On Human Challenge Trials (HCTs):

Disclaimer: I have been completely plugged out of Covid-19 stuff for over a year, definitely not an expert on these things (anymore), and definitely speaking for myself and not 1Day Sooner (which is more bullish on HCTs)

I worked for 1Day sooner last year as one of the main people investigating the feasibility and usefulness of HCTs for the pandemic. At least back then (March 2020), we estimated that it would optimiscally take 8 months to complete  the preparations for an HCT (so not even the HCT itself). Most of this time would be used for manufacturing and approving the challenge virus, and for dose-finding studies. (You give people some of the virus and check if it's enough to induce the disease, then repeat with a higher dose etc.)

I think in a better world, you can probably speed up the approval for the challenge virus, and massively parallize dose-finding to be less lenghty. Not sure how many months that gets you down to, but the 2.5 months for preparation + the actual HCT you assume seem overly optimistic to me. I still think HCTs should have been prepared, but I'm not sure how much speed that would have actually gained us. More details here in the section "PREPARATORY STEPS NEEDED FOR HUMAN CHALLENGE TRIALS" (free access)

There was also some discussion of challenge trials with natural infection (you put people together with infectious people who have Covid-19), which might get around this? But I don't know what came out of that (I think it wasn't pursued further?). Not sure how logistically feasible that actually is. (I think it would at least be more difficult politically than a normal HCT.)

Don't think this changes the general thrust of your post, but wanted to push back on this part of it.

(There's some chance I missed followup work, perhaps even by 1Day Sooner itself, that corrects these numbers, in which case I stand embarrassed :) )

Is there any public organisation which can be proud of last year?

This is an important question, because we want to find out what was done right organizationally in a situation where most failed, so we can do more of it. Especially if this is a test-run for X-risks.

There are two examples that come to mind of government agencies that did a moderately good job at a task which was new and difficult. One is the UK's vaccine taskforce, which was set up by Dominic Cummings and the UK's chief scientific advisor, Patrick Vallance and responsible for the relatively fast procurement and rollout. You might say similar for the Operation Warp Speed team, but the UK vaccine taskforce overordered to a larger extent than Warp Speed and was also responsible for other sane things like the simple oldest-first vaccine prioritization and the first doses first decision, which prevented a genuine catastrophe due to the B117 variant. (Also credit to the MHRA (the UK's regulator) for mostly staying out of the way.)

See this from Cummings' blog, which also outlines many of the worst early expert failures on covid, and my discussion of it here:

This is why there was no serious vaccine plan — i.e spending billions on concurrent (rather than the normal sequential) creation/manufacturing/distribution etc — until after the switch to Plan B. I spoke to Vallance on 15 March about a ‘Manhattan Project’ for vaccines out of Hancock’s grip but it was delayed by the chaotic shift from Plan A to lockdown then the PM’s near-death. In April Vallance, the Cabinet Secretary and I told the PM to create the Vaccine Taskforce, sideline Hancock, and shift commercial support from DHSC to BEIS. He agreed, this happened, the Chancellor supplied the cash. On 10 May I told officials that the VTF needed a) a much bigger budget, b) a completely different approach to DHSC’s, which had been mired in the usual processes, so it could develop concurrent plans, and c) that Bingham needed the authority to make financial decisions herself without clearance from Hancock.

This plan later went on to succeed and significantly outperform expectations for rollout speed, with early approval for the AZ and Pfizer vaccines and an early decision to delay second doses by 12 weeks. I see the success of the UK vaccine taskforce and its ability to have a somewhat appropriate sense of the costs and benefits involved and the enormous value of vaccinations, to be a good example of how it's institution design that is the key issue which most needs fixing. Have an efficient, streamlined taskforce, and you can still get things done in government.

The other example of success often discussed is the central banks, especially in the US, which responded quickly to the COVID-19 dip and prevented a much worse economic catastrophe. Alex Tabarrok:

So what lessons should we take from this? Lewis doesn’t say but my colleague Garett Jones argues for more independent agencies in his excellent book 10% Less Democracy. The problem with the CDC was that after 1976 it was too responsive to political pressures, i.e. too democratic. What are the alternatives?

The Federal Reserve is governed by a seven-member board each of whom is appointed to a single 14- year term, making it rare for a President to be able to appoint a majority of the board. Moreover, since members cannot be reappointed there is less incentive to curry political favor. The Chairperson is appointed by the President to a four-year term and must also be approved by the Senate. These checks and balances make the Federal Reserve a relatively independent agency with the power to reject democratic pressures for inflationary stimulus. Although independent central banks can be a thorn in the side of politicians who want their aid in juicing the economy as elections approach, the evidence is that independent central banks reduce inflation without reducing economic growth. A multi-member governing board with long and overlapping appointments could also make the CDC more independent from democratic politics which is what you want when a once in 100 year pandemic hits and the organization needs to make unpopular decisions before most people see the danger.

I really would like to be able to agree with Tabarrok here and say that, yes, choosing the right experts and protecting them from democratic feedback is the right answer and all we would need, and the expert failures we saw were due to democratic pressure in one form another, but the problem is that we can just look at SAGE in the UK early in the Pandemic or Anders Tegnell in Sweden, who were close to unfireable and much more independent, but underperformed badly. Or China, which is entirely protected from democratic interference and still didn't do challenge trials.

Just saying the words 'have the right experts and prevent them from being biased by outside interference' doesn't make it so. But, at the same time, it is possible to have fast-responding teams of experts that make the right decisions, if they're the right experts - the Vaccine Taskforce proves that. I think the advice from the book 10% less democracy still stands, but we have to approach implementing it with far more caution than I would have thought pre-covid.

It seems like following the 10% less democracy policy can give you either a really great outcome like the one you've described, and like we saw a small sliver of in the UK's vaccine procurement, or a colossal disaster like your impossible to fire expert epidemiologists torpedoing your economy and public health and then changing their mind a year late.

Suppose the UK had created a 'pandemic taskforce' with similar composition to the vaccine taskforce, in February instead of April, and with a wider remit over things like testing and running the trials. I think many of your happy timeline steps could have taken place.

One of the more positive signs that I've seen in recent times, is that well-informed elite opinion (going by, for example, the Economist editorials) has started to shift towards scepticism of these institutions and a recognition of how badly they've failed. We even saw an NYT article about the CDC and whether reform is possible.

Among the people who matter for policymaking, the scale of the failure has not been swept under the rug. See here:

We believe that Mr Biden is wrong. A waiver may signal that his administration cares about the world, but it is at best an empty gesture and at worst a cynical one.

...

Economists’ central estimate for the direct value of a course is $2,900—if you include factors like long covid and the effect of impaired education, the total is much bigger. 

This strikes me as the sort of remark I'd expect to see in one of these threads, which has to be a good sign.

Going to take an actual look at this later (my thesis is probably on COVID-19 x IIDM so I'm excited!) but wanted to let you know that I really appreciate the humorous flair in your post!

I'm pretty late to this! Something I notice in this post, which is mentioned in one of the comments, is that it focuses on money and competence as the main barriers to tackling Covid. I would say that the way institutions are set up to make decisions and implement them is a much bigger factor.

The fast timeline described would only be possible in a world where our institutions were set up completely differently. For example, when thinking about how things should have gone, it's easy to say person X and person Y should have talked to each other without realising that they probably didn't have each other's phone numbers, and might not have known each other existed!

We can and should look at how our institutions could have been set up differently to handle Covid better, but that requires some thought too. Institutions that are optimised for one thing are by default not optimised for other things - if we redesigned our institutions to prepare for the next Covid, that might not help us very much in dealing with a super-volcano, or everyday life.

The reason I point this out is because I think this kind of naive analysis is actually very useful - I think it does achieve the goal of showing us where we could have done better - and at its most useful, it highlights weaknesses in systems that can be improved. But I'm concerned that if this kind of analysis were shared without recognizing its limitations it could come across badly.

"I am extremely puzzled why China or one of the other ahem non-individualist governments didn't do these." 

Even in China, politicians and scientists fear public backlash, especially considering how to Chinese eyes the virus seems much more dangerous/lethal than to Europeans, given what happened in Wuhan:

In mainland China, scientists are intrigued by the idea, but they said it would be difficult for the public to accept.

“It is difficult to do it in China. Recently there were some articles [online about HCT] and they drew a lot of criticisms,” said Zhu Fengcai, deputy director of the Jiangsu Provincial Centre for Disease Control and Prevention.

Tao Lina, a Shanghai-based vaccine expert, said the risks were too great for researchers.

“Most people would not accept it … it is also hard to pass the ethical requirements,” he said.

https://www.scmp.com/news/china/science/article/3082570/coronavirus-vaccine-who-issue-guidelines-proposed-use-human

I could not agree more with your sentiment, but the "We did ok" side has a point: If there was a much better policy or intervention, why was it  done by no country, and no philanthropist?  As a country, not much was stopping you a year ago to unilaterally prepurchase tons of vaccines and start manufacturing them. Getting 20 million doses manufactured early is much easier than 2 bn, you do not need to spend time coordinating with others etc., so what happened? From memory:

China only really started to vaccinate its citizens in March (but is doing it really fast now), despite approving the Sinopharm vaccine for EUA in July. Phase 3 data for their vaccines came in at the end of 2020, and seeing how urgent China is vaccinating now, it really does seem like manufacturing was their bottleneck.  Russia approved its Sputnik Vaccine in August and started mass production immediately, but appears to only have been able to produce 2 million doses instead of the estimated 30 million by 2020  because of manufacturing problems.

But you do not have to design your own vaccine, you could just prepurchase  a comparatively low amount of vaccines. There are enough oil states with no democratic decision making, so why did nobody say to Pfizer: "Here are 100 dollars per dose (9 times what the EU pays you) to start producing them now.  The same day you publish your Phase 3 trial results, we expect the doses at our doors so that we can vaccinate our citizens."? E.g. Qatar only has 2 million citizens, so surely they could have procured enough early on, from different manufacturers? 

And that is just the procurement/manufacturing side of things. There's also population wide rapid screening tests (AFAIK only Slovakia and Germany), pool testing (China and Rwanda), large, multicenter drug trials (only UK with the RECOVERY trial) as things that seem like extremely low hanging fruits but were neglected almost anywhere,  despite strong economic incentives to  get things right. 

I am noticing my confusion: Are our institutions really so bad at dealing with crises? Or is it much more difficult than it looks to implement changes and react to completely novel situations?

"The EU's sluggishness, bullying, pandering to risk aversion, and total lack of (short-term) accountability for its own decisions. AZ approval came three months after UK approval, Pfizer three weeks after. Supposedly this was mostly taken up with haggling prices down from crazy low to crazy low."

The last sentence is uncharitable and wildly inaccurate. Do you have any evidence for this? Prior to approval, the contracts had already been finalized, and anyway, it's not the EMA (Europe's FDA equivalent) that is doing the haggling.  AZ approval was delayed because of the shoddy quality of their studies (and even more so in the US). Why Pfizer took longer is unknown, but it certainly included, meanwhile leaked, working through problems like this: 

For the Pfizer product, mRNA integrity for clinical batches came in at about 78%, compared with 55% for the proposed commercial batches, an EMA email dated November 23 states. That difference led to the concerns that Pfizer and the regulators worked through.

It is to the credit of the EMA that they did not publicly release these problems, thus not fuelling vaccine skepticism but instead taking the reputation hit of seemingly needlessly delaying  the approval.

I think your happy timeline is still too conservative. Moderna didn't suddenly gain the ability to make a vaccine in 2 days, just before the pandemic began. Realistically they must have had the ability for some fraction of their decade-long existence. In the world where our institutions didn't get in the way as you describe, Moderna would have long since launched mRNA vaccines against other infectious diseases like the flu or malaria. The factories (at least a few) would have already been built and could have been repurposed without massive new investment, the public (or at least public institutions) would already be familiar and somewhat comfortable with the technology, and distribution channels would already be in place.

Novavax shows that the old way of creating vaccines of giving an adjuvant along with the protein (or a subunit) works fine and works with less side-effects.  While Novavax does use their own patented adjuvant that needs rare ingridients other adjuvants are possible. Stoeker was likely right when he proposed to vaccinate everyone in Germany with the vaccine he used to vaccinate himself and his family. 

We accept mask use based on the precautionary principle and we should have accepted Stoekers vaccine that demostrable produced antibodies on the same principle. While Stoeker only has data for side-effects for hundred patient the fact that the side effects on average are so much lower then that of viral vector and mRNA vaccines suggests that it's likely a safer vaccine (and the fact that Novavax has less side effects supports this).

Suing Stoeker on the allegation of running an unregistered clinical trial on his family was the height of ignorance. 

Focusing clinical trial resources on untested and hard to scale up vaccine technology was a very bad idea when it was easy to take existing adjuvants, synthezise the spike protein (/domains of it) and scale up the production. 

Any self-respecting COVID rant must foreground vaccination. It is the solution, where other policies just buy time, or else consume old or disabled people.

This is false. Vaccines are not the only possible policy to drive COVID-19 to extinction. While we haven't spend the amount on clinical trials that would be necessary to know for certain the best guess for the effect of prophylactic ivermectin we have at the moment is Low-certainty evidence found that ivermectin prophylaxis reduced COVID-19 infection by an average 86% (95% confidence interval 79%–91%). 

The case for challenge trials for prophylactic ivermectin is the same as the case for challenge trials for vaccines. 

While taking taffix multiple times per day is more annoying it also is a potential of doing the work of bringing infection risk down. It getting completely ignored instead of running more studies was a policy failure. 

Several times (fomites, masks, asymptomatic spread, long COVID, schools, lab-leak) we saw dramatic reversals of global policy, based not on dramatic new evidence, but on shifts in how elite factions decided to interpret the evidence. 

While it's popular to say that the lab-leak shift wasn't because of new evidence I think it was because people like Ian Lipkin who published in the beginning of the pandemic that he considers the natural origin the only possible explanation, because they thought that the WIV was doing gain-of-function experiements in biosafety 3 or 4 actually read the papers from the WIV and discovered that they did the experiements in biosafety 2. 

While the papers certainly existed beforehand I don't think they were in the expert awareness. 

From the very beginning, the top-down systems have worked to help the virus. FDA literally banned hospitals from using their own PCR labs, and forced the nonworking CDC "test" on everyone. 
 

The vaccine companies were and are forbidden from paying to get volunteers from the high-risk groups... a trial in the NY inner-city nursing homes would have been done in a month, while the actual PFE trial using white female volunteers took 35,000 volunteers to get 96 cases... and burned up most of the year doing it. 
 

And of course, the successful Scandi Bio Phase 3 trial results are only in the Turkish drug approval process... and nowhere else, because they use non-pharma molecules. 38% reduction in recovery time as a treatment, and completely safe and GRAS. As a preventive, this protocol could save most of the people in the non-vaccinated countries:

https://onlinelibrary.wiley.com/doi/10.1002/advs.202101222

This post seems to fall victim to the planning fallacy.

One explanation for why people commonly underestimate project completion time is this: people consider a best-case scenario where everything goes smoothly. Like the "happy timeline" in this post. Alas, reality is not like this at all.

When people are asked for a “realistic” scenario, they envision everything going exactly as planned, with no unexpected delays or unforeseen catastrophes—the same vision as their “best case.”

Reality, it turns out, usually delivers results somewhat worse than the “worst case.”

-- Eliezer Yudkowsky, in the post linked above.

The popular solution for countering the planning fallacy is taking an outside view (aka reference class forecasting). In that light, Covid vaccines looks surprisingly good. As you note at the top of your post, Covid vaccines were developed quickly compared to the reference class of vaccines.

I'm very sympathetic to the idea of writing down our collective mistakes and trying to learn from them. It just seems to me that this post contrasts our mistakes with a highly unrealistic, idealized timeline. My guess is that more realistic expectations might lead to better goals for improving the world 🤔

Couldn't eg India have variolated their entire population and developed a robust process for it within a month in March 2020?