GOF – A raging controversy

Late last year, the US Government halted work on “Gain Of Function” (GOF) virology research (1), a subset of an area of scientific investigation known as “dual use research of concern”. This field includes any life science research that, based on current understanding, could be reasonably anticipated to provide knowledge, products, or technologies that could be directly misused to pose a significant threat with broad consequences to public health and safety, agricultural crops and other plants, animals, the environment, or national security.

The USG’s concerns and action originally stem from work on a genetically engineered strains of H5N1 (2,3,4) that allowed the virus to transmit between ferrets by air; the media and scientific fire-storm that ensued rapidly led to a pause on further H5N1 research. Shortly after research picked up again (4) , two scientists in particular weighed in with their views; Simon Wayne-Hobson (8) a virologist at the Pasteur Institute and Marc Lipsitch (5, 7) an epidemiologist at Harvard. Both have published papers, editorials and been a rich source of verbiage for all manner of media (The Times, The New York Times and The Guardian to name just a few); both feel (for different reasons) that the US Government’s decision is fully justified and of course, it seems obvious. Why would we want microbiologists beavering away in laboratories, spending taxpayer’s money to produce novel viruses that are potentially lethal?

A number of quite eminent physicists voiced concerns over the dangers potentially posed by the Large Hadron Collider before it was finally “switched on”. They cited “micro black holes” and “strangelets” in particular. However, research and construction cotinued, there was no pause, no white coated breast beating or any such. Good job too; the Higgs boson, tetraquarks and a whole bunch of “Oh … now it makes sense!”

So, what we now have are two camps of life scientists; some (championed by Wayne-Hobson) believe all of the research that they would deem to be speculative (at best) and potentially dangerous (with little mitigating benefit) should be halted and others (see 9 for a sample) that argue that since the benefits of biomedical research are often unanticipated, crude risk-benefit analyses do not work. It’s somewhat intuitive, perhaps, that Wayne-Hobson’s “camp” (I should add, that as is typical amongst scientists – there are no “leaders”, we are a pretty anarchic bunch) is right; he is, a somewhat eminent HIV researcher and must know what he’s talking about, right? He does … but so does side two (the “blue team”) – a casual glance down their list of gladiators (9) throws out some major league hitters (it’s a baseball term … I have no idea what the UK equivalent is) who clearly know what they’re talking about too.

What prompted the US government’s intervention into life-science research? Well, it comes after as many as 75 scientists at the US Centers for Disease Control and Prevention (CDC) were exposed to anthrax in June 2014 (10) and, a few weeks later, US Food and Drug Administration (FDA) employees found 16 forgotten vials of smallpox in storage (11). The US Government quickly released new regulations regarding dual-use research, but interestingly, gain-of-function research were originally omitted from the report. After a short delay, the US then began specifically reviewing GOF experiments, and is now pausing funding for gain-of-function research projects “that may be reasonably anticipated to confer attributes to influenza, MERS, or SARS viruses such that the virus would have enhanced pathogenicity and/or transmissibility in mammals via the respiratory route.”

So, should research into GOF go ahead as the Blue Team want? Or should this US pause for careful risk-assessment project-by-project continue? Critically, to my mind, is the whole business of timely vaccine production. As pointed out by Schultz-Cherry et al (12), GOF work is a valuable tool in the preparation of vaccines for emerging viral threats and an invaluable predictive warning system.

The Manhattan Project began to coalesce in Dec 1941 with the aim of producing a weapon from the research scattered all over Europe and the US. At around £17 billion the US got The Fat Man, The Little Boy, ended a war and ushered in The Atomic Age. When the Project’s Director handed over control of the military facilities and research to the Atomic Energy Commission in 1947 he commented:

Five years ago, the idea of Atomic Power was only a dream. You have made that dream a reality. You have seized upon the most nebulous of ideas and translated them into actualities. You have built cities where none were known before. You have constructed industrial plants of a magnitude and to a precision heretofore deemed impossible. You built the weapon which ended the War and thereby saved countless American lives. With regard to peacetime applications, you have raised the curtain on vistas of a new world .

Go Blue Team!

  1. http://www.phe.gov/s3/dualuse/Documents/gain-of-function.pdf

  1. Imai M, Watanabe T, Hatta M, Das SC, Ozawa M, et al. (2012) Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets. Nature 486: 420–428.

  1. Herfst S, Schrauwen EJ, Linster M, Chutinimitkul S, de Wit E, et al. (2012) Airborne transmission of influenza A/H5N1 virus between ferrets. Science 336: 1534–1541.

  2. Troy C. Sutton, Courtney Finch, Hongxia Shao, Matthew Angel, Hongjun Chen, Ilaria Capua, Giovanni Cattoli, Isabella Monne, and Daniel R. Perez (2014) Airborne Transmission of Highly Pathogenic H7N1 Influenza Virus in Ferrets. Journal of Virology 88 (12): 6623–6635

  1. http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1001646

  2. http://www.virology.ws/2013/02/18/harvard-university-great-virology-bad-science-writing

  3. http://harvardmagazine.com/2013/03/h5n1-the-deadliest-virus

  1. http://www.nature.com/news/h5n1-viral-engineering-dangers-will-not-go-away-1.12677

  1. http://www.scientistsforscience.org/

  1. http://www.the-scientist.com/?articles.view/articleNo/40316/title/Dozens-of-Researchers-Exposed-to-Anthrax/

  2. http://www.the-scientist.com/?articles.view/articleNo/40449/title/Smallpox-Vials-Found-in-FDA-Storage/

    1. Schultz-Cherry S, Webby RJ, Webster RG Kelso A, Barr IG, McCauley JW, Daniels RS, Wang D, Shu Y, Nobusawa E, Itamura S, Tashiro M, Harada Y, Watanabe S, Odagiri T, Ye Z, Grohmann G, Harvey R, Engelhardt O, Smith D, Hamilton K, Claes F, Dauphin G. 2014. Influenza gain-of-function experiments: their role in vaccine virus recommendation and pandemic preparedness. mBio 5(6):e02430-14. doi:10.1128/mBio.02430-14




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