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Biological Chemistry

More On H5N1

by Rudy M. Baum
February 20, 2012 | APPEARED IN VOLUME 90, ISSUE 8

If William Shakespeare had never lived, the plays he wrote would not exist. Someone might have written:

To be or not to be, that is the question:

But it most certainly would not have been followed with:

Whether ’tis Nobler in the mind to suffer

The Slings and Arrows of outrageous Fortune

Or to take Arms against a Sea of troubles

And by opposing end them

On the other hand, if Albert Einstein had never lived, it is quite certain that someone else would have deduced E = mc2. Unlike Shakespeare, who created Hamlet’s famous soliloquy, Einstein discovered a fact of nature that was there for anyone to discover. That fact does not lessen Einstein’s brilliance, but it does underline the difference between creation and discovery.

This distinction is germane, it seems to me, to the controversy over publication of two papers in Science and Nature on the H5N1 bird flu virus. C&EN News Editor William Schulz examines the details of that controversy in this week’s lead Government & Policy Department story (see page 34).

H5N1 naturally infects birds. In 600 cases, humans have been infected with H5N1 from poultry and other people, and more than half of those infected died. While that is a horrifying mortality rate, there is no evidence thus far that the virus can be transmitted from human to human through the air.

The controversy is over the work of two teams of flu researchers in the U.S. and the Netherlands. They have demonstrated that H5N1 can acquire the ability to be transmitted from ferret to ferret by air, and they have documented the five genetic changes that give the virus this capability. They have also shown that the mutated virus is just as lethal in ferrets as the natural virus is when it infects humans.

The U.S. National Science Advisory Board for Biosecurity (NSABB) has recommended that the journals publish only highly redacted versions of the papers, omitting the details of how the experiments were conducted and the identity of the mutations that confer air transmissibility. The argument is that this information is too dangerous to be made public lest a terrorist decide to use it to create a bioweapon.

There are a number of problems with the NSABB recommendation, and I discussed several of them in an earlier editorial (C&EN, Jan. 9, page 3). Another real issue involves the distinction between creation and discovery. The H5N1 virus exists; it has infected billions of birds and hundreds of humans; it is constantly evolving and eventually it will very likely hit on the combination of five mutations that will confer on it air transmissibility among humans. Yes, the Dutch and American researchers whose work NSABB wants to censor created viruses that can be transmitted by air among ferrets. But this is creation in a trivial sense because nature is quite capable of doing the same thing. Intellectually, the researchers’ success was in discovering the set of mutations that lead to the new trait.

How they did it isn’t really much of a secret. Google “increasing avian viral virulence through passaging,” as Schulz did while working on his story. One of the first hits is a 2001 Journal of Virology paper on “­Generation of a Highly Pathogenic Avian Influenza A Virus from an Avirulent Field Isolate by Passaging in Chickens.” One of the co­authors is Yoshihiro Kawaoka, one of the lead scientists on the H5N1 work in ­ferrets.

Google “air transmissibility of flu virus in ferret model,” and a top hit is a 2006 PNAS paper on “Lack of Transmission of H5N1 Avian-Human Reassortant Influenza Viruses in a Ferret Model.” The goal of work reported then was exactly the same as the work now causing a furor. The “Discussion” section of the paper begins: “If H5N1 viruses acquire the ability to undergo efficient and sustained transmission among humans, a pandemic would be inevitable. An understanding of the molecular and biologic requirements for efficient transmissibility is critical for the early identification of a potential H5N1 pandemic virus and the application of optimal control measures.”

Exactly. And the way to further that goal is to publish the papers in full.

Thanks for reading.



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