The article is about how (well akshually) deployment of new ideas has greater impact than the inventions themselves.
Since this is HN, there is a canonical translation of this, something like "Ideas are worth nothing, execution is everything".
The Eureka Theory of History Is Wrong
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Re: The Eureka Theory of History Is Wrong
#12Earlier quoted context omitted.
Do you have any evidence to suggest mRNA research was slowed by regulation that was loosened up in the face of COVID? My understanding is 1) it builds on decades of publicly funded research, originating in military programs, and 2) it was being developed nonstop and every prior attempt had serious adverse effects (specifically serious allergic reactions).
Then where are all the other mRNA vaccines? If it is a tech change rather than a regulatory exception there should be a whole bunch of other vaccines coming out by now, they've had long enough. COVID appeared in March, they had the vaccine in clinical trials by April. The technical aspects aren't a factor here - the time taken to develop a vaccine is basically instant.
Covid vaccines were a repurposing of MERS vaccine research which is also a coronavirus and has a similar spike protein. So, some vaccine companies had a leg up as they were already pursuing MERS vaccines. The problem was that progress was slow because nobody was willing to put large amounts of development money behind a vaccine for a disease with such a small number of cases.
Covid poured accelerant on MERS vaccine research. Suddenly, there was a disease with lots of cases with lots of people willing to sign up for trials. In addition, there was a lot of money sloshing around so companies were willing to take the financial risk to combine Phase II and Phase III trials (to be fair--a Covid vaccine passing a Phase II trial was always going to pass a Phase III trial until we had many different vaccines). And, please do remember, nobody knew if mRNA for Covid was actually going to work.
Other mRNA vaccines are in the pipe. However, they have to go through trials with a lot less funding and a lot less money at the end. Rabies(!) got a Phase I trial--but it's hard to get to Phase II since rabies is so rare. mRNA flu vaccines are in Phase III. mRNA HIV vaccines are in Phase I and may be in Phase II by now.
What you see is that if we drop the equivalent of the Manhattan Project at producing a vaccine, we can pretty much produce a vaccine for a virus in a hurry. However, if we're not willing to drop that kind of cash, progress is slow.
If you want more vaccines, tell some of these multi-jillionaires to quit fucking around with virtual crap like Bitcoin and Twitter and start dropping some non-virtual gigabucks on vaccine companies that are trying to produce real products.
Re: The Eureka Theory of History Is Wrong
#13There is a Strugatsky brothers short story, in which most of the inhabitants of a planet seem to have suddenly left via some portals, but there are a few who remain, highly armed, violent, and apparently seeking to prevent anyone else from using the portals. TFA reminds me of this story (which reminded me of the situation sketched by TFA when I had read it, except perhaps for the ratio of leavers to left behinds) but…
I know one familiar-sounding, but different (without violent armed remainers) novel by Clifford Simak: "City".
It’s such a weird collection of ( chronologic ) novels.
One of my favorite book. I read it every 5 years or so.
Re: The Eureka Theory of History Is Wrong
#14The article is about how (well akshually) deployment of new ideas has greater impact than the inventions themselves.
Since this is HN, there is a canonical translation of this, something like "Ideas are worth nothing, execution is everything".
Re: The Eureka Theory of History Is Wrong
#15Earlier quoted context omitted.
Then where are all the other mRNA vaccines? If it is a tech change rather than a regulatory exception there should be a whole bunch of other vaccines coming out by now, they've had long enough. COVID appeared in March, they had the vaccine in clinical trials by April. The technical aspects aren't a factor here - the time taken to develop a vaccine is basically instant.
Covid vaccines were a repurposing of MERS vaccine research which is also a coronavirus and has a similar spike protein. So, some vaccine companies had a leg up as they were already pursuing MERS vaccines. The problem was that progress was slow because nobody was willing to put large amounts of development money behind a vaccine for a disease with such a small number of cases. Covid poured accelerant on MERS vaccine r…
The COVID vaccines were rolled out on the basis that they were more-or-less safe and probably efficacious. A lot of them turned out not to be as safe as anticipated - eg, the blood clotting issue in the Astra-Zeneca virus or the myocarditis issues in the Moderna vaccine that have gotten its use limited in Scandinavian countries [0]. It turns out that the evidence that was collected at speed wasn't actually enough to justify the actions taken.
That was a good standard and an appropriate thing to do. But that standard is lower than what the medical regulators usually accept. As you point out, Phase 3 trials are good to do but it is going to make it a lot harder to get a vaccine to market if people have to take them seriously. Vaccine makers should be allowed to sell vaccines that are merely safe and effective; they shouldn't have to pass a higher standard than that to sell the things with a disclaimer label.
As an aside I'd also question the efficacy results as the vaccines are probably a lot less effective now. It appears the virus has mutated quite substantially. But that hasn't changed the vaccine approval status, raising interesting questions around why efficacy is even a requirement to sell the thing. Why not just a safety study with the requirement that efficacy data will be collected and made available? We need to figure out if something is efficacious, but there will be more money to do that - and better data - if it is allowed to go to market. As we can see from COVID, jabs in arms and money are the two things missing to make vaccine development fast. The normal regulatory framework makes both those things hard to get.
> If you want more vaccines, tell some of these multi-jillionaires to quit fucking around with virtual crap like Bitcoin and Twitter
Didn't most of the wealthy people in Bitcoin make their money in Bitcoin? There weren't a lot of ultra-wealthy people putting serious money behind it as I recall.
[0] https://www.reuters.com/world/europe/finland-pauses-use-mode...
Re: The Eureka Theory of History Is Wrong
#16> WHY THE AGE OF AMERICAN PROGRESS ENDED
Actual title? Are they testing out titles.
Things of the genre “everything is going to shit and here’s what to blame” are not worth reading. Exposing “The decline” of whatever the target audience cares about sure is good for attention but it’s just a toxic emotional manipulation and not useful to actually enlighten anyone.
It comes down to things always changing and having a bad attitude about the present and an unreasonable positive attitude about the past is very prevalent.
Re: The Eureka Theory of History Is Wrong
#17Earlier quoted context omitted.
Covid vaccines were a repurposing of MERS vaccine research which is also a coronavirus and has a similar spike protein. So, some vaccine companies had a leg up as they were already pursuing MERS vaccines. The problem was that progress was slow because nobody was willing to put large amounts of development money behind a vaccine for a disease with such a small number of cases. Covid poured accelerant on MERS vaccine r…
The COVID vaccines were rolled out on the basis that they were more-or-less safe and probably efficacious. A lot of them turned out not to be as safe as anticipated - eg, the blood clotting issue in the Astra-Zeneca virus or the myocarditis issues in the Moderna vaccine that have gotten its use limited in Scandinavian countries [0]. It turns out that the evidence that was collected at speed wasn't actually enough to…
You're completely ignoring just how big of a threat Covid was, which is a part of the risk-to-benefit ratio of a Phase III trial. The same vaccines, with the same P3 results, may well have not been approved for, say, a mild cold virus, but would have also been approved for Alzheimer's.
The reality of drug approvals is that they always take into account proven benefits and risks (including some room for yet-unknown risks) compared to the available alternatives (including other vaccines, other medication, or even not treating the disease at all).
This calculation was not necessarily changed for Covid in some special way. The bug difference with Covid was that governments pumped billions into getting the research done, as did the companies themselves knowning that they will likely be able to literally sell tens of billions of doses of this vaccine if they make it work even a little bit.
Re: The Eureka Theory of History Is Wrong
#18Earlier quoted context omitted.
Do you have any evidence to suggest mRNA research was slowed by regulation that was loosened up in the face of COVID? My understanding is 1) it builds on decades of publicly funded research, originating in military programs, and 2) it was being developed nonstop and every prior attempt had serious adverse effects (specifically serious allergic reactions).
Then where are all the other mRNA vaccines? If it is a tech change rather than a regulatory exception there should be a whole bunch of other vaccines coming out by now, they've had long enough. COVID appeared in March, they had the vaccine in clinical trials by April. The technical aspects aren't a factor here - the time taken to develop a vaccine is basically instant.
I just want to confirm here that you are asserting that COVID-19 appeared in March 2020? Obviously this is not the case or it would be called COVID-20.
Re: The Eureka Theory of History Is Wrong
#19The part of the article which explains how the smallpox vaccine was distributed around the world before cold storage and airplanes is just incredible.
1) Recruit 22 orphaned boys
2) Inject two of them with the cowpox virus (which is the actual smallpox vaccine)
3) Put all the boys on a ship leaving Spain for Venezuela
4) Scrape material from the two boy's pustules (appearing after a couple of days) and inject two more boys with that - the first two boys recover
5) Continue this daisy-chain approach until reaching Venezuela
6) Go on with people in Venezuela, arm-to-arm
7) Continue to Mexico and other places
8) Go global
Re: The Eureka Theory of History Is Wrong
#20Earlier quoted context omitted.
The COVID vaccines were rolled out on the basis that they were more-or-less safe and probably efficacious. A lot of them turned out not to be as safe as anticipated - eg, the blood clotting issue in the Astra-Zeneca virus or the myocarditis issues in the Moderna vaccine that have gotten its use limited in Scandinavian countries [0]. It turns out that the evidence that was collected at speed wasn't actually enough to…
You're completely ignoring just how big of a threat Covid was, which is a part of the risk-to-benefit ratio of a Phase III trial. The same vaccines, with the same P3 results, may well have not been approved for, say, a mild cold virus, but would have also been approved for Alzheimer's. The reality of drug approvals is that they always take into account proven benefits and risks (including some room for yet-unknown ri…
Fair enough. This may be where there is nothing more to say. But just in case - why is it necessary to centralise the decision for making risk-to-benefit ratio assessments? Everyone has different risk profiles and may have reasonable disagreements about how dangerous the risks are vs the benefits. We've learned that several widely used vaccines were more damaging than the health authorities realised, but nearly nobody has a problem with them having been rolled out to the masses. This suggests the standards of the health authorities are unreasonably high. When they lowered their standards for COVID there was barely any extra damage done, we're measuring the incidents in single digit cases per million.
A lot of people - dare I say most - have a higher tolerance for risk than the health authorities do. Why is it necessary to hold back progress because of nervous bureaucrats? We could make faster progress by letting people willing to take risks take risks.