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 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 
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 
0:43:53 First Mover Advantage 
0:54:24 Genomics in dating 
1:01:06 Ancestral populations 
1:08:33 Is this eugenics? 
1:16:34 Tradeoffs to intelligence 
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 

If you prefer audio-only click here.

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: 

0:00 Anonymous student’s academic background and admission to Harvard 
21:37 Intellectual curiosity at Harvard 
29:36 Academic rigor at Harvard and the difference between classes in STEM and the humanities 
46:47 Access to tenured professors at Harvard 
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 
1:26:52 Z-scores and other metrics to add to the admissions process 

Harvard Admissions and Meritocracy: 

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.



Panic bells, it's red alert 
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 

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: 
Academic Freedom in Crisis: 

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 


Physicist Steve Koonin on climate change

Note added
: 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:

Polygenic Health Index, General Health, and Disease Risk 

Complex Trait Prediction: Methods and Protocols (Springer 2022)

Sunday, July 03, 2022

BLADE RUNNER - Commentary by Ridley Scott


Fascinating director's commentary by Ridley Scott. Video cued to start at a point where Scott talks about the conceptual background for the film. The subsequent ~15m are really great, including dreams of unicorns, memories of green, origami, Deckard as replicant.

He also mentions that he envisioned Alien and Blade Runner taking place in the same universe.
... a special feature on the Prometheus Blu-ray release makes the film even more interesting by tying it into the Blade Runner universe. Included as an entry in the journal of Peter Weyland (Guy Pearce), who in the film was obsessed with creating artificial life, is the following gem: 
A mentor and long-departed competitor once told me that it was time to put away childish things and abandon my “toys.” He encouraged me to come work for him and together we would take over the world and become the new Gods. That’s how he ran his corporation, like a God on top of a pyramid overlooking a city of angels. Of course, he chose to replicate the power of creation in an unoriginal way, by simply copying God. And look how that turned out for the poor bastard. Literally blew up in the old man’s face. I always suggested he stick with simple robotics instead of those genetic abominations he enslaved and sold off-world, although his idea to implant them with false memories was, well… “amusing,” is how I would put it politely.
Bonus: at 1h18m in the video, Tyrell cryogenically preserved at the heart of his great pyramid!

Thursday, June 30, 2022

Kishore Mahbubani: A Nuanced View of Asia & China's Rise — Manifold Podcast #15


Kishore Mahbubani is Distinguished Fellow at the Asia Research Institute, National University of Singapore. 

Kishore enjoyed two distinct careers: in diplomacy (1971 to 2004) and in academia (2004 to 2019). He is a prolific writer and speaker on geopolitics and East-West relations. He was twice Singapore’s Ambassador to the UN and served as President of the UN Security Council in January 2001 and May 2002. Mr. Mahbubani joined academia in 2004, when he was appointed the Founding Dean of the Lee Kuan Yew School of Public Policy (LKY School), NUS. He was Dean from 2004 to 2017. 

In this episode Steve and Kishore discuss: 

0:00 Introduction 
2:52 Upbringing in Singapore and Asia's rise 
11:35 How western thinking influences China-U.S. relations 
23:05 Is China a threat to U.S. hegemony in Asia? 
25:52 The United States' long-term strategy for China 
32:13 How trade with ASEAN influences U.S.-China relations 
40:58 Can ASEAN countries play a diplomatic role between U.S. and China 
43:05 Xi Jinping's leadership and the zero-sum view of China 


This Dutch documentary, which also features Mahbubani, is an excellent complement to our conversation.

Thursday, June 23, 2022

Polygenic Health Index, General Health, and Disease Risk

New paper!

Informal summary: We built a polygenic health index using risk predictors weighted by lifespan impact of the specific disease condition. This index seems to characterize general health. Individuals with higher index scores have decreased disease risk across almost all 20 diseases (no significant risk increases), and longer calculated life expectancy. When estimated Disability Adjusted Life Years (DALYs) are used as the performance metric, the gain from selection among 10 individuals (highest index score vs average) is found to be roughly 4 DALYs. We find no statistical evidence for antagonistic trade-offs in risk reduction across these diseases. Correlations between genetic disease risks are found to be mostly positive and generally mild.
Polygenic Health Index, General Health, and Disease Risk 
We construct a polygenic health index as a weighted sum of polygenic risk scores for 20 major disease conditions, including, e.g., coronary artery disease, type 1 and 2 diabetes, schizophrenia, etc. Individual weights are determined by population-level estimates of impact on life expectancy. We validate this index in odds ratios and selection experiments using unrelated individuals and siblings (pairs and trios) from the UK Biobank. Individuals with higher index scores have decreased disease risk across almost all 20 diseases (no significant risk increases), and longer calculated life expectancy. When estimated Disability Adjusted Life Years (DALYs) are used as the performance metric, the gain from selection among 10 individuals (highest index score vs average) is found to be roughly 4 DALYs. We find no statistical evidence for antagonistic trade-offs in risk reduction across these diseases. Correlations between genetic disease risks are found to be mostly positive and generally mild. These results have important implications for public health and also for fundamental issues such as pleiotropy and genetic architecture of human disease conditions. 

Some figures:

Extrapolating the DALY gain vs Health Index score curve (top figure) to the entire human population (e.g., 10 billion people) results in +30 or +40 DALYs more than average, or something like 120 total years of life.  The individual with the highest Health Index score in the world is predicted to live about 120 years.

I wanted to use this in the paper but my collaborators vetoed me 8-)
The days of our years are threescore years and ten; and if by reason of strength they be fourscore years, yet is their strength labour and sorrow; for it is soon cut off, and we fly away 
Psalm 90:10

Monday, June 20, 2022

Amsterdam, Utrecht, Split, Hvar

Last week I was in Amsterdam and Utrecht to give seminars on quantum hair and black hole information at the Universities of Utrecht and Amsterdam. The organizers told me I was the first external visitor to give an in-person talk since the COVID lockdowns. 

The Utrecht seminar went over 2 hours (unfortunately, 't Hooft was away) and the other over 90 minutes. 

I will post video of the seminars at some point. 

Now I am at the John Bell Institute on Hvar, Croatia for a special workshop on the black hole information puzzle

This is the view of the Adriatic from the John Bell Institute, and the beach:


Institute of Physics, University of Amsterdam:

Thursday, June 16, 2022

Greg Clark: Genetics and Social Mobility — Manifold Episode #14


Gregory Clark is Distinguished Professor of Economics at UC-Davis. He is an editor of the European Review of Economic History, chair of the steering committee of the All-UC Group in Economic History, and a Research Associate of the Center for Poverty Research at Davis. He was educated at Cambridge University and received a PhD from Harvard University. His areas of research are long-term economic growth, the wealth of nations, economic history, and social mobility. 

Steve and Greg discuss: 

0:00 Introduction 
2:31 Background in economics and genetics 
10:25 The role of genetics in determining social outcomes 
16:27 Measuring social status through marriage and occupation 
36:15 Assortative mating and the industrial revolution 
49:38 Criticisms of empirical data, engagement on genetics and economic history 
1:12:12 Heckman and Landerso study of social mobility in US vs Denmark 
1:24:32 Predicting cognitive traits 
1:33:26 Assortative mating and increase in population variance 


For Whom the Bell Curve Tolls: A Lineage of 400,000 English Individuals 1750-2020 shows Genetics Determines most Social Outcomes http://faculty.econ.ucdavis.edu/faculty/gclark/ClarkGlasgow2021.pdf 

A Farewell to Alms: A Brief Economic History of the World https://en.wikipedia.org/wiki/A_Farewell_to_Alms 

Sunday, June 12, 2022

Von Neumann: The Interaction of Mathematics and Computing, Stan Ulam 1976 talk (video)


Von Neumann: The Interaction of Mathematics and Computing, by Stan Ulam. 

See A History of Computing in the Twentieth Century, Edited by: N. METROPOLIS, J. HOWLETT and GIAN-CARLO ROTA.
More videos from the conference here. (Konrad Zuse!)

See at 50 minutes for an interesting story about von Neumann's role in the implosion mechanism for atomic bombs. vN apparently solved the geometrical problem for the shape of the explosive lens overnight after hearing a seminar on the topic. Still classified?
To solve this problem, the Los Alamos team planned to produce an “explosive lens”, a combination of different explosives with different shock wave speeds. When molded into the proper shape and dimensions, the high-speed and low-speed shock waves would combine with each other to produce a uniform concave pressure wave with no gaps. This inwardly-moving concave wave, when it reached the plutonium sphere at the center of the design, would instantly squeeze the metal to at least twice the density, producing a compressed ball of plutonium that contained about 5 times the necessary critical mass. A nuclear explosion would then result.
More here.

Saturday, June 11, 2022

Genomic Prediction on WHYY The Pulse

This 20 minute podcast segment is very well done. Congratulations to science journalist Teresa Carey.



Startup offers genetic testing that promises to predict healthiest embryo 
Aurea toddles around in her pink sparkly sneakers, climbing up the steps that, to her, are nearly waist high. Her tiny t-shirt is the epitome of how adorable she is. It says “you + me + snuggles.” Aurea’s father, Rafal Smigrodzki, watches over his little girl. He is clearly proud of her. “She’s very lively. I think she’s a pretty, pretty happy baby,” Smigrodzki said, “a very often smiley baby.” 
Of course, Smigrodzki thinks his baby is special — most parents do. But Aurea is indeed unique. She was born almost two years ago and happens to be the first child born as the result of a new type of genetic screening, which carefully selected her embryo. Smigrodzki and his girlfriend used in vitro fertilization and an advanced selection process from a startup called Genomic Prediction. 
The New Jersey startup offers genetic tests and promises to help prospective parents select embryos with the best possible genes. The company says its test can screen embryos for a variety of diseases and health conditions, like heart disease, diabetes, or breast cancer. 
Smigrodzki, a neurologist with a PhD in genetics, stumbled across the company in 2017. 
“I was always interested and reading about all kinds of new developments,” he said. “And just happened to read an article in the MIT Technology Review about Genomic Prediction.” 
For more information, see (audio + transcript): 


Thursday, June 02, 2022

John Mearsheimer: Great Powers, U.S. Hegemony, and the Rise of China — Manifold Podcast #13


This interview with John Mearsheimer was conducted in 2020 on the original Manifold podcast with Corey Washington and Steve Hsu. Parts of the conversation are prescient with respect to US-China relations and the situation in Ukraine. 

John Joseph Mearsheimer is an American political scientist and international relations scholar, who belongs to the realist school of thought. He is the R. Wendell Harrison Distinguished Service Professor at the University of Chicago. He has been described as the most influential realist of his generation. 

Mearsheimer is best known for developing the theory of offensive realism, which describes the interaction between great powers as being primarily driven by the rational desire to achieve regional hegemony in an anarchic international system. In accordance with his theory, Mearsheimer believes that China's growing power will likely bring it into conflict with the United States. 

Steve, Corey, and John discuss: 

0:00 A quick message for listeners 
1:21 Introduction 
2:39 Realist foreign policy worldview 
15:46 Proxy conflicts and the U.S. 
21:31 U.S. history: a moral hegemon, or just a hegemon? Zinn and Chomsky 
29:50 U.S.-China relationship, competing hegemonies? 
36:44 Will Europe become more united? 
41:23 China’s ambitions 
46:12 Europe’s fragmentation and population trends 
47:57 What drove U.S. interventions after the Cold War? 
51:36 Coalitions and U.S.-China competition 

Resources: John Mearsheimer - https://www.mearsheimer.com/ 

The Great Delusion: Liberal Dreams and International Realities - https://www.amazon.com/Great-Delusion-Liberal-International-Realities-ebook/dp/B07H3XRPQS

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