Embryo Screening and Risk Calculus

Over the weekend The Guardian and The Times (UK) both ran articles on embryo selection. 

Polygenic screening of embryos is here, but is it ethical? Philip Ball for The Guardian 

Genetics firms screen embryos to create designer babies Danny Fortson, The Sunday Times.

I recommend the first article. Philip Ball is an accomplished science writer and former scientist. He touches on many of the most important aspects of the topic, not easy given the length restriction he was working with. 

However I'd like to cover an aspect of embryo selection which is often missed, for example by the bioethicists quoted in Ball's article.

Several independent labs have published results on risk reduction from embryo selection, and all find that the technique is effective. But some people who are not following the field closely (or are not quantitative) still characterize the benefits -- incorrectly, in my view -- as modest. I honestly think they lack understanding of the actual numbers.

Some examples:

Carmi et al. find a ~50% risk reduction for schizophrenia from selecting the lowest risk embryo from a set of 5. For a selection among 2 embryos the risk reduction is ~30%. (We obtain a very similar result using empirical data: real adult siblings with known phenotype.) 

Visscher et al. find the following results, see Table 1 and Figure 2 in their paper. To their credit they compute results for a range of ancestries (European, E. Asian, African). We have performed similar calculations using siblings but have not yet published the results for all ancestries.  

Relative Risk Reduction (RRR): 

Hypertension: 9-18% (ranges depend on specific ancestry) 

Type 2 Diabetes: 7-16% 

Coronary Artery Disease: 8-17% 

Absolute Risk Reduction (ARR): 

Hypertension: 4-8.5% (ranges depend on specific ancestry) 

Type 2 Diabetes: 2.6-5.5% 

Coronary Artery Disease: 0.55-1.1%

I don't view these risk reductions as modest. Given that an IVF family is aleady going to make a selection they clearly benefit from the additional information that comes with genotyping each embryo. The cost is a small fraction of the overall cost of an IVF cycle.

But here is the important mathematical point which many people miss: We buy risk insurance even when the expected return is negative, in order to ameliorate the worst possible outcomes. 

Consider the example of home insurance. A typical family will spend tens of thousands of dollars over the years on home insurance, which protects against risks like fire or earthquake. However, very few homeowners (e.g., ~1 percent) ever suffer a really large loss! At the end of their lives, looking back, most families might conclude that the insurance was "a waste of money"!

So why buy the insurance? To avoid ruin in the event you are unlucky and your house does burn down. It is tail risk insurance.

Now consider an "unlucky" IVF family. At, say, the 1 percent level of "bad luck" they might have some embryos which are true outliers (e.g., at 10 times normal risk, which could mean over 50% absolute risk) for a serious condition like schizophrenia or breast cancer. This is especially likely if they have a family history. 

What is the benefit to this specific subgroup of families? It is enormous -- using the embryo risk score they can avoid having a child with very high likelihood of serious health condition. This benefit is many many times (> 100x!) larger than the cost of the genetic screening, and it is not characterized by the average risk reductions given above.

The situation is very similar to that of aneuploidy testing (screening against Down syndrome), which is widespread, not just in IVF. The prevalence of trisomy 21 (extra copy of chromosome 21) is only ~1 percent, so almost all families doing aneuploidy screening are "wasting their money" if one uses faulty logic! Nevertheless, the families in the affected category are typically very happy to have paid for the test, and even families with no trisomy warning understand that it was worthwhile.

The point is that no one knows ahead of time whether their house will burn down, or that one or more of their embryos has an important genetic risk. The calculus of average return is misleading -- i.e., it says that home insurance is a "rip off" when in fact it serves an important social purpose of pooling risk and helping the unfortunate. 

The same can be said for embryo screening in IVF -- one should focus on the benefit to "unlucky" families to determine the value. We can't identify the "unlucky" in advance, unless we do genetic screening!

Some useful references:

Embryo Screening for Polygenic Disease Risk: Recent Advances and Ethical Considerations (Genes 2021 Special Issue) 

First Baby Born from a Polygenically Screened Embryo

Dune 2021

I have high hopes for this new version of Dune.

 

Below, a re-post with two Frank Herbert interviews. Highly recommended to fans of the novel. 

Frank Herbert interview on the origins of Dune (1969)

The interviewer is Willis E. McNelly, a professor of English (specializing in science fiction). Herbert discusses artistic as well as conceptual decisions made in the writing and background world building for Dune. Highly recommended for any fan of the book.

See also Dune and The Butlerian Jihad and Darwin Among the Machines.

The Bene Gesserit program had as its target the breeding of a person they labeled "Kwisatz Haderach," a term signifying "one who can be many places at once." In simpler terms, what they sought was a human with mental powers permitting him to understand and use higher order dimensions.

They were breeding for a super-Mentat, a human computer with some of the prescient abilities found in Guild navigators. Now, attend these facts carefully:

Muad'Dib, born Paul Atreides, was the son of the Duke Leto, a man whose bloodline had been watched carefully for more than a thousand years. The Prophet's mother, Lady Jessica, was a natural daughter of the Baron Vladimir Harkonnen and carried gene-markers whose supreme importance to the breeding program was known for almost two thousand years. She was a Bene Gesserit bred and trained, and should have been a willing tool of the project.

The Lady Jessica was ordered to produce an Atreides daughter. The plan was to inbreed this daughter with Feyd-Rautha Harkonnen, a nephew of the Baron Vladimir, with the high probability of a Kwisatz Haderach from that union. Instead, for reasons she confesses have never been completely clear to her, the concubine Lady Jessica defied her orders and bore a son. This alone should have alerted the Bene Gesserit to the possibility that a wild variable had entered their scheme. But there were other far more important indications that they virtually ignored ...

"Kwisatz Haderach" is similar to the Hebrew "Kefitzat Haderech", which literally means "contracting the path"; Herbert defines Kwisatz Haderach as "the Shortening of the Way" (Dune: Appendix IV).

Another good recording of Herbert, but much later in his life.

Leo Szilard, the Intellectual Bumblebee (lecture by William Lanouette)

 

This is a nice lecture on Leo Szilard by his biographer William Lanouette. See also ‘An Intellectual Bumblebee’ by Max Perutz.

Wikipedia: Leo Szilard was a Hungarian-American physicist and inventor. He conceived the nuclear chain reaction in 1933, patented the idea of a nuclear fission reactor in 1934, and in late 1939 wrote the letter for Albert Einstein's signature that resulted in the Manhattan Project that built the atomic bomb.

How Alexander Sachs, acting on behalf of Szilard and Einstein, narrowly convinced FDR to initiate the atomic bomb project: Contingency, History, and the Atomic Bomb. 

Szilard wrote children's stories and science fiction. His short story My Trial as a War Criminal begins after the USSR has defeated the US using biological weapons.

I was just about to lock the door of my hotel room and go to bed when there was a knock on the door and there stood a Russian officer and a young Russian civilian. I had expected something of this sort ever since the President signed the terms of unconditional surrender and the Russians landed a token occupation force in New York. The officer handed me something that looked like a warrant and said that I was under arrest as a war criminal on the basis of my activities during the Second World War in connection with the atomic bomb. There was a car waiting outside and they told me that they were going to take me to the Brookhaven National Laboratory on Long Island. Apparently, they were rounding up all the scientists who had ever worked in the field of atomic energy ...

This story was translated into Russian and it had a large impact on Andrei Sakharov, who showed it to his colleague Victor Adamsky:

A number of us discussed it. It was about a war between the USSR and the USA, a very devastating one, which brought victory to the USSR. Szilard and a number of other physicists are put under arrest and then face the court as war criminals for having created weapons of mass destruction. Neither they nor their lawyers could make up a cogent proof of their innocence. We were amazed by this paradox. You can’t get away from the fact that we were developing weapons of mass destruction. We thought it was necessary. Such was our inner conviction. But still the moral aspect of it would not let Andrei Dmitrievich and some of us live in peace.

See also The Many Worlds of Leo Szilard (APS symposium). Slides for Richard Garwin's excellent summary of Szilard's work, including nuclear physics, refrigeration, and Maxwell's Demon. One of Garwin's anecdotes:

Ted Puck was a distinguished biologist, originally trained in physics. ‘With the greatest possible reluctance I have come to the conclusion that it is not possible for me personally to work with you scientifically,’ he wrote Szilard. ‘Your mind is so much more powerful than mine that I find it impossible when I am with you to resist the tremendous polarizing forces of your ideas and outlook.’ Puck feared his ‘own flow of ideas would slow up & productivity suffer if we were to become continuously associated working in the same place and the same general kind of field.’ Puck said, ‘There is no living scientist whose intellect I respect more. But your tremendous intellectual force is a strain on a limited person like myself.’

Puck was a pioneer in single cell cloning, aided in part by Szilard:

When Szilard saw in 1954 that biologists Philip Marcus and Theodore Puck were having trouble growing individual cells into colonies, he concluded that “since cells grow with high efficiency when they have many neighbors, you should not let a single cell know it’s alone”. This was no flippant excursion into psychobiology. Rather, Szilard’s idea to use a layered feeder dish worked, while the open dish had not (Lanouette, 1992: 396–397).

After the war Szilard worked in molecular biology. This photo of Jacques Monod and Szilard is in the seminar room at Cold Spring Harbor Lab. Monod credits Szilard for the negative-feedback idea behind his 1965 Nobel prize.

“I have … recorded” in my Nobel lecture, said Monod, “how it was Szilard who decisively reconciled me with the idea (repulsive to me, until then) that enzyme induction reflected an anti-repressive effect, rather than the reverse, as I tried, unduly, to stick to.”

 

DNA forensics, genetic genealogy, and large databases (Veritasium video)

 

This is a good overview of DNA forensics, genetic genealogy, and existing databases like GEDmatch (Verogen).

@15:35 "Multiple law enforcement agencies have said that this is the most revolutionary tool they've had since the adoption of the fingerprint."

See Othram: the future of DNA forensics (2019):

The existing FBI standard (CODIS) for DNA identification uses only 20 markers (STRs -- previously only 13 loci were used!). By contrast, genome wide sequencing can reliably call millions of genetic variants. 

For the first time, the cost curves for these two methods have crossed: modern sequencing costs no more than extracting CODIS markers using the now ~30 year old technology. 

What can you do with millions of genetic markers? 

1. Determine relatedness of two individuals with high precision. This allows detectives to immediately identify a relative (ranging from distant cousin to sibling or parent) of the source of the DNA sample, simply by scanning through large DNA databases. 

...

More Othram posts.

Picking Embryos With Best Health Odds Sparks New DNA Debate (Bloomberg Technology)

Bloomberg Technology covers polygenic embryo screening. Note, baby Aurea is well over a year old now. 

I am informed by Genomic Prediction's CEO that the company does genetic testing for ~200 IVF clinics on 6 continents. The overall scale of activity is increasing rapidly and also covers more traditional testing such as PGT-A (testing for aneuploidy or chromosomal normality) and testing for monogenic conditions, PGT-M. Here, PGT = Preimplantation Genetic Testing (standard terminology in IVF). 

I believe that polygenic screening, or PGT-P, will become very common in the near future. It is natural for parents to want as much information as possible to select the embryo that will become their child, and all of these types of testing can be performed simultaneously by GP using the same standard cell biopsy. Currently ~60% of all IVF embryos produced in the US (millions per year, worldwide) undergo some kind of genetic testing.

Picking Embryos With Best Health Odds Sparks New DNA Debate

By Carey Goldberg

Rafal Smigrodzki won’t make a big deal of it, but someday, when his toddler daughter Aurea is old enough to understand, he plans to explain that she likely made medical history at the moment of her birth.

Aurea appears to be the first child born after a new type of DNA testing that gave her a “polygenic risk score.” It’s based on multiple common gene variations that could each have tiny effects; together, they create higher or lower odds for many common diseases.

Her parents underwent fertility treatment in 2019 and had to choose which of four IVF embryos to implant. They turned to a young company called Genomic Prediction and picked the embryo given the best genetic odds of avoiding heart disease, diabetes and cancer in adulthood.

Smigrodzki, a North Carolina neurologist with a doctorate in human genetics, argues that parents have a duty to give a child the healthiest possible start in life, and most do their best. “Part of that duty is to make sure to prevent disease -- that’s why we give vaccinations,” he said. “And the polygenic testing is no different. It’s just another way of preventing disease.”

The choice was simple for him, but recent dramatic advances in the science of polygenic risk scoring raise issues so complex that The New England Journal of Medicine in July published a special report on the problems with using it for embryo selection.

‘Urgent’ Debate

The paper points to a handful of companies in the U.S. and Europe that already are offering embryo risk scores for conditions including schizophrenia, breast cancer and diabetes. It calls for an “urgent society-wide conversation.”

“We need to talk about what sort of regulation we want to have in this space,” said co-author Daniel Benjamin, an economist specializing in genetics -- or “genoeconomist” -- at UCLA.

Unlike the distant prospect of CRISPR-edited designer babies,“this is happening, and it is now,” he said. Many claims by companies that offer DNA-based eating or fitness advice are “basically bunk,” he added, “but this is real. The benefits are real, and the risks are real.”

Among the problems the journal article highlights: Most genetic data is heavily Eurocentric at this point, so parents with other ancestry can’t benefit nearly as much. The science is so new that huge unknowns remain. And selection could exacerbate health disparities among races and classes.

The article also raises concerns that companies marketing embryo selection over-promise, using enticements of “healthy babies” when the scores are only probabilities, not guarantees -- and when most differences among embryos are likely to be very small.

The issues are so complicated and new that the New England Journal article’s 13 authors held differing views on how polygenic embryo scoring should be regulated, said co-first author Patrick Turley, a University of Southern California economist. But all agreed that “potential consumers need to understand what they’re signing up for,” he said. 

...

I have thought this outcome inevitable since laboratory methods became advanced enough to obtain an accurate and inexpensive human genotype from a sample equivalent to the DNA in a few cells (2012 blog post). The information obtained can now be used to predict characteristics of the individual, with applications in assisted reproduction, health science, and even criminal forensics (Othram, Inc.).

Related:

Polygenic Embryo Screening: comments on Carmi et al. and Visscher et al. (discussion of the NEJM paper described in the Bloomberg article). 

First Baby Born from a Polygenically Screened Embryo (video panel) 

Embryo Screening for Polygenic Disease Risk: Recent Advances and Ethical Considerations (Genes 2021 Special Issue)

Carey Goldberg is Boston bureau chief for Bloomberg. She appears in this recent WBUR On Point episode with Kathryn Paige Harden:

 

Compare to this 2013 "Genius Babies" episode of On Point in which I appeared.

   

War Nerd on US-China-Taiwan

Highly recommended. Read this article, which will enable you to ignore 99% of mass media and 90% of "expert" commentary on this topic.

THE WAR NERD: TAIWAN — THE THUCYDIDES TRAPPER WHO CRIED WOOF 

... The US/NATO command may be woofing just to get more ships and planes funded, but woofing can go badly wrong. The people you’re woofing at may think you really mean it. That’s what came very close to happening in the 1983 Able Archer NATO exercises. The woofing by Reagan and Thatcher in the leadup to those exercises was so convincing to the Soviet woof-ees that even the moribund USSR came close to responding in real—like nuclear—ways.

That’s how contingency plans, domestic political theatrics, and funding scams can feed into each other and lead to real wars.

Military forces develop contingency plans. That’s part of their job. Some of the plans to fight China are crazy, but some are just plausible enough to be worrying, because somebody might start thinking they could work. 

... What you do with a place like Xinjiang, if you’re a CIA/DoD planner, is file it under “promote insurgency” — meaning “start as many small fires as possible,” rather than “invade and begin a conventional war.”

And in the meantime, you keep working on the real complaints of the Uyghur and other non-Han ethnic groups, so that if you do need to start a conventional war in the Formosa Straits, you can use the Uyghur as a diversion, a sacrifice, by getting them to rise up and be massacred. Since there’s a big Han-Chinese population in Xinjiang, as the map shows, you can hope to stir up the sort of massacre/counter-massacre whipsaw that leaves evil memories for centuries, leading to a permanent weakening of the Chinese state.

This is a nasty strategy, but it’s a standard imperial practice, low-cost — for the empire, not the local population, of course. It costs those people everything, but empires are not sentimental about such things. 

... The Uyghur in Xinjiang would serve the same purpose as the Iraqi Kurds: “straw dogs destined for sacrifice.” If you want to get really cynical, consider that the reprisals they’d face from an enraged Chinese military would be even more useful to the US/NATO side than their doomed insurgency itself.

Atrocity propaganda is very important in 21st c warfare. At the moment, there’s no evidence of real, mass slaughter in Xinjiang, yet we’re already getting propaganda claims about it. Imagine what US/NATO could make out of the bloody aftermath of a doomed insurgency. Well, assuming that US/NATO survived a war with China, a pretty dicey assumption. More likely, CNN, BBC, and NYT would be the first to welcome our new overlords, Kent Brockman style. Those mainstream-media whores aren’t too bright but Lord, they’re agile. 

... Xinjiang, by contrast, can easily be imagined as One Giant Concentration Camp. After all, our leading “expert” on the province has never been there, and neither have his readers.

... The era of naval war based on carrier groups is over. They know that, even if they won’t say it.

If there’s a real war with China, the carriers will wait it out in San Diego harbor. I don’t say Honolulu, because even that wouldn’t be safe enough.

I’m not denigrating the courage or dedication of the crews and officers of USN vessels. At any level below JCOS, most of them are believers. But their belief is increasingly besieged and difficult to sustain, like an Episcopalian at Easter. You just can’t think too long about how cheap and effective antiship missiles are and still be a believer in aircraft carriers. As platforms of gunboat diplomacy against weak powers, they’re OK. 

... The thing is, and it’s weird you even have to say this: China is a big strong country coming out of an era of deep national humiliation and suffering, proud of its new prosperity. China’s success in lifting a desperately poor population into something like prosperity will likely be the biggest story from this era, when the canonical histories get distilled.

A nation hitting this stage is likely to include a lot of people, especially young men, who are itching to show what their country can do. Their patriotic eagerness is no doubt as gullible as most, but it’s real, and if you pay any attention in the online world, you can’t help seeing it.

People who mouth off about China never seem to imagine that anyone in China might hear, because as we are told over and over again, China-is-an-authoritarian-state. The implication is that nobody in China has any of the nationalistic fervor that we take for granted in our own Anglo states.

... Given the history of US/China relations, from the pogroms against Chinese immigrants to the Chinese Exclusion Act of 1882, through the demonization of Chinese mainlanders in the Cold War (which I remember distinctly from elementary school scare movies), the endless attempts to start insurgencies in Tibet, Xinjiang, and Fujian, to the nonstop violence and abuse of Asians in America, you don’t need to find reasons for Chinese people to want a war.

The odd thing is that most of them don’t seem to. That’s a remarkable testimony to the discipline and good sense of the Chinese public…so far. And it’s also, if you’re thinking clearly, a good reason not to keep provoking China in such gross, pointless ways. A population with that level of discipline and unity, matched with zooming prosperity, technical expertise, and pride on emerging from a long nightmare, is not one to woof at.

Of course the plan in the Pentagon is not real war. The plan is to slow China down, trip it up, “wrong-foot it” as they say in the Commonwealth. 

... So what will China do about Taiwan? China could take it right now, if it wanted to pay the price. Everyone knows that, though many fake-news sites have responded with childish, ridiculous gung-ho stories about how “Taiwan Could Win.” 

But will China invade? No. Not right now anyway. It doesn’t need to. The Chinese elite has its own constituencies, like all other polities (including “totalitarian” ones), and has to answer to them as circumstances change. 

So far China has been extraordinarily patient, a lot more patient than we’d be if China was promising to fight to the death for, say, Long Island. But that can change. Because, as I never tire of repeating, the enemy of the moment has constituencies too. And has to answer to them. 

So what happens if the US succeeds in hamstringing China’s economy? Welp, what’s the most reliable distraction a gov’t can find when it wants to unite a hard-pressed population against some distant enemy? 

That’s when China might actually do something about Taiwan. ...

See also Strategic Calculus of a Taiwan Invasion.

Note Added: Some readers may be alarmed that the War Nerd does not seem to accept the (Western) mass media propaganda about Xinjiang. Those readers might have poor memories, or are too young to know about, e.g., fake WMD or "babies taken out of incubators" or the countless other manufactured human rights abuses we read about in reliable journals like the New York Times or Washington Post.

Take these recent examples of US journalism on Afghanistan: 

The fake drone strike that killed 10 innocent family members, one of our last acts as we abandoned Afghanistan. (Fake because we probably did it just to show we could "strike back" at the bad guys.) Non-Western media reported this as a catastrophic failure almost immediately. But very few people in the US knew it until the Pentagon issued an apology in a late Friday afternoon briefing just recently. 

The drone strike was in retaliation for the suicide bombing at Kabul airport, in which (as reported by the Afghan government) ~200 people died. But evidence suggests that only a small fraction of these people were killed by bomb -- most of the 200 may have been shot by US and "coalition" (Turkish?) soldiers who might have panicked after the bombing. This is covered widely outside the US but not here.

If you want to understand the incredibly thin and suspicious sourcing of the "Uighur genocide" story, see here or just search for Adrian Zenz. 

Just a few years ago there were plenty of Western travelers passing through Xinjiang, even by bicycle, vlogging and posting their videos on YouTube. I followed these YouTubers at the time because of my own travel interest in western and south-western China, not for any political reason.

If you watch just a few of these you'll get an entirely different impression of the situation on the ground than you would get from Western media. For more, see this comment thread:

I want to be clear that because PRC is an authoritarian state their reaction to the Islamic terror attacks in Xinjiang circa 2015 was probably heavy handed and I am sure some of the sad stories told about people being arrested, held without trial, etc. are true. But I am also sure that if you visit Xinjiang and ask (non-Han) taxi drivers, restaurant owners, etc. about the level of tension you will get a very different impression than what is conveyed by Western media. 

... 

No nation competing in geopolitics is without sin. One aspect of that sin (both in US and PRC): use of mass media propaganda to influence domestic public opinion. 

If you want to be "reality based" you need to look at the strongest evidence from both sides. 

...

Note to the credulous: The CIA venture fund InQTel was an investor in my first startup, which worked in crypto technology. We worked with CIA, VOA, NED ("National Endowment for Democracy" HA HA HA) on defeating the PRC firewall in the early internet era. I know a fair bit about how this all works -- NGO cutouts, fake journalists, policy grifters in DC, etc. etc. Civilians have no idea. 

At the time I felt (and still sort of feel) that keeping the internet free and open is a noble cause. But do I know FOR SURE that state security works DIRECTLY with media and NGOs to distort the truth (i.e., lies to the American people, Iraq WMD yada yada). Yes, I know for sure and it's easy to detect the pattern just by doing a tiny bit of research on people like Cockerell or Zenz. 

... 

Keep in mind I'm not a "dove" -- MIC / intel services / deep state *has to* protect against worst case outcomes and assume the worst about other states. 

They have to do nasty stuff. I'm not making moral judgements here. But a *consequence* of this is that you have to be really careful about information sources in order to stay reality based...

Men Without Women

This short story has it all -- genetic genealogy, ultra high net worth physics quant banker, stripper, cop, marriage, family, New Yorker writer. It's fiction, but based on real characters and stories. 

There is an audio version, read by the author, at the link.

Satellites by Rebecca Curtis (The New Yorker July 5, 2021) 

My husband and Tony were anxiety-ridden workaholics who’d focussed, from a young age, on earning cash. Tony wanted enough for a good life; Conor, enough to feel safe. They were fifty-six years old, though Conor looked forty-five and Tony thirty-five. They were meticulous, but owing to oversights they’d each had five kids by four women. They were two nerds from New Hampshire. ... 

His ancestors, he told me, had founded America. He’d started working at age twelve, as a farmhand, and eventually acquired a Ph.D. in quantum physics from Harvard, then served for decades as the “head quant” at a world-renowned investment bank. But he wasn’t smart enough to be skeptical when go-go dancers said, Don’t worry, I’m on the pill. ... 

After high school, Tony turned down a scholarship to the University of New Hampshire. He wanted to work. He did active duty in the Marines for eight years, then served in the Air National Guard for twenty while working as a cop. Now he collected his police pension and, for fun, drove a delivery truck. 

... 

Conor smiled. By the way, he said, had Tony ever done 23andMe or Ancestry.com? 

Tony squinted. Ancestry. Sinead bought them kits for his birthday. Why? 

Conor peered up at Jupiter, approaching Saturn for the great conjunction, and the murky dimmer stars. I studied shuttered restaurants. A few bars had created outdoor dining rooms and were busy; the 7-Eleven was dark, but the ever-glowing “Fortune Teller!” sign on the adjacent cottage was lit. 

No reason, Conor said. Had Tony, he asked, opted into his family DNA tree, to see his matches who’d already done Ancestry? Or elected to receive text alerts whenever some new supposed relative signed on? 

Tony walked swiftly. Nah, he said. He’d done Ancestry to make Sinead happy. He shrugged. She’d made their accounts, he said. She probably opted him in; he wasn’t sure. 

When we got home, Tony’s phone had twenty missed calls. 

...

Men Without Women, Ernest Hemingway 1927. "Hemingway begins to examine the themes that would occupy his later works: the casualties of war, the often uneasy relationship between men and women, ..."

Rebecca Curtis interview

In “Satellites,” your story in the Fiction Issue, a woman and her husband, a retired banker, host the husband’s friend at their Jersey-shore mansion. The woman is a frustrated writer, and, to inspire her, her husband, Conor, asks the friend, Tony, a retired police officer, to tell her cop stories. How would you describe the woman’s views of these two men? 

The narrator is awed by how smart Tony and her husband are, and by how hard they work. She’s impressed that they’ve read so much and educated themselves about so many diverse topics while performing demanding and often unpleasant jobs, and by the fact that they’re two of the most generous, kind people she knows. She appreciates that they’ve maintained lifelong friendships, something that she wishes she’d done herself. She doesn’t agree with all their political ideas. Earlier in her life, she believed that, one, bankers cared about money but not about art, literature, world hunger, etc.; and, two, that anyone who supported Trumpish policies (or who voted for anyone like Trump) must be an ignorant jerk. Meeting her husband (and Tony) punctured those beliefs. 

The narrator views herself as the proverbial grasshopper: someone—possibly frivolous, vapid, and solipsistic—who wants to enjoy her life, sing, dance, make “art,” while working various hip-but-not-very-remunerative jobs to pay rent, never truly planning for winter. Tony and Conor are ants: anxious, alert to the dangers the world can pose, doing difficult (and sneered-upon) jobs diligently so they’ll be protected when scarcity comes. The narrator aspires to be more ant-like while remaining a grasshopper. 

Tony and Conor are, in some ways, obsessed with genetics and lineage—they discuss Ancestry.com and bloodlines—but their own families (they each have five children by four women) are somewhat of a disappointment, or even an afterthought, to them. Can you say a little about that tension? 

Conor and Tony suffer because—in several cases—they don’t have the ability to see their children. In the case of divorce, a time-sharing agreement may be in place, but, if the mother has principal custody and won’t permit the father’s visits, what can the father do? Possession sometimes is nine-tenths of the law. Hiring lawyers and going to court to try to force a mother who won’t honor custody agreements to do so requires copious energy, oodles of spare time, and a small fortune. Conor and Tony care deeply about their children, but they’ve lost control—in some cases, of seeing their kids, and, in others, of influencing them. They may feel powerless.

PGT-P with Elizabeth Carr and Dr. Serena Chen

 

This is a discussion of Preimplantation Genetic Testing in IVF with Dr. Serena Chen (IRMS and Rutgers medical school) and Elizabeth Carr (first US IVF baby, fertility patient advocate). 

We mostly focus on polygenic embryo screening, or PGT-P, but at the end I discuss some recent results showing that Genomic Prediction's aneuploidy test (PGT-A, which screens for chromosomal issues, such as trisomy 21) is more accurate than other existing technologies and leads to significantly higher pregnancy success rates. The results, which were obtained independently (not by GP) in a large sample size study, will be presented at the annual American Society of Reproductive Medicine meeting in October. 

This is a video version of the podcast.

Chinese Air Power: Justin Bronk RUSI UK

 

This is a good overview. Bronk (Research Fellow for Airpower and Technology in the Military Sciences team at Royal United Services Institute, UK) is good, Rupprecht also. (See show notes for links.)

However, both are looking at open source information and someone fluent in Mandarin with a technical background can do even better. 

Just a few notes for now -- I may revisit to add more detailed analysis. 

1. J10 and J20 are world class fighters, largely indigenously designed. J16 is best flanker variant in the world today. 

2. PLAAF missiles (PL12, PL15, cruise missiles, etc.): some argue that PL12 and PL15 are among the best AAM in the world right now. Note use of AESA seeker in individual missiles while IIRC Russians have not incorporated AESA radar in their fighters yet. 

3. WS10 and WS15 engines nearly mature -- WS10 now deployed in single engine J10. 

4. Note remarks about S400 sales to PRC and relatively small gap between PRC SAMs / air defense and Russian systems. 

5. Individual fighter characteristics are becoming less important compared to missile and sensor technology. For example, the low cost JF-17 (co-developed by PRC and Pakistan) is respectable (roughly comparable to early F-16 capabilities) as a plane, but with its block 3 sensor package and PL-12/15 missiles is competitive with much more expensive generation 4+ fighters. The fighter (eventually, drone or UCAV) becomes just a sensor and missile platform...

6. Slightly off-topic: I think the window for utility of stealth is closing fast as radar technology improves. Ubiquitous drones (which can, for example, image stealth opponents from above or behind) and sensor fusion mean that stealth missions over enemy territory against a peer opponent with good SAMs/air defense look very risky.

The two very obvious and critical technology gaps between PRC and the West were jet engines and semiconductors. It looks like both are on a clear trajectory to close in the next ~5y or so. My guess is that PRC military radar (EM hardware and hardware/software for post-processing), missile technology, and AI/ML are already on par with the US. Sensors, Missiles/Drones, and AI/ML will be the most important technologies for warfare in the coming decades. [1] [2]

With effectively no technology gap between US and PRC the military equation tilts in their favor over coming decades. Once a country has developed the full stack of military technology their costs are better estimated in PPP rather than exchange rate units: local costs such as compensation for engineers, factory workers, etc. predominate. Since the PRC economy is already significantly larger than the US economy in PPP terms, and growing faster, they can afford more (new, advanced) military hardware than we can in the coming decades. Add to this that their focus is concentrated in the Asia-Pacific region, while the US spreads its capability over the entire world, and it seems almost inevitable (barring economic collapse) that the military balance of power in the Asia region will shift in favor of PRC.

Kathryn Paige Harden Profile in The New Yorker (Behavior Genetics)

This is a good profile of behavior geneticist Paige Harden (UT Austin professor of psychology, former student of Eric Turkheimer), with a balanced discussion of polygenic prediction of cognitive traits and the culture war context in which it (unfortunately) exists.

Can Progressives Be Convinced That Genetics Matters? 

The behavior geneticist Kathryn Paige Harden is waging a two-front campaign: on her left are those who assume that genes are irrelevant, on her right those who insist that they’re everything. 

Gideon Lewis-Kraus

Gideon Lewis-Kraus is a talented writer who also wrote a very nice article on the NYTimes / Slate Star Codex hysteria last summer.

Some references related to the New Yorker profile:

1. The paper Harden was attacked for sharing while a visiting scholar at the Russell Sage Foundation: Game Over: Genomic Prediction of Social Mobility 

2. Harden's paper on polygenic scores and mathematics progression in high school: Genomic prediction of student flow through high school math curriculum 

3. Vox article; Turkheimer and Harden drawn into debate including Charles Murray and Sam Harris: Scientific Consensus on Cognitive Ability?

A recent talk by Harden, based on her forthcoming book The Genetic Lottery: Why DNA Matters for Social Equality

Regarding polygenic prediction of complex traits 

I first met Eric Turkheimer in person (we had corresponded online prior to that) at the Behavior Genetics Association annual meeting in 2012, which was back to back with the International Conference on Quantitative Genetics, both held in Edinburgh that year (photos and slides [1] [2] [3]). I was completely new to the field but they allowed me to give a keynote presentation (if memory serves, together with Peter Visscher). Harden may have been at the meeting but I don't recall whether we met. 

At the time, people were still doing underpowered candidate gene studies (there were many talks on this at BGA although fewer at ICQG) and struggling to understand GCTA (Visscher group's work showing one can estimate heritability from modestly large GWAS datasets, results consistent with earlier twins and adoption work). Consequently a theoretical physicist talking about genomic prediction using AI/ML and a million genomes seemed like an alien time traveler from the future. Indeed, I was.

My talk is largely summarized here:

On the genetic architecture of intelligence and other quantitative traits 

https://arxiv.org/abs/1408.3421 

How do genes affect cognitive ability or other human quantitative traits such as height or disease risk? Progress on this challenging question is likely to be significant in the near future. I begin with a brief review of psychometric measurements of intelligence, introducing the idea of a "general factor" or g score. The main results concern the stability, validity (predictive power), and heritability of adult g. The largest component of genetic variance for both height and intelligence is additive (linear), leading to important simplifications in predictive modeling and statistical estimation. Due mainly to the rapidly decreasing cost of genotyping, it is possible that within the coming decade researchers will identify loci which account for a significant fraction of total g variation. In the case of height analogous efforts are well under way. I describe some unpublished results concerning the genetic architecture of height and cognitive ability, which suggest that roughly 10k moderately rare causal variants of mostly negative effect are responsible for normal population variation. Using results from Compressed Sensing (L1-penalized regression), I estimate the statistical power required to characterize both linear and nonlinear models for quantitative traits. The main unknown parameter s (sparsity) is the number of loci which account for the bulk of the genetic variation. The required sample size is of order 100s, or roughly a million in the case of cognitive ability.

The predictions in my 2012 BGA talk and in the 2014 review article above have mostly been validated. Research advances often pass through the following phases of reaction from the scientific community:

1. It's wrong ("genes don't affect intelligence! anyway too complex to figure out... we hope")

2. It's trivial ("ofc with lots of data you can do anything... knew it all along")

3. I did it first ("please cite my important paper on this")

Or, as sometimes attributed to Gandhi: "First they ignore you, then they laugh at you, then they fight you, then you win.”

See also To Predict the Future it is useful to understand the Past.

Technical note: 

In 2014 I estimated that ~1 million genotype | phenotype pairs would be enough to capture most of the common SNP heritability for height and cognitive ability. This was accomplished for height in 2017. However, the sample size of well-phenotyped individuals is much smaller for cognitive ability, even in 2021, than for height in 2017. For example, in UK Biobank the cognitive test is very brief (~5 minutes IIRC, a dozen or so questions), but it has not even been administered to the full cohort as yet. In the Educational Attainment studies the phenotype EA is only moderately correlated (~0.3 ?) or so with actual cognitive ability.

Hence, although the most recent EA4 results use 3 million individuals [1], and produce a predictor which correlates ~0.4 with actual EA, the statistical power available is still less than what I predicted would be required to train a really good cognitive ability predictor.

In our 2017 height paper, which also briefly discussed bone density and cognitive ability prediction, we built a cognitve ability predictor roughly as powerful as EA3 using only ~100k individuals with the noisy UKB test data. So I remain confident that  ~million individuals with good cognitive scores (e.g., SAT, AFQT, full IQ test) would deliver results far beyond what we currently have available. We also found that our predictor, built using actual (albeit noisy) cognitive scores exhibits less power reduction in within-family (sibling) analyses compared to EA. So there is evidence that (no surprise) EA is more influenced by environmental factors, including so-called genetic nurture effects, than is cognitive ability.

A predictor which captures most of the common SNP heritability for cognitive ability might correlate ~0.5 or 0.6 with actual ability. Applications of this predictor in, e.g., studies of social mobility or educational success or even longevity using existing datasets would be extremely dramatic.

US debt, dollar-rmb, digital rmb (Gavekal)

 

I agree with Louis Gave's take on most of the topics discussed. Gavekal manages a China fixed income fund and some other China-focused funds, so he is talking his book. But the arguments stand on their own.

At ~45m, a good discussion of digital RMB and why it will break the technology record for fastest adoption by first 1 billion users. See earlier discussion (Ray Dalio) on de-dollarization and digital RMB here. 

This is a scary graph from Gave's presentation:

This is another good interview:

Finitism and Physics

New paper on arXiv today.

A brief precis: Gravitational collapse limits the amount of energy present in any space-time region. This in turn limits the precision of any measurement or experimental process that takes place in the region. This implies that the class of models of physics which are discrete and finite (finitistic) cannot be excluded experimentally by any realistic process. Note any digital computer simulation of physical phenomena is a finitistic model.

We conclude that physics (Nature) requires neither infinity nor the continuum. For instance, neither space-time nor the Hilbert space structure of quantum mechanics need be absolutely continuous. This has consequences for the finitist perspective in mathematics -- see excerpt below.

Fundamental Limit on Angular Measurements and Rotations from Quantum Mechanics and General Relativity 

arXiv:2108.11990 

Xavier Calmet, Stephen D.H. Hsu 

We show that the precision of an angular measurement or rotation (e.g., on the orientation of a qubit or spin state) is limited by fundamental constraints arising from quantum mechanics and general relativity (gravitational collapse). The limiting precision is 1/r in Planck units, where r is the physical extent of the (possibly macroscopic) device used to manipulate the spin state. This fundamental limitation means that spin states S1 and S2 cannot be experimentally distinguished from each other if they differ by a sufficiently small rotation. Experiments cannot exclude the possibility that the space of quantum state vectors (i.e., Hilbert space) is fundamentally discrete, rather than continuous. We discuss the implications for finitism: does physics require infinity or a continuum?

From the conclusions:

IV. FINITISM: DOES PHYSICS REQUIRE A CONTINUUM? 

Our intuitions about the existence and nature of a continuum arise from perceptions of space and time [21]. But the existence of a fundamental Planck length suggests that spacetime may not be a continuum. In that case, our intuitions originate from something (an idealization) that is not actually realized in Nature. 

Quantum mechanics is formulated using continuous structures such as Hilbert space and a smoothly varying wavefunction, incorporating complex numbers of arbitrary precision. However beautiful these structures may be, it is possible that they are idealizations that do not exist in the physical world. 

The introduction of gravity limits the precision necessary to formulate a model of fundamental quantum physics. Indeed, any potential structure smaller than the Planck length or the minimal angle considered here cannot be observed by any device subject to quantum mechanics, general relativity, and causality. Our results suggest that quantum mechanics combined with gravity does not require a continuum, nor any concept of infinity. 

It may come as a surprise to physicists that infinity and the continuum are even today the subject of debate in mathematics and the philosophy of mathematics. Some mathematicians, called finitists, accept only finite mathematical objects and procedures [25]. The fact that physics does not require infinity or a continuum is an important empirical input to the debate over finitism. For example, a finitist might assert (contra the Platonist perspective adopted by many mathematicians) that human brains built from finite arrangements of atoms, and operating under natural laws (physics) that are finitistic, are unlikely to have trustworthy intuitions concerning abstract concepts such as the continuum. These facts about the brain and about physical laws stand in contrast to intuitive assumptions adopted by many mathematicians. For example, Weyl (Das Kontinuum [21, 22]) argues that our intuitions concerning the continuum originate in the mind’s perception of the continuity of space-time. 

There was a concerted effort beginning in the 20th century to place infinity and the continuum on a rigorous foundation using logic and set theory. However, these efforts have not been successful. For example, the standard axioms of Zermelo-Fraenkel (ZFC) set theory applied to infinite sets lead to many counterintuitive results such as the Banach-Tarski Paradox: given any two solid objects, the cut pieces of either one can be reassembled into the other [23]. When examined closely all of the axioms of ZFC (e.g., Axiom of Choice) are intuitively obvious if applied to finite sets, with the exception of the Axiom of Infinity, which admits infinite sets. (Infinite sets are inexhaustible, so application of the Axiom of Choice leads to pathological results.) The Continuum Hypothesis, which proposes that there is no cardinality strictly between that of the integers and reals, has been shown to be independent (neither provable nor disprovable) in ZFC [24]. Finitists assert that this illustrates how little control rigorous mathematics has on even the most fundamental properties of the continuum. 

David Deutsch [26]: The reason why we find it possible to construct, say, electronic calculators, and indeed why we can perform mental arithmetic, cannot be found in mathematics or logic. The reason is that the laws of physics “happen to” permit the existence of physical models for the operations of arithmetic such as addition, subtraction and multiplication. 

This suggests the primacy of physical reality over mathematics, whereas usually the opposite assumption is made. From this perspective, the parts of mathematics which are simply models or abstractions of “real” physical things are most likely to be free of contradiction or misleading intuition. Aspects of mathematics which have no physical analog (e.g., infinite sets, the continuum) are prone to problems in formalization or mechanization. Physics – i.e., models which can be compared to experimental observation, actual “effective procedures” – does not ever require infinity, although it may be of some conceptual convenience. Hence it seems possible, and the finitists believe, that the Axiom of Infinity and its equivalents do not provide a sound foundation for mathematics.

See also 

ICML notes:

We experience the physical world directly, so the highest confidence belief we have is in its reality. Mathematics is an invention of our brains, and cannot help but be inspired by the objects we find in the physical world. Our idealizations (such as "infinity") may or may not be well-founded. In fact, mathematics with infinity included may be very sick, as evidenced by Godel's results, or paradoxes in set theory. There is no reason that infinity is needed (as far as we know) to do physics. It is entirely possible that there are only a (large but) finite number of degrees of freedom in the physical universe.

Paul Cohen: I will ascribe to Skolem a view, not explicitly stated by him, that there is a reality to mathematics, but axioms cannot describe it. Indeed one goes further and says that there is no reason to think that any axiom system can adequately describe it.

This "it" (mathematics) that Cohen describes may be the set of idealizations constructed by our brains extrapolating from physical reality. But there is no guarantee that these idealizations have a strong kind of internal consistency and indeed they cannot be adequately described by any axiom system.

Horizons of Truth 

Chaitin on Physics and Mathematics 

The History of the Planck Length and the Madness of Crowds

Note added: I should clarify the paragraph from our paper that begins

There was a concerted effort beginning in the 20th century to place infinity and the continuum on a rigorous foundation using logic and set theory. However, these efforts have not been successful. ...

This refers to Hilbert's Program:

In the early 1920s, the German mathematician David Hilbert (1862–1943) put forward a new proposal for the foundation of classical mathematics which has come to be known as Hilbert’s Program. It calls for a formalization of all of mathematics in axiomatic form, together with a proof that this axiomatization of mathematics is consistent. The consistency proof itself was to be carried out using only what Hilbert called “finitary” methods. The special epistemological character of finitary reasoning then yields the required justification of classical mathematics. Although Hilbert proposed his program in this form only in 1921, various facets of it are rooted in foundational work of his going back until around 1900, when he first pointed out the necessity of giving a direct consistency proof of analysis. ...

which Godel showed is not possible to carry out. Note that one of Hilbert's main motivations was the continuum (e.g., construction of the Reals in analysis). What has subsequently been adopted as the rigorous basis for analysis does not satisfy Hilbert's desire for axiomatic, finitary methods. 

The remaining sentences in the paragraph are meant to elucidate aspects of the modern treatment that its critics find unappealing. Of course, judgements of this type are philosophical in nature. 

... For example, the standard axioms of Zermelo-Fraenkel (ZFC) set theory applied to infinite sets lead to many counterintuitive results such as the Banach-Tarski Paradox: given any two solid objects, the cut pieces of either one can be reassembled into the other [23]. When examined closely all of the axioms of ZFC (e.g., Axiom of Choice) are intuitively obvious if applied to finite sets, with the exception of the Axiom of Infinity, which admits infinite sets. (Infinite sets are inexhaustible, so application of the Axiom of Choice leads to pathological results.) The Continuum Hypothesis, which proposes that there is no cardinality strictly between that of the integers and reals, has been shown to be independent (neither provable nor disprovable) in ZFC [24]. Finitists assert that this illustrates how little control rigorous mathematics has on even the most fundamental properties of the continuum. 

See also Paul Cohen on this topic (source of the quote above about Skolem and axiomatization):

Skolem and pessimism about proof in mathematics 

Abstract: Attitudes towards formalization and proof have gone through large swings during the last 150 years. We sketch the development from Frege’s first formalization, to the debates over intuitionism and other schools, through Hilbert’s program and the decisive blow of the Go¨del Incompleteness Theorem. A critical role is played by the Skolem–Lowenheim Theorem, which showed that no first-order axiom system can characterize a unique infinite model. Skolem himself regarded this as a body blow to the belief that mathematics can be reliably founded only on formal axiomatic systems. In a remarkably prescient paper, he even sketches the possibility of interesting new models for set theory itself, something later realized by the method of forcing. This is in contrast to Hilbert’s belief that mathematics could resolve all its questions. We discuss the role of new axioms for set theory, questions in set theory itself, and their relevance for number theory. We then look in detail at what the methods of the predicate calculus, i.e. mathematical reasoning, really entail. The conclusion is that there is no reasonable basis for Hilbert’s assumption. The vast majority of questions even in elementary number theory, of reasonable complexity, are beyond the reach of any such reasoning ... 

... The startling conclusion that Skolem drew is the famous Skolem Paradox, that any of the usual axiom systems for set theory will have countable models, unless they are contradictory. Since I will not assume that my audience are all trained logicians, I point out that though the set of reals from the countable model is countable seen from outside, there is no function ‘living in the model’ which puts it in one-to-one correspondence with the set of integers of the model. This fact and other considerations led Skolem to this viewpoint:

I believed that it was so clear that axiomatization in terms of sets was not a satisfactory ultimate foundation of mathematics, that mathematicians would, for the most part, not be very much concerned by it.

The view that I shall present differs somewhat from this, and is in a sense more radical, namely that it is unreasonable to expect that any reasoning of the type we call rigorous mathematics can hope to resolve all but the tiniest fraction of possible mathematical questions.

The theorem of Lowenheim–Skolem was the first truly important discovery about formal systems in general, and it remains probably the most basic. ...

Conclusion: ...Therefore, my conclusion is the following. I believe that the vast majority of statements about the integers are totally and permanently beyond proof in any reasonable system. Here I am using proof in the sense that mathematicians use that word. Can statistical evidence be regarded as proof ? I would like to have an open mind, and say ‘Why not?’. If the first ten billion zeros of the zeta function lie on the line whose real part is 1/2, what conclusion shall we draw? I feel incompetent even to speculate on how future generations will regard numerical evidence of this kind. 

In this pessimistic spirit, I may conclude by asking if we are witnessing the end of the era of pure proof, begun so gloriously by the Greeks. I hope that mathematics lives for a very long time, and that we do not reach that dead end for many generations to come.

Tragedy of Empire / Mostly Sociopaths at the Top

 

Ecclesiastes 1:9 (KJV) The thing that hath been, it is that which shall be; and that which is done is that which shall be done: and there is no new thing under the sun.

Turn off the TV and close the browser tabs with mainstream media content produced by middlebrow conformists. Watch this video instead and read the links below. 

If you were surprised by events in Afghanistan over the past weeks, ask yourself why you were so out of touch with a reality that has been clear to careful observers for over a decade. Then ask yourself what other things you are dead wrong about...

Ray McGovern is a retired CIA analyst who served as Chief of the Soviet Foreign Policy Branch and preparer/briefer of the President’s Daily Brief. Prior to that he served as an infantry/intelligence officer in the 1960s. 

McGovern wrote Welcome to Vietnam, Mr. President (addressed to President Obama, about Afghanistan) in 2009. 

See also: The Strategic Lessons Unlearned from Vietnam, Iraq, and Afghanistan: Why the Afghan National Security Forces Will Not Hold, and the Implications for the U.S. Army in Afghanistan (Strategic Studies Institute and U.S. Army War College Press 2015) M. Chris Mason  

Related posts:

Tears before the Rain: An Oral History of the Fall of South Vietnam (Afghanistan darkness over Kabul edition) 

Resistance fighter negotiates with former torturer (Afghanistan edition) 

Decline of the American Empire: Afghan edition (stay tuned for more)

Afghanistan is lost (2012)

Podcast version of the interview at top:

   

More color here from Danny Sjursen, West Point graduate, former US Army Major. Sjursen is a combat veteran who served in Iraq and later as an Army captain in Afghanistan in command of 4-4 Cavalry B Troop in Kandahar Province from February 2011 to January 2012.

Added from comments:

At the strategic level it has been clear for 10+ years that our resources were better used elsewhere. It was obvious as well that we were not succeeding in nation building or creating a self-sustaining government there. I could go into more detail but you can get it from the links / interviews in the post. 

At the tactical level it should have been obvious that a quick collapse was very possible, just as in S. Vietnam (see earlier oral history post). Off-topic: same thing could happen in Taiwan in event of an actual invasion, but US strategists are clueless. 

Biden deserves credit for staying the course and not kicking the can down the road, as effectively a generation (slight exaggeration) of military and political leaders have done. 

The distortion of the truth by senior leaders in the military and in politics is clear for all to see. Just read what mid-level commanders (e.g., Sjursen) and intel analysts with real familiarity have to say. This was true for Vietnam and Iraq as well. Don't read media reports or listen to what careerist generals (or even worse, politicos) have to say. 

Execution by Biden team was terrible and I think they really believed the corrupt US-puppet Afghan govt could survive for months or even years (i.e., they are really stupid). Thus their exit planning was deeply flawed and events overtook them. However, even a well-planned exit strategy would likely not have avoided similar (but perhaps smaller in magnitude) tragic events like the ones we are seeing now. 

ISS attack on airport was 100% predictable. I don't think most Americans (even "leaders" and "experts") understood ISS and Taliban are mortal enemies, etc. etc. 

There is more of a late-stage imperial decline feel to Afghanistan and Iraq -- use of mercenaries, war profiteering, etc. -- than in Vietnam. All of these wars were tragic and unnecessary, but there really was a Cold War against an existential rival. The "war on terrorism" should always have been executed as a police / intel activity, not one involving hundreds of thousands of US soldiers. 

All of this is (in part) an unavoidable cost of having intellectually weak leaders struggling with difficult problems, while subject to low-information populist democracy (this applies to both parties and even to "highly educated" coastal elites; the latter are also low-information from my perspective). This situation is only going to get worse with time for the US. 

BTW, I could describe an exactly analogous situation in US higher ed (with which I am quite familiar): leaders are intellectually weak, either do not understand or understand and cynically ignore really serious problems, are mainly concerned with their own careers and not the real mission goals, are subject to volatility from external low-information interest groups, etc.

Resistance fighter negotiates with former torturer (Afghanistan edition)

The Taliban could easily turn Kabul airport into a trap, creating another Dien Bien Phu for the US. However I suspect they are advised by the Russians and Chinese to grant the Americans a peaceful exit from their 20 year disaster. The negotiations are presumably about the ~$9 billion of frozen assets in the Afghanistan treasury, future sanctions against a Taliban-led government, etc.

See also Decline of the American Empire: Afghan edition, Afghanistan is lost (2012), etc.

CIA Director William Burns held secret meeting in Kabul with Taliban leader Abdul Ghani Baradar (WaPo) 

President Biden dispatched his top spy, a veteran of the Foreign Service and the most decorated diplomat in his Cabinet, amid a frantic effort to evacuate people from Kabul international airport in what Biden has called “one of the largest, most difficult airlifts in history.” 

The CIA declined to comment on the Taliban meeting, but the discussions are likely to have involved an impending Aug. 31 deadline for the U.S. military to conclude its airlift of U.S. citizens and Afghan allies. The Biden administration is under pressure from some allies to keep U.S. forces in the country beyond the end of the month to assist the evacuation of tens of thousands of citizens of the United States and Western countries as well as Afghan allies desperate to escape Taliban rule. 

Britain, France and other U.S. allies have said more time is needed to evacuate their personnel, but a Taliban spokesman warned that the United States would be crossing a “red line” if it kept troops beyond the 31st, which he said would trigger unspecified “consequences.” 

For Baradar, playing the role of counterpart to a CIA director comes with a tinge of irony 11 years after the spy agency arrested him in a joint CIA-Pakistani operation that put him in prison for eight years. ...

There are many more like Baradar. Taliban leader Gholam Ruhani (circled in the photo at top) enjoyed America's tender embrace for many years at Guantanamo.  

I highly recommend The Battle of Algiers for context, as did the Pentagon in 2003 -- to no avail.

Wikipedia: 

The highly dramatic film is about the organization of a guerrilla movement and the illegal methods, such as torture, used by the colonial power to contain it. Algeria succeeded in gaining independence from the French, which Pontecorvo addresses in the film's epilogue.[3] 

The film has been critically acclaimed. Both insurgent groups and state authorities have considered it to be an important commentary on urban guerrilla warfare. 

2003 Pentagon screening 

During 2003, the press reported that United States Department of Defense (the Pentagon) offered a screening of the movie on August 27. The Directorate for Special Operations and Low-Intensity Conflict regarded it as useful for commanders and troops facing similar issues in occupied Iraq.[38] 

A flyer for the screening said: How to win a battle against terrorism and lose the war of ideas. Children shoot soldiers at point-blank range. Women plant bombs in cafes. Soon the entire Arab population builds to a mad fervor. Sound familiar? The French have a plan. It succeeds tactically, but fails strategically. To understand why, come to a rare showing of this film.[39] 

According to the Defense Department official in charge of the screening, "Showing the film offers historical insight into the conduct of French operations in Algeria, and was intended to prompt informative discussion of the challenges faced by the French."[39]

Re: Dien Bien Phu, colonial wars, and Iraq / Afghanistan:

General Georges Catroux presided over a commission of inquiry into the defeat. The commission's final report ("Rapport concernant la conduite des opérations en Indochine sous la direction du général Navarre") concluded: 

"... The event itself was in fact, both in terms of public opinion and of the military conduct of the war and operations, merely the end result of a long process of degradation of a faraway enterprise which, not having the assent of the nation, could not receive from the authorities the energetic impulse, and the size and continuity of efforts, required for success. ..."

John Preskill interview by Sean Carroll

 

This is a great interview of John Preskill by Sean Carroll. 

Both are many worlders. At about 20 minutes John says:

I'm an Everettian... 

I'm comfortable with nothing happening in the world besides unitary evolution ... 

Measurement isn't something fundamentally different. ... 

It seems minimal: you know there's nothing happening but the Schrodinger equation and things are evolving, and if we can reconcile that with what we observe about physics ...

In Ten Years of Quantum Coherence and Decoherence I listed a number of prominent theorists who have expressed some degree of belief in many worlds.

Q1. (largely mathematical): Does the phenomenology of pure state evolution in a closed system (e.g., the universe) reproduce Copenhagen for observers in the system? 

This is a question about dynamical evolution: of the system as a whole, and of various interacting subsystems. It's not a philosophical question and, in my opinion, it is what theorists should focus on first. Although complicated, it is still reasonably well-posed from a mathematical perspective, at least as far as foundational physics questions go. 

I believe the evidence is strong that the answer to #1 is Yes, although the issue of the Born rule lingers (too complicated to discuss here, but see various papers I have written on the topic, along with other people like Deutsch, Zurek, etc.). It is clear from Weinberg's writing that he and I agree that the answer is Yes, modulo the Born rule. 

Define this position to be 

Y* := "Yes, possibly modulo Born" 

There are some theorists who do not agree with Y* (see the survey results above), but they are mostly people who have not thought it through carefully, in my opinion. 

I don't know of any explicit arguments for how Y* fails, and our recent results applying the vN QET strengthen my confidence in Y*. 

I believe (based on published remarks or from my personal interactions) that the following theorists have opinions that are Y* or stronger: Schwinger, DeWitt, Wheeler, Deutsch, Hawking, Feynman, Gell-Mann, Zeh, Hartle, Weinberg, Zurek, Guth, Preskill, Page, Cooper (BCS), Coleman, Misner, Arkani-Hamed, etc. 

But there is a generational issue, with many older (some now deceased!) theorists being reticent about expressing Y* even if they believe it. This is shifting over time and, for example, a poll of younger string theorists or quantum cosmologists would likely find a strong majority expressing Y*. 

[ Social conformity and groupthink are among the obstacles preventing broader understanding of Q1. That is, in part, why I have listed specific high profile individuals as having reached the unconventional but correct view! ]

Tears before the Rain: An Oral History of the Fall of South Vietnam (Afghanistan darkness over Kabul edition)

Ecclesiastes 1:9 (KJV) The thing that hath been, it is that which shall be; and that which is done is that which shall be done: and there is no new thing under the sun.

If you are following events in Afghanistan you know that the tragedy described below will soon be repeated.

The oral histories collected in this volume are heartbreaking and real, but today the events they describe are all but forgotten.

There was never any reckoning for the crimes and stupidity of the Vietnam war, and there won't be any in the wake of our 20 years in Afghanistan and Iraq. 

Our pathetic leaders and apathetic voters will find plenty of other things to distract them from a serious consideration of what happened. Strike up the band, and salute the flag.

Saigon, US Embassy evacuation, 29 April, 1975:

Kabul, US Embassy evacuation, 15 August, 2021:

From the introduction:

On March 10, 1975, the North Vietnamese Army launched what was to be its final major offensive against South Vietnam, assured that America had lost its will to fight or to finance the independence of South Vietnam. No longer fearful of American intervention, the North Vietnamese were certain that victory and the forceful unification of Vietnam was, after nearly thirty years of conflict, soon to be accomplished. Now the social and military fabric of South Vietnam began to unravel rapidly in many places at the same time. The South suddenly began to lose the war faster than the North could win it. The military forces of the South seemed to be imploding toward Saigon. Cities and provinces were abandoned to the North without a fight. ...Victory for the armies of North Vietnam became, in many strategically important places, a mere matter of marching. 

On March 29, the chaotic and desperate situation was recorded graphically by a CBS news crew that flew aboard a World Airways Boeing 727 to Danang, Vietnam's second largest city, to evacuate refugees. The plane was mobbed by soldiers who shot women and children and each other in a frenzied attempt to scramble aboard the aircraft and escape from the advancing North Vietnamese. As the plane took off with people clinging to the wheels, soldiers on the ground fired at it and a hand grenade blew up under one wing. The plane limped back into Saigon, and that evening a tape of the flight was shown on the CBS Evening News. American television viewers that Easter weekend saw the almost unbelievable horror of an army transformed into murderous rabble and a country thrashing about helplessly in the throes of a violent death. 

... As if to leave no doubt as to America's determination not to intervene again in Vietnam, on the evening of April 23, in a major address at Tulane University, President Gerald Ford announced that the war in Vietnam was "finished as far as America is concerned." The audience of students gave him a standing ovation. 

... On the morning of April 29, Operation Frequent Wind began. The exercise involved the evacuation of American and Vietnamese civilians and military personnel from Tan Son Nhut Airbase and from the American Embassy in Saigon to the Seventh Fleet in the South China Sea. The operation was completed early in the morning of April 30, a few hours before the surrender of the South. When the last Marines were airlifted from the roof of the American Embassy on the morning of April 30, they left behind more than four hundred Vietnamese waiting to be airlifted out of the compound. Throughout the previous day and night those same Vietnamese had been promised again and again that they would never be abandoned by the United States. They watched in silence as the last American helicopter left the roof of the Embassy. Even the final American promise to Vietnam had been broken.

Thomas Polgar was CIA Saigon station chief. This is his last transmission from the embassy before destroying the communications equipment:

“This will be final message from Saigon station,” Mr. Polgar wrote. “It has been a long and hard fight and we have lost. This experience, unique in the history of the United States, does not signal necessarily the demise of the United States as a world power. 

“The severity of the defeat and the circumstances of it, however, would seem to call for a reassessment... Those who fail to learn from history are forced to repeat it. Let us hope that we will not have another Vietnam experience and that we have learned our lesson.”

From his oral history:

... we got word to go, and the ambassador was finally told, ... "No, it's going to be from the roof after all." ...

I didn't have a great emotional attachment to Vietnam like some of my colleagues who really fell in love with the country. But in the end, seeing how it ended, I thought that we really did a miserable job for these people and they would have been much better off if we had never gone there in the first place. 

Our reception on the Blue Ridge [ship] showed the American military at its worst. They started out by searching everybody. I think the ambassador was the only one who was not searched. And in normal peacetime I far outranked the admiral commanding the ship. Nobody objected, though. We were tired. We were pretty placid. And we were a defeated army.

From the epigraph:

Maybe if enough people know what happened to Vietnam, then my memories will never be lost. Maybe then they will be like tears before the rain. So listen. This is very important. This is what I remember. This is what happened to me. These are my tears before the rain. --Duong Gang Son

More from Son's oral history:

As we left Saigon, there was an American soldier standing at the back door of the plane, and he was shooting at the ground. He just kept shooting as we pulled away. And people were still crying inside the plane. I watched the soldier shooting and I wondered what he was shooting at. I think he was just trying to show American power one last time. ... But I can only guess. I don't think he knew what was happening, either. We were all confused. 

Anyway, that was my last look at my country. I saw Vietnam as we flew away and at the back door of the plane was a soldier with a gun shooting at it.

 

Tears before the Rain: An Oral History of the Fall of South Vietnam by Larry Engelmann 

CBS camera-man Mike Marriott was on the last plane to escape from Danang before it fell in the spring of 1975. The scene was pure chaos: thousands of panic-stricken Vietnamese storming the airliner, soldiers shooting women and children to get aboard first, refugees being trampled to death. Marriott remembers standing at the door of the aft stairway, which was gaping open as the plane took off. "There were five Vietnamese below me on the steps. As the nose of the aircraft came up, because of the force and speed of the aircraft, the Vietnamese began to fall off. One guy managed to hang on for a while, but at about 600 feet he let go and just floated off--just like a skydiver.... What was going through my head was, I've got to survive this, and at the same time, I've got to capture this on film. This is the start of the fall of a country. This country is gone. This is history, right here and now." 

In Tears Before the Rain, a stunning oral history of the fall of South Vietnam, Larry Engelmann has gathered together the testimony of seventy eyewitnesses (both American and Vietnamese) who, like Mike Marriott, capture the feel of history "right here and now." We hear the voices of nurses, pilots, television and print media figures, the American Ambassador Graham Martin, the CIA station chief Thomas Polgar, Vietnamese generals, Amerasian children, even Vietcong and North Vietnamese soldiers. 

Through this extraordinary range of perspectives, we experience first-hand the final weeks before Saigon collapsed, from President Thieu's cataclysmic withdrawal from Pleiku and Kontum, (Colonel Le Khac Ly, put in command of the withdrawal, recalls receiving the order: "I opened my eyes large, large, large. I thought I wasn't hearing clearly") to the last-minute airlift of Americans from the embassy courtyard and roof ("I remember when the bird ascended," says Stuart Herrington, who left on one of the last helicopters, "It banked, and there was the Embassy, the parking lot, the street lights. And the silence"). 

Kabul Update: right on schedule...

Biden, July 8: "There’s going to be no circumstance where you see people being lifted off the roof of a embassy in the—of the United States from Afghanistan....The likelihood there’s going to be the Taliban overrunning everything and owning the whole country is highly unlikely." pic.twitter.com/VO17x0wKi9

— Peter Baker (@peterbakernyt) August 15, 2021

See also Decline of the American Empire: Afghan edition (stay tuned for more).