Month: December 2020
From my email, on bioethicists
Hi Tyler. I had a brief career as an ethicist. I realized quickly that the incentives are all wrong if what we want is people who will think hard about humanity’s pressing ethical dilemmas and who will suggest intuitively appealing solutions.
Since almost all ethicists are academics, they have to publish, and in order to publish you have to be novel, and since the basic principles of ethics are little changed for millennia the incentives to do thorough homework on the basis of principles which are widely understood and accepted is not great.
Furthermore, if you decide to be a utilitarian, then basically all ethical issues will boil down to cost/benefit analyses which you have to outsource to technocrats, so your unique expertise as an ethicist will be worth little.
For whatever it’s worth, one could justify most of the widespread opinions of bioethicists and other ethicists who reach conclusions quite repugnant to utilitarians on the basis of “care ethics”. The result is not important and even the rule is not important, what is important is the amount of personal concern you project to specific human beings. Most people would prefer not to expose their close family members to mortal danger so adopting a policy deliberately exposing strangers to such danger appears un-caring.
If ethicists could manage to get themselves thought of as humble, competent people on a level with dentists, that would be splendid.
The name of the author has been anonymized to protect the innocent.
Sunday assorted links
1. That Biogen conference in Boston was worse than you thought. And Swedish deaths now at 2/3 of April peak.
2. The bull semen storage culture that is India.
3. Will the French invest in “enhanced soldiers”?
4. The Economist on hydrogen-powered flight.
5. James Flynn has passed away.
6. Very good Ross piece (NYT).
What might an end to the Great Stagnation consist of?
If indeed it did, they are asking a similar question at The Economist. In recent times you might cite the onset of Apple’s M1, GPT-3, DeepMind’s application of AI to protein folding, phase III for a credible malaria vaccine, a CRISPR/sickle cell cure, the possibility of a universal flu vaccine, mRNA vaccines, ongoing solar power progress, wonderful new batteries for electric vehicles, a possibly new method for Chinese fusion (?), Chinese photon quantum computing, and ongoing advances in space exploration, most of all from SpaceX. Tesla has a very high market valuation, and Elon is the world’s second richest man.
Distanced work is very important, and here is a separate post on that.
I would say that almost certainly the great stagnation is over in the biomedical sciences. It is less obvious that the great stagnation is over more generally, as we might simply retreat into our former sloth and complacency once we are mostly vaccinated. Applied Divinity Studies has posed some pointed questions about why we might think that stagnation is over.
If you are looking for a quick metric to indicate the great stagnation might be over, consider total factor productivity. It is entirely possible that tfp in 2021 will be 5 or more, its highest level ever. (To be sure, this will show up as a measured increase in inputs more than as tfp, but we all know why those inputs will be increasing and that is because of science…yes this is a problem with tfp measures!) Over the two years to follow after that, we should be seeing very high tfps around the world. So that will be very high tfp for a few years.
Again, that is not proof of a permanent or even an ongoing end to the great stagnation. But it is something.
Two more general points seem relevant. First, many of the biomedical advances seem connected to new platforms, new modes of computation, new uses of AI, and so on, and they should be leading to yet further advances. Second, there are (finally!) some very real advances in energy use, and those tend to bring yet other advances in their wake, and not just advances in bit space.
But not all is rosy. If you recall my paper with Ben Southwood, the obstacles standing in the way of faster scientific progress, such as specialization and bureaucratization, mostly remain and some of them will be getting worse.
My The Great Stagnation, published in 2011, offered some pointed predictions. It argued that the “next big thing” was already with us, namely the internet, but we simply hadn’t learned to use it effectively yet. Once we put the internet at the center of many more of our institutions, rather than treating it as an add-on, the great stagnation would end. Numerous times (using roughly a 2011 start date) I predicted that the great stagnation would be over within twenty years time, though not in the next few years. The Great Stagnation in fact was an optimistic book, at least if you read it to the end and do not just mood affiliate over the title.
By no means would I say that specific scenario has been validated, but as a prediction it is looking not so crazy.
The gains from truly mobilizing the internet may in fact right now be swamping all of the accumulated obstacles we have put in the way of progress.
I also wrote, in 2011, that as the great stagnation approaches its end, we will all be deeply upset, and long for the earlier times. That too is by no means obviously wrong.
That was then, this is now; science and chaos edition
A blast from the past, circa 1688 and thereabouts:
Even as the House of Lords was starting to consider what to do after the departure of James, many sprang to settle old scores and reopen old issues. Legal toleration made the Church of England more defensive and less tolerant of sceptical or heterodox opinions. The Nine Years War from 1688, in which England at first suffered severe reverses at sea, strained the economy and finances of the country almost to breaking. The great silver recoinage of the late 1690s aggravated the problems; Halley was then deputy controller of the country Mint in Chester. He may have suffered from the great disaster of 1693, the loss of many ships of a Levant Company fleet off Lagos. The war lasted for much of the time that Halley was Clerk, and it undoubtedly delayed his project to observe the magnetic variation in the Atlantic. It was an anxious decade, a dangerous decade for anyone holding responsible office; in it [Edmond] Halley had some of his most original and influential ideas.
That is from Alan Cook’s Edmond Halley: Charting the Heavens and the Seas. Halley was a contemporary of Newton, Wren, Pepys, Hooke, Purcell, Locke, and Dryden, among others.
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…