I read the news today, oh boy, virologists are making the world more dangerous. One group has just made a chimeric COVID coronavirus that is more lethal in transgenic mice than the natural virus. The data are posted on a preprint server for all to see. For monkeypox, analogous studies are being discussed.
The endpoints sought are viruses that are more pathogenic and/or lethal in animals, which means transgenic or normal lab mice. These are gain of function (GOF) virology experiments and fall into the controversy that engulfed virology a decade ago. In a nutshell, these 2011 GOF experiments engineered avian influenza viruses that presently cause dead end infections among humans into ones that are readily transmissible by aerosols in a ferret model - and presumably among humans.
The purported benefits of GOF virology on avian influenza A viruses, according to the senior authors of the seminal papers (1,2), were the prediction of the next human pandemic strain and the pre-emptive development of tailor-made antivirals and vaccines. These are pipedreams and they have been exposed (3,4).
The crux of the matter is that it is not possible to predict a pandemic viral strain – and, with that, the purported benefits bite the dust. We can never establish what these engineered viruses are capable of because i) animal models are of limited predictive value for human infections while ii) infecting humans is out of the question.
Yet despite this, GOF virology is proceeding apace.
And on the risk side? Lab accidents involving viruses and bacteria occur and, since many countries have no obligatory reporting system, are greatly underreported. As long asAlthough they are occupational hazards with the microbiologists on the receiving end, they are perceived as professional failures with a tendency to be hushed up. This And this is unfortunate, as learning by mistakes can be very effective. In short, we’re failing researchers at the heart of microbiology.
Perhaps the best-known accident involving a dangerous virus resulted in the death of Janet Parker who caught smallpox in Birmingham Medical School in 1978, one year after the last natural death in Somalia. More recently, a researcher was bitten by a ferret infected with the resurrected 1918 Spanish flu virus. In a very different context, litres of attenuated poliovirus escaped into a stream in Belgium. There are calculations of the risk of a lab leak of a dangerous virus, and for some studies, the numbers are well over zero.
It is a no-brainer to calculate a risk benefit analysis where the benefit is zero and the risk is small but non-zero. However, there is a big but.
We’re not talking about getting run down while crossing the road. We are contemplating the escape of a virus that could infect individuals one after the other, leading to an large outbreak, epidemic, or pandemic involving hundreds to millions of deaths, not to mention the humongous economic impact – put bluntly, a small risk with catastrophic consequences.
Yet, as a director of an Australian research institute told me, if GOF virology was performed and went awry in his outfit, ‘just one death and the programme would be shut down and I’d be thrown out’. This is a uniquely candid remark. It is also a good lead into another issue.
The NIH refers to enhanced Potential Pandemic Pathogen research. Most microbes do not produce pandemics. There are spillovers, outbreaks, epidemics, and pandemics, their occurrence dropping drastically as you go from the former to the latter.
Pandemics are the big ones, using Richter scale earthquake language. But if a man-made outbreak killed ‘just’ a dozen people, the backlash and consequences would be phenomenal. Accordingly, we should also monitor studies that enhance the pathogenesis of any microbe that can spill over to humans, and not just those that might have pandemic potential.
The fascination with GOF virology may well spread over time - for example, trying to predict viral spillovers, epidemics, and pandemics among animals and plants. Imagine if someone developed a novel highly pathogenic GOF modified rice virus. As rice is a staple food in SE Asia and an important export commodity, I’d hope their governments would go ballistic. Lest I’m accused of suggesting a noxious idea, this was the cornerstone of the 1956 sci-fi book The Death of Grass which was made into the film No Blade of Grass in 1970.
GOF virology has been kept alive by defying data. Very few virologists have spoken openly: omertà was the default response. Bacteriologists tell me that engineering a naturally susceptible bacteria like anthrax to become resistant to penicillin is a no-no.
When speaking to medics, there is even more concern over GOF research and the question ‘why’ (actually ‘WHY’) comes up frequently. And when I speak to neighbours and informed citizens, ‘WHAT?!’ is a more than common reply - along with the occasional expletive.
Time after time, people have said to me: ‘Why make novel and dangerous human viruses? Scientists should not be doing harm.’
Point. PhDs do not take the equivalent of the Hippocratic Oath. Yet the 2005 InterAcademy Panel statement on biosecurity IAP signed by the Royal Society, US National Academy of Sciences and 64 other national academies of science, has as its first principle that: ‘Scientists have an obligation to do no harm.’ Unfortunately, these learned societies did not spread the message effectively – not even to their members. I have encountered fewer than 10 members of these two academies who knew about it. Of course, this IAP document was never meant to have teeth.
Science is essential to modern societies, underpinning economic prowess, helping to tackle human suffering and more. The importance of basic science is not questioned. While it is correct that researchers, aka “experts” in lay parlance, obviously understand the nitty gritty better than others, there are times or moments when scientists must embrace openness and discussion with society who, let’s face it, fund us. On top of which, sunlight is a strong oxidant.
New technologies such as nuclear power or the phenomenal power to manipulate and synthesize genomes are but two examomentsmples. Microbial outbreaks, epidemics, and pandemics such as AIDS, mad cow disease, antibiotic resistance, Zika and COVID required pedagogy which was frequently lacking.
As GOF virology spans both categories, we desperately need a far more open discussion before the inevitable accident. A recent opinion piece in the New York Times is most welcome and a conference organized by the Bulletin of Atomic Scientists addressing the risks of handling pathogens which is set for 2023 are going in the right direction.
Simon Wain-Hobson is Emeritus Professor with the Pasteur Institute, Paris
