Quest for holy grail of influenza may be near end

1918 strain closer to genetic sequencing

The genetic secrets of the deadliest influenza virus in human history may be finally given up by three people among the more than 20 million who died in 1918.

In the latest case, a tissue specimen containing RNA fragments from the virus — which has remained unidentified since the 1918 pandemic — has been recovered from a long-buried flu victim in Brevig Mission, AK. The specimen is being studied at the molecular pathology division of the Armed Forces Institute of Pathology (AFIP) in Washington, DC, which has been working with genetic fragments from two archival samples from two U.S. servicemen who died during the pandemic.

"I think with all three [specimens] we will be able to sequence the whole virus," says Ann Reid, MA, AFIP molecular biologist.

Identifying the infamous flu strain could help explain its striking virulence and ease of transmission, as well as shed light on whether the same virus is still present in wild bird populations.

"With a full-length genetic code for all the segments, we should be able to get a better idea of where this virus came from," Reid says. "That would be important for surveillance. Presumably the ancestor of the 1918 flu is out there somewhere, but also presumably something about it changed to make it so supremely adapted to spread in humans."

The most recently discovered tissue sample in Alaska was obtained by Johan V. Hultin, MD, a pathologist and veteran flu researcher in San Francisco. Hultin obtained permission to open graves and perform biopsies at Brevig Mission, formerly called Teller Mission, which lost approximately 85% of a population of some 200 people to influenza during one week in November 1918. Hultin participated in a similar expedition to Brevig Mission in 1951, when researchers tried to culture live virus from 1918 flu victims buried in the permafrost. No live virus was found, and molecular genetic analysis of the samples was not possible at that time.

However, after reading reports last year of the discovery of genetic material in the two archival samples, Hultin returned to Brevig in August 1997 and exhumed the bodies of 11 victims.1 Four of those retained soft tissue, and lung biopsies were taken directly from the frozen remains without removing the bodies. The 1918 strain was recovered from one of the four, a native Alaskan female. No attempt to culture live virus was undertaken in the expedition last year. Since none could be recovered in 1951, the likelihood of finding it nearly a half century later was considered minuscule. Beyond that — even in an era of emerging infections, cloning, and increasing discussion of bioterrorism — there is no realistic risk of unleashing the pathogen again, Reid adds.

"Certainly in the material that we received there were no fragments larger than about 120 base pairs of RNA, so there is no question there was no live virus there," she says. "I don’t think there is any danger of this virus being resurrected in that way. I suppose it is conceivable that once the entire thing is sequenced someone could reconstruct it, but that would not be a trivial task."

Reference

1. Taubenberger JK, Reid AH, Krafft AE, et al. Initial genetic characterization of the 1918 "Spanish" influenza virus. Science 1997; 275:1,793-1,796.