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Thursday, April 23, 2015

CRISPR edits in human zygotes

Results such as these had been the subject of rumors for some time. Also covered in Nature News.

It is very early days for this technology -- the off-target rate can probably be reduced significantly using better methods. But in the near term, safety and efficacy issues make PGD a better technique for improving human reproduction. See, e.g., PGD in the US and Israel and Single Cell Sequencing in PGD.
CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes
(Protein and Cell -- open access)

Genome editing tools such as the clustered regularly interspaced short palindromic repeat (CRISPR)-associated system (Cas) have been widely used to modify genes in model systems including animal zygotes and human cells, and hold tremendous promise for both basic research and clinical applications. To date, a serious knowledge gap remains in our understanding of DNA repair mechanisms in human early embryos, and in the efficiency and potential off-target effects of using technologies such as CRISPR/Cas9 in human pre-implantation embryos. In this report, we used tripronuclear (3PN) zygotes to further investigate CRISPR/Cas9-mediated gene editing in human cells. We found that CRISPR/Cas9 could effectively cleave the endogenous β-globin gene (HBB). However, the efficiency of homologous recombination directed repair (HDR) of HBB was low and the edited embryos were mosaic. Off-target cleavage was also apparent in these 3PN zygotes as revealed by the T7E1 assay and whole-exome sequencing. Furthermore, the endogenous delta-globin gene (HBD), which is homologous to HBB, competed with exogenous donor oligos to act as the repair template, leading to untoward mutations. Our data also indicated that repair of the HBB locus in these embryos occurred preferentially through the non-crossover HDR pathway. Taken together, our work highlights the pressing need to further improve the fidelity and specificity of the CRISPR/Cas9 platform, a prerequisite for any clinical applications of CRSIPR/Cas9-mediated editing.
The table below is from the Supplement.

Wednesday, April 22, 2015

Earnings by educational attainment 1990-2013

This graphic is from today's NYTimes: Why American Workers Without Much Education Are Being Hammered.

Aside from the human capital (education) point the figure makes, I'm a bit puzzled by the following: real per-capita GDP is probably up at least ~50% (e.g., ~2% x 23 years) over the 1990-2013 period. Where did those gains go? Into the pockets of a small invisible group that doesn't show up in the graph (note use of medians, not averages)? It seems that everyone except the members of this small group were "hammered" over the last two decades ...

Note added (with better data): This source has 2013 GDP at $16 trillion versus $9 trillion in 1990 (both figures in 2009 dollars). Total US population went up 26% (316 million from 249 million). The percentage of the population with college degrees went from about 20% to 30%. It still appears to me that much of GDP increase during the period did not go to workers or ordinary people.

If you annualize any of the real income changes in the graph over 23 years, the change is small -- less than 1% per year. Yet real GDP grew at about 3% per year on average during the period. The graph below (from this 2007 post) might shed some light on the mystery (even the top quintile saw little income appreciation):

More here.

Tuesday, April 21, 2015

China's Ideological Spectrum

These researchers identify a dominant principal component in the Chinese ideological spectrum. Discussed on Sinica podcast.

China's Ideological Spectrum

Jennifer Pan (Harvard University - Graduate School of Arts and Sciences)
Yiqing Xu (MIT - Department of Political Science)

We offer the first large scale empirical analysis of ideology in contemporary China to determine whether individuals fall along a discernible and coherent ideological spectrum, and whether there are regional and inter-group variations in ideological orientation. Using principal component analysis (PCA) on a survey of 171,830 individuals, we identify one dominant ideological dimension in China. Individuals who are politically conservative, who emphasize the supremacy of the state and nationalism, are also likely to be economically conservative, supporting a return to socialism and state-control of the economy, and culturally conservative, supporting traditional, Confucian values. In contrast, political liberals, supportive of constitutional democracy and individual liberty, are also likely to be economic liberals who support market-oriented reform and social liberals who support modern science and values such as sexual freedom. This uni-dimensionality of ideology is robust to a wide variety of diagnostics and checks. Using post-stratification based on census data, we find a strong relationship between liberal orientation and modernization -- provinces with higher levels of economic development, trade openness, urbanization are more liberal than their poor, rural counterparts, and individuals with higher levels of education and income and more liberal than their less educated and lower-income peers.
Warning: PCA is the tool of the devil ;-)

Sunday, April 19, 2015

Ulam on physical intuition and visualization

The picture above is of von Neumann, Feynman, and Ulam. More Ulam. See also the nature of intuition and intuition and the two brains.
Adventures of a Mathematician: (p.147-148) ... the main ability to have was a visual, and also an almost tactile, way to imagine the physical situations, rather than a merely logical picture of the problems.

The feeling for problems in physics is quite different from purely theoretical mathematical thinking. It is hard to describe the kind of imagination that enables one to guess at or gauge the behavior of physical phenomena. Very few mathematicians seem to possess it to any great degree. Johnny [vN], for example, did not have to any extent the intuitive common sense and "gut" feeling or penchant for guessing what happens in given physical situations. His memory was mainly auditory, rather than visual.

Another thing that seems necessary is the knowledge of a dozen or so physical constants, not merely of their numerical value, but a real feeling for their relative orders of magnitude and interrelations, and, so to speak, an instinctive ability to "estimate."

I knew, of course, the values of constants like the velocity of light and maybe three or four other fundamental constants—the Planck constant h, a gas constant R, etc. Very soon I discovered that if one gets a feeling for no more than a dozen other radiation and nuclear constants, one can imagine the subatomic world almost tangibly, and manipulate the picture dimensionally and qualitatively, before calculating more precise relationships.

Most of the physics at Los Alamos could be reduced to the study of assemblies of particles interacting with each other, hitting each other, scattering, sometimes giving rise to new particles. Strangely enough, the actual working problems did not involve much of the mathematical apparatus of quantum theory although it lay at the base of the phenomena, but rather dynamics of a more classical kind—kinematics, statistical mechanics, large-scale motion problems, hydrodynamics, behavior of radiation, and the like. In fact, compared to quantum theory the project work was like applied mathematics as compared with abstract mathematics. If one is good at solving differential equations or using asymptotic series, one need not necessarily know the foundations of function space language. It is needed for a more fundamental understanding, of course. In the same way, quantum theory is necessary in many instances to explain the data and to explain the values of cross sections. But it was not crucial, once one understood the ideas and then the facts of events involving neutrons reacting with other nuclei.
This "dynamics of a more classical kind" did not require intuition for entanglement or high dimensional Hilbert spaces. But see von Neumann and the foundations of quantum statistical mechanics for examples of the latter.

Saturday, April 18, 2015

Summer of '69

I love this video. The clothes, the hair, the faces -- they're all so familiar. Every person in the video looks like someone I grew up with in the midwest :-)

Tuesday, April 14, 2015

2:1 faculty preference for women on STEM tenure track (PNAS)

The results described below suggest that faculty evaluators of STEM job applicants tend to favor women over men. Certainly, most departments receive strong incentives and signals from above to increase numbers of women and underrepresented minorities among their faculty. Women could still face obstacles at other points in their careers, such as during promotion or merit reviews, or in the competition for resources such as grant funding or lab space. Nevertheless, I think gender discrimination has decreased significantly during my adult life.

This article is also discussed in Nature. See also STEM, Gender, and Leaky Pipelines and Gender differences in preferences, choices, and outcomes. Earlier blog posts citing research by Ceci and Williams.
National hiring experiments reveal 2:1 faculty preference for women on STEM tenure track (PNAS)

Wendy M. Williams and Stephen J. Ceci

National randomized experiments and validation studies were conducted on 873 tenure-track faculty (439 male, 434 female) from biology, engineering, economics, and psychology at 371 universities/colleges from 50 US states and the District of Columbia. In the main experiment, 363 faculty members evaluated narrative summaries describing hypothetical female and male applicants for tenure-track assistant professorships who shared the same lifestyle (e.g., single without children, married with children). Applicants' profiles were systematically varied to disguise identically rated scholarship; profiles were counterbalanced by gender across faculty to enable between-faculty comparisons of hiring preferences for identically qualified women versus men. Results revealed a 2:1 preference for women by faculty of both genders across both math-intensive and non–math-intensive fields, with the single exception of male economists, who showed no gender preference. Results were replicated using weighted analyses to control for national sample characteristics. In follow-up experiments, 144 faculty evaluated competing applicants with differing lifestyles (e.g., divorced mother vs. married father), and 204 faculty compared same-gender candidates with children, but differing in whether they took 1-y-parental leaves in graduate school. Women preferred divorced mothers to married fathers; men preferred mothers who took leaves to mothers who did not. In two validation studies, 35 engineering faculty provided rankings using full curricula vitae instead of narratives, and 127 faculty rated one applicant rather than choosing from a mixed-gender group; the same preference for women was shown by faculty of both genders. These results suggest it is a propitious time for women launching careers in academic science. Messages to the contrary may discourage women from applying for STEM (science, technology, engineering, mathematics) tenure-track assistant professorships.

Saturday, April 11, 2015

IQ prediction from structural MRI

These authors use machine learning techniques to build sparse predictors based on grey/white matter volumes of specific regions. Correlations obtained are ~ 0.7 (see figure).

I predict that genomic estimators of this kind will be available once ~ 1 million genomes and cognitive scores are available for analysis. See also Myths, Sisyphus and g.
MRI-Based Intelligence Quotient (IQ) Estimation with Sparse Learning (PLOS)

In this paper, we propose a novel framework for IQ estimation using Magnetic Resonance Imaging (MRI) data. In particular, we devise a new feature selection method based on an extended dirty model for jointly considering both element-wise sparsity and group-wise sparsity. Meanwhile, due to the absence of large dataset with consistent scanning protocols for the IQ estimation, we integrate multiple datasets scanned from different sites with different scanning parameters and protocols. In this way, there is large variability in these different datasets. To address this issue, we design a two-step procedure for 1) first identifying the possible scanning site for each testing subject and 2) then estimating the testing subject’s IQ by using a specific estimator designed for that scanning site. We perform two experiments to test the performance of our method by using the MRI data collected from 164 typically developing children between 6 and 15 years old. In the first experiment, we use a multi-kernel Support Vector Regression (SVR) for estimating IQ values, and obtain an average correlation coefficient of 0.718 and also an average root mean square error of 8.695 between the true IQs and the estimated ones. In the second experiment, we use a single-kernel SVR for IQ estimation, and achieve an average correlation coefficient of 0.684 and an average root mean square error of 9.166. All these results show the effectiveness of using imaging data for IQ prediction, which is rarely done in the field according to our knowledge.
Training and testing of models was performed as described below. They had only 164 individuals in their sample, so IIUC the average correlation is computed on test samples of ~16 individuals. It would be good to see their predictors tested on larger data sets. I wonder how stable the predictor variables (feature coefficients) were across partitions.
We performed experiments with 10-fold cross-validations. Specifically, we randomly partitioned each dataset into 10 subsets with no replacement, and used 9 out of the 10 subsets for training and the remaining one for testing. To further avoid a possible bias during partitioning, we repeated the experiments 10 times.
Some background from the paper. Strangely, they don't cite the Thompson lab (UCLA) results on brain size and intelligence (21k individuals). IIRC from their results, brain size alone correlates 0.4 with IQ.
... Uncovering human intelligence has always been of major interest in cognitive neuroscience. With the advent of brain imaging, there have been efforts to investigate the relation between brain anatomy and intelligence [3,4], and substantial understanding has been achieved in the field. For example, Supekar et al. showed that the size and circuitry of certain parts of children’s brains could be a potential predictor for how well they would respond to intensive math tutoring [5]. Chen et al. [6] demonstrated that the volumetric analysis of gray matter (GM) from structural Magnetic Resonance Imaging (MRI) could be used to predict a subsequent decline in IQ in children with sickle cell disease. McDaniel et al. [3] found that the volume of the brain is positively correlated with IQ according to MRI-based experiments. Frangou et al. [7] reported positive correlations between IQ score and GM density of the orbitofrontal cortex, cingulate gyrus, cerebellum, and thalamus, but negative correlation between IQ score and the caudate nucleus. On the other hand, Navas-Sanchez et al. [8] investigated the relationship between IQ score and microstructure of white matter (WM) tracts using diffusion tensor imaging (DTI), and found that IQ score is positively correlated with fractional anisotropy (FA). Kim et al. [9] found that lower performance in verbal IQ score is correlated with the decrease of FA values. In another DTI-based study, Welcome et al. [10] discovered that the volume of WM fiber tracts is correlated with nonverbal IQ score. Inspired by these strong correlations between brain anatomy and IQ score, we propose, in this study, a novel framework to estimate IQ by using GM and WM features extracted from structural MRI. ...
Their results might give some indication as to which regions of the brain are responsible for most of the population variation in IQ. Below are the brain regions most commonly identified as "features" by sparse learning methods.

From the comments (55% of variance means a correlation just larger than 0.7):
There are lots of recent studies that have tried to estimate IQ from MRI or EEG readings (sometimes called "neurometric" IQ); many of the teams are based in South Korea and Malaysia. The Malaysian group, based at the MARA University of Technology, has published about a dozen papers over the past two years, involving hundreds of subjects. They can now use EEG readings to sort subjects into one of seven IQ ranges (e.g. 90-100, 120-130) with 83% accuracy; this figure jumps to 98% when subjects are sorted into one of three IQ ranges (low, medium, or high). The South Korean researchers, at Seoul National University, have been combining MRI and fMRI scans to predict IQ scores, and in late 2012 they were granted a patent for their "neurobiological method for measuring human intelligence," which can explain up to 55% of the variance between individual IQ scores. An example (from Dec 2013) is at

Additional links:

Thursday, April 09, 2015

For this you went to Harvard?

Personal assistants of the world, unite!

Better to reign in Hell, than serve in Heaven  ;-)
Dissent Magazine: ... When I was an undergrad at Harvard, the English department produced fancy brochures about the opportunities available to its majors: teacher, editor, Rhodes scholar. Personal assistant was not listed. I hadn’t even heard of such positions until senior year, when older friends, artistically inclined friends, started snagging them. It’s the position I think I’ve heard most about now.

Nearly every exclusive field runs on assistants. The actor James Franco, like Buddha before him, had an assistant keep track of his meals and school assignments. The critic and writer Daphne Merkin has employed a steady stream of Ivy-educated elves. They’re tasked with everything from editing to returning dead houseplants. Bestselling novelist John Irving (The Cider House Rules, A Prayer for Owen Meany) has an assistant who types up his roughly twenty-five pages of handwritten manuscript a day. He recruits exclusively from liberal arts schools in cold climates like Middlebury and Vassar, to ensure his hires can survive the winter at his home in Dorset, Vermont. During the 2008 presidential season, recent Harvard grad Eric Lesser impressed senior advisor to the president, David Axelrod, with his color-coded system for tracking Obama’s campaign luggage. Lesser was taken on as Axelrod’s “special assistant,” assuming responsibility for everything from supervising his boss’s diet to organizing the first-ever presidential Seder.

Welcome to the main artery into creative or elite work—highly pressurized, poorly recompensed, sometimes exhilarating, sometimes menial secretarial assistance. From the confluence of two grand movements in American history—the continued flight of women out of the home and into the workplace, and the growing population of arts and politically oriented college graduates struggling to survive in urban epicenters that are increasingly ceded to bankers and consultants—the personal assistant is born. ...

... One of the most exceptional—and mysterious—personal assistantship programs is run by a hedge fund billionaire in New York. For years, his human resources staff used to tuck the same discreet, neatly boxed advertisement in alongside the dense criticism of the New Republic and the New York Review of Books, as well as in Ivy League alumni magazines:
RESEARCH ASSOCIATE/PERSONAL ASSISTANT New York City—Highly intelligent, resourceful individuals with exceptional communication skills sought to undertake research projects and administrative tasks for one of Wall Street’s most successful entrepreneurs. We welcome applications from writers, musicians, artists, or others who may be pursuing other professional goals in the balance of their time. $90-110k/yr to start (depending on qualifications). Resume to:
The firm recruits and interviews year-round, whether there are openings or not. In addition to ads, the billionaire’s people email Phi Beta Kappa and summa students from top colleges about openings at the firm, though they are also likely scouting for assistants. “Although much of our work involves the use of advanced mathematical and computational techniques,” the email reads, “we are equally interested in speaking with brilliant liberal arts graduates, regardless of major, who are open to the possibility of a career they may never have previously considered.” It might be the only time in their lives that art students or English majors are courted by a potential employer. “The firm,” the email continues, “ . . . can give serious consideration only to individuals having extraordinary intellectual capabilities, communication skills, and general ‘real world’ competence.” Of the many who apply, a handful are called to New York, where their “real world competence” is quantified in no fewer than five management consulting-style interviews. Interviewees sign non-disclosure forms, and if hired as personal assistants, are essentially barred from saying where they work. When pressed, they might say they are writing books or “making music.” ...

Saturday, April 04, 2015

Multigenerational mobility: does the Son Also Rise?

The working paper below on multigenerational mobility arrives at smaller intergenerational correlations than Greg Clark obtained (e.g., 0.4 vs 0.7). I found Clark's results hard to explain, at least in genetic terms, because estimates of assortativity in mating are much lower than required.

Related posts here and here. From the second link:
Correlations as high as 0.7 -- 0.8 are implausible from genetic factors alone without highly assortative mating. Traits such as height and IQ have narrow sense heritabilities as large as h2 ~ 0.6, so fraction of variance accounted for is ~ 60%, and midparent-child correlation as high as ~ 0.8, but under even somewhat random mating the parental midpoint is significantly closer to average than the phenotype of the more exceptional parent. This would cause children to regress to the mean much faster in height and IQ than in social status as indicated in Clark's data. It's also important to note that social status itself is only imperfectly correlated to observable phenotypes such as IQ, Conscientiousness or Extraversion. See Intergenerational mobility: Bowles, Gintis, Clark for more.
Solon's results seem to be consistent with Bowles and Gintis.
What Do We Know So Far about Multigenerational Mobility?

Gary Solon
Michigan State University

“Multigenerational mobility” refers to the associations in socioeconomic status across three or more generations. This article begins by summarizing the longstanding but recently growing empirical literature on multigenerational mobility. It then discusses multiple theoretical interpretations of the empirical patterns, including the one recently proposed in Gregory Clark’s book The Son Also Rises.

... contrary to Clark’s prediction, most group-average studies other than his own – including the surnames-based work by Chetty et al. – have estimated much smaller intergenerational associations.
Clark was recently interviewed on KQED Forum. Michael Krasny was willing to entertain Clark's Social Darwinistic perspective ;-)

Income, wealth, and IQ

I'm occasionally asked about financial returns to cognitive ability. As a rough rule of thumb, judging from the graphs below (obtained here), I would say:
On average, an increase of IQ by one SD corresponds to  ~ $30k per annum of additional income. (Somewhat less than 1 SD in income; the distribution is far from normal.)

By early middle age, individuals > 90th percentile in IQ have, typically, more than twice the wealth of individuals who are of average IQ.
If you can find better data than what is shown below, please let me know. (How do bottom decile adults manage to earn ~ $40k per annum, on average? Does this include transfer payments?)

Of course, you can turn this around to estimate the increased (heritable) cognitive ability endowments of high income parents relative to average parents. That might help to clarify causality in results such as this one: "Studies show that children from low-income families have smaller brains and lower cognitive abilities." (Even Nature susceptible to faulty logic.)

Note, there is good evidence that positive returns to IQ persist above high thresholds (e.g., IQ=120, or even top 1 percent ability). See here and here.

Income mobility is strongly affected by IQ. In fact, IQ is a much stronger predictor variable than race for escaping the bottom quintile of income (Pew Trust report; NLSY again, AFQT=IQ scores):

This last figure is very problematic for the "Social Status/Wealth causes IQ" position. It seems to be the other way around: the kids escaping bottom quintile childhoods all experienced poverty, but the ones with higher cognitive ability were more likely to move up. (Recall that adopted children tend to resemble their biological parents much more than their adoptive ones; family environment has a limited effect on IQ, which is highly heritable.)
Pew: Individuals with higher test scores in adolescence are more likely to move out of the bottom quintile, and test scores can explain virtually the entire black-white mobility gap. Figure 13 plots the transition rates against percentiles of the AFQT test score distribution. The upward-sloping lines indicate that, as might be expected, individuals with higher test scores are much more likely to leave the bottom income quintile. For example, for whites, moving from the first percentile of the AFQT distribution to the median roughly doubles the likelihood from 42 percent to 81 percent. The comparable increase for blacks is even more dramatic, rising from 33 percent to 78 percent. Perhaps the most stunning finding is that once one accounts for the AFQT score, the entire racial gap in mobility is eliminated for a broad portion of the distribution. At the very bottom and in the top half of the distribution a small gap remains, but it is not statistically significant.

Wednesday, April 01, 2015

Gene drive

IIUC, there is a self-referential ("auto-catalyzing") aspect to this method which is very interesting. The Cas9 gene (payload) also encodes the guide RNA (target) information, which determines the location of the DNA cut.

Needless to say, this is a very powerful and potentially dangerous technology.

Enrico Fermi (speaking about atomic weapons): Once basic knowledge is acquired, any attempt at preventing its fruition would be as futile as hoping to stop the earth from revolving around the sun.
Biologists devise invasion plan for mutations (Science): On 28 December 2014, Valentino Gantz and Ethan Bier checked on the fruit flies that had just hatched in their lab at the University of California (UC), San Diego. By the classic rules of Mendelian genetics, only one out of four of the newborn flies should have shown the effects of the mutation their mothers carried, an X-linked recessive trait that causes a loss of pigmentation similar to albinism. Instead, nothing but pale yellow flies kept emerging. “We were stunned,” says Bier, who is Gantz's Ph.D. adviser. “It was like the sun rose in the west rather than the east.” They hammered out a paper and submitted it to Science 3 days later. [ Bier and Gantz Science paper ]

... George Church, a geneticist at Harvard Medical School in Boston who is a leader in the field, believes the new study should not have been published, because it does not include measures to restrain the spread of unintended mutations. “It is a step too far,” he says. ...

... Creating a gene drive system wasn't Gantz's original goal, Bier says. “We were just trying to solve a practical problem.” Gantz studies the development of fruit fly wing veins, for which he must create flies with multiple mutations. That's typically painstaking work, requiring large numbers of flies over many generations to create a single multimutant. Last summer, Gantz made a tweak to the CRISPR system, in which an engineered bacterial protein, Cas9, uses a string of RNA to find and delete, replace, or otherwise edit a target DNA sequence. By equipping the CRISPR gene cassette with DNA sequences flanking the targeted gene, Gantz hoped to create a mutation that would “auto-catalyze.” Once incorporated on one chromosome, it would produce new copies of the CRISPR complex that would target and edit the gene everywhere it appeared. ...

Similar demonstration in yeast by the Church lab:
... Because synthetic gene drives would alter the global environmental commons, the decision to deploy such a drive must be made collectively by society. ... Fortunately, a simple and costless precaution is both available and already utilized for different reasons by many laboratories: avoid delivering the Cas9 gene on a DNA cassette that also encodes a guide RNA. ...
See also Regulating Gene Drives (Science). More on how to avoid making a gene drive:

The following paper from Harvard's Wyss Institute (which also produced the video below) provides a nice overview of CRISPR gene drives. The paper appeared last summer.
Emerging technology: Concerning RNA-guided gene drives for the alteration of wild populations

Abstract: Gene drives may be capable of addressing ecological problems by altering entire populations of wild organisms, but their use has remained largely theoretical due to technical constraints. Here we consider the potential for RNA-guided gene drives based on the CRISPR nuclease Cas9 to serve as a general method for spreading altered traits through wild populations over many generations. We detail likely capabilities, discuss limitations, and provide novel precautionary strategies to control the spread of gene drives and reverse genomic changes. The ability to edit populations of sexual species would offer substantial benefits to humanity and the environment. For example, RNA-guided gene drives could potentially prevent the spread of disease, support agriculture by reversing pesticide and herbicide resistance in insects and weeds, and control damaging invasive species. However, the possibility of unwanted ecological effects and near-certainty of spread across political borders demand careful assessment of each potential application. We call for thoughtful, inclusive, and well-informed public discussions to explore the responsible use of this currently theoretical technology.

... We submit that Cas9 is highly likely to enable scientists to construct efficient RNA-guided gene drives not only in mosquitoes, but in many other species. In addition to altering populations of insects to prevent them from spreading disease (Curtis, 1968), this advance would represent an entirely new approach to ecological engineering with many potential applications relevant to human health, agriculture, biodiversity, and ecological science. ...

Monday, March 30, 2015

The rich (and powerful) are different

Discussions at the meeting I just attended are off the record, so I have nothing to report. But I will link to some previous posts of relevance:

Creators and Rulers

How the World Works

Educational background of US elites

A word cloud produced from the collective bios would feature: Harvard, Stanford, Goldman Sachs, Rhodes, Marshall, Venture, Private Equity, Acquired, IPO, Technology, Energy, SEALs, Family Office, White House, Society of Fellows, ...

My wife looked at the book of bios and concluded "You don't stand out."  8-/

See also Status-Income Disequilibrium.

Thursday, March 26, 2015

Dialog 2015

I'm at a fancy meeting with a bunch of money folk, tech entrepreneurs, and scientists. No, it's not Foo Camp, but might be similar ... don't know yet.

I doubt there will be an Illuminati / Dark Enlightenment initiation ceremony, but one can always hope ;-)
Dialog is an biannual 2-day thought retreat, gathering 150 global leaders to discuss how to change the world. Dialog was created in 2006 to bring together global leaders across industries to discuss some of the most pressing world issues, to provide an opportunity for cross-pollination & collaboration.

There are no speakers. No panels. All attendees participate in break-out facilitated discussions. And we limit the discussion to only 150 global leaders who can have an impact now and emerging leaders who can help implement the plans we develop.

There are no speeches, just many coordinated, moderated break-out discussions of 6-15 people. The agenda is determined by the attendees directly, based on their interests and needs.

Dialog is an invite-only retreat and we carefully curate all participants. Dialog is 100% off-the-record and not-for-attribution. Dialog is hosted by Auren Hoffman and Peter Thiel.


Summertime Sadness

See also Lana Del Rey.

Sunday, March 22, 2015

Lee Kwan Yew dead at 91

Lee Kwan Yew has passed at 91. See the 2005 interview with Der Spiegel below for some interesting comments from 10 years ago.

Lee: "I always tried to be correct, not politically correct." —From Third World to First: The Singapore Story.

Mr. Lee: I faced this problem myself. Every year, our unions and the Labour Department subsidize trips to China and India. We tell the participants: Don't just look at the Great Wall but go to the factories and ask, "What are you paid?" What hours do you work?" And they come back shell-shocked. The Chinese had perestroika first, then glasnost. That's where the Russians made their mistake.

SPIEGEL: The Chinese Government is promoting the peaceful rise of China. Do you believe them?

Mr. Lee: Yes, I do, with one reservation. I think they have calculated that they need 30 to 40 -- maybe 50 years of peace and quiet to catch up, to build up their system, change it from the communist system to the market system. They must avoid the mistakes made by Germany and Japan. Their competition for power, influence and resources led in the last century to two terrible wars.

SPIEGEL: What should the Chinese do differently?

Mr. Lee: They will trade, they will not demand, "This is my sphere of influence, you keep out". America goes to South America and they also go to South America. Brazil has now put aside an area as big as the state of Massachusetts to grow soya beans for China. They are going to Sudan and Venezuela for oil because the Venezuelan President doesn't like America. They are going to Iran for oil and gas. So, they are not asking for a military contest for power, but for an economic competition.

SPIEGEL: But would anybody take them really seriously without military power?

Mr. Lee: About eight years ago, I met Liu Huaqing, the man who built the Chinese Navy. Mao personally sent him to Leningrad to learn to build ships. I said to him, "The Russians made very rough, crude weapons". He replied, "You are wrong. They made first-class weapons, equal to the Americans." The Russian mistake was that they put so much into military expenditure and so little into civilian technology. So their economy collapsed. I believe the Chinese leadership have learnt: If you compete with America in armaments, you will lose. You will bankrupt yourself. So, avoid it, keep your head down, and smile, for 40 or 50 years.

SPIEGEL: What are your reservations?

Mr. Lee: I don't know whether the next generation will stay on this course. After 15 or 20 years they may feel their muscles are very powerful. We know the mind of the leaders but the mood of the people on the ground is another matter. ...

Educational background of US elites

Jonathan Wai writes in Quartz about returns to elite education in the US. Wai also notes that more than ten percent of all Senators, billionaires, Federal judges, and Fortune 500 CEOs hold Harvard degrees of some kind.

See also Credentialism and elite performance, and further links therein.

Blue = attended elite undergraduate college or graduate school (no more than ~few percent of US population, so highly overrepresented in the groups listed above).

Red = earned a graduate degree but did not attend elite school.

Green = earned an undergraduate degree but not in either category above.

Thursday, March 19, 2015

Après nous le déluge

You can always blame the Chinese.

See also A prudent path forward for genomic engineering and germline gene modification (Baltimore et al.) and Germ line editing and human evolution.
Science: Embryo engineering alarm

... In 1975, the Asilomar conference center hosted a meeting where molecular biologists, physicians, and lawyers crafted guidelines for research that altered the DNA of living organisms. Now, scientists are calling for another Asilomar—this time to discuss the possibility of genetically engineered human beings.

... Rumors are rife, presumably from anonymous peer reviewers, that scientists in China have already used CRISPR on human embryos and have submitted papers on their results. They have apparently not tried to establish any pregnancies, but the rumors alarm researchers who fear that such papers, published before broad discussions of the risks and benefits of genome editing, could trigger a public backlash that would block legitimate uses of the technology.

... But scientists don't yet understand all the possible side effects of tinkering with germ cells or embryos. Monkeys have been born from CRISPR-edited embryos, but at least half of the 10 pregnancies in the monkey experiments ended in miscarriage. In the monkeys that were born, not all cells carried the desired changes, so attempts to eliminate a disease gene might not work. The editing can also damage off-target sites in the genome.

Those uncertainties, together with existing regulations, are sufficient to prevent responsible scientists from attempting any genetically altered babies, says George Church, a molecular geneticist at Harvard Medical School in Boston. Although he signed the Science commentary, he says the discussion “strikes me as a bit exaggerated.” He maintains that a de facto moratorium is in place for all technologies until they're proven safe. “The challenge is to show that the benefits are greater than the risks.”

... Although many European countries ban germline genetic engineering in humans, the United States and China do not have such laws. Research with private funds is subject to little oversight in the United States, although any attempts to establish a pregnancy would need approval from the U.S. Food and Drug Administration. In China, any clinical use is prohibited by the Ministry of Health guidelines, but not by law.

... Church hopes such discussions will tackle a question that he says both commentaries avoid: “What is the scenario that we're actually worried about? That it won't work well enough? Or that it will work too well?”
Enrico Fermi (speaking about atomic weapons): Once basic knowledge is acquired, any attempt at preventing its fruition would be as futile as hoping to stop the earth from revolving around the sun.

Wednesday, March 18, 2015

Fischer Black: "a vision of the future that came true"

This is Barnard professor Perry Mehrling on the origin of interest rate and credit derivatives in the mind of Fischer Black. I highly recommend Mehrling's biography of Black, which I discussed previously here:
Black was both an undergrad and grad student at Harvard in physics. He didn't really complete his PhD in physics, but sort of drifted into AI-related stuff(!) at MIT, under cover of math or applied math.

The bio says the only course he ever had trouble with was Schwinger's course on advanced quantum. The biographer suggests Black did poorly due to lack of interest, but I find that hard to believe given the subject matter, the lecturer, and the times ;-)

Black's point of view was clearly that of a physicist or applied mathematician. He really was a fascinating guy, and the biographer, an academic economist, can appreciate a lot of Black's thinking -- it's not an entirely superficial book despite being non-technical.

After reading the book, I don't feel so bad about questioning some of the fundamental assumptions made by academic economists. Black was asking some of the very same questions during his career.
From the book jacket:
... Although the options formula made him famous, it was only one of Black's numerous contributions to finance, including portfolio insurance, commodity futures pricing, bond swaps and interest rate futures, and global asset allocation models that have become standard in the world of finance. Amazingly, he did it all despite having no formal training in finance or economics, and despite spending the bulk of his career in business settings. Certainly the most notable non-academic theoretician of modern finance, Fischer Black was one of a kind...
For more on derivatives history, see Pricing the Future and The World is our Laboratory.

Sunday, March 15, 2015

Eight thousand years of natural selection in Europe

The latest from the Reich lab at Harvard. The availability of ancient DNA allows for direct comparisons between ancestral and descendant populations. These methods will only become more powerful as technology and access to samples improve.

Note the evidence for polygenic selection on height, over timescales of less than 10k years. (Fig. 3 from paper displayed above.) See also Recent human evolution: European height.
Eight thousand years of natural selection in Europe

The arrival of farming in Europe beginning around 8,500 years ago required adaptation to new environments, pathogens, diets, and social organizations. While evidence of natural selection can be revealed by studying patterns of genetic variation in present-day people, these pattern are only indirect echoes of past events, and provide little information about where and when selection occurred. Ancient DNA makes it possible to examine populations as they were before, during and after adaptation events, and thus to reveal the tempo and mode of selection. Here we report the first genome-wide scan for selection using ancient DNA, based on 83 human samples from Holocene Europe analyzed at over 300,000 positions. We find five genome-wide signals of selection, at loci associated with diet and pigmentation. Surprisingly in light of suggestions of selection on immune traits associated with the advent of agriculture and denser living conditions, we find no strong sweeps associated with immunological phenotypes. We also report a scan for selection for complex traits, and find two signals of selection on height: for short stature in Iberia after the arrival of agriculture, and for tall stature on the Pontic-Caspian steppe earlier than 5,000 years ago. A surprise is that in Scandinavian hunter-gatherers living around 8,000 years ago, there is a high frequency of the derived allele at the EDAR gene that is the strongest known signal of selection in East Asians and that is thought to have arisen in East Asia. These results document the power of ancient DNA to reveal features of past adaptation that could not be understood from analyses of present-day people.
From the paper:
... We also tested for selection on complex traits, which are controlled by many genetic variants, each with a weak effect. Under the pressure of natural selection, these variants are expected to experience small but correlated directional shifts, rather than any single variant changing dramatically in frequency, and recent studies have argued that this may be a predominant mode of natural selection in humans40. The best documented example of this process in humans is height, which has been shown to have been under recent selection in Europe41. At alleles known from GWAS to affect height, northern Europeans have, on average, a significantly higher probability of carrying the height-increasing allele than southern Europeans, which could either reflect selection for increased height in the ancestry of northern Europeans or decreased height in the ancestry of southern Europeans. To test for this signal in our data, we used a statistic that tests whether trait-affecting alleles are more differentiated than randomly sampled alleles, in a way that is coordinated across all alleles consistent with directional selection42. We applied the test to all populations together, as well as to pairs of populations in order to localize the signal (Figure 3, Extended Data Figure 5, Methods).

We detect a significant signal of directional selection on height in Europe (p=0.002), and our ancient DNA data allows us to determine when this occurred and also to determine the direction of selection. Both the Iberian Early Neolithic and Middle Neolithic samples show evidence of selection for decreased height relative to present-day European Americans (Figure 3A; p=0.002 and p < 0.0001, respectively). Comparing populations that existed at the same time (Figure 3B), there is a significant signal of selection between central European and Iberian populations in each of the Early Neolithic, Middle Neolithic and present-day periods (p=0.011, 0.012 and 0.004, respectively). Therefore, the selective gradient in height in Europe has existed for the past 8,000 years. This gradient was established in the Early Neolithic, increased into the Middle Neolithic and decreased at some point thereafter. Since we detect no significant evidence of selection or change in genetic height among Northern European populations, our results further suggest that selection operated mainly on Southern rather than Northern European populations. There is another possible signal in the Yamnaya, related to people who migrated into central Europe beginning at least 4,800 years ago and who contributed about half the ancestry of northern Europeans today9 . The Yamnaya have the greatest predicted genetic height of any population, and the difference between Yamnaya and the Iberian Middle Neolithic is the greatest observed in our data. ...

If the analysis leading to the figure below is correct, shifts on the order of 1 SD are possible over timescales less than 10k years, due to natural selection in human populations. Say it with me again: Selection, Not Drift.  (Click for larger version.)

Friday, March 13, 2015

Rigorous inequalities

The Effects of an Anti-grade-Inflation Policy at Wellesley College
Journal of Economic Perspectives, 28(3): 189-204 (2014)
DOI: 10.1257/jep.28.3.189

Average grades in colleges and universities have risen markedly since the 1960s. Critics express concern that grade inflation erodes incentives for students to learn; gives students, employers, and graduate schools poor information on absolute and relative abilities; and reflects the quid pro quo of grades for better student evaluations of professors. This paper evaluates an anti-grade-inflation policy that capped most course averages at a B+. The cap was biding for high-grading departments (in the humanities and social sciences) and was not binding for low-grading departments (in economics and sciences), facilitating a difference-in-differences analysis. Professors complied with the policy by reducing compression at the top of the grade distribution. It had little effect on receipt of top honors, but affected receipt of magna cum laude. In departments affected by the cap, the policy expanded racial gaps in grades, reduced enrollments and majors, and lowered student ratings of professors.
Jim Schombert and I discovered similar disparities in our study of University of Oregon student grades. The inequities would be even larger after controlling for student ability. Eventually employers may demand learning outcomes testing (see Measuring college learning outcomes: psychometry 101), and the results won't be pretty.

Via Carl Shulman and orgtheory.

The Fourth Law of Behavior Genetics?

I believe the law stated below almost follows from the observation that humans brains are complex machines: hence the DNA blueprint has many components, and variance is spread over these components  :^)

However, note the evidence for discrete genetic modules of large effect in other species: Discrete genetic modules can control complex behavior (burrowing behavior in cute mouse in picture at bottom), As flies to wanton boys are we to the gods (discrete genetic controls on drosophila behavior).


Christopher F. Chabris, Union College
James J. Lee, University of Minnesota Twin Cities
David Cesarini, New York University
Daniel J. Benjamin, Cornell University and University of Southern California
David I. Laibson, Harvard University

Behavior genetics is the study of the relationship between genetic variation and psychological traits. Turkheimer (2000) proposed “Three Laws of Behavior Genetics” based on empirical regularities observed in studies of twins and other kinships. On the basis of molecular studies that have measured DNA variation directly, we propose a Fourth Law of Behavior Genetics: “A typical human behavioral trait is associated with very many genetic variants, each of which accounts for a very small percentage of the behavioral variability.” This law explains several consistent patterns in the results of gene discovery studies, including the failure of candidate gene studies to robustly replicate, the need for genome-wide association studies (and why such studies have a much stronger replication record), and the crucial importance of extremely large samples in these endeavors. We review the evidence in favor of the Fourth Law and discuss its implications for the design and interpretation of gene-behavior research.

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