Category: Medicine

Covid and reverse discrimination

Earlier in the pandemic, you might have had various theories about who was most likely to infect you, who was most likely not to be vaccinated/boosted, or who was most likely to have been going around without proper mask precautions.  Perhaps you went to some greater lengths, either large or small, to avoid those people or to take greater precautions around them.  Today, at least in most of the United States, we have entered the funny “reverse discrimination” phase of the pandemic.  The higher status the person, the more you should beware!  In the last few weeks, some of the higher status people I know have come down with Covid (they are all fine, to be clear), and at much higher rates than “people I know” were getting Covid before.

So behave accordingly, have a beer with your garbage collector, and I suspect this moment won’t last but another week or two.

How can we improve the NIH?

The NIH’s extramural research is systematically biased in favor of conservative research. This conservatism is a result of both institutional inertia, concerns by the NIH leadership that the organization could lose the support of Congress, and efforts by NIH beneficiaries to maintain the status quo.

The extramural grant distribution process, which is run through peer review “study sections,” is badly in need of reform. Though there is considerable variability among study sections, many are beset by groupthink, arbitrary evaluation factors, and political gamesmanship. The NIH may be hamstringing bioscience progress, despite the huge amount of funds it distributes, because its sheer hegemony steers the entire industry by setting standards for scientific work and priorities.

Most problematic, the NIH is highly resistant to reform. Many proposals have been shot down during discussion phases, or scaled back before implementation. The NIH’s own internal review board has been inactive since 2015, as mentioned at the start of this report section. Still, many of the NIH’s problems are likely a natural product of being a $40 billion+ per year government bureaucracy.

That is from Matt Faherty, and here is 33,000 or so words more on why the NIH is a good idea, what is wrong with the NIH, and how to improve it.  It is by far the best piece written on the NIH, and if it were to count as a book would be on the year’s “best of” list.

The piece is based on extensive interviews, and here is one reflection of that:

An anonymous comment on an NIH article reflected the sentiments of the most negative interviewees: 

“It is well known that NIH ‘confidentiality’ [of the primary reviewer to the grant applicant] is anything but, and a young PI risks career and reputation if they shoot down big names (not all, but there is a mafia of sorts). I’ve sat on panels, I’ve seen the influence from afar. Young PIs fall over themselves to get it good with the power brokers. I’ve seen young PIs threatened when they mentioned quietly that Big Boss X has data that is wrong. Some fields are worse than others, but it is overall a LOT uglier than most would believe.”

As for two meta-points, a) it is striking how little quality analysis of the NIH has been done, and b) how many of the respondents to this current work feared consequences for their careers, some responding only on an off the record basis.  I am proud to have supported this work through Emergent Ventures.

Britain fact of the day

In 1990, out-of-pocket spending by Britons on medical expenses was equivalent to 1 per cent of GDP, while across the Atlantic, uninsured Americans forked out more than twice as much, at 2.2 per cent. Thirty years on, that gap has all but disappeared. Americans’ non-reimbursable spending now stands at 1.9 per cent, and Britons’ has doubled to 1.8 per cent.

That is from John Burn-Murdoch the FT.  And this:

And the bulk of the increase in spending is from those who can least afford it. Between 2010 and 2020, the portion of UK spending that went on hospital treatments increased by 60 per cent overall, but more than doubled among the lowest-earning fifth of the population. The poorest now spend as much on private medical care as the richest, in relative terms. One in 14 of Britain’s poorest households now incurs “catastrophic healthcare costs” in a typical year — where costs exceed 40 per cent of the capacity to pay. This is up from one in 30 a decade ago…

Hmm….And here is a relevant (ungated) visual.  Via Ilya Novak.

The equilibrium

The South African drugmaker Aspen Pharmacare earlier this year finalized a deal to bottle and market the Johnson & Johnson vaccine across Africa, a contract that was billed as an early step toward Africa’s development of a robust vaccine production industry. Aspen geared up for production, but no buyers, including the African Union and Covax, have placed orders yet, said Stephen Saad, Aspen’s chief executive.

The Serum Institute of India, the world’s largest vaccine maker, stopped its production of Covid shots in December last year, when its stockpile grew to 200 million doses; Bharat Biotech, another Indian firm that was a major producer, also stopped making vaccines in the face of low demand. The companies say they have no further orders since their contracts with the Indian government ended in March.

Here is more from The New York Times.

An Operation Warp Speed for Nasal Vaccines

I have been pushing for more funding for nasal vaccines since early last year when I wrote about trypanophobia and see also my Congressional testimony. The Washington Post reports that the idea is gaining traction among scientists but funding is limited:

As the omicron variant of the coronavirus moved lightning-fast around the world, it revealed an unsettling truth. The virus had gained a stunning ability to infect people, jumping from one person’s nose to the next. Cases soared this winter, even among vaccinated people.

That is leading scientists to rethink their strategy about the best way to fight future variants, by aiming for a higher level of protection: blocking infections altogether. If they succeed, the next vaccine could be a nasal spray.

…Scientists at the National Institutes of Health and the Biomedical Advanced Research and Development Authority — known as BARDA — are vetting an array of next-generation vaccine concepts, including those that trigger mucosal immunity and could halt transmission. The process is similar to the one used to prioritize candidates for billions of dollars of investment through the original Operation Warp Speed program. But there’s a catch.

“We could Operation Warp Speed the next-generation mucosal vaccines, but we don’t have funding to do it,” said Karin Bok, director of Pandemic Preparedness and Emergency Response at the National Institute of Allergy and Infectious Diseases. “We’re doing everything we can to get ready … just to get ready in case we have resources available.”

In my estimation, Operation Warp Speed was the highest benefit to cost ratio of any government program since the Manhattan Project. Amazingly, despite having now seen the benefits of the program and the costs of the pandemic, a government that spends trillions every year can’t get behind millions for a nasal vaccine.

To be sure, the emergency is over. The risk to the vaccinated are now tolerable and the benefits of further investment are much less than before vaccines were available. But the costs are also lower. Much of the research on nasal vaccines has already been done–what is needed is funding for clinical trials.

A nasal COVID vaccine will also pay off in future vaccine programs. If in a future pandemic we were able to use nasal vaccines to vaccinate more quickly, that alone could save many lives.

Addendum: Here’s my post on RadVac the do it yourself nasal vaccine.

NIH sentences to ponder

“I mean, everybody is frustrated about how slow things are,” said Walter Koroshetz, the director of the National Institute of Neurological Disorders and Stroke and a co-chair of the initiative, in an interview with STAT. He added, however, that while starting enrollment “took way too much time,” the NIH stood up the study “much faster than we’ve done anything else before,” pointing out the agency’s usual pace can be even slower.

Here is the full story, via a loyal MR reader.  So far they have brought in just three percent of the patients they plan to recruit.  Why oh why is our public health establishment failing us?

Far UVC Sanitization Kills COVID

A new type of ultraviolet light that is safe for people took less than five minutes to reduce the level of indoor airborne microbes by more than 98%, a joint study by scientists at Columbia University Vagelos College of Physicians and Surgeons and in the U.K. has found.

…Far-UVC light has a shorter wavelength than conventional germicidal UVC, so it can’t penetrate into living human skin cells or eye cells. But it is equally efficient at killing bacteria and viruses, which are much smaller than human cells.

In the past decade, many studies around the world have shown that far-UVC is both efficient at destroying airborne bacteria and viruses without causing damage to living tissue. But until now these studies had only been conducted in small experimental chambers, not in full-sized rooms mimicking real-world conditions.

…The efficacy of different approaches to reducing indoor virus levels is usually measured in terms of equivalent air changes per hour. In this study, far-UVC lamps produced the equivalent of 184 equivalent air exchanges per hour. This surpasses any other approach to disinfecting occupied indoor spaces, where five to 20 equivalent air changes per hour is the best that can be achieved practically.

“Our trials produced spectacular results, far exceeding what is possible with ventilation alone,” says Kenneth Wood, PhD, lecturer in the School of Physics and Astronomy at the University of St. Andrews and senior author of the study. “In terms of preventing airborne disease transmission, far-UVC lights could make indoor places as safe as being outside on the golf course on a breezy day at St. Andrews.”

Summary here. Study here.

Here and here and here are my previous posts on UV-C sanitization. We are moving slower than I would like but the picture is of a UVC robot being used at Pittsburgh airport so kudos to them.

In praise of Paul Farmer

From an email by John Quattrochi:

There are no mentions of Paul Farmer, who recently passed away, on MR. This is a shame, because he excelled in two areas of interest to you: talent identification and cross-cultural integration of ideas.

Paul did so much for so many people that it’s easy to lose sight of what set him apart. He was a leader in the social movement to improve health among the most vulnerable. He did so by building organizations and writing and speaking across multiple cultures.

He began by going to an important center in his industry and becoming an understudy to a master practitioner. Rural Haiti is to health vulnerability what Silicon Valley is to tech innovation. In his early 20s, Paul went there to work for Fritz Lafontant, a Wozniak-like Haitian priest pioneering a community-based approach to the social determinants of health.

Paul then identified the talent with whom he would co-found, in 1987, aged 28, the central organization for his work, Zanmi Lasante (“Partners in Health”). In 1983, he met and recruited the 18-year-old Ophelia Dahl. She has been in PIH leadership for 35 years. Around the same time, he met and recruited fellow medical student Jim Kim, who also led PIH, before stints as president of Dartmouth and the World Bank.  From his undergrad friends, he brought on Todd McCormack, son of the founder of one of the world’s leading talent management agencies, IMG. And finally, for startup capital, he successfully pitched Tom White, a 67-year-old Boston construction magnate.

To expand his movement, he adapted his ideas to the peculiar idioms of many cultures and subcultures: medicine, anthropology, Christianity, Washington DC, Haiti, Russia, Rwanda, and more. He lectured widely, and always lingered afterward, forging brief but powerful individual connections. His charisma included equal parts moral exhortation and dry humor. As a Harvard professor for over 30 years, he convinced many students to join his movement in lieu of (or in addition to) rent-seeking careers in finance or management consulting.

Paul is often called a hero. Yet, if a hero is someone who sacrifices much, Paul may not qualify. By all appearances he loved his work and was richly rewarded in status and attention. What’s not debatable is his genius. From boardrooms to bedsides, lecture halls to shanty stalls, he channeled the idea that every human life has equal moral worth in irreplicable ways. His legacy is immense.

RIP.

What Operation Warp Speed Did, Didn’t and Can’t Do

Operation Warp Speed was a tremendous success and one that I was pleased to support from the beginning. Many people, however, are concluding from the success of OWS that big Federal funding can solve many other problems at the same speed and scale and that is incorrect.

First, it’s important to understand that OWS did not create any scientific innovations or discoveries. The innovative mRNA vaccines are rightly lauded but all of the key scientific ideas behind mRNA as a delivery mechanism long predate Operation Warp Speed. The scientific advances were the result of many decades of work, some of it supported by university and government funding and also a significant fraction by large private investments in firms such as Moderna and BioNTech. It was BioNTech recall that hired Katalin Karikó (and many other mRNA researchers) when she couldn’t get university or government funding. Since OWS created no new scientific breakthroughs there isn’t much to learn from OWS about the efficacy of large scale programs for that purpose.

Second, it’s important to understand that we got lucky. OWS made smart bets and the portfolio paid off but it could have failed. Indeed, some OWS bets did fail including the Sanofi and Glaxo-Smith-Klein vaccine and the at-best modest success of Novavax. Many other vaccines which we didn’t invest in but could have invested in also failed. To be clear, my work with Kremer et al. showed that these bets and more were worth taking but one should not underestimate the probability of failure even when lots of money is spent.

So what did Operation Warp Speed do? There were four key parts to the plan 1) an advance market commitment to buy lots of doses of approved vaccines–this was important because in past pandemics vaccines had entered development and then the disease had disappeared leaving the firms holding the bag with little to show for their investment 2) the lifting of FDA regulations to allow for accelerated clinical trials, for example, phase 3 trials could start before phase 2 trials were fully complete 3) government investment in large clinical trials–clinical trials are the most expensive part of the development process and by funding the trials generously, the trials could be made large which meant that they could be quick 4) government investment in capacity, building factories not just for the vaccines but also for the needles, vials and so forth, even before any of the vaccines were approved–thus capacity was ready to go. All of these steps shaved months, even years, off the deployment timeline.

The key factor about each of these parts of the plan was that we were mostly dealing with known quantities that the government scaled. It’s known how to run clinical trials, it’s known how to produce vials and needles. The mRNA factories were more difficult but scaling problems are more easily solved with investment than are invention problems. It’s also known how to lift government regulations and speed the bureaucracy. That is, no one doubts that lifting regulations and speeding bureaucracy is within our production possibilities frontier.

It also cannot be underestimated that OWS funded people who were already extremely motivated. The Pfizer and Moderna staff put in near super-human effort–many of them felt this was the key moment of their life and they stepped up to their moment. OWS threw gasoline on fire–don’t expect the same in a more normal situation.

Another factor that people forget is that with vaccines we had a very unusual situation where the entire economy was dependent on a single sector–a macroeconomic O-ring. As a result, the social returns to producing vaccines were easily a hundred times (or more) greater than any potential vaccine profits. Thus, by accelerating vaccine production, OWS could generate tremendous returns. Most of the time, markets internalize externalities imperfectly but reasonably well which means that even if you accelerate something good the total returns aren’t so astronomical that you can’t overspend or spend poorly. Governments can spend too much as well as too little so most of the time you have to factor in the waste of overspending even when the spending is valuable–that problem didn’t really apply to OWS.

So summarizing what do we need for another OWS? 1) Known science–scaling not discovering, 2) Lifting of regulations 3) Big externalities, 4) Pre-existing motivation. Putting aside an Armageddon like scenario in which we have to stop an asteroid, one possibility is insulating the electrical grid to protect North America from a Carrington event, a geomagnetic storm caused by solar eruptions. (Here is a good Kurzgesagt video.) Does protecting the grid meet our conditions? 1) Protecting the electrical grid is a known problem whose solution does not require new science 2) protecting the grid requires lifting and harmonizing regulations as the grid is national/inter-national but the regulations are often local, 3) The social returns to power far exceed the revenues from power so there are big externalities. Indeed, companies could have protected the grid already (and have done so to some extent) but they are under-incentivized. (The grid is aging so insulating the gird could also have many side benefits.) 4) Pre-existing motivation. Not much. Can’t have everything.

I think it’s also notable that big pandemics and solar storms seem to occur about once in every one hundred years–just often enough to be dangerous and yet not so often that we are well prepared.

Thus, while I think that enthusiasm for an “OWS for X” is overblown, there are cases–protecting the grid is only one possibility–where smart investments could pay big returns but they must be chosen carefully in light of all the required conditions for success.

Hong Kong and Shenzhen

I was asked by the NYTimes to comment on the lockdown of Shenzhen. This is what I said:

Shenzhen is China’s Silicon Valley so shutting it down will raise the cost of exporting electronics. Why would China shut down a vital export region? Next door is Hong Kong with currently the highest daily death rates from COVID ever reported. China’s population is highly vaccinated but with what may be less effective domestic vaccines and there are still millions of elderly people who are unvaccinated. China remains in a precarious position.

You can see why China is worried in these two pictures of daily deaths (left) and cumulative deaths (right) per million people in Hong Kong. Hong Kong is likely to exceed Canada’s death rate per capita before this is over, despite having had much lower rates for the previous two years. China is more vaccinated than Hong Kong. By some reports only 37% of the over-80s were vaccinated in Hong Kong while the rate is over 50% in China but still that leaves many very elderly unvaccinated. By the way, I have been somewhat skeptical about the three C’s story for Japan’s success but Japan has now gotten 95% of their over-80s vaccinated so Japan is in good shape regardless.

Shut-ins

Millions of people continue to curtail work and social activities for fear of COVID and they apparently have no plans to change their behavior.

NYTimes: Throughout the pandemic, many people in the United States desperately hoped for an end to mask wearing, isolation from friends and co-workers, and six feet of social distance. Others not so much.

In fact, new research suggests, millions have no intention of ending some pandemic behaviors even if the threat from the coronavirus and its variants were to fully subside.

Roughly 13 percent of people in the study reported that they did not intend to change their protective behaviors, like avoiding elevators, mass transit and eating indoors at restaurants.

As Nick Bloom, one of the researchers, puts it this is long social distancing a psychological version of long COVID.

The original research from Jose Maria Barrero, Nicholas Bloom & Steven J. Davis is here.

Peginterferon Lambda is looking good

Eiger BioPharmaceuticals, Inc. (Nasdaq:EIGR), a commercial-stage biopharmaceutical company focused on the development of innovative therapies to treat and cure Hepatitis Delta Virus (HDV) and other serious diseases, today announced that Peginterferon Lambda (Lambda) significantly reduced the risk of COVID-19-related hospitalizations or emergency room visits greater than six hours by 50% (primary endpoint) and death by 60% in the Phase 3 TOGETHER study, a multi-center, randomized, double-blind, placebo-controlled study of non-hospitalized adult patients with COVID-19, who are at high risk of progressing to severe illness.

The Phase 3 TOGETHER study of Lambda is the second largest study to date of a COVID-19 therapeutic. Final analyses evaluated data from 1,936 patients, with 84% of patients having received at least a single dose of any COVID-19 vaccine.

Here is the full press release, with original support from Fast Grants.

US Pandemic Policy: Failures, Successes, and Lessons

My talk at Bowling Green State University on US Pandemic Policy: Failures, Successes, and Lessons

This was not a black swan event. This was an entirely predicted and predictable event. We knew it was going to happen….And yet, we weren’t ready.

I am told that my talk made many people angry (not at me, natch).

Emergent Ventures winners, eighteenth cohort

Zvi Mowshowitz, TheZvi, New York City, to develop his career as idea generator and public intellectual.

Nadia Eghbal, Miami, to study and write on philanthropy for tech and crypto wealth.

Henry Oliver, London, to write a book on talent and late bloomers.  Substack here.

Geffen Avrahan, Bay Area, founder at Skyline Celestial, an earlier winner, omitted from an early list by mistake, apologies Geffen!

Subaita Rahman of Scarborough, Ontario, to enable a one-year visiting student appointment at Church Labs at Harvard University.

Gareth Black, Dublin, to start YIMBY Dublin.

Pradyumna Shyama Prasad, blog and podcast, Singapore.  Here is his substack newsletter, here is his podcast about both economics and history.

Ulkar Aghayeva, New York City, Azerbaijani music and bioscience.

Steven Lu, Seattle, to create GenesisFund, a new project for nurturing talent, and general career development.

Ashley Lin, University of Pennsylvania gap year, Center for Effective Altruism, for general career development and to learn talent search in China, India, Russia.

James Lin, McMaster University gap year, from Toronto area, general career development and to support his interests in effective altruism and also biosecurity.

Santiago Tobar Potes, Oxford, from Colombia and DACA in the United States, general career development, interest in public service, law, and foreign policy.

Martin Borch Jensen of Longevity Impetus Grants (a kind of Fast Grants for longevity research), Bay Area and from Denmark, for a new project Talent Bridge, to help talented foreigners reach the US and contribute to longevity R&D.

Jessica Watson Miller, from Sydney now in the Bay Area, to start a non-profit to improve the treatment of mental illness.

Congratulations to you all!  We are honored to have you as Emergent Ventures winners.

Jesse Michels interviews me at Hereticon

Jesse’s description was “Wide ranging discussion with the brilliant @tylercowen. Topics include: Satoshi’s identity, Straussian Jesus, the Beatles and UFOs. Taped in early January but he presciently expresses concerns around Russia/Ukraine”

Great fun was had by all, and they added in nice visuals.