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Bioterrorism and Pandemic Flu Preparedness in 2005

Recombinomics Commentary
February 22, 2005

>>  If we are seriously concerned about the possibility that nefarious individuals or groups might make bioweapons using state-of-the-art genetic manipulations, the chain of events leading to recognition that such experiments were under way might look very much like what occurred with these Korean swine strains. The WHO would be under pressure--by international agreement under the Bioweapons Convention of 1972--to definitively prove, or disprove, allegations. Does WHO have sufficient funding, manpower, and clout to do this job at this time? No. <<

As more and more announcements on the looming flu pandemic hit the news services and the public realizes that pandemic preparedness in 2005 is not much better than it was in 1918, the issue of bioterrorism preparedness is again being raised. The bird / human  flu situation in South Korea is being cited as a "scary near miss" to show how unprepared the US is for bioterrorism.

However, the characterization of the WSN/33 situation in pigs on farms in South Korea is clearly not in the "near miss" category at this time.  The situation is unresolved and although several explanations have been offered, the likelihood of the explanations being correct is very close to zero.

The WSN/33 are clearly on deposit at GenBank and Los Alamos and publicly available.  They were deposited at GenBank on Oct 24, 2004 and were publicly available at the end of November.  WHO was notified in early December about potential public health issues, and the possibility of Bioterrorism was also publicly raised in early December.

It is now 2 1/2 months later and the location and existence of the viruses is unresolved.  The Korean lab that isolated the viruses, and deposited the WSN/33 sequences, says the sequences are in many pigs on many farms in Korea.

The human portions of the Korean swine sequences at the databases are clearly WSN/33 related and present in reassortants, which have human and avian influenza genes as well as recombined genes.

South Korea is calling the sequences a lab error and claiming that the WSN/33 sequences exist only in cyberspace, and the sequences they generated point to yet another virus as the source of the human sequences.

Clearly someone is mistaken, but no one at this time can say who.

The South Korean official explanation certainly would fall into the "least likely" category.  There were six sequences on eight genes that were deposited at GenBank last year.  Of these 48 sequences, 30 are over 99% homologous to WSN/33 and virtually all are slightly different than WSN/33 and slightly different than each other.  Moreover, these differences are not random sequencing errors.  They are differences consistent with well defined rules of influenza evolution.

Since the Korean lab has indicated that it does not have WSN/33 growing in the lab, and the viruses were isolated in chicken eggs, it is hard to see how any WSN/33 would contaminate the viruses or the data.  Thus, at this time there is no credible data refuting the presence of these combinations in pigs.

The existence and location of the sequences is not an academic exercise.  WSN/33 is quite lethal in mice and two of the sequences are H1N1 which would be readily transmissible from human-to-human.  Since these sequences are from 1933, most people would be immunologically naïve to these proteins, so infections in humans could have severe consequences.  Moreover, the sequences indicate the isolates have reassorted and recombined genes.  Recent data of 2003 isolates shows extreme genetic instability in South Korean isolates.  Not only were H9N2, H3N2, and H6N1 subtypes identified, but some of these genes were also recombinants.

Since South Korea is saying that there are no WSN/33 sequences in pigs and the data are lab errors, the source of these swine sequences is not being investigated.

Thus, the existence of the sequences in swine has not been resolved for four months after they were placed on deposit at Genbank.

Bioterrorism and Pandemic Preparedness are interesting concepts, but avian influenza continues to evolve and gain pandemic potential as governments spin wheels, issue warnings, and hope for the best.

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