Results for “human challenge”
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Should we value human life at replacement cost?

Earlier this week I asked whether we should value human life at replacement cost.  Michael Vassar wrote me in response:

We should value human life at replacement cost, and we actually value generic human life less than that (negatively?), as demonstrated by the existance of late term abortion (there are almost certainly potential adoptees who would pay many women enough to motivate them to go through labor once late in a pregnancy in exchange for the child, especially considering the actual expenses many incur to adopt), but we should value a particular human life at the lower of total preference for the continuation of that life and replacement cost for that life.  For the latter, today replacement cost is infinite, though it needn’t be forever.  For the former, the preference varies dramatically depending on situation, but is frequently very high.  For simplicity’s sake, and because economical thinking is confusing or corrupting to people below a very high IQ threshold, we maintain a convenient fiction of infinite value.  Although we violate this fiction continuously, we do so in an extremely inconsistent manner because the cost of strict obedience or careful public analysis are greater than the costs of irrationality on particular instances.  The "ethical questions" raised by science are rather consistently actually situations where new scientific data challenges the viability of convenient fictions, but in the end it always turns out to be possible to ignore the new data and maintain these fictions, or to integrate the new data into life rather seamlessly without disruption.  However, the frequency with which these questions occur is increasing.

The Winners of the MR Challenge

As expected, President Bush’s plan for a moon base and eventual trip to Mars failed to ignite. MR readers have some better ideas.

Honorable mention goes to Roger Meiners for suggesting that a moon base is a good idea so long as Congress and the President must occupy it. Now I am inspired!

Third place goes to Chris Rasch for brain freezing. Chris Rasch writes “I believe that reversible cryopreservation of the human brain could be developed. Remarkable advances have already been made on a shoestring budget. Such a technology would allow people dying today to halt the dying process until technology can advance to the point that we can cure their disease or repair their injuries. I would wager that, for a mere billion dollars, which is far more than has probably been spent on cryobiology during the entire existence of the field, we could have effectively unbounded lifespans. We could then use those extra years to pursue all of the other goals that other submitters may send to you.”

Here is a good, short summary of cryonics and you can sign up to have you brain (or more) frozen here.

I like the cryonics idea and have thought seriously about signing up (believe it or not, one of my colleagues (not Tyler) has already done so). The reason the idea takes third place is that we don’t see a big private demand for cryonics and the public is more likely to think this idea crazy than inspiring.

Second place goes to Nick Shultz for suggesting that we “provide potable water for everyone on the planet.” A number of other ideas were also motivated by the goal of alleviating abject third-world poverty. I think these ideas are inspiring but am unsure whether we can deliver on them given that so many of the problems of the third world have to do with poor governance. My suggestion would be to work on something related but more under our own control. We could do far worse, for example, than following Bill Gates’s lead and put a billion or so into the Malaria Vaccine Initiative.

First place goes to David Wood and Robin Hanson both of whom suggested a space elevator. At first, the space elevator idea seems impossible, even absurd. The idea is to string a cable some 62,000 miles long from a spot on the equator up into outerspace. Wouldn’t it fall down? No, recall that a sateillite some 22,000 miles up is in geosynchronous orbit. The space elevator would extend enough past this point so that gravity at the lower end and centripetal acceleration at the far end would keep the cable under tension. Once the cable is strung, reaching outerspace is as simple as Jack climbing the beanstock.

The most difficult part of the space elevator is finding a material strong enough to carry a load yet light enough not to collapse under its own weight – a short time ago there was no such material but today it’s believed that carbon nanotubes could do the job (nano-technology more generally was another favourite of MR readers and this proposal would advance that cause.)

A space elevator is a game-changer because it dramatically lowers the cost of putting payloads into space. Moreover, once you have one elevator it becomes much easier to get a second. In contrast, rockets are always going to be expensive because you have to carry a lot of fuel just to lift the fuel and sitting on top of 4 million pounds of explosive is always going to be dangerous. The space elevator would provide a permanent access point to the stars and it can be had for less than 100 billion. Going up anyone?

More on the space elevator idea here and here.

The Big Fail

The Big Fail, Joe Nocera and Bethany McLean’s new book about the pandemic, is an angry book. Rightly so. It decries the way the bien pensant, the self-righteously conventional, were able to sideline, suppress and belittle other voices as unscientific, fraudulent purveyors of misinformation. The Big Fail gives the other voices their hearing— Martin Kulldorff, Sunetra Gupta, Jay Bhattacharya and Emily Oster are recast not as villains but as heroes; as is Ron DeSantis who is given credit for bucking the conventional during the pandemic (Nocera and McLean wonder what happened to the data-driven DeSantis, as do I.)

Amazingly, even as highly-qualified epidemiologists and economists were labelled “anti-science” for not following the party line, the biggest policy of them all, lockdowns, had little to no scientific backing:

…[lockdowns] became the default strategy for most of the rest of the world. Even though they had never been used before to fight a pandemic, even though their effectiveness had never been studied, and even though they were criticized as authoritarian overreach—despite all that, the entire world, with a few notable exceptions, was soon locking down its citizens with varying degrees of severity.

In the United States, lockdowns became equated with “following the science.” It was anything but. Yes, there were computer models suggesting lockdowns would be effective, but there were never any actual scientific studies supporting the strategy. It was a giant experiment, one that would bring devastating social and economic consequences.

The narrative lined up “scientific experts” against “deniers, fauxers, and herders” with the scientific experts united on the pro-lockdown side (the following has no indent but draws from an earlier post). But let’s consider. In Europe one country above all others followed the “ideal” of an expert-led pandemic response. A country where the public health authority was free from interference from politicians. A country where the public had tremendous trust in the state. A country where the public were committed to collective solidarity and public welfare. That country, of course, was Sweden. Yet in Sweden the highly regarded Public Health Agency, led by state epidemiologist Anders Tegnell, an expert in infectious diseases, opposed lockdowns, travel restrictions, and the general use of masks.

It’s important to understand that Tegnell wasn’t an outsider marching to his own drummer, anti-lockdown was probably the dominant expert opinion prior to COVID. In a 2006 review of pandemic policy, for example, four highly-regarded experts argued:

It is difficult to identify circumstances in the past half-century when large-scale quarantine has been effectively used in the control of any disease. The negative consequences of large-scale quarantine are so extreme (forced confinement of sick people with the well; complete restriction of movement of large populations; difficulty in getting critical supplies, medicines, and food to people inside the quarantine zone) that this mitigation measure should be eliminated from serious consideration.

Travel restrictions, such as closing airports and screening travelers at borders, have historically been ineffective.

….a policy calling for communitywide cancellation of public events seems inadvisable.

The authors included Thomas V. Inglesby, the Director of the Johns Hopkins Center for Health Security, one of the most highly respected centers for infectious diseases in the world, and D.A. Henderson, the legendary epidemiologist widely credited with eliminating smallpox from the planet.

Nocera and McLean also remind us of the insanity of the mask debate, especially in the later years of the pandemic.

But by the spring of 2022, the CDC had dropped its mask recommendations–except, incredibly, for children five and under, who again, were the least likely to be infected.

…Once again it was Brown University economist Emily Oster who pointed out how foolish this policy was…The headline was blunt: Masking Policy is Incredibly Irrational Right Now. In this article she noted that even as the CDC had dropped its indoor mask requirements for kids six and older, it continued to maintain the policy for younger children. “Some parents of young kids have been driven insane by this policy,” Oster wrote, “I sympathize–because the policy is completely insane…”

As usual, her critics jumped all over her. As usual, she was right.

Naturally, I don’t agree with everything in the Big Fail. Nocera and McLean, for example, are very negative on the role of private equity in hospitals and nursing homes. My view is that any theory of what is wrong with American health care is true because American health care is wrong in every possible way. Still, I don’t see private equity as a driving force. It’s easy to find examples where private equity owned nursing homes performed poorly but so did many other nursing homes. More systematic analyses find that PE owned nursing homes performed about the same, worse or better than other nursing homes. Personally, I’d bet on about the same overall. Covid in the Nursing Homes: The US Experience (open), my paper with Markus Bjoerkheim, shows that what mattered more than anything else was simply community spread (see also this paper for the ways in which I disagreed with the GBD approach). More generally, my paper with Robert Omberg, Is it possible to prepare for a pandemic? (open) finds that nations with universal health care, for example, didn’t have fewer excess deaths.

The bottom line is that vaccines worked and everything else was a sideshow. Had we approved the vaccines even 5 weeks earlier and delivered them to the nursing homes, we could have saved 14,000 lives and had we vaccinated nursing home residents just 10 weeks earlier, before the vaccine was approved, as Deborah Birx had proposed, we might have saved 40,000 lives. Nevertheless, Operation Warp Speed was the shining jewel of the pandemic. The lesson is that we should fund further vaccine R&D, create a library of prototype vaccines against potential pandemic threats, streamline our regulatory systems for rapid response, agree now on protocols for human challenge trials and keep warm rapid development systems so that we can produce vaccines not in 11 months but in 100 days.

The Big Fail does a great service in critiquing those who stifled debate and in demanding a full public accounting of what happened–an accounting that  has yet to take place.

Addendum 1: I have reviewed most of the big books on the pandemic including the National Covid Commission’s Lessons from the COVID WAR, Scott Gottlieb’s Uncontrolled Spread, Michael Lewis’s The Premonition, Andy Slavitt’s Preventable and Abutaleb and Paletta’s Nightmare Scenario.

Addendum 2: I also liked Nocera and McLean’s All the Devils are Here on the financial crisis. Sad to say that the titles could be swapped without loss of validity.

From the Comments

The context is that human challenge trials were “ethically fraught” but, Sure writes:

…I think we had more than a few instances in history where restricting movement, shuttering houses of worship, and stratifying the economy into favored and disfavored sectors was considered ethically fraught.

I mean we know that limiting visitation to old folks shortens their lives. We know that child abuse becomes harder to find the fewer the number of folks who lay eyes on them each day. We know that initimate partner violence increases when the housing market gets frozen. And we know that suicides crest when businesses go under.

Yet no such epistemic humility and wariness followed with public health recommendations to be tried on a scale reserved hitherto for literal wars and genocides. And we blindly went ahead full speed.

Or consider even the better defined but wildly more mundane issue: proof of vaccination. For decades health ethicists told us that merely revealing a patient’s name, let alone which medications they have taken, was an unconscionable ethical violation. One which we instituted balkanized medical systems to manage and where the cost has been literal lives lost as we have had untold numbers of patients fall through the cracks thanks to duplicate profiles, failure of providers to communicate, and of course scads and scads of useful data locked away from effective statistical analysis that could spot patterns of medical error.

Yet when the powers that be decided that we needed vaccine passports so we could enjoy dining again? Well, every waiter in the country becomes a safe repository of PHI.

No formal study. No deliberations. Precious little if any publications.

And even then, it went only for what was the most expedient option for the enlightened. No ability to get an antibody titer card for medical equivalence. No ability to substitute PCR results with a physician evaluation of recent disease recovery.

Professional medical ethics are bogus. There is no consistency and the entire profession serves to pander to the prejudices of the educated.

What I’ve been reading

1. Dan Werb, The Invisible Siege: The Rise of Coronavirus and the Search for a Cure.  An excellent book on the history of coronaviruses more generally, with much of the strongest material coming on how earlier coronavirus investigations fed into the progress we have made on Covid-19.  Recommended, not just what all the other Covid books are telling you.

2. James Poskett, Horizons: The Global Origins of Modern Science.  A useful account of what the title promises, with a look at contributions from pre-conquest Mexico, China, and other non-Western locales.  Maybe the book pushes the non-Western theme a little too much at points, but this is basically a sane and readable account, and most of the cross-cultural connections are valid rather than strained.

3. Evan Lieberman, Until We Have Won Our Liberty: South Africa After Apartheid.  An interesting book, and one which contains a lot of useful information.  Yet the author works too hard to avoid recognizing just how badly matters have gone.  Overall, incomes are down and the racial wealth gap has not improved…and that is after getting rid of one of the most inefficient economic systems of all time, namely apartheid.  For sources try this and this, among others.  The income gains you can find are focused in a super-small group.

4. Paul Mango, Warp Speed: Inside the Operation that Beat Covid, the Critics, and the Odds.  Written by an HHS insider and participant, this is kind of cheesy and fanboyish.  But probably it should be!  For one thing, the book gives you a sense of just how much talent was involved in OWS, an under-discussed lesson.  On p.69, you can learn that they repeatedly considered human challenge trials and learn their question-begging reasons for refusing to do them.

5. David Hackett Fischer, African Founders: How Enslaved People Expanded American Ideals.  An extended history of U.S. slavery, focusing on regional differences, for instance Carolina Gullahs vs. New Orleans vs. Mississippi.  As you might expect, the broader story is integrated with that of the particular African origins of the slaves as well.  A strong book, recommended.

Michael Magoon’s From Poverty to Progress: Understanding Humanity’s Greatest Achievement is a very good introduction to the importance of progress and material wealth in history.

In defense of extremism

That is my latest Bloomberg column, the argument is super-simple:

Calling something “extremist” is not an effective critique. It’s a sign that the speaker or writer either doesn’t want to take the trouble to make a real argument, or is hoping to win the debate through rhetoric or Twitter pressure rather than logic. It’s also a bad sign when critics stress how social media have fed and encouraged “extremism.”

I favor plenty of extremist ideas. For instance, I think that the world’s major cities should adopt congestion rush-hour pricing. (I know, it hardly sounds extreme, but I assure you that many drivers consider it extremely outrageous to have to pay to drive on roads that were free a few hours before.) London and Singapore have versions of congestion pricing, with some success, but given the public reaction and that most other major cities do not seem close to enactment, it has to count as a relatively extreme idea.

I also favor human challenge trials, arguably an even more extreme idea. In human challenge trials, rather than waiting for a virus to infect those vaccinated (randomly) with the placebo, scientists recruit volunteers and infect them deliberately and immediately. This accelerates the speed of a biomedical trial. To many people there is something repugnant about asking for volunteers and then deliberately doing them harm by injecting them with the virus.

Maybe human challenge trials aren’t a good idea. But calling them extreme or repugnant does not help explain why.

We then get into some more “extreme” ideas…

Someone complaining about “extremism” is a likely predictor of an epistemic vice.

Wednesday assorted links

1. U.S.A. fact of the day.

2. Short of replication, the errors in papers can be increasingly difficult to find.  What should we infer from that?

3. Good James Wood review of the new Fintan O’Toole book on Ireland (New Yorker).

4. Would the Chinese opt for a blockade against Taiwan?

5. When does Matt Levine publish Money Stuff? (Cowen’s Third Law)

6. A guy live-tweeting his human challenge trial for a dysentery vaccine.

7. Revisionist defense of Star Trek: The Motion Picture.

Wednesday assorted links

1. English-language music is losing relative ground in global markets (The Economist).

2. Would you take free land in rural Kansas?

3. One woman (Anna Gát) who is giving up drinking.

4. Redux of November post on how the Covid pandemic is evolving.

5. “Today, Leo Strauss is more popular in the Chinese-speaking world than he has ever been in the English-speaking world.

6. South Korea’s new nose-only mask.  And Human Challenge Trial going OK so far.

7. Texas philanthropist who supported the work to prove Fermat’s Last Theorem (NYT).

Thursday assorted links

1. Paul Simon and Malcolm Gladwell collaboration.

2. Farhad Manjoo sanity about Instagram (NYT).

3. Is Wang Huning the world’s most important public intellectual?

4. Average guy vs. 100 mph fastballs.  What is the meta-lesson here?

5. The importance of rare gene variants for autism.

6. We are winning the war on oil spills.

7. Freddie on Ross.  I tend to side with Ross, but still a good piece.

8. NYT covers Human Challenge Trials — amazing how lame is the quoted response of the biomedical establishment.

Fractional Dosing Trials Now!

Fractional dosing has the potential to massively increase the supply of COVID vaccine. The Moderna Phase I clinical trial and Pfizer Phase I/II trials already indicated a substantial immune response with smaller doses but the vaccine companies are under-incentivized to run additional fractional dosing trials (they won’t gain trillions, at best they will gains billions and might even lose some profit) and governments and private organizations are not picking up the ball. There are just two small trials underway that I am aware of:

N.B. now that we know that the vaccines work. we don’t need to study every dosage for efficacy against the virus. Instead of efficacy studies we can study how the vaccine is working in the body compared to those fully immunized, immunogencity trials (which is what the above trials are doing) and then use data and theory to infer effectiveness. If we felt it necessary to study effectiveness, human challenge trials would be ideal in this situation as you can study gradually smaller doses with little risk to the patients. But given the urgency, immunogenicity trials should provide enough information to make decisions on the ground. To limit risk, one could do a half-dose on the second dose or one could do a half-dose in people under the age of 50. Both of these regimens would still create significant increases in supply. Recall that in 2018, facing a yellow fever epidemic and a shortage of vaccine, Brazil used 1/5th doses to break the epidemic.

There are no guarantees but the world is ignoring a potential trillion dollar bill lying on the sidewalk.

Hat tip for discussion: Witold and Amrita.

Tuesday assorted links

1. John Naisbett has passed away.

2. Suicides down for 2020, misery loves company?

3. What it is like to be in a human challenge trial.  The argument that the muon results are for real.

4. Eric Weinstein on geometric unity.  Is he right?  Is that the right question?

5. “Dowbak utilizes the mechanics of the smart contract imbedded in the NFT to create a self-generating Genesis piece which will continue to create new, discreet NFTs over the course of approximately one year.”  With sixty bids, the current value is well over $2 million, do take a look at the image.  And it is stochastically not a Crusonia plant: “However, Dowbak has also introduced the element of chance into the work’s algorithm through another self-referential twist–REPLICATOR can also jam. A jam comes in the form of a unique “Jam Artwork,” which will stop a generation from continuing to replicate, curbing exponential growth.”

6. In Houston, autonomous cars are delivering Domino pizza.

7. DC’s rising libertarian star.

8. Canadian border quarantine arbitrage.

9. Mariner Eccles poem about the New Deal.

In praise of Alex Tabarrok

Here’s a question I’ve been mulling in recent months: Is Alex Tabarrok right? Are people dying because our coronavirus response is far too conservative?

I don’t mean conservative in the politicized, left-right sense. Tabarrok, an economist at George Mason University and a blogger at Marginal Revolution, is a libertarian, and I am very much not. But over the past year, he has emerged as a relentless critic of America’s coronavirus response, in ways that left me feeling like a Burkean in our conversations.

He called for vastly more spending to build vaccine manufacturing capacity, for giving half-doses of Moderna’s vaccine and delaying second doses of Pfizer’s, for using the Oxford-AstraZeneca vaccine, for the Food and Drug Administration to authorize rapid at-home tests, for accelerating research through human challenge trials. The through line of Tabarrok’s critique is that regulators and politicians have been too cautious, too reluctant to upend old institutions and protocols, so fearful of the consequences of change that they’ve permitted calamities through inaction.

Tabarrok hasn’t been alone. Combinations of these policies have been endorsed by epidemiologists, like Harvard’s Michael Mina and Brown’s Ashish Jha; by other economists, like Tabarrok’s colleague Tyler Cowen and the Nobel laureates Paul Romer and Michael Kremer; and by sociologists, like Zeynep Tufekci (who’s also a Times Opinion contributor). But Tabarrok is unusual in backing all of them, and doing so early and confrontationally. He’s become a thorn in the side of public health experts who defend the ways regulators are balancing risk. More than one groaned when I mentioned his name.

But as best as I can tell, Tabarrok has repeatedly been proved right, and ideas that sounded radical when he first argued for them command broader support now. What I’ve come to think of as the Tabarrok agenda has come closest to being adopted in Britain, which delayed second doses, approved the Oxford-AstraZeneca vaccine despite its data issues, is pushing at-home testing and permitted human challenge trials, in which volunteers are exposed to the coronavirus to speed the testing of treatments. And for now it’s working: Britain has vaccinated a larger percentage of its population than the rest of Europe and the United States have and is seeing lower daily case rates and deaths.

Here is more from Ezra Klein at the New York Times.