A decade-long project to develop genetically modified peas with built-in pest-resistance has been abandoned after tests showed they caused allergic lung damage in mice.

The researchers – at Australia’s national research organisation, CSIRO – took the gene for a protein capable of killing pea weevil pests from the common bean and transferred it into the pea. When extracted from the bean, this protein does not cause an allergic reaction in mice or people.

But the team found that when the protein is expressed in the pea, its structure is subtly different to the original in the bean. They think this structural change could be to blame for the unexpected immune effects seen in mice.

The work underlines the need to evaluate new GM crops on a case-by-case basis, says Paul Foster of the Australian National University in Canberra, who led the immunological work. He also calls for improvements in screening requirements for genetically engineered plants, to ensure comprehensive tests are carried out.


Jeremy Tager, Greenpeace Australia’s campaigner on genetic engineering, agrees. “These results indicate the potential for unpredicted and unintended changes in the structure of transferred proteins. And I’m not aware of any country that requires feeding studies as part of its approval process.”

Completely resistant

Field peas (Pisum sativum) are susceptible to the pea weevil Bruchus pisorum, which lays its eggs on the pea pods. The weevil frequently devastates crops not only in Australia but across the developing world.

The common bean (Phaseolus vulgaris) contains alpha-amylase inhibitor-1, a protein that inhibits the activity of alpha-amylase, an enzyme that is used by pea weevils to help them digest starch.

CSIRO Plant Industry researchers hoped the developing weevils would starve after eating the protein, before they could cause any real damage to the crop. Trials showed that the GM peas were almost completely resistant to the pea weevils.

Hypersensitive skin

Foster and his team then used mice to investigate whether eating the GM peas might have any undesirable immune impact. Generally, digested proteins do not create a specific immune system response.

But researchers found that mice that ate transgenic pea seed did develop antibodies specific to the protein. Some of these mice were later exposed to the purified protein, either through injection into the blood, or by putting the protein into their airways.

This approach is a standard “multiple immune challenge” procedure and is designed to determine if the immune system is tolerant to a protein. The injected mice showed a hypersensitive skin response, while the airway-exposed mice developed airway inflammation and mild lung damage.

The effect was the same whether the protein was taken from raw or cooked peas – so whether the protein was active or denatured. “To my knowledge, this is the first description of inducing experimental inflammation in mice” with a GM food, Foster says. In the early 1990s, researchers engineered a more nutritious strain of soya bean by adding a gene taken from brazil nuts. But the project ended when it was discovered that the hybrid was likely to trigger a major attack in people with brazil nut allergies.

Human consumption

Further investigations by Foster’s team revealed slight differences in the molecular structure of the protein when it was expressed in the bean and in the pea. They think this was caused by differences in the way the two plants produce proteins – particularly in a step called glycosylation, which involves adding saccharides to the protein.

“When expressed in the pea, the protein was glycosylated at different points – that’s the only structural change we’ve been able to identify so far,” says Foster.

He adds that slight differences in protein synthesis might also occur in other plants with other genes, meaning each new GM food should be very carefully evaluated for potential health effects. “If a GM plant is to go up for human consumption, there should be a detailed descriptive list of how one should go about analysing that plant,” he says.

Tager agrees. It is rare for an investigation of the potential health effects of a GM product to be published in a peer-reviewed journal, he adds. “If it had been a private company doing this, it might never have seen the light of day,” he says.

GM Organisms – Is GM the future? Learn more in our continually updated special report.

Journal reference: Journal of Agricultural and Food Chemistry (vol 53, p 9023)