Why Words Matter
"On reading," by Simon Wain-Hobson, is a weekly discussion of scientific papers and news articles around gain of function research in virology.
Since January 2024, Dr. Wain-Hobson has written weekly essays for Biosafety Now discussing risky research in virology. You can read his entire series here.
The origins of the COVID-19 virus have understandably provoked much comment. Quickly we learn that Of the three possibilities - natural, accidental, or deliberate - the most scientific evidence yet identified supports natural emergence. This is surprising as a few lines below we’re told that The SAGO’s preliminary report warned that China was withholding key data. This is WHO’s Scientific Advisory Group for Origins of Novel Pathogens. Logically, if data are not forthcoming, how can anyone draw a conclusion? Use of the qualifier yet identified does not make amends. A military strategist might remark that such action leaves your flank exposed. Unfortunately, it’s not the only example.
We are told that using the RaTG13 sequence as a reference for the COVID-19 coronavirus is a red herring, which of course it is. However, the possibility that the laboratory held a different progenitor strain to SARS-CoV-2 that led to a laboratory leak cannot be unequivocally ruled out. Exactly. The authors double down as the very next paragraph starts China’s obfuscation may mean that we will never have certainty about the origins of the greatest pandemic in more than a century.
So it’s actually cannot be ruled out.
Everybody wants to know if the Wuhan Institute of Virology was conducting molecular genetics with other bat viruses that they had not yet published, something that is possible. Without publications, most of what goes on in any lab is under the radar. Only in research grants would some of the ideas be found and they are confidential.
We learn that Samples from early cases in humans also contained two different SARS-CoV-2 lineages. Although only one lineage spread globally, the existence of multiple lineages suggests that a SARS-CoV-2 epidemic in animals may have led to multiple spillover events. This comes from others. The A and B lineages in question present during the first few months differ by just two mutations which is peanuts. Indeed, a recent manuscript showed that any two pangolin coronavirus genomes in an isolate differed by between 2 to 8 mutations (The pangolin paper).
It is ludicrous to interpret two mutations as proof of distinct spillovers. This hypothesis of two early spillovers is demolished by a very recent paper which concluded All of them may have evolved from one common ancestor, probably lineage A0 or a unidentified close relative, and jumped into human via a single zoonotic event.
The authors make a rare point, After all the world has suffered in loss of life, economic hardship, and exacerbated health disparities, there is intrinsic value in knowing the cause. On reading feels this has gone largely unsaid. Humans are fascinated about the origins of things. Period. Importantly, it can end up soliciting the How question and with it, mechanism which is so important in science. In prehistory, where knowledge was scarce, sun, rain and fertility gods made intrinsic sense. Closer to the present, it was the How question that got Newton and Darwin thinking about mechanism while others were content to describe.
Asking about the origins of the COVID-19 virus is merely being human. The opposite would show a distinct lack of curiosity. And all this apart from the mantra about learning from the past, which, by the way, is challenged by the observation that errors are frequently repeated.
The article then shifts to pandemic preparedness which is a totally different subject. Three points are mentioned. The first starts with a remarkable sentence. Some 60% of outbreaks of diseases previously unseen in humans arise from natural zoonoses. The other 40% - a huge number - arise from what? Accidents, malice?
Re the second, we’re told that, it is important to fortify laboratory safety to reduce the risks of unintentional release of a dangerous pathogen. This article appears in the NEJM, the top ranking medical journal. Everybody knows this.
The third contains multiple threads that need disentangling. GOF research designed to elucidate the transmissibility or pathogenicity traits of pathogens should be appropriately overseen to reduce risks while allowing important research and vaccine development to continue. GOF virus research à la Fouchier and Kawaoka didn’t deliver on the promises these authors made which was not mere transmission and certainly not pathogenesis. Obviously, they should be correctly overseen, although NIH oversight has not been the best. The authors repeat the debunked belief that GOF research is useful for vaccine development. Of course, if they use GOF in the historical sense of the term, then this is embracing confusion and has been dealt with (Deconstructing the portrait).
Such research may result in the creation of microbes with enhanced pandemic potential, which could be released unintentionally or intentionally. Indeed, this is the dual use part of dual use research of concern that nobody is addressing in public. Maybe it is being discussed within the confines of government intelligence agencies. That said, funders, regulators and journals are behooved to address it (Do no harm, 1).
On January 27, 2023, the U.S. National Science Advisory Board for Biosecurity issued a more rigorous framework for oversight of research, which prominent virologists criticized as overbroad and inhibitory to U.S. vaccine development. Such pushback has been discussed (Going places). The sacred cow of vaccine development is rolled out to counter criticism of risky GOF research and more oversight. It doesn’t bear scrutiny.
It is not normal to encounter ambiguities and remarks in the NEJM that are too easily fact checked. The words and thoughts behind them matter.
Unfortunately, this is not an isolated example. Too many articles commenting on GOF research fail to use tight language. Sentences are strung together without much effort while inconsistencies are abundant. The biggest sleight of hand has been the rebranding of DURC GOF (Deconstructing the portrait). The pushback to the NSABB’s recent recommendations is another example (Going places). Virology, without question the Queen of the biological sciences, deserves better.
Aside 1
Aside 2
GOF was not necessarily part of the lab leak hypothesis. It was assumed to be the case given that GOF research was being performed on bat coronaviruses prior to COVID-19 pandemic. Subsequently, the DEFUSE grant proposal unearthed by DRASTIC suggests this was on their minds, including the insertion of proteolytic cleavage sites like furin into the all-important Spike protein. And while the furin cleavage site is important for the COVID-19 virus, a good equivalent was lacking in the 1918 Spanish flu virus (1918 and all that).
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