandoned a long-term experiment involving GM peas at the end of 2005 due to the fact that the GM peas were found to cause lung inflammation in mice.

In Australia, experiments involving genetically modified (GM) peas have been being carried out since 1996. Thomas J. Higgins, Deputy Chief of the Australian CSIRO (Commonwealth Scientific and Industrial Research Organisation) was responsible for a project to develop peas that were resistant against the pea weevil Bruchus pisorum, which, if left uncontrolled, can cause annual yield losses of up to 30 percent.

The peas were genetically engineered to contain a bean gene that produces an inhibitor of the alpha-amylase enzyme. This makes them resistant to beetle infestation since the beetle larvae are no longer able to digest pea starch. The GM peas were fed to mice that subsequently developed lung inflammation as a result of an allergic (IgE) reaction. The decade-long trial was abandoned for safety reasons.

“The work of the Australian scientists demonstrates the effectiveness of case-by-case evaluation of GM plants. This helps us determine whether a particular genetic modification has good or bad effects,” said Jens A. Katzek from BIO Germany.

In the following interview, Dr. Thomas J. Higgins tells us about the trial and its consequences.
Dr. Thomas J. Higgins, Deputy Chief von CSIRO
Dr. Thomas J. Higgins, Deputy Chief of CSIRO 
Dr. Higgins, what is the legal situation in Australia relating to release, production and research with GM plants?

Australia is regarded as having one of the most rigorous regulatory systems in the world. The Office of the Gene Technology Regulator commenced operations in 2001 with the role of administering and, if necessary, enforcing the Gene Technology Act 2000 (the Act). It is now currently undergoing a review as stipulated in the Act, with findings expected in the first half of this year.

Prior to the OGTR, gene technology research in Australia was overseen by the Genetic Manipulation Advisory Committee, which set down guidelines for the conduct of gene technology research in Australia.

The OGTR is responsible for developing, implementing and monitoring Australia’s gene technology regulatory framework. The regulations require the controlled conduct of gene technology research within laboratories, and the controlled and safe release of genetically-modified organisms into the environment. All organisations that undertake gene technology research must be accredited.

Officers of the OGTR can inspect any research sites and facilities at any time and without notice to ensure the provisions of the Act are complied with. The OGTR has the power to withdraw research licences, conduct tests on, or take samples of, anything on a research site that relates to a GMO, report any breaches publicly, and fine an organisation for any breaches of the Act or licence conditions issued under it.

It can prevent a research project from continuing, and it is possible for a person to be personally convicted of an offence against the Act.

Breaches of the Gene Technology Act can result in severe penalties, including imprisonment and fines up to AUD$220,000.
Can you tell us something about CSIRO’s flagship, the project related to nutrition? How much of the funds are used for research on insect resistance?

The Food Futures Flagship is working on a number of projects directed towards human nutrition. We are working on making grains with improved nutritional benefit, particularly in the area of preventative health. Two traits are being incorporated into the seeds of crop plants (1) omega 3s from marine micro algae and (2) resistant starch into wheat. The omega-3 project is conducting research to produce new sources of omega-3 oils. Using sophisticated gene technologies, this project is developing ways to increase the availability of nutritionally-significant omega-3 fatty acids by developing new plant sources. Land plants have been developed that produce DHA, a healthy omega-3 oil component, in their seeds by incorporating the micro algal genes responsible for the omega-3 oil production. The latter project is using GM to enable us to breed a non-GM wheat with resistant starch. In other words we are using GM as a breeding tool to enable us to create a non-GM wheat plant with high levels of resistant starch in its seeds. Resistant starch is implicated in improving bowel health and in particular in preventing colorectal cancer. In the Flagship programme no money is being spent on insect resistance. This occurs in other parts of CSIRO.

The GM pea study in Australia has been going on since 1996. How big was the production of GM peas and how many tons must now be destroyed?

There were 12 tons of the alpha-amylase GM peas. These were stored securely according to OGTR requirements. CSIRO is working with the OGTR to determine the most appropriate way of destroy the remaining peas.

What was the planned duration of the project had its course been positive? What other tests were planned?

CSIRO was conducting further risk assessment trials, namely large-scale feeding trials. This is why it had stored 12 tons of peas.

Are similar studies on the inhibition of alpha-amylase conducted in other countries?

Not that I am aware of.

The study involving genetically-modified peas was stopped for safety reasons. Two reactions are said to have evolved through feeding the peas to laboratory mice. One case refers to an inflammatory reaction caused by the generation of antibodies against the inhibitory compound that resulted in lung inflammation. Second, it was observed that laboratory animals reacted negatively to normally harmless pea proteins. How do you rate the impact of these two reactions?

The alpha-amylase inhibitor GM pea project was stopped because the peas did not satisfy all components of a risk assessment process.

When laboratory mice were administered the purified pea form of the bean protein, either directly to their lungs or into their bloodstream there was evidence of an immune response indicated by mild inflammation in lung tissue and raised serum antibody levels. Ingestion of pea meal made from the transgenic peas also induced an immune response evident by raised serum antibody levels.

When mice exposed to the transgenic peas were also exposed to chicken egg white protein, a well characterised dietary antigen, they also showed an immune response to the chicken egg white protein. This suggested that the pea form of the bean protein primed the mouse immune system to other antigens.
Priming of the immune system in this way is known to occur with other non-GM proteins, however this research did not examine further what might have been the reason for the reaction in mice fed the alpha-amylase GM peas.

How high do you rate the risk for humans if these gene-manipulated peas had been allowed to enter human food? Or asked differently. Can these results be transferred to the situation in humans?

The mouse study cannot be unequivocally translated to humans. There is much debate among immunologists about the best animal model for measuring likely human responses to potential antigens.

In light of this uncertainty, CSIRO made the decision to discontinue the work as it believed it was the responsible thing to do.

You said that the process might potentially be used in another genetic engineering project. What are your plans and how can the currently available results be used for further research?

CSIRO’s research led to the development of a highly effective pea transformation system. This technology is published and publicly available. CSIRO is using the knowledge gained in developing the pea transformation system to develop a similar system for cowpeas, which are a staple in many developing nations. Cowpeas are susceptible to many biotic and abiotic stresses, some of which may be amenable to a biotech solution although this remains to be seen. A good transformation system is a requirement to evaluate this approach.

Pea farmers are faced with infestations of the terrible pea weevil leading to yield losses of up to 30%. Now that the work involving genetically-modified peas has been discontinued, will there be an alternative available for the farmers or are there plans for a different method?

No.

You regard the current result as proof that the current safety measures are working. How do you regard the problem of risk assessment?

I think Australia has a very good regulatory system in place that is transparent and as I said before, quite stringent. The Australian Office of the Gene Technology Regulator (OGTR) conducts risk assessments for any field trials of GM products, and also invites public comment on these proposed activities. For maximum efficiency it is important that GM organisms are considered on a case-by-case basis as each plant and each modification is different, and I think this is clearly demonstrated with CSIRO’s alpha-amylase GM peas.

By testing on a case -by-case basis, we can check the benefits of each project and therefore avoid running the risk of missing out on technology that could be of immense benefit.

Dr. Higgins,thank you very much for the interview.
The interview was conducted by Maria Fleischmann-Greissing for BIOPRO Baden-Württemberg GmbH.

Source: Transgenic Expression of Bean 945; Alpha-Amylase Inhibitor in Peas Results in Altered Structure and Immunogenicity. Vanessa E. Prescott, Peter M. Campbell, Andrew Moore, Joerg Mattes, Marc E. Rothenberg, Paul S. Foster, T. J. V. Higgins, and Simon P. Hogan. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY Volume 53, Issue 23 (November 16, 2005) S. 9023 - 903.

mfg - 18.01.06
© BIOPRO Baden-Württemberg GmbH
22.01.2006

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