The rude people who comment on Derek Lowe’s blog
Gotta love the logic of bioethicists…
>> Hey guys, can we maybe run a vaccine challenge trial to help accelerate research? We’ve got 30k volunteers signed up already
Aw jeez, that would be horrible! Humans are unable to consent to taking a deadly risk! (though lets ignore doctors volunteering to work despite PPE shortages or soldiers volunteering to fight in remote countries) We might harm a few hundred people with this challenge trial so its best if we just run a Phase 3 trial and wait for months and months to get the results. Who cares if lives could be saved by accelerating the research?
>> Hey guys, we’ve got this vaccine candidate that’s only effective on young people. Can we just launch a Phase 3 trial for young people while we run a separate Phase 1/2 trial for older people?
Aw jeez, that would be bad! Old people are people too and we might hurt someone’s feelings if we declare that there’s a vaccine that’s only available for young folks. Lets just delay it by many months instead to the point where it becomes irrelevant, even if it could’ve saved tens of thousands of people in the meantime.
>> Folks, I’ve got this Oxford vaccine that’s 62% effective and has no major side effects. Can we start using it?
Aw jeez, absolutely not! Some people might get offended because they could’ve received the 90% effective vaccine instead, even if that 90% vaccine is in short supply and wouldn’t actually be available to them for many months to come. Rather than offending people, we should just let them die from COVID – that way we’re not to blame for anything. So lock that vaccine up until you run many more trials and ignore the fact that this causes tens of thousands of extra deaths. Bio ethics above all!
Here is the post link. From myst_05.
How should the possible end of the Great Stagnation influence your media diet?
I’ll soon write more on whether the Great Stagnation truly is over, and how we might know, but for now it suffices to mention a lot is going on in science and also in applied science and actual invention, not just nifty articles in Atlantic. On net, this means you should spend more time consuming YouTube videos (try this one on protein folding). They tend to be current, and to explain difficult matters in visual and also in fairly memorable terms. There will be such videos for virtually every new advance. You should read fewer normal books, more vertigo-inducing books, and spend less time on social media. You should read more Wikipedia articles, and when you read books you should select more from the history of science and times of turmoil. You should read this blog more often too.
Are the elites worse than you think?
Here is a new and important paper by Joshua D. Kertzer, noting that it mainly confirms what I observe every day (aren’t those the very best research studies?) Here is part of the abstract:
…political scientists both overstate the magnitude of elite-public gaps in decision-making, and misunderstand the determinants of elite-public gaps in political attitudes, many of which are due to basic compositional differences rather than to elites’ domain-specific expertise.
My rewrite of his sentence is that elites are arguing from their class and demographic biases (a bias can be positive, to be clear), not from their expertise. That lowers the marginal value of expertise, at least given how our world operates. I recall earlier research blogged by Alex showing that if you are a French economist, your views are more influenced by being a French person than by being an economist. And so on.
This is one of the very most fundamental facts about our world, and elites are among the people least likely to have internalized it.
Have a nice day.
What should I ask Noubar Afeyan?
I will be doing a Conversation with him, here is a partial bio:
Noubar was born in Beirut to Armenian parents in 1962, did his undergraduate work at McGill University in Montreal, and completed his Ph.D. in biochemical engineering at MIT in 1987.
He founded Flagship Pioneering:
Flagship has fostered the development of more than 100 scientific ventures resulting in $30 billion in aggregate value, thousands of patents and patent applications, and more than 50 drugs in clinical development.
During his career as inventor, entrepreneur, and CEO, Noubar has cofounded and helped build over 50 life science and technology startups.
Here is that link, and he is by the way co-founder and chairman of Moderna. And on the board of the Boston Symphony Orchestra.
So what should I ask him?
Friday assorted links
1. Using K-Pop to teach economics.
2. Redux of my April 4 post on tethered pairs.
4. Long blog post on DeepMind and protein folding, interesting throughout, but the most interesting section is toward the end on why DeepMind outperformed academic groups.
5. To be clear, I don’t know the answer, but why is no one even asking: “Can’t we just use the Sanofi vaccine on the young people only?” Is it that the answer is so obvious? Or is there excess confomism in this sphere? Is this simply the “this would cause the public to lose confidence in vaccines” mantra, an increasingly under-theorized and unsatisfactory substitute for an actual answer? (Would it even get a “B-” on an undergraduate, upper division psychology term paper or honors thesis?) Inquiring minds wish to know.
5b. And AstraZeneca is testing together with Russian options. Still an open question, but I’ve been saying that the Russian vaccine is underrated.
6. Good evidence for an Italian case of Covid in early December 2019.
The Simple Math of FDA Delay
Two to three thousand people a day are dying from COVID. Thus anything that delays rolling out a vaccine has a very high cost in human lives. People want to deny this, perhaps because it is so horrifying. I get a lot of pushback when I say that FDA delay is deadly. Let’s dispense with a few objections. It is true, of course, that the people who are dying today can’t literally be saved by a vaccine today but they could have been saved had they been vaccinated four or five weeks ago and similarly projecting forward.
Another response that many smart people tell me is that a vaccine can’t be rolled out immediately so even under the best scenarios you couldn’t save that many people immediately. That’s true but irrelevant. Since a lot of people are getting this wrong, I want to show this in a simple model using pictures. Red is for deaths. Green is for life. Suppose two thousand people are dying from COVID a day as in panel 1. Let’s for the sake of the simple model assume that you could deliver a vaccine to everyone on Day 1. You would then save 2000 lives a day going forward for however long the pandemic would have lasted as shown in panel 2. If you delay by one day then two thousand people die who would have lived without the delay, as shown in panel 3. Pretty obvious so far.
Now assume that the vaccine can’t roll out to everyone immediately. For the sake of this simple model let’s assume that on day one you can only vaccinate half the population. By doing so you save 1000 lives on day 1 and 2000 lives every day thereafter for the length of the pandemic. That’s the fourth panel. Now suppose we delay the vaccine rollout by one day. 2000 people die on Day 1 but you save 1000 on Day 2 and 2000 on Day 3 and every day thereafter for the length of the pandemic. How many people were killed by the delay? Compare the 4th and 5th panels. 2000 exactly as before! The slow ramp up doesn’t change the number of deaths caused by delay it just spreads them out over different days. You can adjust the ramp so that it occurs over 10 days or 30 days. Doesn’t change much on the delay margin unless you delay for so long that the pandemic is close to being over.
What could matter is if delay increases the speed at which you can ramp up. I doubt that this is true. We were ready to go with millions of doses in late October (guess why?). (In fact we had a vaccine in January and millions of doses around March-April.) We won’t really be better prepared tomorrow than we are today. It’s learning by doing that matters. See the point Tyler made earlier about economic time versus calendar time.
As Tyler noted, this is hardly the final analysis but many people are not even conceptualizing the problem correctly and this is a good place to begin.
How to build Haitian state capacity
Strengthening state capacity in low income countries requires raising tax revenue while maintaining political stability. The risk of inciting political unrest when attempting to increase taxes may trap governments in a low-tax equilibrium, but public goods provision may improve both tax compliance and political stability. To test these questions empirically, I partner with the national tax authority and a local mayor’s office in Haiti to cross-randomize both tax collection and public goods across one of the country’s largest cities. Effects are measured both via administrative data on tax revenue as well as through novel measures of political unrest. In the paper’s main result, I show that hand-delivering property tax invoices reduces individual tax compliance by 48%, and increases independently observed measures of localized political violence by 192%. In contrast, providing a valuable and visible public good (namely municipal garbage removal) increases tax compliance by 27%, and reduces localized political violence by 85%. Importantly, public goods provision significantly mitigates the adverse effects of tax collection in neighborhoods receiving both treatments. A cost accounting exercise suggests that providing the public good in this setting could pay for itself within the first year. These findings suggest that it may be possible to peacefully shift to a new equilibrium of higher tax compliance with a sufficient initial investment perhaps financed through foreign aid or other transfers.
That is a paper from Benjamin Krause, a job market candidate from UC Berkeley. Here is his home page and CV. He was also four years Chief of Staff to Sean Penn, check out the vita.
One marginal Covid-19 and Fast Grants update
A number of scientists (including, but not only, those funded by Fast Grants) have reported some interesting findings related to fluvoxamine, SSRIs and sigma-1 receptor (S1R) agonists more broadly.
- A small RCT at Washington University (n=152) published in JAMA found that patients receiving fluvoxamine had a 0% hospitalization rate (vs. 8.3% for placebo). https://jamanetwork.com/journals/jama/fullarticle/2773108
- Another group reported (data not yet published but reported here with permission) a 0% hospitalization rate in a fluvoxamine-treated cohort compared to 11% in the non-treated group. (n=146)
- A large observational analysis (n=7345) of hospitalized French patients found that those on SSRIs (of which fluvoxamine is one) had a very substantially reduced risk of death. (n=257, HR = 0.56.). SSRIs with the highest Sigma1 activation showed the greatest protection. https://www.medrxiv.org/content/10.1101/2020.07.09.20143339v2
- Fluvoxamine is a potent sigma-1 receptor agonist. Following their initial report on the role of S1R in SARS-CoV2 – host interaction, Nevan Krogan’s group found that patients receiving another sigma-1 agonist (indomethacin) had a materially reduced likelihood of requiring hospitalization compared to those receiving celecoxib, which doesn’t activate sigma-1. This work was supported by Fast Grants. https://science.sciencemag.org/content/370/6521/eabe9403.full
- Lastly, a genetic screen by a Fast Grants-funded lab (not yet published but reported here with permission) has found that genes upregulated by fluvoxamine significantly inhibit SARS-CoV2 mediated cell death.
On the off chance there is something here, fluvoxamine is relatively safe, cheap, and widely available. We are very open to both positive and negative data in this area, and have funded a further effort. Do let us know if you hear anything on this topic!
That’s it for this week!?
There is a new Toyota battery for electric vehicles:
A trip of 500 km on one charge. A recharge from zero to full in 10 minutes. All with minimal safety concerns. The solid-state battery being introduced by Toyota promises to be a game changer not just for electric vehicles but for an entire industry.
The technology is a potential cure-all for the drawbacks facing electric vehicles that run on conventional lithium-ion batteries, including the relatively short distance traveled on a single charge as well as charging times. Toyota plans to be the first company to sell an electric vehicle equipped with a solid-state battery in the early 2020s. The world’s largest automaker will unveil a prototype next year.
Here is the full story, via Molson Hart. There is still Friday.
Why I changed my mind about Brexit
I wouldn’t quite say I am for it, and I still wouldn’t myself have done it, but the decision is no longer looking like such a mistake. Since 2016, in matters of defense, Covid control, and migration, the EU has been anything but stellar. Here is the link to my Bloomberg column on this topic. Here is one excerpt:
Then there is the rise of illiberalism in Hungary, and to a lesser extent Poland, which is perhaps the EU’s biggest problem right now. The EU is seeking to withhold aid from those nations for weakening their independent judiciaries, and they are in turn threatening to veto the union’s $2.2 trillion budget and recovery package, which requires unanimous support. In response, the EU is considering approving that package outside its normal procedures.
More likely than not, a compromise will be found. But you have to wonder how long a well-functioning EU can tolerate a non-free nation such as Hungary. The EU certainly does not appear on the verge of kicking Hungary out (Germany, for one, would not welcome such a move, given its strong interests in Eastern Europe). But the challenges to the EU model presented by nations such as Hungary are much worse than they were in 2016, when the Brexit referendum was held.
Even if the EU succeeds in pushing Hungary around — and I hope it does — it is not necessarily a good outcome for the U.K. Such a policy would require weakening the EU’s unanimity requirements on many decisions, and that is something the U.K. should feel uncomfortable about. If Hungary can be pushed around, so can the U.K.
Finally, southeast England is emerging as a global technology center, especially in artificial intelligence and biomedical research. That’s great news for the U.K. But how does it square with the EU’s long-term pursuit of tougher regulations on tech companies, higher privacy standards for platforms and apps, and more stringent regulations on AI algorithms?
Will the U.K. find its interests represented by such a process? Will it be able to develop AI innovations and products without requiring prior permission from Brussels?
Of course we do still need to worry about Ireland, but perhaps this will end up being a nudge in the right direction…
Thursday assorted links
Ben Thompson on the Facebook antitrust suit
At the same time, I do have serious rule-of-law reservations about undoing a deal eight years on, particularly given the fact that it appears that the advertising-supported space is doing better than I thought a few years ago: Snapchat in particular is building a great business, LinkedIn is doing much better, and TikTok is obviously on its way.
And:
- Andy Grove famously said “Only the Paranoid Survive”, but the takeaway from many of these emails is that “Only the paranoid get sued for antitrust”; to put it another way, Facebook executives come across as worried about everything, especially Google, which, by the same token, comes across as completely asleep at the wheel (now that is a monopoly indicator if I’ve ever seen one!).
- Facebook’s stock was down less than 2% yesterday; that may reflect investor skepticism about the success of the lawsuit, but you could also argue that splitting up the company would actually unlock value: all three products would keep their audiences, but would have to monetize independently, which, given the fact that Facebook ad prices are set by auction, not artificially propped up as you would expect with an alleged monopolist, could absolutely lead to more revenue in aggregate, not less.
- Relatedly, it’s not clear that advertisers will benefit from a break-up. The entire reason why Facebook owning both Facebook and Instagram is a problem for other consumer tech companies is because advertisers benefit from a one-stop shop and don’t necessarily want to support multiple platforms.
Ben writes for-pay content on Stratechery, you can (and should) subscribe here.
Herd Immunity is Herd Immunity
Some assorted thoughts:
In the big picture, the efficacious of a vaccine doesn’t matter per se what matters is getting to herd immunity. If you have a less efficacious vaccine you need to vaccinate more people but herd immunity is herd immunity, i.e. vaccines mostly protect people not because they are efficacious but because we reach herd immunity. I’ve never had measles mostly because I have probably never been challenged with measles not because I have been challenged but due to a vaccine I fought it off. The AZ vaccine at 70% efficacious will work just fine. (One potential issue, as Josh Gans notes, we don’t yet have data on transmission reduction which could vary by vaccine.)
As I mentioned in The Vaccine Works Fast, the first shot of the Pfizer vaccine seems to work well enough so that one *might* consider delaying the second dose a few weeks to get the first dose out more widely. In fact, the accidental low-dose, standard-dose regime for the AZ vaccine had people getting the second dose 7 to 8 weeks after the first dose and that was the 90% efficacious regime. We don’t have full-information but the exact timing of the second-dose does not seem critical, although everyone should get a second dose.
A related point is that we could mix and match vaccines. The UK will run a trial on this question. Mix and matching has two potentially good properties. First, mix and matching could make the immune system response stronger than either vaccine alone because different vaccines stimulate the immune system in different ways. Second, it could help with distribution. It’s going to be easier to scale up the AZ vaccine than the mRNA vaccines, so if we can use both widely we can get more bang for our shot. (As Tyler has noted the British have really stepped up on rational trial design.)
The mRNA vaccines are getting the press but for the world as a whole the AZ, Chinese, Russian and similar more traditional vaccines are going to be the big players because facilities exist for scaling them up around the world.
Addendum: Countries in the world that now have a vaccine: the UK, Canada, Bahrain, China, Russia. One country without a vaccine: the United States. The US FDA advisory committee is meeting today. You can watch here.
Gary Becker’s theory of punishment?
In the port city of Kaohsiung, in the south of Taiwan, a migrant worker from the Philippines was caught on surveillance cameras briefly stepping into the corridor of a hotel while he was under quarantine in November.
The unidentified man wanted to leave something outside the door of a friend, who was quarantining at the same hotel, according to the Central News Agency, the official Taiwanese news agency, citing the health department.
In a video clip that circulated online, the man, wearing shorts and flip-flops, could be seen taking six lumbering strides between his room and that of his neighbor, before turning around.
The breach cost him $3,550.
Here is the full NYT story, via the excellent Daniel Lippman.
Youyang Gu will estimate vaccination numbers and herd immunity
- We believe COVID-19 herd immunity (>60% of population immune) will be reached in the US by late summer/early fall 2021 (Sep-Nov 2021).
- At the time herd immunity is reached, roughly half of the immunity will be achieved via natural infection, and the other half will be achieved via vaccination.
- New COVID-19 infections may become negligible before herd immunity is reached. Our current best estimate of when daily community transmissions will drop below 1,000 per day is summer 2021 (Jul-Sep 2021).
- Summarizing the above findings, our best estimate of a complete “return to normal” in the US is late summer 2021 (Aug-Oct 2021).
- We estimate around 30% of the US population (~100 million) will have been infected by the SARS-CoV-2 virus by the end of 2021. This translates to a final US COVID-19 death toll of roughly 500,000 (+/-100k) reported deaths.
You can track the data here, his earlier forecasts of cases, hospitalizations, and the like were among the best. He is here on Twitter. For the pointer I thank CatintheHat.