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The Reemergent 1977 H1N1 Strain and the Gain-of-Function Debate (2015) (asm.org)
76 points by medymed on Aug 9, 2020 | hide | past | favorite | 25 comments


As someone who had the 2009 H1N1 strain I wish the authors would have spoken more about whether that strain as well could have come from a lab accident or was just natural.

Has anyone heard anything to that end or was it just random probability that caused it?


It's pretty much known to have been natural; researchers were able to trace out a likely history in the pig populations it's believed to have come from. (https://www.nature.com/articles/nature08182)


H1N1 in 2009 may fit well with the ‘antigenic shift’ paradigm of influenza, where there is a reassortment of genes from different types of flu (which might both infect the same animal at once) that create a new hybrid to which there is little pre-existing immunity and which can be markedly virulent. This is classically in contrast with year to year ‘antigenic drift’ of the flu featuring small accumulated mutations that have tended to be less virulent. Both of these fit well with the random probability idea to some extent, but are very different mechanisms. I don’t know if people have tried to induce antigenic shift in a lab; probably not the safest idea.


This is a spectacularly misleading paper in a non-biological journal that assumes, without any explanation, that somehow scientists thawed out a 1950 H1N1 strain and somehow, through some gain of function process, made the 1977 version.

The obvious question is, How?

In 1977 (or 1976, to produce something that would have infected people in 1977), recombinant DNA technology was new; cloning had just begun. There were very few restriction enzymes, oligonucleotide synthesis was done by hand (literally) and PCR had not been invented yet. Today, GOF studies are easy because we can synthesize virtually any piece of DNA. But in 1977, graduate students got rich because they could synthesize a dozen-ish residues of DNA and sell them (for stock) to Genentech.

What people were not doing was engineering new forms of flu virus.


I don’t think you parsed the paper quite accurately. It was just the same virus as the 50s. There was no gain of function. The mention of gain of function regards debated policy issues in 2015 when the paper was published.


The paper says that the 1977 H1N1 is not identical to the 1950's strains, but very similar, and that a tree build from sequences suggests the 1977 strain is most closely related to the 1950's strains. So there are differences, and the question is, are they natural or synthetic. I do not think the technology was available to make synthetic changes.


No fancy technology is required. Long before that, we created the dog and the apple. The USSR even recreated the wolf-to-dog transition with foxes. Doing something similar with viruses is much easier because the generations are shorter and because exposure to UV is easy.


Yes, we know how to breed animals and plants. But do we know how to breed flu viruses? Animals and plants are outbred, and provide great genetic diversity for selecting desired traits. But these viruses were virtually identical (no diversity), and it is completely unclear how one would "select" for a virus with the desired properties.


We created the live polio vaccine by breeding. That was long before fancy genetic technology.

Flu viruses are particularly easy to breed. Viruses have short generation times and easy vulnerability to genetic damage. Flu viruses even have a genome that isn't in one chunk, sort of like having chromosomes, making them extra easy to breed.

Selection is a simple matter of having it reproduce quickly in the desired cells.


All this is true, but does not explain how to breed a flu virus with the appropriate disease causing attributes while keeping it virtually (>97%) identical.


An interesting relevant precedent for this argument: https://news.ycombinator.com/item?id=23875758


While there isn’t too much clamorous mainstream debate about the current strain (SARS-CoV-2), the first SARS escaped the lab several times:

“SARS has not re-emerged naturally, but there have been six escapes from virology labs: one each in Singapore and Taiwan, and four separate escapes at the same laboratory in Beijing.”

https://www.google.com/amp/s/nationalpost.com/news/a-brief-t...


Exactly so clearly if you even are willing to consider the possibility that SARS-Cov-2 escaped, you are crazy and a right wing nut ok. See how that works.


Good grief. The contention here is that in 1977 the Russians were culturing samples of an existing strain of H1N1 that was known to researchers from an outbreak 26 years previous, but which had dropped out of circulation. And they oopsed, and it got out. That seems not totally improbable, and I'll believe the sequencing results.

I don't know how you get from there to (sigh) "Covid is human-engineered", at all. Can you explain how this is relevant at all, except in the way both hypotheses invoke evil foreign laboratories in totalitarian states?


I’m curious if you have done any research at all into Covid’s origin? For me it would be very surprising to find someone who has now expressing your implied distain for those who are considering the possibility it originated in the Wuhan lab. This isn’t a political topic or at least shouldn’t be.


No, sorry. You can't float a conspiracy theory, cite an unrelated point as "evidence", and then demand that I be a professional virologist before being allowed to tell you the argument is inapplicable.

This doesn't make sense because nothing the Russians did in 1977 (before the invention of PCR!) to culture an existing wild virus tells us anything about what the Chinese were doing in this virology lab.


I think there is enough evidence to suggest the possibility of a human role, but given the fact that a much more virulent virus could easily have been made I think if there was a human role it was an accident.

That and the fact that this harmed China both economically and in terms of reputation. Biological warfare is like using a grenade as a handgun. Yes it will harm the enemy, but...


The fact that it harmed China is not evidence that it wasn't a gain-of-function engineering result. It's evidence that if it was then its leaking was accidental.


Relevant July 24th Science Mag interview of Shi Zhengli:

https://www.sciencemag.org/news/2020/07/trump-owes-us-apolog...


"Shi’s answers were coordinated with public information staffers at the Chinese Academy of Sciences, of which WIV is part, and it took her 2 months to prepare them. Evolutionary biologist Kristian Andersen of Scripps Research says he suspects Shi’s answers were “carefully vetted” by the Chinese government."


Regardless of the optics, the key outstanding questions I had were asked and answered in the full PDF document [1]. Opinion and geopolitics are not substitutes for evidence and rational thought.

[1] https://www.sciencemag.org/sites/default/files/Shi%20Zhengli...


Every expert I've read about thinks the "evidence" is too flimsy to even consider Covid19 being man-made. That post isn't interesting at all. It's just clickbait fodder that appeals to smart people who like to think they've figured shit out as opposed to the experts, even if it's a field that's totally outside their wheelhouse.


New account and I’m guessing you just haven’t read too many experts actually.

https://youtu.be/pRCzZp1J0v0

1:54:50


Yes. Plenty of experts. Actual virologists, epidemiologists and other scientists who've spent their lives researching infectious diseases like Covid. What actual experts have you actually read anything from?


Reminds me of Rob Reid's 2017 novel After On, which included a subplot featuring a man-made virus.




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