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Friday, May 01, 2020

NIH cancels Wuhan Institute grant; possible false hope for remdesivir

More examples of how politics and science don't mix

S cience magazine reported yesterday that the US National Institutes of Health's controversial grant on bat coronaviruses was canceled due to concerns that the Chinese BSL-4 facility, WIV (the Wuhan Institute of Virology), had not “taken all appropriate precautions to prevent the release of pathogens.”

Rumors had been circulating in the scientific community for weeks that, although the scientists at the WIV were doing good work, the institute had serious management problems and may have been careless in its handling of these deadly viruses, which have now caused a worldwide pandemic.

Researchers interviewed by Science sounded distraught, calling it a bad precedent, and accused NIH of bowing to political pressure from President Trump. But NIH's own Safety Guidelines Document specifically states that recipients are required to take biosafety concerns seriously. The document says:

Special hazards that are identified after an award is made may lead to suspension of work under the grant or contract pending corrective action by the awardee. 45 CFR 74, Subpart M, addresses grant suspension and 48 CFR 12.5 addresses contract "stop work" orders.

All scientists have copies of 10 CFR on their computer. Maybe we better grab a copy of 45 as well.

The researchers are naturally concerned that their own grants could be canceled. But NIH cancels grants all the time at the request of university administrators with little regard for their effects on the scientific research, and without giving the researcher a chance to respond—often without explanation. Academia is utterly dependent on a single source of funding, and it's the bureaucrats who hold the cards. It's harmful, and it's a formula for research that panders to fashionable dogma.

I don't know how things work in China, but in the USA the notifications of award (and, presumably, cancellation) are sent to the administrators, not to the people who wrote the grant. The adminis­trators rarely tell the scientist their grant got funded. If the scientist doesn't keep checking, he or she may never know. That's because grants are really just a concealed way of subsidizing the universities—almost all the money goes to the bureaucracy and to offset the investigators' salaries. Often as little as 12% goes to support the actual research.

The Wuhan Institute is China's chance to prove it can handle viruses as safely as other countries, so it will survive regardless of the reputational damage it may have inflicted on itself. But I suspect that being an administrator in China comes with certain extra risks that our bureaucrats don't have.

False hope on remdesivir

Last week Anthony Fauci of NIAID waxed enthusiastic about Gilead's antiviral remdesivir. Based on unpublished reports that treated patients could be discharged in 11 instead of 15 days, he says it shows that “what it has proven is that a drug can block the virus.”

But I don't see much cause for optimism. Gilead's study in NEJM (Grein et al., summarized here), showed no statistically significant change. Seven died during the trial, and it was a dismal result. The Beijing study in Lancet showed the same: no effect whatsoever on the course of the disease.

Cell culture experiments have shown encouraging results with remdesivir[1], as with many other drugs (including hydroxychloroquine). A macaque study on MERS-Cov[2] showed encouraging results. This unfortunately doesn't mean it will work in patients.

One problem with many of these studies, even the ones that have done randomized controls, is that the placebo groups are not really placebos—they're getting other antivirals, interferon, and antibiotics. The goal is to prevent deaths among the patient population, but death is what the drug is intended to prevent. If any of the other drugs touch the same pathways as remdesivir, you'd get a ceiling effect.

But another is that the results are being interpreted through a haze of fear and anxiety.

Crappy science

What's going on is not a mystery: every aspect of this has been politicized, starting with the hysteria created by the press, which led to an economically catastrophic lockdown of the population. Every conspiracy theorist on the planet seems to have their own theory, and now they have time to write about it.

An example is some guy writing today in the UK Guardian who claimed that BPA and perfluoroalkyl substances, which are found in cookware and some food packaging, are to blame. The Guardian's big idea is that these chemicals (which, honestly, they never much liked anyway) are harming our immune system, which increases our risk. It's a classic conspiracy theory: take an isolated study that confirms what you want to believe, and inflate its significance.

It supports my theory that science increases knowledge and politics erases knowledge. Put them together and what do we get? Confusion and entropy. Stephen Hawking said information can never be destroyed. But knowledge can be. Sounds like a good topic for some aspiring expert in information theory.

1. Gordon C, Tchesnokov E, Feng J, Porter D, Götte M (2020). The antiviral compound remdesivir potently inhibits RNA-dependent RNA polymerase from Middle East respiratory syndrome coronavirus https://www.jbc.org/cgi/doi/10.1074/jbc.AC120.013056

2. de Wit E, Feldmann F, Cronin J, Jordan R, Okumura A, Thomas T, Scott D, Cihlar T, Feldmann H (2020). Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection. Proc Natl Acad Sci U S A. 2020 Mar 24;117(12):6771-6776. doi: 10.1073/pnas.1922083117. Epub 2020 Feb 13. https://www.ncbi.nlm.nih.gov/pubmed/32054787 PMID: 32054787 PMCID: PMC7104368 DOI: 10.1073/pnas.1922083117

may 01 2020, 7:11 am

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