Two Plus Two

"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.

Environs de Bologna, Italy, oil on canvas, Julien-Gustave Gagliardini (1846-1927)

On wondering about the last thirty essays.

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There are three ways to do science. The first is the rational approach that respects facts and laws. Let’s call it 2+2=4. Then there are those crazy moments when you have an idea, you see into the future yet know not how you got there. Some come in the shower, others mowing the lawn. The only common denominator is you’re alone, calm, away from text messages, emails and smartphones. Let’s call it 2+2=22.

The third is Orwellian typified by 2+2=5. The example often given is the Soviet agronomist Trofim Lysenko who rejected Mendelian genetics.

There is a variant of 2+2=5 where scientists push their theories beyond the best before date. For example, bosses who cannot back down once their pet hypothesis have been debunked or superseded by a better one.

Most of what is done in research is incremental made by climbing on the shoulders of giants as the expression goes. Basically 2+2=4. When the startling springs forth, 2+2=22, it is frequently not understood. ‘Howard, of course RNA can’t be copied back to DNA’. Howard Temin’s postulate proved right and he was awarded the Nobel Prize in Medicine in 1975 for this discovery along with David Baltimore.

Ditto Stanley Prusiner and his infectious prion protein theory which was crowned by the 1997 Nobel Prize in Medicine. The outrageous can become mainstream. It’s been said before by Arthur Koestler and his paradigm shifts, but novelty is frequently not understood. It takes time. This is captured by Rolf Zinkernagel’s (1996 Nobel for Medicine) neat formula for getting a scientific paper published:

Old data, old method, no way.

Old data, new method, OK.

New data, old method, OK.

New data, new method, no way.

Conclusion: scientists are conservative while incremental change is the norm. They are not always good with novelty.

With the intense competition today, nobody admits an error, far less makes an apology, even though making errors is part and parcel of science. There is too much at stake in terms of grant money and reputation. Occasionally the narrative changes under criticism but only a little. This is compounded by many using social media to enhance their reach, their influence. Sadly, it comes with language that would not make it to print in a scientific paper. Not even in an editorial or opinion where language is changing fast (Sense not Sagas, Gaslighting).

Viewed from outside, scientists and medics are highly appreciated, and it is fair to say rightly so. Society supports them to help solve a vast raft of immediate and long-term health problems as well as underpinning national economies. With their PhDs, MDs, professorships and wot nots they are considered rational, oops a little more rational than the rest. And even though the editor of Science, Holden Thorp, mentions human foibles (Would Healing) how come foibles trump training?

Yet Thorpe must be right although foibles is an euphemism. Why has it been so hard to discuss so-called Gain of Function (GOF) avian flu research without passion? And since nobody has put forth a good rationale in over 12 years, why is this example of 2+2=5 going unchecked?

Answer? The guild mentality is dominant even when lives and national security are at stake (New USG DURC policy, Lab acquired infections). Big Science brooks no criticism. This chill comes from the top and makes it unsafe for a conscientious objector, cum whistleblower, cum someone who thinks differently to speak out (Chilled virology, Sound of silence). And all this under the illusion of control (Pandemic illusions), not to mention the supporting roles of self-appointed arbiters who get virology wrong (Specialist opinion, What we should worry about, Cancel virology), science journal editors (Gaslighting) and main stream media journalists (Chilly New York times).

The reality is that bird flu viruses have been dropping from the skies since they adapted to the avian gut (Skyfall) eons ago and virologists get infected by the beasts they study – accidents which are sometimes brushed under the carpet to various degrees by administrators in universities and institutions (Lab acquired infections).

We’ve been over the fact that science is very tough - you’re always up against the unknown, up against yourself, even at the end of your career when you have so much experience. Scientists are limited by their own creativity which generally, but not always, fades with age. If viral outbreaks and epidemics are hard to handle, pandemics are the hardest. The animal reservoir is replete with candidates. Prediction is intrinsically hard for a whole host of reasons.

During and post-COVID we’ve heard from umpteen ‘pandemic experts’, even though there have been relatively few big pandemics in the period following Pasteur and his germ theory. A pandemic expert just means that they know about past pandemics. It doesn’t mean they are expert in handling an unfolding pandemic by an unknown virus. Indeed, how could that be? This is not to disparage those with immense knowledge, rather to urge for a little humility, transparency and admit that we shouldn’t maintain illusions of control (Pandemic illusions). That may not go down well with a health secretary or minister who will always, repeat always, be looking for ‘can do’ promising subordinates; but it might avoid some errors made in the past. After all, first, do no harm (Do no harm 1, 2).

An upcoming essay will discuss the first report from the UK Governments independent enquiry into the COVID-19 pandemic. Two short excerpts suffice here:

In 2019, it was widely believed, in the UK and abroad, that the UK was not only properly prepared but was one of the best-prepared countries in the world to respond to a pandemic. This Report concludes that, in reality, the UK was ill prepared for dealing with a catastrophic emergency, let alone the coronavirus (Covid-19) pandemic that actually struck.

Across the UK, systems had grown to be overly bureaucratic. Instead of focusing on skills, technology and infrastructure, they were focused on creating groups, sub-groups and documents.

There is much to be learnt from handling the COVID pandemic. Checks and controls can be built into Big Science but in the case of GOF virology it was decided upon high, nonetheless (Chilled virology). Nobody dared rock the boat (Pandemic illusions) even though the work was the equivalent of biological warfare performed in plain sight by highly trained civilian scientists, courtesy of the taxpayer. The new USG regulations (New USG DURC policy) leave a great deal to be desired in that there is still no independent oversight of this work.

There are enough problems on the planet fighting viruses not to mention frizzling the globe. We’ve only eradicated four viruses, smallpox and rinderpest and poliovirus 2 and 3. But not yet poliovirus 1.

And in tackling problems we don’t need distractions for the whole DURC (ex-GOF) saga has been a big one from fighting infectious diseases. Let’s look at a very different, but topical distraction. Have you seen photos of the surface of Mars? Depressing. Rocks & dust. Barren in the extreme although the recent touch of raw sulfur was curious. It’s also irradiated and cold. Unlike the sheen of blue-veined marble seen in Earthrise. Why pretend to settle there?

Billionaire Jared Issaacman who went into space this September on the Polaris Dawn mission said, "Back at home we all have a lot of work to do, but from here Earth sure looks like a perfect world". Thanks for that. Please repeat it endlessly.

The NIH has been spending taxpayers’ money pushing GOF flu research against reason. Critics have been sidelined.

We must keep virology in the bounds of 2+2=4 and absorb the 2+2=22 flashes when they occur. Only a few virologists need to dial down the language. The majority continue to do a great job. Virology is too important a subject to become so polarized. We’re all in it together.

And if the press asks questions, be honest and remind them it takes time for science to accomplish its wonders. Perhaps stop social media as it’s your scientific papers, and what colleagues think of them, that count. That’s not a big ask.

2+2≠5. Never did.

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Aside 1

French Nobel François Jacob wrote about day science and night science. 2+2=4 and 2+2=22 are their equivalents. He knew there was a little voice in your mind trying to speak with you. The problem was always the ambient noise drowning it out. Another signal to noise problem.

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Aside 2

The end of the year is approaching and we’re on the third On wondering. It’s a play on the New England Christmas carol ‘I wonder as I wander’, itself a wonderful description of doing science.

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Aside 3

It is assumed that the reader knows something of the GOF controversy in virology. To ensure the essays remain short, they are best read as a series. Are the essays too dense or difficult to absorb? Comments please. Suggestions for an article around which a future essay could be crafted would be welcome.

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Aside 4

The essay Lab Acquired Infections was perhaps an oddball. It showed up on the radar of consciousness in the last millennium after helping a group of Parisian nurses who had acquired HIV from needlesticks during their work with AIDS patients. As it was a new disease, authorities hadn’t yet added HIV to the list of professional hazards. And if something is not on the list…

The group was denied discussing their plight on three Parisian hospital campuses, despite one nurse having got HBV, HCV and HIV from a single needlestick.

In the end the group met in the historic amphitheater at the Pasteur Institute. They spoke softly although angst was palpable. These were the dark years, before the arrival of triple therapy.

Having worked on HIV, On reading invited a journalist from the biggest French TV network. At the end of the meeting, she asked if one of the nurses would speak on camera. Marie volunteered. It went out on prime-time evening news. The following day Luc Montagnier obtained a meeting with the Health Minister, Simone Weil who was deported to Auschwitz at the age of 16. This has always marked her out among politicians. After a one-on-one meeting with Marie, not her real name, HIV infection was quickly recognized as a professional illness for health care workers.

Finally on the list.

A tiny detail. For a number of years, Simone Weil had her chauffeur deliver a bouquet of flowers to Marie on her birthday. Some simply can.

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Simon Wain-Hobson is an emeritus professor at the Institute Pasteur, Paris, from which he retired in 2021. He and his colleagues were the first to sequence the genome of HIV, and Wain-Hobson has published more than 230 papers on virology and cancer.