The Nih Ordered Me to Stop My 'dangerous' Gain-of-Function Research
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A researcher was ordered to stop their 'dangerous' gain-of-function research on tuberculosis by the NIH, sparking debate about the risks and regulations surrounding such research.
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https://www.sciencedirect.com/science/article/abs/pii/S07554...
https://www.newsweek.com/controversial-wuhan-lab-experiments...
https://www.newsweek.com/covid-lab-leak-china-virus-nuclear-...
https://www.vanityfair.com/news/2022/10/covid-origins-invest...
https://www.propublica.org/article/senate-report-covid-19-or...
https://onlinelibrary.wiley.com/doi/full/10.1002/bies.202000...
The evidence for zoonotic origin of SARS-COV2 is very strong[0] and the conspiracy theorists as usual have little more than speculation.
[0] https://www.annualreviews.org/content/journals/10.1146/annur...
https://www.astralcodexten.com/p/practically-a-book-review-r... https://www.astralcodexten.com/p/highlights-from-the-comment...
However, @hackingonempty's comment shows how dangerous over politicising these topics can be. Claiming lab-accident origin as a conspiracy theory stifles debates like the one linked.
Take a report from the first link where experts in the field still give a 21% chance to lab leak definitely takes it out of the range of conspiracy theories.
The only reason it was "removed" as a plausible origin was politics.
> asked how likely it is that COVID-19 originated from natural zoonosis, experts gave an average likelihood of 77% (median=90%). In fact, four out of five experts stated that a natural zoonotic origin was more than 50% likely. > However, consensus was not complete. Across all experts, the average likelihood they gave for a research-related accident origin was 21%. Overall, one out of five experts reported a 50% or greater chance for an origin other than natural zoonosis.
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.
Which is why "it couldn't be a lab leak" struck me like a ton of bricks when it was said.
My immediate response was "that's not science, he's not speaking like any scientist I know, and I know a few hundred."
My position in Science, as support personnel working on software related to funding requests, grants, research collection, and reporting, for nearly a decade, left me in that moment with a distinct feeling that the difference in communication was about protecting funding, reputations, positions, etc. Scientists are not dummies, and their communications with political agencies are very politically aware. I can see a scenario in which, to preserve public confidence in Science(TM) such false confidence might be presented. Gave me the heebie jeebies.
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.
The "conspiracy theorists" include the director of the CDC at the time who was actually in contact with the Chinese CDC and also a virologist, and also the chair of the one official investigation which visited Wuhan in the early days.
>Obvious evidence against the laboratory leak allegation is that the first documented cases of COVID-19 were not linked to the WIV nor in the same geographical region of Wuhan (44). The WIV laboratory of Prof. Zhengli Shi, who has been the subject of abundant accusations because of her work on bat coronaviruses (10, 11, 13), is located more than 30 km from the Huanan market epicenter. Clearly, if the virus first emerged at the WIV, then that location should be the site of at least some of the earliest cases or linked to those cases. It is not.
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?
I'm skeptical, because Holmes points out that the Huanan market origin is supported by molecular evidence:
>Phylogenetic analysis of SARS-CoV-2 genome sequences also points to the Huanan market being the epicenter of the pandemic, with the Huanan market sequences falling at the root of the SARS-CoV-2 tree. The earliest split in the SARS-CoV-2 phylogeny, which seemingly occurred in Wuhan, is between the A and B lineages that differ by two nucleotide substitutions (45) yet gave rise to many descendent lineages. Remarkably, despite its relatively low number of visitors, both these lineages were present at the Huanan market (44, 46, 47). The odds of this co-occurrence without the market being the global epicenter are extremely low. Molecular clock studies of SARS-CoV-2 evolution also point to a market origin. Estimates of the time to the most recent common ancestor (tMRCA) for the epidemic as a whole, of the specific outbreak in Wuhan, and of the sequences from the Huanan market overlap with a time span encompassing November and December 2019, again suggestive of an outbreak that started at the Huanan market (47). This timescale also means that the virus was circulating for only a short interval before it was first detected by physicians in Wuhan. Additionally, these observations fit the available epidemiological and serological data from Wuhan, which provide no evidence for SARS-CoV-2 in that city prior to December 2019 (44, 48).
They then released the new framework of multi-layered review to clearly define the tradeoffs and how they were managed, and resumed funding for those that could meet the improved criteria.
ie it was standard research advancing regulatory risk management.
So, after the process of inserting Gene A into a batch of bacteria you need to figure out which of the bacteria actually picked up Gene A so you can proceed to the next step of your experiment. So, what you do is you pair Gene A with Gene B, which is a very light resistance to a very specific antibiotic. Now, after you perform the electroporation, you plate the bacteria on agarose gel, let colonies start to develop, and then lightly dose the gel with the antibiotic.
The surviving bacterial colonies are those which have incorporated both Gene A and Gene B (because they are paired). It's just a way of filtering bacteria after electroporation so you can do further work. It's not dangerous to people because A) this antibiotic resistance was already found in nature, B) it's a resistance to a very specific antibiotic, not all antibiotics, and C) you're doing this in a protected lab.
This is an incredibly standard process, to the point where - again - I did this in a Biotech 102 program at community college. You could sign up for a classes where you learn to do this, right now.
I have a question, why not pair Gene A with something still detectable but less "dangerous", like a gene that change body color, or emit different color under UV light.
Sorry i am totally noob here
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.
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.
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.
These are reasonable, but...
> C) you're doing this in a protected lab.
...this one is problematic. It's not taking the concerns of the people you're talking to seriously; namely, that no lab can be protected enough, that there's always a chance of leaking, and that the more GoF research is done the higher chance something is going to leak.
If nothing else, not registering that you even understand someone's concern is a sure-fire way to get them to ignore everything else you say.
And, I'm not sure exactly what your attitude is, but at least the way you put it here does sound overconfident. Sure, protocols should be safe if they're all followed; but the protocols are followed by people, and people make mistakes. Just take a look at all the nuclear accidents that have happened in spite of protocols.
Your best bet, I think, would be to lean on A and B: "There are strict protocols in place around labs to keep things from leaking; but even in the very unlikely event that something like this does leak, it won't really have any impact: as I said, the antibiotic resistance is a mutation that evolved by itself in the wild already; it won't make things worse than they already are."
EDIT: Or, at least, to say: "Look, I know it sounds really scary, but if you'd seen the protocols, you see how basically impossible they are to screw up. <brief descripiton of why it's unlikely to leak even if implemented by lazy or incompetent people.>"
The point is to let people know that you hear and understand their concern, and then to educate them about why their concern is unfounded.
EDIT2: This comment seems to be controversial; it's had at least 3 upvotes and 2 downvotes, which surprises me. Any downvoters care to explain?
Listen, I'm not trying to argue that the containment protocols aren't safe; I don't know what they are. What I am trying to argue is
1. That these fears are reasonable, and deserve to be treated with respect.
2. Even if you don't agree with #1, in a democracy, just insulting and ignoring people with those fears is going to be counterproductive.
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.
(Also, FWIW I have an advanced degree and 10 years employment at research institutions under my belt, including 4 in medicine. Its not that I don't believe the claims in the article, its just that they are outside my field of expertise and I want to understand them)
1. You don't have to be "scientifically under-informed" to find C concerning
Listen, I don't consider myself an under-informed person. I have a PhD in computer science, I regularly watch science videos on YouTube, I click on interesting things (like this article) that show up on Hacker News. But until this thread, I had never heard that the sort of thing described at the top-level comment even went on, much less was I familiar with the containment protocols. (How could I not, if I they're taught in Biology 101? I'm pretty sure I didn't take Biology 101; only Physics and Chemistry.)
My starting assumption coming into this thread was that the protocols described here probably are perfectly safe; and that even for more dangerous GoF research, informed people have done a cost-benefits analysis, and determined that the lives potentially saved are worth the lives potentially risked.
Points A and B of the person I responded to reassured me.
But point C I personally find concerning. In computer science, only an absolute fool would ever say, "This system has absolutely no security vulnerabilities". On the contrary, you generally have to live with the fact that there almost certainly are security vulnerabilities in any system you run, and hope that they're found by the good guys before they're exploited by the bad guys; as well as structuring your system to be able to minimize the potential lost caused if not.
Now sure, maybe I'd have a different attitude if I'd taken Biology 101. But that doesn't change the fact that C, as stated, actually weakened the article towards someone like me, who is generally prone to trust the scientific establishment. How much more would it weaken the argument to someone with a more skeptical, anti-science stance?
2. In a democracy, the opinion of the "scientifically under-informed" matters
I realize it's frustrating to have to explain this to the "scientifically under-informed", many of whom are being misled by bad actors trying to profit by stoking fear. But that's the reality of the world we live in. It's not enough to know the right answer; you must convince other people of the right answer.
And I won't even say "unfortunately", because this is a fundamental feature of democracy. Like checks and balances or trial by jury, having to convince non-experts prevents the system from going wrong.
I'm not suggesting we should butt out entirely as non-experts. I'm saying we should defer to people who really understand the field. In this case, we have plenty of experts who actually know what they're talking about, some on the pro-GoF side and some on the anti-GoF side. The commonality is that I've never once heard any expert from either side express concern about techniques that induce resistance to non-human-use antibiotics. And I suspect the reason I've never heard anyone complain about this is that there isn't really much risk here at all.
So instead of getting upset about how it's scary, and then demanding researchers stop doing research to make us non-experts feel better, we should turn to a stable of people who understand what's happening to help us make these decisions, and stop demanding researchers make us feel better.
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.
You do this by including antibiotic resistance genes alongside your modification. Now all modified cells are resistant to the antibiotic. Then you apply a small amount antibiotic to kill the unmodified cells. Now you only have the cells with your interesting modification.
This is the mainstay of molecular biology. Every lab biologist has done it. We even do it as college students in lab practicals.
Banning the use of antibiotic resistance genes in biological research is effectively banning all wet lab medical research.
Conveniently ignoring the fact that they're literally feeding the stuff to livestock to improve growth rates / feed efficiency [1]. Talk about dangerous gain-of-function "research". Industrial vat grown protein cannot come soon enough [2].
1. http://en.wikipedia.org/wiki/Antibiotic_use_in_livestock
2. https://www.youtube.com/watch?v=6eaTIe_TBZA
This specific use of antibiotics resistance is also extremely common. Pretty much every single microbiology experiment starts this way, and every time you want to genetically modify bacteria you do this. This includes every time you want to produce any protein, because you need genetically modified bacteria for that. This is a large part of all labwork in this field.
As the article notes, the antiobiotic used is one that isn't used for humans. So there is not significant additional danger due to that modification. The bacterium itself is much more dangerous than most that are handled in the lab, but that's why they're in a BSL-3 lab.
https://www.hsgac.senate.gov/wp-content/uploads/Testimony-Qu...
It references a great deal of information from https://project-evidence.github.io/
And I've found Jamie Metzl's collection of resources interesting as well: https://jamiemetzl.com/origins-of-sars-cov-2/
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.
1) We'll never actually know the answer
2) Even if we did, it wouldn't change anything about what we ought to do
There's no way China would be "punished" for something if it was a lab leak, and there's no way that [the actually dangerous end of] GoF research is a good risk-reward tradeoff anymore in light of instant mRNA vaccines.
Every breath spent pointing fingers on origin is another breath not spent on the remediations we have to do no matter who's responsible.
We feel differently about this. Personally, I find all the evidence collected so far quite compelling. And I believe humanity has a responsibility to our children to investigate all worldwide pandemics to the fullest extent possible.
> Even if we did, it wouldn't change anything about what we ought to do
Whether or not it would change what we ought to do, it would absolutely change what we actually do. I think there would be broad public support for increased safety procedures at a minimum. The testimony I linked offers additional suggestions.
Your scenario of ending all GoF research might be on the table, or might not, but there is a broad range of less dramatic options available. Among them, locating GoF research labs away from densely populated metropolitan areas and international airports.
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.
Sadly, the funding to do so will not be made available without reason. Reason which could come from determining the root cause.
So your fixation on root causing is having precisely the effect that I mention, which is preventing mitigation.
Friend, I don't seem to be the one with a fixation here. Please avoid personal attacks.
It's not a personal attack, it is referring to a belief that you stated you have.
Not sure what's triggering about "fixation" but feel free to swap out any of the above phrases.
No, I'm not sure any of those phrases fit a casual conversation on a message board.
> Not sure what's triggering
Are you triggered? I'm not triggered. I just posted a link, and responded when prompted.
And more subtle issues along those lines.
It's a bit like an air crash investigation. You have several million killed and want to understand what happened so as to try to prevent the next one.
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.
It's a bit like looking at the 737-MAX crashes and saying the investigation was pointless. Planes should be designed not to crash regardless, don't you agree?
If so, yes, focusing on debugging a 737-MAX crash that happened to be completely full and hit an occupied building on the ground (therefore extra horrific/attention-grabbing) would be pointless.
Doubly so if the evidence required to root cause it was evaporated upon impact.
Triply so if people decided they had to know what caused that specific crash before they could address the probabilistic falling of airplanes out of the sky.
This statement and others you've made about dice and probability suggest that you think actions of humans bear no weight on probability of infection or outbreak. History teaches us otherwise.
Basic statistics and logic teaches us this.
Brilliantly put.
And past experiences inform future actions. It's called learning, and some of us feel it's worthwhile for no other reason than the knowledge.
Put another way, one might ask your same question about polio or smallpox or any other outbreak of any other disease. Everything we learn about every one of them prepares us in some way for the next.
It's literally the foundation of epidemiology.
But in reality, it isn't. It creates precisely the faulty logic that we're seeing in this thread, where people believe certain mitigations are justified only after certain conclusions are reached about the origin of COVID.
This just isn't true and we do ourselves a disservice to frame the conversation such that people believe that to be the case.
If we discover that COVID came from a lab and therefore decide to eliminate GoF research but not increase surveillance efforts (since eliminating GoF research addresses "the threat"), that is bad.
If we discover that COVID came from a zoonotic origin and therefore decide to continue doing dangerous GoF research in metropolises, that is bad.
If we fail to determine either of these things with sufficient certainty to take action against either threat vector, which is the most probable case, that is really bad.
If we instead acknowledge that it hardly matters where COVID came from because it indicates nearly nothing about where the next pandemic will come from, and therefore we need to mitigate both vectors, that is good.
I'm not following. It seems as though you've run wildly to some conclusion not present in the conversation. Perhaps there's some outside context I'm missing.
> If we instead acknowledge that it hardly matters where COVID came from because it indicates nearly nothing about where the next pandemic will come from
It seems you would do away with the entire field of epidemiology. I find that the discipline has been quite useful to humanity. I'd like to keep it.
How do you know GoF research is bad? By analysing the consequences of previous GoF research.
If lab origin is confirmed, it adds support to GoF research being bad hypothesis helps creating relevant regulations. If zoonotic origin is confirmed, it adds another data point of naturally created dangerous pathogens and weakens the argument of banning GoF research.
There are no _a priori_ truths, only approximations at a time based on past statistics.
Let me know if you are convinced, either way :)
Why would a zoonotic origin of COVID reduce the risk of GoF?
A poor analogy is suppose in 1800s humans encountered nuclear explosion near nuclear research lab. It could have human or natural origin. If natural then it is important for us to accelerate nuclear research with relatively lax regulations and develop countermeasures. If human origin, lack of sufficient regulation is a more probable cause.
This is effectively not true in light of the mRNA platform, which negates the rest of your argument as well, because the existence of the mRNA platform is not contingent upon the origin.
Dangerous GoF was made excessively dangerous by the invention of the mRNA platform regardless of whether COVID itself even happened, never mind the specific origin of it.
Doing GoF research in major metropolitan areas is very obviously unacceptable and should have been considered such prior to COVID, and should be widely considered such after COVID. Again regardless of whether COVID itself came from WIV.
We already know everything we need to know about zoonotic possibilities which is that nature can produce pathogens orders of magnitude worse than COVID on any dimension.
If after learning that COVID was zoonotic, your conclusion is "guess it's okay to keep WIV and WIV-like labs in major cities doing the type of research they were doing," then you are simply insane.
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.
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