However this pandemic evolves, we are going to learn a lot about how pandemics evolve — or maybe even start. A paper just published online in Nature sets out a bit more of what we know about this pandemic strain (yes, we can officially refer to it that way now) and makes some observations about its prehistory (its history before it became known and documented by we mortals). Maryn McKenna has an excellent run-down over at CIDRAP News, which you should read. Here’s our take on it.
First, we’d like to make a “meta-science” observation. This paper is unusual in several ways. The least remarkable is that it is a multi-continent collaboration of scientists (Hong Kong, UK, US). Not so unusual these days, but worth remembering. Science publishing and collaboration is changing and digital communications via the internet is enabling it. That’s not to say that even in those new clothes the old world isn’t still present. Too many of today’s top flu scientists are still keeping their sequences private until publication, a habit sometimes justified as “protecting post docs, young faculty and graduate students.” St. Jude, Mt. Sinai and CDC itself are all guilty of this deplorable (and in the context of a pandemic, frankly unethical) practice. We’ve called them on it multiple times. And that’s the second way this paper is unusual. The authors have been openly sharing and collaborating (via a multi-author wiki platform). The analysis reported in this paper has been done bit by bit out in the open, for all to see. They still were able to publish in one of the highest profile journals in the world (Nature). No post docs or junior faculty or graduate students got hurt by it. On the contrary, by working together they had a much stronger result. The third observation is that Nature published the paper without embargo, meaning it wasn’t provided ahead of time to a favored list of reporters (and often science bloggers; we are on several embargo lists and we abide by the terms. But we hate the idea of it). It is still getting plenty of press. Press embargoes are deplorable and any scientific journal that values transparency and the objective evaluation of merit and interest shouldn’t do it. If they want to call attention to themselves or certain papers they can always issue a press release.
So much for meta-science. What about the contents of the paper? The authors make two interesting points. By a detailed analysis of genetic sequences from 2 outbreak (now pandemic) virus genomes, 15 newly sequenced swine viruses from a Hong Kong surveillance project that goes back into the 1990s and 796 other flu virus genomes representing a diverse spectrum of influenza (285 human, 100 swine, 411 avian isolates) they showed that each of the 8 segments of the new pandemic virus came from an established swine lineage (established meant circulating for more than 10 years before this outbreak). A very nice figure in the paper illustrates the braided origin of the current virus. It has pieces from a 1979 Eurasian swine virus (which in turn was likely of avian origin) and a triple-reassortant North American swine virus (which in turn had pieces of avian H1N1 virus, classical swine virus [which itself may have been derived from humans] and human seasonal H3N2 and later mixed again with classical swine virus replacing H3 with H1). This much was already known. But inclusion of the 15 Hong Kong surveillance sequences showed that combinations of Eurasian swine, North American triple reassortant and classical swine segments were already present, although not the exact combination seen in the outbreak. One that was the same in 7 of 8 segments was isolated in Hong Kong in 2004, referred to by the authors as a sister lineage to the one in the outbreak. They conclude that the components of the pandemic strain have been circulating in swine for years and were widely distributed geographically.
The authors were still not able to say where the final combination came together and then jumped to humans because the genetic record from swine is too sparse. There are long gaps at places where things were likely happening, but we don’t know when or where. Using some assumptions about the rate of molecular evolution, the authors suggest the species jump (to us) may have happened somewhere around the first of the year or perhaps a few months earlier, but the virus may have been circulating undetected for years in pigs.
The final paragraph of the paper is being widely quoted on the newswires:
As reported recently, all three pandemics of the twentieth century seemto have been generated by a series of multiple reassortment events in swine or humans, and to have emerged over a period of years before pandemic recognition. Our results show that the genesis of the S-OIV [swine-origin influenza virus] epidemic followed a similar evolutionary pathway: H1N1 viruses with human pandemic potential had been identified, transmission from swine to humans was known and the disease had been made notifiable. Yet despite widespread influenza surveillance in humans, the lack of systematic swine surveillance allowed for the undetected persistence and evolution of this potentially pandemic strain for many years. (Smith et al., Origins and evolutionary genomics of the 2009 swine-origin H1N1 influenza A epidemic. Nature 2009 (advance online publication Jun 11 [cites omitted])
In our view it’s unlikely that even with systematic swine surveillance we would have been able to predict this event because our knowledge of the relationship of the genetics to the biology is still primitive. It is interesting that the authors imply that the 1918 virus was also the result of multiple reassortment in swine and humans. Taubenberger has maintained that the 1918 virus jumped to humans from birds, displacing the earlier view expressed here. There is a citation to a paper in press at PNAS by the senior author of this paper (Smith), so we’ll have to wait for it to appear to see what this is about.
An influenza pandemic is a public health calamity. But for flu science, it is also a golden opportunity.
Addendum: Just noticed Ed Yong’s terrific post on this paper over at scienceblogs Not Exactly Rocket Science. He includes the figure I referred to above. Some detailed and clear explanaiton of this paper. Highly recommended.