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Physicist, Startup Founder, Blogger, Dad

Friday, May 31, 2013

First GWAS hits for cognitive ability

This is NOT the BGI Cognitive Genomics project, it's the Social Science Genetic Association Consortium. Their main phenotype is educational attainment, but they also have Swedish conscript scores for cognitive ability. IIUC the largest effect size is smaller than that for the corresponding height loci (1/4.5 as big in units of population SD; 1/20 as big in units of variance), which suggests that cognitive ability will be harder than, but perhaps not qualitatively different from, height. The results also support the conclusion from SNP-based heritability estimates that a significant fraction of total genetic variance is due to common variants. I expect we will find that both common and rare (mutational load) variants contribute to variation in cognitive ability.
GWAS of 126,559 Individuals Identifies Genetic Variants Associated with Educational Attainment (Science)

A genome-wide association study of educational attainment was conducted in a discovery sample of 101,069 individuals and a replication sample of 25,490. Three independent SNPs are genome-wide significant (rs9320913, rs11584700, rs4851266), and all three replicate. Estimated effects sizes are small (R2 ≈ 0.02%), approximately 1 month of schooling per allele. A linear polygenic score from all measured SNPs accounts for ≈ 2% of the variance in both educational attainment and cognitive function. Genes in the region of the loci have previously been associated with health, cognitive, and central nervous system phenotypes, and bioinformatics analyses suggest the involvement of the anterior caudate nucleus. These findings provide promising candidate SNPs for follow-up work, and our effect size estimates can anchor power analyses in social-science genetics.
Clueless extremists may want to point and shout "Eugenics!" at these researchers, but I wouldn't recommend it. Sample author affiliations below -- no sinister Chinese institutions as far as I can tell  ;-)
1 Department of Applied Economics, Erasmus School of Economics, Erasmus University Rotterdam, 3000 DR Rotterdam, The Netherlands.
2 Department of Epidemiology, Erasmus Medical Center, Rotterdam 3000 CA, The Netherlands.
3 Queensland Institute of Medical Research, 300 Herston Road, Brisbane, Queensland 4006, Australia.
4 Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO 80309–0447, USA.
5 University of Queensland Diamantina Institute, The University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland 4102, Australia.

...

125 Centre for Medical Systems Biology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
126 Department of Economics, Cornell University, Ithaca, NY 14853, USA.
127 Center for Experimental Social Science, Department of Economics, New York University, New York, NY 10012, USA.
128 Division of Social Science, New York University Abu Dhabi, PO Box 129188, Abu Dhabi, UAE.
129 Research Institute of Industrial Economics, Stockholm 102 15, Sweden.

I expect the future of this kind of research to look like earlier GWAS, with steady accumulation of hits now that we have passed the statistical power threshold.



Related: Myopia GWAS results (Nature Genetics).

Note Added: I've been asked by several people whether this is a discouraging result. If effect sizes are so small, won't it take enormous sample sizes to detect specific alleles accounting for a big chunk of total genetic variance? There is some relevant discussion in the supplement to the paper (see figure S22 and section 7). The answer to the question really depends on the correlation between g and years of education (most of the data these researchers had access to specified educational attainment as the phenotype, with no direct measurement of g). If, for example, the correlation is 0.5, and it is actually g that is driving the effect on years of education, then the corresponding g effect size for these alleles is (1/0.5)^2 or 4 times larger in variance units. This makes the g effect size in variance units about 5 times smaller than for the corresponding largest height locus. However, if the correlation is only 0.25, the g effect is about as big as the largest height locus. Having looked at correlations between SAT and college GPA, I'd guess that 0.5 is too large, but on the other hand in the Swedish sample for which they have both g and years of education the correlation is 0.46. Using 0.5 as the correct correlation, the minimal sample size with actual g data to detect these rs alleles is (see Fig S22) in the 20-50k range. I'd guess that, worst case, the sample size requirements are still less than an order of magnitude larger for g than for height. However, one can't be very confident of any guess because of the uncertainties discussed above, and because we've only seen the first few alleles.

Thursday, May 30, 2013

Long term investing

Will it move the needle? Perhaps.
New Yorker: ... This week, Stephen Schwarzman, the chairman and chief executive of the Blackstone Group, invoked Rhodes’s gift as the inspiration behind a large new scholarship for study not in America but in China. He is hoping that familiarity with the world’s rising superpower will blunt growing American anxiety about changes in status. “Anger can lead to trade problems, and ultimately to military confrontation,” he told me. “We had to find a way to stop or ameliorate that situation.” The scholarship will draw two hundred students a year to a one-year English-language master’s program at a dedicated new college inside Tsinghua University. Twenty per cent of the winners will be from China, forty-five per cent from America, and the remainder from elsewhere. Schwarzman is giving a hundred million of a personal fortune estimated at $6.5 billion, and raising another two hundred million largely from blue-chip companies with big investments in China, to create an endowment that the Times calls “one of the largest single gifts to education in the world and one of the largest philanthropic gifts ever in China.”

[Schwarzman:] ... I sat down with President Chen and I said to him, “If we do this, what I really want to do is construct a program that that has the same prestige as the Rhodes, because those are the students that I’m aiming for.” In 1902, going to Oxford was sine qua non. J. P. Morgan worked in London after he graduated from college, because that’s what you did. And then he came back to the States.

But the world has certainly changed, and one of the things that was really driving me to do this is that I could see the negative attitudes that people had toward China were bubbling. The financial crisis, where growth rates in Europe went to zero or worse— everything went down; jobs in the United States have been very slow to come back. By the same token, in China they’re growing, at that point, nine per cent a year. And meanwhile the West is quite damaged and remains damaged from a job-creation point of view.

And I was convinced that that would create frustration in the West, and frustration would lead to anger, and that anger can lead to trade problems, and ultimately to military confrontation. And if China was going to grow at two to three times the [rate of] so-called developed countries, that within two decades, if those trends continue, they’d go from the No. 2 economy in the world to the No. 1, and whatever problems you are seeing today in these areas of frustration would be that much greater. And at a certain point, it seemed logical to me that you’d start to have some really bad things with a much higher probability of occurring. We had to find a way to stop or ameliorate that situation.

And I looked at this idea, this type of program, as a way to produce people who would have that kind of understanding of China that they wouldn’t have had, as they go back to their regular lives—to observe what’s happening in China and interpret it to their constituencies and their industries and their world. This network, at maturity, will be ten thousand kids; some will be seventy-five years old, but that’s a lot of people, spread around the world at a very high level. And so they can react to China, interpret what they’re doing. They can tell the Chinese that they’ve overdone it in certain cases, and they can also form their own global network to deal with other issues, whether they’re global or bilateral, because they’ll know people who are, I guess you would say, more kindred souls, who have a shared experience. So that’s what’s behind this.
When I met with Stephen Smale recently he said the undergraduate math students at Beida (Beijing University) and Tsinghua were the strongest group he knew of in the world today. See also Tsinghua uber alles.

Monday, May 27, 2013

Inter-universal Geometer Mochizuki



Mathematics certainly does not lack for eccentric geniuses. Mochizuki homepage. See these slides from his "pedagogical" lecture Invitation to Inter-universal Teichmuller Theory  :-)
The Paradox of the Proof: ... The problem, as many mathematicians were discovering when they flocked to Mochizuki’s website, was that the proof was impossible to read. The first paper, entitled “Inter-universal Teichmuller Theory I: Construction of Hodge Theaters,” starts out by stating that the goal is “to establish an arithmetic version of Teichmuller theory for number fields equipped with an elliptic curve…by applying the theory of semi-graphs of anabelioids, Frobenioids, the etale theta function, and log-shells.”

This is not just gibberish to the average layman. It was gibberish to the math community as well.

“Looking at it, you feel a bit like you might be reading a paper from the future, or from outer space,” wrote Ellenberg on his blog.

“It’s very, very weird,” says Columbia University professor Johan de Jong, who works in a related field of mathematics.

Mochizuki had created so many new mathematical tools and brought together so many disparate strands of mathematics that his paper was populated with vocabulary that nobody could understand. It was totally novel, and totally mystifying.

As Tufts professor Moon Duchin put it: “He’s really created his own world.”

It was going to take a while before anyone would be able to understand Mochizuki’s work, let alone judge whether or not his proof was right. In the ensuing months, the papers weighed like a rock in the math community. A handful of people approached it and began examining it. Others tried, then gave up. Some ignored it entirely, preferring to observe from a distance. As for the man himself, the man who had claimed to solve one of mathematics’ biggest problems, there was not a sound.

... When Mochizuki posted his papers, the math community had much reason to be enthusiastic. They were excited not just because someone had claimed to prove an important conjecture, but because of who that someone was.

Mochizuki was known to be brilliant. Born in Tokyo, he moved to New York with his parents, Kiichi and Anne Mochizuki, when he was 5 years old. He left home for high school, attending Philips Exeter Academy, a selective prep school in New Hampshire. There, he whipped through his academics with lightning speed, graduating after two years, at age 16, with advanced placements in mathematics, physics, American and European history, and Latin.

Then Mochizuki enrolled at Princeton University where, again, he finished ahead of his peers, earning his bachelor’s degree in mathematics in three years and moving quickly onto his Ph.D, which he received at age 23. After lecturing at Harvard University for two years, he returned to Japan, joining the Research Institute for Mathematical Sciences at Kyoto University. In 2002, he became a full professor at the unusually young age of 33. His early papers were widely acknowledged to be very good work.

Academic prowess is not the only characteristic that set Mochizuki apart from his peers. His friend, Oxford professor Minhyong Kim, says that Mochizuki’s most outstanding characteristic is his intense focus on work.

“Even among many mathematicians I’ve known, he seems to have an extremely high tolerance for just sitting and doing mathematics for long, long hours,” says Kim.

Mochizuki and Kim met in the early 1990s, when Mochizuki was still an undergraduate student at Princeton. Kim, on exchange from Yale University, recalls Mochizuki making his way through the works of French mathematician Alexander Grothedieck, whose books on algebraic and arithmetic geometry are a must-read for any mathematician in the field.

“Most of us gradually come to understand [Grothendieck’s works] over many years, after dipping into it here and there,” said Kim. “It adds up to thousands and thousands of pages.”

But not Mochizuki.

“Mochizuki…just read them from beginning to end sitting at his desk,” recalls Kim. “He started this process when he was still an undergraduate, and within a few years, he was just completely done.” ...
In other news, "unheralded" mathematician Yitang Zhang proves the (weak) twin primes conjecture. Remarks by his PhD supervisor at Purdue; Zhang was reputed to be one of the top mathematics students in his class at Beijing University, so, despite his difficult career path, he was not exactly an unknown quantity.

I have only limited interest in number theory (for some reason it just does not get me excited), but unlimited admiration for people like Mochizuki and Zhang (and Perelman and so on). I think someone once described Wiles' proof of Fermat's last theorem as a "triumph of the human spirit" -- I could not agree more!

Thursday, May 23, 2013

Sisu: Mikko Salo documentary



Documentary on Crossfit athlete Mikko Salo. His resting heart rate is 31 bpm! See also here.

Great deadlift / burpee metcon @34min. Compare to lullaby :-)
Wikipedia: Sisu is a Finnish term loosely translated into English as strength of will, determination, perseverance, and acting rationally in the face of adversity. However, the word is widely considered to lack a proper translation into any other language. Sisu has been described as being integral to understanding Finnish culture. However sisu is defined by a long-term element in it; it is not momentary courage, but the ability to sustain an action against the odds. Deciding on a course of action and then sticking to that decision against repeated failures is sisu. It is similar to equanimity, except the forbearance of sisu has a grimmer quality of stress management than the latter.
See Pessimism of the intellect, optimism of the will.

Wednesday, May 22, 2013

Next (and Next Next) Generation DNA Sequencing Methods



This is from 2012 but seems to cover most of the Next Gen platforms currently in use (for some reason he skips over the Complete Genomics slide). There seems to have been a slight plateau recently in the sequencing cost curve; I wonder whether when the next jump will happen ... The conventional wisdom is that the bioinformatics costs now dominate the sequencing cost but I think that can be fixed using existing computing technology (i.e., it is more predictable than a big breakthrough in molecular method).

Does anyone know of a comparable talk that is a bit more recent?

Sunday, May 19, 2013

A hockey coach?!?



The last post, entitled To the brainy, the spoils, linked to an Economist article about management consulting. It would appear that in the public sector, the highest paid employees tend to work in a tax-exempt sports-entertainment complex that is, for strange historical reasons, hosted by the higher education system. (Via UOMatters)

Thursday, May 16, 2013

To the brainy, the spoils


Economist: ... Big trends that befuddle clients mean big money for clever consultants. Barack Obama’s gazillion-page health reform has boosted health-care consulting; firms would rather pay up than read the blasted thing. The Dodd-Frank financial reform has done the same for financial-sector work. Energy and technology are hot, too.

Companies are reluctant to talk about their use of consultants, and consultancies are relentlessly tight-lipped. Bain is said to use code-names for clients even in internal discussions. Such secrecy makes this a hard industry to analyse.

It also lets stereotypes flourish. McKinseyites are said to be “vainies” (who come and lecture clients on the McKinsey way). BCG people are “brainies” (who spout academic theory). And the “Bainies” have a reputation for throwing bodies at delivering quick bottom-line results for clients. ...
See here for discussion of hiring practices at what I refer to as "soft-elite" firms such as consultancies.
...

4) In Rivera's research school prestige was the number one signal used by soft elite firms in evaluating prospective hires. Extracurricular activities came in second, but this is probably just a way to differentiate between applicants who have already been filtered using school prestige.

5) It is odd that the soft firms, which market themselves to clients as being super-smart repositories of brainpower (of course this is largely a fiction; see point 3 above), would rely so heavily on university admissions committees. They effectively outsource a big chunk of due diligence on their most important investment (human capital) to a group of people whose judgement they somehow trust, but perhaps without detailed understanding. When I was on the faculty at Yale I knew people in admissions and it's not clear to me that they were the best able to spot potential in 18 year olds. In studies of expert performance admissions people are less good at predicting UG GPA than a simple algorithm. (The "algorithm" is simply a weighted sum of SAT and HS GPA!)

But this doesn't matter if the success of HYPS grads becomes a self-fulfilling prophecy. Once soft elite firms and large parts of the rest of society (in particular, clients) have accepted the idea that elite universities should be trusted to do the filtering, these schools will automatically produce large numbers of successful alumni -- the imprimatur itself has value. The outsourcing of human capital filtering is more dangerous for hard elite firms, with their more objective criteria: if they find that Yale grads aren't actually any good at pricing derivatives, writing code or designing chips, then they'll have to adopt a different filter. Fortunately, since even the dumbed down SAT is still pretty g loaded, hard elite firms can be confident that the lion's share of top talent is at elite universities.
An excerpt from Lauren Rivera's article on elite firm hiring:
... In addition to such an intelligence-based perspective on university admissions, evaluators frequently adopted an instrumental and unconstrained view of university enrollment, perceiving that students typically “go to the best school they got into” (lawyer, Hispanic, male). Consequently, in the minds of evaluators, prestige rankings provided a quick way to sort candidates by “brainpower.” When sorting the “mock” resumes, an investment banking recruiter (white, female) charged with screening resumes at her firm revealed how such assumptions played out in application review. She remarked, “Her [Sarah's] grades are lower but she went to Harvard so she's definitely well-endowed in the brain category…Jonathan… went to Princeton, so he clearly didn’t get the short end of the stick in terms of smarts.” This halo effect of school prestige, combined with the prevalent belief that the daily work performed within professional service firms was “not rocket science” (see Rivera, 2010a) gave evaluators confidence that the possession of an elite credential was a sufficient signal of a candidate's ability to perform the analytical capacities of the job. Even in the quantitatively rigorous field of consulting [HA HA HA], a junior partner (white, male) asserted, “I’ve come to the stage where I trust that if the person has gone to Wharton, they can do math.”

By contrast, failure to attend an “elite” school, as conceptualized by evaluators, was an indicator of intellectual failure, regardless of a student's grades or standardized test scores. Many evaluators believed that high achieving students at lesser ranked institutions “didn’t get in to a good school,” must have “slipped up,” or otherwise warranted a “question mark” around their analytical abilities. ...

Tuesday, May 14, 2013

Nature News: Chinese project probes the genetics of genius



This article is mostly correct -- see my comments below in [[ brackets ]]. As usual the Chinese connection is emphasized in the title, even though Plomin (Kings College London) is the more experienced researcher in this area, and most of our DNA samples come from US citizens.

To clarify, my main motivation for understanding the genetics of cognition derives from the observation that the human brain, the most complex object we know of in the universe, is produced from a genetic code of only gigabits in length. How, exactly, this works is one of the greatest scientific mysteries. Genomic selection and other "spin-offs" from this research are of secondary interest.
Nature News: The US adolescents who signed up for the Study of Mathematically Precocious Youth (SMPY) in the 1970s were the smartest of the smart, with mathematical and verbal-reasoning skills within the top 1% of the population. Now, researchers at BGI (formerly the Beijing Genomics Institute) in Shenzhen, China, the largest gene-sequencing facility in the world, are searching for the quirks of DNA that may contribute to such gifts. Plunging into an area that is littered with failures and riven with controversy, the researchers are scouring the genomes of 1,600 of these high-fliers in an ambitious project to find the first common genetic variants associated with human intelligence.

[[ SMPY qualifiers scored at the 1 in 10k level on the math portion of the SAT. Due to the positive correlation between M and V they almost all have V scores in the top half of one percent. ]]

The project, which was launched in August 2012 and is slated to begin data analysis in the next few months, has spawned wild accusations of eugenics plots, as well as more measured objections by social scientists who view such research as a distraction from pressing societal issues. Some geneticists, however, take issue with the study for a different reason. They say that it is highly unlikely to find anything of interest — because the sample size is too small and intelligence is too complex.

Earlier large studies with the same goal have failed. But scientists from BGI’s Cognitive Genomics group hope that their super-smart sample will give them an edge, because it should be enriched with bits of DNA that confer effects on intelligence. “An exceptional person gets you an order of magnitude more statistical power than if you took random people from the population — I’d say we have a fighting chance,” says Stephen Hsu, a theoretical physicist from Michigan State University in East Lansing, who acts as a scientific adviser to BGI and is one of the project’s leaders.

“If they think they’re likely to get much useful data out of this study, they’re almost certainly wrong,” says Daniel MacArthur, a geneticist at Massachusetts General Hospital in Boston. He is not against intelligence studies in principle, despite the visceral reactions they provoke in some people. “Studying intelligence is useful for understanding cognitive function, or diseases” that affect it, he says. But he questions whether the study will work.

[[ Not exactly sure what Dan means by "useful data" here. It's true that we don't anticipate getting more than a few genome-wide significant hits from a GWAS analysis. We may get zero! ]]

... Both Plomin and Hsu are passionate enough to take a shot, although their goals differ. Hsu is focused on the genetic basis of extreme intelligence. “My primary interest is why Einstein or Hawking is different from a normal person,” he says. Plomin is sequencing high-performers as a way of homing in on genes that affect intelligence in the broader population. If enough of these are discovered, he thinks that it may be possible to predict someone’s intelligence from an early age, and to offer help to children who are at risk of learning disabilities.

[[ This may give the false impression that it's a different genetic mechanism that gives rise to "extreme" intelligence as opposed to normal variation. ]]

Publicity around the project has spawned some extreme reactions. An article published in March entitled ‘China is Engineering Genius Babies’ in the US arts and culture magazine VICE branded the study “a state-endorsed genetic-engineering project” that will allow parents to predict the IQs of embryos and selectively breed ever-smarter children. (“That’s nuts,” says Hsu.) “Intelligence does push a lot of buttons. It’s like waving a red flag to a bull,” says Plomin. He argues that there is nothing wrong with using genetic information as the basis of educational interventions. “I’m interested in predicting learning problems early rather than waiting until kids get to school and then fail,” he says. ...

Monday, May 13, 2013

NGS, GATK and all that



This is a nice introduction to the nuts and bolts of next-generation sequencing. Slides. Related talks from a workshop on GATK (Broad Institute's Genome Analysis Tool Kit).

Sunday, May 12, 2013

Dennett and Intuition Pumps



At the bookstore today I spent some time looking at Intuition Pumps And Other Tools for Thinking, Daniel Dennett's new book. I highly recommend his Darwin's Dangerous Idea, discussed earlier here. I'm not a big fan of Dennett's work on free will and determinism (for my views, see this old post and also here), but we seem to share the same opinion of John Searle's Chinese Room.

For more Dennett, see this Stanford Humanities Center lecture (iTunes video).
NYTimes: ... The new book, largely adapted from previous writings, is also a lively primer on the radical answers Mr. Dennett has elaborated to the big questions in his nearly five decades in philosophy, delivered to a popular audience in books like “Consciousness Explained” (1991), “Darwin’s Dangerous Idea” (1995) and “Freedom Evolves.”

The mind? A collection of computerlike information processes, which happen to take place in carbon-based rather than silicon-based hardware.

The self? Simply a “center of narrative gravity,” a convenient fiction that allows us to integrate various neuronal data streams.

The elusive subjective conscious experience — the redness of red, the painfulness of pain — that philosophers call qualia? Sheer illusion.

Human beings, Mr. Dennett said, quoting a favorite pop philosopher, Dilbert, are “moist robots.”

“I’m a robot, and you’re a robot, but that doesn’t make us any less dignified or wonderful or lovable or responsible for our actions,” he said. “Why does our dignity depend on our being scientifically inexplicable?”

If he hadn’t grown up in an academic family, Mr. Dennett likes to say, he probably would’ve been an engineer. From his beginnings in the philosophical hothouses of early 1960s Harvard and Oxford, he had a feeling of being out of step joined by a precocious self-confidence.

As an undergraduate, he transferred from Wesleyan University to Harvard so he could study with the great logician W. V. O. Quine and explain to him why he was wrong. “Sheer sophomoric overconfidence,” Mr. Dennett recalled.

As a doctoral student at Oxford, then the center of the philosophical universe, he studied with the eminent natural-language philosopher Gilbert Ryle but increasingly found himself drawn to a more scientific view of the mind.

“I vividly recall sitting with my landlord’s son, a medical student, and asking him, ‘What is the brain made of?’ ” Mr. Dennett said. “He drew me a simple picture of a neuron, and pretty soon I was off to the races.”

In 1969, Mr. Dennett began keeping his “Philosophical Lexicon,” a dictionary of cheeky pseudo-terms playing on the names of mostly 20th-century philosophers, including himself. (“dennett: an artificial enzyme used to curdle the milk of human intentionality.”) Today, his impatience with the imaginary games philosophers play — “chmess” instead of chess, he calls it — and his preference for the company of scientists lead some to question if he’s still a philosopher at all.

“I’m still proud to call myself a philosopher, but I’m not their kind of philosopher, that’s for sure,” he said. The new book reflects Mr. Dennett’s unflagging love of the fight, including some harsh whacks at longtime nemeses like the paleontologist Stephen Jay Gould — accused of practicing a genus of dirty intellectual tricks Mr. Dennett calls “goulding” — that some early reviewers have already called out as unsporting. (Mr. Gould died in 2002.)

Mr. Dennett also devotes a long section to a rebuttal of the famous Chinese Room thought experiment, developed by 30 years ago by the philosopher John Searle, another old antagonist, as a riposte to Mr. Dennett’s claim that computers could fully mimic consciousness.

Clinging to the idea that the mind is more than just the brain, Mr. Dennett said, is “profoundly naïve and anti-scientific.”

Wednesday, May 08, 2013

Mysteries of the universe: Upstream Color



A new film from Shane Carruth, the director of Primer. I haven't seen it yet but am looking forward to it. Carruth has chosen an independent distribution strategy, so you can watch it right now, e.g., on Amazon or streamed from other sources. Here's a picture of Carruth at Sci Foo back in 2008. When we parted company he was on his way to talk to Steven Soderbergh to start fundraising for his next film. It's been 9 years since Primer was released! Carruth has chosen a difficult path in life ...




Rotten Tomatoes:

It presents us with a glimpse of the vastness of existence, of our inner nature, and of nature without that is as equally dreadful, enveloping, and terrifying as it is beautiful.

Sci-fi might have been too familiar a word, for what may induce a kind of hallucinatory melancholy in its viewers.

Carruth may be something that the movies haven't yet seen, perhaps the first great realization of the democratization of filmmaking that digital technology and the Internet promised.
New Yorker: ... “Upstream Color” is different. Although its story is meticulously conceived and covers a much broader span of action and group of characters, it conveys a sense of having been invented spontaneously by means of the camera, as if Carruth were discovering the story in real time rather than realizing it as planned. The difference—the advance—involves more than aesthetic pleasure or even existential risk; it’s a crucial deepening of Carruth’s ideas, which are among the most philosophically sophisticated in the contemporary cinema. He works in a distinctive mode: science-fiction with overtones of transcendence. His distinctive visual style is one of spiritual impressionism, similar to that of Terrence Malick’s agile, luminous rapture—but Carruth’s images are harder-edged, more confrontational, and, above all, non-religious. Where Malick’s images are tactile, Carruth’s are physical; where Malick’s are metaphysical, Carruth’s are diaphysical—he doesn’t sanctify the mystery but reveals it through hidden realms of the material world. Carruth fulfills the basic premise of science-fiction, to tether the impossible to rational explanations—but the impossible results that he seeks to explain are of the sort that are commonly taken to be religious. His subject is identity—the hazy border zone where the mental shifts, by means of self-consciousness and other, perhaps vaguer biochemical processes, into some higher essence of selfhood that is ordinarily called the soul.
Soderbergh on Hollywood: In my view, in this business which is totally talent-driven, it’s about horses, not races. I think if I were going to run a studio I’d just be gathering the best filmmakers I could find and sort of let them do their thing within certain economic parameters. So I would call Shane Carruth or Barry Jenkins or Amy Seimetz and I’d bring them in and go, ok, what do you want to do? What are the things you’re interested in doing? What do we have here that you might be interested in doing? If there was some sort of point of intersection I’d go: O.K., look, I’m going to let you make three movies over five years, I’m going to give you this much money in production costs, I’m going to dedicate this much money on marketing. You can sort of proportion it how you want, you can spend it all on one and none on the other two, but go make something.

Monday, May 06, 2013

Exercise response



Positive for most people, but with a lot of genetic variation. Interestingly, a fraction of the population (about 10%) can have a negative health or fitness response to training (see @40 min or so in the video). This professor's company claims to be able to predict exercise response by looking at about 30 gene variants. The talk also has some interesting results concerning high intensity training.




NYTimes: ... That original research, published in a landmark 2010 study, looked into the genetics of why some people respond to endurance exercise so robustly, while others do not. Some lucky men and women take up jogging, for example, and quickly become much more aerobically fit. Others complete the same program and develop little if any additional endurance, as measured by increases in their VO12 max, or their body’s ability to consume and distribute oxygen to laboring muscles.

For the 2010 study, Dr. Timmons and his colleagues genotyped muscle tissue from several groups of volunteers who had completed 6 to 20 weeks of endurance training. They found that about 30 variations in how genes were expressed had a significant effect on how fit people became. The new test looks for those genetic markers in people’s DNA. ...

Sunday, May 05, 2013

Nasty, brutish and short?

In such condition, there is no place for industry; because the fruit thereof is uncertain: and consequently no culture of the earth; no navigation, nor use of the commodities that may be imported by sea; no commodious building; no instruments of moving, and removing, such things as require much force; no knowledge of the face of the earth; no account of time; no arts; no letters; no society; and which is worst of all, continual fear, and danger of violent death; and the life of man, solitary, poor, nasty, brutish, and short. — "Chapter XIII.: Of the Natural Condition of Mankind As Concerning Their Felicity, and Misery.", Leviathan, Thomas Hobbes

Not only has natural selection not stopped since the advent of civilization, it has changed in subtle ways.
The Scientist: In 1974, the UK Medical Research Council (MRC) set up clinics in two rural villages in Gambia’s West Kiang district, offering free medical care to locals. The effect was dramatic. Thanks to good health care, better infrastructure, and accessible contraception, the villagers started living longer and having fewer children.

Over a short time, the district went through a modern-day demographic transition—a well-known fall in birth and death rates typically seen when human societies move to industrialized economies—causing natural selection to act upon the population in noticeably altered ways, according to a study published today (April 25) in Current Biology.

Alexandre Courtiol from the Leibniz Institute for Zoo and Wildlife Research and Ian Rickard from Durham University found that before 1974, shorter, fatter women had the highest relative fitness—measured by the number of descendants they leave behind. But since the clinic was built, selection pressures have flip-flopped so that taller, thinner women now have the advantage.

Their results are the latest to challenge the idea that modern humans have stopped evolving due to industrialization and medical advances. Although the team did not find any actual changes in gene frequencies—the gold standard for demonstrating evolution has taken place—“the paper illustrates that natural selection persists in contemporary human populations,” said Jacob Moorad, an evolutionary biologist from Duke University who was not involved in the study. “And this force for evolutionary change is fluid.” ...

BrunoFest 2013



Unfortunately I had to miss this event, but one of our cohort of Berkeley students (Josh Burton) was able to attend. The photos below were taken by Josh. Had LHC discovered superpartners, Bruno Zumino and Julius Wess would have had a decent claim to a Nobel prize for their early work on supersymmetry.

It is strange to see my teachers grow old; to find myself older than some of the younger ones were when I was a student.

I remember Bruno as a consummate gentleman. He was kind to students and an excellent lecturer. The main idiosyncrasy was a small metal chalk holder that kept his hands clean but made the chalk squeak sharply as Bruno wrote his beautiful long equations on the board. In one of his special topics courses I turned in a term paper on string compactification (the Hosotani mechanism) which was returned with some nice comments and an A+. I think he hadn't been familiar with some of the results and attributed their cleverness incorrectly to me. Despite learning differential forms from both Kip Thorne and Bruno I've never used them much and continue to rely on explicit indices ;-)


Signing the guest book for all of us.


Ed Witten with Stanley Mandelstam.


J.D. Jackson, Geoff Chew and Steven Weinberg.



Saturday, May 04, 2013

Lean in, freeze eggs

Better this than Idiocracy. You could also argue that men should freeze sperm as the incidence of de novo mutations in children increases with paternal age.



WSJ: ... Egg freezing stopped the sadness that I was feeling at losing my chance to have the child I had dreamed about my entire life. It soothed my pangs of regret for frittering away my 20s with a man I didn't want to have children with, and for wasting more years in my 30s with a man who wasn't sure he even wanted children. It took away the punishing pressure to seek a new mate and helped me find love again at age 42.

I decided to freeze on the afternoon of my 36th birthday, when I did a fresh round of baby math on the back of a business card at Starbucks. Even if the man I was dating at the time agreed to start a family in the near future, I was cutting it close to have one baby, let alone a second. Several months later, after injecting myself for nearly two weeks with hormone shots, I was in surgery at a Manhattan fertility clinic as my doctor pierced my ovaries, suctioned out nine eggs and handed them to the embryologist to freeze until I was ready to use them. As soon as I woke up in the recovery room, I no longer felt as though I were watching my window to have a baby close by the month. My future seemed full of possibility again.

Amid all the talk about women "leaning in" and "having it all," the conversation has left out perhaps the most powerful gender equalizer of all—the ability to control when we have children. The idea is tantalizing: Once you land the job and man you want, you can have your frozen eggs shipped to your fertility clinic, hand him a semen collection cup and be on your way to parenthood. You mitigate the risk of birth defects by using younger eggs, and you can carry a baby well into middle age. At a time when one in five American women between the ages of 40 and 44 is childless—and half say they would still like to have children—egg freezing offers a once-unimaginable reprieve.

Up until now, a woman who bumped up against her baby deadline could visit a sperm bank, make peace with being "child-free" or eventually break her heart and bank pursuing futile fertility treatments in an attempt to "snatch a child from the jaws of menopause," as the economist Sylvia Ann Hewlett so famously warned a decade ago while encouraging women to plan their families as carefully as their careers.

I spent the majority of my 30s alternately panicked about my love life or feeling kicked in the gut every time I saw an adorable child. Fertility anxiety isn't exactly helpful when you're trying to snag the locker next to Sheryl Sandberg in the executive gym. And it's a buzz kill on dates when you feel compelled to ask the guy sitting across from you, clutching his craft beer, "So do you think you might want kids someday?"

... Last fall, the American Society for Reproductive Medicine removed the procedure's experimental label, citing improved success rates with a new flash-freezing technology known as vitrification. Several trials showed little difference in in-vitro-fertilization success rates using frozen rather than fresh eggs. That rate is 30% to 50% per try, depending on the age of eggs and expertise of the doctor. Despite early fears of how freezing could damage eggs' chromosomes, a recent review of 900 babies born from frozen eggs found they had no more risk of birth defects than those conceived naturally.

See also The price of eggs.

Friday, May 03, 2013

Richard Ford '66

Richard Ford, MSU class of 1966, delivers a commencement address. The President was busy handing out diplomas and shaking hands, so I had Ford to myself for most of the two hour ceremony. I can't remember the last time I had such an enjoyable discussion of life, literature and writing.



Some quotes and excerpts from Ford below. See also this Paris Review interview.
“You can't write ... on the strength of influence. You can only write a good story or a good novel by yourself.”

“A sad fact, of course, about adult life is that you see the very things you'll never adapt to coming toward you on the horizon. You see them as the problems they are, you worry like hell about them, you make provisions, take precautions, fashion adjustments; you tell yourself you'll have to change your way of doing things. Only you don't. You can't. Somehow it's already too late. And maybe it's even worse than that: maybe the thing you see coming from far away is not the real thing, the thing that scares you, but its aftermath. And what you've feared will happen has already taken place. This is similar in spirit to the realization that all the great new advances of medical science will have no benefit for us at all, thought we cheer them on, hope a vaccine might be ready in time, think things could still get better. Only it's too late there too. And in that very way our life gets over before we know it. We miss it. And like the poet said: The ways we miss our lives are life.”

INTERVIEWER: How old were you when James Meredith was enrolled at the University of Mississippi? FORD: I was eighteen. By that time I was at Michigan State. I was not brave enough or committed enough or selfless enough to stay in Mississippi during the civil-rights movement. I wanted to get out of it. I wanted to go as far away from Mississippi as I could. ... I certainly don’t want to paint myself back then in any way to seem what I wasn’t, which is to say, enlightened. I wasn’t enlightened. I was nothing, that’s what I was. But I knew I was a little nothing—which helped. I knew that there were terrible things coming in Mississippi. I just thought, Uh oh, bad times are coming. I’ve got to get out of here to save myself. To reinvent myself.

“When you are sixteen you do not know what your parents know, or much of what they understand, and less of what's in their hearts. This can save you from becoming an adult too early, save your life from becoming only theirs lived over again--which is a loss. But to shield yourself--as I didn't do--seems to be an even greater error, since what's lost is the truth of your parents' life and what you should think about it, and beyond that, how you should estimate the world you are about to live in.” ― Wildlife

“At the exact moment any decision seems to be being made, it's usually long after the real decision was actually made--like light we see emitted from stars.” ― The Lay of the Land

“I know you can dream your way through an otherwise fine life, and never wake up, which is what I almost did.” ― The Sportswriter

“What was our life like? I almost don't remember now. Though I remember it, the space of time it occupied. And I remember it fondly.” ― The Sportswriter

Thursday, May 02, 2013

Everybody digs Bill Evans

Yesterday someone told me I was a techno-optimist, and I replied that I had grown up in an era in which university libraries were the main repositories of high quality information. Sitting in front of the computer, I can share all kinds of things with my kids that weren't available to me as a child. Who could imagine a time when typing in a few words would evoke rich sounds and images of Bill Evans or Chet Baker? Thanks to all the jazz fans who are uploading this rare footage and music!




With vocals (Monica Zetterlund). See also this profile, The Universal Mind of Bill Evans.


Wednesday, May 01, 2013

Learning can hurt

This essay, from 2007, summarizes how progress in genomics came to confront convenient but incorrect views on the genetic clustering of human populations. The vast majority of people, even scientists, are still confused about this subject. See also Human genetic variation, Fst and Lewontin's fallacy in pictures.
The flipside of serendipity: human genetics rediscovers race

... In this paper I investigate the recent re-emergence of genetic race in more detail, and endeavour to ascertain how, after a half-century hiatus, a young team of population geneticists could casually rediscover race in 2002. Was it happenstance? Or was it opportune timing? My tentative conclusions are: (a) the flipside of serendipity is sociopolitical context; and (b) in the first few years of the new millennium, on the face of it, the time was indeed ripe for genetic race to re-emerge within the scientific mainstream.

IT ALL STARTED WITH A CLUSTER ANALYSIS ...

'We have sequenced the genome of three females and two males, who have identified themselves as Hispanic, Asian, Caucasian or African American ... to help illustrate that the concept of race has no genetic or scientific basis. In the five Celera genomes, there is no way to tell one ethnicity from another.'--J Craig Venter, White House press conference, June 2000. (4)

Craig Venter was the 'maverick' geneticist who founded Celera Genomics--a private biotech company that, in the late 1990s, took on a trans-national network of publicly and privately funded researchers in a frantic race to sequence the human genome. In June 2000, at the White House press conference that heralded the completion of the 'first assembly' of the genome, standing next to his public-sector adversary Francis Collins, United States President Bill Clinton, and (via satellite feed) United Kingdom Prime Minister Tony Blair, in a triumphal moment for Big Science and liberal humanism Venter announced: 'the concept of race has no genetic or scientific basis.'

In saying this, he reaffirmed evolutionary biologist Richard Lewontin's oft-cited claim that racial classification is of 'virtually no genetic or taxonomic significance'. (5) He also echoed a gaggle of other geneticists and an army of anthropologists who, since the middle of the twentieth century, have similarly sought to deny that the 'race concept' has any basis in biology. In short, he took up what might be termed the 'race as social construct' position--a position that has come to function as a default setting within the social sciences in recent decades. Never mind that his assertion was based on an analysis of only five individual genomes and thus a statistical fallacy; the important thing was that it befitted the hyperbole of the occasion and had the aura of incontrovertible truth.

[[ Who could have possibly accepted these results as decisive? See Bounded Cognition. ]]

Over the next few years the incontrovertibility of the 'race as social construct' position began to erode. Just four years after Venter's speech, in the pages of a Nature genetics supplement dedicated to the issue of race in genomics, Francis Collins--who had shared both podium and Time magazine cover with Venter on that aforementioned momentous day--offered this cautious qualification: 'As ancestral origins in many cases have a correlation, albeit often imprecise, with self-identified race or ethnicity, it is not strictly true that race or ethnicity has no biological connection.' (6)

... Collins ... is the director of the US National Human Genome Research Institute, a renowned medical genetics researcher, and by all accounts not a racist. So why is a distinguished geneticist, not some racist crackpot on the margins of academia, suddenly making the claim: 'it is not strictly true that race or ethnicity has no biological connection'? What happened in those few short years that separate Venter's exultant assertion and Collins's wary disclaimer?

Ostensibly, the answer to these questions can be found in Collins's paper, for he cites evidence to support his claim: a population genetics study conducted by Noah Rosenberg and his team of researchers that was published in Science in December 2002. Drawing on samples from the Human Genome Diversity Cell Line Panel, (8) these researchers investigated the 'correspondence of predefined groups with those inferred from individual multilocus genotypes'. (9) They used a complex computer algorithm to sort 1,064 genome samples, from fifty-two different populations, on the basis of 4,199 different alleles, at 377 highly variable 'junk-DNA' loci, into varying numbers of statistically significant genetic clusters, and then compared the clusters with the geographical origins of the populations from which they were drawn. Put simply, they took the labels off the samples and tried to see if the computer could sort them back into meaningful groups based solely on their genetic similarities.

They found that 'predefined labels' (such as 'Yoruba', 'Italian' or 'Japanese') were 'highly informative about membership in genetic clusters'. (10) Further, when asked to identify five clusters, the computer grouped the samples into sets roughly corresponding to five geographical regions: (i) sub-Saharan Africa, (ii) Europe and West Asia, (iii) East Asia, (iv) Oceania, and (v) the Americas (see the row marked 'K=5' in Figure 1 below for a graphical representation of these clusters). Curiously, these regions are roughly geographically concordant to those occupied by the 'black', 'white', 'yellow', 'tawny' and 'copper-coloured' 'varieties' outlined in Johann Friedrich Blumenbach's seminal eighteenth-century racial typology. (11)

These results should have come as no surprise to most population geneticists, as it had long been assumed that human groups separated by physical, environmental, linguistic, and/or cultural barriers would display some degree of genetic differentiation. (12) Nonetheless, they were quite significant, as it was the first time that human populations had been comprehensively shown to cluster together on the basis of genetic likeness in a 'blind' test.

Still, Rosenberg and his colleagues were relatively circumspect in their conclusions. Their point was not to show that old anthropological conceptions of race are genetically 'real', but to argue that differentiating between human populations is both methodologically and statistically valid, and that such distinctions can be legitimately used for tracing the origins and migrations of peoples, as well as for medical and epidemiological purposes.

The words 'race' and 'ethnicity' never appeared in their paper, only 'population' and 'ancestry', and they were careful to choose neutral colours to code the continental clusters they identified--sub-Saharan Africa was orange, Europe and West Asia pale-blue, East Asia pink, Oceania green, and the Americas purple (not black, white, yellow, tawny and copper-coloured). Here they seemingly followed a convention established by the father of human population genetics and the prime mover behind the Human Genome Diversity Project, Luigi Luca Cavalli-Sforza, whose co-authored magnum opus, The History and Geography of Human Genes (1994, abridged 2006), featured a colour-coded atlas on its cover (Figure 2), with the caption: 'Four major ethnic regions are shown. Africans are yellow, Australians red, [Mongoloids blue] and Caucasoids green.' (13) A reviewer from Time magazine described Cavalli-Sforza's book as 'a landmark global study' that 'flattens The Bell Curve, proving that racial differences are only skin deep.' (14) Similarly, the Rosenberg study was lauded for its 'humanitarian' findings and adjudged 'paper of the year' by The Lancet in 2003. (15)

On the surface the consensus was that nothing much had changed. Population genetics had proven racial differences were only 'skin deep', and the Rosenberg findings only served to further confirm this incontrovertible fact. Everyone was content to repeat the familiar mantra: 'no race here ... nothing to look at ... move along'. However, beneath the 'race as social construct' ideological edifice a fuse had been lit and a 'race as biological reality' powder keg was about to go off.

THE MESSY FALLOUT

Even before the Rosenberg paper appeared, a group of belligerent geneticists headed up by Neil Risch from Stanford University had published an opinion piece in Genome Biology defending 'the validity of race/ethnicity categories for biomedical and genetic research' on the basis of cluster analyses similar to that used by the Rosenberg study.

[[ See Neil Risch, Portrait of a mathematical geneticist. ]]

The following year A W F Edwards, who had pioneered the statistical techniques behind cluster analysis with Cavalli-Sforza in the 1960s, penned a curt refutation of Lewontin's 1972 claim about the insignificance of racial classification, citing the Rosenberg study to buttress his argument. (17)

Following on from Edwards's assault, over the next few years several review essays appeared in major journals, (18) and the issue exploded onto the pages of the major broadsheets. Two articles from The New York Times tell the story of this re-emergence quite well: in August 2000 the headline read, 'Do races differ? Not really, genes show', with the author quoting Venter and others; (19) by July 2006 another headline read, 'Imperfect, imprecise but useful: Your race', and the article discussed the utility of racial classifications for biomedical research. (20)

A further twist in the plot of this recent race potboiler began on 14 March 2005, when evolutionary biologist Armand Marie Leroi published a now infamous op-ed piece, again in The New York Times (seemingly the arbiter of all things genetic), entitled 'A family tree in every gene'. (21) Taking up the Rosenberg study bait, he heralded their findings as suggesting: 'the consensus about social constructs was unravelling', and 'looked at the right way, the genetic data show that races clearly do exist.' (22) Further, he celebrated new advances in genetics that will soon mean, 'we shall no longer gawp ignorantly at the gallery [of racial differences]; we shall be able to name the painters.' (23)

Of course, more than a few people took exception to this talk of 'genetic painters' and 'racial galleries', and Leroi's article prompted a swift multi-pronged rebuttal. Within a month the US Social Science Research Council (SSCR) had sponsored a web forum collecting together critical responses from many of the usual 'social construct' suspects, including Alan Goodman, Evelynn Hammonds, Joseph Graves, Ruth Hubbard, Richard Lewontin and Jonathan Marks (many of whom also appeared in the 2003 PBS documentary series 'Race--the Power of an Illusion'). (24)

Labouring valiantly to plug the holes emerging in the epistemic dyke separating old race pseudoscience from modern human genetics, these ageing anti-race activists accused Leroi of 'reifying' race, and argued that race is most certainly not a biological category but rather an all-too-real social category that should be kept as far away as possible from the objective realm of science. ...


... This is what more sophisticated constructivists mean when they say race is a social construct--that the social and political aspects of race cannot easily be disentangled from the biological. (28) However, some constructivists want to go as far as to suggest that there is no biological dimension to race at all, with Richard Lewontin being a notorious culprit. Lewontin's research in the 1970s did not show that racial classifications were genetically insignificant, only that differences between racial groups were less significant than within groups. (29) His denial of the genetic significance of race is a non sequitur.

Putting aside Lewontin's fallacy, the major mistakes that unsophisticated social constructivists make are: (a) to suggest that being bound up with social and political concerns renders race 'unscientific' (as if scientific knowledge about human subjects could ever be separated from society and politics); and (b) to believe that by replacing race with the term population we can somehow escape this problem. The latter move just 'purifies' the concept of race, allowing geneticists to investigate racial groups such as 'Yoruba', 'Japanese', 'Caucasoid' or 'Australian' under the rubric of population, whilst denying that their research has anything to do with race. ...

The last amateurs

Is the age of the talented amateur over in science? By amateur here I don't mean a non-scientist doing science (that age probably ended earlier), but rather a specialist from one area making a contribution in another. The example below is George Gamow, a cosmologist and theoretical physicist who migrated into biology.

Wigner:
Specialization of science also robbed us of much of our passion. We wanted to grasp science whole, but by then the whole was something far too vast and complex to master. Only rarely could we ask the deep questions that had first drawn us to science.


Ulam on George Gamow:
Gamow, who was a complete layman in the field of biology ... proposed, with his fantastically unerring instinct, some ideas about how the code really worked. I think he was the first to suggest that the sequence of the four substances of the DNA denoted by the letters A, C, T, C expressed words, and how from these four letters one could build 20 or 23 amino acids ... defining the structure of proteins. Gamow had this idea before anyone else. He even almost had the correct way (later found by Crick) of expressing the formation by triplets. ...

One may see in his work, among other outstanding traits, perhaps the last example of amateurism in science ...

Gamow and Einstein crossing the street:
Quantum uncertainty allows the temporary creation of bubbles of energy, or pairs of particles (such as electron-positron pairs) out of nothing, provided that they disappear in a short time. The less energy is involved, the longer the bubble can exist. Curiously, the energy in a gravitational field is negative, while the energy locked up in matter is positive. If the Universe is exactly flat, then as Tryon pointed out the two numbers cancel out, and the overall energy of the Universe is precisely zero. In that case, the quantum rules allow it to last forever. If you find this mind-blowing, you are in good company. George Gamow told in his book My World Line (Viking, New York, reprinted 1970) how he was having a conversation with Albert Einstein while walking through Princeton in the 1940s. Gamow casually mentioned that one of his colleagues had pointed out to him that according to Einstein's equations a star could be created out of nothing at all, because its negative gravitational energy precisely cancels out its positive mass energy. "Einstein stopped in his tracks," says Gamow, "and, since we were crossing a street, several cars had to stop to avoid running us down".

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