The NIH ordered me to stop my 'dangerous' gain-of-function research

Well, the Wikipedia article is clearly incorrect - the lab leak hypothesis is supported by evidence. Even if you don’t think it’s true, you have to agree that there is at least some supporting evidence that adds weight to the hypothesis. Not a great advert for Wikipedia. The absolutist statement clearly indicates political bias rather than objective enquiry.

I knew that some people still think the market hypothesis is true (despite the lack of good evidence), I was more interested in the response to this particular testimonial? For example, did anyone push back on specific points?

I ran the doc through AI and asked it to form the strongest counter arguments it could muster. It didn’t do well and concluded lab leak was more likely than market.

> Whether or not it would change what we ought to do, it would absolutely change what we actually do.

I actually think the obsession with root cause makes it less likely we'll create the interventions we need. First because it suggests to people that the root cause of this pandemic changes the risk calculation for future pandemics (it doesn't) and secondly because the mitigations of one root cause are distinct from the mitigations for another. And we actually need to mitigate both zoonotic and lab leak threat vectors.

> Your scenario of ending all GoF research might be on the table

To be clear I did not suggest this. GoF is an extremely broad term which includes e.g. mutating E. coli to produce insulin or other biologics. Increasing contagiousness of a lethal agent or increasing lethality of a contagious agent should become much more of a no-go zone though. That's a small subset of GoF research.

> locating GoF research labs away from densely populated metropolitan areas and international airports.

We should do this regardless of whether this pandemic came from a lab.

How specifically does the value of either of those things, which are intended to mitigate the next pandemic, depend on knowing the origin of the previous pandemic?

This is like saying it's important to know whether the last dice roll was a 2 before you decide whether to bet on a 4 or 6 coming up next.

Held accountable in what way?

It's legally permissible for the government to do what it did, at least as far as any of the several court cases have been able to find evidence for, which is merely requesting content moderation.

It's obviously First Amendment protected speech for social media platforms to suppress whatever discourse they feel like for whatever reason they want.

More importantly, neither the legality nor ethical valence of these actions hinge on whether the claims actually end up being true.

Just to elaborate a bit more, the problem is that even a colony which, for example, glows under a blue light, will have some members that didn't uptake the genes. So you need a more proactive filtering method.

There's also the fact that bacteria tend to lose non-adaptive traits pretty quickly once the selection pressure is gone, so having the antibiotic resistance attached to your gene of interest makes it much more likely to stick around for the duration.

Additionally, as others have said, this particular antibiotic (from the post) isn't even used for human treatment so it's not really particularly more "dangerous", we just tend to get nervous around anything "antibiotic resistant" because we jump to thinking about like, MRSA.

Because the antibiotic automatically selects the successful clones. The others that didn't incorporate the plasmid don't grow into colonies. Without antibiotics your plate will be entirely full of bacteria, you can't pick individual clones from that.

And you want clones, so all identical bacteria derived from a single successful integration of your plasmid into a bacterium. You don't want a mixture of bacteria with different DNA. This process isn't perfect and you need to screen out cases where your DNA sequence is not correct. And by far the easiest way to do that is to grow on plates with antibiotics, and an amount of bacteria that results in a few individual colonies, with each clone being full of genetically identical bacteria.

You generally want antibiotics in your media anyway, working without antibiotics makes it much more difficult. You don't have 100% perfectly sterile conditions, with antibiotics you have a much larger margin here.

Best case you’re transforming 10^6 cells and you expect 20 of them to take up the DNA.

Worse case it could be 10^11 cells for a strain of bacteria that doesn’t transform well.

You would have to look at a lot of colonies to find the one that transformed.

My biggest concern when I saw the political controversy around GoF research was that new rules would be used inappropriately to stop important research that keeps us safe. That seems to be happening in this case, more or less as I feared.

As others have pointed out, this is a fairly routine practice that happens even in schools. It’s the nature of the experiment that makes it relatively safe. The fact that it happens in a protected lab is just icing on the cake (they’re dealing with TB bacteria, so it’s inherently non-zero danger just because of that.) You seem to be pointing to the icing and arguing that because one part of the cake might not be perfect, the whole thing is unsafe. But it’s the entire cake that the author is pointing to in their argument. And then rather than engage with the article, you’re arguing that, rather than engage on the substance, we need to engage on the level that some non-experts (who don’t understand the protocols) are scared and hence the correct standard is that we need our practices to reassure them.

But we’ll never be able to reassure terrified, scientifically under-informed people to their satisfaction, particularly when they’ve already decided that GoF is somewhat scary and maybe even partisan. So the result of this attitude is that we can’t do relatively safe but important research on diseases that might save your life or the life of someone you love.

You know some labs with active bioreactors which aren't protected at all? And the waste just dumped into nature... Pigs and cows fed antiobiotics.

As to reassuring you; I don't know what to say.

In the 90's I heard a (possibly apocryphal) story about a computer lab at my school . A student had been thrown out ass-over-kettle for 'dangerous hacking'. Their crime? Opening their mail in PINE over Telnet.

Most of the stuff Sarah Stanley was doing here are things you can technically do in your own kitchen, if you're a little careful. Just because you've never done them personally yourself, doesn't mean lots of other folks can't or haven't! (And I can totally see someone doing it to get some of the scout merit badges even [1] )

There's really no way to reassure you that I can think of though. Except maybe get you over to a (home?) lab and have you mess with some genes yourself. You'll see it's utterly mundane.

Obviously; I wouldn't quite recommend starting with TBC. That one is a wee bit more exciting. hence the protected lab. But what this research group was doing with it is/was otherwise not more dangerous beyond that.

[1] There's several stem badges for biology that include genetics, but none that are specifically molecular genetics - yet.

Yeah, this is both true and tricky. My belief is that the original sin was politicizing the question soon after the beginning of the pandemic; both the Chinese and US governments are at fault here (destroying all the raccoon dogs seems like a very stupid action to me, for example).

I further believe that a lot of people overreacted to the rush to judgement. It is correct to say "we don't know yet" and in March/April 2020 it was wrong to say "this has to be a lab leak." But it's also wrong to overcorrect and say "it couldn't be a lab leak." That's both a political reaction and a human reaction.

From the review I posted above: "Whether such an escape is deliberate or accidental, the laboratory in question almost certainly must have known that an incident had occurred, such that their denial necessarily indicates a cover-up (74)."

That's what makes it a conspiracy theory, as used in the popular lexicon. While there is substantial evidence the initial transmission was from an animal at the Huanan market, the conspiracy theorists are running with a tiny bit of circumstantial evidence and a whole lot of conspiring between researchers and the Chinese government, etc...

> The only reason it was "removed" as a plausible origin was politics.

I disagree, at this point the evidence has stacked up and not in favor of the lab leak allegation. A major reason it persists is because of the efforts of the White House and their political appointees who want to cast blame on China.

I would love to see a peer reviewed review of the scientific evidence by an expert, like I posted above, that leads the author to the conclusion that the virus escaped from a lab.

Holmes also collaborated with Shi in 2018 so is maybe not unbiased. The paper only has the WHO location data which was provided by Chinese government sources who seemed pretty determined to make out it came from the market. There is an earlier data set from a radio phone in, clustered on the other side of the river.

Redfield the CDC head is quite interesting and basically says the Chinese faked the location data https://youtu.be/oMlhvnMpRU0?t=119

Market believers tend to say he's a Republican he must be an anti science crank but what motivation would he have to lie about such stuff which caused a lot of criticism or him?