Researchers’ tests of lab-made version of Covid virus draw scrutiny | Hacker News Reader

Researchers’ tests of lab-made version of Covid virus draw scrutiny

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217 pointsrussfink321 comments

1) talk about failure to read a room

2) even the alleged learning from the experiment: "The conclusion of the study is that mutations in the spike protein of the Omicron variant are responsible for the strain’s ability to evade immunity people have built up via vaccination, infections, or both, but they are not responsible for the apparent decrease in severity of the Omicron viruses."

...does not hold up, because this was in mice. Ordinary lab rats were immune to the original strain of covid-19, but not to Omicron, which shows that it is not at all unlikely for there to be significant differences in the resistance of rodents to one strain or the other, compared to humans.

So, they made a hybrid covid-19 strain, that could conceivably have been as contagious as Omicron but as lethal as the original strain. Nice work, folks.

Well the mice the researchers used were genetically modified mice to have human ACE2 receptors which is standard practice in Virology. But! I will say it 100% is not worth the risk, just last year a researcher in Taiwan got infected with the delta variant in the same level lab BSL3, so any dangerous or novel virus they create has a real possibility of escaping.

Also it's not like this type of research helped us predict or even fight the pandemic. Millions have been spent on studying and modifying wild coronaviruses and it not only failed to predict this pandemic, but none of the research helped in anyway combating it. For example the Ecohealth Alliance the main collaborators with the WIV has still to this day refused to share research and data they have collected over the years. So either the research is worthless and thus why are we funding it despite the dangers, or they have something they want to hide.

This particular research helps to understand how important this particular variant of the spike protein is.

When future virus variants are discovered and sequenced, this information helps understand what to expect. Because the virulence of new Variants can't be estimated for months after their first detection.

This particular variant that didn't exist until humans combined two variants into a new one?

Which is simulating what could and probably will happen in nature, before it really happens

Or could cause it to happen. There's still a decent chance the original covid wouldn't have happened if people weren't doing this type of research.

There is zero indication of the Virus having originated in a lab. Some hand-waving, no actual evidence. No genomic signature. No merging of known lineages (which would happen). No plausible mechanism (to those who know the subject).

Much more likely: This Virus originated just like the thousands before it. From ordinary Human-to-animal contact. Virus particles pass from animals to Humans trillions of times a year. Most of the time exactly nothing happens at all. Even rarer are actual transmissions. Still rarer are chains of transmission that allow the Virus to evolve into an actual threat.

I love how everyone involved always jumps on the most extreme version of the lab leak hypothesis "Chinese government made COVID super weapon" and then use that to discount everything else instead of admitting the much more nuanced reality of the situation.

The lab leak hypothesis has a range from "This virus was created and released by the Chinese government as a bio-weapon against the US and to kill off their own aging population" at the extreme. To the "The virus was being studied at the Wuhan Virology Institute and someone one got lax on safety protocols got exposed accidentally and then took the train home."

Most people that seem to argue against lab leak, seem to assume everyone ascribes to the first position, whereas the majority of the people that believe in the lab leak subscribe to the later position, including myself.

The conflation and smearing that happens whenever an accidental lab leak is brought up, makes me suspicious. As an example, I used to edit Wikipedia articles in the area, but I gave up, because some editors made a concerted effort to discredit it as a "conspiracy theory" and had boundless energy to shut it down.

It seems to be the opposite to the much vaunted "fearless scientific transparency" that's sold to the public as a hallmark of science.

I guess that in a generation or two, when vested interests move on, there may be more willingness to explore this.

> The lab leak hypothesis has a range from "This virus was created and released by the Chinese government as a bio-weapon against the US and to kill off their own aging population" at the extreme. To the "The virus was being studied at the Wuhan Virology Institute and someone one got lax on safety protocols got exposed accidentally and then took the train home."

And people on either end of that spectrum should be expected to have substantial evidence to support their position since the far simpler and common scenario is that it wasn't leaked from the lab at all. "Extraordinary claims require extraordinary evidence" applies much more to the government bio-weapon crowd, but it still absolutely applies to the 'employee mistake' theory too.

There are two indicators, one simply how close it was to a virus lab doing similar studies, and two how immediately and blindly people denied that they could be any connection.

They'd have had to investigate before making a claim, and had not, so obviously they're lying.

A concerted conspiracy to deny an option is some evidence for that option being true.

I don't claim it did come from a lab, but that anyone stating categorically that it did not is lying.

Why is

- a virus unusually adapted to being transmitted between people

- which was released next to one of a handful of labs on earth that studied it

- that the Chinese government and several American scientists tried to cover up

- normally found a thousand of miles away

- that we can't find an origin for unlike SARS and MERS (with far more looking)

isn't also an at least equally extraordinary claim?

> I love how everyone involved always jumps on the most extreme version of the lab leak hypothesis "Chinese government made COVID super weapon" and then use that to discount everything else instead of admitting the much more nuanced reality of the situation.

I think a decent argument could be made that this phenomenon (in its abstract form, not specifically this variation of it) is more dangerous than covid, or even a virus much more dealy. Who knows how much damage this does to the world considering how widely it exists?

"Gain of Function" research is brought up very often in this context.

A natural virus would first need to get into the lab in order to escape from it. I'd argue it's a lot harder and less probably for a bat Virus - which isn't adapted to Humans yet - to be collected by a lab, then infect a researcher, then continue the chain in Humans, rather than the same virus making it from the Jungle to a Human population without involving some researchers. Even more likely, Sars-Cov-2 widely circulated in the intermediary hosts and had thousands of contacts with Humans until one lineage "stuck" because it finally matched.

How would we know if there would be a genomic signature if the database of viruses Wuhan worked with wasn't opened up?

There is not plausible mechanism for anyone from the Wuhan laboratory to get sick with a virus they are studying? This happened several times, and happens 100's of times a year (not Wuhan specifically but labs).

There is some circumstantial evidence it was a lab leak. Like the virus doesn't naturally occur in the Wuhan district, and the Wuhan Institute of Virology is one of the few in the world that study coronaviruses and do gain of function research. Unlike SARS and MERS where we discovered the origins quickly, we still don't know the origins of covid-19. I don't know how you leap to the conclusion it was of natural origins when we don't even know what those natural origins are.

We don't know if it's a lab leak or not, but they do happen and they've fairly common. (10's-100's per year)

The Virus has been sequenced to death. Gene editing technology leaves traces. Hard to explain, but it's partly because of the technology and partly because evolution erodes statistical anomalies in a certain way.

There is no plausible way to "gain of function" your way into a pandemic Virus. Researchers can make a Virus gain a function. Usually by making it lose a few others. There is also no plausible way that an unmodified Virus collected from labs just happens to be the next hot shit on the pandemic scene. If there is a Virus with that potential, you wouldn't need researchers and a leak from a BSL-3 lab to make it go viral, it would just happen on its own.

Except it's not a simulation, it is causing it to "really happen". The only difference hinges on the ability of human institutions to keep it contained, which at the very least we have reason to be concerned about.

A pandemic virus circulating in the wild is an incredibly fine-tuned machine. Just mashing together integral parts from two quite different genomes is not going to result in a Variant that is tuned enough. In order to make a Virus virulent and transmissive, it needs to evolve through multiple, probably dozens of hosts, and only if that is on a broad scale, like thousands of such lineages, does it have a chance of success.

Even one lab leak isn't enough. The Virus would most likely die out on its own, if not it would get outcompeted by naturally developing variants. The risk of a lab leaking a variant in a way that it would outcompete natural strains is so miniscule compared to natural variants arising and doing the same, it's not worth mentioning.

Do we have definite proof that the original SARS-CoV-2 hasn't escaped the lab?

To what standard? It's the same game with climate change. When only 1% of the scientists dissent, that gives certain people enough confidence to believe the opposite of what the 99% believe.

I'm always skeptical when people say x% of scientists agree or disagree with a given hypothesis. Most of the time these numbers are flat out wrong or misleading. Most scientists have very complex views on their own domain. Those complexities lead to a very nuanced understanding of topics that we lay people don't fully understand. Most have subtle disagreements on most topics.

You can have even substantial disagreements with other people in your field without negating the possibility that the bulk of your field is in directional alignment with respect to the core of the matter.

Climate change is a perfect example: 99% of people who study climate likely agree that a) the Earth is getting warmer on average, b) the warming is substantially exacerbated by human-derived emissions, and c) the medium- and long-term destabilization due to that warming has meaningful potential to have catastrophic effects any biomes, including those inhabited by humans. They likely disagree amongst themselves on a) how much warmer and over what timeline, b) how much of the warming is caused by humans, and c) what the specifics and timeline of the catastrophic effects are likely to be.

In situations like the above, attempts to paint disagreement over magnitude as disagreement over direction are misleading at best and disingenuous at worst.

You are totally correct. The problem goes both ways. One camp will say there is significant disagreement on this issue therefore we need to act in a certain way. While the other side will say the scientists all agree so we have to act another way. But you have to be very specific about the claims you're make when you say scientists agree or disagree on a matter. You also cannot extrapolate even slightly when you do.

For example you have made some very specific claims about the climate change consensus. But people often simply say X% of scientists agree on climate change, without defining what they mean about climate change.

All of this is also done to support a given course of action. Those courses of action only make sense with a very specific model of climate change. Often a model that is not totally accurate or agreed upon. Then they often incorrectly quote the scientist. Such as Al Gore's famous prediction “Some of the models suggest to Dr Maslowski that there is a 75% chance that the entire north polar ice cap during some of the summer months could be completely ice-free within the next five to seven years.” When Dr Maslawski was not predicting anything as dramatic. In the other camp you have appeals to Freeman Dyson. But he does agree that man has altered the climate. He simply doesn't think drastic action is required, and that we will be able to counter its impact. Not surprising from the guy that came up with the ideas to harvest the entire energy output of the sun.

The details matter and the appeal to authority that all the scientists agree with me is not as good as an argument on the facts.

You can't handle the facts.

Seriously. If you don't want to believe what 99% of the experts say, and don't know shit about the actual science - which takes years to understand - it's a pretty good bet you're wrong. Lot's of things can't be broken down to a level non-experts can understand.

Of course, I'm sorry I forgot you are the source of all truth and all who disagree with you don't know anything about actual science. I thank you for my chastisement. I will commence with the self flagellation immediately.

An Analysis of the Origins of the Covid-19 Pandemic: Interim Report [pdf] https://news.ycombinator.com/item?id=33360216

You must know that virologists routinely "serial passage" viruses through animal hosts? Evolving a candidate virus "through multiple, probably dozens of hosts" is what virology labs do.

And lab leaks happen All The Time. SARS-1 escaped labs on six separate occasions.

Serial passage actually weakens a Virus because this kind of evolution selects for properties that aren't useful for transmission outside the lab. And virulence usually decreases as well. Animal studies of this nature just don't have the numerical power to modify such properties intentionally.

We have one other piece of evidence: Ecohealth Alliance will not share lab notebooks from Wuhan. As a Bayesian horse, you’ll know this “explains away” the natural origin hypothesis. The belief in a natural origin actually goes down.

Bullshit. Absence of information means the uncertainty is not reduced...

In fact it seems like a reasonable assumption that on many days at a BSL-3+ lab, we're trusting at least one hungover graduate student who is operating on two hours of sleep at 9 in the morning, not to commit human error while implementing biosafety protocols to protect against the accidental release of a synthetic pathogen to the local urban population.

Another comment in this thread suggested building these labs in a desert or some other extreme environment where scientists can be isolated for months at a time. This seems like an obviously necessary mitigation against the unknown risk of introducing synthetic pathogens that haven't been created in billions of years of evolution. And yet, the secretive groups funding and regulating this research instead choose to build their labs in urban centers. Why?

An obvious answer is it's expensive to build and hard to staff and maintain labs in extreme environments.

Bioweapon labs have a history of being built on small islands for this reason.

> This seems like an obviously necessary mitigation against the unknown risk of introducing synthetic pathogens that haven't been created in billions of years of evolution.

I'd wager that it's likely that the COVID variant that was made in a lab was also created through evolution at some point. Every infected person with the virus has billions of viral replications taking place in their body, and each virus itself will have its own mutations. There's a high chance such mutations already took place, somewhere and in someone/something, but those mutants never created their own worldwide outbreaks.

I think it's worthwhile to understand how mutations can affect a virus at the heart of a pandemic. Finding such mutations in the wild is a roll of the dice, and the chances of encountering something like it rise the longer and more widespread the epidemic is.

None of that is practical. In reality, biosafety procedures in those labs are extremely good at preventing any incidents. If you think it's easy to infect yourself as a BSL-3 researcher, you probably have that impression from watching a movie or TV show.

That's why isolating the researchers is not necessary. Also you underestimate the number of such labs and the amount and variety of work that such labs are doing. "Synthetic Pathogens" are not a thing. Synthetic viruses are hardly pathogenic at all.

If it's not practical to mitigate against some risk, then the potential reward isn't high enough. Ignoring the risk and continuing without optimal mitigation is only a logical course of action if the potential reward outweighs the possible downside.

If research is sufficiently dangerous to necessitate a BSL-3+ lab, then it should have to meet a correspondingly high bar for demonstrating its potential reward. It's not clear to me that gain of function research could ever make such a justification.

In an ideal world, we could do this research with remote controlled robots in an orbiting space capsule. If we can't do that yet, then we could at least do it in a desert. Otherwise, shouldn't we be asking the local population to approve each research proposal that could lead to a local outbreak of a dangerous virus?

> This particular variant that didn't exist until humans combined two variants into a new one?

Nature created a very similar hybrid earlier: "Deltacron" was in the news in March 2022.

The gene that encodes the virus’s surface protein — known as spike — comes almost entirely from Omicron. The rest of the genome is Delta.

https://www.nytimes.com/2022/03/11/science/deltacron-coronav...

His team described three patients in France infected with a version of SARS-CoV-2 that combines the spike protein from an Omicron variant with the "body" of a Delta variant.

https://www.reuters.com/business/healthcare-pharmaceuticals/...

And apparently the combined Virus was outcompeted by other Omicron lineages. Otherwise that "Deltacron" would have become a prominent or at the very least an extant variant.

If this research does help us to understand that, it should be done in the highest level safety protocol labs, which this was not.

If it is not able to get funding for being done in such a lab, that's probably because the potential learning does not justify such $$ cost. Which means it's also not worth the risk.

You are correct that the virulence of new variants is hard to predict. That very fact means you shouldn't be making new ones, and assuming you can predict how virulent your new one is going to be (and thus how hard it will be to contain).

The safety protocols have been deemed satisfactory. You overestimate the risk.

New variants are created all the time by natural transmission. Including the recombination of two different strains. So the controlled, artificial recombination is like a grain of sand in a bucket of sand. And even if it "escapes", the escaped variant would still have to evolve and prove itself.

Experts don't see this as a risk.

I read this and dream of the day where the common cold is cured. And it makes it all seem worth it.

There is no common cold. There are over 200 distinct viruses that cause the illness we call "a cold."

s/common cold/over 200 distinct viruses that cause the illness we call "a cold."/

Sure, but investigators need to treat this subject with reverence. Unlike pretty much every other discipline on earth, this one has the potential to disrupt billions of lives from a single mistake.

Virologists were the first ones that jumped to say Covid wasn't a lab leak, yet what they should have been saying was, "we'll get to the bottom of this and then, even if wasn't a lab leak, work to make sure that outcome never comes to pass."

Instead we got a blame game, accusations of racism, and everyone not in their field was called stupid or incapable of understanding the situation if we asked for more light to be shed in the subject.

Also, what happened to the scientific method? There was a whole lot of certainty being prematurely thrown around.

This hubris won't do.

I don't know how Covid came about, and at this point the only reason to know is to prevent the next one. But no matter the case, whatever is next better not be from a lab.

You want a global replace, so the end is "/g"... but I feel you lol.

This is incorrect. I have posted the correction. Which I will repeat here for convenience: s/is no common.*/are over 200 distinct viruses that cause the illness we call “a cold.”/

Lol, I didn’t think this would be a thing… but I would think in your statement that you would want a fix for the multitude of viruses that are considered “conmmon colds” right? That’s what I meant.

So you would want a global replacement.

s/is no common.*/are over 200 distinct viruses that cause the illness we call “a cold.”/

> There are over 200 distinct viruses that cause the illness we call "a cold."

Probably far, far more than that if you count the inevitable mutations that occur during replication.

It's a feature of how our language, labeling systems, and brains can only grapple with so many things. We rarely need to be so precise.

There are millions of human cells in your body right now that don't share "your" DNA [1] due to mutation or specialization (somatic recombination, Barr bodies, etc.)

We've known this since trying to apply species categories.

[1] "your" DNA becomes a population average sometime after fertilization.

Discrete classification of continuous phenomena is always going to be messy. Humans create discrete categories because they are useful to humans, but it's always important to remember the map is not the terrain.

what? nearly nobody's dying from the common cold. covid kills hundreds of people every day. how is fucking around with covid worth a common cold cure?!

Common colds push many people on the brink of death over the edge. But to your point, the years of potential life lost (YPLL) when that happens is minimal.

> Common colds push many people on the brink of death over the edge

Be nice if you could provide some backup cos I've not heard of this, or any idea how bad it is.

We don't know what would happen to humans when the immune system isn't challenged regularly. Especially in the younger years. It's just best to get a couple of colds a year and call it day. Or if you have kids like me, a couple of colds every month haha.

> or they have something they want to hide.

Indeed. I recommend this interview with Jeffrey Sachs, who headed Lancet's commision to investigate Covid-19.

https://infoproc.blogspot.com/2022/10/jeffrey-sachs-lessons-...

You may find your eyebrows a couple inches higher after listening :-)

No thanks, I'd rather trust virologists and the people who are doing the actual engineering. I don't trust directors/executives, by definition. They have ZERO idea about nearly anything, other than sounding confident.

Another interview that Jeffrey Sachs did: https://youtu.be/morj-3rdWwM

sibling throwaway youtube link to interview with Jeffrey Sachs should not be dead.

Disagree as much or as little as you see fit with him. Nothing there needs to be suppressed.

How did it get to be dead? Seems odd.

> Also it's not like this type of research helped us predict or even fight the pandemic. Millions have been spent on studying and modifying wild coronaviruses and it not only failed to predict this pandemic, but none of the research helped in anyway combating it.

I was under the impression this research was partly responsible for quickly identifying parts of the virus that are conserved in evolution, thus making them good targets for mRNA vaccines. If vaccine manufacturers had targeted proteins that have high rates of mutation, it would allow the virus to evade vaccine immunity faster, potentially making vaccines useless by the time they were actually rolled out.

The spike protein was selected because the virus was already well-adapted to humans and they assumed changes to the spike protein would make it less-fit and not able to infect as readily. They were wrong.

> If vaccine manufacturers had targeted proteins that have high rates of mutation, it would allow the virus to evade vaccine immunity faster, potentially making vaccines useless by the time they were actually rolled out.

This is what happened - the variant later named Delta was first identified in Oct 2020, long before the vaccines were released. If anything the vaccines helped it become the dominant one.

I guess I would have assumed the opposite? A virus that just jumped from bats to humans is expected to evolve pretty quickly in the binding domain as it “learns” to better target human ACE2. I thought the reason they targeted spike was that it’s on the surface of the virus and so an obvious target for antibodies to attach, whereas if you target some structural proteins deep inside the viral structure you’re taking a risk that the antibodies won’t be able to reach them.

The spike protein was selected because prior research into SARS and MERS showed that vaccines targeting the spike had the best immune response as compared to other proteins. They were aware it could mutate because the spike of SARS2 was different than SARS or MERS.

Also vaccines against the ancestral stain are still quite effective at preventing serious disease against every variant we've seen so far.

I don't know what point you are trying to make but you are basing it on incorrect information.

This is an important point. The research that, as I understand it (and IANAVirologist), helped jump-start the covid-19 vaccines was related to SARS and MERS, two coronaviruses that were already known to have infected humans, often lethally (and thus of urgent importance to study).

Nobody (that I know of) objects to virologists studying existing viruses such as SARS and MERS. If the researchers in the article had just been studying wild-type covid-19, well it still should have been in a highest-safety lab, but it would have been less objectionable than this. Labs which are below the highest level of containment, could and should be studying coronaviruses of the sort that cause common colds (there are 4 of them, as I understand it). Making new (or hybrid) ones is not something that any but the highest level of containment facilities should be allowed to do.

> Millions have been spent on studying and modifying wild coronaviruses and it not only failed to predict this pandemic [...]

Huh? Coronaviruses have been pointed out as a big area of concern for decades, at least.

What would you have expected as a prediction, exact date and time and genetic sequence?

If they had predicted it with any high degree of accuracy, many people would've considered that as proof that they caused it anyway.

The result of the research is very valuable. It helps predict the attributes of future novel strains.

In reality, infectious success and malignancy are highly anti-correlated, strongly. The combined Virus (which probably has existed in a very similar form in the wild somewhere!!) is actually a lot less dangerous than the two sources.

Also: Both Viruses have become a lot less dangerous to the world population because of immunity.

Why is that valuable? It takes weeks if not days to synthesize a vaccine for a new strain. It then takes months if not years, and massive investment, to test it for safety and efficacy. How the hell does shortening the weeks part of this at the expense of potentially requiring a new expensive test, in case the experiment leaks, make any sense?

Creating a vaccine was not the purpose of this research.

The problem with new variants is that it takes months to know how virulent and how transmissible it is. Such research enables better prediction from the point of detecting and sequencing such variants.

We know now that Omicron's spike protein is responsible for the better transmission and better immunological evasion. If we see a new variant with Omicron's spike protein, but modified, we can first of all tell it's going to be better at evasion. If there are changes in parts that are highly selected, it's probably more transmissive. If that part is less selected-for (there are ways to tell from the sequence) we have a clue that it is probably a little less transmissive. We also know that the spike protein is less associated with the virulence. Which means researchers have to keep looking for what makes the Virus deadly. This could lead to more effective vaccines and antibody treatments or even antiviral agents. Knowing which protein to target is half the game.

“Such research enables better prediction from the point of detecting and sequencing such variants.”

It’s good because the researchers word salad said it was good OK

> It helps predict the attributes of future novel strains.

Prove it.

I think the other part that is appalling is they did this in Biosafety Level 3 labs instead of 4 when COVID has basically brought the entire world to its knees for 3 years. What is wrong with the biosafety review committee?

Also, they completely skirted the NIAID approval process, putting the public at risk, will anyone see jail time for that?

This alone has convinced me, these scientists need to be investigated and punished for biological terrorism. This represents an insane lack of ethics. Did they forget, we've been in a multi-year pandemic lockdown.

> 1) talk about failure to read a room

The people most upset in the room are the same people who have been screaming that Covid was not a lab accident. I wonder why they would be upset at someone showing how easy it is to weaponize a coronavirus?

One of the worst "gotcha" takes I've read in a while. I'm sure people who believe covid was a lab leak are _also_ upset with this.

Try not to interpret everything around you with an us vs them lens.

Establishing the efficacy of a non-existent and artificial pathogen is useless on it's own. Like I bred this dog, and i know for a fact because of it's brown snout its lethality went down 20%. no you don't. it's a whole chimeric dna operation. not a binary tree.

Looks like there needs to be a criminal line drawn somewhere.

Around a decade ago, when Boston University was trying (successfully) to have its campus be the site of a BSL-4 lab, there were protests (articles, even outdoor demonstrations) -- over the risks of a lab leak of the world's nastiest pathogens, in an dense urban area.

In that dialogue, the public heard a lot about histories of safety incidents at other BSL-4 labs, which generally seemed due to negligence.

Today, given all the presumed awareness of lab leak risks, from the BU BSL-4 protests, and from the subsequent Covid pandemic-- I don't know why anyone at BU would risk modifying Covid without the utmost precautions, including at least using BSL-4 rather than BSL-3.

It seems stupid to have these sites in urban areas. If we want to do this sort of stuff, build the facility in the desert, with little population, little wildlife population, and environmental factors inhospitable to long lifetime if there is escape.

But I guess safety measures like that are too inconvenient.

Might be difficult to get people to work there.

Endangering billions of people because virologists prefer to be urbanite yuppies. Research so important that such a risk is accepted, but not so important that it would make sense to simply pay virologists 5x more to live somewhere remote.

This is madness.

Can't a lot of things automated and operated at distance?

After all we can do lab experiences on Mars, why not at 200 miles (300km) ?

So pay them a little more - enough that you can ask them to live there for 6 months at a time to reduce risk of pathogen escape as much as possible. If this type of dangerous research is actually valuable enough to keep doing, then it is valuable enough to implement protocols like this.

It's really not and is quite common. You keep the site out a ways have workers show up and then bus them out to the site. You only have to keep the site where you are doing the work way out there and so people can do their regular non lab related work closer to home.

It's a really common practice. I live near a national nuclear research lab and they do that. I also grew up near an ICBM building and designing facility and when they needed to run tests they drive several hours out to the west desert to do things just to be safe.

It's not that uncommon or inconvenient, and makes a hell of a lot more sense then just slapping it in the middle of a major metro area.

Seriously we've got tons of land out west that is about a million miles from everything let's use some of that.

One difference is the bussing may need to be combined with a quarantine period which wouldn't be necessary with nuclear or chemical research.

Would it though? I mean, I am assuming there aren't quarantine procedures right now. You'd just have to make sure you have appropriate disinfectant/decontamination guidelines.

Heck just require decontamination as you leave the lab and as you get off the bus, two times makes it more safe, and I'd imagine a 40 minute bus ride through the sweltering west desert heat in direct isn't an environment that microorganisms my flourish in.

Plus that's easy to do to if there is a quarantine period, out people on shifts of 5-7 days on site, one week off. That's what they do for the oil rigs, plenty of people live like that, it isn't easy, or cheap for the company but a global pandemic that locked down countries shattered supply chains and wreaked havoc with the global economy was a hell of a lot more expensive.

"Plus that's easy to do to if there is a quarantine period, out people on shifts of 5-7 days on site, one week off."

Exactly.

"have appropriate disinfectant/decontamination guidelines."

Yeah... it seems there have been some issues with people consistently following them. At least with the quarantine you have some defense in depth in case the procedures in the lab failed. (I think a woman in Fance died doing prion research. Why? Because she violated multiple protocols. I want to say she didn't even report it at first, but I could be wrong. And this isnt even a true infectious disease)

It's not like a monkey coughs out the window and we get a pandemic. The spread is to the workers in the lab and then to the general public. The location of the lab doesn't really matter if the workers still live in cities.

Somehow they make this sort of model work for various classified work in places like NM (although population centers have grown around them due to their size and support requirements). I don't see why something similar can't be done for this. Plenty of Government land in those desert areas out west too.

A significant number of military bases operate like this. Edwards and China Lake are great examples. Los Alamos. Even Fermi. Cities developed around these areas over time, but they once were only military/gov projects.

Yeah frankly I can't think of a more dangerous thing humanity could be doing than biological research on infectious diseases in population centers.

Even doing chemical processing in cities is safer since you're only risking the immediate area.

When I was in medical school, I heard mentioned that Galveston, TX was chosen for a BSL4 laboratory in part because it was an island, and if something bad happened the US could blow up the bridges and quarantine the island.

No worries about Hurricane induced lab leak?

Worse yet, before the pandemic there was more political pressure to regulate and discuss the risks of such research. Now it feels like politicians are afraid to even discuss it. Places like NYT used to occasionally post articles like https://www.nytimes.com/2012/03/04/opinion/sunday/the-truth-... and https://www.nytimes.com/2012/06/22/health/h5n1-bird-flu-rese... but now you will never seem anything like this published. It is as if the concerns over lab accidents has all but disappeared!

For one itemization of a lot of the concerns at the time, here's a Massachusetts Nurses Association statement, dated 2005, from their perspective:

https://web.archive.org/web/20101125034813/https://www.massn...

> I don't know why anyone at BU would risk modifying Covid without the utmost precautions

My wife was a laboratory inspector for a while. She'd come home with the craziest stories about how such-and-such lab tried to get away with this or that. I'd have the same question every time. "Why?!" Protocols only work if they're followed. We have such a long history of disasters, major or minor, because of negligence[0]. Cutting corners, operating outside the envelope, etc.

She'd always just shrug and say, "familiarity breeds contempt".[1]

[0] My favorite is Chernobyl.

[1] Also, a lot of scientists have this, "I know what I'm doing" attitude and see safety precautions as holding them back. It doesn't help that most of them see grad students as expendable.

>[0] My favorite is Chernobyl.

Biology is different to physics or chemistry. The worst nuclear accident can kill a few million people. The worst chemistry accident can kill a few hundreds of thousands of people. The worst biology accident can kill _everyone_.

I'm not sure I agree on the numbers, I have a hard time seeing a nuclear power accident leading to millions of dead. That said, the sentiment rings true. If we get the right mix of incubation time, reproduction numer and CFR in a novel virus, we are catastrophically and civilization level screwed. It's unbelievable how eg nuclear fission research has ground to a halt whereas GoF research on Covid(!) in a damn BSL-3 lab can be approved after what we just went through.

I didn't say it was worse. I said it was my favorite.

Yes, but if we can't attract the world's foremost virologists to programs that we have some degree of control over in the middle of international cities where they can engage in serial passaging of airborne HIV in the morning, and then get lunch at places that are trending, authentic and cutting-edge, then they'll just go to a program in another country that doesn't have these restrictions.

No-one wants to live in an underground facility for weeks or months at a time when they could be making the most of living in a major city, not even virologists working on pathogens that are being modified to see what would happen if there was a pathogen whose evolution was guided in a particularly interesting direction and compressed from decades to weeks or even days.

Anyway, if we were to ask the world's foremost experts in the virological community whether we should restrict such research to carefully-controlled remote locations subject to stringent controls, long quarantines and strict oversight, then we might find that the answer was similar to when we asked "is if likely or even within the realm of possibility that SARS-CoV-2 originated from a lab in Wuhan as result of Gain-of-Function research". And they might insist that we listen to them because they were the experts, and they would probably find a lot of support in the government and the media.

Many people seem to believe that lab leaks are exceptionally rare: https://en.wikipedia.org/wiki/List_of_laboratory_biosecurity...

That page offers "only" dozens of examples in recent times, but that is certainly going to be non-exhaustive and the potential magnitude of impact of a single of these incidents is difficult to overstate. Notably while the biosafety levels for each leak are not stated, at least two came from BSL-4 labs - the highest safety standard there is.

Covid has killed something like 20 million people (taken from Wikipedia, estimated based on excess deaths). It's plausible that it came from a lab leak. How bloody fucking valuable do you have to think "making viruses more deadly and studying them" is for this to be worthwhile?

Oh, actually you can calculate this, assuming you're utilitarian and think risking innocent lives is OK as long as it saves that many lives in expectation. If you think there's a 10% chance that Covid came from a lab leak, then the "making viruses more deadly" research that we've done so far ought to have saved more than 10% * 20 million = 2 million people. Did it? From what I've heard it's done fuck-all.

I stand by my pissed off voice here. I think it's appropriate to be pissed off about risking millions of lives for hypothetical benefits.

(To be clear, I'm only talking about research that studies deadly extinct viruses and deadly lab-created viruses. We should absolutely continue to study viruses in general.)

It’s taken 2 years for logic to finally overcome political polarization and you can now express a logical opinion without being removed from the internet! Progress.

I don't think it ever went away. You see people getting massively flagged or downvoted and called "Republican" for going against the grain everyday here on HN.

What makes you think it's easy to distinguish "studying viruses in general" from "making viruses more deadly"?

I'm happy to listen to expert virologists tell me about how they could advance the field without modifying/running viral code. Maybe they're a hell of a lot better at their job than most software types who rely on that. I suspect that's not how it works, though.

And hey, let's do more arbitrary probability space exploration! The Lancet says almost 20 million people have probably been saved by covid vaccinations[0]. If toying with viral DNA|RNA helped produce 10% of the research contributing to that, and/or any additional margin supporting other interventions, then I guess it fits your people-saved profile.

[0] https://www.thelancet.com/journals/laninf/article/PIIS1473-3...

You're conflating two different things: (i) toying with DNA/RNA, and (ii) gain of function research into human viruses.

By all means, let's advance DNA/RNA and virus research. But can we carve out a little hole for purposefully making human viruses more deadly? Like: accidentally making human viruses more deadly, OK; purposefully messing with human viruses but not making them more deadly, OK; purposefully making mouse viruses more deadly OK; purposefully making human viruses more deadly NOT OK? How is this a big ask, when lab leaks are a thing?

The Wuhan lab was doing gain of function research into Coronaviruses. Isn't that exactly what should have been helpful for Covid, if gain of function research is ever helpful for anything? But so far as I've heard, the Wuhan research didn't help with Covid at all.

So kinda funny to use "saving lives from Covid" as an example of gain of function research being useful when (i) Covid itself may have been caused by gain of function research, and (ii) so far as I've heard gain of function research hasn't helped with vaccinations at all (please correct me if I'm wrong on this).

> You're conflating two different things: (i) toying with DNA/RNA, and (ii) gain of function research into human viruses.

If you've got some kind of model where these are in fact two entirely distinct things, that would explain some of the confusion in your position.

"any selection process involving an alteration of genotypes and their resulting phenotypes is considered a type of Gain-of-Function (GoF) research, even if the U.S. policy is intended to apply to only a small subset of such work."

https://www.ncbi.nlm.nih.gov/books/NBK285579/

Perhaps do some reflection on why you've latched onto the phrase "gain of function" and if you really understand what professionals mean by it.

> Like: accidentally making human viruses more deadly, OK

The prep for "accidentally more deadly" is going to be necessarily the same as "we're certain it will be more deadly," and in practice lots of viral research is probably "middling probability something deadly could happen."

> But so far as I've heard, the Wuhan research didn't help with Covid at all.

Where are you getting this high-level graph of coronavirus-related knowledge tagged by origin of research clearly showing a lack of contributions from Wuhan?

> Covid itself may have been caused by gain of function research

Or it might have simply been lab-escaped SARS coronavirus, making its way through an adaptation path.

Or it may have been entirely caused by constant unceasing unimaginably well-resourced natural "lab" of the world that would inevitably have produced something like it at some point, and absolutely will inevitably produce something like it again.

Suppose that a lab created a novel virus, which then leaked and killed 2 million people, including making you very sick so that you had difficulty breathing for a month and killing someone close to you. If that happened, might you conclude that maybe we shouldn't mutate deadly human viruses in the lab? Or at least, that the burden of proof that that research is worth millions of lives should be very high?

A lot of people died from Covid; there's a good chance it was due to virus research; even if it wasn't it certainly could happen in the future; I don't want them to have died in vain.

Point taken about the meaning of GoF, thanks.

Some snippets:

The spike protein of an Omicron version of SARS-2 was fused to a virus of the Wuhan strain, the original version that emerged from China in 2020. The goal was to determine if the mutations in the Omicron spike protein were responsible for this variant’s increased ability to evade the immunity to SARS-2 that humans have built up, and whether the changes led to Omicron’s lower rate of severity. The testing actually showed, though, that the chimeric virus was more lethal to a type of lab mice than Omicron itself, killing 80% of the mice infected. Importantly, the original Wuhan strain killed 100% of mice it was tested in. The conclusion is that mutations in the spike protein of the Omicron variant are responsible for the strain’s ability to evade immunity people have built up via vaccination, infections, or both, but they are not responsible for the apparent decrease in severity of the Omicron viruses.

If it went from 100% IFR (original strain) to 80% IFR (Original + Omicron spike) how did it not reduce the severity? Sure it's more severe than Omicron by itself so there were other factors as well, but it does seem like a decrease in severity to me.

Because it has Omicron's increased ability to avoid people's immunity. That would result in higher infectivity than just a copy of the wuhan strain, with near the same severity. Note that earlier Sars viruses had even higher severity than Sars Covid 2 (Wuhan strain), but weren't as infective and killed far fewer people. Which implies that a slight reduction in severity for a gain in infectivity is not a worthwhile tradeoff.

Exactly, for example Ebola has a mortality rate of around 50% but has only killed around 11 thousand people, SARS-CoV2 has less than 1% can has killed 20 million or more. Wild viruses like SARS1 and MERS are poorly adapted towards humans when the spillover happened making it possible to be contained. But SARS2 a which is a Sarbecovirus a family of gastrointestinal viruses some how was able to bind towards human airways with a binding affinity 20 times that for humans than for bats, all while leaving no traceable trail of mutations that researchers could trace back to the intermediate host.

For context with SARS1 and MERS researchers were able to find the spill over animal within a few months. But after 3+ years we have yet to find an intermediate animal host. Also before anyone says "It took years to find the source for SARS1", but that is for the original bat virus, the intermediate animal where the cross over to humans happened was found within months. Additionally SARS1 and MERS had a rapid period of mutations as it adapted towards humans which allowed researchers to trace back to the source.

You're confusing "severity" and "infectivity". Increased infectivity is not increased severity. The evidence they have shows reduced severity and an unknown (but theorized increased) infectivity.

Errorbars, probably. 80% and 100% might be samples of a true death rate of 90%.

Indeed, beware of round numbers, they tend to indicate very low sample size and very large error range.

The researchers could not be sure of this result before they did it, which is why I believe there's a reasonable case this should be considered GOF work even if the lethality of their chimera (in hu mice) was ultimately less than that of original strain.

Furthermore, strictly speaking I don't believe we know the actual severity of this in humans. While it's possible to make a fairly confident guess, surprises are still possible.

This involves testing the Omicron spike on a Wuhan-Hu-1 backbone.

Damn near every single person in this comment thread has antibodies and T-cells to Omicron spike and everyone naturally infected has T-cells for the original strain as well because T-cell epitopes aren't immune escape targets.

Chances of this "escaping" the lab and producing another coronavirus wave are zero because that already happened.

Like Derek Lowe pointed out nature already did a similar experiment with an Omicron spike and a Delta backbone because coronaviruses undergo recombination naturally:

https://www.science.org/content/blog-post/gain-function-not-...

Nobody has heard of the XD strain because there was so much immunity to it that it never really went anywhere.

> Chances of this "escaping" the lab and producing another coronavirus wave are zero because that already happened.

Are you aware of any situation where the omicron spike and Wuhan backbone could have recombined naturally? As far as I know, the latter was extinct in the wild by the time the former emerged.

It's good that the omicron/delta variant didn't blow up in humans. The omicron/Wuhan variant seems like another throw of the dice, though, and even a very small probability times millions of potential deaths is significant.

You didn't read carefully what I wrote.

The T-cell epitopes in all strains of SARS-CoV-2 are not subject to immune escape and there are thousands of them. Even the neutralizing antibodies to Wu-Hu-1 spike will cross react with omicron still.

Nobody at this point is immune naive to this combination.

And the most recent pandemic strain of SARS-CoV-2 was Omicron. If this Omicron spike containing virus escaped into the wild then it will encounter a human race with substantial neutralizing antibody activity to this exact spike protein sequence.

And there isn't any "but maybe by splicing them together it literally changes everything, you can't possibly prove that isn't true" argument. This isn't science fiction. Inside the cell all of these proteins are diced up into small hexamers and displayed on MHC and it doesn't matter what the combination of the spike and the backbone are, the T-cell epitopes are going to be the same. Omicron spike will have Omicron antibody epitopes and Omicron T-cell epitopes, doen't matter what backbone you splice it onto. If you want to create a new pandemic, particularly one with "millions of potential deaths" you need to change this virus sufficiently that it is no longer identified as SARS-CoV-2 by our T-cells and you don't get that just by combining two different variants.

If that's your argument, then what do you even need the XD strain for? You could simply assert that because natural omicron has spread widely, any lab chimera with the omicron spike must be safe. That seems remarkably cavalier though, considering that (a) natural omicron continues to spread, and kill people every day; and (b) while China's reported case counts are probably inaccurate, they probably do still have a large population that's completely omicron-naive.

I clearly didn't need the XD strain, I thought that would be read as supplementary.

I routinely forget that no matter how clear your argument sounds to you that someone on the Internet will always misunderstand it (and pick apart a detail that has no central relevance).

Except that natural omicron continues to kill people now? So it's empirically true that at least one backbone (i.e., the natural omicron backbone) plus the omicron spike remains able to cause significant sickness and death, despite the immunity we've built up, even outside China. So what's your argument that the risk from a different backbone is "zero"?

Yet more misunderstanding.

First of all they used BA.1 and that spike is nearly extinct and isn't causing much sickness and death, it has been out-competed by BA.5. BA.1 is literally "last years news" and BA.5 is immune evasive against BA.1. Any BA.1 spike is going to be recognized by the same neutralizing antibodies which has suppressed BA.1 circulation in the larger population.

And I should have written something like the additional risk over the existing circulating pandemic strains is zero. It could cause infections and deaths, but just like XD it would be outcompeted quickly by BA.5 and wouldn't go anywhere, and the infected people would run exactly the same risk as they would have against the existing global pandemic. There is no way you get from this lab experiment to "COVID-22", it is still all the same virus, same pandemic, and a variant of the virus which will be substantially less fit against population immunity than BA.5 or whatever new variant winds up circulating this winter.

So you're acknowledging now that the lab chimera might infect some people if it escaped, but you're saying that's okay because those people would otherwise have gotten infected with a natural variant anyways? But if the IFR for the lab chimera is higher than the IFR for natural omicron (which it was, at least in their mice), then those people are paying a higher price in mortality for the same immunity--that's the gain of function of concern.

And really, is there anything in biology that we know with sufficient confidence to risk millions of lives in exchange for no immediate practical benefit? Like I guess whoever did the 1977 flu vaccine trials also assumed that if their virus escaped, it would get outcompeted by the existing natural viruses; but we know what happened there.

You and Derek Lowe are at best apologists who due to your myopic perspective can’t see the obvious risks that many of us outsiders can imagine. At worst you’re part of a group for which “it is difficult to get a man to understand something, when his salary depends on his not understanding it”

If I wind up rotting in hell with Derek Lowe that'll be pretty good company, I think I'll take that.

>Nobody at this point is immune naive to this combination.

My mother did not get vaccinated and she probably was not infected

She's got less to fear from this lab experiment (based on variants that are existing or nearly existing) than from the ongoing natural pandemic.

> As far as I know, the latter was extinct in the wild by the time the former emerged.

Omicron isn't a descendant of Delta. It has an odd lineage that couldn't be explained and (unless new info has come up since I last looked) it was likely a descendant of either Wuhan or Alpha that mutated hidden from most of the world - one of the theories was that Wuhan/Alpha jumped to rats, then back to humans after becoming Omicron.

I agree, but I don't think that's relevant? So I think my terminology was unclear. By "omicron/delta" I meant a recombinant of the omicron spike with the delta backbone, the one that apparently happened naturally and Derek Lowe describes as the XD strain. By "omicron/Wuhan" I meant a recombinant of the omicron spike with the Wuhan backbone, which these researchers created in their lab (and I don't believe had any opportunity to occur naturally, since the two lineages never existed simultaneously).

> since the two lineages never existed simultaneously

Some version of it would likely have existed in the rat-origin theory of Omicron as an intermediate stage, is what I meant.

Ah, got it now. Then I guess the rats (or other cryptic hosts in which omicron evolved) might have been exposed to the omicron/Wuhan recombinant, but not humans.

> Damn near every single person in this comment thread has antibodies and T-cells to Omicron spike and everyone naturally infected has T-cells for the original strain as well because T-cell epitopes aren't immune escape targets.

Checking my layperson understanding by trying to make a dumbed-down version:

"The outside of the new virus is stuff almost everybody's immune system should already be primed to seek and destroy, preferably before it hits a human cell. Even if it does hit a human cell, the inside stuff is old/simple enough that your immune system should easily recognize that the cell is infected and swollen, and kill it quickly too, there are no false everything-is-fine-here tricks."

Correct.

See for example:

https://journals.asm.org/doi/10.1128/mbio.03617-21

"These data suggest that virtually all individuals with existing anti-SARS-CoV-2 CD8+ T-cell responses should recognize the Omicron VOC and that SARS-CoV-2 has not evolved extensive T-cell escape mutations at this time."

https://www.nature.com/articles/s41423-022-00838-5

"Although the Omicron variant escapes neutralizing antibodies induced by COVID-19 vaccination or natural infection [1,2,3], our current analysis demonstrates that T cell epitopes are considerably conserved in the Omicron variant and that substantial proportions of memory T cells elicited by COVID-19 vaccination or natural infection respond to the Omicron spike. These results indicate that memory T cells may provide protective immunity during reinfection or breakthrough infection with the Omicron variant."

Here's a review of all the SARS-CoV-2 T-cell epitopes:

https://www.sciencedirect.com/science/article/pii/S193131282...

"Here, we focus on a specific topic: our current knowledge concerning the definition and recognition of SARS-CoV-2-derived T cell epitopes in humans. While the data related to this topic was initially sparse, 25 different studies have now been published as of March 15, 2021 [...], which collectively report data from 1,197 human subjects (870 COVID-19 and 327 unexposed controls), leading to the identification of over 1,400 different CD4 (n = 382) and CD8 (n = 1052) T cell epitopes."

And I'd highly recommend this video on the adaptive immune system, along with the whole rest of the series:

https://www.youtube.com/watch?v=dXL2TvhNqZI&list=PLGhmZX2NKi...

(I think that covers how proteins get chopped up by proteases and then those short epitopes are displayed on MHC receptors and undifferentiated T-cells learn to identify them)

How there isn't a full on worldwide ban on this now is just beyond me. Our hubris and overconfidence could kill millions more.

It may very well be riskier than not to ban research like that on an endemic airborne virus that has shown a proclivity to mutate.

If no humans are running controlled experiments on the virus, there is still an experiment currently being run as a massive, randomized trial in the form of the natural mutative processes the virus undergoes in the infected human population. How much do we want to trust that it won't hit upon an HIV-category combinatoric mutation before we're aware it has the potential to do that?

The risk tradeoff is difficult here, but we should keep in mind that the risk of doing no such research is way, way higher than zero.

I find this very frustrating. If COVID-19 was a lab leak - wether it had involved gain of function related or just unwisely moving viruses from the animal kingdom into human spaces - what good did any of it do?

Apparently our ability to create vaccines doesn't hinge on messing around with the viruses before they infect humans. COVID-19 vaccine was created after the fact, and it hardly prevented a major global catastrophe.

I just don't see the argument. It sounds like pure imagination - by making viruses more dangerous or increasing the odds we'll expose ourselves to novel ones, someday we'll have the technology to prevent any pandemic. How many millions of lives lost and trillions of dollars wasted before that happens? When is it just not worth it? It seems not worth it to me now.

If it's a bioweapons program, I don't see why we need to be playing along. It's not like nuclear deterrence - someone releases a weaponized virus, the whole world gets infected. It's like a nuke that blows up the entire world.

> Apparently our ability to create vaccines doesn't hinge on messing around with the viruses before they infect humans.

The COVID vaccine built heavily on previous research with flu,. Zika, rabies, and cytomegalovirus.

> The COVID vaccine built heavily on previous research with flu,. Zika, rabies, and cytomegalovirus.

All viruses that are already around. Agree that creating novel viruses is not with the risk.

Additionally, in the same way a banana would never occur in nature, many of these experiments researchers conduct are extremely unlikely or out right impossible. For wild viruses crossing over to humans it needs to go through many mutations and people before becoming adapted and highly infectious towards humans. But in a lab you can insert the exact mutation to make it highly infectious towards humans without having to mutate. For example right now the bird flu which can infect humans who have ingested bird droppings, but it can't spread human to human.

The conditions in the lab are just so artificial the predictive power is practically worthless, especially when you consider the massive possibility space. Just like you'd never find something like a banana evolve to it's current state in the wild, you would won't find these viral chimeras just popping up out of no where.

Remember this?

"H5N1 is a type of avian flu virus that occurs naturally in various types of birds but has surfaced in humans in the last ten years. Although human cases of H5N1 are rare, the virus has a 60% mortality rate."

"They reasoned that it'd be better to tinker with H5N1 in the lab and gain knowledge for its prevention than sit back and wait for mother nature to concoct a human-friendly strain. Both teams of researchers artificially mutated H5N1 to spread easily amongst ferrets. Ferrets are commonly used as stand ins for humans in influenza studies. To clarify what I mean by "easily" spread, at the end of Fouchier's study the strain had gained the ability to transmit through the air- an unprecedented feat!"

https://www.nature.com/scitable/blog/viruses101/avian/

The other thing too is that were just going to do ACE2 receptor research from now til the next pandemic, which I'm sure will have NOTHING to do with ACE2.

The treaties in place to restrict biological weapons have exclusions that permit the development (and use) of incapacitating agents. The DoD/NIAID/Daszak/Fauci model has been that a hostile nation would release a biological weapon that would compromise the ability of members of the Armed Forces to engage in combat operations over a period of months or years, and to address this they had planned to be able to quickly marshal a new transfection to induce neutralising antibodies [in the relevant groups before they were deployed to combat zones], hence the focus of research into these particular areas from the defence establishment and its partners over the last few decades.

Thank you. This is the first time I've seen a true steelman of the pro-GoF poisition.

I would say that viruses, like a lot of other aspects of life, are chaotic and capricious both in their evolution and their affects on an individual humans (COVID really drove that home for me in that it killed some and was asymptotically carried by others).

But we demand explanations where there are none, and so we create them ourselves or accept them from others.

If the increased focus on mRNA vaccine research due to the COVID outbreak leads to successful new anticancer therapies, we could make up for the COVID death toll in a hurry, and benefit enormously from subsequent availability.

In no event is "don't research this, it's too scary" ever the right answer. The question is how to do it safely. For instance, I don't understand why gain-of-function research is less regulated than, say, nuclear research. The work needs to happen, but our risk assessments are hopelessly out of whack.

The pandemic forever cured me of my willingness to participate in Trolley Problems. I would say harming people over some vague future promise of helping them is, from this point forward, always the wrong decision.

> COVID-19 vaccine was created after the fact, and it hardly prevented a major global catastrophe.

What? It immediately dropped the death rate. How many more millions of lives would it have to have saved to get notice?

Knowing about the virus ahead of time wouldn’t help much. By far the most expensive (in time and money) part of a publicly available vaccine is testing it. It is impossible to test a vaccine under any reasonable procedure we have today before the virus is a full blown pandemic.

The best case scenario for putting this kind of research into practice is saving two weeks off a months or years long development schedule. It might not even work. Frankly the risk reward trade off here is so laughably bad that I can’t understand why it’s even a debate.

Ah! I read the parent's comment in a different way, but i see what he was trying to say now. He wasn't saying the vaccine didn't do anything, but that not having it developed before covid19 started wasn't the biggest blocker.

> Apparently our ability to create vaccines doesn't hinge on messing around with the viruses before they infect humans. COVID-19 vaccine was created after the fact, and it hardly prevented a major global catastrophe.

I don't think you can make that conclusion. Sure we didn't make the vaccine before covid existed. But virology research in general certainly builds the body if knowledge required to synthesize vaccines.

Did the Wuhan lab research help the covid vaccines? Maybe not, but it's really _really_ hard to know ahead of time which avenues of research will yield breakthroughs.

The current pandemic was probably caused by such research. But even if you don’t believe that it was probably caused by it, a reasonable person and can admit it was possibly by it. Multiply that “possibly” out by 6.5M deaths or so and that’s your research death toll.

So 1% chance of lab escape? 65,000 deaths. Weigh that against your hypothetical benefits of performing the research and I think it’s hard to conclude that such research is wise.

The 1918 flu involved no lab leak and killed [edit]: 50 million people.

I don't care for the game of fatality calculus, but if one is going to play it, that's the enemy humanity is up against.

Your counterexample would need to be a positive instance, not “other bad things also happen” and that evidence would also need to be strong! Chemotherapy has many terrible side effects but it helps kill cancer! With high certainty!

You wouldn’t subject people to chemotherapy if you lacked any evidence that it was helpful.

I thought it was more like 50 million?

Thank you and good catch; I quoted the infection number where I meant to quote the estimated fatalities.

Yes, but how has the millions we have spent on collecting and modifying wild coronaviruses helped us with this pandemic. Despite over 100 years of technological advancements and the virus is still impossible to stop! So why do we want to risk creating new viruses when the decades of research has proven to be such a colossal failure?

> impossible to stop

I don't think one stops a pandemic; IIUC, one gets out in front of it with vaccination. Which we did, thanks to previous mRNA research conducted on other viruses. GOF research is one of the few ways we're aware of to get out in front of vaccinating viruses that don't yet exist but are probable to exist.

This argument treads suspiciously close to "Sometimes people use fire to burn a house down, so why do we allow cooking? People should only be allowed to use naturally-occurring fires and not create new ones."

And what is the probability that out of the thousands of viruses we identify the exact one that mutates in the exact manner as researches induce in the lab? The possible mutations a virus could take are astronomical, and conditions in a lab using humanized mice models are not something that would ever happen in the wild. Efforts are better spent on surveillance not prediction! https://media.nature.com/original/magazine-assets/d41586-018...

Your article actually argues in favor of the type of research BU was doing because it's being done post-outbreak: "Once an emerging outbreak virus has been identified, it needs to be analysed quickly to establish what type it is; which molecular mechanisms (such as receptor type) enable it to jump between individuals; how it spreads through human populations; and how it affects those infected In other words, at least four kinds of analysis are needed: genomic, virological, epidemiological and clinical.". BU's work is in the genomic and virological categories and addresses the kind of questions the article wants addressed as part of a surveillance strategy.

The article strongly opposes making predictions of whether a pathogen will be pandemic because predictions are a rigged game. There are enough factors that you are very unlikely to be correct, and even then a true positive combined with successful mitigations erodes public trust because "the severity of the virus had been overblown". Geologists avoid making predictions of volcanic eruptions or earthquakes for similar reasons.

It is not directly opposed to study of pre-pandemic animal pathogens: "Surveys of animals will undoubtedly result in the discovery of many thousands of new viruses. These data will benefit studies of diversity and evolution, and could tell us whether and why some pathogens might jump species boundaries more frequently than others." This makes sense, because study of pre-pandemic pathogens is needed to set a foundation such that the post-outbreak analysis the article wants us to focus on can be completed in a reasonable time frame.

The article is arguing for rapid response and against predictions. It's not opposed to basic research of pathogens, and actually supports this specific type of research.

mRNA research was mainly developed to fight cancers, not viruses. To the extent that it was already being researched to stop viruses, it was being tested on existing viruses, not GOF-modified ones.

Well you have to include excess deaths which is at 15M or higher. The reason is that even if you are including drug overdoses, the pandemic was still a catalyst for homelessness and... excess deaths. Covid is still responsible.

I think there's a difference between studying existing viruses, or even their natural mutations, and engineering a virus to be more potent (and not in the highest level lab even).

These "convergent mutation" variants seem to be arriving at a rapid pace, all by themselves without researchers helping (some hypothesize this is due to virus replication in immunocompromised patients.) [1] Since these mutations seem capable of repeatedly emerging, we should understand what they do, both alone and in combination. The cost here is that yes, researchers could make and release a new deadly variant. On the other hand it's just as likely that something very similar will pop up through natural evolution in the next few months. When that happens we can be clueless or we can be armed with knowledge.

[1] https://www.fiercehealthcare.com/payers/preliminary-data-poi...

And how did our decades of Coronavirus research help us prevent/fight this last pandemic? Given the fact it was already known at the time that the spike protein on SARS2 was what researchers have been using to attach to wild viruses so infect humanized mice/cell cultures via the ACE2 receptor we should have already known that Airborne H2H transmission was possible!

> And how did our decades of Coronavirus research help us prevent/fight this last pandemic?

IIUC, the vaccine was synthesized in record time, was it not?

the MRNA vaccine had nothing to do with the research involving modifying wild coronaviruses. The technology was originally built independently and for different reasons, but there was a MERS vaccine they developed and modified for SARS2, but again that was for an existing known virus. The type of research Ecohealth conducted contributed absolutely nothing to the development of the vaccine.

In fact Ecohealth didn't even share their research of any data with anyone since the pandemic began. So the value of the risky research is dubious.

We've had very little GoF research, in large part because it's controversial. There have been several outright bans, and the issue is so emotional that many scientists probably avoid it just because the costs are high.

I am not necessarily in favor of GoF research, but I recognize a broken argument when I see one. In the face of a clear policy preference to dissuade GoF work, the question "why didn't [the very limited GoF work that we allowed to take place] produce huge numbers of beneficial results" isn't really an interesting question about the usefulness of the research, since it might just as easily reflect a (known) pre-existing policy bias.

We're in a rapidly-developing new era and have just seen clear evidence of how devastating a pandemic can be. The question we should be asking is whether we're using every tool at our disposal to defend ourselves from the next one, and that requires some careful and dispassionate weighing of risks/rewards. The arguments I see don't meet that standard at all.

On what? Virus research?

Biology research gives me nightmares. For the low price a an undergraduate degree and a few tens of thousands of dollars you can build a garage lab which can make something like covid in your spare time.

In physics and chemistry you at least have to work hard for your WMD. In biology you get them for free because you're not careful enough.

"There is a lot of evidence that points to the virus spreading from a wet market in the city"

Spreading, yes. Originating no. Note:

This article uses two preprint papers one of which was changed before publication and the other doesn't support zoonotic origin:

https://www.science.org/content/article/do-three-new-studies...

This is an interesting case, making chimeras can always be thought of as "gain-of-function" research because you really only know if you succeeded after you've created and tested the new organism, and there might be failures along the way if indeed creating a more lethal organism is your goal.

In this case there is some handwaving about 80% mortality vs 100% mortality in a mouse host about it technically not being more lethal than the original. But what if the testing revealed 100% mortality plus some other metric of increased transmissibility or something similar after the fact. It would've been unknown to the researchers at the time of synthesis and fit every definition of "gain-of-function" research.

I think in light of this inability to know apriori if a virus is going to be more/less lethal we're splitting hairs when we say this is not technically "gain-of-function" research.

Exactly. Lowe is using a really horrible argument, he is trying to use the results to justify the experiment, but the entire point is it was an experiment and they had no idea how it would turn out. It’s entirely possible it could have been 100% as the result and that somehow this chimera found a spike mutation that provided human immune escape and a lab worker was accidentally infected as patient zero. It’s not what happened obviously but the idea he can use the experiments results to justify the experiment is absurd. He is a dangerous apologist, “it is difficult to get a man to understand something, when his salary depends on his not understanding it”.

It's unfortunate because I like reading Lowe usually, but these pieces that obfuscate and explain to us how we should feel about something so obvious is telling.

IMHO the real question is why would we do this? Just because we can? Is there a hidden bio arms race we can’t stay away from?

> The goal of the research was to determine if the mutations in the Omicron spike protein were responsible for this variant’s increased ability to evade the immunity to SARS-2 that humans have built up, and whether the changes led to Omicron’s lower rate of severity.

Yes, but it's not hidden.

On the one side of it: humanity, and our ability to explore, comprehend, and modify the reality around us.

On the other side of it: naturally-evolved viruses. They have a couple billion years' practice overriding biological countermeasures and massive territory advantage. If we do nothing, odds are they will eventually mutate into something that drops us dead in our tracks or wrecks us slowly, as they have before (smallpox, 1918 flu, HIV). And in our modern, deeply-interconnected world, geographic defenses and population isolation no longer protect us as they did our ancestors.

The main tools we have to avoid this are our ability to explore, comprehend, and modify. The capacity to change something and observe how the change affects it is something the viruses cannot do, and arguably our best chance of "outsmarting" them so that when they naturally mutate into a dangerous form, we already have the tools in place to mitigate or disassemble the danger.

Exactly how does modifying the virus help create prevention measures or treatments for it? Please provide real world examples.

The most banal reason is that groups of researchers generally coordinate to set up little bureaucratic power centers within the national research agencies to ensure themselves a steady stream of grants; this in turn allows them to get tenure at their universities (under 'publish or perish' which more practically means 'get your grant renewed or perish' and grant renewal relies on (1) a steady stream of publications and (2) ensuring the federal agency keeps earmarking funds for your area of research).

This is all perhaps well and good if you're fighting for funds for studying, say, childhood leukemia, but in this case it's been a major disaster and has almost certainly played a central role in this recent global pandemic. Oops.

Some people get a kick out of 3D printing guns in their garage. Why not apply that to other weapons?

No one is 3d printing ballistic nuclear weapons. Scale matter?

If you use weapons-grade plutonium as the feed stock for your 3D printer, you won't live long enough for the scale issues to stop you.

Unlike those who print guns, I don't think virologists are motivated by spite for politicians.

I don't see any reason there would be correlation in those qualities. But it's more that I think that advances in technology will eventually democratize biological weapons in ways that 3d printing have democratized the production of small arms.

Virologists at academic centers like BU are beholden to their paymasters. Grant-writing and groveling day in and day out. I'm not sure what feelings develop in that endless loop of futility.

Yes, there is an arms race, an all-arms race of which bio is only a part. I reccomend the following two books, The Sheild of Achilles: War, Peace, and the Course of History, and The Shadow World: Inside the Global Arms Trade.

The revolution in technology has shifted the global array of national security threat models away from just the nation-state. The low barrier to entry to tech like the latest in bio or cyber research means now a single actor with no grouo or state affiliations is now capable of producing some destructive event on a national or even global scale.

On the backend, this is one of the quiet whispers in the halls of power in DC as a justification for the surveillance systems being enabled. You ask if there is an arms race. No, there are many arms races going on right now.

Just like nuclear, if its possible they will consider building it, potential side effects be damned, as long as we have some force multiplier the "enemy" doesn't.

87. Science and technology provide the most important examples of surrogate activities. Some scientists claim that they are motivated by "curiosity" or by a desire to "benefit humanity." But it is easy to see that neither of these can be the principal motive of most scientists. As for "curiosity," that notion is simply absurd. Most scientists work on highly specialized problems that are not the object of any normal curiosity. For example, is an astronomer, a mathematician or an entomologist curious about the properties of isopropyltrimethylmethane? Of course not. Only a chemist is curious about such a thing, and he is curious about it only because chemistry is his surrogate activity. Is the chemist curious about the appropriate classification of a new species of beetle? No. That question is of interest only to the entomologist, and he is interested in it only because entomology is his surrogate activity. If the chemist and the entomologist had to exert themselves seriously to obtain the physical necessities, and if that effort exercised their abilities in an interesting way but in some nonscientific pursuit, then they wouldn't give a damn about isopropyltrimethylmethane or the classification of beetles. Suppose that lack of funds for postgraduate education had led the chemist to become an insurance broker instead of a chemist. In that case he would have been very interested in insurance matters but would have cared nothing about isopropyltrimethylmethane. In any case it is not normal to put into the satisfaction of mere curiosity the amount of time and effort that scientists put into their work. The "curiosity" explanation for the scientists' motive just doesn't stand up.

88. The "benefit of humanity" explanation doesn't work any better. Some scientific work has no conceivable relation to the welfare of the human racesmost of archaeology or comparative linguistics for example. Some other areas of science present obviously dangerous possibilities. Yet scientists in these areas are just as enthusiastic about their work as those who develop vaccines or study air pollution. Consider the case of Dr. Edward Teller, who had an obvious emotional involvement in promoting nuclear power plants. Did this involvement stem from a desire to benefit humanity? If so, then why didn't Dr. Teller get emotional about other "humanitarian" causes? If he was such a humanitarian then why did he help to develop the H-bomb? As with many other scientific achievements, it is very much open to question whether nuclear power plants actually do benefit humanity. Does the cheap electricity outweigh the accumulating waste and the risk of accidents? Dr. Teller saw only one side of the question. Clearly his emotional involvement with nuclear power arose not from a desire to "benefit humanity" but from a personal fulfillment he got from his work and from seeing it put to practical use.

89. The same is true of scientists generally. With possible rare exceptions, their motive is neither curiosity nor a desire to benefit humanity but the need to go through the power process: to have a goal (a scientific problem to solve), to make an effort (research) and to attain the goal (solution of the problem.) Science is a surrogate activity because scientists work mainly for the fulfillment they get out of the work itself.

90. Of course, it's not that simple. Other motives do play a role for many scientists. Money and status for example. Some scientists may be persons of the type who have an insatiable drive for status (see paragraph 79) and this may provide much of the motivation for their work. No doubt the majority of scientists, like the majority of the general population, are more or less susceptible to advertising and marketing techniques and need money to satisfy their craving for goods and services. Thus science is not a PURE surrogate activity. But it is in large part a surrogate activity.

91. Also, science and technology constitute a power mass movement, and many scientists gratify their need for power through identification with this mass movement (see paragraph 83).

92. Thus science marches on blindly, without regard to the real welfare of the human race or to any other standard, obedient only to the psychological needs of the scientists and of the government officials and corporation executives who provide the funds for research.

This viewpoint is pretty modern (mid-20th century onwards) - historically, many 'pure science' pursuits were the hobbies or obsessions of the relatively wealthy aristrocrat classes, and they really were motivated by curiousity (as their basic physical needs were already well-provided for), with the exception of rather small groups that found funding in other ways (Royal Society of Britain), who even then tended to rely heavily on things like royal patronage (see Euler, Kepler, etc. for example).

Even now, in the era of federal grants provinding the meat & potatoes, a lot of scientists have multiple motivations, as in 'this line of research really is quite useful to industrial progress/understanding nature/fighting disease/etc and thus human civilization' as well as 'hey, I can make a decent living and get a fair amount of social prestige by doing this'.

The internal bureaucratic politics of the modern science world are pretty nasty though, it's like bad office politics on steroids. Possibly the most extreme example of how it call all go wrong is seen in the legacy of Trofim Lysenko in the Soviet Union. Comparing Anthony Fauci to Lysenko might seem a bit extreme but recent events show how these types can utilize their power to protect their position, even if the kind of 'science' they're promoting is either reckless and dishonest or just manufactured ideological nonsense.

If you follow Ted's arguments, the hobbies of wealthy aristocrat classes are perhaps the purest example of surrogate activities. He explains the concept of surrogate activities using leisured aristocrats as his prime example:

38. But not every leisured aristocrat becomes bored and demoralized. For example, the emperor Hirohito, instead of sinking into decadent hedonism, devoted himself to marine biology, a field in which he became distinguished. When people do not have to exert themselves to satisfy their physical needs they often set up artificial goals for themselves. In many cases they then pursue these goals with the same energy and emotional involvement that they otherwise would have put into the search for physical necessities. Thus the aristocrats of the Roman Empire had their literary pretensions; many European aristocrats a few centuries ago invested tremendous time and energy in hunting, though they certainly didn't need the meat; other aristocracies have competed for status through elaborate displays of wealth; and a few aristocrats, like Hirohito, have turned to science.

39. We use the term "surrogate activity" to designate an activity that is directed toward an artificial goal that people set up for themselves merely in order to have some goal to work toward, or let us say, merely for the sake of the "fulfillment" that they get from pursuing the goal. Here is a rule of thumb for the identification of surrogate activities. Given a person who devotes much time and energy to the pursuit of goal X, ask yourself this: If he had to devote most of his time and energy to satisfying his biological needs, and if that effort required him to use his physical and mental faculties in a varied and interesting way, would he feel seriously deprived because he did not attain goal X? If the answer is no, then the person's pursuit of goal X is a surrogate activity. Hirohito's studies in marine biology clearly constituted a surrogate activity, since it is pretty certain that if Hirohito had had to spend his time working at interesting non-scientific tasks in order to obtain the necessities of life, he would not have felt deprived because he didn't know all about the anatomy and life-cycles of marine animals. On the other hand the pursuit of sex and love (for example) is not a surrogate activity, because most people, even if their existence were otherwise satisfactory, would feel deprived if they passed their lives without ever having a relationship with a member of the opposite sex. (But pursuit of an excessive amount of sex, more than one really needs, can be a surrogate activity.)

This viewpoint seems to imply that anything not directly related to biological survival and procreation is a 'surrogate activity' which then includes all of art, science, literature, etc. Would this author also classify some of the earliest human technologies (controlling fire, making tools, propagating plants from seeds) as 'surrogate activities' as well?

It seems like a logical quandry. If the only measure of non-surrogate activity is something like 'does this activity contribute to the survival of the individual, the family, the society, the species', and if science is a surrogate activity, then why isn't learning how to control fire also an unnecessary and frivolous activity?

> This viewpoint seems to imply that anything not directly related to biological survival and procreation is a 'surrogate activity' which then includes all of art, science, literature, etc.

Pretty much yeah. I don't think he's implying it as much as saying that outright. He doesn't condemn all surrogate activities equally though. He has ire specifically for those surrogate activities he believes inevitably restrict the freedom of individuals to go through their own power process, specifically science and industrialization. I'll not dump more large quotations in this thread, but read the section "Restriction of Freedom is Unavoidable in Industrial Society" if you want to hear his reasoning for this.

I am not an anarcho-primitivist so the above is not the point I am trying to make. I provided the quotations in my previous comments to answer the question "why would we do this? Just because we can?" I believe the answer is this: "scientists work mainly for the fulfillment they get out of the work itself."

I read Industrial Society to my parents, and we were all shocked how cogent it came across as. the bits about AI were especially chilling, very ahead of his time. I disagree with his conclusions about leftists (I am one), but I have to hand it to him for an excellent take.

> But it is easy to see that neither of these can be the principal motive of most scientists. As for "curiosity," that notion is simply absurd. Most scientists work on highly specialized problems that are not the object of any normal curiosity. For example, is an astronomer, a mathematician or an entomologist curious about the properties of isopropyltrimethylmethane? Of course not. Only a chemist is curious about such a thing, and he is curious about it only because chemistry is his surrogate activity. Is the chemist curious about the appropriate classification of a new species of beetle? No. That question is of interest only to the entomologist, and he is interested in it only because entomology is his surrogate activity. If the chemist and the entomologist had to exert themselves seriously to obtain the physical necessities, and if that effort exercised their abilities in an interesting way but in some nonscientific pursuit, then they wouldn't give a damn about isopropyltrimethylmethane or the classification of beetles.

What rubbish. One need only look at Euclid's Elements to see that a small portion of humanity has always been interested in completely irrelevant but highly specialized formal knowledge manipulation. That a single book about math has survived for longer than the Bible and been translated to a few dozen languages, across a dozen civilizations tells you all you need to know about the universality of curiosity.

Yes, if you're starving you won't be spending your time on curiosity, but you also won't be doing much of anything but looking for food. You might as well say that sex is a surrogate activity that we'd give up if we found something better to do.

I believe fairly little is known of Euclid's personal life, so it is hard for me to see Euclid as a clear counter example. Can you be more specific?

See also Derek Lowe’s article about the preprint: https://www.science.org/content/blog-post/gain-function-not-...

The linked article mentions a BU response via email. There’s also one via the web [0]. The preprint is way outside of my field of expertise so I can’t confidently evaluate the news stories against the preprint. But if journalists misinterpreted scientific research it would certainly not be the first time.

[0] https://www.bu.edu/articles/2022/neidl-researchers-refute-uk...

That response is an exercise in obfuscation. For example:

> Corley says the line pulled out of context actually had nothing to do with the virus’ effect on humans. The study began in a tissue culture, then moved to an animal model.

So they're saying we don't know if their lab-created chimera is actually more dangerous in live humans, because they (fortunately!) haven't tested in live humans. That completely misses the point of those models, though--the reason why tissue cultures and animals are used is that they're often predictive of the effect in humans.

By that standard in their mice, their chimera is possibly less deadly than the original Wuhan wild type, but definitely more deadly than omicron. They didn't study the effect on transmissibility, but we know that's determined mostly by the spike.

So their chimera may combine most of the deadliness of the Wuhan wild type with the transmissibility of omicron. We can't prove that without experiments in live humans that I hope will never be conducted, but that sure sounds like a gain of function research of concern to me.

>There is no evidence the work, performed under biosecurity level 3 precautions in BU’s National Emerging Infectious Diseases Laboratories, was conducted improperly or unsafely. In fact, it was approved by an internal biosafety review committee and Boston’s Public Health Commission, the university said Monday night.

Theat doesn't mean it can't be accidentally released, it just means there is less of a chance.

'Ask for forgiveness, not permission' is really not something we want in biotech.

Sweet maybe after this we can go ahead and extract DNA from a mosquito in amber and use that to make dinosaurs and open a theme park with them. Sounds like that is the next Chriton movie on the list now that we are checking of "The Andromeda Strain".

I'm totally in favor of bringing back dinosaurs. I'm also in favor of modifying animals to have more human-like brains.

I understand that many/most people would oppose this on ethical grounds. I could probably even articulate those positions if I tried.

But, deep down in my inner child, I think the world would be much more interesting if these things existed.

I will consent to your argument on the grounds that we provide equal funding and research to the construction of giant robots to fight the dinosaurs when they escape.

Sounds like a win-win!

Speaking of The Andromeda Strain, I used to assume the safety measures of real life labs for pathogen research were comparable to what Crichton described in that book. Well, probably not with nuclear bombs rigged to sterilize the facility in case of an accident, but at least built remote and with serious quarantine procedures.

Apparently not. Apparently they build these places in the middle of cities and let workers go home every evening. Insanity.

I live right around the corner from here and pass this place daily. There was a lot of concern when this place was built in the heart of a major city and I understand the concern (though I’m guessing the risk a place like this poses is really in that an individual who works there gets infected with something and goes out into society - which means the location doesn’t matter much.)

On the flipside, I also understand that research like this needs to happen for us to learn and make progress. All that being said, this just comes off as sloppy, which is exactly the feeling I don’t want to have about a BSL-3 lab in my neighborhood.

Just like the progress when they invented nonstick fireproof and water proof forever chemicals

Not wrong, but it all depends on how you look at it. It’s also progress that got us life-saving vaccines and medications within a year of a deadly pandemic emerging.

Why have one pandemic when you can have two pandemics for twice the price

Don't let China have all the fun.

In this snippet from the abstract, S stands for spike protein:

> "We generated chimeric recombinant SARS-CoV-2 encoding the S gene of Omicron in the backbone of an ancestral SARS-CoV-2 isolate and compared this virus with the naturally circulating Omicron variant. The Omicron S-bearing virus robustly escapes vaccine-induced humoral immunity, mainly due to mutations in the receptor-binding motif (RBM), yet unlike naturally occurring Omicron, efficiently replicates in cell lines and primary-like distal lung cells. In K18-hACE2 mice, while Omicron causes mild, non-fatal infection, the Omicron S-carrying virus inflicts severe disease with a mortality rate of 80%. This indicates that while the vaccine escape of Omicron is defined by mutations in S, major determinants of viral pathogenicity reside outside of S."

https://www.biorxiv.org/content/10.1101/2022.10.13.512134v1....

See russfink comment above for the relative mortality compared to the original Wuhan strain (100% for Wuhan compared to 80% for this hybrid). So this researcher-generated strain appears to be intermediate in mortality between the original Wuhan strain and Omicron, BUT it escapes vaccination relative to the Wuhan strain, making it more dangerous in that regard and more likely to spread through a vaccinated population causing significant mortality. I'd classify this as reckless and irresponsible research.

As far as the original Wuhan strain, we have about four theories of origin. (1) natural wild type with no lab research involvement, (2) natural wild type collected by a lab and accidentally released from that lab, (3) wild type 'heated up' by serial passage through mice and cloned human-type cells without explicit genetic engineering, and (4) deliberate engineering using a CRISPR system to insert a furan cleavage site in a collected wild-type virus, which allowed a bat virus to leap to a human host.

Really (4) has the most evidence at this point, and note that this is not entirely the fault of the Chinese Wuhan Institute of Virology as the research concept was partially developed in the USA and continued (despite an Obama-era ban on gain-of-function research) in China with Ecohealth Alliance funding.

As far as why doing gain-of-function research to predict 'emerging disease outbreaks' is a godawfully stupid idea, it's that it appears that almost any infectious animal virus can be converted to a human pathogen by selective transfer of human-receptor-binding motifs, even though such transfer would never take place under natural conditions. An immediate global ban on this kind of research (under the Biological Warfare Convention) is needed.

> such transfer would never take place under natural conditions

How confident are we that is the case?

HIV resulted from the fusion of, IIRC, three virii in a host animal.

The odds of any single such event are vanishingly small, but that stacks against how many cells per second a virus can infect, worldwide. Life is a frightening goodness-of-fit optimizer at the scale of microorganization.

It would never take place between animals that don't naturally cohabitate.

Studying rare historical accidents of evolution that resulted in pandemics to see how they took place is one thing, but creating hundreds of such accidents of evolution deliberately to see how many novel deadly pathogens one can create is quite another.

In the case of HIV:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3234451/

Now, should we start taking all the viruses known to infect every species of squirrel, rat, monkey, gorilla and chimpanzee and start splicing in motifs that bind, say, the top 100 most common human cell-surface receptors in order to see what's the most dangerous virus - with the optimal mix of mortality and transmissibility (R factor) - we can create, the one best able to cause a global human pandemic? That's insane, and there's no justification for it.

Is that research done? I don't think that's an accurate description of gain-of-function research; I thought it was more focused than "just throw everything in a beaker and see what happens." I agree that's a bad idea.

It's more focused exactly in the sense that it is specifically targeting known-dangerous characteristics - hence gain of function: they're aiming to increase the virus' ability to do something.

Thank you for posting this. Racists are claiming that COVID came from China. But WHO-China investigation has found that COVID couldn't have come from China. Even virologists have been expressing their support for Chinese scientists.

[1] https://www.thelancet.com/journals/lancet/article/PIIS0140-6...

> Really (4) has the most evidence at this point

No, there is literally zero evidence of this.

The BANAL viruses are a couple of mutations away from a workable furin cleavage site, nature can engineer them just as easily as we do, and has done so multiple different times that we know of across beta-coronaviruses.

> The BANAL viruses are a couple of mutations away from a workable furin cleavage site,

That's true, but you can argue it in either direction. It proves the mutations to create that FCS are possible and indeed likely; but it also proves they're selected against in their usual hosts, or else we'd have observed the complete FCS. So you need the mutation to happen concurrently with the species jump (or in a yet-undiscovered intermediate host), which gets less likely.

> it also proves they're selected against in their usual hosts

No it doesn't. They can be neutral. And BtCoV-HKU5 is a MERS-like bat coronavirus with a functional FCS and BtHpCoV-ZJ13 is even closer to sarbecoviruses than MERS and is another bat coronavirus with an FCS. It is more likely that the absence of an FCS in BANAL-like viruses is due to us not having found them yet, our surveillance coverage is immeasurably poor.

And a species jump involving coinfection with proto-SARS-CoV-2 and some other coronavirus and a recombination event is actually a likely way to start a pandemic. The 2009 H1N1 pandemic was started by a triple reassortment with three viruses in a pig. Pandemics are very uncommon infection events so the conditions that create them are necessarily highly unlikely.

> No it doesn't. They can be neutral.

That's a fair point. Properly I guess we should try to quantify the number of samples expected before we observe an FCS if it's neutral, but that math seems nontrivial. It's at least definitely not beneficial, though. I do agree that the FCS could have evolved naturally, though I guess we'll continue to disagree on the relative probabilities of natural vs. lab-inserted.

That sick pig was probably infected with each virus for days or longer, so that coinfection seems less unlikely to me than a simultaneous species jump and mutation to create the FCS (since those are both roughly instantaneous by comparison). I'm not sure what I'd consider the most likely zoonotic path now; the close identity between the BANAL and SARS-CoV-2 spikes seems like it removes the need for an intermediate host with human-like ACE2, though it's pretty mysterious.

> a simultaneous species jump and mutation to create the FCS (since those are both roughly instantaneous by comparison).

I don't know why you think this is necessary.

The FCS shouldn't preclude the infection continuing in the original species, like I said it probably doesn't infectivity in bats and is neutral.

And if the intermediate animal was infected with a common coronavirus for the species, all it takes is coinfection from a bat with the precursor to SARS-CoV-2 and a recombination event to create the FCS. Animals and humans across china are almost certainly getting infected with novel sarbecoviruses from bats every day. Most of them don't go anywhere. This one got "lucky" and stole some genetic material which made it better in the new host organism and now it is off to the races. Which is unlikely, but, again, pandemics are unlikely.

Assuming the FCS is neutral in bats (which I don't think we could prove or disprove without more sampling, but which I agree is possible), I agree that the mutation wouldn't have to happen concurrently with the species jump. Even if the FCS is negative in bats, it's also possible that the FCS evolved naturally in a different animal host. I agree there's no evidence to exclude those scenarios; I just don't see any specific evidence to favor them either.

The notion that sars-cov-2 arose naturally is risible.

From https://s3.documentcloud.org/documents/21066966/defuse-propo...

> “We will conduct in vitro pseudovirus binding assays, using established techniques2, and live virus binding assays (at WIV to prevent delays and unnecessary dissemination of viral cultures) for isolated strains.” (D1, p.12)

> “We will validate results from chimeric viruses by re-characterizing full-length genome versions, testing whether backbone genome sequence alters full length SARSr-CoV spillover potential. QS for full-genome characterization will be selected to reflect strain differences in antigenicity, receptor usage, growth in human cells and pathogenesis.”(D1, p.13)

> “We will test growth in primary HAE cultures and in vivo in hACE2 transgenic mice. We anticipate recovering ~3-5 full length genome viruses/year.”(D1, p.13)

> “We will analyze all SARSr-CoV S gene sequences for appropriately conserved proteolytic cleavage sites in S2 and for the presence of potential Furin cleavage sites74,75.

SARSr-CoV S with mismatches in proteolytic cleavage sites can be activated by exogenous Trypsin or Cathepsin L.

Where clear mismatches occur, we will introduce appropriate human-specific cleavage sites and evaluate growth potential in Vero cells and HAE cultures.”

> “We will also review deep sequence data for low abundant high risk SARSr-CoV that encode functional proteolytic cleavage sites, and if so, introduce these changes into the appropriate high abundant, low risk parental strain.” (D1, p.13)

SARS-CoV-2 isn't based on a SARS-CoV-1 backbone or spike or any known backbone or spike that would have been used in a lab.

The closest known viral backbone is a few decades of random mutations away from SARS-CoV-2 and there's no evidence that WIV even tried to work with RaTG13 and did anything beyond sequencing it.

And you have the usual Schroedingers-Information problem that plagues conspiracy theories. You have to assume that on the one had all that information you just cited would be available to you, while a fairly massive project involving forming a chimera from an unknown spike protein and unknown backbone would have been going on in perfect secrecy in 2019 before there was any reason to keep that information secret. In 2019 if they had sequences of those viruses they would have just published them, they certainly would have published them before going through the effort to create chimeras from them. They would have used those sequences to get justification to get grants to do studies. The idea that all of that happened in perfect secrecy, before there was a need for perfect secrecy is the idea that is fucking laughable.

And nature creates "chimeras" and does "gain of function experiments" all the time on a massive scale using many billions of animals in the "lab". That is what recombination and serial passage does -- particularly as viruses burn through bioreactors in animal farms in close proximity to humans.

And when it comes to the FCS, the PRRAR sequence is unlike any other known FCS. If humans engineered it they would have picked another one that they already knew worked. That sequence absolutely screams that it was zoonotic in origin. It was novel and never previously seen before. Nobody would have added that in a lab.

> “We will use a large dataset of S protein sequences and full-length genomes generated from prior work and DEFUSE fieldwork to estimate SARSr-CoV substitution rate and its genome-wide variation.” (D1, p.15)

> “Sub-Task 1.2 Collect monthly specimens from bats at cave sites in Yunnan, China for SARSr-CoV screening and sequencing. Oral, fecal, and blood sample collected from 360 Rhinolophus spp. bats per month using live- capture and non-invasive sampling. Specimens shipped to laboratory for analysis. Associated morphological, demographic, and physiological data for individual bats collected (EHA, consultant Zhu).”(D1, p.25)

“Deliverables: Specimens from 3,240 bats and fecal pellets collected from high-risk reservoir populations which have been obtained with all proper permits and permissions and shipped to WIV for analysis; real-time telemetry and mark-recapture data uploaded and made available to DARPA collaborators; completed database maintained.” (D1, p.25)

Most of that collected and sequenced virus will be dead. For samples like blood it would be very difficult to infect labworkers, it would need to be something like an accident with aerosolized fecal samples which were inhaled. But assuming there was any live virus in those samples the human exposure will be dwarfed by the workers in mines and those who collect bat guano for fertilizer without any PPE at all. There's many times more bat-human contact around rural China which doesn't involve labworkers and where there's no precautions (as we know from the Mojiang miners who died).

And there's still a vast gulf from collection sampling to engineered chimeric viruses and gain of function experiments.

Except there was no gulf. The purpose of the proposed collection of novel bat coronaviruses was to facilitate gain of function experiments at WIV involving the alteration of spike proteins, including the introduction of ‘appropriate human-specific cleavage sites’.

In a recent interview Jeffrey Sachs said that he spoke to one of the original reviewers of the DEFUSE proposal, who said ‘the research was done before the proposal went in.’ https://youtu.be/vtfIIG8iYIk 32:10s

So, researchers propose to create a novel corona virus with precisely the attributes of sars-cov-2 in 2018. At the Wuhan Institute of Virology. Having already secretly completed the research. And we are supposed to believe that sars-cov-2 originated naturally, despite no evidence of such an origin, as in sars-1 and mers, and after almost three years spent searching for the reservoir.

> literally zero evidence of this.

What about the Moderna patented sequence?

[1] https://www.thelancet.com/journals/lancet/article/PIIS0140-6...

https://news.ycombinator.com/item?id=33244592

https://archive.ph/neAYI

Whether natural or escaping from a lab, I fully expect a mass casualty disease in my lifetime. We saw what a shitshow covid was, and it wasn't even that bad.

Fast global travel is spreading the endemic ranges of many diseases and make it essentially impossible to stop many diseases depending on the traits of the disease.

A potential lab leak of many types of diseases is more of a threat and will likely kill more people than a limited nuclear deployment. At least with the nuclear issue someone has to push the button. With the lab leak it's almost a certainty that equipment will fail in some unprecedented way, or someone will absent-mindedly violate protocol. It's a lot harder to keep track of a microbe than a warhead.

I don't think so. I think Covid was unique in that it occupied a sweet-spot in it's severity. A more severe virus would play out very differently. I don't think we'd see such a huge conspiracy movement around it and much greater compliance from the population.

The danger of the covid virus was concentrated in specific demographics such that a lot of people didn't directly see how dangerous it was. This created a disconnect between what was being reported vs what people saw with their own eyes, creating the perfect environment for conspiracy theories to run rampant. For example, I don't know anyone that died or had a bad time with it, nor does anyone else in my family/close circle. But that's because I don't really know any old or medically vulnerable people, but with our aging populations in the western world this group is actually huge. We had people dropping like flies in certain sub-groups while in others nothing much happened and only where the groups intersected was it visible how bad it really was (healthcare workers, people with old grandparents not taking it seriously). It also doesn't help that older demographics almost always have something else wrong with them and Covid a lot of the time was one contributing factor that pushed them over the edge, this really fueled the conspiracy theorists narrative of falsely attributing causes of death to "inflate" numbers.

I also think the media took a wrong turn in it's messaging and told too many noble lies. It was really important that the young and healthy also thought that this might be real threat to them personally so they'd actually take it seriously and stop spreading it. But young people would lookup the statistics for their own risk and would see fatality/complication rates of sub 1%, and also note that those affected were primarily the morbidly obese and immuno-compromised. I recall seeing a lot of articles indicating that there was a surge of young people in ER and articles showing obituaries of young people in order to hammer home the message that it was a real danger to them too. The problem is the official statistics didn't back that message up to the degree that it needed to, so you had this big disconnect that was exploited heavily by conspiracy theorists. IMO this was likely a misguided effort directed towards reducing spread, because it was determined that quarantining to save other people wasn't a strong enough incentive to curb risky behavior (which is depressing), but backfired heavily and likely caused more harm than good.

If a more serious virus came around that had fatality rates in the double digits, I don't think conspiracy theories would be able to form. Because very quickly people would see people they know in their lives dying/becoming extremely sick. There's no uncertainly/disconnect to exploit in that scenario like there was with covid.

"A more severe virus would play out very differently."

It wouldn't necessarily. It could still be nearly impossible to contain given the right characteristics, like asymptomatic carriers, a latency period, or benign early onset symptoms. With the right parameters and fast global travel, it would be global before any measures could even be implemented (theory is this was the case with Covid).

"I don't think we'd see such a huge conspiracy movement around it and much greater compliance from the population."

There might be better compliance, but not likely enough to make a difference. Many of the things that they're supposed to be complying with were misunderstood, ineffective (maybe marginally effective), and wouldn't prevent transmission. Even if you were to lock almost everyone in their homes, you still have some essential personnel who must travel/work/etc. Most lack the training necessary for consistently complying with prevention protocols.

Just look at the number of people dying of drugs every year. They know it's bad. Some think it won't happen to them. Others don't care. There's no reason to believe that a non-zero portion of the population would share these two thought processes in this sort of situation and still cause significant damage. Including the people who see no/limited risk for themselves.

> IMO this was likely a misguided effort directed towards reducing spread, because it was determined that quarantining to save other people wasn't a strong enough incentive to curb risky behavior (which is depressing), but backfired heavily and likely caused more harm than good.

Perhaps a large set of people have a different set of values and consider the tradeoff between endless (and mostly useless) lockdowns and restrictions not worth it compared to taking their risks of getting covid.

Perhaps they have decided that the costs to society far outweigh any benefits from these mitigations. These are a perfectly valid set of values, just different than your own--it requires absolutely no "conspiracy theories" to think this.

> conspiracy theorists

There is not many conspiracy theories about covid and a very small set of people peddle them. Most of the "conspiracy theories" turned out to be perfectly true. For example requiring proof of vaccination to sit down at a starbucks turned out to be true. Vaccines turned out to do very little to stop infection or transmission. Masks not working as well as some people would like to believe. Lockdowns and school closures hurt children--especially those who are low-income.

Writing off everything you disagree with as "conspiracy theory" is poor intellectual thinking. Maybe if you put aside your preconceived notions and dug harder into the arguments people have against everything society has done for covid, you'd discover that they have very valid points.

it was calculated how many lives were saved thanks to vaccines, wearing masks, social distancing, lockdowns etc. just because some people with different sets of values don't believe those numbers doesn't mean they aren't true...

"We estimate that across these 6 countries, interventions prevented or delayed on the order of 61 million confirmed cases, corresponding to averting approximately 495 million total infections."

"COVID-19 vaccination has substantially altered the course of the pandemic, saving tens of millions of lives globally. However, inadequate access to vaccines in low-income countries has limited the impact in these settings, reinforcing the need for global vaccine equity and coverage."

I agree with your broader point, but this statement strikes me as odd:

> "I recall seeing a lot of articles indicating that there was a surge of young people in ER and articles showing obituaries of young people in order to hammer home the message that it was a real danger to them too. The problem is the official statistics didn't back that message up to the degree that it needed to, so you had this big disconnect that was exploited heavily by conspiracy theorists. "

That seems like whitewashed phrasing for what was, at best, manipulation and at worst, outright lies. The 'official statistics' were hidden from everyone, and particularly the young, because telling someone under 40 that their IFR for COVID was only about 5-10X what it is for the flu just isn't that scary.

> There is a lot of evidence that points to the virus spreading from a wet market in the city, not the Wuhan lab. But proving something didn’t happen three years after the fact is a challenge that may be impossible to meet.

I find the anxious disclaimer about the Wuhan lab interesting, because of course there were a lot of things the lab itself could have done to clear any doubt at the time, including not muzzling researchers who worked there, and even releasing their virus database (which had been taken offline a couple months earlier, under the pretext that 'someone' had attempted to 'hack' it and has still not been made available three years later).

Important underline: the lab database is not available to us.

> Important underline: the lab database is not available to us

Genuine question, as I'm not aware that it's been made externally available to anyone - do you mean it's available to researchers around the world but not the general public? Or do you mean it's available to Chinese labs?

It's a dumb conspiracy theory about a rarely-used database that "went down" in September 2019 which was a smoking gun about how the Chinese knew about Covid. Except it turns out that it only came online in June 2019, it went down all the time from the view of the tracking website, was available into 2020, and has absolutely nothing useful to say about SarsCov2;

https://twitter.com/flodebarre/status/1577401140345507859

I'm certain that everyone who used this as a prominent 'datapoint' for the LL hypothesis will immediately reconsider and update their priors.

I think the GP's point is that it's a dumb conspiracy theory data-point that would be incredibly easy to eliminate, and it's frustrating that it's not.

The thread you've linked is deliberately misleading, refuting a strawman version of the "conspiracy theory". Everyone has always agreed that the server was intermittently available until Feb 2020. It's a particular database that went unavailable in Sep 2019, not the whole server. Quoting from a document written by the "conspiracy theorists" more than a year before that thread:

> Batvirus.whiov.ac.cn had been online for a few years, saw a version 2 released in June 2019, went inactive for a week during the second half of August 19, before becoming definitely inaccessible (out of the WIV at least) on the 12th Sep 19. It was online intermittently after this date from mid-December 2019, and occasionally until February 2020, but was not accessed from outside of the WIV after 12 September 2019.

https://www.researchgate.net/publication/349073738_An_invest...

Were you aware of that? If not, then you might update your priors yourself.

The disappearance of that database obviously isn't proof that the WIV did anything nefarious. It continues their pattern of zero transparency, though. That might just be the reflexive secrecy of an authoritarian state; but the nature of zero transparency is that we don't know.

Their own evidence shows the September 2019 date is correct, and that it wasn't just flakiness like previously, it stayed down for months.

That's probably true, but so is what's written in the article. A much bigger factor in the lab leak theory is that it played into various conspiracy theories and, for some people, was convenient politically. It's much easier to believe that someone you don't like created covid maliciously than that it evolved naturally thanks to a huge number of factors no one person can control.

In the voice of superintendent Chalmers: A rare novel bat Coronavirus

Emerged in Wuhan.

Down the street from a virology institute

That was studying coronaviruses

That was studying novel bat Coronaviruses

That had multiple breaches of safety protocol in the years leading up to it

Is not where the virus originated?

Skinner: Um yes

"Can we inspect the site freely?"

"No"

"CCP a global pandemic is destroying the world."

"That's just misinformation mother"

Except substitute “down the street” with “30 km away on the other side of a river”, and notice that everybody who got sick initially was next to the market, none of them anywhere near the lab.

So the lab-leak hypothesis is: this virus created at the lab accidentally escaped to someone who subsequently only infected people on the other side of town.

It’s certainly a possibility (viral transmission is irregular with high variance, and people can easily travel that distance), and the lack of transparency by the government is alarming (though not particularly surprising to folks studying China), but most of the experts who have studied it still think it’s relatively unlikely.

> Except substitute “down the street” with “30 km away on the other side of a river”, and notice that everybody who got sick initially was next to the market, none of them anywhere near the lab. > So the lab-leak hypothesis is: this virus created at the lab accidentally escaped to someone who subsequently only infected people on the other side of town.

But this isn't necessarily how it works, at all.

The Wuhan market is one of Wuhan's most population-dense areas, in close proximity to three hospitals where the first cases were identified, and was therefore the concentration for infection-tracing.

In other words, the dataset for early cases was based on a belief that the market was where the infection was spreading, rather than the location of a spreading event that came from elsewhere in the city. Even pneumonia cases that were reported were only post-hoc assigned as probably covid if they were in close proximity to the market.

Again, it’s not impossible or even implausible that the spread could have happened like that, or that there were cases elsewhere that went unrecognized. But that’s not nearly the same as flippantly describing this as the lab just “down the street” from the market.

The possibility hasn’t been incontrovertibly ruled out (and maybe never can be at this point), and it’s important to do independent investigations and examine the lab’s research, etc. It’s just not considered by most experts to be the most likely possibility.

As a geographical comparison, it would be like having a new disease outbreak where all of the known cases for the first several weeks were in Brooklyn, NY and concluding that the source could have been a lab in Newark, NJ. It’s possible, but not the first place to look.

The “lab leak hypothesis” refers to the lab literally down the street, as per the WHO report. The lab was moved to that location about a week before the outbreak at the wet market. The WHO report speculates perhaps an accident occurred during the move.

It does not refer to the WIV as you think, again as per the WHO report.

This entire conversation (the article, the posts here, and in general the speculation about a lab leak possibility, comments about US grant money, etc. etc.) is explicitly about the Wuhan Institute of Virology.

Which WHO report are you thinking of? The 2021 WHO report called the lab leak possibility “extremely unlikely”. This more recent report from 4 months ago merely calls for more investigation into laboratories in the area and more transparency: https://cdn.who.int/media/docs/default-source/scientific-adv...

If you are interested in Covid origins look at this NPR story from March https://www.npr.org/sections/goatsandsoda/2022/03/03/1083751...

Which refers to this paper in Science, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9348750/

Maybe one of the people who works at the lab lives/works close to the market.

But you can do this too for the Chinese version of the conspiracy too.

——

Emerged after military games in Wuhan.

Where the US competed.

Who is a geopolitical rival of China.

With soldiers that work at a military biolab.

That had a major biosafety breach the same year.

And the US doesn’t let the site be inspected freely.

——

Each of these are true on their own, that doesn’t mean we can conclude the implied conclusion is true.

But the military games happened in October, the previously public database of the WIV was taken down in September a month prior due to "hacking" which why would someone hack a publicly available database is hard to imagine. And why has the database not been shared via database dumps or uploaded somewhere else since? Also if the outbreak occurred in the US there would have been major spikes in hospitalizations months earlier in the US than what happened in Wuhan.

Also animal-to-human viruses usually go over two phases: first animal to human contagion is possible but human to human is hard, then human to human gets easier as the virus evolves.

If Covid-19 started in the wet market it went over the first phase very quickly.

Part of fighting disinformation and conspiracy theories is also learning to distinguish when things are just lies (eg. sandy hook was an hoax) or truish but misused (eg. chemical waste in river does affect the sex of frogs).

It is also important not o make a strawman of the opponent. For some people the "Lab Theory" is "The CCP was trying to exterminate the US but failed" for others it is "A researcher got bit by a bat in a lab". The former is paranoid, the latter is completely plausible.

Overall there is good circumstantial evidence for both, and reasonable people can disagree.

It's frustrating that people make the argument that the lab leak theory is "politically convenient" and that it "played into various conspiracy theories" and then go on to list ridiculous things that no one here is arguing. A lot of people look at covid, which was first seen in wuhan, and think "hmm, it seems like there's a good chance it came from the lab in wuhan that studies coronaviruses." You don't have to involve politics at all for it to be easy to believe.

You have to ignore all the evidence and data that makes this extremely unlikely.

Just as someone might want to believe the moon is made from cheese. It looks a bit like it, after all. But to believe that, you have to ignore all that scientists have uncovered about the moon.

What data makes this extremely unlikely? Worobey and Pekar are hardly convincing.

Just google it. There's enough out there, but you don't want to believe the experts even though you don't know the science. There is no signature of manipulation in the Genome. Zero sign of it being "recombined". Experts just don't see a clear way it could have happened. Just the inability to say it's impossible and will never happen is seen as confirmation of the hypothesis.

Proponents of the lab-leak hypothesis often believe the researchers have somehow enhanced the virus. The only way we actually know to do this is through evolution in lab animals. And even then it's pretty damn hard. Maybe multiple industrial-scale facilities could evolve a threatening Virus. At horrendous cost. Maybe. And even China couldn't hide that.

The most likely research-origin scenario is either a naturally-evolved novel virus collected and accidentally released by the WIV, or a chimera of multiple such viruses. No genomic evidence could distinguish that from natural spillover. For example, here's David Relman back in 2020:

> This argument [that SARS-CoV-2 must be natural since it doesn't use a known backbone] fails to acknowledge the possibility that two or more as yet undisclosed ancestors (i.e., more proximal ancestors than RaTG13 and RmYN02) had already been discovered and were being studied in a laboratory—for example, one with the SARS-CoV-2 backbone and spike protein receptor-binding domain, and the other with the SARS-CoV-2 polybasic furin cleavage site. It would have been a logical next step to wonder about the properties of a recombinant virus and then create it in the laboratory.

https://www.pnas.org/doi/10.1073/pnas.2021133117

The WIV had the world's largest effort to collect novel sarbecoviruses from nature, often from remote caves that no other humans would routinely visit; so I don't see any reason to discount that possibility.

You don't see the reason because you think like a computer scientist. Having two NPM packages whose versions interfere with each other is often called "dependency hell". But it is way worse for proteins in a Virus.

In order to make a pandemic Virus the components must be finely tuned to each other. That is only possible through massively parallel evolution. A lab can't do that. When a lab combines Viruses, it's mostly to learn the individual contributions of the proteins. These Viruses are way less "fit" overall.

Except that we're currently discussing an article about researchers who achieved gain-of-function in a laboratory recombinant of a pandemic virus? Their chimera has the immune escape of omicron, with most of the mortality of the Wuhan wild type. The decrease in mortality compared to the Wuhan wild type is both statistically insignificant and irrelevant regardless; the correct comparison is against natural omicron, since that's the only natural virus with the omicron spike's immune escape properties.

A subsequent BU press release denies that the research involved gain of function, with bizarre arguments including the fact that since it's never been tested in humans (good?) we can't know it's actually more lethal in humans. This is obviously wrong, as many people have pointed out. For example, here's Marc Lipsitch at Harvard:

https://twitter.com/mlipsitch/status/1582574061062098946?cxt...

My original quote is from David Relman, a professor of microbiology at Stanford who I wouldn't expect to "think like a computer scientist". Laboratories have been enhancing potential human pandemic pathogens for literally decades now, as measured by reproduction rates in vitro, mortality in their lab animals, and other similar metrics, and publishing in the open literature. For example, here's Relman asking Baric a question back in 2014:

https://www.youtube.com/watch?v=Aw-nR6-4kQQ&t=2466s

If you were really unware that labs are successfully enhancing potential human pandemic pathogens, then a Google Scholar search for Baric will find many examples.

Anyways, even if you believe (quite falsely) that laboratory gain-of-function on such pathogens is impossible, that doesn't exclude a research-related origin for SARS-CoV-2. That could be a naturally-evolved virus, but one that was sitting harmlessly in a remote cave until the WIV sampled and accidentally released it. The WIV sampled remote areas that no other humans routinely entered, so it's possible in that scenario that the lineage would have died out in bats (or other zoonotic hosts) if the WIV hadn't released it into humans.

Nobody is asserting that genomic evidence shows SARS-CoV-2 to be natural anymore. Even the strongest proponents of zoonotic origin have moved on, to more complicated epidemiological and phylogenetic arguments like Pekar's paper.

>all the evidence and data that makes this extremely unlikely.

Please, do share.

Why did the lab in Wuhan study coronaviruses? Is it that there are convenient natural reservoirs nearby?

nope. hundreds of miles away actually.

It is not. In the words of Dr. Shi herself:

> We have done bat virus surveillance in Hubei Province for many years, but have not found that bats in Wuhan or even the wider Hubei Province carry any coronaviruses that are closely related to SARS-CoV-2. I don't think the spillover from bats to humans occurred in Wuhan or in Hubei Province.

https://web.archive.org/web/20210727042832/https://www.scien...

Coronaviruses are basically everywhere, as are bats. The greatest abundance of sarbecoviruses is far from Wuhan, though. The closest relatives to SARS-CoV-2 were found in Yunnan and surroundings, near Kunming or Pu'er, and now in Laos.

I'm not really familiar with Dr Shi or your source (seems a bit obfuscated via archive.org), but it does seem like a very sober and careful analysis from an expert.

Also, she says what I always assumed was the case:

> Scientists from around the world have overwhelmingly concluded that SARS-CoV-2 originated naturally rather than from any institution.

An expert indeed; Dr. Shi discovered the bat virus ancestors of SARS-1. Her subsequent research at the WIV is the matter of controversy here, as to whether that could have caused the SARS-CoV-2 pandemic. The interview is with Science, the well-known academic journal. That journal seems to have reorganized their website recently and broken my old link, so I used archive.org instead of hunting down the new URL.

So Dr. Shi is obviously going to say the pandemic is of natural origin. Even if she personally believes otherwise, she's under the physical control of the PRC government, and would suffer grave consequences if she went against their official story. My point is that not even she thinks spillover in Wuhan is likely, though. The idea that the WIV was situated in Wuhan because of an abundance of nearby sarbecoviruses is bizarrely common, but it's neither anti-lab-origin nor pro-lab-origin, just wrong.

Indeed, I really don't know why there is a virology lab in Wuhan, or why they would be located in any given part of the world.

I tend to assume that covid-19 came about like (presumably) every other virus since time eternal; through random mutation in the wild. What I don't really understand is any sort of singular alternative theory of how it arose - it seems that every alternative is anomaly hunting or god of the gaps type arguments in search of some greater meaning behind it.

I agree there's no conclusive evidence for any specific origin of SARS-CoV-2, unnatural, natural, or otherwise. I don't see the "god of the gaps" analogy, though. There's no evidence that god exists, and attributing actions to god has no predictive or practical benefit. But there's certainly evidence that virologists exist, and were collecting and manipulating novel SARS-like viruses near the origin of a novel SARS-like pandemic. (Are you familiar with the DEFUSE grant proposal?)

So with millions dead, shouldn't we investigate? There are many paths unexplored within reach of American or European subpoena, both in the WIV's collaborators and in sequencer reads from unrelated work that may contain early viral genomes as contamination.

What would you like to investigate? This is what I don't understand - what is the alternative to a natural origin?

That researchers at the WIV collected two novel viruses from nature, built a chimera with a synthetic FCS, infected themselves by accident, and spread the virus into the world? The first two steps are exactly what they proposed in DEFUSE; that proposal got rejected, but it's still an indication of the work they might have continued with other funders.

Or that they collected one naturally-evolved virus, got infected in the field, and spread it from there? The WIV sent grad students into remote caves that no other humans routinely entered, specifically selected for their abundance of novel potential pandemic pathogens, with nothing more than nitrile gloves and a surgical mask. So while there are far more farmers and guano collectors (and others creating risk of natural spillover) than WIV grad students, the risk per WIV grad student seems orders of magnitude higher.

I'm not really familiar with the acronyms, but I wonder if it would be possible to prove that the virus is not artificially constructed? The other theory just sounds like natural origin with an extra step.

But what I wonder most would be, say that it was proven that covid-19 was artificially constructed through some method or other - what would it matter? I wonder if more people would get vaccines? Would China now know that they can unleash something like this on the world with relative impunity? Would it incentivize further research into biological weapons?

It's usual to investigate after a disaster, to seek the cause and try to prevent future similar disasters; we do it after plane crashes, or building collapses, or nuclear reactor explosions. A pandemic seems to me like the same basic category. If wildlife traffickers are taking actions that we know have caused past pandemics, then I believe those should be restricted. Likewise, if virologists are taking actions that we know have caused past pandemics, then those should also be restricted. This is true regardless of whether the mechanism is simple (like a researcher infected in the field) or complex (like genetic engineering).

The DEFUSE proposal was described in this Intercept article:

https://theintercept.com/2021/09/23/coronavirus-research-gra...

For the previous two coronaviruses that emerged in humans (SARS-1 and MERS), animal hosts (civet cats and camels) were found within about a year. That's pretty good evidence of natural origin. For SARS-CoV-2, no such animal has yet been found, excluding animals known to be infected by humans like housecats or mink. That's not proof of unnatural origin--for example, Ebola is unquestionably natural but its zoonotic hosts remain mysterious. That's not what anyone expected, though.

For overall background, Alina Chan has a book. I haven't read it myself, but I've found her comments elsewhere to be cautious and reasonable.

And what ability do you see us as having to restrict Chinese viral research?

I imagine telling an American that they are not allowed to hunt wildlife and sell it at market, and I don't think that would work. I wonder if China really has a much greater ability to enforce such a provision?

That seems out of our control, but I wonder what would be? Would preparations include mask stockpiles, and can we force people to wear them? It seems that mRNA vaccines can be created quickly, but can we mandate that people get them?

> And what ability do you see us as having to restrict Chinese viral research?

The ability to appeal to their self-interest? I doubt that any evidence would cause the CCP to deviate from its preferred story (which I think now is natural zoonosis outside China, then import on frozen food?), but they don't want a pandemic any more than I do.

So I'd guess that given evidence that certain research activities likely caused this pandemic, the Chinese government would quietly act to restrict them, all while publicly denying that they're doing so. Indeed, they might have already--Dr. Shi's group hasn't published anything even as dangerous as these BU researchers' experiment since before the pandemic.

Is the work complete then? Or would the investigation need to continue? And what sort of evidence would it take to conclude?

I do think it's possible that Chinese virology is safer than American virology now. The latter doesn't seem too safe though, judging from the work at BU that we're discussing here.

As noted above, I believe that subpoenas should be obtained for all relevant records of the WIV's collaborators, and for any sequencer reads that potentially contain early viral genomes as contamination. The evidence for a lab origin so far is scattered and circumstantial, but that's just from various leaks and amateur open source intelligence; perhaps a formal investigation with subpoena power could learn more.

We’ve restricted Chinese nuclear weapons tests just fine.

Have we? I'm far from an expert, but doesn't China have a mature nuclear program that includes enough of an arsenal for their strategic purposes?

It does not seem that we've been able to contain the ambitions of North Korea, and Iran isn't looking so good either.

Wuhan is a global biotech hub. There’s a bunch of R&D and manufacturing there.

Unfortunately the politics makes it comforting to believe (even though all the evidence points to natural origin - explained at length here and elsewhere).

It is so much easier to believe that the bad thing was made by bad people somewhere else, instead of confronting the reality that in fact we did it with our ever greater encroachment on the last remaining natural reservoirs - and will do it again, probably soon.

> It's much easier to believe that someone you don't like created covid maliciously than that it evolved naturally

Ah! and there you did that thing to make an accidental lab-leak a crazy nut job conspiracy theory.

Lab-made viruses like that have a close to zero chance of being more successful in the wild, even if the researchers had attempted that goal.

Evolution can try gazillions of variations. Humans can't. No, computer simulation doesn't help that much. No, drawing conclusions from differences in natural strains also doesn't help.

Because...?

I'm not saying you're wrong, just that most of us aren't virologists.

I'm neither. But basically designing a Virus would mean composing a 30k long string of RNA (in this case) which creates the proteins and RNA molecules which do all the things a Virus does. And it does more than you'd think. It makes the cell copy the Virus, make the proteins, often interferes with other processes in the cell.

Copying the genome is easy. Making specific modifications isn't even that hard, as long as you don't have the illusion to know the result beforehand. But for the Virus to change its behavior in a meaningful/useful way requires multiple changes. The best someone could do is recombine changed parts from multiple variants. But they don't necessarily fit together. And the recombination also happens in nature, probably a lot more often than in the lab.

And yet H5N1 virus has yet to spread between mammals, but an airborne version of H5N1 that can spread between ferrets(and by extension humans) was achieved in a lab: https://www.science.org/doi/10.1126/science.1213362?cookieSe....

Yes. It has spread. And was very non-virulent. And they got valuable data on what to do when H5N1 does become transmissible in Humans.

However, had this Virus escaped, it would have fizzled. Showing airborne transmission does not mean the Virus would spread among ferrets and Humans under normal conditions. Mammalian H5N1 viruses might have already existed but failed to survive subsequent passage and thus did not evolve to become transmissible enough. Such lab experiments only add a minuscule risk to the much bigger risk of such a Virus occurring naturally.

This isn't a random 'lab made virus' this is a virus made by taking the specifically deadly aspects of one strain and adding the specifically infectious aspects of another. There is a very high likelihood of it being successful, because it already is. What is unlikely are these mutations happening naturally, which is why this should never be researched in sub-BSL-4 environments.

None of the proteins of this Virus had been known before. Even if hypothetically the Virus would have been constructed out of Bat viruses only known to some top-secret Chinese scientists, there is no way they could have known those components to be "deadly" (to Humans).

You underestimate evolution and wildly overestimate the capabilities of genome engineering.

We're not talking about Covid itself, but the virologists in the article building a new form of covid.

Seems like this kind of work, if deemed neccessary, should at least be done somewhere remote.

It's not the possibility that a simple lab accident could kill a billion people, the headline is that it "draws scrutiny".

Why are we fucking with nature? Like literally what is the point of this? To show that we can? Some fucked up biological arms race with the other great powers?

When you fuck with nature, nature wins. Always.

> When you fuck with nature, nature wins. Always.

There's, like, an entire human civilization on this planet right now that begs to differ.

Ever been to Vegas? Not a single thing natural about that place; it's been there over 100 years.

Do you not understand Nature does not operate on the same timescales as humanity?

Do you realize that place's entire existence is predicated on a massive logistical network that if left untrnded for a week would likely result in a completely inhospitable environment for the residents?

Civilization as we know it is excruciatingly fragile, and maintained by active expenditure of human energy. Nature, is self'sustaining, closed loop, enthalpy decreasing and Just Frigging Works. It just may take a while for us to see/realize something that makes it click that, wow, nature finds a way.

I'd think the modern hiccups in the supply chain recently would have provided sufficient examples of how fragile the entire artifice is...

Nature isn't magic, and our species has exterminated enough species and ecosystems to respect how fragile it is.

And while you speak of nature at large, we tend to care more about subsets of it. Life, in the large, survived the extinction of the dinosaurs, but a rock from space could easily fuck with nature in a way that it wouldn't "bounce back" in any way relevant to us.

But that's also a major problem. We have deemed life so unimportant, that if Russia wants San Francisco obliterated tomorrow, they have the power to do that. Literally nothing can stop them if they are hell-bent on that, damn the consequences.

I think the only people that realize things like this are those that have lost others. Perhaps by mistake even- perhaps especially - his hand slipped and he is dead now. Someone's wife out there is thinking that ALL the time. Perhaps in a year we'll be mourning permanently for New York like that.

Humanity has peaked sometime around 1960s-1980s, it's all been downhill since then. My theory is that we're in a self-destructive mode now. The technology we possess keeps advancing while our control over it and intellectual abilities are diminishing, partially because we rely on tech so much (smartphones, automation, "AI"). So in retrospect, we were meant to go (mostly) extinct during the cold war, by some miracle it was narrowly avoided, so we survived past our peak, and now we're just existing on borrowed time, the whole planet is a ticking time bomb, and the question is if we manage to become multi-planetary species before then or go (mostly) extinct. I think Elon has the same view on things, that would explain Neuralink, Starlink, SpaceX.

If by “humanity” you mean the United States’ population, possibly. But for most people in most countries, life is much better today than in the 1980s.

> Humanity has peaked sometime around 1960s-1980s

I'm 99% certain they would have said the same things in the 60's to 80's about the 20's to 40's (maybe stopping somewhere around 1939) and in the 20's they would certainly be reminiscing about the industrial revolution and gilded age.

Considering all the negative comments here, I'd say we should be just as careful trusting "science" news reporting as we think science itself should be (which it is). The official statement from BU makes a good point on that [0].

The sensationalism perpetuated by far right-wing news outlets is in fact the main danger here. Yes, there's always room for improvement, but if we are not experts able to understand the research as it was actually conducted, imho we should not jump to conclusions and blame the scientists etc. This only serves one goal (of those far-right orgs) to further diminish trust in science among the general public.

[0] https://www.bu.edu/articles/2022/neidl-researchers-refute-uk...

First, Statnews is not a "far right-wing news outlet".

Second, quoting from said Statnews article:

>But it has become apparent that the research team did not clear the work with the National Institute of Allergy and Infectious Diseases, which was one of the funders of the project. The agency indicated it is going to be looking for some answers as to why it first learned of the work through media reports.

>Emily Erbelding, director of NIAID’s division of microbiology and infectious diseases, said the BU team’s original grant applications did not specify that the scientists wanted to do this precise work. Nor did the group make clear that it was doing experiments that might involve enhancing a pathogen of pandemic potential in the progress reports it provided to NIAID.

>“I think we’re going to have conversations over upcoming days,” Erbelding told STAT in an interview.

The BU press release does not address this at all.

Yes, but the initial report was in Daily Mail, which is far-right. This is what I was referring to.

They picked up a story and sensationalized it. Without that report, this wouldn’t be a story because this kind of research is done all the time and no one makes a big deal out of it.

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