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A modest Jurassic Park: Simultaneous recreation of a certified bioweapon and a pandemic diagnostic tool


Part 1

A decade's concerted effort has culminated in the reconstruction of the 1918 Spanish Flu (H1N1) pandemic flu virus:

  • Armed Forces Institute of Pathology: secured lung tissue samples from three 1918 victims, extracting and sequencing genome structures, publishing the sequences of five of the eight genes.
  • Mount Sinai School of Medicine: Using AFIP coding data, employed reverse genetics to create strings of genes called plasmids
  • Centers for Disease Control and Prevention: Inserted Sinai's plasmids into human kidney cells whereupon H1N1 reassembled itself
  • GenBank, National Institutes of Health: H1N1 genetic sequences stored in a public genetic sequence database

The outcome was the publishing of remaining three genes, completing the genetic sequence, and the production of ten vials of H1N1 virus, with more on order as research demands dictate. What is reasonably the "most effective bioweapons agent ever known" and noted for "preferentially striking the young and the healthy" is in the public domain. It seems a Faustian bargain, but I agree with D.A. Henderson that it is critical for its ability to inform our analysis of potential lethality of the current H5N1 avian flu.

What we've learned is useful: H1N1 was actually a bird flu that had leapt to human-to-human transmission without apparently mixing with a human form of flu. It is this co-infection of a human host with both avian and human flu producing a human transmissible strain that is being watched for with H5N1. It would be startling if H5N1 could make an H1N1-like leap.

It has been found that H1N1 and H5N1 share some critical genetic changes, but not all the 25 to 30 that turned H1N1 into a pandemic:

The new studies could have an immediate impact by helping scientist focus on detecting changes in the evolving H5N1 virus that might make widespread transmission among humans more likely.

We now know that H1N1 was very different from ordinary human flu viruses in that it infected cells deep in the lungs such as the cells lining air sacs that are normally impervious to flu. H1N1's similarity to H5N1 confirms current fears of current avian flu strains migrating from China and Southeast Asia through Russia and into Europe.

Crucial requirements for human adaptation are already being discovered:

In gene-swapping experiments, for example, they put the hemagglutinin gene from the 1918 virus for one from a more recent human virus. Suddenly, the reconstructed virus could no longer replicate in the lungs of mice and no longer killed the animals. It also could not attach itself to human lung cells in the lab. Yet the 1918 virus' hemagglutinin protein differs in just two critical amino acids from the protein of a typical avian flu virus.

A desired outcome would be a likely checklist of pandemic-inducing changes in H5N1 and other wildfowl flu variants.

As one who researches low tech asymmetric production of chem-bio agents, I am aware that advances in molecular biology will make it more feasible for small groups to harvest this genetic sequencing for production of a new weapons strain for which human immune systems may be unprepared. Given the threat of an H5N1 pandemic it is a daunting but necessary compromise.

Researchers Reconstruct 1918 Flu Virus
The Associated Press
October 5, 2005; 3:30 PM

Deadly 1918 Epidemic Linked to Bird Flu, Scientists Say
New York Times
October 5, 2005

Gordon Housworth

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