[pfisherman]

> the most alarming aspect of the lab leak hypothesis is that gain-of-function research is STILL being done, and that the same thing could happen AGAIN.

This right here is an example of why we can’t have reasoned discussion around the topic.

You can explain one of the many reasons why gain of function research is necessary: anticipating next year’s version of the flu, designing drugs and vaccines such that resistance mutations reduce evolutionary fitness.

You can explain how it is done: lots of computational simulations, and some benchtop with results feeding back into computational methods.

You can explain some of the safeguards in place: BSL 3/4 facilities, regulatory / institutional oversight, security services, etc.

And then someone will stand up on a chair and yell “SUPER VIRUS!”

Anyway from my perspective, the “lab leak” theory tends to be people pushing an unsubstantiated theory to either (1) blame China for an “act of god/nature” or (2) argue for a moratorium on infectious disease / vaccine / therapeutic research.

Please note that no one here is calling you a racist. But I think calling parts of your comment uninformed or misinformed is fair game for discussion.

[stormfather]

> the “lab leak” theory tends to be people pushing an unsubstantiated theory to either

For me it's just common sense. It probably came from the coronavirus lab with a bad safety record it popped up next to. Duh. And I "push" it because I value the truth and want to live in a rational society where the truth isn't gamed for emotional or political reasons. And that's probably the same for most of us.

[shlant]

> For me it's just common sense

> Duh

This is the kind of argument one makes when they don't have an argument

[stormfather]

It's so obvious that an appeal to common sense is all that's necessary. How many markets do you think are in China? 100,000? 1,000,000? And how many of those are within driving distance of the one lab where:

- They study novel coronaviruses - They sampled the same regions where the closest relatives to the virus were found - They applied to put a furin cleavage site in a coronavirus before the pandemic - They were cited in diplomatic cables for poor safety standards - The database containing records of the viral sequences was taken down right before the pandemic - A scientist working at the lab at the time of the origin disappeared - A scientist who patented a coronavirus vaccine a few months into the pandemic "jumped off the roof"?

Does a lab accident not immediately jump out as the obvious leading possibility to you?

[chimprich]

>It's so obvious that an appeal to common sense is all that's necessary. How many markets do you think are in China? 100,000? 1,000,000?

This is why "common sense" is very often wrong and we have to refer to data instead. You're making assumptions that are very wrong.

The wet market was over 50,000 square metres in size and one of the largest in China. The idea that there are hundreds or millions of these things is completely backwards.

The conditions were unsanitary, animals were slaughtered on site, and large numbers of wild animals were sold.

This is exactly the sort of place you'd expect a zoonotic spillover event to occur. It was flagged beforehand as a danger site.

It's not impossible that it could have been a lab leak, but consider that this market had hundreds of thousands of animals being kept, slaughtered and sold, in unsanitary conditions, shitting and pissing on each other, bleeding everywhere and biting humans and each other.

Now compare that to a secure biolab holding a small number of samples whilst following biosecure protocols. Even if they weren't perfect, which environment provides the best chance of a spillover event?

[stormfather]

Well, according to a quick search there are 40k wet markets in China. How big do you think the average wet market is? Even guessing 1000 square meters, which is very conservative, the wuhan wet market only represents about 0.1% of wet market square footage in China. By this back of the envelope math, the chance that a zoonotic spillover at a wet market would occur so close to the lab is less than 0.1%.

And sure, the wuhan market is a great place for a zoonotic spillover to occur, but any wet market would be, so the wuhan market in particular isn't the exact place you would expect. In fact I would expect it to occur at a market much closer to where the most similar viruses were found.

However, since the wuhan market is the enormous unsanitary market near the novel coronavirus lab, it is the exact place I would expect the first super spreader event to occur following a leak at that lab.

[Eisenstein]

'Common sense' says that the thing which has occurred periodically throughout human history (plagues and epidemics) completely naturally and is occurring around the same period after the last one ('Spanish' flu of 1918-20) would have the same causes as those before it, but with accelerated time frames due to ease of travel and population density.

[stormfather]

There have been plenty of lab leaks in history too.

[Eisenstein]

There have been more cases of 'almost epidemic but for action by health officials' with SARS and avian flu etc which makes it 'common sense' that these things occur pretty frequently and would be happening more often naturally if not for luck and structures in place to mitigate them. Those structures also happened to be dissolved by the US leaders in charge at the time, which seems to fit the puzzle.

So, 'things happened before' are heavily tilted towards 'nature did it' in any case.

[randomperson01]

from the WHO in 2006, page 236 on SARS: "the risk of a laboratory source is potentially greater"

  https://apps.who.int/iris/handle/10665/207501

[Eisenstein]

That's great. I am countering the notion that evidence is not required because it is 'common sense'.

[snowwrestler]

It’s absolutely not common sense, we have tens of thousands of years of evidence that viruses can evolve to cause human illness, and zero documented examples of a man-made novel virus doing so.

It would be an extraordinarily rare and noteworthy event in human history. The bar to prove that it happened to cause COVID is very high and the direct evidence (not circumstantial) for it is so far very low.

[wizofaus]

Did GP imply if a virus was leaked it must be man-made? Obviously the fact that the exact virus hadn't been seen before is suggestive of that but it's not inconceivable the lab happened to have samples of a never-before-seen naturally occurring virus that they were planning to do research on. That wasn't the same lab that released the first genome sequencing of the virus though (I gather it was in Shanghai). Not sure how virus research is usually done but I would have thought genome sequencing would be one of the first procedures you'd undertake, and there's no suggestion the Wuhan lab had done such sequencing (implying if they had, it was covered up).

[wizofaus]

Btw this seems to be a pretty thorough and technical overview of the various hypotheses: https://journals.asm.org/doi/10.1128/mbio.00583-23 It concludes zoonotic origin to be the most likely, though certainly doesn't rule out other alternatives.

[randomperson01]

Imperiale, the last author is a known gain of function proponent with a history of downplaying the possibility of a lab leak

https://twitter.com/emilyakopp/status/1620884457032155136?t=...

[snowwrestler]

> Did GP imply if a virus was leaked it must be man-made?

This is what the “lab leak” theory is. It’s why every conversation of lab leak is tied up with comments about gain of function, etc.

The interesting thing about SARS-COV-2 is that it can infect humans and cause illness (unlike the vast majority of known viruses). When people talk about the origin of the pandemic, it is the origin of this property specifically that they mean. The lab leak theory is that this property originated in a lab.

[wizofaus]

The paper I linked to above has as one hypothesis that it was a naturally occurring virus, cultures of which had been stored or worked on at the lab, and "leaked" by way of infection of workers there. Seems just as plausible as some source virus having been manipulated to increase its infectiousness to humans.

[oneshtein]

There is significant delay between lab leak in mid-September-mid-October 2019 and start of epidemic in December in Wuhan.

Can such contagious virus as SARS-CoV-2 cross the distance between lab in Wuhan and wet market in Wuhan in few days? Of course. In few months? No way.

[stormfather]

Not all the early cases could be traced back to the wet market, so there is no reason to suspect it started there if you don't already suspect a zoonotic spillover origin. And exponential curves ramp up slowly at first.

[neffy]

fwiw... there were posts floating around at the beginning of 2020 claiming that the epidemic was well established in Wuhan by December, and that cases were seen back to September, October.

It's unfortunate in so many way - admit a mistake was made, acknowledge the problem, and clean it up is so much more respectful of everybody's time and resources. Between Asian traditions of saving face, and US traditions of lawyers suing anything that moves, that approach never stood a chance of course.

[oneshtein]

Yes, there is correlation between World Military Games in Wuhan in October 2019 and Covid[0].

Also, Russian media informed about spike of pneumonia cases in November 2019[1].

[0]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813667/

Note: This page below crashes my browser (Firefox at Fedora Linux) even when requested from Wayback archive. Beware!

[1]: http://web.archive.org/web/20191119113457/https://www.1tv.ru...

[baja_blast]

Yes, covid was in the US months before we bothered to check and count cases. There were rumors of a virus spreading months before it was officially acknowledged

[oneshtein]

Most likely, Covid19 was introduced into USA from World Military Games[0], or from Russia in October-November 2019.

If someone went to Novosibirsk to check situation after blast at BSL4 lab "Vector", then (IMHO!) he may contracted the virus and spreaded it in USA after return, which (IMHO!) explains why USA three letter agency covers that blast.

[0]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813667/

[naasking]

> You can explain one of the many reasons why gain of function research is necessary: anticipating next year’s version of the flu, designing drugs and vaccines such that resistance mutations reduce evolutionary fitness.

None of these require gain of function research.

> You can explain some of the safeguards in place: BSL 3/4 facilities, regulatory / institutional oversight, security services, etc.

All of these have a long history of failures [1,2]. And those are just the acknowledged, some have actually been covered up [3].

[1] https://en.wikipedia.org/wiki/List_of_laboratory_biosecurity...

[2] https://www.amazon.ca/Pandoras-Gamble-Leaks-Pandemics-World/...

[3] https://health.wusf.usf.edu/health-news-florida/2023-04-25/d...

[pfisherman]

> None of these require gain of function research.

Please elaborate on this. How should I go about anticipating which mutations in which genes / protein will result in resistance to a candidate therapy / molecule / mechanism that I am considering advancing into phase 1 trials?

[PM_me_your_math]

It is dangerous to play bio-engineer, and then handle what you create like Gomer Pyle.

[ochoseis]

I think a lot of it comes down to: if it has happened once, it is likely to happen again. If it was indeed a leak from WIV, which ended up killing millions, then what can we do to prevent that kind of thing from happening again in the future? Surely some more transparency would be helpful toward that goal.

[bitemaja]

I think real risk is testing these chimera viruses on mice with humanized cells.

Letting viruses evolve in-vivo is the problem especially when they are so viral.

There needs to be limitations on what R is allowed to be produced in-vivo, even more so because calculating the risk of virality of the outbreak is trivial if in-vitro studies are done.

[pfisherman]

Chimera virus. You mean like a spike protein expressing VSV? Do you think that (pseudo virus) requires a higher or lower BSL certification to work with than bonafide Coronavirus? Why?

And why are you worried about humanized mice and not human cell lines like HEK or CALU? Why not primary cells or organoids? Somewhere the “Outbreak” monkey is crying.

I admit that I am being a bit snarky and passive aggressive here; but for the past few years I have watched people butcher bioscience in online discussions. Imagine being a classically trained pianist and having to watch people misattribute all of Mozart’s work to Brahms. It is enough to drive anyone mad.

[baja_blast]

A classically trained pianist's profession does not carry the risk of killing millions of people! There is zero proof outside of circumstantial conjecture that SARS2 has a natural origin. Up to 20 million people have died due to an animal virus modified to be highly infectious towards humans and you expect everyone to just take your word for it?

I mean it sucks if it hurts your career or impacts your profession, but highly dangerous work needs to be reviewed and banned if need be!

Humanity > Your personal career

[thatguy0900]

I'm honestly under the impression that people are just too irresponsible to do some things. People are not machines who go into a bsl 4 lab and do proper safety precautions each and every day without slipping or becoming lax. If you have a lab making viruses, eventually, it will escape. If the viruses they are making are capable of shutting the whole world down for a year, then we really need to ask whether we should have them.its not a question of "is doing this useful?", because I'm sure it is. It is a question of is this worth doing even though we know it will inevitably go bad? You can talk about all the precautions and regulations you want, if people are involved then eventually someone or a group of someones will do something idiotic or malicious and break everything. There's literally an entire Wikipedia page about lab outbreaks. https://en.m.wikipedia.org/wiki/List_of_laboratory_biosecuri...

[ifyoubuildit]

> You can explain one of the many reasons why gain of function research is necessary: anticipating next year’s version of the flu, designing drugs and vaccines such that resistance mutations reduce evolutionary fitness.

If this research indeed caused the pandemic (and might cause more), do those things make the juice worth the squeeze?

A chance at a better flu vaccine doesn't seem like enough reward for what we all went through.

[P_I_Staker]

The answer is simple: yes.

[baja_blast]

> You can explain one of the many reasons why gain of function research is necessary: anticipating next year’s version of the flu, designing drugs and vaccines such that resistance mutations reduce evolutionary fitness

A few problems with this. First modifying wild animal viruses to be infectious towards humans is different than modifying human viruses to model potential mutations. Modifying animal viruses to be infectious towards humans has done nothing but cause risks. Despite this research being conducted for almost a decade it has yet to predict or prevent any pandemic and probably started this one.

Additionally the idea that modifying animal viruses to easily transmit towards humans will allow us to develop vaccines is absurd. You can't test a vaccine that is not circulating in humans, so trails can not start until the pandemic has already started.

So yes, there should be moratorium on research that modifies infectious diseases! The public has a right to consent on whether such research is worth the risks.

[kosievdmerwe]

I frankly can't think of a more dangerous thing humanity can be doing than gain of function research.

Especially if done near population centers.

[aero-deck]

It's really arrogant to think that any argument for a moratorium must be based in lack of information.

[migro23]

To be fair, vaccines can be created in a matter of days now so the benefit of gain of function research to anticipate the virus that will cause the next pandemic is modest at best.

Temper this proposed modest benefit with the potential cost in terms of human adapted viruses being accidentially/intentionally released in the wild given the vagaries of both biolab security protocols in the labs accross the world conducting this kind of research and individual human psychology makes the justification of such research a pretty hard sell.

[tengbretson]

By this standard, the only people sufficiently qualified to make policy regarding this research are the people currently cashing checks to perform this research.

See any issues there?