On reading Virology under the Microscope – a Call for Rational Discourse by Felicia Goodrum and 155 others. Journal of Virology, 92, January 26, 2023.

Grenache vines for rosé, southern Var, France. Oil on paper, Julien Wain-Hobson 2022

 

The straw man is set up in the abstract. A small but vocal group of individuals has seized upon these concerns – conflating legitimate questions about safely conducting virus related research with uncertainties over the origins of SARS-CoV-2. Are these internet trolls or conspiracy theorists? Or members of DRASTIC or US Right To Know (USRTK) who have unearthed some pretty worrying findings? We are never told who although USA Today gets a fleeting mention.

If the first group, a commentary or opinion like this has never impacted webspeak, although the authors may feel good.

The result has fueled public confusion and, in many instances, ill-informed condemnation of virology. Again, who? If the latter, then at least DRASTIC and USRTK have given chapter and verse.

On reading focuses on GOF research and learns that over the origins of SARS-CoV-2 more data is needed while China has been uncooperative – the opinion of the WHO head none less. If there are not enough data, then the jury has to be out. Otherwise, comment is somewhere between hypothesis and speculation, which is fine, although it doesn’t change the fact that the jury is out. It’s always been this way in science.

By the second paragraph there is something a little more tangible. After the 2022 US midterm elections Congress was returning to session and virology, COVID, biosafety and a lot more were expected to come under scrutiny. Our hope is that these hearings will highlight the enormous contributions of virology, including gain-of-function experiments, to human health (Table 1). The table lists human viruses for which there are vaccines and antivirals. The vaccines start with Louis Pasteur and rabies and finish with SARS-CoV-2.

Reference to gain-of-function here can only rely on its historical use in biology that has been addressed (Deconstructing the Portrait). It cannot refer to the risky research that sparked the GOF controversy at the end of 2011, research that cannot generate human vaccines. And this from the former head of Merck Vaccines.

But why? After the unprecedented generation and deployment of a vaccine in less than one year, COVID PCR tests on street corners across the globe, why go back to Pasteur? Most people are impressed. What’s there to be afraid of? A small but vocal group of individuals? Nah.

Historically speaking human microbes have spilled over from animals causing disease, epidemics and occasionally pandemics. Yet it is a fact that the number of virology labs across the world has mushroomed ever since HIV/AIDS. Now add to this easy synthesis of viral genomes and with it the viruses. Accordingly, a lab accident as a source of an epidemic or pandemic is a viable hypothesis today. As ever, data are needed to distinguish between the two.

GOF then gets a section to itself. Although the phrase ‘gain-of-function’ is very problematic and inexact the reference used is that of a freelance writer who did nothing, repeat nothing, to dispel the confusion between the conventional meaning and that surrounding the work of Drs. Fouchier and Kawaoka. Goodrum et al generate a list of examples of useful gain-of-function experiment (their Table 2). Within the table is the Fouchier/Kawaoka experiment apparently for showing that avian H5N1 influenza A viruses have the capacity to transmit between ferrets. This is the one GOF experiment that blew the lid, unlike the other 21. Two points: first, transmission wasn’t the touted benefit of the work back in 2012. Second, formally speaking, this is an extrapolation as proving human to human transmission requires infecting humans which is unethical.

Despite these clear benefits, a narrative has developed suggesting that gain-of function research is synonymous with high-risk or nefarious activity to engineer or enhance pandemic pathogens. This is the consequence of rebranding DURC GOF when the former was the far better term. Proof of this is to be found in the remarkably lucid sentences just downstream. The vast majority of virology experiments could not enhance pandemic potential (referred to in the United States as gain-of function research-of-concern). Exactly! This was the point about separating them from the Fouchier/Kawaoka experiments that generated a potential for catastrophic risk. Those rare experiments that could are currently subject to stringent oversight through the U.S. Government under programs known as dual-use- research-of-concern (DURC). So it’s DURC after a decade of controversy. Thanks. The rebranding and confusion were needless and a disservice.

Incidentally, there was nothing nefarious about the Fouchier and Kawaoka papers on engineering avian H5N1 flu virus genomes. Following peer review the work was funded by the NIH, performed and talked up by Dr. Fouchier at a flu virus conference in Malta. The much overlooked study from Dr. Chen’s lab in China was published with much less fanfare.

Some people will say pretty much what they want. By contrast, researchers should be able to distinguish between science and science fiction.

Without qualification, appropriate precautions should be taken to minimize laboratory accidents or the unjustified engineering of pathogens with enhanced pandemic potential. Why take appropriate precautions to minimize the unjustified engineering of pathogens? If unjustified, then it shouldn’t be done. On reading would have appreciated a list of unjustified engineering of pathogen experiments which would have the merit of providing some guidance. Others too, no doubt.

In the conclusion we learn that post COVID the scientific establishment has been the most effective shield protecting humanity from this calamity through the delivery of rapid tests, vaccines, antibody therapies, and small molecule antivirals. Millions are alive today that would otherwise be dead thanks to society’s investment in creating and maintaining a vibrant scientific enterprise.

300%. Yet it’s the job of firemen to put out big fires. Who else? Over COVID science and industry rose to the big occasion. It’s for others to do the thanking.

The real reason for the article finally appears: In the debate on further restrictions around gain-of-function research and new regulations on virology in general…  Regulations that are redundant with current practice or overly cumbersome will lead to unwarranted constraints on pandemic preparation and response…  Gain-of-function research has been an extremely valuable tool in the development of vaccines and antivirals (Table 2).

Regulations have already been discussed (Going Places) while the language has slipped back to GOF instead of DURC. Incorrigible. The logic is that as GOF has produced so many positives, while the Fouchier and Kawaoka experiments in Table 2 are examples of GOF, this work should proceed.

They want us to go back to unfettered GOF. Nothing has been learnt over the past decade. Avian GOF flu research made promises that did not deliver, could not deliver. It generated potential catastrophic risk without benefits. This doesn’t seem to be an issue for the authors.

It is critical to use reason. We’ve seen too many flights from reason.

 

Aside 1

The title comes from the book The Flight from Science and Reason, edited by Paul Gross, Norman Levitt and Martin Lewis, 1996, The New York Academy of Sciences. We are reminded of the continual difficulty of keeping hypotheses distinct from data, of using words to convey precise meaning, no matter the issue. A clever word play starts Langdon Gilkey’s chapter: Flights from reason take off in our day as frequently as planes from O’Hare.

Aside 2

More than one researcher went into science because they were not so strong on languages and the arts, among which On reading. And as is quickly learnt, along with the bench work comes writing. Worse, everything in science is short story writing – papers, grant proposals, peer reviews and abstracts – which is the hardest genre. Downloading what is on your mind simply isn’t easy unless you’re in the Shakespeare or Mozart category. Words have meaning. Many writers have come up with variants of Easy reading is hard writing, hard reading is easy writing. This particular version came from a former editor of the now defunct International Herald Tribune eons ago. Do be precise.

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