Tuesday, December 29, 2020

China CDC Director interview: vaccine progress, viroid sequencing, transmission via food/packaging

 

This is a recent interview with the PRC CDC head, which includes: 

1. Discussion of various vaccines. He confirms that their vaccine(s) are using the standard method (inactivated viruses), which a priori one might consider safer than the new mRNA type. Efficacy remains to be seen but he seemed to hint that they would be releasing some data/results in the next few days. 

2. He notes (at ~7m) that PRC is sequencing every new case of covid. They see all the mutant versions, and find that infections are coming both from visitors to PRC as well as from imported food/packaging! So the latter really happens. 

If anyone can find primary sources related to these topics I would be very interested.

Here is some discussion of the different vaccines: costs, ongoing validations, etc.

Thursday, December 24, 2020

Peace on Earth, Good Will to Men 2020



When asked what I want for Christmas, I reply: Peace On Earth, Good Will To Men :-)

No one ever seems to recognize that this comes from the Bible (Luke 2.14).

Linus said it best in A Charlie Brown Christmas:
And there were in the same country shepherds abiding in the field, keeping watch over their flock by night.

And, lo, the angel of the Lord came upon them, and the glory of the Lord shone round about them: and they were sore afraid.

And the angel said unto them, Fear not: for, behold, I bring you good tidings of great joy, which shall be to all people.

For unto you is born this day in the city of David a Saviour, which is Christ the Lord.

And this shall be a sign unto you; Ye shall find the babe wrapped in swaddling clothes, lying in a manger.

And suddenly there was with the angel a multitude of the heavenly host praising God, and saying,

Glory to God in the highest, and on earth peace, good will toward men.

Merry Christmas!

This has been a difficult year for many people. Please accept my best wishes and hopes for a wonderful 2021. Be of good cheer, for we shall prevail! :-) 


The first baby conceived from an embryo screened with Genomic Prediction preimplantation genetic testing for polygenic risk scores (PGT-P) was born in mid-2020.  

Genomic Prediction has now performed embryo genetic tests for almost 200 IVF clinics in many countries. Millions of embryos are screened each year, worldwide.

Five years ago on Christmas day I shared the Nativity 2050 story below. See also The Economist on Polygenic Risk Scores and Embryo Selection.


And the angel said unto them, Fear not: for, behold, I bring you good tidings of great joy, which shall be to all people.
Mary was born in the twenties, when the tests were new and still primitive. Her mother had frozen a dozen eggs, from which came Mary and her sister Elizabeth. Mary had her father's long frame, brown eyes, and friendly demeanor. She was clever, but Elizabeth was the really brainy one. Both were healthy and strong and free from inherited disease. All this her parents knew from the tests -- performed on DNA taken from a few cells of each embryo. The reports came via email, from GP Inc., by way of the fertility doctor. Dad used to joke that Mary and Elizabeth were the pick of the litter, but never mentioned what happened to the other fertilized eggs.

Now Mary and Joe were ready for their first child. The choices were dizzying. Fortunately, Elizabeth had been through the same process just the year before, and referred them to her genetic engineer, a friend from Harvard. Joe was a bit reluctant about bleeding edge edits, but Mary had a feeling the GP engineer was right -- their son had the potential to be truly special, with just the right tweaks ...

Monday, December 21, 2020

Lianda


The videos below are about Lianda, a wartime university located in Kunming that was formed by the merger of Peking University, Tsinghua University, and Nankai University.
Lianda: A Chinese University in War and Revolution 
In the summer of 1937, Japanese troops occupied the campuses of Beijing’s two leading universities, Beida and Qinghua, and reduced Nankai, in Tianjin, to rubble. These were China's leading institutions of higher learning, run by men educated in the West and committed to modern liberal education. The three universities first moved to Changsha, 900 miles southwest of Beijing, where they joined forces. But with the fall of Nanjing in mid-December, many students left to fight the Japanese, who soon began bombing Changsha. 
In February 1938, the 800 remaining students and faculty made the thousand-mile trek to Kunming, in China’s remote, mountainous southwest, where they formed the National Southwest Associated University (Lianda). In makeshift quarters, subject to sporadic bombing by the Japanese and shortages of food, books, and clothing, students and professors did their best to conduct a modern university. In the next eight years, many of China’s most prominent intellectuals taught or studied at Lianda. ... 
Lianda’s wartime saga crystallized the experience of a generation of Chinese intellectuals, beginning with epic journeys, followed by years of privation and endurance, and concluding with politicization, polarization, and radicalization, as China moved from a war of resistance against a foreign foe to a civil war pitting brother against brother. The Lianda community, which had entered the war fiercely loyal to the government of Chiang Kai-shek, emerged in 1946 as a bastion of criticism of China’s ruling Guomindang party. Within three years, the majority of the Lianda community, now returned to its north China campuses in Beijing and Tianjin, was prepared to accept Communist rule. ...
My father attended this university at age 16, admitted via Tsinghua. Among its most famous alumni are the Nobel Prize winning theoretical physicists C.N. Yang and T.D. Lee. As the university only existed for 8 years, there are very few alumni still living.


 

I came across the 一条 Yit channel because I recently bought an Android Smart TV and it caused an increase in consumption of YouTube, etc. I got the TV to use as a big monitor but it's great for content as well. One of the most enjoyable things I do with it is watch seminars (e.g., in theoretical physics or AI)!

In case you are wondering I bought a 70inch HiSense on sale for under $400: good 4k picture and sound -- highly recommended!

Sunday, December 20, 2020

PPP and the Shanghai Girl

After PPP correction the PRC economy is significantly larger than the US economy, so it's important to understand what nominal GDP and its adjusted counterpart represent. 

This 2019 video follows a 26 year woman around during a typical weekend day. She lives in a $330 per month apartment in central Shanghai, a short walk to her office where she works as an advertising copywriter. You get a look at the apps she uses to order food and household supplies, keep up with fashion and culinary trends, pay at restaurants, etc.

Her monthly budget is about $2300 USD per month, and as far as I can tell her lifestyle would cost more than twice as much in NYC (e.g., Brooklyn), San Francisco, Chicago, or even a somewhat smaller US city. So the nominal to PPP correction of 2x may actually be conservative! Some have suggested that the PRC government deliberately understates its GDP in order to continue to claim "developing nation" status, and to not alarm US hawks (as if that were possible).



In late 2010 I was in Shanghai for a physics meeting, and blogged about dollar-yuan purchasing power parity (PPP).
Shanghai: PPP on the ground  
1 USD = 6.64 RMB. Average salary in Shanghai is reportedly 65k RMB or about USD $10k per annum. ... The IMF estimates that the PPP (purchasing power parity) vs nominal exchange rate adjustment for China is about a factor of 2 (i.e., PPP GDP is about twice nominal GDP). That doesn't sound entirely crazy to me but it's very dependent on choice of goods for the PPP basket. ... 
Haircut 10 RMB = $1.50. (My barber in Eugene = $11.) 
 
Dinner on campus 9 RMB = $1.35. 

Monday, December 14, 2020

The Celestial Empire

This lifestyle channel delivers daily vignettes from China (~5 minutes each), with an occasional episode from Taiwan. They have English subtitles, so offer a unique window into modern Chinese life. 

When I blogged from Beijing in the summer of 2019, some readers were surprised that I found parts of the city as aesthetically interesting as places in Tokyo or other iconic cities. 

Everything is advancing very rapidly in China, as you can tell from the videos. Below are some episodes I recommend. There are many more...


Kindergarten in renovated Beijing courtyard house.

 


Tibetan lodges.



Boat house in Fujian.

 


Struggles of an independent film maker.

 


Photographer documents lives of factory workers in Guangdong.

 


Buddha collection in Guangzhou.



See also China 1793 -- it looks like the 200 year down cycle may be over... Celestial Empire returns?

Amasa Delano was an American ship captain and distant relative of FDR who circumnavigated the globe several times as a fur trader. Most of the fur went to China in the 18th and early 19th century: Delano brought back porcelain to America. Even then there was a manufacturing trade deficit! He appears in Herman Melville's novella Benito Cereno.

Delano's book A Narrative of Voyages and Travels in the Northern and Southern Hemispheres (1817) describes his impressions of China in that era: 

China is ... the first for greatness, riches, and grandeur, of any country ever known.


Saturday, December 12, 2020

Hot and Cold Wars in the 21st Century

Both panels below are, in my opinion, realistic and focused on the key issues. Good discussion of competition in military technology is, in my experience, difficult to find for various reasons. On the US side there are strong MIC vested interests (e.g., in preserving the carrier-centric Navy) that lead to self-censorship of difficult realities. Also, very few analysts have actual technical and military expertise -- they are more likely to be "policy entrepreneurs" without deep knowledge.

See also The East Is Red, The Giant Rises and Ditchley Foundation meeting: World Order today.


See T.X. Hammes' report:  An Affordable Defense of Asia and this podcast interview with Marine Radio.


 


Robert Atkinson was also a guest on Manifold:



Bonus: blockchain based digital RMB?

 

Wednesday, December 09, 2020

Theory & Practice of Grand Strategy: Di Dongsheng, Renmin University (PRC)

Professor Di of Renmin University (a top university in Beijing, closely associated with the CCP) is now world famous, after Tucker Carlson and Donald Trump focused attention on his recent discussion of high level ties between PRC officials and US financial firms (second video below).
Di Dongsheng (LinkedIn CN) Professor Di’s research focuses on Political Economy of China’s Foreign Policy, Theories and Practices of Triangularity in International Relations, the Politics of Global Financial, Monetary and Investment Affairs, and the Theory & Practice of Grand Strategy.

Watch the first video below and decide for yourself whether he understands US politics and foreign policy better than most professors in the US.

I was more interested in the top video than the original one featured by Tucker/DJT. A few comments: 

1. He maps the US Deep State a bit too much onto government ministries in places like China or Japan, which also constitute a Deep State but are probably more meritocratically staffed. 

2. He is right that DJT's instincts lean more toward tariffs and trade deals (it often seemed he was reliving the US-Japan trade frictions of the 1980s) than towards hardcore technology and supply chain battles. 

3. Some of the really aggressive Deep State plotting against PRC came from DJT's own team -- it wasn't all pre-existing. In fact Trump's NSC green lighted a lot of nasty stuff that might now be reined in under Biden. I suppose you could argue that Trump's own NSC and cabinet were mostly Deep State people, but some like Navarro and Bannon certainly were not.





Glenn Greenwald (remember him? used to be a good guy until he started noticing too much stuff embarassing to the Left): The Hunter Biden Criminal Probe Bolsters a Chinese Scholar's Claim About Beijing's Influence With the Biden Administration Professor Di Dongsheng says China's close ties to Wall Street and its dealings with Hunter both enable it to exert more power now than it could under Trump.
... a Chinese scholar of political science and international finance, Di Donghseng, insisted that Beijing will have far more influence in Washington under a Biden administration than it did with the Trump administration. 
The reason, Di said, is that China’s ability to get its way in Washington has long depended upon its numerous powerful Wall Street allies. But those allies, he said, had difficulty controlling Trump, but will exert virtually unfettered power over Biden. That China cultivated extensive financial ties to Hunter Biden, Di explained, will be crucial for bolstering Beijing’s influence even further. 
Di, who in addition to his teaching positions is also Vice Dean of Beijing’s Renmin University’s School of International Relations, delivered his remarks alongside three other Chinese banking and development experts. Di’s speech at the event, entitled “Will China's Opening up of its Financial Sector Attract Wall Street?,” was translated and posted by Jennifer Zeng, a Chinese Communist Party critic who left China years ago, citing religious persecution [[ Falun Gong? ]], and now lives in the U.S.A source fluent in Mandarin confirmed the accuracy of the translation.
AddedWSJ Dec 10 : Barr Worked to Keep Hunter Biden Probes From Public View During Election. The attorney general knew for months about investigations into Biden’s business and financial dealings.

See also The East Is Red, The Giant Rises.

Sunday, December 06, 2020

AlphaFold 2: protein folding solved?

 

This is a good discussion of DeepMind's AlphaFold 2, a big breakthrough in protein folding. The details of how AlphaFold 2 works have not been published -- the video mainly discusses the January 2020 paper on the earlier version of AlphaFold, which already had world leading performance. However, it provides a good introduction both to protein folding as a physical / biological problem, as well as to AI/ML approaches.

I visited DeepMind in 2018 to give a talk on genomic prediction. I was hoping to get them interested! However, they were already focused on the protein folding problem. Most of my time there was spent discussing the latter topic with some of the AlphaFold team. They probably thought that a physicist who works on genomics might be worth talking to about protein folding, but I'm sure I learned more from them about it than vice versa...

In 2013 I blogged about a talk by Fields Medalist Stephen Smale on ML approaches to protein folding. He convinced me that ML approaches might work better than solving physics equations by brute force. 

Deep neural nets excel at learning high dimensional nonlinear functions that have some internal hierarchical structure (e.g., by length scale). Protein folding falls into this category. AlphaFold was able to utilize 170k training samples and extensive information from MSA (Multiple Sequence Alignment) which gives estimates of 3D distances: see, e.g., here.



Wednesday, December 02, 2020

Ditchley Foundation meeting: World Order Today


Thursday and Friday (Dec 3 and 4) I will participate in this Ditchley Foundation event, in honor of Henry Kissinger. I'm unsure whether I'm allowed to say who the other participants are.

Unfortunately the event is entirely virtual, unlike the meeting on genetic engineering I attended there in 2019. (Slides

A big focus of this meeting will be the role of China in the World Order (their terminology). Apropos of that, see this analysis by German academic Gunnar Heinsohn. Two of his slides appear below.

1. It is possible that by 2050 the highly able STEM workforce in PRC will be ~10x larger than in the US and comparable to or larger than the rest of the world combined. Here "highly able" means roughly top few percentile math ability in developed countries (e.g., EU), as measured by PISA at age 15.

2. The trajectory of international patent filings shown below is likely to continue. Note the catch-up pattern of S. Korea vs Germany over 25 years.

See earlier post The East is Red, the Giant Rises.

Wednesday, November 25, 2020

Macroscopic Superposition States in Isolated Quantum Systems


Happy Thanksgiving! :-)
Macroscopic Superposition States in Isolated Quantum Systems 
https://arxiv.org/abs/2011.11661   
Roman V. Buniy and Stephen D.H. Hsu 
For any choice of initial state and weak assumptions about the Hamiltonian, large isolated quantum systems undergoing Schrodinger evolution spend most of their time in macroscopic superposition states. The result follows from von Neumann's 1929 Quantum Ergodic Theorem. As a specific example, we consider a box containing a solid ball and some gas molecules. Regardless of the initial state, the system will evolve into a quantum superposition of states with the ball in macroscopically different positions. Thus, despite their seeming fragility, macroscopic superposition states are ubiquitous consequences of quantum evolution. We discuss the connection to many worlds quantum mechanics.
It may come as a surprise to many physicists that Schrodinger evolution in large isolated quantum systems leads generically to macroscopic superposition states. For example, in the familiar Brownian motion setup of a ball interacting with a gas of particles, after sufficient time the system evolves into a superposition state with the ball in macroscopically different locations. We use von Neumann's 1929 Quantum Ergodic Theorem as a tool to deduce this dynamical result. 

The natural state of a complex quantum system is a superposition ("Schrodinger cat state"!), absent mysterious wavefunction collapse, which has yet to be fully defined either in logical terms or explicit dynamics. Indeed wavefunction collapse may not be necessary to explain the phenomenology of quantum mechanics. This is the underappreciated meaning of work on decoherence dating back to Zeh and Everett. See talk slides linked here, or the introduction of this paper.

We also derive some new (sharper) concentration of measure bounds that can be applied to small systems (e.g., fewer than 10 qubits). 

Related posts:



Fun fact: Professor Buniy was a postdoc in my group at Oregon. Before coming to the US for graduate school in theoretical physics he was among the last group of young men to serve in the Soviet Army (Strategic Missile Forces IIRC!)

I suppose he has a document like this one:

Here he is in 2011, working on the null energy condition and instabilities in quantum field theories: 
 

Monday, November 23, 2020

Bruno Maçães on the election and Trump 2024

 

Post-election observations from Bruno Maçães. 

TrumpTV? Spectacle over Substance in 21st century American politics? Ivanka 2024? The Meme Industrial Complex?

If Bruno is correct the best we can hope for in the US is managed decline -- which is at least better than unmanaged decline!

Wednesday, November 18, 2020

Polls, Election Predictions, Political Correctness, Bounded Cognition (2020 Edition!)

Some analysis of the crap polling and poor election prediction leading up to Nov 2020. See earlier post (and comments): Election 2020: quant analysis of new party registrations vs actual votes, where I wrote (Oct 14)
I think we should ascribe very high uncertainty to polling results in this election, for a number of reasons including the shy Trump voter effect as well as the sampling corrections applied which depend heavily on assumptions about likely turnout. ... 
This is an unusual election for a number of reasons so it's quite hard to call the outcome. There's also a good chance the results on election night will be heavily contested.
Eric Kaufmann is Professor of Politics at Birkbeck College, University of London.
UnHerd: ... Far from learning from the mistakes of 2016, the polling industry seemed to have got things worse. Whether conducted by private or public firms, at the national or local, presidential or senatorial, levels, polls were off by wide margins. The Five Thirty-Eight final poll of polls put Biden ahead by 8.4 points, but the actual difference in popular vote is likely to be closer to 3-4 points. In some close state races, the error was even greater. 
Why did they get it so wrong? Pollsters typically receive low response rates to calls, which leads them to undercount key demographics. To get around this, they typically weight for key categories like race, education or gender. If they get too few Latinos or whites without degrees, they adjust their numbers to match the actual electorate. But most attitudes vary far more within a group like university graduates, than between graduates and non-graduates. So even if you have the correct share of graduates and non-graduates, you might be selecting the more liberal-minded among them. 
For example, in the 2019 American National Election Study pilot survey, education level predicts less than 1% of the variation in whether a white person voted for Trump in 2016. By contrast, their feelings towards illegal immigrants on a 0-100 thermometer predicts over 30% of the variation. Moreover, immigration views pick out Trump from Clinton voters better within the university-educated white population than among high school-educated whites. Unless pollsters weight for attitudes and psychology – which is tricky because these positions can be caused by candidate support – they miss much of the action. 
Looking at this election’s errors — which seems to have been concentrated among white college graduates — I wonder if political correctness lies at the heart of the problem
... According to a Pew survey on October 9, Trump was leading Biden by 21 points among white non-graduates but trailing him by 26 points among white graduates. Likewise, a Politico/ABC poll on October 11 found that ‘Trump leads by 26 points among white voters without four-year college degrees, but Biden holds a 31-point lead with white college graduates.’ The exit polls, however, show that Trump ran even among white college graduates 49-49, and even had an edge among white female graduates of 50-49! This puts pre-election surveys out by a whopping 26-31 points among white graduates. By contrast, among whites without degrees, the actual tilt in the election was 64-35, a 29-point gap, which the polls basically got right.
See also this excellent podcast interview with Kaufmann: Shy Trump Voters And The Blue Wave That Wasn’t 

Bonus (if you dare): this other podcast from the Federalist: How Serious Is The 2020 Election Fraud?

Added: ‘Shy Trump Voters’ Re-Emerge as Explanation for Pollsters’ Miss
Bloomberg: ... “Shy Trump voters are only part of the equation. The other part is poll deniers,” said Neil Newhouse, a Republican pollster. “Trump spent the last four years beating the crap out of polls, telling people they were fake, and a big proportion of his supporters just said, ‘I’m not participating.’” 
In a survey conducted after Nov. 3, Newhouse found that 19% of people who voted for Trump had kept their support secret from most of their friends. And it’s not that they were on the fence: They gave Trump a 100% approval rating and most said they made up their minds before Labor Day. 
Suburbanites, moderates and college-educated voters — especially women — were more likely to report that they had been ostracized or blocked on social media for their support of Trump. ... 
... University of Arkansas economist Andy Brownback conducted experiments in 2016 that allowed respondents to hide their support for Trump in a list of statements that could be statistically reconstructed. He found people who lived in counties that voted for Clinton were less likely to explicitly state they agreed with Trump. 
“I get a little frustrated with the dismissiveness of social desirability bias among pollsters,” said “I just don’t see a reason you could say this is a total non-issue, especially when one candidate has proven so difficult to poll.”

Tuesday, November 17, 2020

The East Is Red, The Giant Rises

Apologies for my recent inactivity. I've been busy finishing several projects and also distracted by our recent election.

Possibly the biggest global impact of this election is on US-China relations.

It seems likely that Biden will be our next president (although I am interested to see what closer inspection of the election reveals), and based on this I think odds have shifted in favor of a continued rise of the PRC in global economic and military power. I now think that the US lacks the will to counter China's continued rise: their main potential failure mode over the next 20 years is internal, not likely a consequence of external pressure. (Although of course there is still a chance the US and China will blunder into a war, with terrible consequences for the whole world.) 

Note I am not saying the US-China cold war or supply chain decoupling are off, just that the US is unlikely to put sufficient pressure on China to significantly retard its development over the next 20 years. This will have to be re-evaluated in 2024, of course, but we may pass the tipping point.

In 2004 I made some forecasts of where China would be in 2020. These forecasts were met with skepticism then but have mostly been correct. See

Benchmarks in China development: emergence of a middle class

Sustainability of China economic growth

My main assumptions were that the differential in growth rates between China and developed countries would average about 5 percent per year -- e.g. 7% vs 2%, and that China would largely close the technology gap.

A growth differential of +2-3% between now and 2050 would lead to a PRC economy which is about twice as large as the US economy (PPP). In 2004 I expected the PPP and nominal measures of Chinese GDP to narrow (I said over the next ~30 years, so I still have about 15 years for that to happen). If that occurs by 2050 then the PRC economy would be about twice as large as the US economy in nominal terms as well. GDP per capita in China would still be only half that of the US, but a 2-1 total GDP ratio has huge implications for geopolitics, the military balance of power, etc. (Note I am not even factoring in COVID-related impacts on the two economies, which are strongly in favor of PRC.) 

Another metric which should be carefully monitored is the ratio of STEM human capital between the two countries, which will continue to move significantly in China's favor.

I displayed the IMF figures below in my 2004 post on sustainability of Chinese economic growth. I felt that +20y along the trajectories described was realistic for PRC, and I was correct.

It would be interesting to see updated 2020 versions.

 

See also 

In my earlier post on Beijing I emphasized the issue of scale in China -- massive scale that is evident in the video above. 
I traveled in SE Asia before the 1997 currency / economic crisis. At that time there was plenty of evidence of a bubble in those countries -- unused infrastructure and real estate built on spec, few signs of real technological or productive capability, etc. China had aspects of that 10 years ago, but now it's apparent that earlier infrastructure investment is being put to good use. 
As I walked around Beijing I strained to find things around me -- buildings, solar panels, batteries, cars, high speed trains, electronics, software infrastructure, even airplanes -- that couldn't be sourced in China. Other than a few specific tech stacks that will get serious attention in coming years (e.g., CPUs) I was not able to think of many areas in which China has not caught up technologically. 
See Can the US derail China 2025?
There is a consistent Western cognitive bias concerning China: a severe underestimate of her capabilities and the capabilities of her people. This bias persists and analysts should carefully recalibrate in light of their previous predictions and the actual outcomes. Separate from this bias is an overall lack of knowledge and a willingness to accept lazy generalizations...

Saturday, October 31, 2020

Precision Embryo Genotyping and CRISPR Chromosome Deletions (Genomic Prediction)


This recent Cell paper received a lot of attention as it suggests that CRISPR editing can result in chromosome loss. It was cited in the recent National Academies report Heritable Human Genome Editing (2020) as an example of unexpected consequences / side-effects from CRISPR.
Allele-Specific Chromosome Removal after Cas9 Cleavage in Human Embryos 
https://doi.org/10.1016/j.cell.2020.10.025  
Correction of disease-causing mutations in human embryos holds the potential to reduce the burden of inherited genetic disorders and improve fertility treatments for couples with disease-causing mutations in lieu of embryo selection. Here, we evaluate repair outcomes of a Cas9-induced double-strand break (DSB) introduced on the paternal chromosome at the EYS locus, which carries a frameshift mutation causing blindness. We show that the most common repair outcome is microhomology-mediated end joining, which occurs during the first cell cycle in the zygote, leading to embryos with non-mosaic restoration of the reading frame. Notably, about half of the breaks remain unrepaired, resulting in an undetectable paternal allele and, after mitosis, loss of one or both chromosomal arms. Correspondingly, Cas9 off-target cleavage results in chromosomal losses and hemizygous indels because of cleavage of both alleles. These results demonstrate the ability to manipulate chromosome content and reveal significant challenges for mutation correction in human embryos. 
BioRxiv preprint 

My Genomic Prediction colleagues Jia Xu, Diego Marin, and Nathan Treff are co-authors of the paper. GP's precision embryo genotyping capabilities were necessary to determine that a paternal chromosome is sometimes deleted in the embryo due to CRISPR. In GP's standard embryo testing process both parents are genotyped as well as the embryo. The parental genotypes are used to error correct the embryo genotype: DNA amplification starting from just a few biopsied cells introduces noise, but it can be removed. GP can determine whether specific alleles from a parent are present in the embryo. Detection of the deletion of an entire chunk of chromosome would be fairly straightforward.

Thursday, October 29, 2020

Othram helps solve cold case: killer of Siobhan McGuinness (age 5) identified after 46 years




Othram, a DNA forensics company I co-founded, has helped to solve another cold case. 




Montana Girl, 5, Was Abducted Near Home and Found Dead in Drain — and Killer ID'd 46 Years Later 
For 46 years, the family of Siobhan McGuinness waited to find out who killed the spunky 5-year-old back in 1974 
On a frigid February afternoon in 1974, Siobhan McGuinness was walking the short distance home from a friend’s house in Missoula, Montana, when she vanished. Two days later, the 5-year-old’s body was found in a snow-covered drain culvert near the exit for Turah on I-90, just outside the city limits. She had been sexually assaulted. She also sustained trauma to her head and stab wounds to her chest, according to the FBI. 
Detectives at the time searched tirelessly for the little girl’s killer, but came up empty. The case went cold for decades. 
On Monday, authorities announced that after 46 years, the Missoula County Sheriff’s Office Cold Case Squad, detectives from the Missoula Police Department and others had finally identified the man who took the life of the spunky child who was always smiling. Richard William Davis was 32 when he was traveling through the area at the time of Siobhan’s murder, Missoula Police Chief Jason White said at a press conference on Monday. ... 
Using DNA left behind at the crime scene, specialists at private technology company Othram Inc. were able to create a genealogical profile of the suspect, which led them to Davis, the company says in a press release.


See Othram: the future of DNA forensics

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

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

What can you do with millions of genetic markers? 

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

If you have contacts in law enforcement, please alert them to the potential of this new technology.

Sunday, October 25, 2020

David Goldman (Spengler): China's Plan to Sino-Form the World



The latest from the always entertaining David Goldman, who writes (wrote?) the Spengler column at Asia Times.
 

In the lecture below, Goldman summarizes the main themes of his new book You Will Be Assimilated: China’s Plan to Sino-Form the World.

 


In this next interview (on the China-Iran deal of summer 2020) Goldman drops his guard a bit and waxes poetic with anti-Chinese rhetoric, as he discusses Israel, Iran, and China.

He refers to the Chinese (speaking broadly) as philo-semitic, but then jokes that this means anti-semites who like jews! In light of that remark I wonder how one should characterize Goldman's views on China and the Chinese: philo-sinic or just plain anti-Chinese?

Saturday, October 24, 2020

Composite Polygenic Risk Score predicts longevity

The paper below (senior author at Johns Hopkins University) builds a composite polygenic risk score for mortality (longevity). Outliers (top vs bottom 5%) differ by about 5 years in life expectancy. 

I expect longevity prediction to improve considerably with more and better data to analyze. See also Live Long and Prosper: Genetic Architecture of Complex Traits and Disease Risk Predictors:
We found that genetic risks are largely uncorrelated for different conditions. This suggests that there can exist individuals with, e.g., low risk simultaneously in each of multiple conditions, for essentially any combination of conditions. There is no trade-off required between different disease risks ... One could speculate that a lucky individual with exceptionally low risk across multiple conditions might have an unusually long life expectancy.

If I read the graph below correctly, in their late 70s a positive outlier (male) has ~90% chance of surviving (not sure of timescale, might be next few years? See comments), whereas for a negative outlier the odds are only ~75%.
Combined Utility of 25 Disease and Risk Factor Polygenic Risk Scores for Stratifying Risk of All-Cause Mortality 
Allison Meisner, Prosenjit Kundu, Yan Dora Zhang, Lauren V. Lan, Sungwon Kim, Disha Ghandwani, Parichoy Pal Choudhury, Sonja I. Berndt, Neal D. Freedman, Montserrat Garcia-Closas, Nilanjan Chatterjee 
doi: https://doi.org/10.1101/2020.03.13.20035527 
The American Journal of Human Genetics doi: 10.1016/j.ajhg.2020.07.002 
While genome-wide association studies have identified susceptibility variants for numerous traits, their combined utility for predicting broad measures of health, such as mortality, remains poorly understood. We used data from the UK Biobank to combine polygenic risk scores (PRS) for 13 diseases and 12 mortality risk factors into sex-specific composite PRS (cPRS). These cPRS were moderately associated with all-cause mortality in independent data: the estimated hazard ratios per standard deviation were 1.10 (95% confidence interval: 1.05, 1.16) and 1.15 (1.10, 1.19) for women and men, respectively. Differences in life expectancy between the top and bottom 5% of the cPRS were estimated to be 4.79 (1.76, 7.81) years and 6.75 (4.16, 9.35) years for women and men, respectively. These associations were substantially attenuated after adjusting for non-genetic mortality risk factors measured at study entry. The cPRS may be useful in counseling younger individuals at higher genetic risk of mortality on modification of non-genetic factors.

Thursday, October 22, 2020

Replications of Height Genomic Prediction: Harvard, Stanford, 23andMe

These are two replications of our 2017 height prediction results (also recently validated using sibling data) that I neglected to blog about previously.

1. Senior author Liang is in the Deptartments of Epidemiology and Biostatistics at Harvard.
Efficient cross-trait penalized regression increases prediction accuracy in large cohorts using secondary phenotypes 
Wonil Chung, Jun Chen, Constance Turman, Sara Lindstrom, Zhaozhong Zhu, Po-Ru Loh, Peter Kraft and Liming Liang 
Nature Communications volume 10, Article number: 569 (2019) 
We introduce cross-trait penalized regression (CTPR), a powerful and practical approach for multi-trait polygenic risk prediction in large cohorts. Specifically, we propose a novel cross-trait penalty function with the Lasso and the minimax concave penalty (MCP) to incorporate the shared genetic effects across multiple traits for large-sample GWAS data. Our approach extracts information from the secondary traits that is beneficial for predicting the primary trait based on individual-level genotypes and/or summary statistics. Our novel implementation of a parallel computing algorithm makes it feasible to apply our method to biobank-scale GWAS data. We illustrate our method using large-scale GWAS data (~1M SNPs) from the UK Biobank (N = 456,837). We show that our multi-trait method outperforms the recently proposed multi-trait analysis of GWAS (MTAG) for predictive performance. The prediction accuracy for height by the aid of BMI improves from R2 = 35.8% (MTAG) to 42.5% (MCP + CTPR) or 42.8% (Lasso + CTPR) with UK Biobank data.


2. This is a 2019 Stanford paper. Tibshirani and Hastie are famous researchers in statistics and machine learning. Figure is from their paper.


A Fast and Flexible Algorithm for Solving the Lasso in Large-scale and Ultrahigh-dimensional Problems 
Junyang Qian, Wenfei Du, Yosuke Tanigawa, Matthew Aguirre, Robert Tibshirani, Manuel A. Rivas, Trevor Hastie 
1Department of Statistics, Stanford University 2Department of Biomedical Data Science, Stanford University 
Since its first proposal in statistics (Tibshirani, 1996), the lasso has been an effective method for simultaneous variable selection and estimation. A number of packages have been developed to solve the lasso efficiently. However as large datasets become more prevalent, many algorithms are constrained by efficiency or memory bounds. In this paper, we propose a meta algorithm batch screening iterative lasso (BASIL) that can take advantage of any existing lasso solver and build a scalable lasso solution for large datasets. We also introduce snpnet, an R package that implements the proposed algorithm on top of glmnet (Friedman et al., 2010a) for large-scale single nucleotide polymorphism (SNP) datasets that are widely studied in genetics. We demonstrate results on a large genotype-phenotype dataset from the UK Biobank, where we achieve state-of-the-art heritability estimation on quantitative and qualitative traits including height, body mass index, asthma and high cholesterol.

The very first validation I heard about was soon after we posted our paper (2018 IIRC): I visited 23andMe to give a talk about genomic prediction and one of the PhD researchers there said that they had reproduced our results, presumably using their own data. At a meeting later in the day, one of the VPs from the business side who had missed my talk in the morning was shocked when I mentioned few cm accuracy for height. He turned to one of the 23andMe scientists in the room and exclaimed 

I thought WE were the best in the world at this stuff!?

Saturday, October 17, 2020

Down the Rabbit Hole: Mark Lane, the Zapruder film, and the JFK Conspiracy

Putting these here for future reference. From comments:
At minimum the evidence is strong for a CIA JFK coverup -- see last video, for example. It doesn't mean they did it, ofc. Johnson pressured Warren to lead the commission with the argument that if the public became convinced the Soviets/Cubans were behind it WW3 would result. This could have affected CIA actions post-Dallas as well. But I suspect something more sinister on the part of certain elements of CIA, and there is tons of evidence to that effect leaking out over the years. 
I enjoy listening to Mark Lane speak even if he turns out to be incorrect in some or many of his allegations. I think he destroys Buckley in their debate: Lane the Rationalist and Buckley a good example of motivated or biased reasoning. 
I've followed Spygate for 4 years now, with the media covering it up and FBI/CIA refusing to produce documents, Barr probably acting to protect the institutions, FISA court obviously corrupt, etc. The JFK matter has a very familiar feel to it. [ Should add the Epstein matter, which unfolded in plain sight over 20y, as another example. ]
Mark Lane, at the peak of his powers, discusses the Warren Commission report with William F. Buckley (1966):

   

 Mark Lane, near the end of his life:

    


Astonishing 2014 claims about the Zapruder film in CIA hands in the days after Dallas: the creation of two different briefing boards, one seen by CIA director John McCone, the other given to the Warren Commission. The interview is remarkable.

 

Horne and Brugioni strike me as very credible. CIA NPIC's main activity was interpreting U2 spy plane photographs, and had some of the most advanced photographic technology of the era. They were a logical choice to have a first look at the Zapruder film, but Brugioni did not learn until decades later that the CIA modified the film (removing certain frames, esp. near #313 which shows Kennedy's head exploding) and only gave a full briefing to McCone while witholding information from the Warren Commission. 
While serving as chief analyst of military records at the Assassination Records Review Board in 1997, Douglas Horne discovered that the Zapruder Film was examined by the CIA's National Photographic Interpretation Center two days after the assassination of President Kennedy. 
In this film, Horne interviews legendary NPIC photo interpreter Dino Brugioni, who speaks for the first time about another NPIC examination of the film the day after the assassination. Brugioni didn't know about the second examination and believes the Zapruder Film in the archives today is not the film he saw the day after the assassination.

Bonus: Interview with son of E. Howard Hunt (CIA, convicted Watergate Plumber), including audio of Hunt's confession. Note link to Cord Meyer, also see Mary Meyer 1964 execution in Georgetown...


James Jesus Angleton -- "A Wilderness of Mirrors"



Note Added in response to a question in the comments:
I suggest you invest an hour or two in 
1. Brugioni interview: establishes that a conspiracy at the highest level of CIA to alter the film evidence was in place within ~24h of the shooting. Hard to explain unless there was very strong motivation already... bureaucracies usually can't react that fast when *surprised* by events. 
2. Interview with Hunt's son, concerning his deathbed confession of being aware of (and playing a minor role in) the assassination conspiracy. Hunt is a well-known CIA figure who was involved in lots of covert ops including Watergate. You don't have to accept this as fully credible of course, but you can't say that conspiracy didn't happen because otherwise information would have leaked out. It may very well have leaked out! But few pay attention because of the groupthink against "conspiracy theory" (this term was literally invented and promulgated by CIA to discourage public attention to what it was doing during the Cold War).   
I would say I am very confident of an active cover up post assasination, less confident of a CIA role in the killing. 
Other facts that have leaked out (now confirmed by official documents and the official CIA historian) include the fact that CIA was very closely monitoring Oswald starting in 1959 and that his file was closely held by none other than CIA prince of darkness James Jesus Angleton. Now look into the unsolved killing of Angleton's friend Mary Meyer (who was having an affair with JFK when he was shot) in 1964 and you are off to the races... Their common friend Ben Bradlee (WaPo editor of Watergate fame) wrote in his memoirs of catching Angleton, having broken into Meyer's house, with her diary... 
BTW, over the years it was wrongly reported that RFK did NOT believe in a conspiracy against his brother. The evidence is pretty convincing now that he always believed in a conspiracy but didn't admit it in public.

Wednesday, October 14, 2020

Election 2020: quant analysis of new party registrations vs actual votes

I think we should ascribe very high uncertainty to polling results in this election, for a number of reasons including the shy Trump voter effect as well as the sampling corrections applied which depend heavily on assumptions about likely turnout. 

Graphs below are from a JP Morgan quant analysis of changes in number of registered voters by party and state, and the correlation with actual votes in subsequent election. Of course it is possible that negative covid impact has largely counteracted the effect discussed below (which is an integrated effect over the last 4 years) -- i.e., Trump was in a strong position at the beginning of 2020 but has declined since then. 

This is an unusual election for a number of reasons so it's quite hard to call the outcome. There's also a good chance the results on election night will be heavily contested.

The author of this analysis is Marko Kolanovic, Global Head of Macro Quantitative and Derivatives Strategy at J.P. Morgan. He graduated from New York University with a PhD in theoretical high-energy physics.

Anyone with high conviction about the election is welcome to post their analysis in the comments.

Sunday, October 11, 2020

US and China: A New Cold War (video interview with Lanxin Xiang)

 

This is an excellent discussion of the US-China geopolitical situation with Professor Lanxin Xiang. Xiang was trained at SAIS (JHU PhD), and currently holds an academic position in Geneva while directing a research institute in Shanghai.

He has a uniquely deep understanding of both Western and Chinese perspectives on globalization, economic development, US-China competition. 

Interestingly, he recently translated Skidelsky's biography of Keynes.

Two related articles in Asia Times by the Brazilian journalist Pepe Escobar:





Bonus: Bill Owens interview. See comments about Huawei at ~50m.

 

Wikipedia: William A. Owens (born May 8, 1940) is a retired admiral of the United States Navy and who served as Vice Chairman of the Joint Chiefs of Staff from 1994 to 1996.[1][2] Since leaving the military in 1996, he served as an executive or as a member of the board of directors of various companies, including Nortel Networks Corporation.

Sunday, October 04, 2020

Othram Helps Solve 1974 Cold Case: Carla Walker Murder


Othram, a DNA forensics company I co-founded, has solved another cold case. 


Carla Walker of Fort Worth TX was tortured, raped, and murdered in 1974. Finally the killer has been identified and arrested.



This was an open and high profile case just a few months ago. See this April 2020 episode of The DNA of Murder (Oxygen channel), hosted by Paul Holes, the detective who caught the Golden State Killer.

Who Killed Carla Walker? In 1974, 17-year-old Carla Walker’s reported abduction out of the arms of her boyfriend sent a Texas town on a massive manhunt. She was discovered murdered in a culvert three days later. Paul Holes interviews the only witness, Carla’s boyfriend. 
Walker and her boyfriend, Western Hills High School football quarterback Rodney McCoy, attended a Valentine’s dance on Feb. 16, 1974. After the dance, they met up with friends and then stopped by a Fort Worth bowling alley. 
McCoy has always maintained that a man approached the couple while they were sitting inside his car at the bowling alley parking lot and pointed a gun at him. He was beaten unconscious, and when he awoke, he found his cheerleader girlfriend missing.

 



See Othram: the future of DNA forensics

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

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

What can you do with millions of genetic markers? 

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

If you have contacts in law enforcement, please alert them to the potential of this new technology.

Genomic Prediction and Embryo Selection (video panel discussion)

 


This is a recent panel discussion on genomic prediction, and applications in IVF and health systems (e.g., early screening of high risk individuals for breast cancer, heart disease). 

Jamie Metzl and Simon Fishel are my co-panelists. Metzl is the author of the best seller Hacking Darwin: Genetic Engineering and the Future of Humanity. Fishel was part of the team that produced the first IVF baby in 1978, and has been a leader in IVF research ever since. 

Today millions of babies are produced through IVF. In most developed countries roughly 3-5 percent of all births are through IVF, and in Denmark the fraction is about 10 percent! But when the technology was first introduced with the birth of Louise Brown in 1978, the pioneering scientists had to overcome significant resistance. There may be an alternate universe in which IVF was not allowed to develop, and those millions of children were never born.
Wikipedia: ...During these controversial early years of IVF, Fishel and his colleagues received extensive opposition from critics both outside of and within the medical and scientific communities, including a civil writ for murder.[16] Fishel has since stated that "the whole establishment was outraged" by their early work and that people thought that he was "potentially a mad scientist".[17]
I predict that within 5 years the use of polygenic risks scores will become common in some health systems and in IVF. Reasonable people will wonder why the technology was ever controversial at all, just as in the case of IVF.

Previous discussion: Sibling Validation of Polygenic Risk Scores and Complex Trait Prediction (Nature Scientific Reports)

Monday, September 28, 2020

Feynman on AI

Thanks to a reader for sending the video to me. The first clip is of Feynman discussing AI, taken from the longer 1985 lecture in the second video.

There is not much to disagree with in his remarks on AI. He was remarkably well calibrated and would not have been very surprised by what has happened in the following 35 years, except that he did not anticipate (at least, does not explicitly predict) the success that neural nets and deep learning would have for the problem that he describes several times as "pattern recognition" (face recognition, fingerprint recognition, gait recognition). Feynman was well aware of early work on neural nets, through his colleague John Hopfield.  [1] [2] [3]

I was at Caltech in 1985 and this is Feynman as I remember him. To me, still a teen ager, he seemed ancient. But his mind was marvelously active! As you can see from the talk he was following the fields of AI and computation rather closely. Of course, he and other Manhattan project physicists were present at the creation. They had to use crude early contraptions for mechanical calculation in bomb design computations. Thus, the habit of reducing a complex problem (whether in physics or machine learning) to primitive operations was second nature. Already for kids of my generation it was not second nature -- we grew up with early "home computers" like the Apple II and Commodore, so there was a black box magic aspect already to programming in high level languages. Machine language was useful for speeding up video games, but not everyone learned it. The problem is even worse today: children first encounter computers as phones or tablets that already seem like magic. The highly advanced nature of these devices discourages them from trying to grasp the underlying first principles.  

If I am not mistaken the t-shirt he is wearing is from the startup Thinking Machines, which built early parallel supercomputers.

Just three years later he was gone. The finely tuned neural connections in his brain -- which allowed him to reason with such acuity and communicate with such clarity still in 1985 -- were lost forever.



Monday, September 21, 2020

Foreign Observers of US Empire

Four recommended discussions, with perspectives largely absent from US media and establishment sources. 

1. US, Russia, China, Iran: Geopolitics and Realpolitik, discussed by a former UK diplomat, a professor at Tehran University, and a Brazilian journalist who covers Eurasia, living in Thailand.

   


2. Carl Zha, Caltech alumnus and China watcher. TikTok, WeChat, Huawei, semiconductors. The insidious role of US intelligence agencies in the tech war. Part 2.

      


3. Columbia economic historian Adam Tooze: World Order, Then And Now, ChinaTalk Podcast. Among other topics: State Capitalism, or National Socialism? Why Carl Schmitt is widely studied among Chinese intellectuals. The US won the cold war in Europe, but perhaps not in Asia...  More Tooze


4. The New Great Game: Bruno Maçães and diplomat, writer and former National Security Adviser Shivshankar Menon discuss Asia’s search for a constructive new equilibrium in the wake of growing tensions between China and its neighbours.

 


Bonus! Energy, Geopolitics, And The New Map: A Book Talk With Daniel Yergin.

 

Manhattan Institute: 

The shale revolution brought about not only an American competitive advantage in the global oil and gas market, but also an entirely new geopolitical dynamic. Energy is the bedrock of every industrial economy, and even minor shifts in production and prices have had resounding impacts on international diplomacy. 

Today, the global energy landscape differs drastically from a decade ago. The U.S. now leads the world in oil production thanks to fracking, and the world is reacting. But even as Russia pivots to China, and Middle Eastern producers try to recalibrate, every oil-producing country faces the same questions about the future of energy: Will renewable energy reign? And how will international relationships fare with this new map? These issues will become even more controversial during the presidential campaigns.

See also Remarks on the Decline of American Empire for earlier discussion of the impact of fracking on geopolitics.

Saturday, September 19, 2020

When Machine Learning Met Genetic Engineering | CogX 2019 (video)

 

I recently came across this video on YouTube. 

Hard to believe it's been over a year since the conference. 2020 versions of these meetings were all killed by the pandemic.



I'm in London again to give the talk below and attend some meetings, including Founders Forum and their Healthtech event the day before.
CogX: The Festival of AI and Emerging Technology
King's Cross, London, N1C 4BH

When Machine Learning Met Genetic Engineering

3:30 pm Tuesday June 11 Cutting Edge stage

Speakers

Stephen Hsu
Senior Vice-President for Research and Innovation
Michigan State University

Helen O’Neill
Lecturer in Reproductive and Molecular Genetics
UCL

Martin Varsavsky
Executive Chairman
Prelude Fertility

Azeem Azhar (moderator)
Founder
Exponential View

Regent's Canal, Camden Town near King's Cross.





CogX speakers reception, Sunday evening:



HealthTech


Commanding heights of global capital:



Sunset, Camden locks:


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