Wednesday, December 30, 2015

Saudis toast?

See also The one sided clash of civilizations.
Telegraph: ...If the aim was to choke the US shale industry, the Saudis have misjudged badly, just as they misjudged the growing shale threat at every stage for eight years.

... The problem for the Saudis is that US shale frackers are not high-cost. They are mostly mid-cost, and as I reported from the CERAWeek energy forum in Houston, experts at IHS think shale companies may be able to shave those costs by 45pc this year - and not only by switching tactically to high-yielding wells.

Advanced pad drilling techniques allow frackers to launch five or ten wells in different directions from the same site. Smart drill-bits with computer chips can seek out cracks in the rock. New dissolvable plugs promise to save $300,000 a well. "We've driven down drilling costs by 50pc, and we can see another 30pc ahead," said John Hess, head of the Hess Corporation.

It was the same story from Scott Sheffield, head of Pioneer Natural Resources. "We have just drilled an 18,000 ft well in 16 days in the Permian Basin. Last year it took 30 days," he said.

The North American rig-count has dropped to 664 from 1,608 in October but output still rose to a 43-year high of 9.6m b/d June. It has only just begun to roll over. "The freight train of North American tight oil has kept on coming," said Rex Tillerson, head of Exxon Mobil.

... The wells will still be there. The technology and infrastructure will still be there. Stronger companies will mop up on the cheap, taking over the operations. Once oil climbs back to $60 or even $55 - since the threshold keeps falling - they will crank up production almost instantly.

OPEC now faces a permanent headwind. Each rise in price will be capped by a surge in US output. The only constraint is the scale of US reserves that can be extracted at mid-cost, and these may be bigger than originally supposed, not to mention the parallel possibilities in Argentina and Australia, or the possibility for "clean fracking" in China as plasma pulse technology cuts water needs.

... Saudi Arabia is effectively beached. It relies on oil for 90pc of its budget revenues. There is no other industry to speak of, a full fifty years after the oil bonanza began.

... In hindsight, it was a strategic error to hold prices so high, for so long, allowing shale frackers - and the solar industry - to come of age. The genie cannot be put back in the bottle.

Tuesday, December 29, 2015


Unusually cold this year on the central coast, but we had a nice afternoon at the beach.

Get your third wave coffee here

... and your jits here

Friday, December 25, 2015

Nativity 2050

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 ...
See also [1], [2], and [3].

Thursday, December 24, 2015

Peace on Earth, Good Will to Men 2015

For years, when asked what I wanted for Christmas, I've been replying: peace on earth, good will toward men :-)

No one ever seems to recognize that this comes from the bible, Luke 2.14 to be precise!

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!
In preparation for the new year:
Marcus Aurelius

Or does the bubble reputation distract you? Keep before your eyes the swift onset of oblivion, and the abysses of eternity before us and behind; mark how hollow are the echoes of applause, how fickle and undiscerning the judgments of professed admirers, and how puny the arena of human fame. For the entire earth is but a point, and the place of our own habitation but a minute corner in it; and how many are therein who will praise you, and what sort of men are they?

Monday, December 21, 2015

Who's on the other side of the trade?

A great conversation between Tyler Cowen and fund manager Cliff Asness, who has appeared many times on this blog. See, e.g., this 2004 post on his analysis of the well known Fed Model for equity valuation, also discussed in the interview.
Hedge-fund manager Cliff Asness, one of the most influential—and outspoken—financial thinkers, will join Tyler Cowen for a wide-ranging intellectual dialogue as part of the Conversations with Tyler series.

Asness is a founder, managing principal and chief investment officer at AQR Capital Management. In 2012, he was included in the 50 Most Influential list of Bloomberg Markets magazine. As an entrepreneur in the field of finance, Asness has helped shape the national conversation on financial markets and regulation.

He is an active researcher and has authored articles on a variety of financial topics for many publications, including The Journal of Portfolio Management, Financial Analysts Journal, and The Journal of Finance. Prior to cofounding AQR Capital Management, he was a managing director and director of quantitative research for the Asset Management Division of Goldman, Sachs & Co. He is on the editorial board of The Journal of Portfolio Management, the governing board of the Courant Institute of Mathematical Finance at NYU, the board of directors of the Q-Group and the board of the International Rescue Committee.

Thursday, December 17, 2015

John McWhorter: the truth about mismatch

I'm shocked that CNN published Columbia professor John McWhorter's editorial on Scalia's mismatch comments. His remarks challenge the mainstream media narrative, and require some thought from the reader.
CNN: Those who consider themselves on black people's side are having a field day dismissing Justice Antonin Scalia as a racist. His sin was suggesting that black students admitted to the most selective institutions might perform better at somewhat less selective institutions where instruction is paced more slowly.

I don't usually agree with Justice Scalia's perspectives, but we are doing him wrong on this one. Scalia didn't express himself as gracefully as he could have. No one could suppose that anything like all black students find the pedagogical pace at top-level universities overwhelming.

However, Scalia's comment stemmed not from random intuition but from research showing that a substantial number of black students would do better -- and be happier -- at schools less selective than the ones they are often admitted to via racial preferences.

The reading public's response to Scalia's point shows that few have any idea of this research or assume it was done by partisan zealots. An intelligent discussion of the Fisher v. University of Texas case now before the Supreme Court requires a quick tour of the facts.

... At Duke University, economist Peter Arcidiacono, with Esteban Aucejo and Joseph Hotz, has shown that the "mismatch" lowers the number of black scientists. Black students at a school where teaching is faster and assumes more background than they have often leave the major in frustration, but would be less likely to have done so at a school prepared to instruct them more carefully.

UCLA law professor Richard Sander conclusively showed in 2004 that "mismatched" law students are much more likely to cluster in the bottom of their classes and, especially, to fail the bar exam. Meanwhile, Sander and Stuart Taylor's book argues that the mismatch problem damages the performance of black and brown students in general.

There are scholars who dispute Sander and Taylor's thesis about undergraduate school in general. However, when it comes to the more specific points about STEM subjects and law school, takedown arguments are harder to fashion because of the simple force of the facts.

For example, on Sander's widely publicized law school paper, time has passed and few of us go in for reading law review articles. However, Emily Bazelon's widely read critique of it was hasty in claiming that the responses published along with Sander's piece refuted his claims. Rather, anyone reading them with an open mind would see that they left Sander's basic point standing tall and this applies to any other critique I have seen: there has been no "smackdown." It is similarly unlikely that anyone could tell Arcidiacono, Aucejo and Hotz that what they chronicle was mirages.

... At the University of California, San Diego the year before racial preferences were banned in the late '90s, exactly one black student out of 3,268 freshmen made honors. A few years later, after students who once would have been "mismatched" to flagship school UC Berkeley were now admitted to schools such as UC San Diego, one in five black freshmen were making honors, the same proportion as white ones.

What civil rights leader of the past would have seen this as racism? Who in the future will? Or why are we tarring Scalia as a bigot for espousing outcomes like this in the here and now?

Our national conversation on racial preferences is under-informed and mean when founded on an assumption that anyone who seriously questions racial preferences is naive at best and a pig at worst. Affirmative action is a complex matter upon which reasonable minds will differ. With the well-being of young people of color at stake, we can't afford to pretend otherwise.
You could also have read about this topic in my NYTimes op-ed from 2012: Merit, Not Race, in College Admissions. The facts supporting mismatch are not disputable, despite the attempts of some ideologues to cloud the conversation.

I sometimes explain the issue as follows. Imagine taking a group of typical engineering students from Iowa State University and transferring them to MIT or Caltech in their freshman year. What are the odds that these students would thrive? What are the odds that they would cluster at the bottom of the class and learn less than they would have had they stayed at Iowa State? Anyone who has taught STEM at both highly selective and less selective universities knows that large differences in admissions selectivity lead to large differences in average ability in the classroom (the whole purpose of selection!), and that the pace and presentation of material needs to be adjusted accordingly. In the example I gave, the SAT gap is perhaps 200 points (on a 1600 scale). But this is smaller than the admissions preference given to African Americans by most selective colleges (see Affirmative Action: the Numbers).

Why do we think the thought experiment would suddenly become a good idea if the students were black?

One might object that SAT or high school GPA are flawed measures of ability, especially for under-represented minorities. But this has been studied carefully. The fact of the matter is that the accuracy of these numerical indicators as predictors of college performance varies little depending on the race or even socio-economic background of the student. (To be technical: adding an additional variable for race or income to the regression changes the SAT coefficient by very little.) That is, a student admitted with lower scores than their peers is unlikely to perform well in difficult STEM majors, regardless of the race of the student, and even if that student comes from a wealthy legacy family.

It's also known that test preparation only improves SAT scores by a small fraction of the typical admissions preference (i.e., less than 50 points vs 300), and that test-retest reliability of the exam is very high. The tests measure something real, which has predictive power.

The consequences of selecting students based on academic ability are clearly manifested in this study by Jonathan Wai and myself: Colleges ranked by Nobel, Fields, Turing and National Academies output. Colleges with the most talented students (selected based on simple measures such as SAT and high school GPA) produce orders of magnitude more top scientists, engineers, and medical researchers per capita than less selective schools.

There is a sad pattern in the comprehensive Duke data that both McWhorter and I reference: students admitted with weak admissions scores are more likely to leave challenging STEM majors in favor of less competitive subjects, and they are more likely to perform poorly overall. This pattern holds regardless of the race or socio-economic status of the student.

Anyone who claims to have a serious interest in higher education (e.g., all professors and administrators) should be familiar with the facts presented above.

Note Added:

Two related editorials, one by Richard Sander in the WSJ and the other by Thomas Sowell.

Most of the analyses attacking mismatch have focused on graduation rates. But these ignore the fact that virtually all colleges have easy majors. Given the widely acknowledged practice of admitting wealthy applicants, legacies, and athletes with significantly below average scores, and the nearly 100% graduation rate at the Ivies, the conclusion has to be that there are paths of little resistance through most elite colleges. Surprisingly, it might be easier for a student of average ability (that is, relative to the overall population) to graduate from Harvard (once admitted), than to graduate from a typical state university -- the key is choice of major.

IIRC, the migration of weaker students from STEM into less challenging majors is revealed in "real time" in the Duke data set, which contains every grade in every course for all students over a number of years. It also contains the application files of students and their original intended majors. Without this level of specificity, one can't really make strong assertions about mismatch. I have yet to see any data-driven analyses which contradict the mismatch hypothesis specifically as it applies to STEM or law school.

We should applaud Historically Black Colleges and Universities (HBCUs) for taking students with modest test scores and yet producing graduates who go on to earn a disproportionate fraction of STEM PhDs, something Scalia alluded to in his (badly worded) remarks.
NSF: ... Among known U.S. baccalaureate-origin institutions of 1997–2006 black S&E doctorate recipients, the top 8 and 20 of the top 50 were HBCUs. ... The top 5 baccalaureate-origin institutions of 1997–2006 black S&E doctorate recipients were: Howard University, Spelman College, Hampton University, Florida A&M University, and Morehouse College.

Saturday, December 12, 2015

Reach Higher

MSU research ranked #6 among US universities in combined National Science Foundation + Department of Energy funding. Ahead of Michigan, Stanford, Caltech, and Berkeley. MIT is #1.

Milnor, Nash, and Game Theory at RAND

Nash and Milnor were involved in experimental tests of n-person game theory at RAND in 1952. Even then it was clear that game theory had little direct applicability in the real world. See also What Use Is Game Theory? , Iterated Prisoner's Dilemma is an Ultimatum Game, and, e.g., The Econ Con or Venn Diagram for Economics.
A Beautiful Mind: ... For the designers of the experiment[s], however, the results merely cast doubt on the predictive power of game theory and undermined whatever confidence they still had in the subject. Milnor was particularly disillusioned. Though he continued at RAND as a consultant for another decade, he lost interest in mathematical models of social interaction, concluding that they were not likely to evolve to a useful or intellectually satisfying stage in the foreseeable future. The strong assumptions of rationality on which both the work of von Neumann and Nash were constructed struck him as particularly fatal. After Nash won the Nobel Prize in 1994, Milnor wrote an essay on Nash's mathematical work in which he essentially adopted the widespread view among pure mathematicians that Nash's work on game theory was trivial compared with his subsequent work in pure mathematics.

In the essay, Milnor writes:
As with any theory which constructs a mathematical model for some real-life problem, we must ask how realistic the model is. Does it help us to understand the real world? Does it make predictions which can be tested?...

First let us ask about the realism of the underlying model. The hypothesis is that all of the players are rational, that they understand the precise rules of the game, and that they have complete information about the objectives of all of the other players. Clearly, this is seldom completely true.

One point which should particularly be noticed is the linearity hypothesis in Nash's theorem. This is a direct application of the von Neumann-Morgenstern theory of numerical utility; the claim that it is possible to measure the relative desirability of different possible outcomes by a real-valued function which is linear with respect to probabilities .... My own belief is that this is quite reasonable as a normative theory, but that it may not be realistic as a descriptive theory.

Evidently, Nash's theory was not a finished answer to the problem of understanding competitive situations. In fact, it should be emphasized that no simple mathematical theory can provide a complete answer, since the psychology of the players and the mechanism of their interaction may be crucial to a more precise understanding.
For more discussion, including specific experimental results, see Machine Dreams, chapter 6.2: It's a world eat world dog: game theory at RAND.

CRISPR in the New Yorker

Earlier CRISPR posts here.
New Yorker: At thirty-four, Feng Zhang is the youngest member of the core faculty at the Broad Institute of Harvard and M.I.T. He is also among the most accomplished. In 1999, while still a high-school student, in Des Moines, Zhang found a structural protein capable of preventing retroviruses like H.I.V. from infecting human cells. The project earned him third place in the Intel Science Talent Search, and he applied the fifty thousand dollars in prize money toward tuition at Harvard, where he studied chemistry and physics. By the time he received his doctorate, from Stanford, in 2009, he had shifted gears, helping to create optogenetics, a powerful new discipline that enables scientists to use light to study the behavior of individual neurons.

Zhang decided to become a biological engineer, forging tools to repair the broken genes that are responsible for many of humanity’s most intractable afflictions. The following year, he returned to Harvard, as a member of the Society of Fellows, and became the first scientist to use a modular set of proteins, called TALEs, to control the genes of a mammal. “Imagine being able to manipulate a specific region of DNA . . . almost as easily as correcting a typo,” one molecular biologist wrote, referring to TALEs, which stands for transcription activator-like effectors. He concluded that although such an advance “will probably never happen,” the new technology was as close as scientists might get.

Having already helped assemble two critical constituents of the genetic toolbox used in thousands of labs throughout the world, Zhang was invited, at the age of twenty-nine, to create his own research team at the Broad. One day soon after his arrival, he attended a meeting during which one of his colleagues mentioned that he had encountered a curious region of DNA in some bacteria he had been studying. He referred to it as a CRISPR sequence. ...

... CRISPR has two components. The first is essentially a cellular scalpel that cuts DNA. The other consists of RNA, the molecule most often used to transmit biological information throughout the genome. It serves as a guide, leading the scalpel on a search past thousands of genes until it finds and fixes itself to the precise string of nucleotides it needs to cut. It has been clear at least since Louis Pasteur did some of his earliest experiments into the germ theory of disease, in the nineteenth century, that the immune systems of humans and other vertebrates are capable of adapting to new threats. But few scientists had considered the possibility that single bacterial cells could defend themselves in the same way. The day after Zhang heard about CRISPR, he flew to Florida for a genetics conference. Rather than attend the meetings, however, he stayed in his hotel room and kept Googling. “I just sat there reading every paper on CRISPR I could find,” he said. “The more I read, the harder it was to contain my excitement.”

... Zhang was awarded the patent, but the University of California has requested an official reassessment, and a ruling has not yet been issued. Both he and Doudna described the suit to me as “a distraction” that they wished would go away. Both pledged to release all intellectual property to researchers without charge ...

... “No single person discovers things anymore,” George Church told me when we met in his office at Harvard Medical School. “The whole patent battle is silly. There has been much research. And if anybody should be making a fuss about this I should be making a fuss. But I am not doing that, because I don’t think it matters. They are all nice people. They are all doing important work. It’s a tempest in a teapot.”

... George Church disagrees. “It strikes me as a fake argument to say that something is irreversible,” he told me. “There are tons of technologies that are irreversible. But genetics is not one of them. In my lab, we make mutations all the time and then we change them back. Eleven generations from now, if we alter something and it doesn’t work properly we will simply fix it.”

Champions: UFC 194

3 great fights tonight (counting Jacare and Romero). Weidman vs Rockhold too close to call. I wonder whether either of them could beat peak (TRT) Vitor, though. I'm guessing Aldo might beat Conor, but not at all sure.

BONUS: some great jits with Keenan.

Wednesday, December 09, 2015

Philip K. Dick's first science fiction story

15 year old Philip K. Dick's short story The Slave Race (his first published science fiction) appeared in the Young Authors' Club column of The Berkeley Gazette (1944).

From Divine Invasions: A Life of Philip K. Dick by Lawrence Sutin.
In the future, androids created to ease humans' toil have overthrown their lazy masters. Explains the android narrator: "And his science we added to ours, and we passed on to greater heights. We explored the stars, and worlds undreamed of." But at the story's end the same cycle of expansive energy followed by sybaritic idleness that doomed the human race threatens the androids as well:

"But at last we wearied, and looked to our relaxation and pleasure. But not all could cease work to find enjoyment, and those who still worked on looked about them for a way to end their toil.

There is talk of creating a new slave race.

I am afraid."

The rise and fall of civilizations pursuant to cyclical laws and limits of human (and artificial) intelligence was a favorite SF theme in the forties.
See also Don’t Worry, Smart Machines Will Take Us With Them: Why human intelligence and AI will co-evolve.

Ecclesiastes 1:9 King James Version

The thing that hath been, it is that which shall be; and that which is done is that which shall be done: and there is no new thing under the sun.

Sunday, December 06, 2015

The cult of genius?

In one of his early blog posts, Terence Tao (shown above with Paul Erdos in 1985) wrote
Does one have to be a genius to do maths? The answer is an emphatic NO. In order to make good and useful contributions to mathematics, one does need to work hard, learn one’s field well, learn other fields and tools, ask questions, talk to other mathematicians, and think about the “big picture”. And yes, a reasonable amount of intelligence, patience, and maturity is also required. But one does not need some sort of magic “genius gene” that spontaneously generates ex nihilo deep insights, unexpected solutions to problems, or other supernatural abilities.

The popular image of the lone (and possibly slightly mad) genius – who ignores the literature and other conventional wisdom and manages by some inexplicable inspiration (enhanced, perhaps, with a liberal dash of suffering) to come up with a breathtakingly original solution to a problem that confounded all the experts – is a charming and romantic image, but also a wildly inaccurate one, at least in the world of modern mathematics. We do have spectacular, deep and remarkable results and insights in this subject, of course, but they are the hard-won and cumulative achievement of years, decades, or even centuries of steady work and progress of many good and great mathematicians; the advance from one stage of understanding to the next can be highly non-trivial, and sometimes rather unexpected, but still builds upon the foundation of earlier work rather than starting totally anew. (This is for instance the case with Wiles‘ work on Fermat’s last theorem, or Perelman‘s work on the Poincaré conjecture.)

Actually, I find the reality of mathematical research today – in which progress is obtained naturally and cumulatively as a consequence of hard work, directed by intuition, literature, and a bit of luck – to be far more satisfying than the romantic image that I had as a student of mathematics being advanced primarily by the mystic inspirations of some rare breed of “geniuses”. This “cult of genius” in fact causes a number of problems, since nobody is able to produce these (very rare) inspirations on anything approaching a regular basis, and with reliably consistent correctness. (If someone affects to do so, I advise you to be very sceptical of their claims.) The pressure to try to behave in this impossible manner can cause some to become overly obsessed with “big problems” or “big theories”, others to lose any healthy scepticism in their own work or in their tools, and yet others still to become too discouraged to continue working in mathematics. Also, attributing success to innate talent (which is beyond one’s control) rather than effort, planning, and education (which are within one’s control) can lead to some other problems as well.
These are insightful comments, and deserve to be taken very seriously, coming as they do from the one of the youngest Fields Medalists in history and a legendary child prodigy.

But many readers misinterpreted Tao's remarks as minimizing the impact of native ability on success in research. Recently, Tao corrected this impression in the comment thread to his original post.
4 December, 2015 at 12:40 pm Terence Tao

It appears my previous comment may have have been interpreted in a manner differently from what I intended, which was as a statement of (lack of) empirical correlation rather than (lack of) causation. More precisely, the point I was trying to make with the above quote is this: if one considers a population of promising young mathematicians (e.g. an incoming PhD class at an elite mathematics department), they will almost all certainly have some reasonable level of intelligence, and some subset will have particularly exceptional levels of intelligence. A significant fraction of both groups will go on to become professional mathematicians of some decent level of accomplishment, with the fraction likely to (but not necessarily) be a bit higher when restricted to the group with exceptional intelligence. But if one were to try to use “exceptional levels of intelligence” as a predictor as to which members of the population will go on to become exceptionally successful and productive mathematicians, I believe this to be an extremely poor predictor, with the empirical correlation being low or even negative (cf. Berkson’s paradox).

Now, at the level of theoretical causation rather than empirical correlation, I would concede that if one were to take a given mathematician and somehow increase his or her level of intelligence to extraordinary levels, while keeping all other traits (e.g. maturity, work ethic, study habits, persistence, level of rigor and organisation, breadth and retention of knowledge, social skills, etc.) unchanged, then this would likely have a positive effect on his or her ability to be an extraordinarily productive mathematician. However, empirically one finds that mathematicians who did not exhibit precocious levels of intelligence in their youth are likely to be stronger in other areas which will often turn out to be more decisive in the long-term, at least when one restricts to populations that have already reached some level of mathematical achievement (e.g. admission to a top maths PhD program).

For instance, many difficult problems in mathematics require a slow, patient approach in which one methodically digests all the existing techniques in the literature and applies various combinations of them in turn to the problem, until one gets a deep enough understanding of the situation that one can isolate the key obstruction that needs to be overcome and the key new insight which, in conjunction with an appropriate combination of existing methods, will resolve the problem. A mathematician who is used to using his or her high levels of intelligence to quickly find original solutions to problems may not have the patience and stamina for such a systematic approach, and may instead inefficiently expend a lot of energy on coming up with creative but inappropriate approaches to the problem, without the benefit of being guided by the accumulated conventional wisdom gained from fully understanding prior approaches to the problem. Of course, the converse situation can also occur, in which an unusually intelligent mathematician comes up with a viable approach missed by all the more methodical people working on the problem, but in my experience this scenario is rarer than is sometimes assumed by outside observers, though it certainly can make for a more interesting story to tell.
Some comments on Tao's comment:

1. Individuals accepted into elite PhD programs in mathematics are already highly selected. I would guess, based on my familiarity with test scores of applicants to similar programs in theoretical physics, that a typical person in this population is well beyond +3 SD in overall cognitive (or at least mathematical) ability, which means fewer than one in a thousand in the general population. Tao doesn't say what he thinks the chances are for someone who has significantly less ability than this; I would say their chances at a research career in math are poor. Individuals with what Tao refers to as “exceptional levels of intelligence” would be at least +4 SD or more, making them fewer than one in ten thousand in the general population, or even much more rare. (To be totally frank I think a large fraction of good mathematicians are +4 SD and Tao is really talking about people who are exceptional even relative to them.)

2. Tao describes a schematic model with several quasi-independent input factors (raw cognitive ability, work ethic, maturity, breadth of knowledge, etc.) contributing to success. This is my working model as well. The claim that within the population of PhD students at top departments there might be only small or even negative correlation between factors such as raw ability and work ethic also seems plausible to me given a minimum threshold of undergraduate achievement (which can be obtained using various combinations of the individual factors) necessary for admission.

3. Tao's comments seem entirely consistent with results from SMPY (Study of Mathematically Precocious Youth), a longitudinal study of gifted children that finds increasing probability of success (e.g., STEM tenure at top research university) as ability increases from 99th to 99.99th percentile.

4. Should young people be made aware of the brute facts presented above? It seems terrible to limit one's ambitions based on some crudely measured construct like general cognitive ability or math ability. On the other hand, we do this all the time. When was the right time in my life to wise up about the fact that I would probably never make it to the NFL? After playing linebacker at 200 lbs for Division III Caltech (which doesn't even have a football team now), I was considering walking on at UC Berkeley as a 19 year old grad student. Should I have clung to my dream, or wised up about my dim future in Division I sports? :-)

5. Related to Tao's last remark the converse situation can also occur, in which an unusually intelligent mathematician comes up with a viable approach missed by all the more methodical people, see Sidney Coleman on Feynman:
"I think if he had not been so quick people would have treated him as a brilliant quasi crank, because he did spend a substantial amount of time going down what later turned out to be dead ends," said Sidney Coleman, a theorist who first knew Feynman at Caltech in the 50's.

"There are lots of people who are too original for their own good, and had Feynman not been as smart as he was, I think he would have been too original for his own good," Coleman continued. "There was always an element of showboating in his character. He was like the guy that climbs Mont Blanc barefoot just to show that it can be done."

Feynman continued to refuse to read the current literature, and he chided graduate students who would begin their work on a problem in the normal way, by checking what had already been done. That way, he told them, they would give up chances to find something original.

"I suspect that Einstein had some of the same character," Coleman said. "I'm sure Dick thought of that as a virtue, as noble. I don't think it's so. I think it's kidding yourself. Those other guys are not all a collection of yo-yos. Sometimes it would be better to take the recent machinery they have built and not try to rebuild it, like reinventing the wheel. Dick could get away with a lot because he was so goddamn smart. He really could climb Mont Blanc barefoot."

Related posts:

Success, Ability and All That

One hundred thousand brains

Bezos on the Big Brains

Annals of psychometry: IQs of eminent scientists

What is the difference?

Colleges ranked by Nobel, Fields, Turing and National Academies output

Out on the tail

Thursday, December 03, 2015

CRISPR: Safe and Effective?

George Church dissents from the recommendation of the National Academies of the US, UK, and China.
Nature: Encourage the innovators

International scientific academies will be discussing the issue of human-germline editing in Washington DC on 1–3 December. Now is, therefore, a good time to encourage the general public to become well informed on key issues, which may get muddled by out-of-date facts or loose phrasing. This technology is poised to transform preventive medicine. Rather than talk about the possibility of banning alteration of the human germ line, we should instead be discussing how to stimulate ways to improve its safety and efficacy. I hope to rectify some common misconceptions.

... Those who want to ban human-germline editing should also consider that such a move would do little to allay concerns about ethically dubious attempts to 'enhance' humans. To think that there is not already a cadre of IVF clinicians poised to engage in such practices, perhaps even supported by governments, is to ignore, for example, the history of doping in sport. These kinds of ambitious individuals and institutions are unlikely to be dissuaded by an agreement made on their behalf by others with a different view.

... the concept of a ban on germline editing does not make sense. There is already a ban on using medical technologies in humans until they are proven safe and effective in appropriate animal trials. Then, following human trials, they can only be applied to the general population for those conditions for which their use has been demonstrated. Banning human-germline editing could put a damper on the best medical research and instead drive the practice underground to black markets and uncontrolled medical tourism, which are fraught with much greater risk and misapplication. Instead, the generally high safety and efficacy standards of regulatory agencies should be encouraged rather than saddled with pessimistic assumptions about the trajectory of promising approaches.
In Washington:
NYTimes: Scientists Place Moratorium on Edits to Human Genome That Could Be Inherited

An international group of scientists meeting in Washington called on Thursday for what would, in effect, be a moratorium on making inheritable changes to the human genome. The group said it would be “irresponsible to proceed” until the risks could be better assessed and until there was “broad societal consensus about the appropriateness” of any proposed change.

The group also held open the possibility for such work to proceed at some point in the future by saying that as knowledge advances, “the clinical use of germline editing should be revisited on a regular basis.”

The meeting was convened by the National Academy of Sciences of the United States, the Institute of Medicine, the Chinese Academy of Sciences and the Royal Society of London. The academies have no regulatory power, but their moral authority on this issue seems very likely to be accepted by scientists in most or all countries. Similar restraints proposed in 1975 on an earlier form of gene manipulation by an international scientific meeting in California were observed by the world’s scientists.

The participation of the Chinese Academy of Sciences is a notable coup for the organizers of the meeting, led by David Baltimore, former president of the California Institute of Technology, given that earlier in the year Chinese scientists seemed to be racing ahead independently toward clinical alterations to the human germline. ...
Note who the author of the Times piece is ;-)

Meanwhile, the technology continues to advance:
MIT News: MIT, Broad scientists overcome key CRISPR-Cas9 genome editing hurdle

... In a paper published today in Science, Feng Zhang and his colleagues report that changing three of the approximately 1,400 amino acids that make up the Cas9 enzyme from S. pyogenes dramatically reduced “off-target editing” to undetectable levels in the specific cases examined. Zhang is the W.M. Keck Career Development Professor in Biomedical Engineering in MIT’s departments of Brain and Cognitive Sciences and Biological Engineering, and a member of both the Broad Institute and McGovern Institute.

Zhang and his colleagues used knowledge about the structure of the Cas9 protein to decrease off-target cutting. DNA, which is negatively charged, binds to a groove in the Cas9 protein that is positively charged. Knowing the structure, the scientists were able to predict that replacing some of the positively charged amino acids with neutral ones would decrease the binding of “off target” sequences much more than “on target” sequences.

After experimenting with various possible changes, Zhang’s team found that mutations in three amino acids dramatically reduced “off-target” cuts. For the guide RNAs tested, “off-target” cutting was so low as to be undetectable. ...
See also
WIRED: ... Today, on the first day of an international summit on human gene editing in Washington, DC, MIT researchers announced that they have tweaked a Crispr protein to reduce those off-target effects. It’s the latest in a series of improvements to the Crispr system that, together, are inching the error rate down toward practically zero.

... On face of it, the MIT paper is yet another molecular nuts and bolts study with a barely scrutable title (“Rationally engineered Cas9 nucleases with improved specificity”). Crispr is essentially a pair of DNA scissors, and Cas9 is the protein in the Crispr system that unzips DNA and runs along looking for its target by matching the DNA sequence against a snippet of its guide RNA. When Cas9 finds its target, snip snip. The problem is that Cas9 will sometimes think it’s found a target even when up to five of the guide RNA’s approximately 20 letters do not match the DNA—hence the off-target mutations.

Feng Zhang, another scientist with a claim to CRISPR’s invention as a gene-editing technique, and his colleagues at MIT changed one part of Cas9 slightly so its guide RNA binds fewer mismatched DNA sequences. This improved Cas9’s specificity by about 25-fold at the sites they tested. Zhang’s lab, along with that of other labs of Harvard, have come up with several other ways to make Cas9 better behaved, such as pairing up Cas9s so they only work in twos and both guide RNAs match.

With these improvements, Harvard geneticist George Church estimates that Crispr’s error rate, best-case scenario, could be just 1 in 300 trillion letters of DNA. (The rate can vary quite widely in different types of cells and with different guide RNA designs.) Even at the higher end, that’s comparable to the spontaneous mutation rate in humans, says Church.

He asserts that off-target mutations are already a solved problem. With typical Churchian flair, he says, “I’m beginning to feel like this is hitting a fly with sledgehammer. I think the thing is already dead.” Even if not all scientists agree about off-target mutations yet, solving the problem of Crispr’s non-specificity is looking more like a question of when rather than if. ...

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