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Ann Bernstein interview with Lant Pritchett

Ann Bernstein: From your knowledge of India and Indonesia, what are the core causes of their lack of educational
progress? These are places with highly qualified civil servants and, at least in India’s case, a democratic
government. How do you see this problem? How do we get out of this trap?

Lant Pritchett: I’m head of this very large research project called RISE and we’re spending millions of dollars to
find out the answer to that question. One of the countries where education improvements have been dramatic
is Vietnam. At a tiny fraction of the spending in most countries – including South Africa – Vietnam is achieving
OECD levels of learning. When we asked our Vietnam team why the country has produced this amazing success,
they told us: ‘because they wanted it’.

On one level, that seems silly; on another level, it is the key. Unless, as a society, you agree on a set of achievable
objectives and actually act in a way that reveals that you really want those objectives, you cannot achieve
anything.

Recommended throughout.

Patents are Not the Problem!

For the last year and a half I have been shouting from the rooftops, “invest in capacity, build more factories, shore up the supply lines, spend billions to save trillions.” Fortunately, some boffins in the Biden administration have found a better way, “the US supports the waiver of IP protections on COVID-19 vaccines to help end the pandemic.”

Waive IP protections. So simple. Why didn’t I think of that???

Patents are not the problem. All of the vaccine manufacturers are trying to increase supply as quickly as possible. Billions of doses are being produced–more than ever before in the history of the world. Licenses are widely available. AstraZeneca have licensed their vaccine for production with manufactures around the world, including in India, Brazil, Mexico, Argentina, China and South Africa. J&J’s vaccine has been licensed for production by multiple firms in the United States as well as with firms in Spain, South Africa and France. Sputnik has been licensed for production by firms in India, China, South Korea, Brazil and pending EMA approval with firms in Germany and France. Sinopharm has been licensed in the UAE, Egypt and Bangladesh. Novavax has licensed its vaccine for production in South Korea, India, and Japan and it is desperate to find other licensees but technology transfer isn’t easy and there are limited supplies of raw materials:

Virtually overnight, [Novavax] set up a network of outside manufacturers more ambitious than one outside executive said he’s ever seen, but they struggled at times to transfer their technology there amid pandemic travel restrictions. They were kicked out of one factory by the same government that’s bankrolled their effort. Competing with larger competitors, they’ve found themselves short on raw materials as diverse as Chilean tree bark and bioreactor bags. They signed a deal with India’s Serum Institute to produce many of their COVAX doses but now face the realistic chance that even when Serum gets to full capacity — and they are behind — India’s government, dealing with the world’s worst active outbreak, won’t let the shots leave the country.

Plastic bags are a bigger bottleneck than patents. The US embargo on vaccine supplies to India was precisely that the Biden administration used the DPA to prioritize things like bioreactor bags and filters to US suppliers and that meant that India’s Serum Institute was having trouble getting its production lines ready for Novavax. CureVac, another potential mRNA vaccine, is also finding it difficult to find supplies due to US restrictions (which means supplies are short everywhere). As Derek Lowe said:

Abolishing patents will not provide more shaker bags or more Chilean tree bark, nor provide more of the key filtration materials needed for production. These processes have a lot of potential choke points and rate-limiting steps in them, and there is no wand that will wave that complexity away.

Technology transfer has been difficult for AstraZeneca–which is one reason they have had production difficulties–and their vaccine uses relatively well understood technology. The mRNA technology is new and has never before been used to produce at scale. Pfizer and Moderna had to build factories and distribution systems from scratch. There are no mRNA factories idling on the sidelines. If there were, Moderna or Pfizer would be happy to license since they are producing in their own factories 24 hours a day, seven days a week (monopolies restrict supply, remember?). Why do you think China hasn’t yet produced an mRNA vaccine? Hint: it isn’t fear about violating IP. Moreover, even Moderna and Pfizer don’t yet fully understand their production technology, they are learning by doing every single day. Moderna has said that they won’t enforce their patents during the pandemic but no one has stepped up to produce because no one else can.

The US trade representative’s announcement is virtue signaling to the anti-market left and will do little to nothing to increase supply.

What can we do to increase supply? Sorry, there is no quick and cheap solution. We must spend. Trump’s Operation Warp Speed spent on the order of $15 billion. If we want more, we need to spend more and on similar scale. The Biden administration paid $269 million to Merck to retool its factories to make the J&J vaccine. That was a good start. We could also offer Pfizer and Moderna say $100 a dose to produce in excess of their current production and maybe with those resources there is more they could do. South Africa and India and every other country in the world should offer the same (India hasn’t even approved the Pfizer vaccine and they are complaining about IP!??) We should ease up on the DPA and invest more in the supply chain–let’s get CureVac and the Serum Institute what they need. We should work like hell to find a substitute for Chilean tree bark. See my piece in Science co-authored with Michael Kremer et. al. for more ideas. (Note also that these ideas are better at dealing with current supply constraints and they also increase the incentive to produce future vaccines, unlike shortsighted patent abrogation.)

Bottom line is that producing more takes real resources not waving magic patent wands.

You may have gathered that I am angry. I am indeed angry that the people in power think they can solve real problems on the cheap and at someone else’s expense. This is not serious. I am also angry that they are sending the wrong message about business, profits and capitalism. So let me end on positive note. Like the Apollo program and Dunkirk, the creation of the mRNA vaccines by Pfizer and Moderna should be lauded with Nobel prizes and major movies. Churchill called the rescue at Dunkirk a “miracle of deliverance,” well the miracle of Moderna will rescue many more. Not only was a vaccine designed in under a year, an entirely new production process was set up to produce billions of doses to rescue the world. The creation of the mRNA vaccines was a triumph of science, logistics, and management and it was done at a speed that I had thought possible only for past generations.

I am grateful that greatness is still within our civilization’s grasp.

Addendum: Lest I be accused of being reflexively pro-patent, do recall the Tabarrok curve.

My Congressional Testimony

I thought the meeting went well. I made four points.

  • It is not too late to do more.
  • We should invest in nasal and oral vaccines.
  • We should vaccinate the world.
  • We should stretch doses through fractional dosing and delaying the second dose, this will be important to vaccinate the world quickly.

One observation. Lots of people are talking about vaccine hesitancy but I am one of the few people who have been talking about nasal and oral vaccines which are the only really solid approach to the issue that I have seen.

My best line:

The unvaccinated are the biggest risk for generating mutations and new variants. You have heard of the South Africa and Brazilian variants, well the best way to protect your constituents from these and other variants is to vaccinate South Africans and Brazilians.

I also got in the last word in Q&A when discussing the pause of J&J:

For the rest of the world it is important to underline that it is most important to get vaccinated now. Use the AstraZeneca vaccine, use the Johnnson & Johnson vaccine…don’t wait for Moderna or Pfizer, it is going to take too long…start your vaccination program early…vaccinate as quickly as possible, that is the route to health and wealth.

See Western Warnings Tarnish Vaccines the World Badly Needs for the beginnings of a disaster. Note that if J&J and AZ are tarnished or knocked out of the vaccine arsenal then dose stretching and investing in more capacity are going to be even more important.

I also submitted five excellent and important pieces to Congress:

Canadian statement on delaying the second dose.

National Advisory Committee on Immunization (NACI) Canada. 2021. “COVID-19 Vaccine Extended Dose Interval for Canadians: NACI Recommendation.” Government of Canada. March 3, 2021. https://www.canada.ca/en/public-health/services/immunization/national-advisory-committee-on-immunization-naci/rapid-response-extended-dose-intervals-covid-19-vaccines-early-rollout-population-protection.html.

Value of vaccine capacity and additional investments.

Castillo, Juan Camilo, Amrita Ahuja, Susan Athey, Arthur Baker, Eric Budish, Tasneem Chipty, Rachel Glennerster, et al. 2021. “Market Design to Accelerate COVID-19 Vaccine Supply.” Science, February. https://doi.org/10.1126/science.abg0889.

Efficacy of the first dose from NEJM.

Skowronski, Danuta, and Gaston Serres De. 2021. “Letter to the Editor on Safety and Efficacy of the BNT162b2 MRNA Covid-19 Vaccine.” New England Journal of Medicine, February 17, 2021. https://doi.org/10.1056/NEJMc2036242.

Overview of dose stretching policies (with links in the online version).

Tabarrok, Alex. 2021. “What Are We Waiting For?” Washington Post, February 12, 2021, sec. Outlook. https://www.washingtonpost.com/outlook/2021/02/12/first-doses-vaccine-rules-fda/

A plan to vaccinate the world.

Agarwal, Ruchir, and Tristan Reed. 2021. “How to End the COVID-19 Pandemic by March 2022” SSRN. 2021. https://documents.worldbank.org/en/publication/documents-reports/documentdetail/181611618494084337/how-to-end-the-covid-19-pandemic-by-march-2022

The whole thing is here. My written testimony is here.

Monday assorted links

1. The FATF crypto recommendations.

2. Markets in everything.

3. “The swan in question has been terrorizing the neighbourhood with its persistent door-knocking over the last five years, residents say.

4. Survey on body-worn police cameras, mostly positive results.

5. Funny (yet sort of true?) that I (along with @pmarca!) am viewed as the big socializer on this list.

6. Vaccinated people should return to greater socializing.  And good news on the South African strain.

Dose Stretching Policies Probably *Reduce* Mutation Risk

One objection to dose-stretching policies, such as delaying the second dose or using half-doses, is that this might increase the risk of mutation. While possible, some immunologists and evolution experts are now arguing that dose-stretching will probably reduce mutation risk which is what Tyler and I concluded. Here’s Tyler:

One counter argument is that letting “half-vaccinated” people walk around will induce additional virus mutations.  Florian Kramer raises this issue, as do a number of others.

Maybe, but again I wish to see your expected value calculations.  And in doing these calculations, keep the following points in mind:

a. It is hard to find vaccines where there is a recommendation of “must give the second dose within 21 days” — are there any?

b. The 21-day (or 28-day) interval between doses was chosen to accelerate the completion of the trial, not because it has magical medical properties.

c. Way back when people were thrilled at the idea of Covid vaccines with possible 60% efficacy, few if any painted that scenario as a nightmare of mutations and otherwise giant monster swarms.

d. You get feedback along the way, including from the UK: “If it turns out that immunity wanes quickly with 1 dose, switch policies!”  It is easy enough to apply serological testing to a control group to learn along the way.  Yes I know this means egg on the face for public health types and the regulators.

e. Under the status quo, with basically p = 1 we have seen two mutations — the English and the South African — from currently unvaccinated populations.  Those mutations are here, and they are likely to overwhelm U.S. health care systems within two months.  That not only increases the need for a speedy response, it also indicates the chance of regular mutations from the currently “totally unvaccinated” population is really quite high and the results are really quite dire!  If you are so worried about hypothetical mutations from the “half vaccinated” we do need a numerical, expected value calculation comparing it to something we already know has happened and may happen yet again.  When doing your comparison, the hurdle you will have to clear here is very high.

(See my Washington Post piece for similar arguments and additional references.).

Now here are evolutionary theorists, immunologists and viral experts Sarah Cobey, Daniel B. Larremore, Yonatan H. Grad, and Marc Lipsitch in an excellent paper that first reviews the case for first doses first and then addresses the escape argument. They make several interrelated arguments that a one-dose strategy will reduce transmission, reduce prevalence, and reduce severity and that all of these effects reduce mutation risk.

The arguments above suggest that, thanks to at least some effect on transmission from one dose, widespread use of a single dose of mRNA vaccines will likely reduce infection prevalence…

The reduced transmission and lower prevalence have several effects that individually and together tend to reduce the probability that variants with a fitness advantage such as immune escape will arise and spread (Wen, Malani, and Cobey 2020). The first is that with fewer infected hosts, there are fewer opportunities for new mutations to arise—reducing available genetic variation on which selection can act. Although substitutions that reduce antibody binding were documented before vaccine rollout and are thus relatively common, adaptive evolution is facilitated by the appearance of mutations and other rearrangements that increase the fitness benefit of other mutations (Gong, Suchard, and Bloom 2013; N. C. Wu et al. 2013; Starr and Thornton 2016). The global population size of SARS-CoV-2 is enormous, but the space of possible mutations is larger, and lowering prevalence helps constrain this exploration. Other benefits arise when a small fraction of hosts drives most transmission and the effective reproductive number is low. Selection operates less effectively under these conditions: beneficial mutations will more often be lost by chance, and variants with beneficial mutations are less certain to rise to high frequencies in the population (Desai, Fisher, and Murray 2007; Patwa and Wahl 2008; Otto and Whitlock 1997; Desai and Fisher 2007; Kimura 1957). More research is clearly needed to understand the precise impact of vaccination on SARS-CoV-2 evolution, but multiple lines of evidence suggest that vaccination strategies that reduce prevalence would reduce rather than accelerate the rate of adaptation, including antigenic evolution, and thus incidence over the long term.

In evaluating the potential impact of expanded coverage from dose sparing on the transmission of escape variants, it is necessary to compare the alternative scenario, where fewer individuals are vaccinated (but a larger proportion receive two doses) and more people recover from natural infection. Immunity developing during the course of natural infection, and the immune response that inhibits repeat infection, also impose selection pressure. Although natural infection involves immune responses to a broader set of antibody and T cell targets compared to vaccination, antibodies to the spike protein are likely a major component of protection after either kind of exposure (Addetia et al. 2020; Zost et al. 2020; Steffen et al. 2020), and genetic variants that escape polyclonal sera after natural infection have already been identified (Weisblum et al. 2020; Andreano et al. 2020). Studies comparing the effectiveness of past infection and vaccination on protection and transmission are ongoing. If protective immunity, and specifically protection against transmission, from natural infection is weaker than that from one dose of vaccination, the rate of spread of escape variants in individuals with infection-induced immunity could be higher than in those with vaccine-induced immunity. In this case, an additional advantage of increasing coverage through dose sparing might be a reduction in the selective pressure from infection-induced immunity.

…In the simplest terms, the concern that dose-sparing strategies will enhance the spread of immune escape mutants postulates that individuals with a single dose of vaccine are those with the intermediate, “just right” level of immunity, more likely to evolve escape variants than those with zero or two doses (Bieniasz 2021; Saad-Roy et al. 2021)….There is no particular reason to believe this is the case. Strong immune responses arising from past infection or vaccination will clearly inhibit viral replication, preventing infection and thus within-host adaptation…. Past work on influenza has found no evidence of selection for escape variants during infection in vaccinated hosts (Debbink et al. 2017). Instead, evidence suggests that it is immunocompromised hosts with prolonged influenza infections and high viral loads whose viral populations show high diversity and potentially adaptation (Xue et al. 2017, 2018), a phenomenon also seen with SARS-CoV-2 (Choi et al. 2020; Kemp et al. 2020; Ko et al. 2021). It seems likely, given its impact on disease, that vaccination could shorten such infections, and there is limited evidence already that vaccination reduces the amount of virus present in those who do become infected post-vaccination (Levine-Tiefenbrun et al. 2021).

I also very much agree with these more general points:

The pandemic forces difficult choices under scientific uncertainty. There is a risk that appeals to improve the scientific basis of decision-making will inadvertently equate the absence of precise information about a particular scenario with complete ignorance, and thereby dismiss decades of accumulated and relevant scientific knowledge. Concerns about vaccine-induced evolution are often associated with worry about departing from the precise dosing intervals used in clinical trials. Although other intervals were investigated in earlier immunogenicity studies, for mRNA vaccines, these intervals were partly chosen for speed and have not been completely optimized. They are not the only information on immune responses. Indeed, arguments that vaccine efficacy below 95% would be unacceptable under dose sparing of mRNA vaccines imply that campaigns with the other vaccines estimated to have a lower efficacy pose similar problems. Yet few would advocate these vaccines should be withheld in the thick of a pandemic, or roll outs slowed to increase the number of doses that can be given to a smaller group of people. We urge careful consideration of scientific evidence to minimize lives lost.

Sunday assorted links

1. Rohit Krishnan reviews Stubborn Attachments.

2. “South Korea was the only country in the Organization of Economic Cooperation and Development (OECD) that had total fertility rate below 1 for two consecutive years.

3. Israel-Syria barter markets in everything prisoners for vaccines (NYT).

4. “Mary Beard, a professor of classics at Cambridge University, posited that while Caligula might have been assassinated because he was a monster, it is equally possible that he was made into a monster because he was assassinated.” (NYT)  How much do we really know about the ancient world anyway?

5. Good news on the South African strain.

6. Gelassenheit.

Monday assorted links

1. NYT tech coverage still a train wreck.  And reporters using aliases to stalk non-criminal subjects?  Isn’t that against NYT rules?

2. Scott Sumner on the Romney child plan.

3. Update on South African strain, vaccines, and confidence intervals.

4. Monopsony it ain’t.

5. “The average EV increases overall household load by 2.9 kilowatt-hours per day, less than half the amount assumed by state regulators. Our results imply that EVs travel 5,300 miles per year, under half of the US fleet average. This raises questions about transportation electrification for climate policy.”  Link here.

6. Vaccine efficacy update.

Tuesday assorted links

1. Is the English strain picking up some features of the South African strain? And the new strains do seem somewhat more dangerous.

2. Joe Stiglitz comes perilously close to the Austrian theory of the business cycle.

3. Update on the Russian vaccine (New Yorker).  And this WSJ piece.  It seems to work?  And yet more.

4. ““What we didn’t anticipate was that they would break the law,” Goldenfeld said — that some students, even after testing positive and being told to quarantine, would attend parties anyway.”  A look at some of the models.

5. “Dubai announced Monday the creation of a “space court” to settle commercial disputes, as the UAE — which is sending a probe to Mars — builds its presence in the space sector.”  Link here.

6. My on-line talk to PayPal.  Mostly Q&A, and they did ask me about Nirvana’s “Aneurysm.

7. Incoming vaccine data from Israel.

The Experts are Very Worried

Here is an interview with Dr. Peter Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine and the lead developer of a COVID vaccine being produced in India. He thinks the AstraZeneca vaccine should be approved immediately, as I have long argued.

President Biden himself announced Tuesday that we’re going to have maybe enough additional doses of the mRNA vaccines to fully vaccinate 300 million Americans by the end of summer or fall.

I’m saying, “Well, no, that’s that’s not gonna work.” Telling us “by the fall” is like telling us “when the glaciers are gonna come back down from Quebec.” I mean, that’s not adequate.

We’re going to have to figure out a way to vaccinate the American people by late spring. That’s a tall order. To beat back the virus we need to give two doses to three-quarters of the population, to 246 million Americans. That’s half a billion immunizations. To get there, we’d need a rate of immunizations two or three times higher than what’s proposed.

….We need vaccinations now.

..things have been slowed down with the AstraZeneca-Oxford adenovirus vaccine. My understanding is that the FDA insisted that they conduct a full-scale Phase Three trial in the U.S., and we won’t have results for that until April. Meanwhile, the European Medicines Agency, the EMA, is going to make a ruling on the AstraZeneca Oxford vaccine on Friday based on studies done in Europe and also probably on data from Brazil and South Africa. [The EMA authorized, AT].

Those are large, reliable studies?

Yeah….Because of these new variants, there’s great urgency here in the U.S. So I’m saying that sometimes we have to do things that take us out of our comfort zone in order to save lives. That means, rather than focusing only on the new study that we’re doing in the U.S., we also look at the dossier presented to the EMA.

As a regulatory agency the EMA is up there with our U.S. FDA. They’re the two best regulatory agencies in the world. So if they sign off, I think we should say, “Look, let’s do it. Let’s use that vaccine.”

We’ve already bought 300 million doses of the AstraZeneca-Oxford vaccine. We’ve paid for it — over a billion dollars — so let’s use it.

…And there’s also the recombinant protein vaccine our lab has developed at Baylor College of Medicine and Texas Children’s Hospital. In India they’re scaling that up to a billion doses. Nobody from the White House has approached us to say, “Hey, Peter, what can we do to bring that vaccine in.”

There seem to be blinders: All they can see is getting the mRNA vaccines. I don’t quite know what’s driving that. We have to figure out a way to bring the other ones on board.

And soon! We’re in the eye of the hurricane.

Hat tip: Jim Ward.

Sunday assorted links

1. Fauci.  Compare that to revisiting the Balaji thread.

2. Why are grandiose narcissists more effective at organizational politics?

3. Angus and I joke around.

4. What is the quality of CDC software?

5. Migrants to the U.S. are much more productive than migrants to other locales.

6. Atif Mian is still caught up in the Junker Fallacy.

7. Why the South African strain may not become dominant in the U.S.

Friday assorted links

1. The next Michael Lewis book (NYT).

2. Novovax data, including against the South African strain.  And wide confidence intervals.

3. Carolyn Hopkins.

4. Chinese government is collecting Americans’ DNA.

5. John Cochrane on GameStop, etc.

6. And how Robinhood ran out of cash (NYT).  The misinformation in the MR comments section and elsewhere on this is egregious.  Here is yet more common sense, though I don’t quite agree with all the framing.

It is a marathon, not a sprint

For all of its achievements, we still do not know if New Zealand will have ended up doing a good job against Covid-19:

New Zealand’s “go hard, go early” strategy to combat Covid-19 attracted global praise and eliminated local transmission of the virus. But the country’s slow rollout of vaccines is putting people at unnecessary risk and threatens to delay its economic recovery, critics warned.

Wellington plans to start vaccinating frontline workers in April and the general public from July under a cautious strategy that avoids the emergency authorisation of vaccines pursued by crisis-stricken nations such as the US and UK.

And note this:

There are at least 19 cases of the coronavirus variants first identified in the UK or South Africa in managed quarantine facilities in New Zealand for overseas arrivals, according to government data.

And this:

Mr Hipkins said there was “absolutely no complacency” in the government’s response.

Here is the full FT story.

Friday assorted links

1. SinoVac vaccine looking pretty good, and 300 million doses already sold (NYT).  And Pfizer-Biontech seems to work against the South African strain.

2. “Marginal-utility neglect.”

3. Covid in Zambia.

4. Alex redux: why do experiments make people uneasy?

5. Cocanha.

6. Sperm markets in Covid times, and disintermediation (NYT).  Recommended.  But a 1400 chess rating is nothing to boast about!

7. Angry people are more vulnerable to misinformation — Serenity Now!