BSL-4 Lab Worker - Photo Credit –USAMRIID
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Last year, in H2N2: What Went Around, Could Come Around Again, we looked at a cautionary report from researchers at St. Jude Children's Research Hospital that warned that avian H2N2 viruses – similar to the one that sparked the 1957 pandemic – continue to circulate in the avian species.
Those born after 1968 – when H2N2 was supplanted in the human population by the H3N2 virus – are likely to have little immunity to an H2 flu virus, and so concerns remain that the virus could re-emerge as a pandemic.
The H1N1 virus – which disappeared for 20 years after H2N2 arrived on the scene – returned in 1976, and has co-existed with H3N2 ever since. Given the near-universal exposure we all have to H1N1, few scientists thought another H1N1 could pose a substantial pandemic risk.
That theory was disposed of when, in 2009, a `new’ H1N1 variant appeared and did just that.
All of which brings us to a new study, published today in Cell Host & Microbe, that begins by looking at the current reservoir of avian flu viruses in the wild for gene segments similar to those found in the deadly 1918 H1N1 pandemic virus. And as you might expect, they found what they were looking for.
Gene segments with a `high homology’ to the 1918 virus still exist in the wild, and given the ability of flu viruses to reassort, may pose a future pandemic risk.
How big that risk is, is unknown.
This story gets more complicated, when - in what some scientists consider a risky step - the researchers assembled their own version of the 1918 pandemic virus using these different gene segments, and proceeded to test it on ferrets.
This virus was `close’ to the 1918 version – but not an exact match - off by a few amino acid substitutions. And so the virus didn’t kill or spread between the ferrets.
These researchers then introduced a small number of mutations (and some arose spontaneously), that increased both the virus’s transmissibility and virulence, making the virus deadly (at least to ferrets).
A press release from the University of Wisconsin-Madison describes the experiment:
Genes found in nature yield 1918-like virus with pandemic potential
(EXCERPT)To assess the risk posed by a virus that could acquire all eight of the 1918-like genes, the team used reverse genetics methods to generate a virus that differed from the 1918 virus by only 3 percent of the amino acids that make the virus proteins. The resulting virus was more pathogenic in mice and ferrets that an ordinary avian flu virus, but was not as pathogenic as the 1918 virus and it did not transmit in ferrets via respiratory droplets, the primary mode of flu transmission.
Since pandemic risk escalates when a virus become transmissible, Kawaoka's group then conducted additional experiments to determine how many changes would be required for the avian 1918-like virus to become transmissible in ferrets, a well accepted model for influenza transmission studies. The researchers identified seven mutations in three viral genes that enabled the pathogen to transmit as efficiently as the 1918 virus. The resulting virus, composed of genetic factors circulating in wild and domesticated birds, demonstrates that the genetic ingredients for a potentially deadly and pandemic pathogen exist in nature and could combine to form such a virus, according to Kawaoka.
<SNIP>
The transmission studies were conducted under specially designed high-containment conditions, using commensurate biosafety practices, at UW-Madison with approval of the university's Institutional Biosafety Committee. The draft manuscript was reviewed by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH), in keeping with the institute's implementation of the United States Government Policy for Oversight of Life Sciences Dual Use Research of Concern.
First, the link to the article, then I’ll have a little bit more on the controversy that surrounds Gain of Function (GOF) research.
Circulating Avian Influenza Viruses Closely Related to the 1918 Virus Have Pandemic Potential
Tokiko Watanabe12,Gongxun Zhong12, Colin A. Russell12 , Noriko Nakajima , Masato Hatta , Anthony Hanson , Ryan McBride , David F. Burke , Kenta Takahashi , Satoshi Fukuyama , Yuriko Tomita , Eileen A. Maher , Shinji Watanabe , Masaki Imai , Gabriele Neumann , Hideki Hasegawa , James C. Paulson , Derek J. Smith , Yoshihiro Kawaoka
DOI: http://dx.doi.org/10.1016/j.chom.2014.05.006
Highlights
- •Current circulating avian flu viruses encode proteins similar to the 1918 virus
- •A 1918-like virus composed of avian influenza virus segments was generated
- •The 1918-like virus is more pathogenic in mammals than an authentic avian flu virus
- •Seven amino acid substitutions were sufficient to confer transmission in ferrets
Despite the safety precautions taken, there is considerable concern among some in the scientific community over the safety of these so called `gain of function’ (GOF) experiments, and that has led to increasingly heated exchanges and increasing polarization in academia.
Proponents argue that these experiments can help us discover what strains have the most pandemic potential, and could help in the early development of a vaccine. Opponents argue that these potential benefits are overstated, and the risks of an accidental release from the lab are too great.
This is an area where reputable – indeed, world renown – scientists and researchers do not agree. I’ve covered both sides of this issue previously, including:
Lipsitch & Galvani: GOF Research Concerns
Laurie Garrett On Biosecurity Reforms
Unfortunately, despite considerable debate over this issue, we seem no closer to a consensus than we were two and half years ago when fate of the Fouchier H5N1 Ferret studies was still on the table. Worse, the long promised `thorough public discussion of the risks and benefits involved; has yet to happen in any substantive way.
We seem to have reached a sort of equilibrium, an uneasy state of status quo on this issue, where nothing really changes.
Which pretty much assures that a month, perhaps two from now, we’ll likely see another controversial GOF study released, followed by another round of criticism and concern. Ad infinitum.
Perhaps not the worst possible state of affairs, but it does tend to make a mockery of the phrase `scientific progress’.
