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Nature goes ahead and publishes study explaining how to create deadly mutant bird flu

Illustration for article titled emNature/em goes ahead and publishes study explaining how to create deadly mutant bird flu

After months of controversy, the journal Nature has published the details of an experiment describing how the avian flu can be modified into a human-contagious form.

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The publication has prompted critics to warn of a possible human disaster, should the details of study get into the wrong hands or the mutant virus accidentally escape the lab. And this incident highlights growing concerns about unchecked scientific inquiry, the mounting potential for academic censorship, and the ongoing development of increasingly powerful and dangerous biotechnologies.

The research was conducted by Yoshihiro Kawaoka and his team at the University of Wisconsin-Madison to determine the likelihood of the H5N1 influenza virus naturally mutating on its own in the wild. Their findings were alarming. The research team discovered that the virus was as little as one mutational step away from being able to spread effectively between other animals through airborne transmission. The virus is highly pathogenic and often lethal in humans, but in its current incarnation cannot spread efficiently between people.

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Illustration for article titled emNature/em goes ahead and publishes study explaining how to create deadly mutant bird flu

To determine the possibility of increased human transmissibility, Kawaoka created a hybrid virus by mutating H5N1's haemagglutinin (HA) gene, which produces the protein that the virus uses to stick itself to host cells. His team then exposed this updated virus to ferrets in separate cages to see if it could spread — which it did after just four mutations.

This is of particular concern because some Middle Eastern strains of H5N1 are already recognizing human receptors. This finding suggests that a more devastating version of the virus — one that could affect humans — could be as little as one stabilizing mutation away.

Supporters of Kawaoka's work claim that this information is crucial for a number of reasons, including pre-emptive awareness, and most importantly, by offering a blueprint to help create countermeasures should such a mutation actually happen in the future. It also points to the importance of ongoing research in these areas to prevent the onset of other viruses, including such pathogens as SARS. As virologist Jeremy Farrar noted in a Nature article about today's announcement, "this work reminds us just how vulnerable we potentially are to relatively small changes." It's for this reason that Farrar and a number of other scientists support the work and the ongoing freedom that scientists have to pursue seemingly dangerous work.

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But not all agree. Writing in an editorial in the journal Science last January, virologist Michael Osterholm of the University of Minnesota claimed that, "The desire to disseminate the entirety of the methods and results of the two H5N1 studies in the general scientific literature will not materially increase our ability to protect the public's health from a future H5N1 pandemic." Other scientists worry that bioterrorists could use the information to weaponize the disease. Others simply fear that an accident could happen in which the virus gets away from researchers and infects the general population.

And according to a report in Wired magazine, many prominent virologists are afraid to criticize the findings publicly for fear of retribution from such groups as the National Institutes of Health and other funders. It's quite possible, therefore, that many concerned scientists are keeping a tight lip on the matter, for fear of a backlash and an end to their funding.

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With today's publication of the study in Nature, the genie is officially out of the bottle. The future is unclear, both in terms of the benefits and threats that such open knowledge may bring. Moreover, when considering the temporary moratorium on similar research that was put into place several months ago, it's clear that this issue is far from settled.

The full publication of the study in Nature can be found here.

Sources here and here. Top image via Wikipedia. "Making Mutant Flu" image via Nature.

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DISCUSSION

There are a number of glaring factual, and conceptual, flaws in this article, starting with the title and working down from there. Perhaps the most obvious would be the word "deadly".

1) In fact, while Kawaoka and his team were able to engineer a virus with an H5 variant HA protein that could be spread by aerosal transmission, none of the ferrets infected this way died. None. In this and the related Dutch paper, if they gave the ferrets 100 or 1000 times more virus by direct innoculation then yes, they could die. But calling it "deadly" is a clear misnomer. This does go to show just how complicated viruses are. There are dozens of factors that mediate virus virulence and pathogenicity (HA and NA specificity, replicating temperature, evasion of host defences, etc, etc...). Imagining that anyone could take this data and have a lethal flu strain while working in some hidden bunker ignorant at best.

2) This virus is nowhere near "one mutation" away from being able to spread by an aerosol route in mammals. The first step that Kawaoka's group did was to put just one gene (HA) from H5N1 "bird flu" into an H1N1 virus from 2009. Right off the bat, then, they changed 7/8ths of the genome (influenza has 8 gene segments) before making any point mutations. While reasortments like this can happen in the wild, it would take a patient (or animal) who was simultaneously infected with both kinds of flu, and even then would be highly unlikely. And after all that, it still took multiple mutations to get any sort of transmission between animals. And even then, as mentioned above, it still wasn't nearly as pathogenic as the strains of flu we have running around in the wild right now.

3) You're worried about "precedent"? The entire genomes of everything from the 1918 Spanish pandemic flu to Ebola are already freely available online. As is a ton of other research into how, or how not, to get flu to transmit between mammals. The basic techniques these researchers used: making mutants and serially passaging the quasi-species in mammalian hosts to adapt them, has been done for decades! Most of the controversy around this research was when all we knew amounted to Fouchier bragging in a meeting without presenting any data. Once that was made available, the major in the virology community that I've seen has been "Oh, that's all?" On the other hand, once you start refusing to publish information because some might possibly use it to get closer to something that could be dangerous, where do you draw the line?

4) While there are reasonable concerns about accidental release (The 1977 Russia Flu may have been caused by an accidental release), we already have measures in place to deal with those sorts of hazards. Step up the containment to BSL4 if you're really, really concerned. It would probably set the work back 2-5 years, but maybe that's what needs to be done. Refusing to address the issue at all is just monumentally short-sighted.

So that was a bit of a rant. Hopefully it was informative. However, as someone doing microbiology research, I've had my share of run-ins with people panicking over the media scare story of the week. Unfortunately it's most often due to miss-information, and articles like this go a long way towards spreading those inaccuracies, even when they try to be non-partial.