Monday, July 31, 2006

Sliding toward panmictia?   posted by Razib @ 7/31/2006 11:14:00 PM
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Not quite, but interesting article in the Minnesota Star Tribue. Skip all the sentiment and hand-wringing and just jump to the statistics. Also, this is eye-opening: "By the year 2000, no large U.S. city anywhere other than on the intensely multiracial Pacific Coast had a higher share of multiracial children than Minneapolis." Of course, the Upper Midwest and the Pacific Northwest are whiter than average regions of the country, reinforcing Steve Sailer's point that overly large minority communities retard assimilation.




On being your mother's son   posted by JP @ 7/31/2006 02:22:00 PM
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John Hawks and Tara Smith both have posts on a New York Times article describing the role of events during development on health later in life. A recent article pushed for the development of a framework to describe these kind of effects.

The basic concept is simple: during development (development in utero), the fetus recieves signals that allow it to "predict", as it were, the environment where it will live. For example, there may be some way to sense whether the environment will be nutrient-poor or nutrient-rich. Based on this information, development proceeds in a way to favor adaptation to the predicted environment. However, if the prediction is wrong, for whatever reason, disease may result later in life. Importantly, the mother acts as the conduit for the environmental information, and may alter it to suit her needs.

The main example given in the article concerns metabolic disease like type II diabetes and obesity. The argument goes like this: due to basic physics, a fetus can't exceed a certain size (or couldn't, before the C-section). Thus, in a nutrient-rich environment like we have today, where a fetus would "want" to get much bigger, the mother limits the environmental signal )so as not to have a giant child), leading to a fetus that "predicts" an environment much poorer than what really exists. Once developed, the grown individual is then predisposed to gain weight. The authors put is thusly:
We argue that it is this differential rate of change between the limitations imposed by maternal constraint (which set the fetal prediction) and the reality of the enriched modern postnatal environment that has created the current high incidence of cardiovascular and metabolic disease in humans.

This is a broader framework for what some have called the "thrifty phenotype" hypothesis for the prevelance of type II diabetes, an alternative to the "thrifty genotype" hypothesis.




Gould's citation record   posted by the @ 7/31/2006 02:34:00 AM
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A comment that crossed my screen via that series of tubes:
There is a perception, alluded to in the discussion above, that while Gould was a remarkably adept and influential writer of popular science, his work as a scientist per se was less notable and much less influential/respected. This is not a view universally held, as a historian of science his contributions are widely described as being outstanding, and he is said to have been very well respected in his own field of paleao biology. However I have tried to establish how influential his science was by establishing how often his scientific papers (not his popular works) have been cited in the scientific literature, through the ISI databases. For comparison, Richard Dawkins' most highly cited scientific paper has 100 citations, Ernst Mayr's has 173, CG Williams' has 253 and D Tutyama's has 394. Gould's most highly cited paper (in Proc R Soc 1979) has 1,613 citations, and the next eight have 863, 609, 291, 169, 138, 121, 121, and 109 citations - the last of these published in 1974 is on antler size. I do not think that any claim that Gould was not highly influential as a scientist is objectively sustainable. His citation record is exceptional by any standards.


Informative and thoughtful comments welcome.



Sunday, July 30, 2006

Dick Lamm speaks   posted by Razib @ 7/30/2006 09:55:00 PM
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I don't blog much politics anymore because I think most of it is trivial epiphenomena. That being said, I want to point to Dick Lamm's recent comments. Lamm says that this country is "overdue for a candid dialogue on race and ethnicity." No shit sherlock! Back in 1996 when Lamm tried to get nominated on the Reform Party ticket I was pretty supportive because he seemed like he wasn't much of a bullshitter. I didn't agree with everything that Lamm promoted (Lamm changed his mind on free trade to become a skeptic, I still support free trade in the generality as a good for this nation), but his candid manner and "straight talk" (before that term was trademarked by John McCain) appealed to me. Lamm is not your typical "straight talker" on race. He is an old style environmentalist, and as a Unitarian Universalist he isn't a rock-ribbed right-winger in the style of fellow Coloradoan Tom Tancredo (I'd be willing to bet money he's not a theist but a humanist). Only Nixon could go to China, and only sincere progressives in the old style can transcend the excessive sentiment which seems to the consensus as exemplified by the Democratic party and the George W. Bush wing of the Repulican party when it comes to quality of life and civilizational issues. I don't really read "political" books anymore, but I've just ordered Two Wands, One Nation. You'd figure with a name like Dick Lamm someone would think up a better title, but sometimes I guess we've got to go with substance.




Knocking out stimulant reward   posted by rosko @ 7/30/2006 06:16:00 PM
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I just posted this on my own blog last night and thought I'd cross-post it here, as there have been a few posts lately about neurotransmitters, neurons, and behavior.

About a month ago I saw this article about the role of the dopamine transporter in cocaine reward. For those that don't know, the modified amino acids dopamine, norepinephrine, and serotonin, collectively known as monoamines, are neurotransmitters that are released by specific neurons in the brain and activate receptors on other neurons, sending a message from one cell to another. There are "pumps" in the membranes of the neurons that release these transmitters, which "clean up" the released monoamines so that they don't keep activating receptors for too long. These pumps are blocked by many psychotherapeutic and recreational drugs, producing a change in brain function. While each neurotransmitter has multiple effects in the brain, the transmitter dopamine in particular is believed to participate in the behavior-reinforcing properties of both natural (food, sex, etc.) and pharmacological (drug) stimuli. Among many scientists dopamine is still believed to be a kind of "pleasure chemical" whose concentration determines the degree of positive subjective sensation produced by the environment, regardless of the specific nature of the stimulus. This idea has been called into question especially lately, though, for a number of reasons, many of which have nothing to do with this article. For instance, the effect of drugs that directly activate dopamine receptors is not euphoric in humans.

The finding that concerns us here is one made by Sora et. al. in 1998. To understand the significance of this study, it is important to know that the stimulant cocaine blocks the transporters ("pumps") for all three monoamines. Given the assumed responsibility of dopamine for reinforcement, it has long been assumed that the block of the dopamine transporter (DAT) produces the euphoric effect of cocaine by allowing dopamine to sit around and activate its receptors longer. To test this, Sora et. al. deleted ("knocked out") the gene encoding DAT from mice, and showed that they still prefer to spend time in a chamber in which they have previously received cocaine. This so-called conditioned place preference suggests that cocaine can act as a reward even when it cannot block DAT (because DAT doesn't exist in these mice). Knocking out the serotonin transporter (SERT) also left cocaine reward intact (This SERT is the same as the 5-HTT mentioned in the Caspi and Moffitt study-geneticists seem to like the name 5-HTT and biochemists SERT, and some use the alternative SLC6A4 occasionally). A follow-up study showed that knocking out both DAT and SERT makes mice that do not prefer an environment they associate with cocaine. Sora et. al. took this to mean that blocking SERT is rewarding as well, which flies in the face of the fact that blocking SERT with drugs like fluoxetine (Prozac) does not produce signs of euphoria. An obvious caveat here is that the brains of DAT knockout mice are flooded with dopamine and the animals are very hyper even when they aren't on any drugs, so findings may not generalize to normal mice.

The new study by Chen et. al. took a different approach. They found that by mutating part of DAT, they could prevent cocaine from binding to it without breaking the pump. When this mutant DAT was added back into DAT knockout mice, cocaine no longer made the mice hyperactive like normal or DAT knockout mice (paradoxically, it even calmed them) and was not rewarding. This confirms what I--and probably many other researchers--suspected was going on: the mice with DAT knocked out only showed a response to cocaine because it slightly amplified the effect of the high baseline dopamine. Possible explanations are that increased activation of serotonin receptors overcomes some negative feedback mechanism limiting dopamine levels, or that lack of DAT induces a form of plasticity in the reward pathway such that SERT blockade becomes rewarding. This still doesn't explain other results questioning the idea of dopamine as a "pleasure chemical", but at least it shows that cocaine, and probably methylphenidate (Ritalin) and amphetamines, do produce their reinforcing effects through inhibition of dopamine reuptake.

*I just corrected the links. For some reason the first time I posted the URLs got all messed up, even though it worked perfectly fine for my own blog when I cut and pasted from the same file on my computer.



Saturday, July 29, 2006

Genotype, Recidivism and Indefinite Commitment Laws   posted by TangoMan @ 7/29/2006 10:57:00 PM
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This month Nature Reviews:Neuroscience published an opinion piece "Gene-environment interactions in psychiatry: joining forces with neuroscience" by Avshalom Caspi and Terrie E. Moffitt who follow-up on their well-cited 2002 article in Science "Role of genotype in the cycle of violence in maltreated children." In the opinion piece the authors present a broad overview of the opportunities and challenges present in studies that address the gene-environment interactions that exist within nature. In their earlier earlier paper they:


. . studied a large sample of male children from birth to adulthood to determine why some children who are maltreated grow up to develop antisocial behavior, whereas others do not. A functional polymorphism in the gene encoding the neurotransmitter-metabolizing enzyme monoamine oxidase A (MAOA) was found to moderate the effect of maltreatment. Maltreated children with a genotype conferring high levels of MAOA expression were less likely to develop antisocial problems. These findings may partly explain why not all victims of maltreatment grow up to victimize others, and they provide epidemiological evidence that genotypes can moderate children's sensitivity to environmental insults.


It's quite plausible that as this science develops it will enter into the social and legal arena where it will be useful in questions dealing with Indefinite Commitment Laws. David Rose tackles this subject, and provides a useful historical overview on "genetic determinism" scaremongering, in the latest issue of Prospect (UK). I want to add to the topic, but first a little background.



Indefinite Commitment Laws are designed to keep dangerous individuals from being released from prison after they've completed their terms of incarceration, have been passed in 16 U.S. States and have passed through Constitutional challenges by claiming that the commitment is a medical treatment, rather than a double-jeopardy penalty of continuing incarceration. The case law can be sampled here, here and here.

The impetus for these types of laws clearly centers on fears of high recidivism probabilities of the ex-convict. Because the legal proceedings are dealing with civil commitment rather than criminal commitment, the standard of evidence must only meet a clear and convincing threshold, rather than the higher bar of beyond a reasonable doubt. Due in large part to this lower evidenciary standard the adjudicating authority becomes a de facto actuary and much of the focus deals with probability of recidivism. To gauge the boundaries of the probability estimate there are prescribed protocols which must be followed by the State. More details in this Handbook for "Sexually Violent Predator Assessment Screening Instrument for Felons: Background and Instruction" and in this Memorandum on "Civil Commitment of Sexually Violent Predators" that was prepared for Virginia Circuit Court Judges. But what are the actual probabilities of recidivism that have spurred on this legislation? In their meta-analysis of recidivism studies, Predicting Relapse: A meta-Analysis of Sexual Offender Recidivism Studies, R. Karl Hanson and Monique T. Bussiere find:


On average, the sex offense recidivism rate was 13.4% (n = 23,393; 18.9% for 1,839 rapists and 12.7% for 9,603 child molesters). The average follow-up period was 4 to 5 years. The recidivism rate for nonsexual violence was 12.2% (n = 7,155), but there was a substantial difference in the nonsexual violent recidivism rates for the child molesters (9.9%; n = 1,774) and the rapists (22.1%; n = 782). When recidivism was defined as any reoffense, the rates were predictably higher: 36.3% overall (n = 19,347), 36.9% for the child molesters (n = 3,363), and 46.2% for rapists (n = 4,017).


Margaret A. Alexander performed a meta-analysis of 79 studies that looked at recidivism rates after the criminals participated in various treatments regimes in her study, Sexual Offender Treatment Efficacy Revisited and found the following recidivism rates: Rapists (treated 20.1%, untreated 23.7%); Child Molestors (treated 14.4%, untreated 25.8%); Exhibitionists (treated 19.7%, untreated 57.1%) and the by far largest group, Types not specified (treated 13.1%, untreated 12.0%). The last entry isn't a typo, the untreated did in fact have lower recidivism rates.

I thought it would be useful to survey the probability universe that we're dealing with when we deprive people of their freedom via Indefinite Commitment Laws for they do work on the basis of probabilities rather than certainties and it's quite likely that genotypic information will significantly improve the accuracy of assessments, especially when such information is combined with data on the life history of the subject. Rose summarizes the 2002 Caspi and Moffitt paper:


The paper's hypothesis was that one of the factors that differentiates individuals' propensity for antisocial behaviour is a particular gene-the one responsible for generating the enzyme monoamine oxidase A (MAOA). This enzyme regulates neurotransmitter levels in the brain: one of its roles is to get rid of excess serotonin, dopamine and so on, in order to keep neurological circuits working smoothly.

In fact, there are five known variants-known as alleles or genotypes-of the MAOA gene, although three of them are rare. The authors of the 2002 paper examined the two main types. The low-activity allele, which programmes the body to produce low levels of the MAOA enzyme, is found in about one third of males. The more normal, high-activity allele is found in almost all of the rest. In order to test their hypothesis about the role of MAOA, the researchers went back to the Dunedin cohort. Its members' history had already been examined and described, so that it was already known that between the ages of eight and 11, 8 per cent of the cohort's children had suffered "severe" maltreatment, and 28 per cent had experienced "probable" maltreatment. As we have seen, the team already knew which members of the study had exhibited antisocial behaviour, and when. Now researchers also found which of the MAOA genotypes they had by examining their DNA.

As might have been expected, the Dunedin study found that maltreatment in childhood would, on its own, make someone more likely to commit crime and display antisocial behaviour. About 35 per cent of the maltreated men with the normal high-activity genotype had shown conduct disorder, and 20 per cent had a conviction for violence. But when the two risk factors were found together-the low-activity genotype and childhood maltreatment-the correlation with antisocial behaviour was far stronger. More than 80 per cent of the men in this category had exhibited conduct disorder, and more than 30 per cent had convictions for violence. As a group, they were all among the most violent third of men. No fewer than 85 per cent of the cohort's men with the low-activity genotype who had also been severely maltreated went on to develop antisocial behaviour.


Notice that the rate for conviction of violent crime was 50 percent greater in the low-activity genotype group than in the high-activity genotype group. In absolute terns the former group has a conviction rate that is 10 percent greater than the latter group. Compare these rates to the the recidivism rates for rapists (18.9%), child molestors (12.7%) and violent offenders (12.2%.) When we're dealing with probabilities of recidivism it seems that genotypic information will only serve to improve the decision process underlying indefinite commitment proceedings.

An added benefit of developing this research will be the likely erosion effect on the Axiom of Discrimination as it pertains to the question of race and crime. We already have studies which have charted monoamine oxidase activity across demographic groups:


Reported here are variations for all three demographic variables such that significantly greater enzyme activity is seen in female, older, and white subjects relative to male, younger, and black subjects.


Note that the groups most prone to low enzyme activity are males, the young, and black subjects. Another study makes the implication more explicit:


Overall, low MAO activity appears to be associated with restless and uninhibited behavior patterns, and may reflect some of the mediating effects of serotonin and sex hormones (especially androgens) on criminal behavior. Lower MAO activity is more characteristic of males than females, and appears to be lower in Blacks than Whites, and lowest during the second and third decades of life.


Of course, a research design that broaches the sensitive topic of race, genetics, and criminality is certain to dissuade many scientists from getting involved, for as Stanford's David Botstein remarks about genetic causes of violence:


"I think there's more scientifically to that one, a greater likelihood of finding it, more than IQ. But it's COMPLETELY unacceptable at the moment. You can't even talk about it. Go to any university, research center, no one -- NO ONE -- will talk to you about this. Why? Simple. Because of the fear that there will be a racial correlation.


We need look no further than Rose's essay for a sampling of what the future portends:


The academy can be a compartmentalised place, with surprisingly little dialogue between disciplines, and mainstream sociological criminology is only beginning to become aware of the work described here. It may not evoke a favourable response. A recent issue of the journal Criminal Justice Matters, published by the Centre for Crime and Justice Studies at King's College London, contained a fierce attack on the work of Terrie Moffitt and others. The article accused researchers at the Institute of Psychiatry and elsewhere of "genetic fundamentalism-a belief in a mythic, not a real genetics," and suggested that twin studies that found a genetic component in antisocial behaviour were without value. Moffitt and her colleagues have, in fact, stressed that genetic predispositions must be "switched on" by childhood maltreatment, and that the important thing was to concentrate on eliminating this and other types of adverse environment.

Asked to give an after-dinner speech to Liberal Democrat lawyers, I caught a different glimpse of the hostility that behavioural genetic research into the causes of crime can evoke. After I had presented an account of some of the work described here, the response was viscerally critical. Speakers claimed that it was "deterministic," and would surely lead to a wanton attack on civil liberties. One distinguished legal practitioner went so far as to demand who had funded these investigations, claiming that they must have been cooked up according to some pre-ordered, authoritarian agenda.


For most of the regular readers of this blog these types of frothing-at-the-mouth attacks are old hat. Just a few weeks ago we saw Stanford's Barres preparing the ground for classifying science he didn't like as hate crimes:


. . . what is the difference between a faculty member calling their African-American students lazy and one pronouncing that women are innately inferior? Some have suggested that those who are angry at Larry Summers' comments should simply fight words with more words (hence this essay). In my view, when faculty tell their students that they are innately inferior based on race, religion, gender or sexual orientation, they are crossing a line that should not be crossed - the line that divides free speech from verbal violence - and it should not be tolerated at Harvard or anywhere else.


The Leftist Creationists who believe that humans are immune to evolutionary processes will not go down without a fight. Unfortunately, these types of creationists are a monolithic bloc within Academia and they can indeed put up impediments to research or simply resurrect the tactics used during the Sociobiology Wars. However, even if they can groom an obscurantist of Gouldian proportions, they're going to have a difficult time refuting the work of good scientists, work which been replicated many times over. In the end these new insights should aid society in furthering the cause of justice, just as DNA testing has been instrumental in setting unjustly incarcertated people free and helping to convict those who are guilty of crimes. The science and technology are neutral but they do aid in guiding the decisions made by our arbitors of justice.




Gonna make you fall in love with...Spines   posted by Coffee Mug @ 7/29/2006 01:18:00 PM
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Never ever let a n* ride if you think he's gonna slide pop'em in the spine...fo' the money. - Bone Thugs N Harmony

The Genius is dead. Genius Re-post:

Your standard neuron in the cortex is called a pyramidal neuron. It generally has on big apical dendrite sticking out the top and a few basilar dendrites radiating around the bottom. Here's a glowing one:


This one comes from a somewhat troublesome paper from the lab of Karel Svoboda who as far as I can tell is a guru of new imaging techniques who happens to have an interest in the details of dendrites as well. The reason why the paper was a little vexing is because the results seemed to run against a large literature showing that the major identifiable morphological problem with neurons in Fragile X Syndrome brains has to do with dendritic spines. Let me back up. Your standard neuron in the cortex has dendrites and an axon. The axon is the output structure that goes and pokes at another neuron and can fire action potentials that release neurotransmitters from its tip to send signals. The dendrites are the parts that receive signals from axons. Where an axon and a dendrite meet is called a synapse. Dendrites are studded with these little knobby-doos called spines. Spines are where most excitatory synapses in the cortex are made.

Spines go through a maturation process whereby they initially come out as long wormy things called filopodia and then kind of settle back into a variety of shapes often resembling the power-up mushrooms in Super Mario Bros. or like a large kind of extended comma. The fat part at the end is referred to as the spine head and the thin part connecting to the dendritic shaft is the spine shaft.

Spine shapes change in the lifespan of the spine, but also change over the lifespan of the organism. And along side the changes in shape come changes in the number of spines per dendrite (the spine density). Since people had looked at adult human Fragile X brains and seen abnormalities with regard to spine morphology and density it seemed clear that something must be occurring during development.

Nimchinsky et al (2001) wanted to see what happens in development so they got some normal mice and some mice lacking fragile X mental retardation protein (FMRP) that are a pretty good model for what's happening in humans with the disorder. When the mice were one, two, or four weeks old they injected a particular part of the cortex with a fancy shmancy virus that lights up a good portion of neurons (anyone who reads science crap knows about GFP the magical jellyfish protein, that's how they're doing this). This allowed them to use laser microscopy to do detailed quantitative analysis on the spine lengths and density. The troublesome bit is that while they found the expected differences between FraX mice (the fragile X model) and wild-type (read: normal) mice at one week (shown below), the differences disappeared by 4 weeks. How can this be?!


They offered up a number of considerations including that they were looking at a different chunk of cortex than other people usually do and that perhaps there were some limitations to their visualization technique. The most important limitation, as it turns out, is that they can't use their technique past about 6 weeks of age because the virus they used is too bad at infecting neurons after that. A more recent paper from the Greenough group in Illinois, who were some of the major reporters of these fragile X spine abnormalities in the first place, arrived at a resolution to this conflict.

Galvez and Greenough (2005) took basically the same tack as the Svoboda group except they chose a couple of different ages. They used 25-day old mice to map onto the 4-week time point previously reported and they took another sample at age 73-76 days old. For those of you who have trouble dividing by 7, that's about 10-11 weeks. The reason for doing this is that it is understood that a major developmental process called pruning might be at play here. Initially developing brains produce huge amounts of connections during a period of widespread synaptogenesis. They don't need all of these connections. So they have to be 'pruned' back. There are lots of tree metaphors when talking about dendrites that can make it very pleasant for a neuroscientist to contemplate a tree in the park on a summer afternoon. This apparently happens in mice some time after one month of age.

The Greenough paper used a more rudimentary staining procedure so they could look at spines in the older brains. They managed to replicate for the most part the finding that FraX mice and wild-type mice don't differ at 4 weeks with regard to spine shape and density. But at the much later time point they differ pretty radically as illustrated here:


It appears that the major malfunction with Fragile X spines then isn't that they can't grow out right or anything like that. Its that they can't be eliminated after the fact. Notice how much more bare the adult wild-type dendrite (Figure 1C from the paper) looks compared to the FraX dendrite (Fig 1D). This is awfully nice to see for two reasons. One, because it clears up an apparent discrepancy in the literature and it turns out that everyone was right which ought to make all the labs involved feel marvelous. It's also nice because it indicates that the real neurological problems in Fragile X development start later than expected in development. I'm not quite clear on when this massive pruning event is supposed to happen in human development, but it opens a window whereby if we ever get the means to replace this protein we might ameliorate some of the effects of the syndrome.

References:

Nimchinsky EA, Oberlander AM, Svoboda K (2001). Abnormal development of dendritic spines in FMR1 knock-out mice. J. Neurosci. 21:5139-5146.

Galvez R, Greenough WT (2005). Sequence of abnormal dendritic spine development in primary somatosensory cortex of a mouse model of the fragile X mental retardation syndrome. Am. J. Med. Genet. 135A:155-160.



Friday, July 28, 2006

Sports political donations   posted by Razib @ 7/28/2006 10:19:00 PM
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For those of you who are, or in my case, were, into professional sports, this site lists their political donations. I was surprised that Joe Theismann or Barry Switzer gave mostly Democrats. Also, the African Americans were more Democratic than I had expected (I'd assumed that their wealth would have worn away their cultural orientation in regards to politics).




Mendelian epigenetics   posted by JP @ 7/28/2006 01:45:00 PM
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A paper in Nature Genetics describes a mutation in a tomato gene that leads to fruits that don't ripen. This would be an important discovery in itself--the ripening of fruits is certainly an economically interesting trait--but a further twist makes it even more interesting. The twist: the mutation is actually an epimutation. That is, the two alleles--the non-ripening allele and the wild type allele--have no difference is sequence, but rather a difference in the methylation status of the promoter. The methylated allele is expressed at a lower level, leading to an inhibition of ripening.

Also interesting is that the methylation status of the allele seems to be fairly stable-- they claim to have seen a tomato revert from the non-ripening phenotype to wild type three times in 3000 plants grown since 1993. So this epimutation acts essentially in a Mendelian fashion. Whether this will be a common occurrence in plants (or other taxa) remains to be seen.

Related: epigenetics in humans




Reinventing the Wheel   posted by Alex B. @ 7/28/2006 05:33:00 AM
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The NYT has an article up about how supposedly malleable IQs are by a professor trying to get more money for early childhood education programs. Aside from the arguments about funding a program that is not that effective , the merits of the NYT article are questionable.

Kirp's argument is based on two studies by the same researcher: Michel Duyme. Before anything is stated about the studies, I'll point out that while the participants in these studies may be new, the theory and designs are not. Herman Spitz's masterful work goes over many of these types of studies, and the overall result is not too impressive for those thinking IQ is easily changed. If your educational psychology professor didn't make that book a required reading, join Questia and read it, or snag it from the local library.

Now on to the NYT article.......

About the first study, Kirp writes:
Regardless of whether the adopting families were rich or poor, Capron and Duyme learned, children whose biological parents were well-off had I.Q. scores averaging 16 points higher than those from working-class parents. Yet what is really remarkable is how big a difference the adopting families' backgrounds made all the same. The average I.Q. of children from well-to-do parents who were placed with families from the same social stratum was 119.6. But when such infants were adopted by poor families, their average I.Q. was 107.5 - 12 points lower. The same holds true for children born into impoverished families: youngsters adopted by parents of similarly modest means had average I.Q.'s of 92.4, while the I.Q.'s of those placed with well-off parents averaged 103.6. These studies confirm that environment matters - the only, and crucial, difference between these children is the lives they have led.


Darth Quixote has already deeply delved into this study, and there is no need to repeat him here. I will add:

  • the design was non-experimental, post-test only. While these designs have merit, to infer causality is tenuous as the adoptees' IQ could easily have fit the same pattern before adoption. Moreover, since there was no randomness in the adoption process, we have no idea as to why the children were placed where they were.

  • the researcher's did not test to see if the instrument they were using was functioning the same across comparison groups. A (good) way to check this Multigroup confirmatory factor analysis (e.g.,), but with the n so small, it is difficult to do.1 As a proxy, I checked for equality of covariances: B+ vs B-: not significantly different; A+ vs A-: not significantly different; B+A+ vs B-A-: significantly different! (chi-square: 154.79, df= 55, p < .0001). This could mean multiple things. Two that come to mind are: a) the B-A- group's pattern of cognitive functioning has not matured at the same rate as the B+A+ group, so give them some time and it may converge. b) the B- kids were placed into the A- home for a specific reason (i.e., they had some type of deficit that made A+ parents pass on them).


  • So where does leave us? Capron and Duyme sum it up best:
    Although these findings clearly indicate that the biological parents' background contributes to observed differences in IQ between extreme groups, as does that of adoptive parents, more detailed interpretation is difficult (p. 553)

    which is a far cry from Kirp's interpretation:
    the only, and crucial, difference between these children is the lives they have led.


    About the second study, Kirp writes:
    A later study of French youngsters adopted between the ages of 4 and 6 shows the continuing interplay of nature and nurture. Those children had little going for them. Their I.Q.'s averaged 77, putting them near retardation. Most were abused or neglected as infants, then shunted from one foster home or institution to the next.

    Nine years later, they retook the I.Q. tests, and contrary to the conventional belief that I.Q. is essentially stable, all of them did better. The amount they improved was directly related to the adopting family's status. Children adopted by farmers and laborers had average I.Q. scores of 85.5; those placed with middle-class families had average scores of 92. The average I.Q. scores of youngsters placed in well-to-do homes climbed more than 20 points, to 98 - a jump from borderline retardation to a whisker below average. That is a huge difference - a person with an I.Q. of 77 couldn't explain the rules of baseball, while an individual with a 98 I.Q. could actually manage a baseball team - and it can only be explained by pointing to variations in family circumstances.


    One has to do some digging elsewhere, but the study he is referring to is from PNAS. Since the study is free to read, I'll only go over the major points:

  • The research team picked children/teenagers who met five criteria: They had all been (1) neglected and/or abused during infancy, having been definitively removed from their biological family by court order after judicial procedures; (2) placed in many foster families and/or institutions before adoptive placement; (3) had an IQ <86 and >60 in the year preceding adoptive placement; (iv) aged 4-6 at the time of the adoptive placement and (v) aged 11-18 and being raised by the same two adoptive parents at the time of the second IQ test (i.e., 5-14 years with same adoptive parents)


  • The original IQ test was either a) the first or second edition of the Stanford Binet (their wording and reference date makes it hard to discern), b) the original Bayley Scale of Infant Development, or c) "other French tests of Intelligence". The post-adoption IQ was either the WAIS or the WISC-R.


  • The Children/teenagers were classified into one of three groups based on adoptive father's occupation: High, Middle, or Low


  • There was a universal gain in IQ scores for all participants, averaging 13.88 points.


  • There was a (range restriction corrected) correlation of 0.67 between IQs before and after adoption, which "indicates a degree of stability close to the stability found in longitudinal studies of biological children who have not undergone an environmental change. . . Thus, on the basis of IQ at the end of the preschool period, the results show that there is a moderate stability for rank. This is a near-universal finding.


  • As to a critique, first the selection criteria is loaded. No one with any sense about them would think that being abused/neglected from birth so bad that the legal system has to intervene would not decrease cognitive functioning. This is not at all what is meant when discussing "Average Expectable Environment." So right off the bat we know that these kids are not at all the same as a regular Joe (or Jane) off the street who has Borderline IQ. Thus, right off the bat we would expect that after any semblance of stability, the kids' cognitive functioning would improve (i.e., return to its normal state).

    Second, while there is some difference between the IQs across groups, it isn't major (max: Low SES PIQ vs High SES PIQ, d = .9 [r2=.17]; min: Low SES VIQ vs. High SES VIQ, d=.5 [r2=.06]), indicating SES explains somewhere between 6 and 17 percent of the variance in post-adoption IQ scores. While there is definitely an effect, given the extreme nature of the study's categories, it does not appear to be much of one.

    Third, it is very difficult to say with much certainty that IQ scores from scale, developed with one set of theoretical guidelines and one set of 1950s norms are directly comparable other IQ scores from a different scale, developed with a totally different theoretical orientation that uses a set of 1970s/1980s norms. This is even more so when the Bayley scale is used. For those of you that have given the Bayley (all 2 of you!), you know it is an extreme pain to administer and that it is about as unlike the Wechsler instruments as you can find a test that still measures cognitive ability.

    Fourth, while there was an overall mean increase in IQ, in addition, there was a universal gain in variance (stnd. dev. increased approx 9 IQ points). Thus, assuming that the before and after IQs were directly comparable, the majority of the scores fell into these ranges:




    95% Range of IQ (i.e., -/+ 2 SD)
    Pre-Adoption
    Post-Adoption
    Low SES64.2391.4350.54118.54
    High SES64.9790.1768.81272


    A few things to notice. 1. There were at least some kids in both categories who, pre-adoption, were in the average range. Given the stark conditions of their pre-adoption upbringing, that is amazing - and likely has little to due with a nurturing environment. 2. There were at least some kids in both categories who, post-adoption, were in the Mild to Moderately Deficient range. Meaning - they still were classified as MR. If the environment is so powerful, why didn't their IQ rise also? 3. It is a fair assumption that even the Low SES households were much better off for the kids than their abusive/neglectful original home. If the environment is so powerful, then why are some children doing worse, IQ-wise, post-adoption?

    Fifth, buried in the next to last paragraph of the study, we find this statement:
    This study shows that stability for rank can be found following a marked environmental change after 4 years of age regardless of the SES of adoptive families. The factors explaining this stability are undoubtedly different from those explaining the gains in mean IQs.


    Interpretation: the worst performers before the adoption tended to be the worst performers after the adoption. The only thing that happened was a linear transformation of scores (i.e., post-score ≈ a*pre-score + b) across all SES groups, which could be due to many things, including: changing IQ scales and/or many years of living in an "average expectable environment."

    So, what we end up with is a picture much more complex and intricate than Kirp allows. What we can definitely conclude is that abusing or neglecting your children so bad that the government has to take them away tends to produce lower IQs (although some kids will still be in the average range), but was this really in question? What we can also conclude is that for some children in the MR range, adoption into high SES environments will not significnalty improve thier IQ. If the environment is so powerful to change cognitive abilities, then how did this happen? Last, I think we can conclude that Kirp's attempt to glorify the ability of the environment to change IQ is not much more than the wheel, reinvented.


    [1.] I did it using the bootstrap feature in AMOS. I can go into more detail by email or in the comment box.



    Thursday, July 27, 2006

    Jaakkeli says....   posted by Razib @ 7/27/2006 11:25:00 PM
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    That northern Europeans are different from southern Europeans, that Ashkenazi Jews are more like southern Europeans than northern Europeans, and that Finns are really strange. From this paper, European Population Substructure: Clustering of Northern and Southern Populations. Of course, this is Jaakko Tuomilehto. Anyway:

    Under a variety of conditions and tests there is a consistent and reproducible distinction between "northern" and "southern" European population groups: most individual subjects with southern European ancestry (Italian, Spanish, Portuguese, and Greek) have >85% membership in the "south" population; and most northern, western, eastern and central Europeans have >90% in the "north" population group.


    This is in PLOS Genetics, so you can read the whole thing for free. Do so. And then comment!

    (via Dienekes)




    Heredity podcasts   posted by Coffee Mug @ 7/27/2006 11:14:00 PM
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    Heredity, the official journal of the Genetics Society, has a podcast.




    The end is nigh...for the Flynn Effect   posted by Razib @ 7/27/2006 07:44:00 PM
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    Of course, you knew this, but now so do others.

    TangoMan Adds: See the related post - Intelligence in UK declining?




    PC on the Front Lines of Policing   posted by TangoMan @ 7/27/2006 07:16:00 PM
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    Steve has already reported on the issues that New Jersey State Police are having with an ever rising number of women and minority applicants who are applying for positions but who are disproportionately failing the background checks, physical exams and written tests. But what happens when some of these applicants do pass the tests? Another case of a woman officer being overpowered by a handcuffed suspect has made the news:


    A suspected burglar put in handcuffs after his arrest attacked a woman police officer and then escaped by driving off in her car.

    The female officer was driving the man to Slough police station when he forcibly took control of the car.

    The man, one of three arrested on suspicion of burglary, dumped the car in Keel Drive about six minutes away.


    Also, recall the case of the black police officer who sued for racial discrimination because the police force promoted him beyond his level of competence and his incompetence led to disciplinary action:


    A BLACK police bodyguard who protected the Duchess of Cornwall has won $70,000 compensation after suing Scotland Yard for "over-promoting" him because of political correctness.

    Sgt Leslie Turner -- the first black personal protection officer to guard the royal family -- will receive the "racial discrimination" payout after reaching an out-of-court settlement with London's Metropolitan Police.

    His representatives argued he landed the prestigious job as Camilla's bodyguard only because he was black.

    It was claimed that as a result of being over-promoted and not receiving proper training and support, Sgt Turner made mistakes which led to him being re-assigned.

    He launched legal proceedings against the force in October and Scotland Yard chiefs have agreed to pay "substantial" compensation -- understood to be about $70,000 -- to the married father of two.

    Colleagues of Sgt Turner, who was born in Britain, say he is a "model professional"' who had a good relationship with Prince Charles and Camilla.

    He began guarding Charles in August, 2004 and was re-assigned to Camilla in February last year when the royal couple were engaged.

    But in June, it emerged he had suddenly been replaced.

    Royal insiders stress that the decision to move him was not taken directly by Clarence House. But they concede that the race row is extremely embarrassing for Charles and Camilla.

    Had Sgt Turner's case reached a tribunal, potentially embarrassing secrets about Charles and Camilla's lives may have been aired.

    A Met spokesman refused to confirm the compensation deal.





    Wednesday, July 26, 2006

    An analogy   posted by Razib @ 7/26/2006 08:26:00 PM
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    Allelic introgression between populations:horizontal gene transfer between bacteria. Does it work?




    Too Much Time On My Hands   posted by TangoMan @ 7/26/2006 06:24:00 PM
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    Great juxtaposition of Monty Python storyline with Star Trek clips, but how much time do you think it must have taken to cull through 3 years worth of Star Trek episodes looking for just the right snippets to fit in with the Monty Python sketch? Congratulations to the creators for their imagination and most of all their patience.




    What is the soundtrack of our genome?   posted by rosko @ 7/26/2006 05:19:00 PM
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    Okay, this is my first post, and I must admit it has no interesting science news in it. However, I think many on here will find this funny.

    A few days ago I took a look at Mendel's Garden #3, and among the featured posts is a discussion of the work of Japanese biologist Susumu Ohno. He took a part of the gene encoding the large subunit of RNA polymerase II and converted it into music, considering both the base sequence itself and the properties (size and charge) of the encoded amino acids. He thought that this piece sounded like a Chopin nocturne, so he took the nocturne and "reverse translated" it to a DNA sequence. He proceeded to demonstrate that this sequence contains a 160-codon open reading frame (see this site for more), and went on to make lots of philosophical speculations about how DNA sequences and music evolve in the same manner. The probability that any given sequence of 160 base triples would start with a start codon and not contain stop codons is a little less than 1/130,000. However, this could be artificially raised by many orders of magnitude by assigning the start and stop codons to sequences of notes that are very frequent and rare, respectively, in the nocturne, which shouldn't be difficult to find with the right software.

    Perhaps most interesting is the musician Colin Angus of the group The Shamen, who teamed up with biologist Ross King to create the piece "S2 Translation" containing the full sequence of a serotonin receptor. The program they used for this, called ProteinMusic, is available as a free download. I got the program and tried some random gene sequences, making sure to trim off any bases before the start codon (ProteinMusic doesn't do this automatically). The program went straight through the stop codon at the end of the transcript, calling it "Z". I could not hear any difference in the sound between the actual polypeptide and the 3' UTR. The poly(A) tail was easy to recognize because of its repetitiveness, but that's about it. Someone commented that

    "It may be possible for somebody who has heard the pattern of a calcium-binding site or an enzyme active site to recognize its occurrence in a novel protein."

    Yeah right. I doubt 1% of bioinformatics scientists could identify the seven transmembrane helices in that serotonin receptor by ear, something that is typically easy to do by eye using hydropathy plots. This isn't to say that the idea of turning DNA sequences into music isn't neat in a purely fun sense, just that it doesn't do anything for science except maybe increase popularity.




    It's hard out here for a vole   posted by Coffee Mug @ 7/26/2006 01:54:00 AM
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    I'm sure many here are familiar with the prairie vole - montane vole story regarding mammalian monogamy. Prairie voles are more monogamous than montane voles. The two types have different distributions of Arginine Vasopressin Receptor 1a (avpr1a) expression in the brain. In a Science paper a little over a year ago, Hammock and Young reported that the DNA upstream of the avpr1a gene in prairie voles contains a bunch of short tandem repeats (STRs), and that the number of these repeats tracked with receptor distribution and with monogamous behavior. They also took a look at the DNA upstream of human, chimp, and bonobos and found repeat elements in common between humans and bonobos (more monogamous) that aren't found in chimps (less monogamous). The implication is that tandem repeats work the same way in primates as in voles, and that polymorphisms here are directly linked to the complex behavior of monogamy.

    It was a damn fine story, and it's a shame to see it go, but check this PNAS paper out:

    Mammalian monogamy is not controlled by a single gene.
    Sabine Fink, Laurent Excoffier, and Gerald Heckel


    Complex social behavior in Microtus voles and other mammals has been postulated to be under the direct genetic control of a single locus: the arginine vasopressin 1a receptor (avpr1a) gene. Using a phylogenetic approach, we show that a repetitive element in the promoter region of avpr1a, which reportedly causes social monogamy, is actually widespread in nonmonogamous Microtus and other rodents. There was no evidence for intraspecific polymorphism in regard to the presence or absence of the repetitive element. Among 25 rodent species studied, the element was absent in only two closely related nonmonogamous species, indicating that this absence is certainly the result of an evolutionarily recent loss. Our analyses further demonstrate that the repetitive structures upstream of the avpr1a gene in humans and primates, which have been associated with social bonding, are evolutionarily distinct from those in rodents. Our evolutionary approach reveals that monogamy in rodents is not controlled by a single polymorphism in the promoter region of the avpr1a gene. We thus resolve the contradiction between the claims for an evolutionarily conserved genetic programming of social behavior in mammals and the vast evidence for highly complex and flexible mating systems.

    The paper makes two major points:
    1. There are a whole lot of non-monogamous vole species missing the STRs.
    2. The STRs in primates are about 5X further away from the avpr1a gene, and they are repeats of a different motif.
    While there is still room for the STRs to modulate behavior one way or another, this report seems really damaging to the notion that arginine vasopressin receptor expression is a central component.



    Tuesday, July 25, 2006

    Cooperation, Punishment, and Asymmetrical Warfare   posted by Matoko Kusanagi @ 7/25/2006 10:53:00 PM
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    I was arguing with Dave Schuler at the Glittering Eye about the concept of a "just war". Dave argues that hizb' actions do not comprise a "just" war. I told Dave that there was no such thing as a "just" war. But that is not strictly true. War is a case where individuals sacrifice their chances to reproduce by aiding others.
    Darwin (1874:178-179)says:
    It must not be forgotten that although a high standard of morality gives but slight or no advantage to each individual man and his children over other men of the tribe, yet that an increase in the number of well-endowed men and an advancement in the standard of morality will certainly give an immense advantage to one tribe over another. A tribe including many members who, from possessing in a high degree the spirit of patriotism, fidelity, obedience, courage, and sympathy, were always ready to aid one another, and to sacrifice themselves for the common good, would be victorious over most other tribes; and this would be natural selection.

    In theory, the tribe with Right on their side would win any war. Darwin is, of course, talking about genomes. I am lately (like MC Coffee Mug) kindasorta interested in memomes. In the MC's post, he quotes Joshua Green--
    "...our social instincts were not designed for the modern world. Nor, for that matter, were they designed to promote peace and happiness in the world for which they were designed, the world of our hunter-gatherer ancestors."

    And perhaps this is true. But we also have a built-in mechanism to compensate for our hard-wiring, culture. I quote from Chapter 9 (Punishment allows the Evolution of Cooperation (or anything else) in Sizeable Groups) of the swell new book i am reading, The Origin and Evolution of Cultures.
    In most existing models, reciprocators retaliate against noncooperatives by witholding future cooperation....[but there are] alternative forms of punishment known as retribution. It seems possible that selection may favor cooperation enforced by retribution even in sizeable groups of unrelated individuals because, unlike withholding reciprocity, retribution can be made only against noncooperators, and because the magnitude of the penalty imposed on noncooperators is not limited by the effect on the outcome of cooperative behavior.

    The death penalty is a good example of retribution. Now to return to the topic of this post, can asymmetrical warfare ever be considered a "just" war? It is most likely "immoral" to deliberately draw fire on civilians of the host population. It is possibly "immoral" to deliberatly target civilians in the adversary population. Neither of these behaviors is punished by terrorist groups.

    Strategypage says, "Terror is the tactic of the weak, or those short of better ideas." But is it really? What if it is a new paradigm? That is what i think, a mutant strategy that rewards immoral actions. Not punishment, not retribution, but reward. In a "just war", the society with higher moral values will triumph. But what about an unjust war?




    Cryptic cultural variation   posted by Razib @ 7/25/2006 10:20:00 PM
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    Over at Sepia Mutiny I learned something new the other day, that not all brown people consider white the color of death! You see, in a review of Parminder Nagra's TV wedding, a brown American writer stated "I did laugh at the effort to bridge cultures, though, when Nagra's character got married wearing a white sari. White is the Hindu color of mourning." Well, not only do South Indian Hindus reject this claim, but white is the color of mourning among Bengali Muslims (personal experience) and in China. Last year an attempt to portray Diwali as the pan-brown Hindu holiday was rejected by some who noted that Bengalis, for one, did not focus on this holiday. I bring this up because as brown Americans we are used to "representing" and "communicating" "our culture" to the greater society, but we often don't really know how our own specific experience blinds us to non-existent generalities. I joked to Manish Vij that someone should write a book for browns about all the things about browns they don't know that they don't know (from this Bengali to other browns, not all browns are hairy & stinky! Especially those of us who are a little chinky :).

    But it isn't all ethnic. When I was a freshman in college a girl commented in an offhand manner that "That's so funny that I'm going to pee my pants!" I really didn't "get this," and I had never really understood this assertion, so I asked where it came from. She explained that when people laugh hard they pee. I observed that this never happened to me, and when I asked around the dormitory I found that females understood immediately the reference and many of the males were as confused as I was. It turns out that there were physiological differences between males and females, and the propensity to urinate in response to laughter is more of a "girl thing."

    Honestly, I started thinking about this because of prosopagnosia. I mean, "we celebrate diversity," but I'm not sure if we really know how diverse we are....




    MCCM Live   posted by Coffee Mug @ 7/25/2006 09:42:00 AM
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    A few Coffee Mug-related things:
    1. I made my website less irritating.
    2. My album is available via iTunes and CD Baby.
    3. I have a gig at the Larimer Lounge in Denver, CO on Saturday Aug. 5th, so if you're in the area you should come check it out. I'm first at around 2 pm, and I make no guarantees about any of the other performers.




    Ask GNXP - personal genome sequence   posted by the @ 7/25/2006 01:01:00 AM
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    In previous 10 Questions, Razib has asked:

    If you could have your full genome sequenced for $1000, would you do it? (assume privacy concerns are obviated)


    By genotyping ~500,000 tag SNPs, it's actually possible to approximate a full genome sequence for $1000 using current technologies. So my question(s) is (are): if you could have your genome "sequenced" (to a good approximation) for $1000, would you do it? What would you want to know from the data?

    Leave your answers in comments.




    ...on the other blog   posted by Razib @ 7/25/2006 12:35:00 AM
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    I open my mouth on Neandertal interbreeding, quickly hit the first chapter of R.A. Fisher's Genetical Theory and explain why SJ Gould would be outraged.




    10 questions for Charles Murray   posted by Matt McIntosh @ 7/25/2006 12:00:00 AM
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    (This is the latest in GNXP's semi-regular "10 questions" feature; links to previous editions can be found along the sidebar or by searching the blog.)

    The geneticist J.B.S. Haldane famously remarked that important theories went through four stages of acceptance: "i) this is worthless nonsense; ii) this is an interesting, but perverse, point of view; iii) this is true, but quite unimportant; iv) I always said so." This process would be quite familiar to Charles Murray, a resident scholar at the American Enterprise Institute who has gained a reputation for staking out controversial positions a decade before they become mainstream. Starting with Losing Ground in 1984, later with Richard Herrnstein in 1994's The Bell Curve, and most recently with In Our Hands, Murray has made his name as a public intellectual by dropping well-researched bombshells onto policy debates. In between, he's published shorter books on political philosophy and a thorough historical study of human accomplishment in the arts and sciences.

    Below the fold is our e-mail interview with Murray.

    1. Let's talk first about your latest project. You've stated that In Our Hands is an attempt to strike a compromise between your libertarian ideals and the current socio-political reality. The biggest worry about your plan from a libertarian point of view is that in practice it would create a large constituency who would vote to raise the grant on a regular basis, leaving the fiscal situation largely unchanged or possibly even worse. How does your plan deal with these kinds of public choice objections?

    Mancur Olson and other public-choice theorists taught us that sugar farmers can get sugar subsidies because they care passionately about getting their benefit while no other constituency cares enough about preventing them from getting it. Under the Plan, the grant will be the only game in town (every other transfer is gone), and will affect every adult in the country. Every time Congress debates a change in the grant, it will be the biggest political news story in the country, and a very large chunk of the population--and people holding a huge majority of the monetary resources for fighting political battles--will lose money if it's raised. Compare the prospects for jacking up the grant with the certain knowledge we have of the trends in spending under the current system. They have sky-rocketed and will sky-rocket, through classic public choice dynamics. The Plan uses the only strategy I can conceive to get out of the public-choice box.

    2. One modification to your plan which has been suggested is to index the guarenteed income to GDP instead of inflation. This way everyone benefits from policies that increase economic growth, seemingly a perfect bargain between welfare statists and economic dynamists. What do you think of this idea? Have there been any other suggested modifications to (or criticisms of) to your plan which have impressed you thus far? More broadly, how has the reaction so far compared to what you were expecting?

    An early draft linked the size of the grant to median earned income, which would have a similar effect. But the real purpose of the book was to put an idea on the table that doesn't have a prayer of being enacted now, but could become conventional wisdom down the road. To achieve that purpose, I wanted to avoid getting hung up on bits and pieces. If the idea of converting all the transfer programs to a cash grant is a good idea, we can figure out a way to control changes in the size of the grant. Worry about it after we've decided what we think of the idea: that's the logic of the book's presentation.

    As for reaction, I've been surprised by the number of libertarians who are attracted to the idea (though perhaps I shouldn't have been, given that Milton Friedman thought up the negative income tax). Liberals don't know what to say: I'm proposing a much larger transfer of resources to poor people than they've ever dreamed of, which they should like, but they're obsessed with the people who would waste the money. They really do think that most people aren't capable of running their own lives without their help. Overall, IOH has accomplished pretty much what I'd hoped in the way of reaction.

    3. It's interesting to consider what kind of downstream social effects your plan might have. For example, it's likely to encourage people to take greater risks (such as starting their own business at a younger age) or to pursue alternative "low remuneration" paths -- academic research, writing, charity work, etc. It would likely remove support for harmful labour regulations like the minimum wage, and one can also think of ways in which this might alter the impact of imigration and illegal labor. How much did you think about these kinds of downstream effects when writing In Our Hands, and what do you think the most significant social impact of the plan would be?

    I hadn't thought about the way it would work against labor regulation, but you're right. It would. I did discuss other downstream effects--on families, the underclass, and most broadly on what might be called a climate of virtue. As far as I can see, the downstream, unintended effects of the Plan have a strong tendency to be positive, while the unintended effects of conventional social programs are always negative. Why the difference? Because the Plan taps positive human tendencies that are deeply embedded in human nature as it actually exists--self-interest, the innate desire for approbation, the innate tendency to take responsibility to the extent that circumstances require. They set up extremely positive feedback loops. For example, what happens if I squander my monthly deposit? I have to seek help from relatives, friends, or private social service agencies like the Salvation Army. I'm not going to starve--but I'm going to get that help with a whole lot of encouragement--to put it politely--to get my act together. And it won't be a one-time thing, but a continuous process. Conventional social programs are precisely the opposite. They make assumptions about human nature that are blatantly not true (e.g., bureaucracies are not governed by the self-interest of the people who run them) and the unintended consequences are destructive.

    4. In Human Accomplishment, you come to the conclusion that accomplishment has been on a decline roughly since the industrial revolution. How does this square with the exponentially accelerating accumluation of data in the sciences (along with computing power, DNA sequencing, etc.)? Also, how does it square with the Flynn effect? You would think that ceteris paribus an increase in intelligence would result in an increase of genius, but by your reckoning this doesn't seem to be the case.

    The chapter on the decline in accomplishment explicitly deals with that point, so my main answer is: Read the book, or at least chapter 21. The short answer is that, in the sciences, a certain kind of accomplishment--the discovery of basic knowledge about how the universe works--is declining, inevitably. Genetics is a good example. The applications of genetic knowledge are increasing nonlinearly; but the knowledge about the basic workings of genetic transmission has been close to complete for decades. Filling in the details permits all kinds of new applications, but they are details. In large numbers of disciplines--anatomy, for example, or geography--there is little new to learn. They're effectively closed to new accomplishment as I used the word for science.

    As for the Flynn effect, it has nothing to do with the number of geniuses. It appears that the increases have little to do with g (the general mental factor), and that they are concentrated at the low end of the distribution. There is still a lot to be understood about the Flynn effect, but don't count on it for producing advances in string theory.

    5. The decline in individual accomplishments in the arts is prima facie a bad thing, but is it possible that a decline in major discoveries in the sciences could be good thing? If you measure accomplishment by means other than outstanding singular accomplishments, could there be a case for collective, incremental progress?

    The distinction is not between singular and collective (I include collective accomplishments in my science inventories), but between acquisition of new knowledge and the application of scientific knowledge to daily life. By the latter measure, accomplishment did not decline after the mid 19th century. It continued to increase very rapidly.

    6. One of our contributors has conjectured the existence of "genius germs" to explain the examples of what could be called "pathological genius". The elegant thing about this hypothesis is that it would explain the decline in individual achievement even in the face of the Flynn effect, which tracks temporally with improvements in hygiene and immunology. What's your take on this?

    Beats the hell out of me. Or, more dignified: I am not competent to comment. Being born on January 8 (along with Elvis, I would point out), the theory intuitively appeals to me.

    7. In the wake of the Larry Summers flap, you wrote an article in Commentary revisiting familiar themes concering differences in intelligence. What was your impression of the response to that article? Were people as venomous as when The Bell Curve came out, or were they more accepting of the fact that group differences exist? More generally, where do you see the public debate on intelligence differences going in the medium- to long-term?

    I got no flak for the Commentary article that I can recall (not counting blogs), which may be a straw in the wind. I took a much more aggressive position about the intractability of the B-W IQ difference than Dick Herrnstein and I took in TBC (understandably, given what we've learned in the last 12 years), and I said some pretty inflammatory things about sex differences. Perhaps the parsimonious explanation for the lack of flak is that no one reads Commentary. But I think in fact the dialogue is changing. Here's a quick illustration: In the Commentary article, which appeared in September 2005, I took great pains to present the recent work demonstrating that gene markers produced results corresponding to self-identified ethnicity in 99.9% of a large sample. Later that fall, PBS had a special with people like Oprah Winfrey and Henry Louis Gates (if I remember correctly) talking cheerfully about the precise percentages of their heritages that were sub-Saharan-African versus Caucasian, etc., based on DNA tests using similar gene-marker technology. The times are changing.

    8. You and Richard Herrnstein attracted a lot of really thoughtless and absurd criticism, but there were also a few more reasonable voices amid the cacaphony. Which of the critics of The Bell Curve do you respect the most as an intellectual opponent, and why?

    I thought Howard Gardner treated the book more or less fairly in his review. That's the only person I can recall who was on the other side who didn't go nuts. There isn't much I'd retract in a new version, because Dick and I were so mainstream in our science. We weren't out on any limbs that could be sawed off, as far as the data are concerned (my favorite line about TBC came from Michael Ledeen: "Never has such a moderate book attracted such immoderate attention.") But I would write a major expansion of our discussion of cognitive stratification. Living as we do in rural Maryland, my wife and I have been struck by the number of bright kids in our local high school who still go to nearby colleges and return to live where they grew up. I don't know how this anecdotal evidence translates into macro data, but I'd like to explore it. There may be an interesting interaction between urbanization and stratification--it's just an hypothesis, but perhaps stratification is much more severe in urban areas than in small town and rural areas.

    9. Any scholar with a sincere devotion to seeking the truth is bound to have their own beliefs, expectations and prejudices falsified on occaision. Can you tell us about occaisions on which you've discovered something which profoundly altered your beliefs?

    My epiphany came in Thailand in the 1960s, when I first came to understand how badly bureaucracies dealt with human problems in the villages, and how well (with qualifications) villagers dealt with their own problems given certain conditions. I describe that epiphany at some length in In Pursuit. The turnaround that led to TBC occurred in 1986, when Linda Gottfredson and Robert Gordon asked me to be on an American Psychological Association panel discussing their two papers on the relationship of IQ to unemployment and IQ to crime respectively, both of which discussed the B-W difference. The bibliographies astonished me--I had no idea that so much scholarly work had been done in these fields that so decisively contradicted what I had assumed (taught by the New York Times) to believe. If you want to see how far I moved: in Losing Ground, published in 1984, I cite The Mismeasure of Man approvingly.

    My other movement has been less dramatic, but has been intensifying--and will not please the founders and probably most of the readers of Gene Expression. I have been an agnostic since my teens. But I am increasingly drawn to the proposition that of all the hypotheses about God, simple atheism is the least probable. That to be a confident atheist is the silliest of intellectual positions. That thinking about spiritual issues, despite all the difficulties, must be part of being a grown-up.

    10. It has seemed to some of us that you regard libertarianism as really a procedural means to an all-important substantive end: the promotion and preservation of the Good Life as embedded in human wisdom and experience over many generations. Yet those of us with a futuristic orientation see a shadow looming over this project. If science and technology continue to advance unfettered, and individual liberty remains upheld more or less in its current form, then sooner or later we will achieve the means to alter the very substrate of human nature itself. Do you feel this shade as well? Among the many values now held dear by this or that faction of the human race--the pursuit of scientific knowledge, the fellow feeling of families and nations, etc.--which do you think should be actively maintained by our unimaginably evolved descendants of the perhaps not-so-distant future?

    I am conflicted. I think human beings are hard wired to find certain institutions satisfying. E.g., in a libertarian state established immediately (before the hard-wiring is changed), I am confident that traditional marriage would flourish, because a good marriage with children provides such a deeply satisfying form of intimate human contact, far superior to any other arrangement such as serial cohabitation, and is also such a good way to provide for one's security. A libertarian state would do nothing to prevent people from taking other routes. Absent a welfare state, stable marriage with children would be the voluntarily preferred choice of the vast majority of people.

    I am also confident that we will learn how to change the wiring, in many ways, including ones that might tweak the sources of our deepest satisfactions. That's in our future. It's also right to be worried. I am not confident that we are competent to make the right choices. For example, it is possible that increasing longevity dramatically--which is the primary goal of many, many people, including many scientists--will be inimical to human happiness, for reasons that science fiction writers have explored persuasively. But we don't have the option of choosing especially wise humans who can guide the science to the right paths. Long-term, I'm an optimist. We'll muddle through. Short-term, I think the coming technology for fiddling with human nature will produce some awful mistakes.

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    Monday, July 24, 2006

    Test of new features   posted by Razib @ 7/24/2006 08:01:00 PM
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    As you can see above, I added links to stuff like Reddit. I don't use those services, so I would have to register to make sure that the template changes worked, so can users please submit the Charles Murray interview and tell me if there is a bug? Thanks ahead!




    A Parody of Feminist "Logic"   posted by TangoMan @ 7/24/2006 12:17:00 PM
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    It's not really surprising to see that some stereotypes are in fact based on reality. If you're seeking to confirm the stereotype of the all-empathy feminist who spouts Leftist dogma and does so in a fashion that garbles the rules of logic, then look no further than this essay from the law-student blogger who publishes Feministe. In her latest blog posting she unwittingly does harm to her fellow feminists by confirming the worst stereotypes of feminists. She objects to the existence of a non-profit agency, Project Prevention which is headed by Barbara Harris, because it offers $300 to crack-addicted women as an incentive for the women to seek either long term birth control or sterilization.

    In order to make her case against this service Jill bends logical reasoning into a pretzel by:



    -redefining coercion so as to encompass the voluntary exchange of money for compliance with birth control measures;

    -invokes historical injustices going back to the days of slavery and how the women who were victimized during those times were not able to control their own reproduction;

    -throws out charges of "It's racist. It's classist. It's ableist" without bothering to make a case for each charge, for the charges alone are deemed to be the equivalent of argumentation;

    -Invokes sympathy for females who are incarcerated, (innocent victims) and chastises the non-profit agency (evil eugenicists) for extending the cash offer to these women;

    -Decides on a narrative and then bends the facts and logic to support her desired thesis. Consider the following excerpt:


    They're drug addicts, which severely compromises their abilities to reason and make healthy decisions.


    Here she lays the groundwork for allowing others to make reproductive choices for women, but expect her to flip-out if some pro-life advocate used her reasoning to withdraw reproductive choice from pregnant women. So long as the narrative supports her ideological position then logic or consistency is immaterial.

    -Next up, Jill proclaims that there is a correct way to spend a non-profit's resources, and coincidently that correct way happens to be a method she favors. Odd though that she feels entitled to counsel others on how they should spend their money but she doesn't put up her own money or own effort to further the process she favors. In the end she wants to compell action and restrict choice.

    -She infers racism from the fact that 43% of the recipients of these grants are Black, when Blacks only comprise 12% of the American population. No exploration of the details concerning drug abuse patterns across racial groups, nor of the reliance of drug abusers on the public welfare system, nor of the racial background of the mothers of crack babies. No, if there isn't racial proportionalism then of course there is racism at work. Funny that the proponents of diversity seem to expect uniformity.

    -Feeble attempts at smearing by invoking the names of Steve Sailer, Jim Woodhill, Richard Mellon Scaife and Dr. Laura Schlessinger. I suppose in her imagination the case is now closed for anything these folks could support must by defintion be racist and eugenicist.

    -Quote Lynn Paltrow as one of my feminist heroes for she disputes the notion that there are such things as crack babies, for


    The harm that drugs cause during pregnancy is impossible to measure or single out from other factors (poverty, malnutrition, stress, inadequate pre-natal care and so on). . . . Other symptoms of drug dependence - such as craving' and compulsion' - cannot be detected in babies.


    Never mind that:


    the fact that most of these children appear normal should not be overinterpreted as indicating that there is no cause for concern. Using sophisticated technologies, scientists are now finding that exposure to cocaine during fetal development may lead to subtle, yet significant, later deficits in some children, including deficits in some aspects of cognitive performance, information-processing, and attention to tasks-abilities that are important for success in school."


    To cap off her essay, Jill invokes her Leftist-Racist bona fides by quoting from Steve Sailer's interview of Barbara Harris:


    Harris: One of the women who came through our program had 14 babies. She doesn't know who the fathers are, and that's usually the case. A lot of times they don't even know what race the kids are. How sad is that?

    Jill: You mean these women might not know if they're giving birth to a darkie? How tragic.


    The lesson here is not to expect logic or rhetorical rigor from a feminist intent on posturing.

    Update: Amber at Prettier than Napoleon addresses the issue.

    Related: Feminist != Support for Reproductive Rights



    Sunday, July 23, 2006

    Fisher, Wright and evolution of dominance   posted by Razib @ 7/23/2006 01:32:00 PM
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    Robert Skipper has an enormous post on R.A. Fisher & Sewall Wright's theories of dominance. I think Wright was more in the right on this issue, remember, it is easier to break (lose function) than make (gain function).




    Celts and Anglo-Saxons, part n + 2   posted by DavidB @ 7/23/2006 12:58:00 AM
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    Today's UK Sunday Times has an interesting article following up this week's news story about the Anglo-Saxon conquest of England. It includes comments by some of those involved in the research.



    Saturday, July 22, 2006

    The naturalistic fallacy fallacy   posted by Coffee Mug @ 7/22/2006 10:33:00 AM
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    I have an mild interest in ethics, and I came up with something I haven't read yet. I'm assuming some philosopher has thought this through. Soliciting opinions or pointers where to pursue this line of thought:

    Any ethical system that requires more of its adherents than they are capable of is nonsensical. Therefore, we are limited in our range of ethical systems by our natural abilities. For instance, we cannot be asked to perform superhuman physical acts to limit suffering of others.

    Now what about superhuman mental acts? The natural source of ethics with regard to other organisms is empathy. I think we are limited in our capacity for empathy. Joshua Greene (pdf) has been laying this out explicitly from a neuroscience and evolutionary perspective.

    ...our social instincts were not designed for the modern world. Nor, for that matter, were they designed to promote peace and happiness in the world for which they were designed, the world of our hunter-gatherer ancestors.

    He doesn't take the step from 'is' to 'ought', but I'm beginning to wonder if one can escape it. I suppose I ought to start by reading the rest of the stuff on his webpage.




    The appearance of large satellites   posted by Coffee Mug @ 7/22/2006 10:00:00 AM
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    I'm finally shutting down the old website, but I thought it might be nice to have some of these older posts to link to. Plus I'm moving to NYC and writing up a thing for my actual work, so not as much time for original writing for a month or so. This was my first ever blog post (with slight modification).

    The title comes form Herbert Lubs, the first person to describe the chromosomal aberration for which Fragile X syndrome is named. The more extended quote goes "In one-third of the proband's metaphase figures, an unusual secondary constriction was seen at the ends of the long arm of a group C chromosome. This gave the appearance of large satellites, but the chromosome was never seen in association with the acrocentric chromosomes."

    Part of the appeal of talking about Fragile X is that it covers so many levels of research. In this post, I'm going to give the basic features, a little history, and a little cytogenetics. I had planned on trying to explain why the Fragile X chromosome looks the way it does anyway, and it's fortuitous that there is an a blip on the chromosome radar coming up right as I prepare to do this. So without further ado, here's the litany of facts that you could've got if you'd only just googled Fragile X Syndrome:
    • Fragile X syndrome (aka FRAXA) is the leading cause of inherited mental retardation. (The most common cause overall is Down's syndrome.) It causes mental retardation in approximately 1 in 4000 boys and 1 in 7000 girls.
    • The mental effects include moderate-to-severe mental retardation sometimes associated with autism or hyperactivity.
    • Sometimes, but not always, males with the syndrome have tall stature, larger ears, a long face, and machroorchidism (large testicles).
    • The effects in females are often milder. This has to do with the phenomenon of X chromosome inactivation. Since the syndrome appears to result from an inactivated gene much of the function can be take care of by the copy on the other X chromosome if she's lucky enough to have the right one inactivated. Actually there is some evidence out there that there may be some bias towards inactivating the chromosome with the abnormality.
    • The problem is caused by a trinucleotide repeat expansion. I mentioned before that this has already been covered probably more clearly, but I'm going to go into more detail about that here in a minute. What this means is that somehow the DNA copying mechanism gets stuck on this long chain of CGGs and kind of gets it stuck in its little DNA polymerase head and just keeps repeating itself like you do when you listen to too much of your local top 40 station and keep repeating "Back then ho's didn't want me, now I'm hot ho's all on me," in your head even though you think Mike Jones might be developing a little slowly himself. And you know how he says "I said" before the fourth repetition and then we can finally move on to the much anticipated chorus? The same thing goes for the triplet repeat problem. When you have a long chain of CGGs and it's interrupted by an AGG every once in a while you have less of a chance of getting stuck and causing the disease (by you I mean DNA polymerase.) This will not be my last bad hip-hop analogy.
    • One last thing for the basics is that the result of all of this is that a gene called FMR1 in humans is silenced so there is no FMRP (Fragile X Mental Retardation Protein). This causes manifold problems at different organizational levels and I'll get into all of that one of these days because learning about that stuff is what got me interested in Fragile X to begin with.
    These discoveries have been about 50 or 60 years in the making, and I thought I'd point out the salient bits of the history. I'm getting most of this from the Neri and Opitz commentary cited at the bottom. The first hint came from a 1938 survey of 1280 mentally retarded patients. 55% were male and 45% were female, pointing to a potential role for gender in mental deficits. Further evidence came in 1943 when Martin and Bell reported a pedigree showing mental retardation linked to the X chromosome. Fragile X is also referred to as Martin-Bell syndrome, although there is some confusion as to whether the diseases are one and the same. 20 years later, a Robert Lehrke and a John M. Opitz performed a more systematic study with larger samples all around and once again found an abundance of evidence pointing to an X-linked cause for "25-50% of all retardation." I should point out that there are a number of other X-linked mental retardations resulting from the disruption of various genes, but even considering all of these different causes the number is a bit of an overshoot and has been toned down through the years. A year after Lehrke's thesis came out, Herbert Lubs published his work showing the karyotype for which fragile X is named. It took some time before the cytogenetic test really became popular though because other cytogeneticists found it difficult to replicate his findings. Grant Sutherland, who is still researching the molecular mechanisms of genetic disease down in Australia, is credited with discovering that the fragile sites were much more easily observed in conditions of reduced folate in 1977. This led to a flurry of attempts to use folic acid as a preventative measure during pregnancy, but it doesn't appear to do the trick. The last milestone in this brief history came in 1991 when three independent labs (Oostra-Warren-Nelson; Sutherland; and Mandel groups) reported the final link to a single gene dubbed FMR1 on the X chromosome and indicated the triplet repeat expansion nature of the disease. We may be considered to be either going through or just past another milestone with the emergence of the mGluR theory of fragile X syndrome, but I won't get into all of that now since I want to use it as an excuse to write about the electrophysiological phenomena of long-term potentiation and long-term depression and some of the molecular biology of the synapse.

    Since I started off with the appearance of fragile X chromosomes I thought I'd try to explain why they look the way they do. This information was harder to find than I expected. It would appear that people are still working on this problem while I thought it would have been an almost immediate fallout from the discovery of the disease mechanism. Here's what I've got so far. "Microscopy" turned out to be a useful search term. First, there is a bit of an excuse to add a couple more pretty pictures. I found something of a methods paper describing a new way to mount chromosomes for transmission electron microscopy (TEM). These authors don't waste any time theorizing or introducing or giving background information. They want everyone to be aware of this new awesome technique and that's it. So it's kind of hard to understand, but the gist of it is that not only can you see the fragile site on these X chromosomes depicted as a reduction in electron density at the boundary between the main chromosome and the satellite, but you can also see other pockets of reduced electron density throughout the satellite. The picture below shows the tip of a normal chromosome on the left and a fragile one on the right. See how the fragile one is less dense? They can even see this pattern at least one chromosome that doesn't show a fragile sight when they use regular fluorescence light microscopy which may indicate a burgeoning fragile site. My understanding is that low electron density means that there are less proteins there. This is consistent with the story from this other paper.

    DNA during metaphase, which is when the pictures of chromosomes that you always see are taken, is coiled up and packed really tightly and part of the way this is achieved is to wrap the DNA strand around proteins complexes called nucleosomes. This is not the only case where DNA is wrapped around nucleosomes. It is pretty much happening all the time and DNA is getting wrapped and unwrapped all the time. Wang et al looked at the effect of having a bunch of CCGs repeated on this process. The way they did this was to mix small pieces of DNA (with or without a CCG repeats near one end) that were ostensibly not attached to any protein at the time with purified histones and let nature run its course. Then they took pictures with an electron microscope and counted places where nucleosomes had hooked up with the DNA. They found that while the distribution was fairly even across the non-CCG repeat DNA, there were hardly any nucleosomes at the location of the CCG repeats. So having a bunch of CCG's in a row makes it hard for nucleosomes to get involved. In fact, in later experiments, they found that nucleosome assembly was 62% less effective when there was a set of 76 repeated CCG's. They suggest that this leaves the DNA vulnerable to a process called methylation, by which one of those C's basically gets an extra carbon molecule sticking off of it that can alter the way the DNA interacts with proteins later on and lead to gene silencing. The consensus is that methylation is probably the mechanism by which the FMR1 gene gets turned off. One thing I'm not clear on is that I had thought that the way that methylation leads to gene silencing was by recruiting an enzyme that helps lead to nucleosome assembly on that particular chunk of DNA. The DNA wrapped around nucleosomes is relatively unavailable for transcription and therefore the gene is switched off. But in this case the methylation is supposed to be in conjunction with a lack of nucleosomes. How does that work?

    Here are a couple really good websites from Fragile X research/education/fundraising organizations:
    Fragile X Research Foundation, National FragileX Foundation.

    References:
    Mandel JL, Biancalana V (2004). Fragile X mental retardation syndrome: from pathogenesis to diagnostic issues. Growth Horm IGF Res. 14: S158-S165.
    Neri G, Opitz JM (2000). Sixty years of X-linked mental retardation: a historical footnote. Am J Med Genet. 97: 228-233.
    Wen GY, Jenkins EC, Goldberg EM, Genovese M, Brown WT, Wisniewski HM (1999). Ultrastructure of the Fragile X chromosome: new observations on the fragile site. Am J Med Genet. 83: 331-333.
    Wang YH, Gellibolian R, Shimizu M, Wells RD, Griffith J (1996). Long CCG triplet repeat blocks exclude nucleosomes: a possible mechanism for the nature of fragile sites in chromosomes. J. Mol. Biol. 263: 511-516.




    Family Connections - part n   posted by DavidB @ 7/22/2006 05:34:00 AM
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    I have previously written on the subject of creativity apparently running in families, like the Darwins and the Huxleys, so I was intrigued to see in the UK Times book reviews this morning a rave review of a first novel by Emma Darwin. I wondered if this was indeed an addition to the illustrious lineage of Darwins, or merely a pseudonym, perhaps taken in hommage to Charles Darwin's wife Emma, a remarkable woman in her own right. But a little Googling confirmed that the budding novelist is indeed a great-great-granddaughter of Charles and Emma. It is curious that the Darwins appear to deliberately choose names for their children to emphasise their family connections, so, for example, one of the grandsons of CD was named Charles Galton Darwin (a double whammy!), one of CD's great-grandsons is named Richard Darwin Keynes, and another one is named Erasmus Darwin Barlow. It must give them a lot to live up to.
    Added: I have worked out Emma Darwin's line of descent from CD.
    She is the daughter of Henry Galton Darwin, former adviser to the British Government on international law.
    Henry Galton Darwin is the son of Sir Charles Galton Darwin, physicist and Director of the National Physical Laboratory.
    Sir Charles Galton Darwin was the son of Sir George Howard Darwin, mathematician and professor of astronomy at Cambridge. ('Howard' is another family name. It was the maiden name of CD's grandmother.)
    Sir George Howard Darwin was a son of Charles and Emma Darwin.
    Emma (the novelist) appears to be the first woman in the family to have had that name since her great-great-grandmother.




    Just so....   posted by Razib @ 7/22/2006 03:02:00 AM
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    Wow, Snake-spotting may have helped us evolve-study, serious bullshit. No "study" really, just story telling. This kind of crap makes evolutionary biology look bad.

    Update: The full paper is up in the forum as "snakes" (PDF).

    Update by Darth Quixote: John Hawks, while critical, does have some nice things to say about this paper.



    Friday, July 21, 2006

    Mendel's Garden #3   posted by Razib @ 7/21/2006 09:54:00 AM
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    Is up.



    Thursday, July 20, 2006

    German Baby-Making: Spurts and Stalls   posted by TangoMan @ 7/20/2006 08:08:00 PM
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    What was going on in Germany in April of 2001 that so distracted people that many of them forgot to get busy making babies that month? And when the sudden forgetfulness was likely noted shortly after January of 2002, did the Germans feel guilty and make a concerted effort to get back on track by getting extra busy in March of 2002, or was there a massive power failure which left people with little to do but seek their own form of entertainment?

    Check this graph of Germany's birth data and note the deviation from expected norms in the months of January 2002 and December 2002. I've graphed 10 years of data and the monthly average for births in January is 62,881, usually in a narrow range of 59,000-65,000 but in January of 2002 the births dropped to 47,613. Then to close out the year there were 73,104 births in December when the monthly average is 61,916 ranging between 56,000 - 67,000.

    What I've done for the graph is taken the annual mean and then charted the monthly variance from the mean. Quite clearly there are annual cycles to conception (and these vary by country - more data in subsequent posts) and there are two very noticable deviations from the norm in 2002.

    So, what was going on in Germany back then?





    Neandertal autosomal sequence goes live   posted by Razib @ 7/20/2006 07:46:00 PM
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    Most of you probably know this, but the race is on to sequence the Neandertal genome. Nick Wade has a decent story on it. Important point:

    The chimp and human genomes differ at just 1 percent of the sites on their DNA. At this 1 percent, Neanderthals resemble humans at 96 percent of the sites [the first 3 million base pairs], to judge from the preliminary work, and chimps at 4 percent.


    No surprise, the putative last common ancestor between chimps and humans is 6 million years BP, Neandertals and modern humans is 500,000 years BP, and order of magnitude difference.

    But these "last common ancestor" numbers derived from coalescence of uniparental lineages (e.g., mtDNA) should be taken with a grain of salt as sister speies often interbreed, see the work on baboon hybrid zones. Here's a money shot for GNXP readers:

    A longstanding dispute among archaeologists is whether the modern humans who first entered Europe 45,000 years ago, ultimately from Africa, interbred with the Neanderthals or forced them into extinction. Interbreeding could have been genetically advantageous to the incoming humans, says Bruce Lahn, a geneticist at the University of Chicago, because the Neanderthals were well adapted to the cold European climate - the last ice age had another 35,000 years to run - and to local diseases.

    Evidence from the human genome suggests some interbreeding with an archaic species, Dr. Lahn said, which could have been Neanderthals or other early humans.




    Highly parallel genomic assays   posted by the @ 7/20/2006 06:55:00 PM
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    A review of Highly parallel genomic assays

    Recent developments in highly parallel genome-wide assays are transforming the study of human health and disease. High-resolution whole-genome association studies of complex diseases are finally being undertaken after much hypothesizing about their merit for finding disease loci. The availability of inexpensive high-density SNP-genotyping arrays has made this feasible. Cancer biology will also be transformed by high-resolution genomic and epigenomic analysis. In the future, most cancers might be staged by high-resolution molecular profiling rather than by gross cytological analysis. Here, we describe the key developments that enable highly parallel genomic assays.


    Summary:

    • Highly parallel genomic assays have two fundamental characteristics: a highly parallel array-based read-out and an intrinsically scalable, multiplexing sample preparation.

    • The power of highly parallel genomic assays is that they tend to follow the principle behind Moore's law: the amount of information extracted from a sample increases linearly with the number of probes on the array, whereas the overall cost of the assay tends to increase at a much slower rate.

    • These general concepts are being applied successfully to an increasing variety of assays, including gene-expression profiling, SNP genotyping, genomic copy-number analysis, measurement of allele-specific expression levels, and methylation status.

    • Early genomic assays, such as gene-expression profiling, relied only on sequence-specific probe hybridization to confer specificity. The next generation of assays have made use of enzymatic discrimination in addition to hybridization to increase specificity and to enable assay designs that extract more information.

    • Data quality, reproducibility and robustness of intrinsically parallel assays that use enzymatic discrimination have been shown to be high, defying the conventional wisdom that increasing sample complexity automatically results in lower data quality.

    • The technology of highly parallel assays is enabling a revolution in genomics that has far-reaching implications for molecular biology and human health. Increasingly, ambitious projects that aim to be more comprehensive in their approach to genomic analysis, such as the International HapMap Project, the ENCODE Project, and the Cancer Genome Atlas, are reliant on new, highly parallel assay technologies.

    • The orders of magnitude decrease in cost and increased speed and accuracy that are provided by highly parallel assays have brought us to the dawn of a potentially revolutionary new era of discovery in human genetics that will be based on comprehensive, high-resolution genetic mapping.

    • Such studies might require about a billion or more genotypes, and were impractical prior to the advent of the assays that are described in this Review. A few years ago, the genotyping costs for such a study would have been in the hundreds of millions of dollars. Today, the costs would be a few million dollars, with far higher data quality and completeness, and genotyping can be carried out in a few weeks instead of many years.

    • Parallel assay systems are assisting a similar revolution in the field of DNA sequencing, and will probably enable powerful new comprehensive studies that are prohibitively costly today.





    Lynn's latest   posted by the @ 7/20/2006 06:42:00 PM
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    National differences in intelligence and educational attainment

    We examine the correlations between the national IQs of Lynn and Vanhanen (Lynn, R. and Vanhanen, T. (2002). IQ and the wealth of nations. Westport, CT: Praeger. Westport, CT: Praeger, Lynn, R. and Vanhanen, T. (2006). IQ and global inequality. Athens, GA: Washington Summit Books.) and educational attainment scores in math and science for 10- and 14-year olds in 25 countries and 46 countries (respectively) given in the TIMSS 2003 reports. It was found that national IQs had (attenuation corrected) correlations of between 0.92 and 1.00 with scores in math and science. The results are interpreted as a validation of the national IQs. They suggest that national differences in educational attainment may be attributable to differences in IQ, or alternatively that national IQs and in educational attainment are both indicators of the mental ability of national populations. It is also shown that national IQs are positively associated with national per capita income (r = .61). It is proposed that these have a reciprocal positive feedback relationship such that each augments the other.




    Predicting academic achievement with cognitive ability   posted by the @ 7/20/2006 06:39:00 PM
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    Predicting academic achievement with cognitive ability

    The purpose of the present study is to explain variation in academic achievement with general cognitive ability and specific cognitive abilities. Grade point average, Wide Range Achievement Test III scores, and SAT scores represented academic achievement. The specific cognitive abilities of interest were: working memory, processing speed, and spatial ability. General cognitive ability was measured with the Raven's Advanced Progressive Matrices and the Mill Hill Vocabulary Scales. When controlling for working memory, processing speed, and spatial ability, in a sample of 71 young adults (29 males), measures of general cognitive ability continued to add to the prediction of academic achievement, but none of the specific cognitive abilities accounted for additional variance in academic achievement after controlling for general cognitive ability. However, processing speed and spatial ability continued to account for a significant amount of additional variance when predicting scores for the mathematical portion of the SAT while holding general cognitive ability constant.




    Social Class and Life Expectancy   posted by DavidB @ 7/20/2006 04:17:00 AM
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    It is well known that people in the lower social classes on average die earlier than those in higher social classes. Obviously this could be due to factors of nature, nurture, or any combination thereof.

    A new study by a reputable twin research unit in England casts some light on this. As reported by the BBC here, the study included some female MZ pairs who had married into different social classes. The results showed a significant difference in a physical indicator of ageing (telomere length), with those twins who married lower-class husbands ageing faster. As the twins have the same genes (quibbles about somatic mutations aside) this must be an environmental effect. The authors speculatively attribute it to the stress of lower social class life. Or maybe it is just the stress of marrying low class husbands??

    An important caveat: the sample size is small, and another study is said not to have found significant effects.



    Wednesday, July 19, 2006

    Celts and Anglo-Saxons - part n + 1   posted by DavidB @ 7/19/2006 04:38:00 AM
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    Clearly I will have to get up very early in the morning to beat Razib to the punch! (see his post below).

    On reading the UK Times this morning I was pleased to see that a new study claims to show that (and how) a relatively small number of Anglo-Saxon invaders in the early middle ages (5th to 7th centuries) could have made a disproportionate contribution to the genetic make-up of England. I was even more pleased to find that the study in question (published in Proceedings of the Royal Society B) is available as a free open access download here.

    My pleasure turned to mild disappointment on reading the paper and finding that it (apparently) contains no new genetic research. As I have pointed out in a previous post, the genetic evidence on the Anglo-Saxon contribution is unclear, if not contradictory.

    The new study does nothing to resolve this uncertainty, but it does have the merit of showing that a minority ethnic group (the Anglo-Saxons, on this hypothesis) can still make a major contribution to the male ancestry of a population if it has sufficient social and military dominance. But as I argued in my earlier post, recent politically-correct interpretations of the Anglo-Saxon invasion may have underestimated the ease with which a small but militarily superior invader may 'ethnically cleanse' a larger indigenous population.

    I note also that in their interpretation of early Anglo-Saxon society the authors of the new study rely heavily on the Laws of Ine, King of Wessex, which clearly recognise the continuing existence of a Celtic population (as I pointed out in my earlier post). But this is hardly surprising, as we know from other sources (e.g. place-names) that parts of Wessex had a substantial Celtic survival. In other parts of England (e.g. Mercia and East Anglia) the Anglo-Saxon takeover may have been more brutal and complete.



    Tuesday, July 18, 2006

    Stem Cells and Ramesh Ponnuru   posted by the @ 7/18/2006 07:20:00 PM
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    Ramesh Ponnuru has an article in NRO on the embryonic stem cell (ESC) vote. I can't comment on Ponnuru's arguments about Reagan, but I can speak to the science. Ramesh critizes the claims of ESC research advocates. Although these advocates do often stretch the truth on the promise of ESCs, Ramesh's corrections snap back way too far.

    264 pro-funding congressmen write, "As you know, embryonic stem cells have the potential to be used to treat and better understand deadly and disabling diseases and conditions that affect more than 100 million Americans, such as cancer, heart disease, diabetes, Parkinson's, Alzheimer's, multiple sclerosis, spinal cord injury, and many others." The claim is worded vaguely enough so that it is not exactly false: You couldn't prove that the research has no "potential" to improve our understanding of the common cold. Under the influence of the pro-funding lobby, relatives of ailing people now believe even stronger claims. Patti Davis's Newsweek article called stem-cell research "the miracle that can cure not only Alzheimer's but many other diseases and afflictions."

    But Rick Weiss reported in the Washington Post that, "of all the diseases that may someday be cured by embryonic stem cell treatments, Alzheimer's is among the least likely to benefit." (Embarrassingly for the Post, it ran its editorial arguing that increased funding could lead to Alzheimer's treatments on the same day it ran the Weiss story.) Cancer and heart disease are pretty far down the list, too, although they're useful in generating the figure of "more than 100 million Americans."


    These criticisms seem to be based on the belief that the promise of ESCs is as a material source for cell-replacement therapy. Such therapies would ostensibly require the perfection of cloning techniques, a vast resource of human eggs, and large amounts of money. The more likely avenue from ESCs to cures is via the creation of ESC culture systems that model common diseases. From these cell culture models, the molecular basis of each disease could be examined in otherwise unavailable detail... drug targets, blah blah blah.

    Ramesh:
    The president's critics say his numbers have proven wrong: Only 19 subsidized lines are available to researchers. Wittingly or not, the critics are conflating eligibility and availability. The lines that were eligible for funding were not immediately available. Legal rights had to be parceled out, and the lines had to be developed. These processes took time, and not because of Bush's funding restrictions. But the number of available lines has been increasing, and will continue to increase — possibly to as many as 55. The congressmen claim that if Bush's policy were liberalized, research could be done on 400,000 embryos currently frozen at IVF clinics. But the study from which that estimate comes notes that most of those embryos have been stored for future reproductive use. The study indicates that at most 275 additional lines could be generated from these embryos.


    Sounds like non-sense, but 275 is 5x more than 55 and 15x more than 19. What's needed are lines that are genomically intact and genetically diverse. Who wants to use the 2001 model when the 2006 model could be made available?

    Ramesh:
    It is certainly true that if the president's goal were to maximize embryonic stem-cell research, to the exclusion of other concerns, he would adopt a more liberal policy. The director of the National Institutes of Health has said as much, in a statement that pro-funding polemicists have treated as a devastating admission. But it is also true that no researcher has complained that the current policy is impeding him; the complaints have been more along the lines that the policy is keeping people from going into the field.


    This implies a serious lack of understanding of how biomedical science is done... it's done by grad students, post docs and assistant profs (i.e. new people). Additionally, ESC research is relatively new and relatively small. Keeping it from growing means keeping it from happening.

    Ramesh:
    Funding proponents have sometimes been willing to imply that Bush has prohibited embryo research rather than limited government funding for it. Patti Davis wrote in her Newsweek op-ed that her mother had "emerged as a central figure in the effort to get the federal government out of the way." That is becoming a talking point of the campaign, and it is deeply misleading: The effort is to get the federal government to pay, not get out of the way.


    Until such a time when most research is privately funded, this is a serious problem. The prohibition against using government funds means that ESC research (on prohibited lines) cannot commingle with other research. Slight exaggeration: the usual pattern for getting NIH grants is that you have already done most of the work that you propose to do. Then you use that money to fund the work that will be proposed in your next grant. The funding prohibition keeps new research from being started in this fashion.




    Celts & Anglo-Saxons, part n   posted by Razib @ 7/18/2006 07:17:00 PM
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    One of the topics we've touched on before on this weblog is historical genetics, the use of genetical methods to elucidate historical questions. This technique has been particularly fruitful in exploring the "history" of the British Isles between the withdrawl of the Romans in the early 5th century to the time of the Venerable Bede in the early 8th I place "history" in quotation marks because we really don't know that much about this period. When the Romans left Britain was a land with a Christian and romanized Latinate elite and a predominantly Celtic and pagan rural population. By the 7th century most of the geographic expanse of the British Isles was occupied by Anglo-Saxon kingdoms and principalities (Update: Theresa points out that I am overstating the expanse of Anglo-Saxon Britain, see here). The period between is a historical dead spot, with only a few lights like Gildas to tell us what was going on from the "inside."


    In regards to demographics, the past 100 years has seen a periodic swing back and forth as to the nature of the Anglo-Saxon invasions. Prior to World War II it was certainly accepted that the 6th century marked a turning point as masses of Germanic tribesmen swarmed the islands and exterminated the native Britons, with only a few exceptions to the rule such as the battle of Badon Hill, to stem the flow enough so that the Celts could consolidate their redoubts on the extremities. But over the last few generations the scholarly consensus has shifted, and the model has generally been one of elite emulation, where arriving warbands of Anglo-Saxons imposed their language and customs upon the native Britons. This was the story that I read in The Isles, Norman Davies' magisterial historical survey of the nations of England, Scotland, Wales and Ireland. Davies points out that there are references to non-Anglo-Saxons in the early documents when it comes to taxes levied upon townsmen, so it is clear than an indigenous substratum remained. He also alludes to economic historians who suggest that Anglo-Saxon domination was one of slow and gradual cultural hegemony, exploitation and assimilation, as local Celts abandoned their own folkways so as to ascend up the ladder of social status and avoid taxation levied upon the subjegated peoples.

    But, there were a priori historical problems with this narrative. Every other Roman province of substantial civilization, and Britain was such, it was not a marchland, retained Latinate speech. The Franks, Lombards and Visigoths took upon the speech of their subject population. The Anglo-Saxons did not, to the extent that very few words of Celtic origin remain in English (the Thames is one). Additionally, in every other post-Roman society conquered by barbarians Christianity did not recede, but held fast and quickly converted the new elites. In the case of the Visigoths or Lombards, they were often heretical Christians, but Christians nonetheless (the fact that they had an institutional high culture religion already probably insulated them from immediate conversion to Catholicism). In what became England Christianity disappeared for nearly a century, and when it returned it was a Roman, not Celtic Christianity, as the latter was by and large perceived as much a religion of foreigners (the Welsh & Gaels) as was the faith brought directly from the south. Separately these issues may have solutions, but taken together they make one suspicious as to how a small Germanic pagan elite both Germanized and paganized a local semi-Latinate and semi-Christian population. Granted, one could make an appeal to the relative sizes of the two groups being different in that on the Continent the Latin speaking Christian contingent was simply too large for the German pagans (or heretics) to absorb.

    So enter genetics. Are the English a German "race," or a British one? You can follow the link above for older articles, but there is a new article, to be published in Proceedings of the Royal Society: B, where the author makes makes the following argument:

    The Anglo-Saxons, who invaded Britain from the 5th century AD, used a system of "medieval apartheid" to drive the indigenous population to extinction, according to new genetic research.


    The term "apartheid" shows up in all the articles about this research, suggesting this is the "hook" that the papers know will draw in readers. The authors seem to suggesting that the invading Germans outbred the Celtic natives, the beauty of compounding growth led to rough parity in 15 generations. In the generality how plausible is this? I find it very plausible, primarily for the two historical reasons above, the replacement of language and religion suggests a very powerful asymmetry between the two groups above and beyound what we understand elsewhere, and it is reasonable that this would be reflected in the genetic record.

    But, there are important caveats. The newspapers of course make the Anglo-Saxons to be Germanic eugenicists in the manner depicted in 2004's King Arthur. Previous work in fact suggests that there is a lot of genetic overlap between British Celts (at least ancestral Celts) and English on the mitochondrial DNA. The research above looks at the Y chromosomal lineage, the father's line. It is a common historical pattern for roving bands of warlike males to take native wives, so "apartheid" was not in sense we are imagining as in South Africa, but rather something like what happened in Mexico, where Iberian men marginalized native males, but the scarcity of Iberian females results in mtDNA that is predominantly Amerindian. Though the British case is not as extreme, if you survey some of the previous studies (follow the link as I said above) you'll see what I'm getting at. Additionally, the Y chromosomal lineage doesn't always tell us much (necessarily) about the autosomal genome (most of the genome). If Germanic patrilineages were privileged in the noble system then you should have social selection for those Ys out of proportion to what is found in the rest of the genome (though the spread of German language and the regress of Christianity strongly suggests to me that demographic growth in a more straightforward fashion was part of the dynamic). Finally, one should not neglect regional substructure, earlier studies have shown that East Anglia in particular seems to be strongly skewed toward Germanic Y chromosomes, which stands to reason as this is the proverbial "Saxon Shore."

    And one last note, in pre-modern times aristocratic elites could have rather high rates of growth in comparison to the majority of the population . In Victorian England for example during the early years noble women were baby factories while the masses barely reproduced. So one part of equation might simply be that the native Celtic nobility had fled across the border to Wales or over the water to Brittany, and the Celtic peasantry was being constantly replenished with the excess offspring of the Anglo-Saxon nobility.

    (via Dienekes)




    Common disease, common variant   posted by JP @ 7/18/2006 01:53:00 PM
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    In the years after whole-genome association scanning was proposed as a more powerful alternative to linkage studies for locating the alleles involved in "complex" (i.e. involving multiple genetic and environmental factors) phenotypes, there was much debate about the true prospects of this approach. One of the major points of contention in this debate centered around what is now called the CDCV (common disease, common variant) hypothesis, which proposed that common polymorphisms would confer susceptibility to common diseases like heart disease, diabetes, etc.

    Why was this an important question? If common polymorphisms were underlying these traits, it would explain the inability of linkage studies to find them, as linkage studies have low power in this situation. In this case, association studies might succeed in places where linkage studies could never come up with any consistent results (see linkage versus association). However, if complex diseases were caused by multiple rare loci, the association approach would still be powerless and, well, human geneticists would be out of luck. For population genetic models supporting either side (multiple rare variants versus common variants) see the links in this post.

    Five to ten years on, what's the emerging consensus? Well, as is often the case in these kinds of scientific debates, both sides are kind of right. In some cases, rare variants play a role, and in others, common variants. But it's clear that those who argued against the whole-genome association approach and the development of the HapMap on the grounds that the CDCV hypothesis was unfounded are currently in the process of ending up looking a little Luddite.

    A new paper in Nature Genetics gives another example of a common disease being influenced by a common polymorphism. In this case, the risk of a heart attack in a Japanese population was shown to be slightly increased by the presence of a mutation, present on 35% of chromosomes, in a gene that regulates inflammation. The increase in risk is slight-- on the order of a 20% increase in the probability of having a heart attack, but significant nonetheless.

    This suggests where population genetic models in the past have gone wrong: common disease phenotypes are products of underlying variation in quantitative traits, and assigning a "fitness" to a certain level of a trait is extremely difficult, as different genetic backgrounds and environmental variation can absolutlely swamp small effects. So assuming a polymorphism that causes a disease must be detrimental, as opposed to neutral, nearly neutral or even beneficial, creates a model that may not track reality. As I've argued before, new paragims for describing alleles that influence disease are arising; "associated with disease = negative fitness" is out.

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    Sunday, July 16, 2006

    Women in science, Part 3595726061058   posted by agnostic @ 7/16/2006 03:10:00 PM
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    Update #1 at Bottom of the post.

    Update #2: We have followed up with a briefer rejoinder here. PLoS Blogs has linked to both posts responding to the commentary by Ben Barres.

    In my view, when faculty tell their students that they are innately inferior based on race, religion, gender or sexual orientation, they are crossing a line that should not be crossed - the line that divides free speech from verbal violence - and it should not be tolerated at Harvard or anywhere else. -- Ben Barres

    Good god, not again! There's a current buzz in parts of the blogosphere about potential discrimination against women in science, initially sparked by a commentary letter (pdf, also available in our GNXP forum -- under the Frappr ad) to Nature by female-to-male transgendered Ben Barres, a professor of neurobiology at Stanford. It's mostly a rehash of the innate sex difference denial, an extreme viewpoint that is not only false, but by this point in time, annoying. We've covered the issue here at GNXP before (see here, here, and here), and in response to the Larry Summers fiasco of 2005, Steven Pinker debated Elizabeth Spelke here (slides which contain his references here; another list of relevant literature compiled by Pinker here in pdf form). As I consider this issue decided in favor of the camp that believes the contribution of innate biological factors is greater than zero, I won't waste any more space repeating what others like Pinker have already said; I'll consider them background reading. So then, let me turn specifically to the charges that Barres brings up, as well as some other points relevant to the debate but which Pinker did not specifically address in his debate or popular writings -- namely sex differences in personality that are relevant to scientific creation, as well as the nature of scientific creation itself.

    Before getting to the hard data, allow me to voice my utter disgust for the exploitation of personal information in Barres' commentary, as well as in any other difference-denying writing. No readers of Nature, or any other journal, are interested in anecdotal evidence -- and given how brief the articles are in top-tier journals, even a single sidebar or consistent parenthetical musings constitute disproportionate allotment of space to the anecdotal compared to the data-driven. [1]

    First, Barres defines the "Larry Summers Hypothesis," which he ascribes to Summers, Pinker, and Peter Lawrence, in this way: "women are not advancing because of innate inability rather than because of bias or other factors" (my emphasis). Already we've constructed a straw man, as none of these fellows, nor I, nor anyone else who believes innate sex differences play a role, assume that they are the only role, leaving no room for bias or "other factors." On the contrary, the claim is merely that innate factors are non-trivial, not that they account for 100% of the variance in career outcomes. He then proceeds to review irrelevant literature showing that the average test scores in math for males & females from ages 4-18 are the same -- in Pinker's debate against Spelke, he covers the relevant literature that addresses greater male variance, which leads to increasingly disproportionate male representation in both the upper and lower tails of the bell curve: "more prodigies, more idiots," as he says. And indeed, it's the far upper tail that we're interested in -- to become a tenured math prof at Harvard, no one cares if you can do long division; at a very minimum, they care about your ability to quickly solve those brain-teaser problems at the end of the SAT math sections (for example, if you take a grapefruit and make 3 slices all the way through it, what's the most number of pieces you could end up with?). [2]

    However, not only does the different variance matter for IQ or some other measure of cognitive ability -- it matters for every single variable that is involved in eminence in the world of science. Here I reviewed the relationship between g and creativity / eminence (scientific or artistic) -- the punchline is that the distribution of eminence in science and art is log-normally distributed, meaning that whatever factors are involved interact multiplicatively rather than additively [3]. The difference, recall, is that in an additive mix of things, the components don't "see" or "talk to" the others, whereas in a multiplicative mix, the components interact in a "synergy," mutually enhancing each other. Subtract a high score on one variable from an additive mix, and the overall score isn't affected that much -- since all the pieces are working blind of one another's doings. Subtract a high score on one variable from a multiplicative mix, and the whole thing crashes since the pieces are mutually reinforcing -- as if a Miss Universe contestant had ideally proportioned eyes, full pouty lips, neotonous facial geometry, lustruous hair, pearly white teeth ... as well as boils encrusting the majority of her face. It's difficult for us to isolate each component feature, assign it a score, and then add them up (in which case this contestant might score quite high). Facial perception is more of a gestalt process, so we can't help but view it as a synergistic entanglement of features, and hence this contestant wouldn't stand a snowball's chance in hell of winning.

    Now, the exact same thing applies to the factors involved in becoming a top scientist (or artist). First, and probably most important, is an IQ of roughly 125 to 130 (so, roughly +2 SD), and again males are overrepresented here due to greater variance. Francis Galton, the first modern psychologist to study genius, suggested that another key factor is a disposition for "doing a great deal of very laborious work" [4] -- slaving your butt off to discover or create something. In slide 25 of Pinker's debate, there is a convenient graph of how many hours per week a group of 33 year-old males vs females desired to work. They (n = 1,729) were pre-selected to have math skills in the top 1%. In the range of 60-69 hours a week, males outnumber females by about 2 to 1, and ditto for the range of 70+ hours a week. If for no other reason than that women on average are more likely to be wired to want to raise a family or take care of elder relatives, the biological contribution to this discrepancy in slavish commitment to work is non-trivial.

    Another key personality trait, in the estimation of researcher of genius Dean Simonton [5], is the Big Five factor called Openness to Experience -- specifically, its lower-order facets called Openness to Fantasy and Openness to Ideas, which the Big Five manual describes, respectively, as: "receptivity to the inner world of imagination" and "intellectual curiosity." The other facets of Openness measure Aesthetics "appreciation of art and beauty," Feelings "openness to inner feelings and emotions," Actions "openness to new experiences on a practical level," and Values "readiness to re-examine own values and those of authority figures." The latter four may make one more cultured, in touch with one's feelings, willing to vacation in strange lands, and search for further moral improvement by questioning received moral values -- but surely "imagination" and "intellectual curiosity" are what matter for making a good scientist (though arguably Openness to Feelings would matter for artists in addition to Fantasy and Ideas). But is there any evidence of male advantage in these two facets of Openness? Indeed, that is exactly the case.

    The best meta-analysis of sex differences in personality traits is Costa, Terracciano, & McCrae's (2001) review [6] (available in GNXP forum), which specifically measured differences in the Big Five factors and their facets, an improvement on Feingold's (1994) meta-analysis [7]. Across cultures (N = 21,642) and in the US (N = 1,000), males scored higher on Ideas (= "intellectual curiosity"), with a difference in means of roughly 0.165 SD outside the US and 0.32 SD inside the US. Now, "outside the US" is a big place, and their data show that the other Western, Individualist countries show differences quite similar to those of the US, with most of the non-Western, Collectivist countries showing differences under 0.2 (thus, considered "weak" effects). As for Openness to Fantasy, data from the rest of the world is quite weak, while in the US the male-female difference in means is 0.16 SD -- still considered "weak" but significant. In fact, the cross-cultural data are so consistent that the authors developed a new construct called "feminine Openness" which added the scores of Aesthetics, Feelings, and Actions, and subtracted the score for Ideas because it turns out the stereotype about women being more likely to explore their feelings and men more likely to explore ideas is true. And remember, we're really interested in the tails -- even a difference of 0.32 SD between means has a more appreciable consequence when we look at the level of people who are very intellectually curious. Let's operationally define "very intellectually curious" as 2 SD above the male mean (like "very intelligent" might be set at IQ 130). Then males would outnumber females by 2.2 to 1.

    Moving on, another key personality trait (or traits) is mild psychopathology, not only on Simonton's (1999, 2004) account, but Eysenck's (1995), Rushton's (1997), as well as the whole tradition that views genius as intricately linked with madness [8]. Keep in mind we don't mean someone so schizophrenic that they're non-functional but rather someone with schizotypal traits who can still function -- in plain English, someone nutty enough to think up novel ideas or approaches but composed enough to develop them to fruition. In Eysenckian terms, the relevant trait is Psychoticism, which is likely the multiplicative result of the Big Five terms Agreeableness and Conscientiousness (namely, a person who is disagreeable and lacks conscientiousness). The Costa et al. meta-analysis shows that there are no appreciable cross-cultural sex differences in any of the facets of Conscientiousness; in the US, there are no differences except a weak one of 0.2 SD between men and women for Competence, which measures "belief in own self-efficacy" -- in the US, males score higher than females.

    However, for Agreeableness, there is a significant moderate effect size at the factor level of 0.57 SD, where women are more agreeable than men across all facets. That means women will tend to excel as social workers, teachers, and in other professions that involve getting along well with others. But it also means that in careers that require a certain level of tough-mindedness, and often callousness towards the feelings of others -- say, when delivering criticism of another's work -- men will be at an advantage. Again, a scientist (or artist) can't be too much of a son-of-a-bitch to others, so let's define "tough-minded" as 1 SD above the male mean. Then men would outnumber women by 2.7 to 1. If we think "tough-minded" scientists should instead be 2 SD above the male mean, then men would outnumber women by about 4.5 to 1.

    Next, top scientists and artists tend to be introverted rather than extraverted [9]. The Costa et al. meta-analysis shows a pattern in Extraversion similar to that in Openness, where the sex difference is at the level of facets: women score higher on Warmth "interest in and friendliness towards others," Gregariousness "preference for the company of others," and Positive Emotion "tendency to experience positive emotions;" while men score higher on Assertiveness "social ascendancy and forcefulness of expression" and Excitement Seeking "need for environmental stimulation." There is no sex difference in Activity "pace of living." The authors again develop the novel construct "feminine Extraversion" which adds the scores of the female-typical facets and subtracts the male-typical ones. This is particularly instructive as it gives a good measure of which facets of Extraversion matter for scientific or artistic achievement -- most of the work is more solitary (as opposed to a career in sales), despite the occasional chat, but in order to get one's voice heard (and thereby to somewhat boost one's self-confidence) one must be socially dominant rather than submissive. On this measure of "feminine Extraversion," Costa et al. found a difference of 0.25 SD between men and women in the US (again, similar figures hold for other Individualist countries, while in Collectivist countries the difference dwindles below 0.2). Again adopting the convention of 2 SD above the male mean (that is, preferring solitary work and remaining cool towards others, while being socially dominant), then men would outnumber women by 1.9 to 1.

    Last of the Big Five is Neuroticism, and as with Agreeableness, there is a clear factor-level sex difference around the world: 0.55 SD difference between the US male and female means, with equal or higher figures in other Individualist countries, and more modest or even weak differences in Collectivist countries. This trait has to do with how prone one is to negative emotions, anxiety, depression, and so on, and I know of no studies linking it to scientific achievement. Presumably for scientists, a more emotionally stable temperament leads to greater success -- though this could well go the other way for the revolutionary scientists. Given how prone artists are to mood and affective "disorders" [10], this would actually be a strength in artistic creation. Let's say for science the optimal level is exactly the male mean -- not incredibly stable but not very unstable either. At this level, men would outnumber women by 1.7 to 1. (For poets, though, the optimal level might be 2 SD above the female mean, in which women would outnumber men by 4.2 to 1.)

    As an aside, let's note that the Costa et al. and Feingold meta-analyses thus thoroughly refute Barres' lazy claim that "There is absolutely no science to support this contention," i.e. "that women are more emotional than men." Women across cultures are score significantly higher on all facets of Neuroticism and are more Open to Feelings. What Barres should have said in noting, correctly, that most violent crimes are committed by men, is that men are more likely to behave violently when something pisses them off -- as shown by the cross-cultural tendency for men to score significantly lower on Agreeableness -- not that they're more emotional (we already saw that they are more Open to Ideas). He also dismisses the notion that men are more competitive on average, suggesting that such a sex difference wouldn't matter anyway because he believes "powerful curiosity and the drive to create sustain most scientists far more than the love of competition." I quite agree. But we already saw that if we define "power [intellectual] curiosity" as 2 SD above the male mean, there would be more than twice as many men as women. And as Pinker pointed out in he debate against Spelke, citing the Benbow et al (2000) study of mathematically gifted youngsters, the variable of "inventing or creating something" was more important to males than females [11].

    Barres then claims that most of the reason why female scientists leak out of the pipeline is due to lack of self-esteem -- perhaps, but a National Science Foundation study [12] found that females more than males were likely to report dissatisfaction with their doctoral field, explaining that they felt pressured into the sciences by others and felt the need to respect these others' wishes rather than follow their own desires. And if lack of self-esteem, despite equal qualifications as a confident male, were the root of the problem, that predicts that females could never make any headway into the sciences, arts, or professions at all -- rather than the reality in which, once the artificial barriers were removed, they flooded in, even if not constituting 50%. The same could be said for Ashkenazi Jews -- though anti-Semitism is largely absent in the top levels of Anglo society today, earlier in the 20th Century and before, Jews suffered not just discrimination but vilification as well. And yet, rather than be crushed by lack of self-esteem, they poured into the arts, sciences, and professions at a rate far disproportionate to their number in the population [13].

    Incidentally, Barres himself notes that after his 10 years of testosterone treatment, three salient consequences have emerged: "my spatial abilities have increased," largely losing "the ability to cry easily," and being able to "complete a whole sentence without being interrupted by a man." Perhaps it is this trio of better spatial reasoning (important in scientific problem-solving), increased emotional stability, and increased social dominance that led a faculty member of his to remark that, "Ben Barres gave a great seminar today, but then his work is much better than his sister's.” Barres is under the impression that spatial abilities and personality traits couldn't make much of a difference in the quality of work one produces as a scientist, but as we've seen, that's not the case. Maybe his new work really has, in part, benefited from his more male-typical profile, a hypothesis he doesn't see fit to entertain.

    Returning to the data, to get an idea of how such tail-end sex differences, together with the multiplicative rather than additive nature of scientific eminence, can have drastic consequences when mixed together, consider the following crude illustration. We actually don't know how strongly weighted each of the variables is -- well, we're sure IQ matters more than Neuroticism, but does Openness matter more than Extraversion, and if so how much? Let's assume they all are equally weighted, and see how the moderate male advantages in each variable "percolate up" to the top when we consider the whole mix. Moreover, let's put IQ aside for the moment and just consider the differences in the desire to slave away at work and the four personality traits that show sex differences. In an additive scenario, we could just add up the male to female ratios (again, just a crude way of looking at it): conservatively, 2 + 2.2 + 2.7 + 1.9 + 1.7 = 10.5. Now instead, multiply them and get 38.4. This conveys how a synergistic scenario creates skew that would favor males even more than a non-interactive scenario would. Remember we left out the male advantage in the high-tail of the IQ distribution, so more realistic account would skew it more for scientific careers -- obviously, women would be favored in a career that requires one to be Agreeable, Neurotic, femininely Extraverted, and femininely Open to Experience (teaching?).

    Returning to our Miss Universe contestant, if each of 4 facial features is scored from worst to best as 0 to 4, the distribution of total scores in an additive scenario would range from 0 to 16 and would be roughly normal, while they would range from 0 to 256 in a multiplicative scenario and would be highly skewed -- crucially, she could score perfect 4s on 3 features but a detestable 0 on the last one, making her total score 0. Lykken et al. (1992) call such traits that are close to all-or-nothing, requiring interactions among many independent traits, "emergenic" [14]. The population geneticists will see this as a new word for epistatic interactions among genes, and this is likely the reason why the progeny of top-caliber scientists and artists (say, Nobelists) tend to be rather mediocre scientists or artists at best, on average, leagues below their parent. As far as purely additive effects of genes go (say, just considering IQ), the children will tend to regress toward the mean, and so be noticeably above-average in IQ (though still less so than their parents). But for traits that require one to luck out in the epistatic lottery, the regression toward the mean is rather fierce since failing to meet the threshold for just one of the component traits will produce near nil results.

    So the question now is to what extent are these traits due to genetic and other factors? I won't rehearse the by now large behavior genetic literature which shows that all personality and cognitive ability traits are moderately to strongly heritable, where additive genetic variance (or the "narrow-sense" heritability) is typically around 0.35, non-additive genetic variance (such as epistasic variance) is typically around 0.15 (making the "broad-sense" heritability ~0.5), shared environmental variance (what's typically called "nurture" -- anything that two siblings reared together would share) is typically around 0 to 0.05, with the rest comprising non-shared environmental variance and errors of measurement [15]. Judith Rich Harris has already done a fine job synthesizing the literature and offering her own interesting viewpoints in The Nurture Assumption and No Two Alike [16].

    Hopefully, the arguments and references from Pinker's debate, as well as the above discussion, have built the case for biological factors accounting for a non-negligible portion of the variance in outcomes in scientific careers. But that still leaves open the question of whether bias operates also -- well, does it? Let's look at the specific claims that Barres makes, aside from the purely anecdotal or self-serving (such as MIT professor Nancy Hopkins heading the very inquiry board investigating her claims of discrimination -- can someone say "conflict of interest?"). The only hard data he mentions is a study done in Sweden on potential sex discrimination in awarding of post-doctoral grants. In his words: "one study found that women applying for a research grant needed to be 2.5 times more productive than men in order to be considered equally competent (Fig. 2)." Oddly enough, Razib here at GNXP blogged on this awhile back.

    But first, notice what Barres leaves out: any descriptive statistics -- he leaves the impression that the authors of the Nature sex bias study had access to thousands of data points on post-doctoral grants, whether from a single study or by conducting a meta-analysis. In reality, the study only looked at the awarding of just 20 post-doctoral grants, 16 of which went to men and 4 of which went to women. Four words folks: lack of statistical power! As Razib pointed out, the claim that women would have to be "2.5 times more productive" than equally qualified men to be judged equally competent commits the authors to a reductio ad absurdum proof that their model is dead wrong. It makes the prediction that, in addition to the already insane quality of work a male would have to generate to get funding, females would have to generate either an extra 3 Nature or Science articles or 20-30 articles in the top journal in a specific field. That's all but impossible to accomplish in the same amount of time, and thus women shouldn't be getting funding or professorships at all! Moreover, the authors were unable to determine whether the sex of the judge correlated with whether they favored a male or female applicant.

    A better gender-blinding study (pdf) was conducted in the US in 1999 to see whether the hiring practices for psychologists at two different levels -- first-time job applicants and those being awarded tenure -- showed sex bias [17]. The CVs for job applicants and tenured profs were identical, with only stereotypical male & female names making the difference. The sample size included 238 judges, both male and female, and the authors, who are at pains to uncover insidious discrimination, conclude that there was no difference in how males and females were judged for the tenured prof position, though males were favored over females for the entry-level position -- but both male & female judges showed this favoring. As the Larry Summers debate is over the top tier of the science world, it's really the datum on tenured profs in this study that merits attention, and there was zero evidence of sex bias. The favoring of males over identical females at the lower level could be parsimoniously explained by the judges' using Bayesian reasoning to infer that the females are more likely to burn out and leak out of the "science pipeline" at the earlier stages, and so are a less safe bet when all other data is the same. Once we reach the late stages, though, the judges may infer that the tendency to burn out should have already manifested itself, and therefore males and females are equally safe bets.

    One source of potential bias that I find more credible, and which Pinker moots in his debate against Spelke, is that the tenure process makes ridiculous demands on women at the stage in their lives when their biological urges are pushing them to start a family, raise children, or look after other family members. Men in their 20s or early 30s, however, might find it easier to single-mindedly focus on their career over potential family concerns. This suggests a possible fix: namely, tweak the tenure process so that women aren't penalized for wanting to follow any desire they may have for family relationships. But again, this can't be the only source of the "leaky pipeline," for if biological factors weren't involved, then the degree of leakiness should track the degree to which females in particular fields desire to have children and take after their family. So, the prediction would be that female psychologists are the least likely to focus on family, biologists more so, and physicists & mathematicians are the most likely to want to start a family. To my knowledge, there is no data establishing this pattern, and it certainly goes against the typical disposition of the average scientist in these fields -- surely it's psychologists who show greater interest in other people, feelings, and family, and not physicists or engineers.

    Nevertheless, I should temper this proposal for making the tenure process more family-friendly by noting the costs -- every choice has both costs as well as benefits. One cost would surely be the drop in quality of the woman's scientific output -- indeed, it would impact a man's output as well, should he have to face the same crisis. The reason is simple: in the most mathematical and abstract sciences such as physics and math, scientists tend to make their first major contribution in their late or mid-20s, respectively; their seminal contribution in their late 30s; and their final major contribution in their early 50s [18]. A likely explanation for this ruthlessly ageist pattern compared to, say, geoscience, is that original research in math and physics makes a greater demand on an individual's fluid intelligence (Gf), or the raw pattern-discerning / abstract reasoning ability, as contrasted with crystallized intellgience (Gc), or the store of ideas accumulated by applying one's reasoning skills to particular problems and disciplines. (g is considered isometric with Gf [19].) So, physics and math are fields in which one doesn't progress by having to read thousands of several-hundred-page books filled with words, but instead by doing difficult reasoning gymnastics through fewer books and articles made up of fewer words. Still difficult, but it doesn't take as long to digest the relevant background material. Simonton (2004) relates the following witticism from physicist and former Lucasian Professor Paul Dirac:

    Age is, of course, a fever chill
    that every physicist must fear.
    He's better dead than living still
    when once he's past his thirtieth year. [20]

    For example, Dirac won the Nobel Prize in Physics in 1933 when he was only 31 years old, the work which won him the prize having begun when he was just in his mid-20s at Cambridge! Einstein's extraordinary year papers on the Photoelectric Effect, Brownian Motion, Special Relativity, and Matter-Energy Equivalence won him the 1921 Nobel Prize in Physics -- he was just 26 when he published these four seminal papers in 1905. I'll leave it to the reader to check how much their favorite Canonical poet, painter, or composer had accomplished by their 30th year, to show that this pattern is not restricted just to top scientists. The upshot of all this is that delaying a scientific career in a field that makes demands on abstract reasoning, or apparently in an fine arts field as well, brings quality costs as well as the benefits of following one's desire to start a family. Moreover, let's say this hypothetical female scientist "drops out" of full-time, slavish work for roughly 10 years (whether dropping out altogether, or doing only occasional part-time work). That's 10 years of work that could have been done, just in sheer quantity, regardless of quality. And as strange as it may seem, the best predictor of how eminent a scientist will become is the sheer quantity of output -- in the real world, those who produce the best also produce the most, though clearly that means they produce a lot of ignored work as well [21]. Again, if an individual faces the dilemma of whether to plow full steam ahead in science / art or to delay doing so to start a family -- regardless of whether this person is male or female -- it's up to them to decide how to trade off the competing goods. But it's clear that choosing a family will have non-trivial consequences for quantity and quality of lifetime output, which is what the tenure committees should focus on the most, assuming they want to hire the best and most promising individuals.

    A possibility worth considering is acknowledging largely biological differences between men and women that predispose the latter to want to start a family more than the former, as well as the blow this would deal to their future careers as scientists, but presenting them with research that suggests that their personal happiness is unlikely to skyrocket, or even increase, once they start a family. To be sure, having raised a family gives one the sense of satisfaction to see the children grown up and ready to strike it on their own in the world, as well as the happy memories of their childhood that we tend to remember more selectively than the miserable ones. Yet on a day-to-day level while the kids are actually growing up, a mother's happiness actually declines, reaching a nadir when the children reach adolescence [22] -- a sure shock to anyone who's raised kids through adolescence without killing them, or to anyone who's honestly reflected on how undeservedly bratty they behaved toward their parents during adolescence. Happiness only reaches it's pre-child-rearing level once the kids have gone off to college.

    So, a partial solution could be to present bright, motivated female scientists with this research, which they can digest and decide how to respond. Maybe some will say, "OK, so day-to-day happiness goes down the toilet for 18 years -- but I want to look back when I'm older and have fond memories, a sense of fulfillment, and so on, so I'll take family over maximizing scientific output." Some, though, might say, "Wow, nuts to rosy retrospection in old age -- full steam ahead in my science career!" These latter could still enjoy the good parts of being around kids by volunteering with youngsters, becoming a godmother, and so on, without having to change diapers or be yelled at to "Get outta my room, Mom!" Now, the right thing to do here is present all the evidence in an unbiased way and let the individuals decide their own course of action according to their own temperaments -- a rather different approach from that of the gender warriors whereby fence-sitting women are all but badgered into feeling ashamed for having let down their gender in the crusade to stick it to The Man.

    Lamentably, Barres ends with an exhortation to "enhance leadership diversity in academic
    and scientific institutions" -- in other words, quotas. Open the doors to anyone who's qualified and motivated, and let the chips fall where they may. And as we've already seen in the Steinpres et al (1999) gender-blinding study of how judges would award tenure to hypothetical candidates, neither male nor female judges showed a preference for men or women, and even at the lower-level of first-time applicants, the female as well as the male judges preferred men. Therefore, simply increasing the number of females would do nothing in itself -- what Barres must have in mind, therefore, is to inflate the number of gender warriors in powerful positions to rig the outcomes in advance rather than render disinterested appraisals. Perhaps this is what is meant by his suggestion for "special hiring strategies"? As already discussed, his seemingly commonsense proposal that "merit be decided by the quality, not quantity, of papers published" runs into trouble with reality, as sheer quantity of output is the best single predictor of a scientist's rank in eminence.

    So, to recapitulate: the contribution of biological, partly genetic, factors to the sex disparity in science is greater than zero, and likely substantial since the variables are multiplied rather than added together. Thus, we're not talking about overlapping normal distributions when we talk about scientific research -- we're talking about overlapping log-normal distributions, where the weak or moderate male advantages in the component normal distributions (e.g., for IQ above 130, for Openness to Ideas, the male-typical pattern of Introversion, etc.) are compounded and thus skew the distributions even more. However, that doesn't mean women will be absent, just underrepresented. The source of these weak or moderate male advantages are partly genetic, partly due to non-shared environmental factors, but not at all to shared environmental factors. For this reason, we can label the causes as "intractable," comprising both genetic and chance factors in development. There is no clear evidence of irrational sex discrimination at the highest levels of science, although one could argue that the way tenure is structured discriminates indirectly against those who want a family, who are overwhelmingly women. Still, modifying the tenure system would bring costs of quantity & quality of output, along with whatever benefits it might also bring for increasing sex diversity. Equal opportunity should be given to all, and the only differences in outcome that show up should reflect underlying statistical differences in talent and temperament between the sexes. And last, but perhaps most importantly, honest discussion cannot proceed when gender warriors like Barres label contrary viewpoints as "verbal violence," and neither should participants indulge whatever desire they may have to focus on the personal rather than the data-driven.

    Update by Darth Quixote: I do not have access to the study cited as Figure 1 in Barres's commentary. You can read what GC has to say about it in the comments. But it is clear to me that at best this study is an outlier with respect to a now-massive body of evidence on sex differences in mental abilities. For analyses of relevant (and typical) data, see these two pieces (this and this) by La Griffe du Lion. The most recent results that I know of, an analysis of sex differences in the Minnesota Study of Twins Reared Apart (Johnson & Bouchard, 2006), also clearly bear out the consensus; note the extremely large male advantage on tests of mental rotation. Another very recent paper by Arden and Plomin (2006) confirms the greater male variance in mental test scores. I also urge readers to check out an analysis of the 2000 Program for International Student Assessment (PISA) on p. 232 of the Handbook of Measuring and Understanding Intelligence: the Varimax-rotated principal component scores on the reading achievement portion of the PISA favor females in all 29 countries; the Varimax-rotated PC scores on the math achievement portion favor males in all 29 countries; and the Varimax-rotated PC scores on the science achievement portion favor males in 28 countries (in Iceland females come out on top by 0.01 standard units).

    For whatever it is worth, the lead investigators of the papers that I have cited (the psychometrician Wendy Johnson and the behavioral geneticist Rosalind Arden) are both women. End of update.


    Notes:

    [1] To illustrate the pointlessness of navel-gazing: the summer before my senior year of college, I did my student internship at my school's laboratory for child language acquisition, a field which, as Pinker notes in his debate, is dominated by women. While other guys were striking it rich high-fiving their frat dude buddies in Wall Street investment banks, or else soaking up the sun hitting on topless girls in South Beach, there I was in a windowless basement room for hours transcribing videotapes of a mother and infant linguistically interacting. But I find precocious baby babble to be cute, so I didn't mind. Of the 7 or 8 people working on this project (from undergrad up to tenured prof), I was the only male. My senior year, I took two upper-level seminars on child language acquisition: one that focused on theoretical connectionist modeling, and another that focused on empirical studies of how children develop linguistically. All four participants in the former seminar were male, reflecting the greater male interest in machines and doo-hickies, while in the latter seminar, only 2 of the 14 or so participants (including me) were male, reflecting the greater female interest in people and children in particular. Now, I could write up this personal anecdote as an article, ascribing this state of affairs to discrimination against males in child language acquisition -- no doubt unconscious and not deliberate, but persistent and insidious nonetheless -- but I would be wrong. I would also be wrong in assuming that anyone else cared, a point that eludes others.

    [2] Pretend the answer didn't jump out at you (it didn't for me anyway). If we start simply, take a 1-dimensional line -- if we make 1 cut, we can end up with 2 1-D pieces. If we take a 2-D circle and make 2 cuts, we can end up with 4 2-D pieces if we make the cuts perpendicular to each other (and just 3 pieces if we made the cuts parallel). So, when we move to 3-D grapefruit, the pattern should continue -- we make 3 cuts, but they should be perpendicular to maximize the number of pieces, as we learned with the circle. That makes 8 3-D pieces. (The apparent pattern is that if we make n cuts through an n-sphere, we can produce at most 2^n chunks.) It's this sort of "figuring out weird, unfamiliar stuff by analogy or sequence pattern" that matters more for doing real science than the mere ability to repeat back what your math teacher taught you by solving a problem that's exactly like what you've practiced a gajillion times in class before the test.

    [3] Shockley (1957). On the statistics of individual variations of productivity in research laboratories. Proceedings of the Institute of Radio Engineers 45, 279-90.

    [4] Galton (1869), Hereditary Genius: an inquiry into its laws and consequences. London: Macmillan. Quoted in Simonton (1999). Origins of genius: Darwinian perspective on creativity. New York: OUP.

    [5] Simonton (2004). Creativity in Science: chance, logic, genius, and Zeitgeist. Cambridge: CUP.

    [6] Costa, Terracciano, & McCrae (2001). Gender differences in personality traits across cultures: robust and surprising findings. J of Pers and Soc Psych 81(2), 322-331. Available in pdf form in the GNXP forum.

    [7] Feingold (1994). Gender differences in personality: a meta-analysis. Psychol Bull 116(3), 429-56.

    [8] Eysenck (1995). Genius: The natural history of creativity. Cambridge: CUP. Rushton (1997). (Im)pure genius--intelligence, psychoticism, and creativity. In Nyborg (Ed.), The Scientific Study of Human Nature: Tribute to Hans J. Eysenck at Eighty (pp. 404-21). New York: Elsevier.

    [9] Cattell (1965). The scientific analysis of personality. Baltimore: Penguin. A group of "eminent researchers" he studied using his 16 PF personality questionairre showed a tendency to be unsociable, emotionally stable, dominant, brooding, undependable, bold, sensitive, trusting, radical, self-sufficient, and self-disciplined. Also, Simonton (1999), Ch. 3. The literature on information-processing and Extraversion is reviewed in Ch. 12 of Matthews, Deary, & Whiteman (2003). Personality traits, 2nd Ed. Cambridge: CUP. On p. 343, their Figure 12.4 synthesizes the cognitive strengths and weaknesses of introverts and extraverts, suggesting that the real-world contexts that extraverts are best suited to are "Dating and mating" and "'High-pressure' occupations," while introverts are best suited to "Artistic/literary/scientific occupations." Presumably "high-pressure" refers to jobs like sales.

    [10] For a (not necessarily exhaustive) compilation of top scientists and artists alleged to have suffered from Schizophrenic, Affective, and Personality disorders, see Table 3.1 in Simonton (1999), p. 96. His lengthy list of references for this catalogue is on p. 253, under the bolded heading "Empirical findings."

    [11] Benbow, Dubinski, Shea, & Eftekhair-Sanjani (2000). Sex differences in mathematical reasoning ability at age 13: their status 20 years later. Psychol Sci 11(6), 474-80.

    [12] Strenta, Elliott, Matier, Scott, and Adair (1993). Choosing and leaving science in highly selective institutions: General factors and the question of gender (Report to the Alfred P. Sloan Foundation). New York, NY: Alfred P. Sloan Foundation. Cited in Ch. 3 of National Science Foundation, Women, Minorities, and Persons with Disabilities in Science and Engineering: 1998, http://www.nsf.gov/statistics/nsf99338/.

    [13] Murray (2003). Human Accomplishment: The Pursuit of Excellence in the Arts and Sciences, 800 BC to 1950. New York: HarperCollins.

    [14] Lykken, McGue, Tellegen, & Bouchard (1992). Emergenesis: genetic traits that may not run in families. Amer Psychol 47, 1565-77.

    [15] Eaves, Heath, Neale, Hewitt, & Martin (1998). Sex differences and non-additivity in the effects of genes on personality. Twin Research 1, 131-137.

    [16] Harris (1998). The nurture assumption: Why children turn out the way they do. New York: Free Press. Harris (2006). No two alike: Human nature and human individuality. New York: Norton.

    [17] Steinpreis, Anders, & Ritzke (1999). The Impact of Gender on the Review of the Curricula Vitae of Job Applicants and Tenure Candidates: A National Empirical Study. Sex Roles 41, 509-528.

    [18] Simonton (1991). Career landmarks in science: Individual differences and interdisciplinary contrasts. Dev Psychol 27, 119-130.

    [19] Gustafsson (1988). Hierarchical models of individual differences in cognitive abilities. In Sternberg (Ed.), Advances in the psychology of human intelligence, vol. 4 (pp. 35-71), Hillsdale, NJ: Erlbaum.

    [20] Originally reported in Jungk (1958). Brighter than a thousand suns (J. Cleugh, Trans.). New York: Harcourt Brace.

    [21] Simonton (1997). Creative productivity: A predictive and explanatory model of career trajectories and landmarks. Psychol Rev 104, 66-89.

    [22] Walker (1977). Some variations in marital satisfaction. In Chester and Peel (Eds.), Equalities and inequalities in family life (pp. 127-39). London: Academic Press. Cited in Gilbert (2006). Stumbling on happiness. New York: Knopf.




    Epigenetics and twins   posted by JP @ 7/16/2006 02:51:00 PM
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    Twin studies have somewhat fallen out of favor in genetics-- instead of estimating parameters like the heritability of a trait, it's now common to simply skip to studies designed to locate genes that play a role in them. If the heritability turns out to be zero, then, well, not a whole lot is going to turn up in a genome scan, but it's generally cost-effective to take that risk.

    A new article in Trends in Genetics highlights another use for twin studies-- research in epigenetics. From the abstract:
    Analyses of epigenetic twin differences and similarities might yet challenge the fundamental principles of complex biology, primarily the dogma that complex phenotypes result from DNA sequence variants interacting with the environment

    One could argue that epigenetics might turn out to be the mechanism by which the environment interacts with genetics, rather than an entirely new paradigm, but this is definitely an area to watch.

    Related: Epigenetic information passed through the generations, Nature epigenetics update.




    Gingrich and Biden on Meet the Press   posted by the @ 7/16/2006 01:55:00 PM
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    Gingrich and Biden on Meet the Press apparently in near total agreement

    Sneak peak at 2008?



    Saturday, July 15, 2006

    Focus on the negative   posted by Coffee Mug @ 7/15/2006 06:47:00 PM
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    I ain't affected by the negative. It's the Reflection and we dealin with the positive. It's for the love and cause of that we got a lot to give. It's the Reflection kid. Never gotta look between the lines to get the messages. - Talib Kweli

    The latest Erin Schuman paper came out two and a half weeks ago in Nature, and it emphasizes something I've been mulling over lately. In the field of synaptic plasticity I think there is this tendency to focus on things being increased. For instance, there are ~7000 PubMed results for "long-term potentiation" and ~1500 for "long-term depression". Also, local protein synthesis is considered a major driving process for long-term potentiation, but people haven't paid nearly so much attention to protein degradation. This paper plus another recent report in J. Neurosci. are turning attention toward the role of protein degradation in LTP.

    Bingol and Schuman tagged one of the subunits of the proteasome (the cell's molecular garbage disposal) with GFP and watched it move around in response to stimulation. Depolarization (activity) led to more signal in dendritic spines. Proteins that need to be degraded are often tagged with a protein called ubiquitin. Ubiquitination is a signal to the proteasome that this protein should be destroyed. The authors found that ubiquitination also increases in response in the spine increased 10 minutes after stimulation. After the initial increase, the ubiquitin signal falls off on a time course that matches the increase in the proteasome, implying that activity drives ubiquitination of some synaptic proteins which are then degraded about 10 minutes later when the proteasome shows up. It's important to note that every activity-dependent change in this paper was also shown to be NMDA receptor-dependent. NMDA itself could drive ubiquitin reporter degradation, and using a perfusion system like that I've mentioned before, they were able to show that the degradation occurs local to the site of stimulation rather than being a cell-wide or dendrite-wide event.

    They then do some tricky fluorescence experiments with tagged proteasome subunits that make me feel like I am really missing something. Paging Dan Dright. Can you make sense of this? My understanding of FRAP (fluorescence recovery after photobleaching) is that you quench the fluorescence in a certain area by over-exposing the fluorophore, and then you wait to see how long it takes to get more fluorescence in that area. This gives you an idea of how proteins are moving around in the cell. The authors found less FRAP in bleached dendritic spines after activity. I would simpllstically interpret this as less proteasomes moving into the spine following activity. Instead, they "thus conclude that the immobile fraction of spine proteasomes increases from 35% to 90% upon stimulation, indicating that the proteasome is actively sequestered in spines." I suppose one source of confusion is that they studied proteasome movement on the order of minutes while the FRAP time courses are on the order of seconds. Later, they report (using this and another technique) that the proteasome spine entry rate increases about 1.5-fold while the exit rate rate decrease 6-fold. I'll have to take their word for it until I get smarter. So in this model the proteasome is getting 'trapped' in the synapse by activity.

    They found some evidence for how the 'trap' is carried out. A large proportion of the proteasomes in their hands were associated with the actin cytoskeleton, an important determinant of spine structure and function. Activity induced an increase in the actin-associated portion of proteasomes. Disrupting the actin cytoskeleton, reduced the proteasome staining in dendritic spines. It's interesting to me that the actin disruption didn't seem to affect CaMKII. This indicates that two major structural elements in the spine are dissociable (i.e. CaMKII doesn't depend on an intact actin skeleton to maintain its spot in the post-synaptic density).

    Along with showing that activity regulates protein degradation, the authors also point out that it is a fairly new understanding of the workings of the proteasome to suggest that the proteasome is delivered to its targets instead of vice versa. Along with the recent buzz concerning P-bodies and RNA degradation, I think the negative side of biological processes may be beginning to catch up to the positive. Some may have simplistically mapped protein synthesis onto LTP and synaptic growth, but this isn't the case. LTP and LTD will eventually both be shown to rely on both protein synthesis and degradation. Analogously, I believe an intact memory will rely on both LTP and LTD within the same dendrite. If you do the yin without the yang you just end up paisley.




    Different immune systems...not attenuated ones   posted by Razib @ 7/15/2006 02:59:00 PM
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    A new paper in Proceedings of the Royal Society B: Biological Sciences contends:

    I measured eight indices of immune function (haemolysis, haemagglutination, concentration of haptoglobin and concentration of five leukocyte types) in 15 phylogenetically matched pairs of bird populations from North America and from the islands of Hawaii, Bermuda and the Galapagos. Immune responses were not attenuated in insular birds, and several indices, including the concentration of plasma haptoglobin, were elevated. Thus, I find no support for the specific hypothesis that depauperate parasite communities and the costs of immune defences select for reduced immune function. Instead, I suggest that life on islands leads to an apparent reorganization of immune function, which is defined by increases in defences that are innate and inducible. These increases might signal that systems of acquired humoral immunity and immunological memory are less important or dysfunctional in island populations.


    This is of course a comparison of birds, and biology is the science of exceptions...but, I have to wonder what it means for humans. In 1491 Charles C. Mann reports that some researches in the field of immunology suggest that not only do the indigenous populations of the New World exhibit reduced MHC polymorphism vis-a-vis Eurasian populations (MHC is an extreme case of balancing selection where overdominance and frequency dependent factors seem to perpetuate the maintenance ancient lineages), but, they seem to have specialized defenses against larger parasites (as opposed to microbial pathogens). In other words, not only are they depauperate in their immune system, but, they might have developed different responses due to local selective pressures, and lack of the meta-populational pool which periodically bathes Eurasia in novel plagues. This has implications for insular groups like Andaman Islanders, they might be well adapted in regards to natural selection, but their adaptive immune system might be rather primitive in comparison to Eurasians who have served as the ideal habitats for virulent plagues over the past 10,000 years.




    Not work safe, but eye safe   posted by Reproduction Rocks (mean(W) > 1)) @ 7/15/2006 12:52:00 PM
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    Just an FYI for y'all out there, GCeleb = Not work safe The Superficial. Be warned, page down fast past 'Alecia Moore aka "Pink" Topless Photos.' And you're welcome :) A shout out to those who focus on phenotype and not genotype.



    Friday, July 14, 2006

    Muslim women in 2-pieces   posted by Razib @ 7/14/2006 10:48:00 PM
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    Miss Universe 2006 finally updated their website so I could collect some phenotypic data for analysis! The delegates seem rather thin, so I suspect that the ones who are turned to the side are more shapeless. In any case, below the fold are pictures of Muslim women in 2-pieces. Just in any case any Salafi readers want to go "burning man" and collect evidence to convict these women of inducing arousal in the male sex....



    Egypt. Pharonically naked yo!



















    Kazakhstan...this is what Michael V. goes for (dictators look good for ample tummy!)



    Turkey in the house, yo!

    Statistical analysis of something, later....




    Selection "controversy"   posted by JP @ 7/14/2006 04:44:00 AM
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    In September of last year, Bruce Lahn's group at the University of Chicago published two articles in Science arguing that two genes which, when mutated, cause microencephaly had recently been (and possibly currently are) under selection in humans. The phenotype under selection was (and still is) unclear, but the fact that mutations in the genes lead to reduced brain size led to a number of hypotheses. Criticisms of the work on moral or political grounds were made, but no one really questioned their actual results. Until now.

    The evidence for selection in the two papers based on a couple observations: first, the extent of linkage disequilibrium around an allele is determined primarily by the age of the allele (i.e. when it first mutated from the ancestral state). Second, if an allele is under positive selection, it will probably be at a higher frequency than most alleles "of it's age". So high frequency + long linkage disequilibrium = evidence for selection.

    Of course, other factors play a role in the length of LD around an allele and its frequency, the most important of which is arguably demography-- different models of population growth and bottlenecks lead to different patterns of variation in the genome. Lahn's group simulated a number of different demographic scenarios, and conclude that realistic neutral scenarios could not account for the patterns they see.

    The current issue of Science has a technical comment on the two papers by Currat et al. which considers some additional demogrphic models. In these models, the patterns in the data are perfectly consistent with neutral evolution. However, as is noted in Lahn's group's response, one could come up with a neutral model to create just about any pattern of sequences. The real question is whether the parameters in that model are plausible.

    The plausability of a given parameter in this kind of model is not something I can judge offhand (though perhaps someone else can), but Currat et al. don't cite a single paper to justify their choices, while Lahn's response includes a number of citations to support their decisions and gently suggest that Currat et al. are out of their element. In my book, citations and evidence trump unsupported parameters, so I don't think the case for selection at the two miroencephaly loci is really in question.

    Ideally, Lahn's two loci would have turned up in the Voight et al. scan for selection in the human genome, which was fairly robust to different demographic scenarios due to their use of a non-parametric statistic. But their approach had low power for alleles of lower frequency (like those under selection in ASPM and MCPH1), and with a limited sample size of 90 people, they didn't stand out.

    So what will resolve this "controversy"? Well, for some people who think the case for selection on lactose tolerance is unfounded, nothing. Otherwise, scans like those by Voight et al. with larger sample sizes should increase the statistical evidence for selection, and functional studies will hopefully elucidate the phentype under selection, making the case complete.

    UPDATE: RPM at Evolgen has more.



    Thursday, July 13, 2006

    Science & religion, the war and the tango   posted by Razib @ 7/13/2006 06:18:00 PM
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    In these debates about science & religion, evolution & Creationism, there are implicit assumptions lurking in the background. The primary one in relation to evolution, elucidated by Richard Dawkins in The Blind Watchmaker and A.N. Wilson in God's Funeral, is that Darwin's theory resulted in the natural and necessary decline in religiosity for the elites. Dawkins went so far as to famously state that one could not have been an intellectually fulfilled atheist before Darwin's theory of evolution. And yet one must ask, who is he to look into the mind of men like Pierre-Simon Laplace and declare them intellectually unsatisfied?1 I suspect Dawkins would find objectionable the assertion of a theist that even with Darwinian theory an atheist is fundamentally intellectually unsatisfied. In the end who knows the mind of a man but God himself?

    If someone were to ask me whether the insights of modern science rendered theism implausible, I would have to affirm that. If someone asked me whether modern scientific insights (natural and social) rendered the likelihood of the plausibility of the distinctive truth claims of theism almost certainly false as a matter of necessity, I would have to affirm that. Nevertheless, I would also affirm that the vast majority of humanity would disagree with me, and that a substantial minority of scientists would also disagree with me (scientists as defined as Ph.D. holders in the natural sciences).


    On the first count, just because one knows that modern science can do wonders does not imply that it is any more than a form of wizardy. Though the majority of humanity will take as valid most of science's truth claims because of the manifest reality of predictivity and applications in engineering, when those truth claims conflict at several removes of logical inference from other truth claims science is not necessarily going to win out. That is, if the inferences are subtle or extended enough then it is not a difficult feat to disregard unpleasant or unwanted implications. Contradiction is no great sin for the human mind, divided and modular as it already is.

    The issue in the case of religious scientists is different, because one assumes that they have internalized many of the more subtle and "under the hood" aspects of the "scientific" worldview because of their participation in its culture. Yet the reality is that though scientists may operate as materialists in their vocation, they are not necessarily materialists in their metaphysics. Why not? As I note above, sometimes the integrated and contingent nature of particular inferences may escape people, but this is less likely with scientists. I think this explains why working scientists who are religious nevertheless tend to eschew the most blatant violations of the scientific world view like Creationism. Nevertheless, many religious scientists do not simply ignore or segregate their mental universes, they often attempt to make some connections between their faith and their science. But the connections they make are usually analogical or metaphorical, diffuse and more sentimental than concrete. A concrete application would be something like the theistic science that some Intelligent Design theorists propose.

    One aspect of the religiosity of scientists is that it tends to be rather peculiar, or exhibit more heterodoxy than is the norm. Isaac Newton was a theist, but he was also personally a unitarian who believed that trinitarian theology was a pagan heresy. If one considers Albert Einstein religious, his God of Spinoza was equated with atheism until the 19th century when genuine godlessness could breathe free, and so set itself apart from pantheism. Physicist John Polkinghorne, a physicist and now a theologian and cleric, exposits a peculiar sort of Christianity, where like Newton he asserts the he goes back to the more Hebraic roots of the faith. Like the early Christians he emphasizes God's power in transcending materialism which dominates the world and opines that ideas like souls contradict the worldview of the early Christians and Hebrews, who seemed to accept only the corporeal self, later transcended by the possibility of resurrection by divine fiat. To me the ideas of many religious scientists are rather alien, and I don't quite know if many orthodox Christians would be wholly comfortable with them.

    I suspect that a deep involvement in the scientific enterprise does increase the likelihood of irreligiosity, and atheism. But, I also believe it has a disruptive effect as a whole on the canalization toward a particular set of religious ideas constrained by cultural expectations. That is, scientists like Isaac Newton and John Polkinghorne wander into weird and unfamiliar religious territory because that is their nature, they are not the sorts to simply accept premises and not move with them toward logical conclusions, they are driven to explore, analyze and decompose systems. This, on average, results in a distortion away from the socially dictated set of axioms which define orthodoxy, especially in the case where those axioms pose local problems of integration with a scientific worldview. Also, I must add that figures such as the ~90% atheism of National Academy of Science members are likely not purely a function of their raw cognitive computational power rending asunder religious ideas, I also suspect that the social culture of science and selection biasing of individuals who devote themselves wholly and monomaniacally to their scientific work play roles in elevating the frequency of atheists in relation to the basal rate. I would bet that it is highly likely that many of the 90% are also individuals with a priori cognitive tendencies which make anthropomorphic deities and religious ritual particularly unattractive.

    I bring this up because I believe that the triumphalism of atheist evolutionists and the terror of theistic Creationisms in the face of the "universal acid" is overstated. A mental parasite needs a good host, and most individuals are not particularly congenial hosts for evolutionary biology on a more than superficial level (i.e., they have read The Genetical Theory or something equivalent so that evolution is not simply another form of wizardy). Additionally, the novel and peculiar memetic constructs generated by some theistic scientists suggests even when parasitism is a possibility the mind can generate successful counter-responses. Creationists, like Duane Gish, who assert that if people believe they are animals they will behave like animals simply do not take into account that the manner in which humans behave is not contingent upon one pillar, their conceit that they are made in the image of God and singular in his Creation. Despite their constant attempts to "glorify their lives through God" my own experience is that most evangelical Christians live mundane lives where the impact of abstract or reflective ideas is less than that of the preloaded and preprimed software we all possess (thanks to evolution!). And for atheists who see in evolutionary theory the necessary refutation of theism, one must remember that the death of the gods has been prophesized for several thousand years now by various thinkers. At some point induction and empiricism must be considered so as to reconsider the model of human cognition that this mentality implies. If the lives of the gods and the sanctity of morals rested on one branch their existence would be tenuous indeed, but I do not believe that is so. Gods and morals are both safe for another day, so both militant religionists and militant atheists may claim both victory and defeat.

    Addendum: Some of you might wonder, "What about Intelligent Design theorists?" As I suggest above, the deeper you get into the scientific culture the clearer are the contradictions between specific religious doctrines or assertions and the chain of inferences emerging out of science. Most scientists bend with the wind and rework some of their truth claims in ways that don't challenge scientific inferences head on, and try to balance the equation by suggesting that their faith has some numinous influence on their science (or, it may be more direct in inspiring or driving their search for truth). Nevertheless, some scientists like William Dembski (I'll call him a scientist even though his mathematical, theological and philosophical background doesn't intersect with the natural sciences) and Michael Behe do not bend with the wind, but attempt to rework science to be more in keeping with their orthodoxy. Or do they? Remember, Behe accepts common descent and macroevolution. My understanding is that Dembski does too, and his God is something of a clockwork genius or something to that effect. The deviations from Young Earth Creationist orthodoxy for these two is great, and Behe is and was a Roman Catholic so this was never a starting point for him. Nevertheless, some of these individuals, Dembski for example, do perceive a tension between their striving for societally accepted orthodoxy and their familiarity with the inferences from science. Like Dawkins and Peter Atkins Dembski avers that modern science is by necessity and operation materialistic and atheistic, but unlike them he isn't happy with this and wants to overturn it. His solution to this crisis? The various forms of Intelligent Design related to information theory he's been pushing all these years! If you read Dembski's online writings you'll note he isn't totally hostile or dismissive of Young Earth Creationists, even if he disagrees with their truth claims. One perceives that the orthodoxy of his youth has a deep resonance and power for him, so even if Young Earth Creationists are wrong he can not help by feel for them, and be with them.

    My point is that the Creationism and Intelligent Design especially are particular responses by scientific individuals who attempt to juggle and reconcile their faith and their science. The reality is that the faith which they are so attached to derives from a pre-scientific age, and is mostly espoused by non-scientific mentalities, and so it is naturally going to periodically contradict scientific insights. The God of the scientists in general, as I allude to earlier, is usually more sophisticated than that. Some would wonder if it is really a religion in a convential sense, Freeman Dyson attends a church and yet I am not convinced that he is a theist. But a small minority of scientifically minded individuals wish to retain the God of the non-scientists, the God of the masses with which they identify and whose myths they cherish on a very deep level, and so they are attempting to reshape science into a more congenial form to mitigate their cognitive stress. That is actually one of my major beefs with Intelligent Design: it seems to me very close to being a concern and issue that cropped up at the intersection of high IQs, the raw realities of science, pre-modern religion and a conscientious drive to square all of life's circles. The evolution-Creation controversy need not be any such thing, as evidenced by the reality that in most of the rest of the world it is of little import, the masses accept evolution as deeply as here they reject, that is, rather superficially. But the motivations of a small minority of theistic intellectuals who wish to retain a pre-modern form of their religious beliefs has resulted in their "sicking" their co-religionists upon us, because by and large the intellectuals are of course the "brains" of the religious organism and it will dance to their tune. As I've said before, cognitively the leading Intelligient Design theorists would probably display fMRI patterns more like that of an atheist than a convential religionist, and that I suppose would distress them even more.

    1 - And of course, Darwinian theory was rejected even de jure well into the 20th century by the secularist French. And some would assert even today they have no fully internalized as an intellectual culture Darwin's insights in anything more than a superficial manner.




    Derbyshire on the creationists   posted by dobeln @ 7/13/2006 06:47:00 AM
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    Once again into the breach, etc. Derbyshire, when responding to the latest creationist article published in National Review (link), makes this observation:

    It's a wearying business, arguing with Creationists. Basically, it is a game of Whack-a-Mole. They make an argument, you whack it down. They make a second, you whack it down. They make a third, you whack it down. So they make the first argument again.


    ..Which, I gather, is why this blog has outsourced that fight to "The Panda's Thumb", leaving us time for more worthwhile pursuits, such as extensive headbutting commentary and arguing over Finns in comments. No, I really mean it. Head over to www.freerepublic.com and search for "evolution" if in doubt.



    Wednesday, July 12, 2006

    BONCAT: It's French for "Good Cat"   posted by Coffee Mug @ 7/12/2006 12:56:00 AM
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    Not only have I forgotten my high school French, but also I have forgotten my undergrad organic chemistry. More accurately, I never bothered to learn it very well. Imagine my dismay, then, when I discovered that it might actually come in handy for answering important memory questions. Dieterich et al (2006) recently reported the use of a technique called BioOrthogonal NonCanonical Amino acid Tagging (BONCAT) to see what proteins a cell has made lately. You can use mass spectrometry to find out what proteins a cell has in it in total, and you can use radioactively labeled amino acid incorporation to label recently synthesized proteins, but the great thing about BONCAT is that you can specifically pull the newly synthesized proteins out of the mix and subject them to mass spec analysis, greatly simplifying your sample and increasing your signal-to-noise ratio.

    This technique is not entirely new. The foundations were established in 2002, but this is the first use in mammalian cells. They don't go into much detail about the potential uses, but I'm betting I can guess why Erin Schuman got involved. She has put plenty of time and effort into showing that local protein synthesis at synapses is a key process in producing long-lasting plasticity. The obvious question of which proteins are being synthesized is currently being answered tediously, one protein at a time. It is no surprise then that one of the two mammalian cell lines that they tested their reagents on to check for toxicity was cultured hippocampal neurons.

    What follows could probably be classified as 'hard-blogging', so if you don't feel like briefly reviewing amino acid structure and learning about cycloadditions you should probably click here instead.

    I really just want to give you a vague idea of how the technique works. I'm sure we'll get some data from Schuman before too long telling us about synthesis of synaptic proteins, and then I can link back here. Let's start somewhere near the beginning. Proteins are made up of chains of amino acids. There are 20 naturally occurring biological amino acids, unless someone has snuck some in behind my back. Here are two illustrations of an amino acid called methionine:

    Note that in the 'stick-figure' version there is a blue group on the left with a nitrogen in it. This is the amino group. The green group on the right with a carbon and two oxygens is the carboxylic acid group. Amino + Acid = amino acid. Every amino acid has these two functional groups and proteins are strung together by attaching the carbon of the carboxylic acid to the nitrogen of the amino group via a 'dehydration synthesis' step to produce a peptide bond. The long chain hanging off the bottom is called the 'side chain'. It is what differentiates one amino acid from the next.

    For BONCAT, they just made up a new amino acid called azidohomoalanine (AHA), pictured here:

    When AHA is washed over cells, it calls to them, "Take me up!" They, of course, comply and treat AHA like their very own amino acid, methionine. So if you give cells AHA and wait a while and then harvest the proteins from those cells, only the recently synthesized proteins will have AHA in them.

    Since AHA has that nice little tres nitrogens group (the azide) hanging off of it, it is capable of some special chemistry. See, it's nice to have the new proteins labeled with this funky amino acid, but we want to pull them out of solution and figure out what they are. To do that the authors have to attach something to AHA that they can pull on. A "trypsin-cleavable biotin-FLAG-alkyne tag 1" should do the trick! Since I don't really understand what everything in there is for I am going to concentrate on the parts I do think I understand: the alkyne (in the green box) and the biotin label (in the red box).

    When you mix the proteins from AHA-treated cells with the tag in the presence of copper bromide, the azide group hooks up with the alkyne in a Huisgen cycloaddition reaction. For us, all that matters is that the newly synthesized proteins get attached to the tag. The whole mess is then run through a molecular gauntlet containing a resin that is particularly sticky for biotin (the red box). All the old, played out proteins can get outta here, but the new fresh isht gets to stay. Now you have a resin with freshly synthesized proteins stuck to it. You can release these when you please, I think, by dropping in a protein that does what those scissors are doing in the above picture.

    So finally you have a solution of just the proteins you really like. Tandem mass spectrometry is a whole other complicated topic. In short, the solution is put into a machine that sorts the proteins by size and then blows them up and sorts the fragments by size too. Then a magical algorithm puts all the fragments back together to figure out which proteins were there. Using this technique in human kidney cells that hung out with AHA for 2 hours, Dieterich et al. were able to identify 195 newly synthesized proteins with all sorts of biochemical properties and cellular tasks. This is a lot better than doing it one protein at a time. Hey, I have an idea. Maybe since AHA isn't toxic to hippocampal neurons we could try BONCAT with neuronal proteins that are laser-captured from recently stimulated synapses. That settles it. I am a genius of experimental design. Please contact my agent to confirm the address for delivery of my Nobel. Thank you very much.



    Tuesday, July 11, 2006

    Death to heretics....   posted by Razib @ 7/11/2006 07:09:00 PM
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    This letter to the editor in the Lansing State Journal is making the rounds on the blogosphere:

    ...Islam is a guide for humanity, for all times, until the day of judgment. It is forbidden in Islam to convert to any other religion. The penalty is death. There is no disagreement about it.

    Islam is being embraced by people of other faiths all the time. They should know they can embrace Islam, but cannot get out. This rule is not made by Muslims; it is the supreme law of God.

    Please do not ask us Muslims to pick some rules and disregard other rules. Muslims are supposed to embrace Islam in its totality.

    Nazra Quraishi
    East Lansing


    "Nazra Quraishi," or someone with that name, does live in East Lansing (you can look this up). Now, the reality is that in to my mind many Muslims who emigrate to the West (not all) have a particular view of their own religion and what constitutes blasphemy within that context, but do not truly comprehend the secular sacrality (yes, a paradox?) of the West and what constitutes blasphemy here. An implication that there is compulsion in religion, to use a Muslim phrase, at least for adults, is simply blasphemous to the elites of the West.


    When Abdul Rahman was in the news for being an apostate to Christianity in Afghanistan, I do not truly believe many Muslims understood the reaction in the West (though many secularized elites did intellectually). Westerners were positively hysterical and unhinged, and so they should have been. The outrage and invective aimed at Baruch Spinoza was characterized by disproportionate response when he published Tractatus Theologico-Politicus in the late 17th century because he violated openly and publically the established bounds of reasonable civilized discourse, he transgressed upon the common shared norms which bound Western European civilization together and even restrained the free wheeling capitalism of the Dutch republic. Blasphemy tells us what is incontrovertibly sacred, it tells us what we hold precious and beyond debate, reason or analytic decomposition. Believe as you will we say in the open air of the public space, that is inviolable.

    But as I imply above this was not always so in the West. Though there have always been men who were "heretics" and "unbelievers" privately, outright rejection of the divine was forbidden within Western culture. Even Spinoza himself published his Tractatus ostensibly to refute charges of atheism, he was a pantheist who elucidated upon the character of his religiosity through a refutation of revealed theism. The movement toward religious pluralism and toleration was halting, and within Europe itself nations like Spain have embraced freedom of public conscience only within this century. Our pluralistic consensus is fragile, and I am not one who trusts reason to maintain it, at the end of the day we must be willing to battle to keep the freedoms that which were unveiled before us in the centuries between the 30 years War and the emancipation of the European Jews.

    The attitude of many Muslims that decency demands adherence to basic respect for the tenets of their religion is not surprising, that has been the character of civilization. The prosecution of the Greek philosopher Anaxagoras for atheism in Athens was in large part a function of his relationship to the politician Pericles, but, it shows that blasphemy did have deep pre-Abrahamic roots. The Chinese philosopher Xun Zi was a skeptical in regards to the supernatural, but, he did advise that the rituals and customs of society should be perpetuated in the interests of harmony and stability. Why is rape more vile as a crime than a non-sexual assault which may cause more substantial harm?

    I am conflating and exploring multiple issues above. The issue of rape is not simply one of social mores, there are deep primal cognitive reflexes relating to sexuality which must be acknowledged. Other taboos and "blasphemies" seem almost trivial in their character, shibboleths which serve as tribal markers and now carry the authority of custom through chance. But something like theism and veneration of cultural gods lay in the grey land between, to some extent theism is, I believe, an outgrowth of convential modal psychology. Its particular manifestation though is contingent upon social and historical events, even if its universality seems established. Religion is a melange of private and public commitments, and the decision to aver, reject or convert affiliations or identifications is something of interest and significance. Frankly, the direction of Islamic attitudes toward apostacy is not surprising, though its magnitude is rather substantial.

    The question though moves on to the West and its own values. Do you believe in gods? Despite the de-Christianization of Western Europe, it is still a predominantly religious in its populace, if not its elites. The United States is famously an outlier in its religiosity being out of proportion to its affluence. But, it is acceptable, even if grudgingly, to reject God in the West. These are the freedoms granted to unbelievers by the work of generations past, and the culture has moved in a direction where most believers would even find explicit compulsion in religion offensive. George W. Bush was born an Episcopalian, but he is now an evangelical Methodist, while his brother, Jeb, is a Roman Catholic. This is not to say there is not a prejudice toward atheism in the United States, but, that is different from asserting that it is a blasphemy. Rather, I would contend that the majority of American theists, a famously reactionary lot within the developed world, would still find the compulsory biases of Muslims more offensive than the heresy of an unbeliever. Of course, the ancestors of these same modern Westerners executed Thomas Aikenhead in 1697. I am not quite saying yet that we are in danger of losing the heresies which we have embraced, but the lessons of history show that the alternative is no anomaly.

    Addendum: The individual above works for an Islamic Sunday School in East Lansing. Here is a response from a Muslim doctor to the letter to the editor. He states:

    Death for apostasy is a very successful meme and was adopted with varying degrees of rigor by these schools, but since most of their other rules and regulations are no longer a part of muslim life, one wonders why death for apostasy should continue to be Ms. Qureshi's pet cause?


    I find the use of the term "meme" amusing, as it was coined by a militant atheist and turned against religion as a whole. But, in any case, what is the "real Islam" here? Well, that isn't particularly relevant, what is relevant is that the blasphemer Nazra Quraishi works to indoctrinate children, and it seems quite likely that she promoting anti-liberal heresy. Now, as civilized folk we can not consign Nazra Quraishi to the pyre, or behead her, the punishment for incorrect belief is not death. But, incorrect belief must be fought. The reality is that the types who end up teaching "Sunday School" as a vocation are often rather primitive and cognitively deficient in American Islamic communities, forgive her my fellow citizens, for she knows not what to think. Especially in immigrant Muslim communities stacked with busy successful professionals teaching Sunday school would likely be the lot of those with little better to do and an attenuated life of the mind. But from these isolated bush fires can blasphemous heresy eventually explode in a conflagoration unless counter-measures are taken.

    So what do you do with memes that are pernicious? Why memetic warfare of course! The hysterics emenating from places like Jihad Watch are entirely appropriate here in my opinion, the witch has blasphemed, and her kind should be excised from decent society. Her kind includes all those who refuse to bow to the No-god of freedom of conscience. But the attack must be multi-pronged. From below the foot soldiers may scream and engage in their human wave attacks, but they need air support, and the modern West has a deep well of anti-religious polemic from which it can draw from here. If we unbelievers are to protect our sacred right to unbelief, we must not shirk our duty to engage in proper and pious contempt, condescension and critique at what is clearly savage and unrepentantly primal superstition of a gross sort, idolatry scaffolded in the garb of high culture. Let us bring the precision guided bombs and simply eviscerate them from on high. We have the swords on hand now, and we are no longer blind, we are the gods of our own future history.




    Hard blogging   posted by Razib @ 7/11/2006 12:01:00 AM
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    John Hawks is the Chris of Mixing Memory for paleoanthropology, and Chris of Mixing Memory is the John Hawks of cognitive psychology. And Robert Skipper is the philosopher & historian of science equivalent of the pair. Can you name other weblogs that stand head & shoulders above the pack in terms of their scholarly orientations?



    Monday, July 10, 2006

    Your hippocampus is smarter than you   posted by Coffee Mug @ 7/10/2006 08:23:00 PM
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    If you're an animal wondering around trying to figure out what to eat and not die, you are going to want to remember to avoid any and all substances that made you feel the slightest bit ill. This is why conditioned taste aversion is a prime example of single-trial learning. This post isn't about conditioned taste aversion though. It's about how you know which taste you should be avoiding. The answer is novelty-detection. You automatically note whether you recognize each thing you encounter throughout the day. That way, when something important happens that hasn't happened before, you know what stimulus to attribute it to.

    Some people would probably think, "Hmm... how does the brain detect novelty?," but Schuman and colleagues were like "Pshaw! How 'bout... how do individual neurons in the human brain detect novelty?" Sometimes, in the treatment of epilepsy, deep brain electrodes are implanted, presumably to detect the epileptic focus for more accurate removal. This single neuron recording technique was possible because somebody figured out that as long as you are sticking this huge electrode down into the hippocampus, you might as well stick a bunch of leetle teensy wires down through the middle of the fat electrode.

    This isn't a technique you will see that often, since there simply aren't that many people with epilepsy in need of surgical treatment. However, when you do get to see it, it provides quite an advantage over something like fMRI because the temporal resolution is excellent while still allowing one to definitely implicate this structure or that. I'm not as familiar with the human literature as I probably should be. In the animal literature, there is a sharp distinction between the functions of the amygdala and hippocampus, but in this study they catch a little of both and don't seem too surprised to get largely overlapping data for the two.

    The paradigm is extremely simple and I'm going to simplify it further. Recordings were taken while people were looking at something they had seen before (familiar) or something novel (novel). In the six seconds following stimulus onset some neurons increased their firing when presented with novel stimuli and some some with familiar stimuli. Familiarity-detection appears to be the readout of some sort of memory process, because familiarity-detectors were apparent even 24 hours after the first encounter with some stimulus. Oh yeah, and it only took one encounter to do the trick. The change in single neuron rate-coding was rapid and automatic.

    Novelty and familiarity coding neurons were found in both the amygdala and the hippocampus, but there were about 2.5X more in the hippocampus. One thing that is maybe worth noting at this point is that it is not clear that the process of novelty detection is occurring in these structures. In the discussion, they seem to argue that the only other novelty encoding brain systems are modulatory (read: slow) so they can't explain the effect on these neurons. It seems more likely to me though that novelty detection will occur at each step in stimulus processing. It would be interesting to break this down into different sensory categories instead of complex visual stimuli. An extremely heavy orange apple that squeaks when you bite it and tastes like a coconut will probably add up to being more novel than if just one sensory modality is affected. I guess that might be a good question, can there be such a thing as a novelty gradient or is it all-or-none?

    More than one neuron per stimulus registered as a novel or familiar detector. This leads to questions about how these neurons are coordinated. In the paper, they produce a 'population decoder' computational model that has access to all the firing data. After the decoder was trained up, they fed it info from different numbers of neurons. With one neuron it could tell whether the subject was looking at a novel or familiar object 67% of the time. Give it six neurons and it scores a 93%. Naht bad. Shades of lie-detection. Lucky for the liars we probably still aren't legally allowed to stick electrodes in peoples heads on a hunch.

    The most interesting finding comes when they compare the information in the firing rates to the behavioral response of the patients. When the population decoder has access to all the firing info, it can actually guess whether the stimulus is novel or familiar better than the patient. For the study, this eliminates a strong alternative hypothesis that the neurons are merely representing the patient's intentions or motor sequencing. The neurons can say one thing and the patient can say another. Take that determinists! We have free will after all! It really makes you wonder though which region is sending the wrong signal and tripping them up.

    One last note. In the discussion, they mention that it has been very difficult to find these types of neurons in other primates. I should think that novelty-detection would be conserved way far back. The explanation in the paper is that the paradigms you have to use with primates require lots of trials before they are up to speed. Since we can do weird tasks right off the bat for no reason it is easier to correlate behavior with firing. Your homework is to design a novelty-detection task for primates that they can learn very rapidly in which we can measure their error rate while recording (which generally means they have to sit still).




    Zizou : heros ou connard ?   posted by JP @ 7/10/2006 01:31:00 PM
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    So. A red card for head-butting a dude in the chest, and the career of Zinedine Zidane is over. I've got to disagree with Alex Palazzo at The Daily Transcript on this one: that card may have cost France the game.

    But hey, what aggressive player doesn't blow his top once in a while? And if you're going to lose it, what better time that after 110 minutes of playing your ass off, nearly dislocating your shoulder, coming close to scoring the winning goal, and then listening to some Italian asshole talk shit to you? I like Slate's take on it: this is France, not Hollywood. In my book, Zidane is still a badass, and perhaps even more of a badass after going out in flames like that. Heroic.

    So what did Materazzi say to spark the whole thing? Everyone in France is going to be talking about this until Zidane's press conference in the next few days, but Le Monde (on top of the news as always) has some speculation. They consider three possibilities:
    1. Racist insults, like "dirty terrorist". This seems unlikely to me: head-butting a guy for calling you a terrorist? That's pretty lame.
    2. Something about his family. Classic.
    3. Insunuations about a steroid scandal.

    The world (or at least some small part of it) waits with bated breath...

    UPDATE: John Podhoretz, the resident emmerdeur at The Corner, has some (utterly un-funny) speculation. Va te faire foutre, dude.




    ASPM and schizophrenia-- nada   posted by JP @ 7/10/2006 01:09:00 PM
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    Regular readers know that ASPM is a microencephaly gene under selection in humans, though the particular pressure driving the selection is unknown. A group of Spanish researchers decided to test whether there is an association between variants of the gene and schizophrenia. The result: nothing.

    Of course, with only 233 cases and 161 controls, the actual power to detect an effect was probably around zero (not that that ever stopped anyone from publishing before). There are certainly many genetic factors that play a role in the disease, so any well-designed study should be big enough to detect multiple weak effects. And the authors note this is a preliminary study; presumably there will be larger sample sizes in the future.

    Related: GNXP on ASPM

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    Neandertal DNA & human evolution   posted by Razib @ 7/10/2006 03:05:00 AM
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    Short short commentary on Neandertal DNA. And yes, I'm daring John Hawks to jump in....



    Sunday, July 09, 2006

    Study fails to find pot is a gateway drug, declares pot a gateway drug anyway   posted by Coffee Mug @ 7/09/2006 11:23:00 PM
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    Don't believe everything that you breathe. You get a parking violation and a maggot on your sleeve. - Beck

    This is a little egregious.

    Cannabis use is a hypothesized gateway to subsequent abuse of other drugs such as heroin. We currently assessed whether Delta-9-tetrahydrocannabinol (THC) exposure during adolescence modulates opiate reinforcement and opioid neural systems in adulthood. Long-Evan male rats received THC (1.5 mg/kg intraperitoneally (i.p.)) or vehicle every third day during postnatal days (PNDs) 28-49. Heroin self-administration behavior (fixed ratio-1; 3-h sessions) was studied from young adulthood (PND 57) into full adults (PND 102). THC-pretreated rats showed an upward shift throughout the heroin self-administration acquisition (30 mug/kg/infusion) phase, whereas control animals maintained the same pattern once stable intake was obtained. Heightened opiate sensitivity in THC animals was also evidenced by higher heroin consumption during the maintenance phase (30 and 60 mug/kg/infusion) and greater responding for moderate-low heroin doses (dose-response curve: 7.5, 15, 30, 60, and 100 mug/kg/injection). Specific disturbance of the endogenous opioid system was also apparent in the brain of adults with adolescent THC exposure. Striatal preproenkephalin mRNA expression was exclusively increased in the nucleus accumbens (NAc) shell; the relative elevation of preproenkephalin mRNA in the THC rats was maintained even after heroin self-administration. Moreover, mu opioid receptor (muOR) GTP-coupling was potentiated in mesolimbic and nigrostriatal brainstem regions in THC-pretreated animals. muOR function in the NAc shell was specifically correlated to heroin intake. The current findings support the gateway hypothesis demonstrating that adolescence cannabis exposure has an enduring impact on hedonic processing resulting in enhanced opiate intake, possibly as a consequence of alterations in limbic opioid neuronal populations.

    Pete and friends over at DrugWarRant hit this pretty hard. They seem a little more negative about animal research than I'd like, but give it a look.

    Here are some major criticisms:
    • The gateway hypothesis as presented to the public is that marijuana use will increase the likelihood of use and abuse of other drugs.
    • The study reports the opposite of this prediction:
      The periodic exposure to low-dose THC during adolescence did not appear to predispose animals to an increased sensitivity to initiate heroin self-administration.
    • If anything, THC exposure seems to have made it easier to go off of the stuff when they unhooked the levers from the heroin administration:
      Our experiment showed that in the absence of heroin and associated cues, both THC and vehicle-pretreated rats had similar elevated rates of responding on the active drug lever. Although the vehicle-exposed rats showed a higher percent increase in active responses than the THC rats, the behavior was not discriminative to the active lever since the control rats also had a higher increase in responding on the inactive lever.
    • Nowhere in the study did they compare THC administration in adolescents versus adults, and yet the authors emphasize adolescence. Where on earth does this quote in the Science write-up come from?
      "The important finding is the fact that adolescence is a time of increased vulnerability to drugs," says neuropharmacologist Sari Izenwasser of the University of Miami School of Medicine in Florida, who notes that such behavior may alter fundamental brain processes.
    I don't have any problem believing the gateway drug idea in principle. It seems quite plausible that drugs that have similar effects (positive hedonic value) will act at the same synapses and perhaps alter the future plasticity of those synapses, but please don't try to use this study to scare your kids. You'll lose all your credibility in a few years when the 99% of their little pothead buddies never go near the heavy stuff. If you need a drug to keep your kids off of, try alcohol.




    Plowing through the genome   posted by Razib @ 7/09/2006 04:07:00 PM
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    Just a reiteration on prosopagnosia. Let's assume that the findings as to the extent of face blindness pan out (I am willing to grant they found something seeing as there was an autosomal dominant pattern of inheritance in the pedigree).

    1) I am skeptical that the 2% frequency in the population is due to reduced selection pressure in some populations. This behooves us to believe that we are just "catching" the German population on its way toward fixation. Additionally, this is a dominanttrait, so it seems less likely to be a loss-of-function which emerges because of relaxed selection (loss-of-function also tends toward recessiveness or additivity).

    2) "Hard-wired" face recognition seems a pretty obvious trait that social animals would require to recognize conspecifics. It isn't a lethal mutation obviously, or even highly deleterious, but as I noted, for this allele to increase in frequency and stabilize the mutation rate has to be implausibly high unless the trait is of neutral origin.

    3) But neutrality, where you have mutants of equal fitness in relation to the ancestral allele, implies to me some level of polymorphism, at least in a large effective population. I suspect when you sequence this you'll see that the 2% "face blind" carry the same allele, which likely coalesces back toward the ancestor.

    4) This implies selective forces buffeting the frequency of the putative derived allele.

    5) Seeing as it seems implausible that face blindness itself is the trait being selected for, it seems likely that face blindness is a byproduct of some other evolutionary dynamic. I surmised that the a dominant mutant is likely to indicate a sort of "gain of function" alteration in the protein end product of the locus, even though the phenotype of interest would imply loss of function. Well, that suggests that selection is operating on another phenotype, and the net fitness increased (now or in the past) for those with the mutant allele.

    6) This fits the pattern of positively selected mutants of large effect. The Ashkenazi IQ "overclocking" mutations fall into the same category. R.A. Fisher tended to be skeptical of the power of mutations of large effect because it seemed that they were likely to "overshoot" the fitness optimum of any adaptive landscape. Genes are embedded within complex and contingent molecular networks, so large changes can result in manifold alterations in phenotype. But, consider a situation where a terrible plague sweeps over a population. If a mutant allele conferred resistance to that plague, even if it had other deleterious consequences, its net fitness would be greater than the population median. In this way rapid evolutionary changes due to selection upon alleles of large effect often result in deleterious byproducts. One assumes that over the long term "modifier" genes will emerge to mask and mitigate these deleterious byproducts, unless of course the initial selective event which flipped the fitness of the mutant allele regresses so that it is not longer advantageous. Consider malaria, it no longer confers the fitness it once did in American blacks because malaria is not a selective force in the United States. So sickle-cell anemia, the deleterious byproduct, comes to the fore as a selective force which removes the mutant generated ad hoc in response to a powerful new selective force.

    The title reflects the metaphorical progress of mutations of large effect within the genome, in a given time and place they are quite likely to be "2 steps forward and 1 step behind" affairs. Populations subject to great selective stochasticity might be the perfect candidates for harboring janus faced alleles which both give and take, as ad hoc solutions come and go due to lack of stability. Do humans fit this pattern? Well, cystic fibrosis, sickle-cell anemia, eczema, etc. They might be the tip of the iceberg.




    How does the autistic brain work?   posted by Coffee Mug @ 7/09/2006 02:22:00 PM
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    Found a video program on the topic featuring this autistic guy who writes poetry and some neuroscientists.

    Crammed into our craniums, the three-pound human brain may be the most complex matter in the universe. And, scientists are learning more about how it works by investigating how it doesn't work. A 13 year-old young man named Tito Mukhopadhyay may be the Rosetta stone for autism, revealing what it feels like to be autistic. Joining host Robert Kuhn are Eric Courchesne, Professor of Neuroscience, UC San Diego; Portia Iversen of Cure Autism Now; Teacher Soma Mukhopadhyay; Erin Schuman, Associate Professor of Biology, Caltech; and Terrence Sejnowski, Director of Computational Biology, Salk Institute.

    The transcript is here in case you can't watch videos. From the excerpts I think I might actually like his poetry. Maybe I just like the color orange.

    Every time, like one day he wrote everything about orange, he got so obsessed with that, here he starts orange. "On a hidden back with orange sparks on little dust grains, orange on this and that. Orange on hidden wild flower behind a hidden rock, gathering time with ages to stay, green with gathering moss. Orange on a peeping beam, through the canopy green."




    What a synapse does when it's not doing anything   posted by Coffee Mug @ 7/09/2006 01:37:00 PM
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    The route of neurotransmission that you learn about in an introductory neuroscience class is action potential driven neurotransmitter release. A wave of depolarization travels down the axon to the bouton and activates voltage-sensitive calcium channels allowing calcium in to trigger vesicle exocytosis. Synapses get bored though, sitting around waiting for an action potential, so they dribble a little neurotransmitter across every now and then just for kicks, producing mini excitatory post-synaptic potentials (mEPSPs, minis). Actually, it is not clear what the purpose of mEPSPs is, but recent studies are indicating that they may serve some kind of homeostatic role, suppressing boundless synaptic growth and change. I should probably mention that all these studies that I know of relate to excitatory glutamatergic transmission, and of course AMPARs and NMDARs are the major receptor subtypes for this brand of neurotransmission (somebody tell me when repeating this factoid gets patronizing). The starting point for these investigations is the phenomenon of synaptic scaling. When neurotransmission is pharmacologically blocked for some length of time the strength of synapses starts to crank up. One can observe this even just in the size of minis before and after blockade. What are minis doing? What processes are you disinhibiting when you remove them from the picture?

    Back in 2004, Schuman and colleagues blocked NMDA or AMPA receptors or both and monitored synthesis of a GFP reporter flanked by the regulatory elements from calcium/calmodulin-dependent kinase II (CaMKII). All of these mini-blocking manipulations led to marked increases in the reporter, with the NMDA receptor manipulation alone producing the weakest (~40%) increase. Other studies have indicated that minis regulate spine structure and post-synaptic signaling pathways like CaMKII and MAPK activation. This 2006 Schuman paper (Sutton et al.) is a technical tour de force providing evidence that minis are locally suppressing protein synthesis-dependent insertion of a special plasticity-related type of AMPARs that are later replaced with the more mundane (GluR2-containing) AMPARs. Many papers that have been concerned with spontaneous neurotransmission have blocked action potential firing, but this doesn't quite exactly get at the role of minis. Instead, Sutton et al. blocked action potentials along with glutamate receptors. Since AMPAR transmission provides the largest initial component of minis it is a little difficult to observe scaling of minis while an AMPAR blocker is around, so most of the experiments in this paper focus on the effect of NMDAR blockade + action potential blockade. The effect of this manipulation is to greatly accelerate synaptic scaling as compared to that observed for simple action potential blockade, suggesting that NMDARs serve to inhibit scaling.

    Time for an AMPAR subunit review. Most AMPARs in the nervous system contain GluR2 subunits. Certain properties are associated with GluR2: a short cytoplasmic tail, calcium-impermeability, and resistance to blockade by polyamines. GluR1 and some other subtypes have the opposite characteristics, but you have to have a GluR2-lacking receptor before you can get calcium-permeability and polyamine-sensitivity. So GluR2s sit around in a synapse. Something happens to strengthen that synapse, and GluR1s are inserted. Then the GluR1s are slowly replaced by GluR2s again, but the synapse now has overall greater receptor capacity. Sutton et al. proceed step-by-step showing that NMDAR blockade (using a drug called APV) causes more GluR1 to be synthesized, produces more GluR1 on the cell surface, and produces more GluR1 specifically co-localizing with synaptic markers. They did not detect more surface or synaptic GluR2. There are more synapses containing GluR1 and more GluR1 signal at each synapse where it is found. It seems then that, in the absence of minis, GluR1 is being driven into synapses without GluR2.

    To get at the spatial specificity issue they had to be able to pharmacologically manipulate just a section of a dendrite, so they came up with this dual micropipette perfusion system. They put a marker in with the perfusate so you can see where the drug is going, producing a really nice visual:

    So check it. The red ghost indicates the portion of the dendrite receiving APV. The signal scale in the pics on the right and bottom is for surface GluR1 expression. Effin' cool right? The effect of minis is local. They also inverted the logic and globally blocked NMDARs while locally blocking protein synthesis and got basically the opposite pic. This sez that some protein is being locally translated that is responsible for GluR1 insertion in the absence of minis. I suppose it could just be GluR1, but you sort of feel like there needs to be more scaffolding and whatnot.

    To get at the identity of these new receptors a little more, they used a polyamine derivative that specifically blocks GluR2-lacking AMPARs. This reversed the accelerated scaling that occurs with NMDAR blockade, but not the scaling that occurs after 24 hours of simple action potential blockade. The mechanisms aren't entirely different though, by 24 hours the NMDAR-scaling is also mostly polyamine resistant. This result is consistent the slot hypothesis, and with the time course indicated by McCormack et al, 2006. GluR1s move into synapses to increase strength and bring a structural apparatus with them. Then the GluR1s are slowly exchanged with GluR2-containing AMPARs.

    OK. I know you're getting tired, so just one more pretty picture and I'm out. Schuman and colleagues took advantage of one more property of GluR2-lacking AMPARs that I had no idea about. I really have no idea how they find this stuff. GluR2-lacking AMPARs are cobalt-permeable. There is a fluorescent molecule called calcein that is quenched (turned off) in response to cobalt. So we can track functional GluR2-lacking AMPARs by flooding the cell with calcein, and providing cobalt in the extracellular medium. They combined this with their local perfusion system to get to the final conclusion, the title of figure 7: NMDAR mini blockade induces local, protein-synthesis-dependent insertion of GluR2-lacking AMPARs. I'm gonna skip the protein synthesis part. It is about the same as above. Just look at these dendrites.


    The top red blotch in figure B indicates the portion along the dendrite where APV is flowing. The top dendrite is before adding cobalt to the solution and the bottom is after. Figure C turns this 3D with signal intensity as the Z-axis. Note the specific decrease in signal after cobalt corresponding to the area of APV perfusion. Along with studies indicating that AMPAR transmission suppresses Arc transcription, I think an important new area is developing to focus on the steady-state processes that occur in neurons. The activity level of these processes may also play a role in determining the likelihood of future plasticity.

    Related:
    The Slot Hypothesis

    BDNF and Arc regulation: NMDARs vs AMPARs



    Saturday, July 08, 2006

    Happiness and assortative mating for personality   posted by agnostic @ 7/08/2006 04:51:00 PM
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    I'm sure I'm not the only introverted neurotic who's ever thought that these personality traits would forever doom me to date my fellow melancholics. So here's some good news: at the present time in the US and Britain, there is no assortative mating for any of the Big Five personality traits. Eaves et al (1998) (pdf) investigated the non-additive effects of genes on Extraversion and Neuroticism, making the assumption of random mating. They had access to a large data set (N = 20,554) on these traits in American twins and their spouses, so they were in good position to check for assortative mating -- zippo. They also cite an English study of 889 spouse pairs done by two of the co-authors and Eysenck for a 1989 book, which also found no assortative mating for E and N.

    A later study by Eaves et al (1999) (pdf) looked at biological and non-biological modes of transmission for personality traits and social / political attitudes, examining 29,691 American twins, 4391 of whose spouses also provided data. They were scored for the previously mentioned traits E and N, as well as Psychoticism, which due to its pronounced skew in the population and far greater ratio of non-additive to additive genetic causes compared to E and N (see Table 12 of the pdf), is most likely the multiplicative result of two independent traits: Agreeableness and Conscientiousness, in Big Five terms. Assortative mating for these three (or four) personality traits in this large sample? Nil. However, there was substantial assortative mating for attitudes (e.g., toward taxes, the military, and so on). The upshot is that if you thought those hotheaded, exhibitionist, sensation-seekers would never give you the time of day on account of your quietness, anxiety, and moodiness -- think again, you damned pessimist! On the other hand, they won't necessarily be magnetically drawn to you either...

    All right, but would you be happier if you married someone similar to you, whether based on attitudes or personality? A recent study by Luo and Klohnen (2005) (pdf) looked at 291 American newlyweds to see whether there was assortative mating in the sample as a whole, and whether spousal similarity for attitudes and/or personality correlated with marital satisfaction. On measures of attitudes, there was substantially greater similarity than expected, replicating the Eaves et al (1999) finding. There was very weak positive assortment for the overarching personality measures of the Positive and Negative Affect Schedule (PANAS) and Emotional expression. On the component traits like Neuroticism or Openness, there was no positive assortment -- indeed, there was even extremely weak negative assortment for Extraversion, though this was only significant at the level of p less than 0.1. So, overall, these data replicate the findings for lack of assortative mating for personality reported in both of the Eaves et al studies mentioned above.

    As for happiness, Tables 3 through 8 in the pdf show that, in general, similarity in attitudes had little to no effect (highest r = 0.16) and, to the limited extent that it matters at all, appears to matter somewhat more for the husband's satisfaction than the wive's. In contrast, the personality traits relating to attachment (e.g., Agreeableness) were often at or just above the weak-moderate border of r = 0.3 and appear to matter somewhat more for the wive's satisfaction than the husband's. For the Big Five factors, similarity in Agreeableness matters most, followed by Openness and Neuroticism, while similarity in Extraversion and Conscientiousness were not significant in association with marital satisfaction.

    Makes sense, sort of: if you've committed to marriage, you're not exactly going to be carrying on with all sorts of strange men or women -- you'll be with each other most of the time -- so Extraversion differences shouldn't matter. Agreeableness measures how nurturing & empathetic vs antagonistic & suspicious one is, so again, no surprise that that's the most important Big Five factor for marital satisfaction. Also, if you're emotionally unstable, you want someone who will understand your frustration over what a more stable person would write off as a trifle, which would only frustrate you even more! And vice versa, if you're emotionally stable, you don't want to hear your partner's incessant complaints and worries which you'll discover you can do nothing to diminish. I'm not sure what to make of Openness playing a role -- for Closed people, more things are "out of bounds" for discussion, so relations could become plagued by what the Closed partner sees as the Open partner's flagrant disregard of deserved taboo barriers. The one finding that surprised me was that similarity in Conscientiousness had no effect on marital happiness for either partner -- I would've surely thought that if the wife had a strong work ethic while the husband was lazy, that would create instant friction. But itt may be that only one facet of Conscientiousness (say, work ethic) has an effect on happiness, while the other facets (like punctuality, preferring order & structure) don't have an effect -- the slob views the neat freak's quirks as tolerable, perhaps endearing, but not a deal-breaker.

    These are the kinds of things they should teach in health class in high school -- no one's engaging in sexual acts other than the tiny clique of cool kids, and only a negligible minority are doing hard drugs (well, at a good school anyway). Knowing whether or not So-and-So would date you due to personality differences, or whether you'd be happier with someone similar to you on some social attitude or personality trait -- that's actually worth the time and effort of class attendance. It would also clear up a lot of speculation on who dates who and what makes for a satisfying relationship, and when you're an adolescent, you don't have time to do a mini research project to find out: you want someone to teach you rather than figure it out for yourself, perhaps the hard way.




    Erin Schuman: PubMed the name and syndicate it   posted by Coffee Mug @ 7/08/2006 01:25:00 PM
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    The Journal of Neuroscience dumped a collection of mini-reviews on us this week concerned with mRNA trafficking and dendritic protein synthesis. Most of them covered fairly familiar ground, but one struck me as containing some really novel and interesting perspectives. Schuman, Dynes, and Steward discussed the limitations of protein synthesis at synapses. For instance, there are, on average, 8 ribosomes per polyribosome and maybe 1 or 2 polyribosomes per synapse in the hippocampus. Polyribosomes are what they sound like, several ribosomes in a string presumably reading off of the same mRNA. This seems to indicate a rather stringent limit on the amount of new proteins that could be produced at a synapse, indicating that synapses better pick and choose wisely. Also, it brings some skepticism to recent discussions of activity-dependent protein synthesis regulation that rely on positive regulation of general translation initiation and elongation factors. What good does it do to have an initiation factor activated if you haven't got a free ribosomal subunit to stick it to?

    Another idea that I had not even begun to consider was that the size of mRNAs hanging around synapses might be a factor. They note that dendritically localized mRNAs can be longer than the average dendritic spine when laid out straight and suggest that too many of these might lead to a 'traffic jam,' but mRNAs don't exist in a linearized form very often, so I think a more appropriate indicator might be volume. Let's see. The average spine head diameter in hippocampal CA1 pyramidal cells is 0.4 microns. If we pretend a spine head is a sphere or hemi-sphere we get volumes of either 0.03 or 0.015 microns^3. Schuman et al. provide a length for microtubule-associated protein 2 (MAP2) RNA of 3.17 microns. What is the diameter of a RNA molecule? Let's pretend it is smaller at least than a DNA helix which is about 2.5 nm and that we can approximate the volume as a cylinder: 1.55E-5 microns^3. So, conservatively, I can fit a little less than a thousand of the largest mRNA molecule in an average dendritic spine. Granted there are other proteins in there getting in the way, but I don't think the 'traffic jam' problem is going to end up being an issue.

    A further limit discussed in the paper is that of homeostatic inhibition of synaptic modification. It gets only a cursory treatment in the review, but this is a fast-moving area that has only really begun to be explored. There are synaptic events called mini excitatory post-synaptic potentials (mEPSPs or minis) that result from neurotransmitter sort of leaking out of the pre-synaptic bouton even in the absence of action potentials. I hadn't really thought about what these do at all, but Schuman is doing some of the most interesting recent work in this area indicating that minis serve as a tonic suppressor of a natural drive to increase synaptic strength (synaptic scaling). The work is so interesting that I'm gonna devote another post to it instead of stashing it at the bottom of this one. In fact, I'm going to devote several posts to Schuman's recent work.

    After I read about the work on mEPSPs, I searched "Schuman EM" in PubMed (XML feed) and had a WTF moment. Take a look at these titles, all within the past 5 months:
    • MicroRNA: microRNAs reach out into dendrites.
    • Single-trial learning of novel stimuli by individual neurons of the human hippocampus-amygdala complex.
    • Miniature neurotransmission stabilizes synaptic function via tonic suppression of local dendritic protein synthesis.
    • Selective identification of newly synthesized proteins in mammalian cells using bioorthogonal noncanonical amino acid tagging (BONCAT).
    • Activity-dependent dynamics and sequestration of proteasomes in dendritic spines.
    The breadth is unbelievable. In most of these papers she uses a different cutting edge technique to investigate each area, from inserting microwires to do single-neuron recording in humans to inventing new amino acids. While she hasn't yet published an empirical paper (rather than a review) on miRNAs and synaptic plasticity, I'm willing to bet a large sum of money that one is coming in the next 6 months or less, probably timed to coincide with the Society for Neuroscience meeting.

    In my next five posts, I'll try to get into more detail about each of the five data papers listed there because they are all remarkably creative and apply unique approaches and new techniques to the problems at hand.



    Friday, July 07, 2006

    Over the years   posted by Razib @ 7/07/2006 10:58:00 PM
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    I almost never look at the archives of GNXP. Sometimes I stumble onto old stuff via google searches, and its kind of funny. So I was curious, what was going on on this blog on this date over the past few years?


    2005

    Through the rugged roads of gene land
    Polygyny in Britain...and Darwin in the service of Allah?

    Diamond Days on TV
    Cross-talk on "Intelligent Design"
    Back to the past...or not?
    GNXP update....

    2004

    Lifestyle of myopia
    Balancing selection in color blindness?
    When axioms attack!
    Tip of my tongue....
    Propositional civilizations II
    Defining Group Selection

    2003

    no 'safe' time to avoid pregnancy
    Why archaeology isn't always taken seriously
    Proximate vs. Ultimate
    Human Biodiversity makes the Big Leagues

    2002

    Islamic...fundamentalism
    not about IP, but about logic
    The Economist-7/4/2002
    End of History vs. The Moral Animal (the Clone Wars continue)
    The Victims of Competition




    Darwin Catholic   posted by Razib @ 7/07/2006 08:22:00 PM
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    Check out Darwin Catholic, a traditionalist Roman Catholic who comments on the intersection between his faith and evolutionary biology (and other things).




    Freaky Prosopagnosia disorder   posted by Razib @ 7/07/2006 07:59:00 PM
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    Prosopagnosia is "An inability or difficulty in recognizing familiar faces; it may be congenital or result from injury or disease of the brain." I've talked about this before. Well, Jake "The Superficial" Young now has a follow up post on the paper which elicited my initial skepticism. Since you can read the abstract, here is the conclusion:

    Congenital PA is the only known monogenic dysfunction of a higher cognitive visual skill. Among more than 90 different cognitive functions (e.g., musical mind, absolute pitch) and dysfunctions (e.g., agraphia, dyscalculia, dyslexia) related to specific cognitive behavioral and neurological disorders we could only find a few monosymptomatic conditions in the OMIM database (http://www.ncbi.nlm.nih.gov/Omim/) with proven or suggested heredity: perfect musical pitch, syn. absolute pitch...; specific language impairment (SLI)...; specific dyslexia, syn. word-blindness...familial developmental dysphasia...; tune deafness; syn. dysmelodia..; congenital anosmia; syn. odor blindness...; inability to smell musk...; hereditary whispering dysphonia...; indifference to pain, syn. congenital analgesia.... Gene mapping was successful, in one disorder..., a single but large family in which half of the members had orofacial dyspraxia and severe speech and language impairment. A point mutation was found in the FOXP2 (forkhead box protein 2) gene co-segregating with the disorder.... There are several susceptibility genes described in the heterogeneous group of dyslexia with regular segregation. The resulting phenotypes do not represent this in any case.


    Here is the take home message, around 2-3% of this sample lack a "normal" human cognitive ability, and this is due to an autosomal dominant mutation. First, this is strange because mental abilities are rather complex, and it seems that simple Mendelian inheritance would be unlikely to crop up except in extremely rare pathologies which "break" essential functionality in via pathways.


    It think that it is interesting that this hereditary condition is sharply demarcated not only from other cognitive traits, but, from other aspects of visual peception of the face (expression). This is suggestive (to me) of a hypermodularity that probably would take most people by surprise. Human ability to recognize faces is a gestalt competence that we possess, such as language. It is not part of our general intelligence, it is a specialized ability we as humans evolved to recognize conspecifics with a level of fluidity and rapidity which would no doubt facilitate maximal utility out of social interactions. Other species have their own conspecific recognition capabilities, this isn't rocket science. The lack of this in a non-trivial number of humans is suspicious. I think it would be analogous to (even though the functionality is an order of magnitude less crucial) 1 out of 50 humans lacking the ability to speak.

    A researcher who is involved in this work states:

    Their problem is in recognizing faces, particularly faces out of context. This can occur frequently in modern urban society with its crowds, great mobility plus the surfeit of facial images. It probably occurred less often in traditional societies, thus reducing selection pressure.


    What is a "traditional society"? I think there is considerable evidence that a convential pre-modern circle of friendship, familial relation and aquaintanceship extended to no more than 200 individuals, and more often one would be habituat to only a few dozen at most (the "band" as opposed to the "clan," and above that, the "tribe"). Clearly a facial recognition deficit would not spell death in such a society, and the awkwardness would be mitigated by the familiarity with everyone around you.

    But if you read the paper you will note that these individuals tend to not understand why you have to look at people in the face when you talk to them. This, and other problems which emerge out of this deficit suggest to me that even in pre-modern societies the reproducive fitness of those who possess this allele should be lower than those who do not possess this allele.

    Mutation-selection balance for a dominant allele in a diploid population is:

    Frequency = (mutation rate)/(selection coefficient)

    The selection coefficient is presumably negative. If you assume it is 0.1, that is, someone who carries this allele (and because of dominance exhibits the trait) has 90% of the reproductive output, on average, as someone who does not. Since the population sampled exhibited a frequency of (about) 2%, 0.02 X 0.1 = 0.02. If the selection coefficient is .01, you still have a mutation rate of 0.002 on the locus. The mutation rate in humans is actually much lower than this, on the order of 10-7 to 10-8. Even for putative "polygenes" the mutation rate is on the order of 10-3 to 10-5. You see where I'm going with this?

    It could be that this locus, for whatever reason, is hyperactive in terms of mutations. But, I suspect that a better explanation is that at some point there was selection for this allele because of a pleiotropic side effect. Since this is an autosomal dominant it is not unlikely that there is a trans-acting factor which is interfering with the other copy of the allele which controls this trait. Additionally, this novel variant might have a role in various biochemical and molecula genetic pathways which may be selectively beneficial.

    Anyway, there are many ways you can go with this. But, the study was conducted in Germany. I think a key finding will be that the frequency of this condition varies across populations, because I would not be surprised if the selective event that might have occurred in Northern Europe did not occur elsewhere.




    I'm So Proud of the Part I Played   posted by TangoMan @ 7/07/2006 03:14:00 PM
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    Can anyone beat the number of authors of this paper entitled Top Quark Mass Measurement from Dilepton Events at CDF II with the Matrix-Element Method?

    I counted 729.

    Hat tip ChicagoBoyz




    The Oyrats come west   posted by Razib @ 7/07/2006 12:00:00 AM
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    In a post below I made an allusion to the Oyrat Mongols. If you want to know more about one of their tribes, in particular, the one which is the source of the only indigenous European Buddhist nationality, check out John Emerson's essay on the Torgut exodus. One interesting tidbit about the Oyrats is that some were called "Dzunghars," and they inhabited roughly what is today the northern half of Xinjiang province, Eastern Turkestan, still called Dzungharia. But, there are few, if any, Mongol speaking peoples in this region now, the "indigenous" folk are Kazakhs and Uyghers. What happened? The Manchus & cannon happened (in the 18th century), in short, the Western Mongol tribes were exterminated & expelled, in part because of their meddling with the politics of high Central Asia and their inevitable conflict with the Manchu Empire. So with the connivance of the Khalkha Mongols of the east, who were descended from Genghis Khan and did not appreciate the arriviste Oryat ascendency, the last steppe nomad power was broken by a gunpowder empire. There are two reasons this is important. First, it highlights that genocide is not a European monopoly, given weapons of mass destruction human does as human sees. Second, the idea of "indigenous" peoples like the Uyghers has to run up against the reality that ethnicity in a local area is often fluid and historical roots are not always deep. So the Han colonization of northern Xinjiang is less the displacement of indigenous peoples (the Kazakhs and Uyghers) as it is one in a long sequence of ethnic transitions (the Oryats themselves probaby displaced a Turkic speaking people, perhaps the Kirghiz or even Kazakhs).



    Thursday, July 06, 2006

    The Most Hideous Transmogrification   posted by TangoMan @ 7/06/2006 03:23:00 PM
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    This is too good not to share - Razib takes on the persona of a more "enlightened" being. Could this be a Sokal Hoax in the making or have we lost Razib, as he transcends to a higher plane of being?

    but don't you worry about the perpetuation of heteronormative discourse in a society where we are attempting to value individuals for their character rather than their physical features? this individual, for example, would have illustrated the problems with loss of functionality on the MC1R locus that is endemic to redheads without the distractions of objectification, and, reinforcement of capitalist & patriarchical values of "attractiveness" promoted simply to perpetuate arbitrary power relations. as a white male (generalizing from your photograph) don't you think you in particular can set a progressive example of sensitivity toward those who do not benefit from either your gender or skin color privilege? (speaking as an operational heterosexual non-"native" born male of color who does not benefit from white skin privilege and is excluded from the dominant patriarchal caste by virtue of my origin) one can argue that as highly depigmented individuals who often exhibit brown "freckles" redheads are themselves a demonized minority, a group "of color," so to speak, around whom negative folk mythologies have cohered (how many reheads have had to deal with the slur "firecrotch" during their adolescence?). in other words, they are the internal Other. haven't you read the book how redheads became Colored?

    Later in the day, we see him getting used to his new liberal skin:

    DFX: Plus, you're much better looking than PZ!

    Razib: itz a sad statement of our culture that gratuitous comments about physical appearence are considered "amusing" by some.

    When a commenter, who must obviously be blind to his own privledge, rebukes Razib, we see the full emergence of "Sensitive Man" with this comment:

    DFX: Some might argue that it's a worse statement of our culture when people lose their sense of humor.

    Razib: humor is the Privilege of heterosexist white males. perhaps the key is that for you "our culture" is bounded by your own eurocentric biases, while as a person of color i have to live every day with a culture of oppression.

    I used to have to scour the darkest corners of the feminist and liberal blogospheres to find this kind of mindset, but now we have it close to home.

    What, oh what, could be causing this hideous transmogrification? Could it be a satirical virus of some sorts, too much interaction with people who think like that, or something more sinister? If you ask me, this is a shout out for an intervention!

    Update from Razib: I "explain" myself yo!




    Linkage versus association: a mini-primer   posted by JP @ 7/06/2006 11:32:00 AM
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    So I recently tried to google my way to a decent biologist-but-not-statistical-geneticist summary of the difference in two approaches to gene mapping: linkage and association. I didn't really find anything that did a good job of expressing what, in my opinion, needs to be expressed. So here's my attempt to fill that void:

    I. Linkage mapping

    The principle of a linkage study is the following: if a disease runs in a family, one could look for genetic markers that run exactly the same way in the family (from grandma, to dad, to me, for example). If we find one, we assume the gene that causes the disease is somewhere in the same area of the genome as the marker.

    That's all.

    In theory, one could genotype generations and generations of a family, and follow the inheritance of the disease. That is, however, not practical, as people tend to do bothersome things like die, and digging up bodies to get DNA samples is unlikely to get past an ethical review (and even if it were ethical, it's tough to know the phenotype of a long-dead great-aunt).

    In practice, a popular design is to genotype affected siblings, and use the following logic-- for a given bit of chromosome, each sibling gets two copies, one from mom and one from dad. If the two have inherited the same bits from each parent, the area is more likely to be involved in the disease than if each sibling inherits different bits.

    I purposely didn't use the word "gene" above, because we're not talking about testing specific alleles-- we're talking about chromosomal regions. And that brings me to the first limitation of linkage mapping-- the resolution is low. That is, the chunks of chromosome we're talking about here are millions and millions of base pairs long (recombination over a couple generations doesn't break chromosomes up that much). So even after getting a strong signal, there are generally a number of genes in the area that must be painstakingly tested. This could take years.

    A couple other limitations-- the strongest linkage signals tend to come from recessive and highly-penetrant (and thus generally rare) diseases. Why is this? I noted above that the goal is to find regions where two affected siblings have received the same chromosomal segments from each parents, and these are the conditions that ensure that (for those in the know, these are the conditions that lead to the strongest distortion of the IBD vector).

    So...linkage is the best approach to detect regions involved in recessive, highly penetrant diseases, and can narrow down the the search for causal variants to a few million base pairs, in general.

    II. Association studies

    The principle of an association study is also simple-- gather some people with a disease and some people with out a disease, and look to see if a certain allele (or genotype) is present more often in the cases than the controls.

    If the allele plays a role in causing the disease, or is correlated with a causal allele, it will have a higher frequency in the case population than the control population.

    After a linkage study, one nominates "candidate genes" in the region under the linkage signal, and performs an association study on alleles in the genes. In this way, a specific gene, or even a specific allele, can be identified as playing a possible causal role in the disease. The resolution is much higher, but it was previously implausible to perform these sorts of studies on regions much larger than a couple genes.

    However, with the HapMap and the technology to genotype hundreds of thousands of alleles in parallel, it's now possible to perform association studies on the level of the whole genome. This would essentially skip the step of a linkage scan.

    What are the limitations of this approach? First, many different mutations in a gene might lead to a disease. In linkage studies, this doesn't pose a problem, the different mutations still in the same region. But in population-level association studies, the effect of each mutation is diluted by the presence of the others.

    Further, case-control studies are always subject to problems like population substructure that family-based studies don't have (for those who are really interested in these sorts of questions, see also family-based association studies).

    But to detect low-penetrance alleles in complex disease (or any complex phenotype, really), genome-wide association studies will doubtless provide unprecedented views of the contributions of genetic factors (as they already are).




    Pinker and Jackendoff vs Chomsky, Hauser, and Fitch: Background   posted by agnostic @ 7/06/2006 09:02:00 AM
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    By popular request [1] and on the heels of Darth's interview with Steven Pinker, I'm going to post on the Chomsky, Hauser, & Fitch (CHF) vs Pinker & Jackendoff (PJ) debate on language evolution. For the relevant background, see here, here, and here (& the links therein). There are two papers we haven't discussed yet: the latest reply from PJ (available here as Jackendoff & Pinker 2005, "The nature of..."), as well as this paper (pdf) by Scott Atran, which in part deals with the CHF vs PJ debate. In a few days, I'll address these evolutionary issues in detail, but in this preliminary post, I'll review some basic linguistics. I'll gossip & provide sociological details along the way, since this isn't a sober journal, and these things are must-knows for non-linguists. First, here is an old post of mine outlining what the different components of language are. It's important to keep these components straight, as much of the CHF vs. PJ debate centers around which ones are "uniquely linguistic." Here is a simple diagram of how the parts work in the standard "T model" of Chomsky's particular view:



    First, there are words in the lexicon (our mental dictionary), which are then combined into phrases and sentences via syntactic operations (e.g., "stick a direct object to the right of its verb"). This full sentence is then fed into two separate systems: one for speech production (this form is sometimes called PF for "Phonetic Form"), and the other for semantic interpretation (sometimes called LF for "Logical Form"). For those that have been following CHF and PJ's back-and-forth over the Faculty of Language in the Narrow sense (FLN) vs the Faculty of Language in the Broad sense (FLB), CHF's hypothesis is that only the stuff that's going on in the vertical line in the diagram ("narrow syntax") is what constitutes FLN -- the horizontal branches at the top represent interfaces with systems of the brain used for not uniquely linguistic purposes, and homologues or analogues of these not uniquely linguistic systems may be found in other species. PJ's hypothesis is that, while these non-syntactic components (i.e., the horizontal branches) may interface with other systems of the brain, and while they may have homologues or analogues in other species, that doesn't exclude the possibility that they've been crafted by natural selection such that their present form is uniquely human and uniquely linguistic.

    Just what lies behind this "narrow syntax," on CHF's view? It is recursion, the operation that allows multiple embeddings:

    FLN is just recursion.
    Chomsky believes that [FLN is just recursion].
    Pinker laments that [Chomsky believes that [FLN is just recursion]].
    I'm not surpised that [Pinker laments that [Chomsky believes that [FLN is just recursion]]].
    ad infinitum

    Over the past 10 years or so, Chomsky's approach has been the Minimalist Program, which seeks to identify the sine qua non of syntax, and he believes it is the operation "Merge" -- basically, stick two things together to get a single, hierarchically structured clump of stuff. Note how that allows recursion: merge the verb "sleep" with the adverb "furiously," and you get back yet another verb, "sleep furiously." For those of you who've read some syntax before, maybe just from The Language Instinct or what have you, this is a big change for Chomsky & his fellow travelers, as before the "syntax" part of the T-model included the separate levels of "deep structure" and "surface structure," plus "transformations" that mapped one syntactic level to the next -- for example, simplifying, the deeper, unpronounced sentence You saw who? was transformed by a movement transformation that took the pronoun who and placed it at the front, before the sentence was sent off for pronunciation & interpretation: Who did you see? Within the Minimalist Program approach, by hypothesis, there are no special levels of D-structure and S-structure, and the number of transformations (like "Merge") is greatly reduced.

    As a sociological aside, let me note that this "insight" was proposed decades before by practitioners of the camp within Generative Grammar known as Categorial Grammar (related approaches include Lexical-Functional Grammar and Head-driven Phrase Structure Grammar). In their view, syntactic operations are simply applying a function to an argument. For example, a transitive verb is a function that wants a direct object as one argument, as well as a subject argument to result in a complete sentence. Simplifying, consider the following derivation of the sentence Chomsky likes syntax, where S = sentence, NP = noun phrase, the part to the right of a slash represents the argument of the function, the part to the left of a slash represents the result of function application, and the subscript just below the slash shows in which direction the function looks for its argument.

    Thus, likes (and any transitive verb) is a function that first looks for a direct object noun to its right, and once applied to the argument syntax, has closed off that argument slot, becoming something like an intransitive verb (i.e., likes-syntax). Then this likes-syntax function looks for a subject noun to its left, and once applied to the argument Chomsky closes of its remaining argument slot. With no open argument slots, we are left with a complete sentence. Note that functions in this approach are curried, meaning they take their arguments one at a time, starting with the outermost layer.

    Now, "applying a function to its argument" is bascially the same thing as the Minimalist Program's "Merge," and it too allows recursion: the adverb "furiously" is a function that takes the verb "sleep" as argument and returns yet another verb, "sleep furiously." If this approach was proposed decades ago, why didn't anyone realize this? It's because, within the broad Generative Grammar paradigm which all descendents of Chomsky adhere to, there are rival sub-theories. The particular one proposed by Chomsky himself was at first called Government & Binding, and he has revised this with his work in the Minimalist Program. To be frank, with only the slightest of exceptions, close to zero syntacticians working in Chomsky's particular framework read, let alone cite & debate, the work of those working outside this particular framework yet still within the Generative paradigm. It would not be an exaggeration to say that Chomsky's status is like that of Marx or Freud at the height of their popularity, such that his followers demonstrate an almost religious cult mentality. If Chomsky proposes that the field do X, the next day, without skipping a beat, everyone drops what they were doing and picks up X. A linguistics professor once told me that, when they went to see Chomsky lecture at MIT, the room was so packed and the audience's attention so reverential, that it was as if God were holding court. To be fair, Chomsky is only minimally responsible for this -- it's true that he also doesn't cite or debate the rival Generative groups, but it's really his closest followers who have magnified this fault and made their enterprise almost like a cult of the charismatic leader.

    This may seem like pointless gossip, but it's crucial to understand Chomsky's status in linguistics to get why so many either become quasi-disciples or sworn enemies, leaving marginalized those who agree with his broad Generative and Nativist approach but not the particular details. Because of the history of uncritical acceptance of, indeed devotion to whatever Chomsky proposes, their arguments (especially on evolution) need to be taken with a large grain of salt. Moreover, one advantage that CHF and likeminded thinkers claim on their side of the debate is that strong adaptationist approaches like those of PJ haven't illuminated theoretical linguistics, while weaker adaptationist approaches like their own have -- namely, the idea of purging FLN of as much as possible resulted in boiling transformations down to the Merge operation and shifting away from D-structure and S-structure. But as already noted, this barebones approach is nothing new to any of the rival syntacticians who had always looked askew at the runaway process of baroque architecture in the Government & Binding theories, so claiming that there was something special about the CHF view of language evolution that has illuminated theoretical linguistics is not particularly accurate -- after all the rival views were not informed by evolutionary considerations, just a skeptical attitude toward Rube Goldberg machines and less zealous devotion to God. Though let me note that a semanticist told me that the same cult mentality once prevailed in semantics until the death of the counterpart of Chomsky (namely, Montague) -- afterwards, the field opened up a lot.

    So, mull over this background material, and by all means ask for clarification in the comments. The next installment will specifically address language evolution and the continuing CHF vs PJ debate.

    [1] I know we don't discuss language that much here at this blog, but if there's anything linguistic that the readers are interested in knowing about, just shoot me an email and I'll try to post about it.




    Wikipedia goes political   posted by Coffee Mug @ 7/06/2006 05:57:00 AM
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    I am still green enough to get hopeful about things like this every now and then.
    Let's ramp up the intelligence of politics
    An open letter to the political blogosphere

    Jimmy (Jimbo) Wales, July 4, 2006

    For more than 50 years now, we have been living in the era of television politics. In the 1950s television first began to have a major impact on politics, and the results were overwhelming.

    Broadcast media brought us broadcast politics. And let's be simple and bluntly honest about it, left or right, conservative or liberal, broadcast politics are dumb, dumb, dumb.

    Read the rest at the Campaigns Wikia site





    ...and twins   posted by Razib @ 7/06/2006 02:00:00 AM
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    Why aren't identical twins linguistically identical? Genetic, prenatal and postnatal factors:
    ...twin-based heritability estimates for language rarely exceed .6 and monozygotic (MZ) twins..sometimes have very different linguistic profiles. In addition, twins are more likely to suffer linguistic delays and impairments than singletons. Postnatal factors, such as differences in linguistic input twins receive, are usually assumed to be the major reason for these findings. This paper discusses how genetic, epigenetic, and perinatal environmental factors can lower heritability estimates for language, cause MZ twins to be linguistically discordant, and increase the risk of language impairments in twins...these results support nativist/biological theories of language and language development and call into question empiricist/emergentist theories. These results are also consistent with modularist theories of language. We end by suggesting new methods that can be used to tease apart the effects of prenatal and postnatal environment and to investigate how these factors interact with genetic factors.



    Wednesday, July 05, 2006

    Science fiction Derb   posted by Razib @ 7/05/2006 10:44:00 PM
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    This piece by Derb ruminating on our robotic future got me to wondering about whether his reading of Isaac Asimov's later Robot & Empire books might have had a subconscious influence....



    Tuesday, July 04, 2006

    Many Islam(s)   posted by Razib @ 7/04/2006 03:20:00 PM
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    Aziz has a post titled muslim citizens, not citizen muslims, where he attempts to address the source of the "Muslim problem" which seems to be a serious issue over the waters in Europe. He alludes to post-colonial legacies and relationships, but I do not believe this is fundamentally a main cause of the problem.


    Let me look over the major nations.

    1) The United Kingdom, most Muslims are from South Asia, former colonies, with a residual of Africans, Arabs, etc.

    2) France, most Muslims from North Africa, former colonies, with a minority from the colonies of West Africa.

    3) The Netherlands, most Muslims are of Moroccan origin, with a minority of Turks, Kurds, etc.

    4) Germany, most Muslims are of Turkish origin.

    5) Sweden, most Muslims are of Middle Eastern, often Turkish or Arab, origin.1

    6) Norway, most Muslims are of Pakistani origin.

    In some of these cases the nations which are the source of Muslim immigrants are not former colonial possessions. Norway is pillustrative of this, what does this nation have to do with South Asia? Its only "colonies" seem to have been desolated islands in the Arctic.

    Additionally, in some of these nations non-Muslim minorities of colonial origin do exist. Britain and the Netherlands is an important cases in point, and in both of these nations the alienation by non-Muslims seems to be less pronounced than in the case of the Muslims. The Netherlands is particularly important because Christian Ambonese and Hindu Surinamese are juxtaposed against non-colonial Muslims, and the latter are the source of far greater societal tension than the former. In Britain, you have two communities which are of particular interest when set next to each other: the Muslims from the region of Mirpur are linguistically and racially very close to the Sikhs from Indian Punjab. Additionally, my understanding (ancedotal, I've not had time to find scholarly citations) is that the socioeconomic origins of these two groups did not differ greatly, that both were drawn from the broad "middle" of their societies. And yet the latter exhibit a far greater level of integration, or at least acceptance and rapprochement, with the greater British society than the Muslims from what became Pakistan (though Sikhs do not perform spectacularly, as to Indians who came via East Africa).

    This is not to deny that alienation from the mainstream society is not a factor in the trajectory of separate and unequal which many European Islamic communities seem to be drifting toward (though there is less segregation in places like France than Germany or Britain), but, it is not a sufficient cause. The American Muslim community stands as witness to that, though there are clearly issues of integration the process has been relatively painless in comparison to what is the norm over the waters.

    Here are the reasons why this is so:

    First, the immigrant stream was of higher SES. The child of a scientist, expected to go to college and possibly pursue graduate studies is far more likely to be "corrupted" because by the nature of their lifestyle they are forced to face the "outside" on a day to day basis. Muslims who serve as doctors must see non-Muslims as patients who depend on them. High SES individuals are by their nature more mobile, and operationally more cosmopolitan.

    Second, the immigrants are diverse and there is not a close connection between being Muslism and ethnicity. That is, there are black Muslims, brown Muslims, olive Muslims, Asian Muslims and white Muslims. This prevents the synergistic coupling of Islam with an ethnic identity, because by its nature American Islamic is multi-ethnic and fractured. This reality means that to some extent Islam must be fundamentally about religion as opposed to identity formation, because religion is the commonality between a Syrian, a Pakistani and a Nigerian. In much of Europe one ethnicity becomes identified with Islam, so that to be Turkish or North African is to be Muslim and vice versa.

    Third, the American culture of confessional multiplicity is better equipped to handle the transformation of religious traditionalists than post-Christian European nations. Americans already have a Catholic-Protestant-Jew trichotomy to which Muslims can slot into. American religion, by its nature, tends to be spare and minimalist, but it allows one to keep an attachment to labels, all the while eating away at traditional assumptions. Reform Judaism is powerful and a force in America primarily because of its "Christians with curly hair" connotations. It is fundamentally an "Americanist" religion with ancient packaging. One can say similar things about American Catholicism, and some have argued that Americanism was one of the primary factors in driving Vatican II in the 1960s (that is, Americanist thinkers influenced the reformulation of Church practice and doctrine).

    As an unbeliever and a pragmatist, what I'm alluding to above takes into account two facts:

    1) Much of cognition is not conscious
    2) Consciously chosen and professed markers and tokens of affiliation evoke great emotional attachment

    A few years ago a Muslim columnist for Beliefnet wrote in a manner which seemed to clearly suggest that his views in regards to free will implied a rejection of predestination, which seemed peculiar in that the consensus in Sunni Islam holds to predestination. I pointed this out at the time as "inconsistent" with Islam. Today I wouldn't say such a thing because I've become a thoroughgoing nominalist in regards to religions, and I believe religionists basically reshape their religion to suit their circumstances. But, the key is that they are attached to markers, and all the while they change A to B, they will hold that B is still A.

    By the very fact that American Muslims are a small minority, fractured along ethnicity, and of slightly above average socioeconomic status, they will reshape Islam to be more congenial to their lives and the realities they have to be face. Additionally, to maintain cognitive coherence they will claim that their interpretation of Islam is the "true Islam." Myself, I don't think there is a "true Islam," but a gelded and bourgeoisified religion is fine by me.

    1 - Some will know that Sweden has a large Iranian Muslim immigrant community. You won't hear much about them because their relative affluence, education and secularism mean that they aren't problematic. So even within nations the character of immigrant communities in terms of from which segment of society they are selected is relevant.




    Liberal Duality on Lewontinism   posted by TangoMan @ 7/04/2006 03:19:00 PM
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    The next time you encounter Lewontin's Fallacy in which someone is arguing that between groups differences are not important when compared to the variation within the group, one should discern how they feel about race and gender wage differentials, for:

    It is important to recognize that most wage inequality occurs within and not between groups. The unweighted average Gini coefficient across all race, gender, and education groups was 0.256 in 1995, over 80 percent of the total Gini. Put another way, if all groups had identical mean wage rates (for example, black male dropouts had the same average wages as white male college graduates) but wages differed within groups as they do today, nearly all the inequality in wage rates would remain.

    So, when it comes to genetic variation and the implications which arise from biology, the between group differences are minimized in comparison to the in-group differences and we see a full on embrace of Lewontin's outdated analysis, yet when the topic is a liberal touchstone, income inequality, then the small between group differences matter so much more than do the in-group differences.

    Geez, can't they simply pick a position and stick to it.




    Pandagon Attacks the Bell Jar   posted by TangoMan @ 7/04/2006 12:21:00 PM
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    The cutting edge of feminist thought is being advanced, right over a cliff, over at Pandagon. Amanda starts off her essay with this declaration:

    PZ Myers found a literal goldmine of humor for us science-supporting feminists

    Yeah, she's a science supporting feminist like The Sausage Casing Girls are exemplars of fashion. The Sausage Casing Girls are along for the ride on the fashion train because they want to make a statement to their peers that they too are hip to the cultural and fashionable touchstones of our times. The fact that they're not actually fashionable in appearance is immaterial. Same too with some of these "science supporting feminists" who, in the evolution vs. creation war, side with evolution when they don't have a clue as to the science underlying evolutionary thought. Their embrace of science is merely show for it reaffirms their cultural identity and self-image. They look at the creationists and they find it easy to reject their particular brand of appeal to custom, superstition, and traditionalism, so by default they embrace the antithesis of the creationist position. What they don't do is embrace the fundamental aspects of a science oriented outlook, to wit:

    It's worth noting that there's been plenty of people who have eagerly sought out scientific "proof" to replace the religious justification for racism, in books like The Bell Jar. Unsurprisingly, these attempts suck donkey butt in terms of being good science, but even if these attempts came up with better facts, I don't think that progressives have much to worry about in terms of losing the moral high ground. In order to prove that racism was justified, then evo psych-ers would have to demonstrate that black people are somehow less human than white people-or alternately that we aren't social animals that adapt to our environment-and both those assertions are self-evidently false. Whipping out IQ tests is a perfect example of how a stream of numbers just can't change either the fact that we are social animals or that all people are fully human, since what IQ tests tend to prove more than anything is that if you grew up in an environment that would incline you to do better on a standardized test, you'll do better on standardized tests.

    I found the bolded sentence to be the most telling of what really underlies the motivations of these "science loving feminists" - it's posturing. They use science as a cloak, or perhaps a sausage casing, within which they can wrap their ideology and give it the cover of rationalism and enlightenment, rather than using the scientific method to test their premises, inform their thinking, or guide their lives. They use science as a badge to signal to others that they too are along for the ride, and like the Sausage Casing Girls, these "science loving feminists" are blind to how they present themselves.

    I'll leave it for the commentariat to disassemble the flaws of reasoning within that paragraph, for it's quite apparent that there is no equation between "science loving feminist" and mastery of writing logical arguments.



    Monday, July 03, 2006

    Boy crisis?   posted by the @ 7/03/2006 03:15:00 PM
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    The think tank, Education Sector, has released a new report, "The Truth About Boys and Girls", which down plays the "boy crisis". Positive editorials op-eds in the NY Times and Washington Post, dissenting views in the Wall Street Journal (quotations below the fold).

    My commentary: this is a topic that is begging for, but not getting, a proper psychometrics analysis. Assuming that boys and girls are mostly matched on g, and ignoring the male-female ability sub-score differences, there's little expectation of a male-female difference in achievement test scores, the basis of this report's dismissal of male underachievement. The cause of the male-female gap in college matriculation is going to have more to do with conscientiousness than cognitive abilities, and so this report is mostly missing the mark.


    Judith Warner writes in the NY Times:

    It's been muttered for some time now in feminist academic circles that the "boy crisis" - the near-ubiquitous belief that our nation's boys are being academically neglected and emotionally persecuted by teachers whose training, style and temperament favor girls - is little more than a myth.

    Now a major study has confirmed it. According to "The Truth About Boys and Girls," a report from the nonpartisan group Education Sector, most boys aren't just not failing; they're doing better than ever on most measures of academic performance. The only boys who aren't - the boys who skew the scores because they're doing really, really badly - are Hispanic and black boys and those from low-income homes.

    "But the predominant issues for them," wrote Sara Mead, who based her conclusions in the study on decades of government statistics, "are race and class, not gender." Mead's conclusions echo those of Prof. Caryl Rivers of Boston University and Prof. Rosalind Chait Barnett of Brandeis.


    Jay Mathews writes in the Washington Post:
    A study to be released today looking at long-term trends in test scores and academic success argues that widespread reports of U.S. boys being in crisis are greatly overstated and that young males in school are in many ways doing better than ever.

    Using data compiled from the National Assessment of Educational Progress, a federally funded accounting of student achievement since 1971, the Washington-based think tank Education Sector found that, over the past three decades, boys' test scores are mostly up, more boys are going to college and more are getting bachelor's degrees.

    Although low-income boys, like low-income girls, are lagging behind middle-class students, boys are scoring significant gains in elementary and middle school and are much better prepared for college, the report says. It concludes that much of the pessimism about young males seems to derive from inadequate research, sloppy analysis and discomfort with the fact that although the average boy is doing better, the average girl has gotten ahead of him.


    Christina Hoff Sommers writes in the WSJ:
    Education Sector, a new Washington think tank established this year by the Bill & Melinda Gates and other leading foundations, describes itself as an "honest broker of evidence in key education debates." But its first big study, "The Evidence Suggests Otherwise: Truth About Boys and Girls," is deficient in this virtue.

    The report, written by policy analyst Sara Mead, denies that American boys are in trouble academically. "The real story," says Ms. Mead, "is not bad news about boys doing worse; it's good news about girls doing better." So why do so many fret about boys doing poorly? Ms. Mead explains: "The idea that women might actually surpass men in some areas seems hard for many people to swallow." She also hopes that the nation can have a reasonable "conversation" about gender issues "without unfairly undermining the gains girls have made in recent decades."

    One looks in vain in Ms. Mead's report for any indication that anyone is undermining girls. She seems to think that concern for boys means shortchanging girls. But it does not--because education is not a zero sum game.

    From the study's title, one might think that it contains evidence that boys are not languishing academically. It doesn't. In fact Ms. Mead concedes that vast numbers of boys are doing poorly. She acknowledges that more boys than girls drop out; that girls have higher aspirations and take more rigorous academic programs. The number of boys diagnosed with disabilities, she says, "has exploded in the past 30 years." She admits that "high school boys' achievement is declining in most subjects." And, yes, she says, it is true that our colleges are now 57% female.

    So how does she back up her claim that "in fact, overall academic achievement for boys is higher than it has ever been"? She argues that in "absolute" terms boys are doing better today than they were 20 or 30 years ago. She adds that, in any case, the problem of male underachievement is largely confined to black, Hispanic and low-income white males. Neither claim withstands scrutiny.





    Funniest joke ever?   posted by DavidB @ 7/03/2006 08:13:00 AM
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    Nothing to do with genes - unless you want to start a discussion about the population genetics of comedy - but today's UK Daily Telegraph has what some claim as the funniest joke ever told. I don't think it is, but at least it's better than The Aristocrats.

    Personally, I prefer one that was recently voted Britain's favourite joke.

    A woman gets on a bus, carrying her baby. As she pays her fare, the driver says 'Jesus, that's the ugliest baby I've ever seen.' The woman goes to the back of the bus, fuming with indignation, and sits down next to another passenger. She turns to the passenger, and says 'Did you hear what the driver said to me? I was so shocked, I couldn't even speak!' So the other passenger, sympathetic, says 'Never mind, dear, you go back there and tell him what you think of him. I'll hold your monkey for you.'




    Mendel's Garden #2 is out   posted by Razib @ 7/03/2006 05:10:00 AM
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    Hsien Hsien Lei has Mendel's Garden #2 up.



    Saturday, July 01, 2006

    Adam K. Webb, in his own words   posted by Razib @ 7/01/2006 09:03:00 PM
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    The 10 questions for Adam K. Webb stimulated a lot of discussion. I asked Adam if he wanted to pass along a succinct summation of the overall body of his argument, and he agreed. You'll find it below the fold....


    [Character encoding as "Unicode" for best viewing]

    Adam K. Webb on Beyond the Global Culture War

    [adapted from a speech delivered at Harvard and Princeton, May/June 2006]

    As its title suggests, Beyond the Global Culture War is a book about global questions. In that respect, it joins a myriad of other books from recent years. But I would be the first to admit that this book is rather more contrarian in spirit. For one thing, I do not offer the usual breathless celebration of borders breaking open, as the global market economy sweeps to the ends of the earth, supposedly promising the next generation an Ipod in every pocket and a Lexus beside every olive tree.

    Having misgivings about that vision does not mean being against prosperity as such. Indeed, having seen the mud huts and tin shacks in which much of humanity lives, I wish there were more prosperity to go around. Nor does being a curmudgeon about globalisation mean that I oppose opening borders, and getting past the bloodshed that nationalism has caused over the last century or so. Those who know me can attest that in my own loyalties, I am perhaps more cosmopolitan than most of globalisation’s usual enthusiasts are themselves.

    In short, I am neither a Luddite nor a provincial. Rather, the reason I am a curmudgeon about globalisation is that, at least in its present form, I believe it gets the global scale right but the content wrong. What is the content? Globalisation now entails an impoverished vision of human aspirations and the sort of society that is supposed to fulfil them. That vision promises us—perhaps by 2050, certainly by 2100—what Francis Fukuyama a few years ago called “the end of history.” If history ends on those terms, we shall have a world civilisation besotten with markets and a rampant consumer culture. The moral language of the polity will urge a solicitous regard for individual rights, but reek of an undemanding relativism at its core. And over that civilisation will preside a layer of experts and money-mongers without much in the way of either conscience or character.

    This civilisation already exists in embryo. Look around even today at the alienation, the painful lack of moral direction, the striving for material rewards without larger purpose, that afflict so many in the comfortable classes in the most comfortable societies on the planet. A few decades hence, if trends continue, that fate promises to afflict the rest of the world too—from Cambridge to Kinshasa, and from Tokyo to Tehran.

    Having these misgivings about liberal globalisation, about the supposed end of history, is nothing new. In simple terms, I should call myself an economic leftist concerned with social justice, and a cultural traditionalist alarmed by the unravelling of older decencies. Even if not many people would describe themselves quite that way, much of humanity holds such sentiments almost instinctively. Take an example from even a modern liberal society such as the United States. In some circles of late, we have heard talk of restoring the link between moral values and social justice, of reviving a so-called religious left, to balance the religious right that complacently blends Bible-thumping and big business. Much of that sentiment about tradition and social justice is vague, and not very radical in how it diagnoses the ills of modern life. But it is a sentiment that I largely share.

    And if a modern Western society still has a large bloc of people who look askance at history’s supposed end, how many must think that way elsewhere in the world? In poorer and more traditional countries, there are even more folk who would agree with my misgivings about what globalisation and the end of history are supposed to do to them. Parallel culture wars rage in many countries, between those who welcome the supposed end of history and those who resist it.

    So I am not alone. If I were alone, there would be little point in writing Beyond the Global Culture War. But at the same time, I do not just want to lament the way the world is going. Countless thinkers and movements already do that—from the heartland traditionalists of the US, to the Islamists of the Middle East, to the Hindu revivalists in India, and the like. If I were just going to tell the same tale of woe, there would be little point in writing the book either. Instead, what I try to do in it is rethink what these culture wars really mean. And I try to imagine how they might end in a very different way from what many people now assume.

    The book’s title is Beyond the Global Culture War. That is the crux of the issue, I think. It is all too easy to think of these clashes—between tradition and modernity, between social justice and a self-absorbed consumer culture—as many different culture wars playing out in many different countries and civilisations. The details do vary on the ground, to be sure. But the core of what is at stake does not: it is really one global culture war raging everywhere, with the wrong side winning. That horizontal fault line across civilisations is vastly more important, in the long run, than any vertical fault lines between civilisations.

    One odd feature of this global culture war is that the side that is winning has fewer numbers. If we put the present version of globalisation up to a vote around the world, most people would not vote for it. They would not vote for the growing inequality, for the rise of a new upper class with far less sense of decency and social obligation than any other ruling class in history. Nor, all else being equal, would most people prefer a world a hundred years hence in which villages have given way to shopping centres and temples to rave clubs. Even in the prosperous countries of the West, where consumer culture has already gained so much ground, plenty of discontent with the values it has favoured simmers below the surface.

    How does this vision still hang on, despite opposition? One reason is that only one side in the global culture war really thinks of it as a global culture war. Those who resist the onward march of globalisation and the end of history tend to see the clash as many culture wars. Take just two examples. The Islamists who have fought so hard against liberal modernity in the Middle East think of their battle as one for the Islamic world alone. They want to expel the infidels and erect high walls around a new ummah. And the American cultural conservatives of the heartland, who bemoan the direction of American society, spend much of their time doing such things as denouncing the UN and supporting a chest-thumping American nationalism. I am reminded of the old Indian folk tale in which seven blind men grope around different parts of an elephant, and never agree on the shape of the animal as a whole.

    Meanwhile, the yuppies of London, Hong Kong, and Bangalore alike see themselves everywhere as kindred spirits, purveyors of humanity’s future. Consumer culture and a vapid kind of liberal democracy supposedly tap into some desire lurking in human nature. In every Kazakh tribesman and Bolivian peasant, that desire waits only to be awakened by freedom and bright lights. And as many defenders of liberal globalisation have noted with glee, challenges to it tend to speak in the name of one or another people, one or another culture, not in the name of humanity as a whole. There are global liberals, global free-marketeers, and global secularists; there are no global fundamentalists, populists, and traditionalists.

    We thus have a global culture war being fought globally from one side, the winning side, and in a defensive and fragmented way on the losing side. The self-indulgent are giving the provincial a good hiding.

    Therein lies the problem. Benjamin Franklin said after signing America’s Declaration of Independence that those who did not hang together would most assuredly all hang separately. Traditionalists around the world today are well on their way to hanging separately. Solving the problem is no easy matter. Even if one got the likes of Patrick Buchanan and the likes of Mahmoud Ahmadinejad to sit down together for tea, it is unlikely each would then realise the other is a good chap after all, and then trot off to do battle together against the yuppies. The challenge is greater than that, and I have misgivings about both of them anyway. But I do argue in the book that unless we start seeing the global culture war as global, and start challenging the present vision of globalisation on its own scale, we are doomed. History will end, perhaps with an Ipod in every pocket and a Lexus beside every olive tree, but certainly with a desolation of the spirit.

    Beyond the Global Culture War is about how to make sense of this global culture clash, and move beyond it in the spirit of both traditional values and social justice. Notwithstanding the complacency of the powers that be, matters are not yet decided. Most of humanity remains unconverted to their vision. The great traditions’ steady loss of ground over the last century should not dishearten us. It should inspire us to rethink our diagnosis of what ails the modern world, and to offer a very different image of the future. This book proposes not retreating more slowly in the global culture war, but rather winning it on new terrain.

    I know that many would be tempted to conclude that I am shouting in the wilderness for us to go back to the Dark Ages. I am not. As I explain in the book, I welcome the prosperity, the legal protections, and broadening of horizons, that modernity has brought a large chunk of humanity. But the story I tell in the book makes clear, I think, that we could have had such advances without the moral impoverishment, the self-absorption, and the rise to power of the wrong sorts of people. History did not have to turn out this way. And, since history is not yet over, something can still be done about it, to snatch victory from the jaws of defeat.

    The argument I develop in the book has many parts. While each is fairly straightforward, they build on one another in a way that I can only begin to summarise here. But I do want to highlight a few of the major themes.

    First, the global culture war to be fought is against what we might call liberal modernity. What is liberal modernity? For one thing, it is not “liberalism” in the narrow centrist or left-of-centre sense in which the label is often used in Western politics. It is a deeper self-understanding, which many of us think of as simply modern. In varying degrees, it affects the whole mainstream of the Western political spectrum, from the likes of Reagan and Thatcher on the right to the social democrats and Naderites on the left. Beneath such arguments over details, the liberal worldview has already won and come to define the core political values of Western societies. To challenge it means to rethink a good deal from the ground up.

    To put matters that way is a sweeping indictment, to be sure. If one does not already share it, I know it can seem unnerving. But what is this liberal worldview against which a global culture war must be fought? The modern liberal self-understanding is one that preaches rights over duties, reduces values to mere individual preferences, and sees political institutions as machinery to keep society running rather than as a way to promote worthy ways of life. That sounds quite abstract, but it has quite concrete effects on daily life and culture. Before the last two centuries, no culture, particularly at the highest levels, would declare that “greed is good,” or that wealth had no social obligations beyond the whim of its owner. Nor would any culture have held that personal morality was just a matter of taste, as long as one did not hurt anyone else. These attitudes involved much more than just how to arrange a society’s institutions, important though that was. Nor did they just come down to freedom, or a lack of freedom. They were about a self-understanding, about qualities of character. There was an up and a down within the self, so to speak. And in this respect the contrast between the dominant classes today and the dominant classes of centuries past could not be starker.

    Second, this self-understanding, while dominant today for the first time in history, predates modernity. It has always existed below the surface for some people. Liberalism is the modern version of a timeless self-understanding, which in the book I call “atomist.” To see the world through the eyes of an atomist is to think that human beings have few social obligations, and that human nature has no objectively true higher ends.

    Before the last century or so, atomism was always kept in check. To put it bluntly, it was confined to a few marginal groups in society: wheeling and dealing merchants, hardheaded bureaucratic functionaries, court eunuchs, free-floating types at the edges of mainstream culture, and the like. A few thinkers, like the Sophists in ancient Greece and the Legalists in ancient China, also expressed an atomist view of the world. Other thinkers and history duly cursed them for it. And most of the people who had this outlook did not really want it anyway—in the sense that the circumstances that shaped them to think of themselves in this rootless and somewhat degraded way were hardly desirable.

    Third, alongside atomism were other ways of thinking about oneself, which were much more uplifting. Those self-understandings set the tone of premodern cultures. I shall not dwell on the details here. But think of the traditional peasant with a hearty sense of fellowship and duty to neighbours. Or think of the mystic who meditated in search of a spiritual truth beyond the world, or the literary or aristocratic type who valued certain kinds of honour and nobility. Or think of the clerics or mandarins who brought their own virtues and moral compass to bear on the world around them. These kinds of people were quite unlike each other, to be sure. A peasant who valued fellowship in a small community was not the same as a mystic or a heroic type who cultivated himself above and apart from the world. And neither of them was the same as a cleric or mandarin who thought he had a mission to bring about a morally inspired society. Each of them had their own kinds of virtue, which complemented one another in a society. Moreover, it is striking that, for the most part, one finds these three types of people in all ancient and mediæval civilisations. Just to take a couple of examples, the Catholic clergy corresponded to the Chinese mandarins; the Sufis corresponded to the Daoist mystics; and peasants and people like them were everywhere much the same in basic self-understanding, even if the details varied from culture to culture.

    Fourth, and following from this slicing up of basic self-understandings, we have four different ways of thinking on universal terrain. There are those three uplifting kinds of self-understandings—of the peasant, the mystic or aristocratic hero, and the cleric or mandarin—which call forth the best qualities in human nature. And then there is atomism, the kind of self-understanding that has triumphed in the modern world. Atomism either calls forth the lower qualities in human nature, or pretends there are no higher qualities, or dismisses the whole question as a mere personal taste.

    Each of these four self-understandings—ethoses, I call them in the book—is equally placeless, equally part of the human experience across cultures. Each is a rival universalism, deeply rooted in different directions that human nature can take. So when modern liberals offer us the end of history, they do have good reason to think their vision of the world speaks to all humanity. I agree wholeheartedly. But as I argue in the book, three other kinds of human nature also speak to all cultures. And in the name of those other three, if people recognise as much, we can fight back in a global culture war and meet modern liberalism on its own scale.

    Fifth, the triumph of this degrading self-understanding in modern times has come through a series of manœuvres over several generations. Those manoeuvres happened in culture, ideology, institutions, social movements, education, and the like. They started in western Europe in the nineteenth century, and gained ground elsewhere over the last hundred years. With each manoeuvre, the modern liberal project, with specific social groups and interests behind it, managed to overcome resistance. It shifted the global terrain in its own favour. It escaped all of the checks that well-ordered cultures had placed on it before modernity. Whatever its protestations then and now, its victory was not inevitable. It faced one backlash after another. But it managed to evade those backlashes, by shifting its own form and by playing those backlashes off against one another. It played the working classes off against the declining gentry. One generation it might preach social democracy; the next, free markets. To one audience it might hold out progressive nationalism; to another, global openness. And all the time history rolled on, flattening the old civilisations.

    Sixth, the weakness of resistance today reflects this history of manœuvre, of defeat after defeat. Why are the Islamists and the Chinese populists and the Christian Right and other groups around the world so strident yet so ineffective? They have been reduced to thinking of themselves as speaking for particular cultures rather than for universal human truths. They have also lost the enlightened and more cultivated traditional leadership that they had a century ago. Because of social changes that I trace in the book, hardly any enlightened gentry and clerics and mandarins remain in the world as a political force. Usually a cosmopolitan temper flourishes at the higher levels of a society. Today’s upper classes, around the world, are overwhelming liberal in the broad sense of the word. There is no sophisticated, broadminded, traditionalist bloc, with very few exceptions. Instead we are left with the stridency of lower middle class movements that cling to custom and yearn to build high walls around whatever patch of land they claim. They might slow down consumer culture and moral relativism a bit. But in the long run, can they hope for more than losing the global culture war more slowly?

    Seventh, a challenge to liberal globalisation needs to take all three of those older and more uplifting ethoses, or self-understandings, seriously. An alternative to the emerging global culture will not go very far unless it can speak to different kinds of human aspirations. It must revive the small decencies of plain folk, as well as the more demanding sorts of self-cultivation that only a few souls used to pursue in the past. When liberals protest that today’s fundamentalists would squash everyone into one mould, they have a point. Yet a diversity based on these other three self-understandings, in partnership with one another, would be far richer. It would present a vision of the future that would hark back to the best of premodern civilisations, with their multiple worthy ways of life. And I suspect it would also appeal to many who think of themselves today as liberals—simply because they are not fundamentalists—but who want more than what a vapid liberal culture can offer them. We can have the ethical goods of the past with the prosperity and global horizons of the present, if we frame the issues the right way.

    Eighth, the only way to win the global culture war is to fight it globally. We need more networks of traditionally minded movements across the world, across cultures, with common political aspirations. Every email between an ayatollah in Qom and a neo-Confucian in Taibei would be a step forward. It is quite possible that the kind of globalisation we see now could lead to a world state in another fifty years or so. Can we imagine an alternative world state that is not liberal, not just a machine for depositing an Ipod in every pocket, a Lexus beside every olive tree, and a nightclub on every street corner? A world state that draws from the best of the past and promotes better rather than worse ways of life? A world state that brings civilisations together into a higher synthesis? In Beyond the Global Culture War, I suggest that such visions must be a vital part of the political strategy for fighting the global culture war to victory.

    Ninth and finally, I should return to a point with which I opened. I approach all these big questions from a global perspective, but from the right culturally and the left economically. I think any challenge to the world as it is has to bring together the traditionalist backlash of the right against the modern cultural collapse, on the one hand, with the many pressures from the left for social and economic justice around the world, on the other. As one might imagine, I think the leftist anti-globalisation movement, which stirred things up at Seattle and Genoa and the World Social Forum in recent years, does not take tradition seriously enough, and is too much coloured by the modern world. Yet I do hold out the hope that left and right could one day come together around such a broad alternative. Global social justice needs the moral authority and insights of tradition to lend it weight. And a genuine critique of global capitalism from a traditional vantage point demands economic justice. The modern world has enslaved the spirit to the stomach while satisfying neither. Humanity needs its spirit ignited and its stomach filled, and only a victory in the global culture war can do both.






    Intelligence and Self-Deception?   posted by Matt McIntosh @ 7/01/2006 08:20:00 PM
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    A friend and I were discussing the eventual ubiquity of lie detection technology, and what sorts of social ramifications it would have. I made the point that this would immediately create greater selection pressure for self-deception, since "lie detectors" are better referred to as "sincerity detectors," and as Trivers points out the liar who believes his own bull is the most effective kind. (I now notice that one of Parker's commentors at the link above made the same point, but I thought of it on my own, really!) My friend then mused thusly:

    I'd like to see a study of self-deception v. g and some correlation with careers. If self-deception is highest among those with the lowest g, it might not be worth it because the cost of deception is likely to be rather low. I don't think it's a completely implausible hypothesis: religious belief is correlated negatively with intelligence. While it might be somewhat offensive, much of religious belief does seem predicated on self-deception...

    My initial reaction was that while plausible, this could go either way. Ceteris paribus, the smarter you are the easier it is to concoct believeable bullshit stories on the fly. If there *is* a negative correlation between g and self-deception, it's probably because on the other side of things increased intelligence also makes it harder to fool yourself. There could be something of an internal arms race, and the net effect could be a wash.

    So, does anybody here know of any studies that have looked for correlations between intelligence and self-deception? Alternatively, any ideas about neural mechanisms behind self-deception that might also have some effects on intelligence? Propensity for self-deception isn't easy to measure in itself, but this seems like too interesting a question to leave unexplored.




    Not a new "species" of Great Ape after all   posted by Razib @ 7/01/2006 12:42:00 PM
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    A few years ago there were reports of a new great ape in the Congo, perhaps a chimp-gorilla hybrid. As the story unfolded it seemed more and more plausible that this was a local morph of the common chimpanzee, and genetic tests have confirmed that hunch. It is a subspecies of common chimpanzee, though with unusual morphological features. The latter is important, we see a wide range of phenotypes among humans across small distances, so it should not surprise if chimpanzees also exhibit variation.