Thursday, December 01, 2022

Anna Krylov: The Politicization of Science in Academia — Manifold #25

Anna I. Krylov (Russian: Анна Игоревна Крылова) is Professor of Chemistry at the University of Southern California (USC), working in the field of theoretical and computational quantum chemistry. Krylov is an outspoken advocate of freedom of speech and academic freedom. She is a founding member of the Academic Freedom Alliance and a member of its academic leadership committee.

Her paper, The Peril of Politicizing Science, launched a national conversation among scientists and the general public on the growing influence of political ideology in STEM. It has received over 80,000 views and, according to Altmetric, was the all-time highest-ranked article in the Journal of Physical Chemistry Letters.

Steve and Anna discuss:

0:00 Anna Krylov’s background, upbringing in USSR
7:03 Ideological control and censorship for the greater good?
14:59 How ideology underpins DEI work in academic institutions
30:40 Captured institutions
37:05 How much is UC Berkeley spending on DEI, and where the money is going
41:46 Krylov thinks it can get worse
52:09 An idea for defeating preference falsification at universities

Resources:

Wiki page:

The Peril of Politicizing Science, Journal of Physical Chemistry Letters 2021 https://pubs.acs.org/doi/10.1021/acs.jpclett.1c01475

Thursday, November 17, 2022

Abdel Abdellaoui: Genetics, Psychiatric Traits, and Educational Attainment — Manifold #24

Abdel Abdellaoui is Assistant Professor of Genetics in the Department of Psychiatry, Amsterdam UMC, University of Amsterdam.

Abdel Abdellaoui is a geneticist who has been involved in a wide range of studies on psychiatric genetics, behavioral genetics, and population genetics. He is particularly interested in how collective behaviors, such as migration and mate choice, influence the genetic makeup of populations and the relationship between genetic risk factors and environmental exposures.

Steve and Abdel discuss:

00:00 Abdel’s background: education, family history, research career
10:23 Abdel’s research focus: polygenic traits, geographical stratification
21:43 Correlations across geographical regions
33:21 Educational Attainment
38:51 Comparisons across data sets
44:48 Longevity

Monday, November 07, 2022

Nozick and Leftists

From this interview with Robert Nozick:

I had been at Harvard as an Assistant Professor in the mid-​sixties and then came back in 1969 as a Full Professor. That was immediately after the student uprisings, building takeovers, and so on, at Harvard the previous spring. When I arrived in the fall of 1969, there was a philosophy course listed in the catalog entitled “Capitalism.” And the course description was “a moral examination of capitalism.” Of course, for most students, then, it would be taken for granted that a moral examination would be a moral condemnation of capitalism. But that’s not what I intended. We were going to read critics of capitalism. But we were also planning to read defenses of capitalism, and I was going to construct some of my own in the lectures. Some of the graduate students in the philosophy department knew what ideas I held, and they weren’t very happy about a course being taught in the department defending those ideas. Now it was true that there was another course in the department on Marxism by someone who was then a member of the Maoist Progressive Labor Party and students did not object to that. But still some students objected to my giving a lecture course on capitalism. I remember early in the fall (I guess I was scheduled to give the course in the spring term), a graduate student came to me at a departmental reception we had, and said, “We don’t know if you’re going to be allowed to give this course.” I said “What do you mean, not allowed to give this course?” He said, “Well, we know what ideas you hold. We just don’t know whether you will be allowed to give the course.” And I said, “If you come and disrupt my course, I’m going to beat the shit out of you!” And the student was taken aback and said, “But you are taking all this very personally.” And I said, “What do you mean, personally? You are threatening to disrupt my course! you can do other things; you can stand outside the room and hand out leaflets. You can ask students not to register for my course. But if you come into my classroom while I am lecturing and disrupt the class, then I take that very personally.” In fact, at some point later in the term, this student and some others said they were going to make up leaflets and hand them out outside of my classroom. I said, “That’s fine; that would be really exciting.” Then they didn’t get around to doing it, and so I prodded them, “Where are the leaflets? I was counting on something special happening with the leaflets.” But it turned out that it was a lot of trouble to write up a leaflet, to get them run off on a mimeograph machine, and so they never got around to doing it. Thus I never had the privilege of being “leafleted” at Harvard. It seemed to me that sort of antagonism only lasted for a very short period of time and diminished fast. There was no longer any strong personal animosity after that. Maybe it was the general toning down of things in the country in the early 70’s, and I just benefited from the de-radicalization of the university.

More fun photos from this old post Forever Young :-)

Thursday, November 03, 2022

Richard Sander on SCOTUS Oral Arguments: Affirmative Action and Discrimination against Asian Americans at Harvard and UNC (Manifold #23)

Richard Sander is Jesse Dukeminier Professor at UCLA Law School. AB Harvard, JD, PhD (Economics) Northwestern.

Sander has studied the structure and effects of law school admissions policies. He coined the term "Mismatch" to describe the negative consequences resulting from large admissions preferences.

Rick and Steve discuss recent oral arguments at the Supreme Court in Students for Fair Admissions vs Harvard College and Students For Fair Admissions vs the University of North Carolina.

0:00 Rick’s experience at the Supreme Court
4:11 Rick’s impression of the oral arguments
16:24 Analyzing the court’s questions
29:09 The negative impact on Asian American students
34:41 Shifting sentiment on affirmative action
40:04 Three potential outcomes for Harvard and UNC cases
44:00 Possible reasons for conservatives to be optimistic
50:31 Final thoughts on experiencing oral arguments in person
52:12 Mismatch theory
56:31 The future of higher education

Resources

Background on the Harvard case:

Transcripts:

Previous interview with Richard (Manifold #6)

See the Crimson for some photos of the parties involved

Thursday, October 20, 2022

Discovering the Multiverse: Quantum Mechanics and Hugh Everett III, with Peter Byrne — Manifold #22

Peter Byrne is an investigative reporter and science writer based in Northern California. His popular biography, The Many Worlds of Hugh Everett III - Multiple Universes, Mutual Assured Destruction, and the Meltdown of a Nuclear Family (Oxford University Press, 2010) was followed by publication of The Everett Interpretation of Quantum Mechanics, Collected Works 1957-1980, (Princeton University Press, 2012), co-edited with philosopher of science Jeffrey A. Barrett of UC Irvine.

Everett's formulation of quantum mechanics, which implies the existence of a quantum multiverse, is favored by a significant (and growing) fraction of working physicists.

Steve and Peter discuss:

0:00 How Peter Byrne came to write a biography of Hugh Everett
18:09 Everett’s personal life and groundbreaking thesis as a catalyst for the book
24:00 Everett and Decoherence
31:25 Reaction of other physicists to Everett’s many worlds theory
40:46 Steve’s take on Everett’s many worlds theory
43:41 Peter on the bifurcation of science and philosophy
52:58 How Hugh Everett is remembered now

References:

Saturday, October 15, 2022

Times of Israel on Polygenic Embryo Screening

This is a very nice article on polygenic embryo screening and its prospects in Israel. Worth reading in full. Leading statistical geneticist Shai Carmi is interviewed. See also his interview on Manifold (embedded player at bottom of this post).
The Times of Israel
14 October 2022, 1:27 pm
Designer babies? Hi-tech preimplantation genetic testing may soon come to Israel

For generations, the Yu family of Shanghai has suffered from type 2 diabetes. But this summer, as reported in the China Daily, the family welcomed a baby with a better chance of avoiding this disease.

These rosier prospects are the result of a recent breakthrough in assisted reproduction that was advanced with the help of Israeli scientists, called preimplantation genetic testing for polygenic diseases (PGT-P). In addition to China, PGT-P is also gaining ground among couples in the United States who wish to improve health outcomes for their future children. But in Israel, it is illegal.

PGT-P is carried out on an embryo during in vitro fertilization (IVF), prior to its transfer from the Petri dish to the womb. Viable embryos with the probable lowest disease risk can then be selected for implantation.

Since this innovative testing takes into account a complex combination of factors that are not broached in more traditional testing, in some ways it’s almost like an educated guess. Accordingly, polygenic screening is not a diagnosis: It is a prediction of relative future risk compared to other people.

Israeli academics have published peer-reviewed research advancing the science behind polygenic screening, including Shai Carmi, Ehud Karavani, Or Zuk, Gil Atzmon, and Einat Granot-Hershkovitz.

But Start-Up Nation is not yet implementing this cutting-edge tech in the field of fertility. Although fertility treatments are subsidized by the Israeli government, it is still unclear whether Israeli couples ever will have access to the procedure, which screens for polygenic diseases such as diabetes, heart disease and cancer — or whether they would even want it.

PGT-P is different from prior technology in important ways, creating new opportunities and challenges for parents while raising profound ethical dilemmas for society. Similar to older forms of testing, PGT-P relies on analyzing genetic material from embryos created through IVF before implantation and checking them for certain diseases and conditions. The information then helps the parents and doctors decide which embryos to implant.

However, the biggest difference between PGT-P screening and earlier forms of genetic testing is that the prior tests checked for genetically simple conditions such as Down syndrome, cystic fibrosis, or Tay Sachs disease. These diseases, which are serious or fatal, have extremely high “penetrance,” which means that if the gene mutation is seen in the embryo’s DNA, it is nearly certain that the child will have that condition. The appearance of the disease-linked gene is the basis of a clear diagnosis.

This “simple” genetic screening has already borne fruit in the Jewish community: Decades ago, babies in the Ashkenazi Jewish community were nearly 100 times more likely to be born with Tay Sachs than babies in the general US population. Today, because of genetic screenings, the disease is “virtually wiped out.”

In contrast, PGT-P screening can’t tell you with assurance if an embryo will develop a genetic disease such as cancer or Crohn’s disease. That’s because this new screening checks for polygenic diseases – complex conditions caused by the combined impact of possibly thousands of different genes, as well as lifestyle and other environmental factors.

Instead of a clear diagnosis, prospective parents receive a “polygenic risk score,” basically the probability of a child developing a certain disease or condition.

Noa and her husband went through 10 IVF cycles to build their family. “We now have two wonderful boys,” she says.

If I had an opportunity to reduce disease risk in my kids, I would do it

She knows what she would have said if doctors had offered her polygenic screening: “I want that technology.” As a speech therapist who works with kids facing a lot of health challenges, she was very worried about what her own kids would face.

“If I had an opportunity to reduce disease risk in my kids, I would do it. It would definitely help my peace of mind as a mother. Everyone here in Israel should have the option of using it,” Noa says.

Scientists at the US-based Genomic Prediction, Inc. published an article in 2019 describing the “first clinical application” of polygenic screening of embryos. Genomic Prediction is a polygenic screening company based in New Jersey that partners with various IVF clinics around the world.

However, to date, the Israeli Health Ministry has yet to even issue a statement on the use of polygenic screening on embryos.

For some, the fact that PGT-P screening isn’t available, or even legal, in Israel is somewhat counterintuitive, given Israel’s prominence in the fields of both assisted reproduction and genetic testing.

Israelis undergo more rounds of IVF per capita than any other nation in the world. This is largely due to religious and cultural norms that are highly supportive of child-bearing, combined with the nationally financed healthcare system that provides full coverage for as many IVF cycles as needed, up to two children per family.

In addition, “in Israel there is a lot more openness to preimplantation genetic testing in general because of the high prevalence of various disease mutations in our community,” says Carmi, an associate professor at the Hebrew University School of Public Health and Faculty of Medicine.

Today, Carmi is a leading researcher on the accuracy of polygenic screening. As part of his post-doctoral project at Columbia University in New York, he helped generate important genetic sequencing data for Ashkenazi Jews.

Israel’s embrace of most genetic testing is reflected in the Israeli Health Ministry’s website, which lists dozens of recommended genetic screenings, broken down by ethnic sub-community. But these screenings are for monogenic disorders, easily diagnosed by looking for a single gene mutation.

“In Israel, the Health Ministry controls which diseases can be screened for, and candidate variants need to have high penetrance and lead to diseases with severe symptoms,” says Carmi.

Playing the odds

Miri is a consultant originally from central Israel. Although she did not have any known fertility problems, she chose to undergo IVF specifically because it would allow her to screen for a certain hereditary disease. She and her husband are both carriers of a rare mutation, so a natural conception meant a 25 percent chance of the fetus suffering from this generally fatal condition.

“For me, it was a choice between the extra physical hardship of IVF, or the extra emotional hardship of a pregnancy where, for months, we would not know if the baby would have this disease,” Miri said.

In contrast, PGT-P can’t provide conclusive information, because in the context of polygenic diseases like diabetes and heart disease “nothing is deterministic,” says Carmi.

According to Carmi, a child may develop the condition or may not, and non-genetic factors can certainly affect the outcome. Based on his peer-reviewed research on statistical modeling of polygenic screening, though, Carmi notes that “you can get quite a substantial risk reduction.”

The “relative risk reduction” projected to be accomplished by PGT-P varies depending on the disease. However, according to a 2021 research paper by Carmi and his collaborators, for schizophrenia and Crohn’s disease, around a 45% relative risk reduction is achievable for parents testing five embryos and choosing the best scoring, compared to implanting a randomly chosen one of the five.

The testing, of course, comes with a fee: Costs vary, but Genomic Prediction in New Jersey charges a $1,000 up-front fee, plus$400 per embryo analyzed. Of course, this is an add-on cost for people already doing IVF, which in the US can cost up to tens of thousands of dollars per cycle.

Pricing can get even more complicated, however, because different services end up bundled together, or are offered as add-ons once related costs are already accounted for. But one of the earlier forms of embryonic screening (PGT-A, which checks for aneuploidies, giving rise to Down syndrome for example) can cost several thousand dollars.

By contrast, carrier screening, which is a blood test performed on the parents to check for “simple” monogenic-disease carrier status, costs only several hundred dollars, and is often also covered by insurance.

In Israel, for couples whose family history or carrier-screening blood tests reveal a heightened risk for having children with a specific monogenic disease, the Health Ministry promotes the benefits of traditional genetic testing of embryos prior to implantation in the womb.

According to its website, “Pre-implantation Genetic Diagnosis (PGD) is today considered to be one of the practical options for couples who are at high risk for giving birth to a baby with a chromosomal abnormality or a genetic disease. This is because the process allows pregnancies to be achieved with healthy fetuses, and avoids the need for pregnancy termination, a procedure that constitutes a problem for many couples for religious, ethical and/or moral reasons.”

The nuts and bolts

PGT-P was developed using artificial intelligence technology applied to huge databases containing the genetic and health information of hundreds of thousands of people. Statistical data analysis of DNA and health outcomes allows scientists to see which complex genetic patterns more frequently show up in individuals who also develop a certain disease, such as schizophrenia. By genetically analyzing an embryo and then comparing its genetic information to this population data, the embryo’s polygenic risk score can be calculated for a given disease. This can already be done for a great many common diseases, with varying levels of predictive power, and as genetic databases grow, the reliability of these risk scores will continue to improve.

The couple also receives the raw data about their embryos’ genes and risk scores, so if they prefer to implant the embryo with the lowest risk of type 2 diabetes rather than the lowest combined disease risk, they can do that

“For prospective parents undergoing IVF and electing to use polygenic screening, somewhere between 10 and 20 polygenic risk scores are combined in a weighted average, with more serious diseases given greater weight in the final figure. This averaging provides a single number for each embryo — a health index — that can be used to rank the available embryos, so that the one with the best health index can be implanted,” says Carmi.

“Of course, the couple also receives the raw data about their embryos’ genes and risk scores, so if they prefer to implant the embryo with, let’s say, the lowest risk of type 2 diabetes, rather than the lowest combined disease risk, they can do that,” says Carmi.

An emotional decision

Michal Amrani, 32, lives in the central Israeli town of Ramat Hasharon and is working toward a master’s degree in chemistry from the Weizmann Institute. Through a four-year IVF process, she and her husband Sarel welcomed a son, and later, a set of twins. They say they are unlikely to use polygenic screening, even if it becomes available in Israel.

“As it is, we opted not to do some of the genetic testing that was already available to us,” Amrani says. “I work in science, so I am more open to these things, but my husband doesn’t really like all these genetic tests. For him, there’s risk in lots of things, and his optimistic nature helps him be comfortable that things will work out.”

Others, like Noa, are more interested in trying out preimplantation polygenic screening of their embryos, but even if Israel would change its rules to allow it, it’s a tricky issue. First, there are concerns about the psychological difficulties that this technology may pose for prospective parents.

Rona Langer Ziv is a social worker and cognitive behavioral psychotherapist who counsels IVF patients — both couples and singles — at a large Israeli hospital, as well as through her private clinical practice.

“Due to the potential implications of this new technology,” she says, “I would be concerned about a higher risk for depression and anxiety among the IVF patients.”

“Even if they feel they understand what they are signing up for at the beginning of the journey, they may not appreciate the emotional, ethical, and psychosocial implications of polygenic screening several IVF cycles down the road,” says Langer Ziv. “They may find themselves worrying that the embryos’ scores are not good enough, or that they won’t have any viable embryos left to choose from.”

Even if they feel they understand what they are signing up for at the beginning of the journey, they may not appreciate the emotional, ethical, and psychosocial implications of polygenic screening several IVF cycles down the road

Because polygenic screening predicts relative risk rather than providing an affirmative disease diagnosis, “women, especially those over 40 who may have very few embryos to work with, end up facing a serious dilemma — they may be discarding an embryo that could have resulted in a healthy child,” says Langer Ziv.

Amrani is in a similar situation. She and her husband are ready for more kids, but right now they have just one embryo available, so that’s the embryo they will try to implant. Even though she won’t be using polygenic screening, Amrani says that “it does sound very innovative. It’s nice that there’s something like this.”

Social worker and cognitive behavioral psychotherapist Rona Langer Ziv. (Courtesy) Indeed, Langer Ziv acknowledges that some people would find polygenic screening appealing, particularly those with higher education levels.

“There’s definitely coolness in the technology. It’s scientifically advanced, and it could offer interesting health insights about your future children. Everyone would theoretically like to use a technology that potentially predicts a more healthy child, although there is disagreement among fertility specialists about the benefits involved,” Langer Ziv says.

“And for some IVF patients, it might also provide a feeling of control during a process that involves so much stress, uncertainty, luck, and randomness,” she says.

Risk of eugenics

Regardless of how polygenic screening would be received by potential consumers, there are grave concerns about the impacts of this new technology on society. Various ethical issues have been raised for decades about older forms of genetic screenings, including fears of stigmatizing those living with genetic diseases, and questions about equitable access to these technological advances.

Perhaps the most significant ethical concern, and one that looms larger with polygenic screening than with older tests for monogenic diseases, is the potential for eugenics. This is the infamous and dangerous philosophy, practiced in Nazi Germany and elsewhere, that society should try to promote the creation of the most genetically “superior” babies.

Miri and her husband now have a baby boy and are looking forward to having more children — they still have three embryos to choose from. Asked whether she would be interested in polygenic screening if it became available in Israel, Miri says she’s unsure.

“I would love to see less suffering in the world from diseases. But where do we draw the line?” she says.

Indeed, the potential for eugenics is most stark when screenings cross over from the realm of disease prevention to the world of intelligence and aesthetic traits such as height or eye color. As such, some laboratories preemptively claim they will only screen for health concerns: An American polygenic screening company currently states that it does not test for “high IQ,” nor for “purely cosmetic traits such as hair color and eye color.”

But complicating the “noble” stance, genetic researchers have shown that “IQ is negatively correlated with most psychiatric disorders [and] positively correlated with autism and anorexia,” meaning that a high IQ comes with a lower risk of most psychiatric diseases and a higher risk of certain other neurological and mental health conditions.

As such, while some companies may currently refuse to offer IQ screening, it is not hard to imagine a health-based argument for loosening such protocols in the future, particularly as society becomes more used to the practice of PGT-P.

Similarly, a large study was published this year by researchers at Brown University and Peking University that found that “light eye colors were associated with high risks” of certain forms of skin cancer. Again, one can picture checks for eye color making their way into future genetic screenings through a backdoor of disease relevance.

In Carmi’s view, the responsible way for Israel to approach the prospect of polygenic screening is a gradual one.

“Ideally, we would start by recruiting Israeli participants for local academic research, with oversight by the Health Ministry,” Carmi says. “Once we develop more insight into how predictive polygenic screening is in our population, the relevant stakeholders — including patients, professional organizations, and regulators — can balance competing interests and local values, and come up with tailored guidance on its use in Israel.”

For some Israeli citizens, of particular concern is the idea of the wealthy trying to create perfect babies.

“If polygenic screening came to Israel, I would want to see a lot of regulation about who gets to use it, how it is used, and what reasons it is used for,” Miri says.

Genomic Prediction in Bloomberg

Thursday, October 06, 2022

Jeffrey Sachs: Lessons from the COVID Commission, Lab Leak Questions, and Nord Stream — Manifold Episode 21

Jeffrey D. Sachs is a world-renowned economics professor, bestselling author, innovative educator, and global leader in sustainable development. Professor Sachs serves as the Director of the Center for Sustainable Development at Columbia University and is a University Professor, Columbia's highest academic rank.

Steve and Jeffrey discuss:

0:00 Jeffrey Sachs’ experience on the Lancet Commission for COVID-19
13:41 Potential for bioweapons research
19:06 Why a lab leak is plausible
32:38 Possible defenses for COVID coverup
43:56 Government secrecy and other areas of concern
48:08 Reflections on Nord Stream sabotage

Resources:

The Lancet Commission on lessons for the future from the COVID-19 pandemic, Sachs et al., Sept. 14 2022

Why the Chair of the Lancet’s COVID-19 Commission Thinks The US Government Is Preventing a Real Investigation Into the Pandemic, Current Affairs, Aug 3 2022

My brief summary:

Sachs led a 2 year study of COVID-19 organized for the Lancet. One of the task forces was focused on COVID-19 origins. Sachs feels that members of this task force were engaged in a deliberate cover up which tried to push the natural origin hypothesis from the beginning. His conclusion is that a lab origin hypothesis is still viable, and indeed more likely than the natural origin hypothesis.

The US is treaty bound to only do "defensive" bioweapons research and development, but this includes the creation and study of dangerous viral strains -- e.g., so that vaccine efficacy and related technologies can be studied. As far as I can tell the US spends ~\$10 billion per annum on biodefense research, much of it funneled through NIAID (NIH institute for infectious diseases). Many of the researchers involved in "gain of function" genetic engineering are funded via NIAID and have been for decades. Sachs claims that the genetic engineering research to add a human-specific cleavage site to a coronavirus was actually performed, although the specific 2017 DEFUSE research plan (uncovered in 2021 investigation) was not funded.

Tuesday, October 04, 2022

SAT score distributions in Michigan

The state of Michigan required all public HS seniors to take the SAT last year (~91k out of ~107k total seniors in the state). This generated an unusually representative score sample. Full report

I'm aware of this stuff because my kids attend a public HS here.

To the uninformed, the results are shocking in a number of ways. Look specifically at the top band with scores in the 1400-1600 range. These are kids who have a chance at elite university admission, based on academic merit. For calibration, the University of Michigan median SAT score is above 1400, and at top Ivies it is around 1500.

Some remarks:

1. In the top band there are many more males than females.

2. The Asian kids are hitting the ceiling on this test.

3. There are very few students from under-represented groups who score in the top band.

4. By looking at the math score distribution (see full report) one can estimate how many students in each group are well-prepared enough to complete a rigorous STEM major -- e.g., pass calculus-based physics.

Previously I have estimated that PRC is outproducing the US in top STEM talent by a factor as large as 10x. In a decade or two the size of their highly skilled STEM workforce (e.g., top engineers, AI researchers, biotech scientists, ...) could be 10x as large as that of the US and comparable to the rest of the world, ex-China.

This is easy to understand: their base population is about 4x larger and their K12 performance on international tests like PISA is similar to what is found in the table above for the Asian category. The fraction of PRC kids who perform in the top band is probably at least several times larger than the overall US fraction. (Asian vs White in the table above is about 6x, or 7x on the math portion.) Also, the fraction of college students who major in STEM is much larger in PRC than in the US.

This table was produced by German professor Gunnar Heinsohn, who analyzes geopolitics and human capital.

Note, I will censor racist comments.

Wednesday, September 28, 2022

The Future of Human Evolution -- excerpts from podcast interview with Brian Chau

1. The prospect of predicting cognitive ability from DNA, and the consequences. Why the main motivation has nothing to do with group differences. This segment begins at roughly 47 minutes.

2. Anti-scientific resistance to research on the genetics of cognitive ability. My experience with the Jasons. Blank Slate-ism as a sacralized, cherished belief of social progressives. This segment begins at roughly 1 hour 7 minutes.

1. Starts at roughly 47 minutes.

Okay, let's just say hypothetically my billionaire friend is buddies with the CEO of 23andMe and let's say on the down low we collected some SAT scores of 1M or 2M people. I think there are about 10M people that have done 23andMe, let's suppose I manage to collect 1-2M scores for those people. I get them to opt in and agree to the study and da da da da and then Steve runs his algos and you get this nice predictor.

But you’ve got to do it on the down low. Because if it leaks out that you're doing it, People are going to come for you. The New York Times is going to come for you, everybody's going to come for you. They're going to try to trash the reputation of 23andMe. They're going to trash the reputation of the billionaire. They're going to trash the reputation of the scientists who are involved in this. But suppose you get it done. And getting it done as you know very well is a simple run on AWS and you end up with this predictor which wow it's really complicated it depends on 20k SNPs in the genome ...

For anybody with an ounce of intellectual integrity, they would look back at their copy of The Mismeasure of Man which has sat magisterially on their bookshelf since they were forced to buy it as a freshman at Harvard. They would say, “WOW! I guess I can just throw that in the trash right? I can just throw that in the trash.”

But the set of people who have intellectual integrity and can process new information and then reformulate the opinion that they absorbed through social convention – i.e., that Gould is a good person and a good scientist and wise -- is tiny. The set of people who can actually do that is like 1% of the population. So you know maybe none of this matters, but in the long run it does matter. …

Everything else about that hypothetical: the social scientists running the longitudinal study, getting the predictor in his grubby little hands and publishing the validation, but people trying to force you to studiously ignore the results, all that has actually already happened. We already have something which correlates ~0.4 with IQ. Everything else I said has already been done but it's just being studiously ignored by the right thinking people.

…

Some people could misunderstand our discussion as being racist. I'm not saying that any of this has anything to do with group differences between ancestry groups. I'm just saying, e.g., within the white population of America, it is possible to predict from embryo DNA which of 2 brothers raised in the same family will be the smart one and which one will struggle in school. Which one will be the tall one and which one will be not so tall.

2. Starts at roughly 1 hour 7 minutes.

I've been in enough places where this kind of research is presented in seminar rooms and conferences and seen very negative attacks on the individuals presenting the results.

I'll give you a very good example. There used to be a thing called the Jasons. During the cold war there was a group of super smart scientists called the Jasons. They were paid by the government to get together in the summers and think about technological issues that might be useful for defense and things like war fighting. …

I had a meeting with the (current) Jasons. I was invited to a place near Stanford to address them about genetic engineering, genomics, and all this stuff. I thought okay these are serious scientists and I'll give them a very nice overview of the progress in this field. This anecdote takes place just a few years ago.

One of the Jasons present is a biochemist but not an expert on genomics or machine learning. This biochemist asked me a few sharp questions which were easy to answer. But then at some point he just can't take it anymore and he grabs all his stuff and runs out of the room. ...

Tuesday, September 27, 2022

Quantum Hair in Electrodynamics and Gravity (arXiv:2209.12798)

New paper!
Quantum Hair in Electrodynamics and Gravity
Xavier Calmet, Stephen D. H. Hsu
arXiv:2209.12798
We demonstrate the existence of quantum hair in electrodynamics and gravity using effective action techniques. In the case of electrodynamics we use the Euler-Heisenberg effective action while in the case of quantum gravity we use the unique effective action. We give a general formulation of these effects which applies to both theories and discuss analogies and differences between them. Furthermore, we present a QED analog to black hole evaporation. Spontaneous pair production in the external field of a ball of charge is analogous to Hawking radiation from black holes. Assuming spherical symmetry, the Gauss law prevents the external field from depending on the density profile of the ball. Quantum corrections violate these expectations, showing that quantum radiation can encode classically forbidden information about the source.
We found it interesting that quantum hair can already be found using the familiar Euler-Heisenberg effective action, which results from integrating out the electron in QED.

The paper also contains a general argument for why solutions to the semiclassical field equations resulting from the effective action (both in gravity and QED) carry more information about the state of the source than in classical physics.

From the Conclusions:
The quantum effective actions for both electrodynamics and gravity lead to field equations which couple a compact source (charge current or energy-momentum tensor) to external fields (electromagnetic or graviton field) in a manner which, generically, leads to quantum memory and quantum hair effects. External solutions of the field equations deviate, due to quantum corrections, from the familiar classical forms that satisfy the Gauss law. As a specific consequence, more information about the interior source configuration is encoded in the external field than in the classical theory.
As specific applications, we considered semiclassical sources (large black hole, macroscopic charge distribution), which allowed us to solve the quantum corrected field equations by expanding around a classical solution. However, fully quantum statements regarding quantum hair are also possible, which do not, for example, require a semiclassical source. In [1–3] it was shown that the quantum state of a compact source (e.g., in an energy eigenstate or superposition thereof) determines certain aspects of the quantum state of its external field. In principle, measurements of the external fields can fully determine the interior state of a black hole.

Thursday, September 22, 2022

Rob Henderson: A Journey from Foster Care to the US Military to Elite Academia — Manifold podcast #20

Rob Henderson grew up in foster homes in California, joined the Air Force at 17, attended Yale on the G.I. Bill, and is currently a Gates Fellow at Cambridge University (UK). He is an acute observer of American society and has coined the term Luxury Beliefs to describe ideas and opinions that confer status on the rich at very little cost, while taking a toll on the lower class.

Steve and Rob discuss:

00:00 Early life and foster experience
20:21 Rob’s experience in the Air Force
31:26 Transitioning from the Air Force to Yale and then Cambridge
44:04 Dating and socializing as an older student
50:06 Reflections on the Yale Halloween email controversy
1:01:10 Personal incentives and careerists in higher education
1:09:45 Luxury beliefs and how they show up in elite institutions
1:31:08 Age and moral judgments
1:42:50 Rob on resisting legacy academia and his future

Rob's substack

Luxury Beliefs are the Latest Status Symbol for Rich Americans

Tuesday, September 20, 2022

Sibling Variation in Phenotype and Genotype: Polygenic Trait Distributions and DNA Recombination Mapping with UK Biobank and IVF Family Data (medRxiv)

This is a new paper which uses Genomic Prediction IVF family data, including genotyped embryo samples.
Sibling Variation in Phenotype and Genotype: Polygenic Trait Distributions and DNA Recombination Mapping with UK Biobank and IVF Family Data
L. Lello, M. Hsu, E. Widen, and T. Raben
We use UK Biobank and a unique IVF family dataset (including genotyped embryos) to investigate sibling variation in both phenotype and genotype. We compare phenotype (disease status, height, blood biomarkers) and genotype (polygenic scores, polygenic health index) distributions among siblings to those in the general population. As expected, the between-siblings standard deviation in polygenic scores is \sqrt{2} times smaller than in the general population, but variation is still significant. As previously demonstrated, this allows for substantial benefit from polygenic screening in IVF. Differences in sibling genotypes result from distinct recombination patterns in sexual reproduction. We develop a novel sibling-pair method for detection of recombination breaks via statistical discontinuities. The new method is used to construct a dataset of 1.44 million recombination events which may be useful in further study of meiosis.

Here are some figures illustrating the variation of polygenic scores among siblings from the same family.

The excerpt below describes the IVF family highlighted in blue above:

Among the families displayed in these figures, at position number 15 from the left, we encounter an interesting case of sibling polygenic distribution relative to the parents. In the family all siblings have significantly higher Health Index score than the parents. This arises in an interesting manner: the mother is a high-risk outlier for condition X and the father is a high-risk outlier for condition Y. (We do not specify X and Y, out of an abundance of caution for privacy, although the patients have consented that such information could be shared.) Their lower overall Health Index scores result from high risk of conditions X (mother) and Y (father). However, the embryos, each resulting from unique recombination of parental genotypes, are normal risk for both X and Y and each embryo has much higher Health Index score than the parents.
This case illustrates well the potential benefits from PGS embryo screening.

The second part of the paper introduces a new technique that directly probes DNA recombination -- the molecular mechanism responsible for sibling genetic differences. See figure above for some results. The new method detects recombination breaks via statistical discontinuities in pairwise comparisons of DNA regions.

From the discussion:
...This new sibling-pair method can be applied to large datasets with many thousands of sibling pairs. In this project we created a map of roughly 1.44 million recombination events using UKB genomes. Similar maps can now be created using other biobank data, including in non-European ancestry groups that have not yet received sufficient attention. The landmark deCODE results were obtained under special circumstances: the researchers had access to data resulting from a nationwide project utilizing genealogical records (unusually prevalent in Iceland) and widespread sequencing. Using the sibling-pair method results of comparable accuracy can be obtained from existing datasets around the world -- e.g., national biobanks in countries such as the USA, Estonia, China, Taiwan, Japan, etc.
The creator of this new sibling-pair method for recombination mapping is my son. He developed and tested the algorithm, and wrote all the code in Python. It's his high school science project :-)

Thursday, September 08, 2022

Lyle Goldstein on U.S. Strategic Challenges: Russia, China, Ukraine, and Taiwan — Manifold #19

Professor Goldstein recently retired after 20 years of service on the faculty of the U.S. Naval War College (NWC). During his career at NWC, he founded the China Maritime Studies Institute (CMSI) and has been awarded the Superior Civilian Service Medal for this achievement. He has written or edited seven books on Chinese strategy and is at work on a book-length project that examines the nature of China-Russia relations in the 21st century. He has a longstanding interest in great power politics, military competition, and security in the pacific region.

Goldstein is Director of Asia Engagement at the Washington think-tank Defense Priorities, which advocates for realism and restraint in U.S.defense policy, and also a visiting professor at the Watson Institute for International and Public Affairs at Brown University.

He earned a PhD at Princeton, an MA from Johns Hopkins SAIS, and an AB from Harvard. He is fluent in both Chinese and Russian.

Steve and Lyle discuss:

00:00 Early life and background
18:03 Goldstein’s dissertation on China’s nuclear strategy
37:35 Pushback on “Meeting China Halfway”
41:24 Could the U.S. have prevented war in Ukraine?
46:05 How territorial conflicts are influencing China’s relationship with Russia
1:00:16 Analyzing war games with U.S., China, and Taiwan

Watson Institute, Brown University

Meeting China Halfway (2015)

Here's Why War With China Could Elevate to Nuclear Strikes The National Interest, January 29 2022 https://nationalinterest.org/blog/reboot/heres-why-war-china-could-elevate-nuclear-strikes-200099

Goldstein's articles at The National Interest

Monday, September 05, 2022

Lunar Society (Dwarkesh Patel) Interview

Dwarkesh did a fantastic job with this interview. He read the scientific papers on genomic prediction and his questions are very insightful. Consequently we covered the important material that people are most confused about.

Don't let the sensationalistic image above deter you -- I highly recommend this podcast!

0:00:00 Intro
0:00:49 Feynman’s advice on picking up women
0:12:21 Embryo selection
0:24:54 Why hasn't natural selection already optimized humans?
0:34:48 Aging
0:54:24 Genomics in dating
1:01:06 Ancestral populations
1:08:33 Is this eugenics?
1:25:36 Consumer preferences
1:30:49 Gwern
1:35:10 Will parents matter?
1:46:00 Wordcels and shape rotators
1:58:04 Bezos and brilliant physicists
2:10:58 Elite education

Thursday, August 25, 2022

Harvard Veritas: interview with a recent graduate (anonymous) — Manifold Episode #18

The guest for this episode is a recent graduate of Harvard College, now pursuing a STEM PhD at another elite university. We have withheld his identity so that he can speak candidly.

Steve and his guest discuss:

21:37 Intellectual curiosity at Harvard
29:36 Academic rigor at Harvard and the difference between classes in STEM and the humanities
50:08 The benefits of the Harvard connection and wider pool of opportunities
58:46 Competing with off-scale students
1:00:48 Ideological climate on campus, wokeism, and controversial public speakers
1:23:11 Dating at Harvard

From first link above, The Chosen by J. Karabel.

Typology used for all applicants, at least as late as 1988:

1. S First-rate scholar in Harvard departmental terms.

2. D Candidate's primary strength is his academic strength, but it doesn't look strong enough to quality as an S (above).

3. A All-Amercan‚ healthy, uncomplicated athletic strengths and style, perhaps some extracurricular participation, but not combined with top academic credentials.

4. W Mr. School‚ significant extracurricular and perhaps (but not necessarily) athletic participation plus excellent academic record.

5. X Cross-country style‚ steady man who plugs and plugs and plugs, won't quit when most others would. Gets results largely through stamina and consistent effort.

6. P PBH [Phillips Brooks House] style: in activities and personal concerns.

7. C Creative in music, art, writing.

8. B Boondocker‚ unsophisticated rural background.

9. T Taconic, culturally depressed background, low income.

10. K Krunch‚ main strength is athletic, prospective varsity athlete. [ Sometimes also "H Horse" :-) ]

11. L Lineage‚ candidate probably couldn't be admitted without the extra plus of being a Harvard son, a faculty son, or a local boy with ties to the university community.

12. O Other‚ use when none of the above are applicable.

Friday, August 19, 2022

Geostrategy and US-China Military Competition

I've been asked to write something about PRC military buildup and a potential Taiwan (TW) conflict.

1. My perspective and bona fides: My father was a KMT officer, my mother's father was a KMT general and that side of the family is related to Chiang Kai Shek by marriage. I have relatives both in PRC and TW. My wife is a graduate of National Taiwan University. I should be biased in favor of TW and against CPC but I am a realist and rationalist so I call things as I see them.

2. PRC military technology has reached parity with the US and, overall, surpassed Russia. PLARF (dedicated rocket forces) may be decisive in a conflict in the pacific. They may have achieved A2AD and can make it very costly for the US navy to operate anywhere near TW.

3. Specifically, long range missile attack on surface ships, using initial targeting via satellites and drones, and final targeting from sensors on the missile itself, is probably a mature technology now and difficult to defeat with countermeasures / missile defense.

4. US estimates of PRC nuclear weapons stockpile have barely changed in 30y and are likely highly unreliable. Based on production capabilities alone they may already have ~1000 warheads (if not now, in a few years), and the ability to target the entire US. PRC is building up its arsenal to ensure that the US understands that they have a reliable MAD capability.

5. PRC can easily blockade TW if desired, and (at cost of significant escalation) can probably also blockade Japan and S. Korea as well. All of these countries import ~90% of energy and ~50% of food calories, so a protracted blockade would have serious impact.

6. I don’t believe PRC has near term plans to invade TW, but they have to maintain the capability to deter any change in the status quo. Both sides prefer the status quo but accidents can happen.

7. Thanks to stupid US strategy re: Ukraine, PRC can rely on Russian energy in the future and will become much more resistant to naval blockade (e.g., of oil supplies transiting the Malacca Strait). In other words, dumb US neocons solved PRC’s energy security problem for them.

No one talks about this because US strategy has been brain dead for a long time. No one even talks, in the immediate aftermath, about the trillions of dollars and millions of lives wasted over 20y in the Iraq/Afghanistan tragedies. Cui bono?

8. PRC spends a smaller fraction of GDP on defense than the US, but because they have mastered the entire military technology stack cost estimates should be PPP adjusted. After PPP adjustment the PRC economy is substantially larger than the US economy. This, plus the fact that their manufacturing capacity (e.g., ship building) is far beyond that of the US, means that their overall capability to produce war materiel (i.e., to engage in a rapid buildup on, e.g., a 5y timescale) has easily surpassed ours. Anyone following their recent naval or air power or missile or satellite build up can see that this is the case.

I'll be discussing some of these topics with Lyle Goldstein (US Naval War College, Watson China Initiative at Brown University; BA Harvard, PhD Princeton) in a future podcast.

See also this documentary produced by the US Army University Press. Queued to start at discussion of missile technology and nuclear weapons.

There's something here from somewhere else
The war machine springs to life
Opens up one eager eye
Focusing it on the sky
-- 99 Luftballons

Sunday, August 14, 2022

Tweet Treats: AI in PRC, Semiconductors and the Russian War Machine, Wordcels are Midwits

Some recent tweets which might be of interest :-)

Thursday, August 11, 2022

Manifold Episode #18

You may have noticed the post earlier today about the episode with Amy Chua of Yale Law School. That episode has been removed by request of Amy's publisher. Her new book is not out until 2023 and she has been asked not to do any media until then.

Wednesday, August 03, 2022

A Brief History of Hawking's Information Paradox (European Physics Letters)

This is a short review of our recent work on black hole information for European Physics Letters.
A Brief History of Hawking's Information Paradox

European Physics Letters 139 (2022) 49001

Xavier Calmet and Stephen D. H. Hsu

Abstract
In this invited review, we describe Hawking's information paradox and a recently proposed resolution of it. Explicit calculations demonstrate the existence of quantum hair on black holes, meaning that the quantum state of the external graviton ﬁeld depends on the internal state of the black hole. Simple quantum mechanics then implies that Hawking radiation amplitudes depend on the internal state, resulting in a pure ﬁnal radiation state that preserves unitarity and, importantly, violates a factorization assumption which is central to the original paradox. Black hole information is encoded in entangled macroscopic superposition states of the radiation.

DOI: 10.1209/0295-5075/ac81e8

From Conclusions:
... The radiation amplitudes computed by Hawking, which describe thermal radiation emitted from a black hole at temperature T, already describe a broad distribution of possible radiation types, spins, and momenta emitted at each stage. Thus, even in the semiclassical approximation there are many distinct patterns of radiation in (6). The set of possible final states is already complex even at leading order, resulting in very different coarse grained patterns of energy-momentum density. Small corrections to the amplitudes α(E, r) due to quantum hair do not qualitatively change this situation, but they are necessary to unitarize the evaporation and they determine the precise relations between components of the entangled state.
Importantly, no special assumptions about the amplitudes α(E, r) need to be made to determine that the factorized form of the state (2) does not hold. Factorization is assumed in essentially every formulation of the information paradox, but in reality is violated because the external graviton state depends on the internal black hole state.
Known quantum gravitational effects leading to quantum hair are extremely small and thus difficult to probe experimentally or detect via observations. We cannot prove that our solution to the information paradox is unique. However, the consequences of quantum hair lead, without any speculative theoretical assumptions, to plausible unitary evaporation of black holes. The properties of quantum hair and the evaporation amplitude (6) can be deduced using only long wavelength properties of quantum gravity – they do not rely on assumptions about Planck scale physics or a specific short distance completion. Therefore, Occam’s razor favors quantum hair.

Wednesday, July 27, 2022

Richard Lowery: The War for American Universities — Manifold #17

Richard Lowery is a professor of finance at the McCombs School of Business at the University of Texas, Austin. In this conversation, he describes the ideological climate of his university and the consequent negative effects on undergraduate education and freedom of expression on campus.

Steve and Richard discuss:

0:00 Richard Lowery's academic and political background
9:01 Campus environment for academics and faculty members
12:19 Cultural and political dynamics at academic institutions
23:04 How students experience campus culture and political influences
32:13 Public awareness and interest in campus culture
35:50 What happened to the Liberty Institute at UT Austin
53:44 Donor influence
1:00:55 STEM professors: keep quiet, or else
1:08:25 Lowery on the future of US universities

Richard Lowery at UT Austin:

National Review coverage:

Monday, July 18, 2022

Quantum Hair and Black Hole Information, University of Amsterdam, 17 Jun 2022

As promised, video from my talk in Amsterdam.

Seminar at the Institute of Physics, University of Amsterdam, 17 Jun 2022.

Title: Quantum Hair and Black Hole Information

Abstract: I discuss recent results concerning the quantum state of the gravitational field of a compact matter source such as a black hole. These results demonstrate the existence of quantum hair, violating the classical No Hair Theorems. I then discuss how this quantum hair affects Hawking radiation, allowing unitary evaporation of black holes. Small corrections to leading order Hawking radiation amplitudes, with weak dependence on the external graviton state, are sufficient to produce a pure final radiation state. The radiation state violates the factorization assumption made in standard formulations of the information paradox. These conclusions are consequences of long wavelength properties of quantum gravity: no special assumptions are made concerning short distance (Planckian) physics.

Institute of Physics, University of Amsterdam:

Saturday, July 16, 2022

Meritocracy and Political Leadership in China

Putting this tweet thread here for future reference. If you read this blog you may want to follow me on Twitter as I sometimes say things there that might be of interest.

Thursday, July 14, 2022

Tim Palmer (Oxford): Status and Future of Climate Modeling — Manifold Podcast #16

Tim Palmer is Royal Society Research Professor in Climate Physics, and a Senior Fellow at the Oxford Martin Institute. He is interested in the predictability and dynamics of weather and climate, including extreme events.

He was involved in the first five IPCC assessment reports and was co-chair of the international scientific steering group of the World Climate Research Programme project (CLIVAR) on climate variability and predictability.

After completing his DPhil at Oxford in theoretical physics, Tim worked at the UK Meteorological Office and later the European Centre for Medium-Range Weather Forecasts. For a large part of his career, Tim has developed ensemble methods for predicting uncertainty in weather and climate forecasts.

In 2020 Tim was elected to the US National Academy of Sciences.

Steve, Corey Washington, and Tim first discuss his career path from physics to climate research and then explore the science of climate modeling and the main uncertainties in state-of-the-art models.

In this episode, we discuss:

00:00 Introduction
1:48 Tim Palmer's background and transition from general relativity to climate modeling
15:13 Climate modeling uncertainty
46:41 Navier-Stokes equations in climate modeling
53:37 Where climate change is an existential risk
1:01:26 Investment in climate research

Tim Palmer (Oxford University)

The scientific challenge of understanding and estimating climate change (2019) https://www.pnas.org/doi/pdf/10.1073/pnas.1906691116

ExtremeEarth

Physicist Steve Koonin on climate change

: For some background on the importance of water vapor (cloud) distribution within the primitive cells used in these climate simulations, see:

Low clouds trap IR radiation near the Earth, while high clouds reflect solar energy back into space. The net effect on heating from the distribution of water vapor is crucial in these models. However, due to the complexity of the Navier-Stokes equations, current simulations cannot actually solve for this distribution from first principles. Rather, the modelers hand code assumptions about fine grained behavior within each cell. The resulting uncertainty in (e.g., long term) climate prediction from these approximations is unknown.

Wednesday, July 06, 2022

WIRED: Genetic Screening Now Lets Parents Pick the Healthiest Embryos

This is a balanced and informative article in WIRED, excerpted from author Rachael Pells' forthcoming bookGenomics: How Genome Sequencing Will Change Our Lives.
WIRED: ... Companies such as Genomic Prediction are taking this process much further, giving parents the power to select the embryo they believe to have the best fighting chance of survival both in the womb and out in the world. At the time of writing, Genomic Prediction works with around 200 IVF clinics across six continents. For company cofounder Stephen Hsu, the idea behind preconception screening was no eureka moment, but something he and his peers developed gradually. “We kept pursuing the possibilities from a purely scientific interest,” he says. Over time sequencing has become cheaper and more accessible, and the bank of genetic data has become ever greater, which has provided the opportunity to easily apply machine learning programs to seek out patterns, Hsu explains. “You can have typically millions of people in one data set, with exact measurements of certain things about them—for instance how tall they are or whether they have diabetes—what we call phenotypes. And so it’s relatively straightforward to use AI to build genetic predictors of traits ranging from very simple ones which are only determined by a few genes, or a few different locations in the genome, to the really complicated ones.” As Hsu indicates, the crucial difference with this technology is that it’s not just single mutations like cystic fibrosis or sickle cell anemia that the service makes its calculations on. The conditions embryos are screened for can be extremely complicated, involving thousands of genetic variants across different parts of the genome.
In late 2017, Hsu and his colleagues published a paper demonstrating how, using genomic data at scale, scientists could predict someone’s height to within an inch of accuracy using just their DNA. The research group later used the same method to build genomic predictors for complex diseases such as hypothyroidism, types 1 and 2 diabetes, breast cancer, prostate cancer, testicular cancer, gallstones, glaucoma, gout, atrial fibrillation, high cholesterol, asthma, basal cell carcinoma, malignant melanoma, and heart attacks. ...

Two useful references:

Complex Trait Prediction: Methods and Protocols (Springer 2022)