You mention rapid sequencing, rapid wastewater monitoring, PPE stocking/distribution policies, and more effective local lockdown procedures/policies. Those would all be factors that would reduce the value of "X" (as in, the consequences of bad outcomes in either scenario), rather than any coefficients in front of X.

I don't necessarily agree that the past 25 years, particularly if you are excluding COVID, is a meaningful representative sample... unless you want to compare it to the loss of life from GoF over the past 25 years excluding COVID. In that case, I'd challenge you to demonstrate a loss of life from GoF research that is over 10K. Given the ~100K lives estimate, that puts it at 10x greater benefit than not doing GoF research.

> However if we undergo a similar exercise of chances of Lab leak causing an outbreak we'll probably end up with a similar figure of 1/100. In a lab leak we'll have to contend with a more powerful variant of a pathogen that has caused a prior outbreak which may kill an order more people than the average outbreak.

There's a number of false assumptions here. Your threat assessment seems more rooted in works of fiction than reality. That the probability is equivalent is highly debatable, particularly since it is far easier (and cheaper) to apply risk mitigations to a virology lab than to society as a whole. It's also not a given that a lab leak means we'll have to contend with a more powerful variant of a pathogen. Even if it were a more powerful variant of a pathogen, that does not necessarily relate to a higher death toll. In fact, SARS-COV-2 was far less virulent than SARS-COV-1, and that's a significant contributor to why it had so much more impact.

Even if we ignore ALL of that, in the even that there was an outbreak from a virology lab doing GoF research, that would mean we would be much further ahead on research to combat the virus than if said virus were to occur in the wild. We'd have shorter times to have disease profiles, tests, epidemiological models, and vaccines, and the impact of shorter times is exponential. While it is conceivable that a leak from a lab leads to a higher death count, it is far more conceivable that a virus that didn't come from a lab would end more lives.

> if we entertain that Covid was caused by a lab lead ~10m deaths, or 100x of 100k.

Spanish flu, which existed before anyone knew how to do GoF research, killed far more people than COVID-19. At the lowest estimate, it's about 17 million people, and at the high end closer to 100 million people. The population of the world at the time was ~1/4 the population when COVID-19 hit the scene, so on a per capita basis COVID-19 isn't in the same league. AIDS, which we've been able to track back to its natural origin, has killed 42 million people. The Bubonic Plague killed... 75+ million, or about a third of the European population.

Nature is way better at killing us than any lab.

> Ultimately it seems GoF research is playing with fire without knowing if the effort actually will reduces total deaths on net.

Another way to think of it is that international trade & travel is playing with fire without knowing if the effort actually will reduce total deaths or not. We could therefore return to the days of the horse and buggy, or we could continue with the practice and put in place mitigations, like GoF research, to mitigate the risks it entails.

Dangerous things need to be contained really well, regardless of whether this virus leaked or not.

Natural dangerous respiratory virus outbreaks do occur from time to time so it's better to be ready against them which also steels us against lab leaks.

It's obviously very risky to do, but we should focus on adopting and enforcing better security practices to minimize the risks, not ban GoF altogether.

That's a more important question about whether or not this particular virus came out of a lab or not, because, if the answer to the above is "yes", then we need to take whatever your/whoever's proposed mitigation/prevention steps even if this thing came about via natural pathways. Even banning GOF research in labs might not be sufficient, if malicious people (wooo "bioterrorism") could go about doing this outside of labs.

Also, we need to plan and prepare for the next global respiratory pandemic in any event, as we know they happen periodically regardless of origin. That's true even if we never authoritatively understand the origin of this one.

That said, there's zero question that DEFUSE proposed to collect and enhance replication-competent potential human pandemic pathogens. That proposal wasn't funded, and that proposal indeed anticipated that the GoF work would be done at UNC; but the WIV seems clearly capable of that work too. We don't know what happened next, and I believe we should do everything in our power to find out. If possible, that would occur with China's cooperation; but since that seems impossible for now, it should proceed without. For example, large amounts of raw sequencer reads exist on the servers of American and European research groups and their service providers. Those should be subpoenaed, and searched for evidence of early SARS-CoV-2 genomes as contamination, similar to that found in the Antarctic soil samples. Do you disagree?

I also dislike the framing in terms of "GoF ban" because I agree fully that nature may present a greater risk than anything we could make in a lab. It seems entirely plausible to me that right now, there are viruses deep inside some cave that could end human life as we know it, but that we've simply been lucky enough that the virus has never left the cave. But how could that possibly be a reason to send some grad student into the cave? From pictures and videos of WIV sampling trips, they were sending researchers in with no protection beyond a surgical mask and nitrile gloves. That seems insane to me. If humans will be entering an area regardless--for agriculture, or tourism, or whatever else--then I agree we should be sampling it. But why should we go looking for trouble in areas that no other human is likely to approach?

You keep saying that virology brings potential benefits, and that's obviously true. It also brings potential detriments though, including research-origin pandemics, and it's done so at least once in the past. I see no evidence that you're making anything like a cost/benefit tradeoff here; you're simply disregarding all the costs, somehow classifying deaths quite directly caused by research activities as "natural" and thus unimportant. That's not how anything else in life works--if I'm careless with my campsite, then the resulting wildfire may be indistinguishable from one set by lightning, but the ranger is still going to say it's my fault.

I have no special affection for Ridley, though I still prefer him to the author of the article you linked, who called Alina Chan a "moronic psychopath"[1]. In any case, the messenger shouldn't matter. As to the narrow question of investigating the origin of SARS-CoV-2, I believe Ridley is right and you're dangerously wrong. You've correctly shut down some genuine nonsense here (e.g., Moderna patents on the sequence). You've also posted at least two unequivocal falsehoods yourself though (WIV situated based on diversity of nearby relevant viruses, no prior unnatural pandemic), and presented other evidence in much stronger terms than any scientific consensus (e.g., the two lineages; George Gao[2] thinks they probably evolved in humans, and I presume you're not going to call him a lab leak conspiracist). I don't see how that enhances public knowledge.

1. https://twitter.com/PhilippMarkolin/status/15208575112969994...

2. https://twitter.com/jbloom_lab/status/1497627179965845506?la...

It’s all about blame. Blame is a useful geopolitical tool.

Virologists competing with each other on who can produce the most infectious virus does not make us safer. Pursing research to prove that small pox can indeed mutate to be infectious via airborne aerosols is reckless, it creates a super charged version of a virus that never evolved naturally despite being a common disease for millennia.

See for example: https://en.wikipedia.org/wiki/2007_United_Kingdom_foot-and-m...

In my opinion, gain of function is too dangerous with current security measures, and we should consider a moratorium. Lab biocontainment is exceptionally hard.

So maybe respiratory diseases, no matter how dangerous they currently are should be heavily restricted to labs that can handle them, and then have international monitors at each of them with strict reporting rules not tied to any organization like WHO or UN or whatever, they are just there to report lab leaks no matter how small.

A powered up virus escaping from a lab is almost definitionally not a natural event

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.

You raise a few objectionable assertions that I think is good to contemplate: - GoF was never banned - The ban was NIH funding GoF - The ban was lifted in 2017 anyways - Is this risky? The ban on funding it doesn't mean it's risky, as per se. - The potential pie in the eye risk are infinite, but what are the realistic risks? That really depends on the technical details of how the research is done, and where it's done. - Compare and contrast to activities that are very dangerous and have nearly infinite catastrophic risks but we do every day: driving, flying, operating nuclear power plants, refining oil, and much much more.

All of this research came out of the desire not to be caught flat footed by the next version of SARS or MERS. Overall global research did in fact prep us for SARS-CoV-2. Vaccines "made in months" that have stood the test of efficacy and safety? Months if you ignore the years of research behind it.

Is this particular thing excessively dangerous or not? I'm not 100% sure. Most of the "this is unacceptable" seems to be coming from people who seem to have a visceral hatred of Dr Fauci and who as head of the NIH was indirectly responsible for this funding. But I don't find that a reasonable line of reasoning. One thing I know, is every scientist I know is not paid a boat load, and care deeply about what they are doing and why.

Perhaps GoF is too 'dangerous', but maybe we should also hear about how it can be made safe, how does it compare in hazardousness to other common things that are deemed 'safe' and what the benefits are.

On the surface that might sound ok. However if we undergo a similar exercise of chances of Lab leak causing an outbreak we'll probably end up with a similar figure of 1/100. In a lab leak we'll have to contend with a more powerful variant of a pathogen that has caused a prior outbreak which may kill an order more people than the average outbreak. So perhaps a million deaths alone, or if we entertain that Covid was caused by a lab lead ~10m deaths, or 100x of 100k.

Ultimately it seems GoF research is playing with fire without knowing if the effort actually will reduces total deaths on net.

A much more effective route seems to simply invest in rapid sequencing, rapid wastewater monitoring, PPE stocking/distribution policies, more effective local lockdown procedures/policies.

GoF virus engineering cannot be suppressed now because Covid is obviously an effective military weapon against the USA, whose love of freedom defeats public health policy.

No such problem in Wuhan where authorities reported welded shut the doors of infected households.

Gain of function research is a vital tool in preventing pandemics. Moratoriums are pretty much universally opposed by virologists and are already regulated under DURC/DUCG (which both require unaffiliated oversight from the public). Influenza for example is able to be researched without having to infect human subjects because we used GoF to make lab strains infect rabbits.