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Sequencing the Killer Flu

h1n1.jpgSometimes, the universe has excellent timing. It's Pandemic Flu Awareness Week, and what should we get but two major scientific papers detailing the biology of the virus behind the greatest pandemic the planet has ever seen.

In 1918, when the total world population was about 1.8 billion people, a strain of virus known as the "Spanish Flu" infected about 20% of the planet, killing 50 million people before burning itself out. While records of what happened to the victims are abundant, we've had no clear idea of exactly what kind of virus killed so many -- until now. Scientists at the US Armed Forces Institute of Pathology in Rockville, Maryland led by Dr. Jeff Taubenberger have managed to piece together and sequence the entire genome of the virus known as H1N1 (the research is in the current edition of Nature); with the complete sequence in hand, Dr. Terrence Tumpey at the US Centers for Disease Control in Atlanta was able to recreate the virus for study, as reported in the latest edition of Science. What the biologists found was unexpected, troubling -- and potentially the key to fighting the next influenza pandemic.

The two most recent large-scale flu pandemics, the 1957 'Asian' flu, and the 1968 'Hong Kong' flu, were what specialists call a "reassortant virus," meaning that they were strains of influenza common to humans that picked up two or three genes from bird flu viruses. The 1918 flu, however, is now known to be an avian flu that picked up genes allowing it to be acquired and transmitted by humans. Moreover, it shares key characteristics with H5N1, the current version of Avian Flu now showing up in Asia. And when mice were exposed to the recreated 1918 virus, they died in greater numbers and with greater speed than the biologists had anticipated -- the 1918 strain was at least 50 times more virulent than a contemporary flu strain.

By studying the flu genome and its effects, the biologists intend to determine how this extreme virulence comes about, and the ways in which it relates to the current avian flu. The Spanish Flu sequence is now part of the set of genomes from 399 strains of human influenza virus, sequenced by the Influenza Genome Sequencing Project, a global collaborative effort to build a database of the thousands of types of human and avian influenza viruses. This research will be crucial to our ability to understand, respond to and potentially prevent influenza pandemics.

In an unusual move, Nature has made available the entire text of the genome sequencing article, rather than just the abstract (as is their common practice). Although the article language is heavily technical, it's worth scanning, as a couple of important elements stand out: by sequencing the 1918 genome, the biologists now have a much better idea of which genes play key roles in making a virus that normally only infects birds jump species to pose a threat to humans; in addition, the details of the genome show that the H1N1 sequence shares numerous similarities to the H5N1 virus now extant in Asia, but they are not entirely identical.

051005_bird_flu2.jpgAs usual, the BBC has a good non-specialist summary of the research, as does National Geographic; New Scientist's report is a bit more technical.

Many of the reports, including an editorial in Nature, note the risk of the decision to recreate the 1918 virus. Considering that the 1918 pandemic killed around 3% of the planet's population, concern seems warranted. The biologists emphasize, however, that this version of the flu would have nowhere near the same kind of effect today, for a couple of good reasons: we have anti-virals that would be very effective against it, as this is a version without any evolved resistance to current medicines; and as there are modern influenza viruses carrying pieces of the 1918 strain, most people would have some acquired immunity to the virus, and current vaccines should also be effective. The researchers caution, however, that this has not been tested, and remains educated conjecture. As only one person has access to the recreated virus -- the doctor from the CDC who authored the article in Science detailing the findings -- escape into the wild is unlikely.

The Nature editorial raises a larger question, however. One aspect of the publication of the research is making the genome sequence available on various scientific databases.

Anyone can order DNA to be made to a certain sequence, points out Jonathan Tucker, a policy analyst at the Center for Nonproliferation Studies in Washington DC. There are currently no governmental controls on what sequences can be used, says Tucker, although some DNA synthesis companies now screen their orders for pathogenic sequences. If someone wants to reconstruct the virus, says [1918 virus study author Jeff] Taubenberger, "the technology is available".

The editors at Nature and Science did not discount this possibility, but decided -- with support from US National Science Advisory Board for Biosecurity (NSABB), Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, and Julie Gerberding, director of the Centers for Disease Control. Their reasoning -- with which I strongly agree -- is that the public health risks of greater knowledge of the H1N1 sequence are far outweighed by the benefits the knowledge of the virus will provide for prevention of and response to natural pandemics.

Taubenberger admits that there can be no absolute guarantee of safety. "We are aware that all technological advances could be misused," he says. "But what we are trying to understand is what happened in nature and how to prevent another pandemic. In this case, nature is the bioterrorist."

There are far more scientists who would be willing and able to work on a response to an outbreak than would try to misuse the genetic information for harmful purposes. Although another outbreak of the 1918 virus is highly unlikely, the current research strongly suggests that a better understanding of the virus from nearly a century ago will be of extraordinary value in fighting a pandemic version of the current avian flu strain. Self-imposed ignorance is not a solution.

Comments (1)

Looks like awareness is growing, too. Ask not what your country (town, family, network) can do for you, etc.

Click on my URL, please.

btw, we may be setting up a small hack to help with translating "wikis that grow".

Technology is our extended phenotype, really. Or is it "extended memetype"? Whatever works.

Did I ask you to Click on my URL, please? :)


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