Dutch H5N1 Flu researchers Eager to Restart their Hybridisation work

After six months of dispute, research in the Netherlands that made a deadly H5N1 flu airborne will be published this week. The scientists behind it now want to get on with their work – but they can't.

In December 2011, a US biosecurity committee advised against publishing the research, fearing it was "dual-use research of concern" (DURC) – done for noble reasons, but dangerous if pathogens escaped or if bioterrorists obtained them. Most committee members changed their minds in April, and approved publication.

But in January, before that turnaround, the world's top flu labs declared a moratorium on any further such research in a bid to calm the situation. "Now, we don't know under what conditions we can lift the moratorium," says Ab Osterhaus of the Erasmus Medical Center in Rotterdam, where the research was done.

In theory they can at any time, because the agreement was voluntary. The problem, says Anthony Fauci, head of the US National Institute of Allergy and Infectious Diseases, is that any similar research done before ground rules for DURC are clarified could run into a similar dispute over publishing.

The US hastily published a new DURC policy in March. It says that if work with any of 15 pathogens increases virulence, transmission, hosts or resistance to defences, researchers must apply a mitigation plan to be agreed by relevant authorities. 

This may include increased containment, changing the experiment, withholding results, classifying the work under secrecy rules – or just not doing it.

A further plan will be published soon, says Fauci. It will flesh out what risks are unacceptable and how to mitigate them, and draw up a committee from US government agencies to apply the rules.

Some researchers welcome the move. "The policy adds another layer of oversight to make sure that all angles have been discussed before and after an experiment with potential dual use," says Adolfo García-Sastre at the Mount Sinai School of Medicine in New York City.

Others fear trouble. Ron Fouchier, who led the Dutch work on H5N1, says the Dutch authorities are happy with his biocontainment precautions, but a US committee is re-examining them under the new DURC rules. 

He worries that pathogen research could simply leave the US. Fouchier thinks researchers and authorities should discuss safety while planning research – and that it should apply to more than the 15 pathogens.

"We need international guidelines on how to decide who can do what, based on the risks and benefits of the research," says Osterhaus. At the moment, he adds, not even bio-containment labs are standardised. He has asked the European Commission to get involved.

The World Health Organization will publish new guidelines on biosafety in coming weeks, and plans a global meeting on DURC issues next year.

David Heymann, chairman of the UK Health Protection Agency, agrees that global standards are needed.

"Stronger regulations are easy, but they're false security, as they either are not enforced, or affect law-abiding scientists but not rogues," he says. What will work, he adds, is if scientists agree on how to do research safely – and enforce this through peer pressure.

H5N1: Chickens engineered to be bird flu decoys

Scientists have engineered chickens that block the spread of avian influenza viruses.

These chickens – which are not intended for human consumption – still got the flu and died, but they didn’t pass the virus on to the healthy chickens they lived with.

These genetically modified chickens (pictured) could one day thwart outbreaks of a global threat to poultry production and human health that has caused the destruction of hundreds of millions of birds and the death of 306 people. But whether these chickens will be safe to eat is yet to be determined.

“Chickens are potential bridging hosts that can enable new strains of flu to be transmitted to humans,” says lead investigator Laurence Tiley of University of Cambridge. “Preventing virus transmission in chickens should reduce the economic impact of the disease and reduce the risk posed to people exposed to the infected birds.”

In this new study, chicken cells produced an RNA ‘decoy’ that resembles the viral genome. It binds to an important part of the virus, preventing its spread.

In particular, the researchers introduced a new gene into these chickens that produces a small molecule that mimics a vital enzyme of the H5N1 flu virus. The decoy tricks the virus’s production machinery into recognizing the decoy instead of the virus’s genome. This makes the enzyme useless, interfering with the replication of the virus.

And none of their cagemates – engineered or not – caught the flu. That means that only one or a few chickens would become infected if the virus entered a flock.

This strategy of developing chickens genetically resistant to infection has advantages over vaccinating the birds. Vaccination, the authors say, still allows the virus to circulate undetected through flocks of chickens, possibly mutating and developing resistance.

It costs approximately $79,000 to produce “a small number of stable transgenic birds you can characterize and breed from,” says study author Helen Sang of University of Edinburgh.

A truly disease-resistant bird wouldn’t be available any time soon, but the chicken method could help develop flu-fighting pigs, ducks, quail and turkeys.

Science reports:

Transgenic chickens could theoretically replace nontransgenic breeds worldwide in a few years, says Michael Greger, director of Public Health and Animal Agriculture at the Humane Society of the US. That’s because the trade in both broiler and egglaying chickens has become consolidated in a handful of companies, which essentially determine what stocks are used by chicken farmers worldwide.

It would inevitably be more expensive, not to mention that these companies don’t sell to the vast number of people in the developing world who have a small flock in their backyard or on their rooftop – and that’s where avian influenza has been the most difficult to control [Science].

The study was published in Science last week and was partly funded by Cobb-Vantress, a major international chicken-breeding company.

Image by Norrie Russell, courtesy of Valerie White and The Roslin Institute

H5N1: Bird Flu, Sexually Transmitted Disease - in Ducks

Bird flu may be a sexually transmitted infection – at least in ducks. That's the suggestion of an analysis of flu prevalence and mating behaviour that also proposes an easy way to spot duck populations most at risk of harbouring avian flu.

Surprisingly, the more rampant the sex a particular duck species indulges in, the lower the chance of spreading the virus. It's all to do with penis size and the complexity of the females' vagina.

Lethal strains of avian flu virus can evolve from harmless versions and then jump to other species, so it is important to also monitor less dangerous strains in wild birds. Ducks are the main wild hosts of bird flu, but surveillance is difficult without easy markers of infection risk.

Now Gergely Hegyi at Eötvös Loránd University in Budapest, Hungary, and colleagues think they may have found just such a marker: the "covert" wing patches that ducks display during mating. This finding builds on the previous work by the team, in which they found that species with large penises tend to have smaller wing patches, which are also more likely to be a single colour.

Sexual arms race
Most ducks form monogamous pairs but the males also often force sex on females because, unlike most birds, they have a phallus. This has led to an evolutionary "arms race" between the sexes, with males evolving longer penises the better to inseminate the female, and females responding by evolving more complex vaginal anatomy to make insemination by unwelcome partners less likely.

When the researchers compared data on the prevalence of low-pathogenic bird flu strains in different duck species with what is known about the anatomy of duck reproductive parts and mating behaviour, they found that ducks with the smallest penises and tamest sex lives had the highest flu levels.

"This is intriguing and a bit counter-intuitive because a long phallus prolongs copulation, and forced copulations characteristic to species with a large phallus should further promote virus transfer," says Hegyi.

The explanation may lie in the counter-adaptation of the female ducks. "Long and elaborate vaginas may hinder unwanted fertilisation but may also make it difficult for viruses acquired during copulation to reach the site of egg formation," Hegyi says.

Infection peak
This idea might help to explain why infections often peak during the breeding season. The researchers think that mating may spread flu by pushing water contaminated with the virus onto developing eggs and so infect chicks before or during hatching – and that this will happen more readily in ducks with less complex vaginas.

Bird flu specialist John McCauley at the National Institute for Medical Research in London says that the idea of sexual flu transmission and its dependence on reproductive anatomy and copulation habits is interesting. "It's quite feasible that they are right, but it will be important to make sure that the epidemiological evidence is robust and not biased by differences in sampling methods."

Because duck species with small penises have larger and more colourful wing patches, Hegyi hopes that confirmation of the link between sex and flu might help to identify which wild populations are most likely to spread bird flu. Monitoring effort can then be concentrated on these populations.

In addition, recognition of sexual transmission "may require different biosafety measures in captive birds than those currently implemented," he says.

Journal reference: Behavioral Ecology, DOI: 10.1093/beheco/arp133

Deadly H1N1 Swine Flu outbreak: Pandemic looms

A novel flu virus has struck hundreds of people in Mexico, and at least 18 have died. It has also infected eight people in the US, and appears able to spread readily from human to human. The World Health Organization is calling an emergency meeting to decide whether to declare the possible onset of a flu pandemic.

Ironically, after years of concern about H5N1 bird flu, the new flu causing concern is a pig virus, of a family known as H1N1.

Flu viruses are named after the two main proteins on their surfaces, abbreviated H and N. They are also differentiated by what animal they usually infect. The H in the new virus comes from pigs, but some of its other genes come from bird and human flu viruses, a mixture that the US Centers for Disease Control and Prevention calls "very unusual".

On Wednesday, the CDC announced that routine surveillance had uncovered mild flu cases during late March and April, caused by a novel swine flu virus. Those affected, aged 9 to 54, live in and around San Diego, California, and San Antonio, Texas, near the Mexican border. None was severe. Symptoms were normal for flu, with more nausea and diarrhoea than usual.

Mongrelised mix

On Thursday, Canadian public health officials warned Canadians travelling to Mexico of clusters of severe flu-like illness there. Then on Friday the WHO in Geneva said in a statement there have been around 900 suspected cases of swine flu in Mexico City and two other regions of Mexico, with around 60 suspected deaths. Of those, 18 have been confirmed as H1N1 swine flu, says the WHO, and tests so far have shown that 12 of those are "genetically identical" to the California virus.

On Friday, Richard Besser, head of the CDC, confirmed that Mexican samples tested at CDC were also "similar" to the US virus. "From everything we know to date, this virus appears to be the same," he said.

To be declared a pandemic, Besser said, the virus must be new, cause severe disease, and transmit easily enough to be sustained.

It is new. Anne Schuchat, head of science and public health at the CDC, said that the US virus is an unusually mongrelised mix of genetic sequences from North American pigs, Eurasian pigs, birds and humans. The H protein on its surface, having hitherto circulated only in pigs, is one most human immune systems have never seen, the crucial requirement for a pandemic flu.

Too late to contain

The virus's severity will depend on how many people who catch it die. While suspect deaths in Mexico are being tested for H1N1, is not yet known how many mild cases of virus there may have been in the affected region that have gone untested. Both numbers are needed to calculate how deadly a case might be. One ominous sign, however, is that the Mexican cases are said to be mainly young adults, a hallmark of pandemic flu.