Getting it Right
Getting it Right
"On reading," by Simon Wain-Hobson, is a weekly discussion of scientific papers and news articles around gain of function research in virology.
This essay first appeared on the Biosafety Now website on January 31, 2024. Future “On Reading” essays by Dr. Wain-Hobson will be released here every Wednesday. We will republish his earlier essays on our Substack every Friday, so the full archive will become available here.
The dominant influenza A viruses circulating among birds and chickens today belong to the 2.3.4.4b H5N1 group (clade being the contemporary scientific word) that emerged in Europe in late 2020. There are strains within the group that come and go, just like seasonal flu A viruses among humans.
Strains from the 2.3.4.4b group have infected seals and mink causing massive mortality. The present study concerned two strains derived from infected mink in Spain that differed by a few mutations. When injected into mice they proved to be lethal at high doses. To find out if these viruses could be transmitted by respiratory droplets they used the ferret transmission model, a classic in flu virus experimentation. The ferret transmission model is considered to recapitulate reasonably aspects of human-to-human transmission of influenza A viruses.
Both viruses failed to transmit. The massive loss of life in the mink farms probably reflected the very crowded conditions with spread occurring by direct contact with nasal secretions.
A Canadian group came up with similar findings earlier in 2023 using a virus from a red-tailed hawk.
What is interesting is that this work comes from Yoshi Kawaoka’s lab at the University of Wisconsin. Back in 2011 his group performed gain of function (GOF) research on an avian H5N1 influenza A virus and showed that the resulting strain could be transmitted by respiratory droplets.
That work didn’t deliver on the goals that were touted at the time – the prediction of the next pandemic and with it, preventive drugs and vaccines. A very small number of scientists pushed back on these claims which are hollow from the outset.
With avian H5N1 clade 2.3.4.4b influenza A viruses in mind, the overall recent risk assessment from the European CDC, was ‘low for the general public in EU countries.’
This work from the Kawaoka lab, along with that of their Canadian colleagues, shows how to determine what these avian and mammalian influenza viruses are capable of. And as humans are top dog on the planet, whether they are transmissible between humans by respiratory droplets. They provide answers, albeit negative in this case, to legitimate questions about natural viruses and are of use to public health. It stops short of GOF virology, aka genetic crystal ball gazing, which generates vague terms like potential, possible or wannabe pandemic viruses which are of no help at all.
The case for making novel human influenza viruses from their animal counterparts should be closed, if only on scientific grounds.
An interesting aside. We also learn that there have been at lease 957 cases of human infections by H5N1 virus strains, since the first recorded case in 1997. Infection proves fatal in 60-70% of cases. This comes an average of 24 deaths each year. Contrast this with the approximately 59,000 deaths worldwide per year from rabies virus.
It is never good to compare apples and oranges. It is indeed hard for the virologist to see rabies virus adapting to being transmitted among humans by droplets while this is a distinct possibility for a bird flu virus. We should be worried about avian H5N1 influenza viruses evolving but should not exaggerate. There has been too much drum beating which drowns out thought.
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