While all has gone a little quiet on the Fonterra botulism scare, here is something likely to get everyone in a lather. Flu experts Ron Fouchier and Yoshihiro Kawaoka*, along with 20 other scientists from all over the world, have announced studies they say are needed to better understand the pandemic threat posed by influenza a subtype H7N9 viruses. Since H7N9 first appeared in China in April this year, there have been 134 laboratory confirmed cases with 43 deaths.
While there is no evidence that H7N9 is capable of sustained human-human transmission, in an unprecedented move the scientists have detailed what they believe are important experiments that must be performed to determine what H7N9 may be capable of. In letters published in the journals Science and Nature, the scientists describe the kind of ‘Gain-of-Function’ mutant viruses they wish to develop:
Immunogenicity. To develop more effective vaccines and determine whether genetic changes that confer altered virulence, host range or transmissibility also change antigenicity.
Adaptation. To assist with risk assessment of the pandemic potential of field strains and evaluate the potential of A(H7N9) viruses to become better adapted to mammals, including determining the ability of these viruses to reassort with other circulating influenza strains.
Drug resistance. To assess the potential for drug resistance to emerge in circulating viruses, evaluate the genetic stability of mutations conferring drug resistance, and evaluate the efficacy of combination therapy with antiviral therapeutics. Also, to determine whether A(H7N9) viruses could become resistant to available antiviral drugs, and to identify potential resistance mutations that should be monitored during antiviral treatment.
Transmission. To assess the pandemic potential of circulating strains and perform transmission studies to identify mutations and gene combinations that confer enhanced transmissibility in mammalian models (such as ferrets and guinea pigs).
Pathogenicity. To aid risk assessment and identify mechanisms, including reassortment and changes to the haemagglutinin cleavage site, that would enable circulating A(H7N9) viruses to become more pathogenic.
So, the scientists want to study what mutations will make H7N9 more easily transmitted between humans (most likely using ferrets as a model host), able to resist drug treatment and cause more severe disease. The scientists also outline the strategies in place to mitigate any risks. These include having all experimental plans approved by federal and institutional bodies, carrying out the work under enhanced Biological Safety Level 3 containment (BSL3+) with scientists wearing appropriate personal protective equipment (PPE).
The fact that the scientists are laying out their plans in such a transparent manner is extremely interesting. While many people may find their proposals frightening, I agree that the questions they are asking are important. As Lawrence Fishburne’s character Ellis Cheever says in Contagion: “Someone doesn’t have to weaponize the bird flu.The birds are doing that”. What Fouchier, Kawaoka and colleagues are trying to do is get a heads up as to what nature might be about to throw at us in the future. As the saying goes, forewarned is forearmed.
*If these names sound familiar, it is because Ron Fouchier and Yoshihiro Kawaoka were the authors of the papers under threat of being censored as they described mutations that made another flu subtype H5N1 more transmissible between ferrets, the mammalian model of choice for flu studies.