Details of engineered contagious bird flu finally revealed

Last fall, scientists were about to publish the results of their work in mutating a deadly flu virus. Their big breakthrough? Making the virus easily transmissible from human to human.

Due to fears of bioterrorist attacks, the government asked the two scientific journals to stop publication.

But after much soul-searching within the scientific community, the government decided to allow publication so that the details could help government agencies monitor for outbreaks of bird flu. In May and June, the previously censored stories were finally published in Nature and Science, respectively.

Health officials should be able to use the research to find out what kind of bird-flu genetic signatures could indicate that the flu is mutating in a way that will make it transmissible from human to human. (While such mutations are rare, the Spanish flu of 1918 did originate as a bird flu that mutated to become contagious between humans.)

How many mutations will make it contagious between humans?

Both experiments concern the bird flu virus H5N1, which, since 2003, has killed about 60% of the 600 people who have caught it. (It originated in 1997 but was absent afterward for six years.) Many people catch it directly from infected birds, but even touching contaminated surfaces can lead to infection.

In one of the June papers published in Science, Ron Fouchier of the Erasmus Medical Center in the Netherlands and his colleagues engineered mutations in the virus to see how many were necessary before it could be spread through the air from one ferret to another. (Ferrets, like humans, are mammals, so the team's findings could apply to all mammalian hosts.)

The team found that all that was needed were five particular mutations.

Could it mutate like that in the wild?

Another accompanying paper in Science explored how easy it would be for H5N1 to naturally acquire those five mutations.

A team led by Derek Smith, an evolutionary biologist at the University of Cambridge, found that two of the mutations have arisen on their own in the wild numerous times; in fact, one group of related H5N1 viruses have both mutations, so they would only need three more mutations to become easily transmissible between mammals.

Smith and his colleagues built a mathematical model to see how likely that group of viruses could acquire those three mutations: While they determined that the virus could get all three mutations in one person, the odds that happening were trickier to calculate.

“It’s possible that the chances are one in a thousand, and we’ve just gotten lucky,” Dr. Smith told The New York Times. “Or it’s possible that the chance is one in a million and it might not happen for a long time.”

How many mutations if it combines with another virus?

The Nature paper explored another way that H5N1 could become a pandemic. Their method? To look at how the mutations are affected by the mingling of two viruses in one person, which happens yearly when different human flu strains simultaneously infect a person.

A team led by Yoshihiro Kawaoka of the University of Wisconsin mixed human flu strains with an H5N1 gene: After this "reassortment," as the process is called, only four mutations were needed before the virus spread from ferret to ferret.

Scientists do not yet know of any instances in which a human flu strain has combined with H5N1. For that reason, they also don't know of the probability that it could happen.

While the papers details two ways the virus could mutate to create a human pandemic, there are surely others.

As The Times reports:

Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, hopes scientists will be able to amass a longer list of potential mutations, and even find a common denominator in how they alter H5N1. It might then be possible to monitor emerging strains for signs that they are about to cross over into humans.

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