Scientists to create bird flu strains to assess risk

Scientists are to create mutant forms of the H7N9 bird flu virus that has emerged in China so they can gauge the risk of it becoming a lethal human pandemic.

The genetic modification work will to result in highly transmissible and deadly forms of H7N9 being made in several high security laboratories around the world, but it is vital to prepare for the threat, the scientists say.

The new bird flu virus, which was unknown in humans until February, has already infected at least 133 people in China and Taiwan, killing 43 of them, according to the latest World Health Organization (WHO) data.

Announcing plans to start the controversial experiments, leading virologists Ron Fouchier and Yoshihiro Kawaoka say H7N9's pandemic risk would rise "exponentially" if it gained the ability to spread easily among people.

And the only way to find out how likely that is, and how many genetic changes would need to take place before it could happen, is to engineer those mutations in laboratory conditions and test the virus's potential using animal models, they say.

"It's clear this H7N9 virus has some hallmarks of pandemic viruses, and it's also clear it is still missing at least one or two of the hallmarks we've seen in the pandemic viruses of the last century," says Fouchier.

"So the most logical step forward is to put in those (missing) mutations first."

Writing in the journals Nature and Science on behalf of 22 scientists who will carry out various aspects of the H7N9 work, Fouchier says because the risk of a pandemic caused by a bird flu virus exists in nature, it was critical for risk-mitigation plans to study the likely mutations that could make that happen.

This kind of science is known as "gain of function" (GOF) research. It aims to identify combinations of genetic mutations that allow an animal virus to jump to humans and spread easily.

By finding the mutations needed, researchers and health authorities can better assess how likely it is that a new virus could become dangerous and if so, how soon they should begin developing drugs, vaccines and other scientific defences.

Yet such work is highly controversial. It has fuelled an international row in the past two years after it was carried out on another threatening bird flu virus called H5N1.

Bioterrorism fears

When Fouchier, of the Erasmus Medical Centre in Rotterdam, The Netherlands, and Kawaoka, at the University of Wisconsin in the United States, announced in late 2011 they had found how to make H5N1 into a form that could spread between mammals, the US National Science Advisory Board for Biosecurity (NSABB) was so alarmed that it took the unprecedented step of trying to censor publication of the studies.

The NSABB said it feared details of the work could fall into the wrong hands and be used for bioterrorism. A year-long moratorium on such research followed while the World Health Organisation, US security advisers and international flu researchers sought ways to ensure the highest safety controls.

The laboratory Fouchier will be working in is known as a BSL3 Enhanced lab (Bio-Safety Level 3), the highest level of biosecurity that can be achieved in academic research.

"Nature is the biggest threat to us, not what we do in the lab. What we do in the lab is under very intense biosecurity measures," he says. "There are layers upon layers of layers of biosafety measures such that if one layer might break there are additional layers to prevent this virus ever coming out."

Fouchier concedes that GOF research has been "under fire" recently. "One of the accusations against the flu community was that we were not transparent enough about what experiments were being done, and why and how they were being done," he says. "We're trying to pre-empt such accusations this time."

The H7N9 bird flu outbreak currently appears under control with only three new human cases in May after 87 in April and 30 in March. Experts say this is largely thanks to the closure of many live poultry markets and because of warmer weather.

Yet as winter approaches in China, many experts believe H7N9 could re-emerge, meaning the threat of a pandemic looms if it mutates to become easily transmissible between people.

The first scientific analysis of probable human-to-human transmission of H7N9 raised concern about its pandemic potential and prompted scientists James Rudge and Richard Coker of the London School of Hygiene and Tropical Medicine to warn: "The threat posed by H7N9 has by no means passed."

Fouchier and colleagues say they hope to unravel the molecular processes behind H7N9 by manipulating its genetic material to increase virulence or induce drug resistance.

Wendy Barclay, an Imperial College London flu expert, says it would be ludicrous to shy away from such studies. "This type of work is like fitting glasses for someone who can't see well," she says. "Without the glasses the vision is blurred and uncertain, with them you can focus on the world and deal with it a lot more easily."