Archive for July, 2012

Continuing the search for Indo-Europeans

By Razib Khan | July 15, 2012 2:53 pm

Dienekes P. is often rather laconic in commentary on the papers he links to, but of late he has “come out of his shell.” He has two posts which are important “weekend reading”:

Population strata in the West Siberian plain (Baraba forest steppe)

Hints of East/Central Asian admixture in Northern Europe

I freely admit that much of the conjecture here is above my pay-grade in terms of evaluation. But I do think it’s important think through. My “gut” tends to lean toward a “revenge of the Mesolithic” scenario promoted by some of Dienekes’ critics, but I don’t have a strong position.

CATEGORIZED UNDER: History
MORE ABOUT: Indo-Europeans

Society seen through genes

By Razib Khan | July 15, 2012 2:39 pm

Over the past few months more and more articles like this one in the The New York Times are coming out, Two Classes, Divided by ‘I Do’:

Jessica Schairer has so much in common with her boss, Chris Faulkner, that a visitor to the day care center they run might get them confused.

They are both friendly white women from modest Midwestern backgrounds who left for college with conventional hopes of marriage, motherhood and career. They both have children in elementary school. They pass their days in similar ways: juggling toddlers, coaching teachers and swapping small secrets that mark them as friends. They even got tattoos together. Though Ms. Faulkner, as the boss, earns more money, the difference is a gap, not a chasm.

But a friendship that evokes parity by day becomes a study of inequality at night and a testament to the way family structure deepens class divides. Ms. Faulkner is married and living on two paychecks, while Ms. Schairer is raising her children by herself. That gives the Faulkner family a profound advantage in income and nurturing time, and makes their children statistically more likely to finish college, find good jobs and form stable marriages.

The story is set up to illustrate the importance of contingency. Two women with very similar backgrounds, and presumably aptitudes, make two very different decisions early on in their lives, and that sets their life path via the constraints or options that that choice enables. We’ve come a long way from the early 1990s when there was a debate, at least at the higher cultural strata, about the necessary value of marriage. But this part jumped out at me:

They stayed with Ms. Schairer’s brother, [the single mother -Razib] visited SeaWorld and Gatorland, and brought back happy memories. But the trip soon began to seem long ago, more a break from their life than an embodiment of it.

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CATEGORIZED UNDER: Genetics
MORE ABOUT: Behavior Genetics

Genetic counseling and conflict of interest

By Razib Khan | July 14, 2012 9:33 pm

Article in The New York Times:

Genetic testing raises some vexing ethical questions, like whether it will cause unnecessary anxiety or lead to more medical procedures, including abortions.

Now, as the number of tests and the money to be made from them are exploding, another question is being asked by professionals in the field themselves. Is it ethical for genetic counselors, who advise patients on whether to undergo testing, to be paid by the companies that perform the tests?

While it might not always be immediately obvious to patients, some counselors offering them advice in hospitals and doctors’ offices work for the commercial genetic testing companies, not for the hospitals or doctors themselves.

Conflict of interest in anything medical is pretty bad. On the other hand, medical care is expensive. But I want to add something here: the pre-natal screens by Genzyme are really, really, bad value-for-cost. For example, a non-insurance “sticker price” of thousands of dollars for 200 traits. Speaking from personal experience here. Also, don’t think you can ever get genetic material sent to Genzyme back. I called and tried this for a few months, and there was no response (I wanted to do typing of tissue myself).

CATEGORIZED UNDER: Personal Genomics
MORE ABOUT: Genetic Testing

Who objects to painful tests on animals?

By Razib Khan | July 13, 2012 7:39 pm

In the year 2008 1,400 people were asked this question in the GSS:

Scientists should be allowed to do research that causes pain and injury to animals like dogs and chimpanzees if it produces new information about human health problems. (Do you strongly agree, agree, disagree, or strongly disagree?)

(variable ANSCITST)

I was curious because I ran into some stuff on pro-life sites today about how animal rights activist don’t oppose abortion, and how hypocritical that is. So naturally I was curious about how attitudes varied on that issue.

Allow animal testing which might case pain
Strongly agree Agree Disagree Strongly Disagree
Yes to abortion on demand 8 31 39 22
No to abortion on demand 7 32 39 23

What the results above show is that there is almost no difference in attitudes toward animal research when you vary attitudes toward abortion on demand. In other words, 22 percent of pro-choice people oppose such research strongly, while 23 percent of pro-life people do. How does this vary by demographic?

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CATEGORIZED UNDER: Data Analysis
MORE ABOUT: Animal Rights

Why some people don't think Down Syndrome is bad

By Razib Khan | July 13, 2012 7:16 pm

I often criticize Lefty readers for their lack of reality-basis. Specifically, they often want to align reality with their own normative preferences, even though normative preferences aren’t necessarily contingent upon reality (e.g., sex differences). My post on Down Syndrome has elicited similar responses, but from people one might term social conservatives. So, for example, Ursula and Matthew Hennessey have taken to denouncing me on Twitter, albeit for statements that they no doubt find extremely objectionable. Not too surprising. But I found this post, A gift named Magdalena, particularly instructive:

But we aren’t victims. In fact, we’re the opposite. We are supremely lucky. Magdalena isn’t sick. Down syndrome is not a disease; it’s merely a collection of traits, all of which occur, though not all at once, in so-called “normal” people.

But how could Down syndrome be a gift? Surely that’s taking it too far. How could a lifetime of likely dependency be a gift? How could impaired cognitive development be a gift? How could gastroesophageal reflux disease and its expensive, twice daily medicine be a gift? How could two full years of potty training with no end in sight be a gift?

The truth is that there is no objective bright line between trait and disease. In fact, nature does not know trait or disease, it only knows phenotypes. Being white skinned in a pre-modern world is a disease at the equator, and being black skinned in Scandinavia would also have been a disease. In theory you could argue that Down Syndrome is not a disease either. The Hennessey’s are correct that the collection of traits of DS individuals can be found elsewhere. So imagine that a chemical exposure or some such thing functionally transformed a child with a normal karyotype into one with Down Syndrome. How would most people feel about this? Would parents view it as a gift?

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CATEGORIZED UNDER: Health
MORE ABOUT: Down Syndrome, Theodicy

Native Americans are not special snowflakes

By Razib Khan | July 12, 2012 11:45 pm

Dienekes, in response to Living Anthropologically, Petty identity politics indeed, or, holding a grudge is no excuse for anti-science:

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CATEGORIZED UNDER: Anthroplogy
MORE ABOUT: Native Americans

I think Down Syndrome is bad

By Razib Khan | July 12, 2012 11:04 pm

An interesting comment:

“If you add copies of a gene the result is not always good because of dosage effects (Down Syndrome is an extreme case of this on the smallest chromosome).” [From my post, -Razib]

As a father of a child with Down syndrome, I would take exception to this comment. First DS, is not “bad” – my daughter is an amazing and wonderful person, and her DS is part of that wonderful person. She is one of the most amazingly positive things that has ever happened in my life. So I have a hard time reconciling that with your “extremely bad” synopsis.

Second, DS is not an at all extreme case – it is rather run of the mill. It is so minor of a variant that it is survivable and very common place (1 in 733 births). People with DS lead full, productive and meaningful lives. That is not extreme, it is mild. Extreme would be being born inside out or having no chance of surviving 72 hours.
Please don’t add to the misconceptions around Down syndrome. Most of us parents, siblings, and self-advocates find this to be both untrue and unhelpful.

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CATEGORIZED UNDER: Bioethics
MORE ABOUT: Down Syndrome

The past as a cultural landscape

By Razib Khan | July 12, 2012 10:03 pm

By now you have read that the Clovis people may have had contemporaries. In case you didn’t know, until about ~10 years the “standard model” of the peopling of the Americas was that around ~13,000 years ago one single population crossed into the New World via Beringia, and rapidly swept north to south in ~1,000 years. These were the Clovis people, associated with a particular toolkit, and perhaps implicated in megafaunal extinctions. Today this model is no longer held to be sacrosanct, though no clear successor has emerged. It does seem likely that some sort of pre-Clovis population is presumed to exist. These data are interesting because they indicate that there may have been geographical structure in cultural forms even at this early stage in North America, implying that the original peopling of America was not homogeneous. That is, there may have been several founding groups.

I find this entirely plausible. It strikes me that a fear years ago a tendency toward rhetorical extremism occasionally found purchase when it came to the settlement of the peripheries of the human range, Oceania and the New World. Jared Diamond famously proposed that Australia and Papua may have been colonized by one pregnant woman! (presumably she then reproduced with her own son, as Gaia did with Uranus) In hindsight it seems more likely that migration of pre-modern humans was a far more organized affair, and not an ad hoc expansion in a state of anarchy, with family groups splitting off in a random fashion due to demographic pressures. Note that archaic humans did not settle Oceania and the New World, despite having a million years to do so.

Many researchers suppose that the ancestors of the First Americans sojourned in Berengia before they crossed over into the New World (their progress being blocked by glaciers). This may explain why genetic estimates of the populations’ origin tend to be deeper than the archaeological conclusions, even if you push the dates back due to Monte Verde. From the media reports archaeologists seem to be emphasizing that the original population which settled the New World may have been culturally diverse, even if they are genetically similar. Presumably this is a counterpoint to the paper which posits a “First American” group at the heart of the genomic variation of the New World groups.

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CATEGORIZED UNDER: Anthroplogy

Nomads as post-hunter-gatherers

By Razib Khan | July 12, 2012 12:28 am

There’s a new paper in PLoS ONE which seems to confirm domesticate goat or sheep in southern Africa ~4,000 years ago. This is of particular interest because it may shed some light on the prehistoric migration of the Khoikhoi populations of the region, which predate the Bantu. In First Farmers Peter Bellwood argues that the anthropological evidence indicates that it is difficult for a non-farming population to adopt farming wholesale. Groups such as Pygmies in Central Africa are engaged in the farming economy, but only in symbiosis with farmers proper, and generally as landless laborers. But nomadism might be a contrast. I have observed that it seems while Australian Aboriginals have not taken keenly to farming, they have become integrated in the pastoral economy of Australia. Nomadism is quantitatively different from hunting & gathering, but the skillset is not too different.

CATEGORIZED UNDER: Anthroplogy
MORE ABOUT: Nomadism

The stupid is the mind-killer

By Razib Khan | July 11, 2012 11:19 pm

In the comments below I expressed anger when I realized one of the readers who I had hoped was not stupid was really rather stupid. I don’t have a high toleration for this sort of stuff, which has supposedly become somewhat well known in the blogosphere (judging from comments about me on other weblogs). When I was younger I suspect I had more toleration for this sort of thing, and engaging with the dull is something that needs to be done, just like you need to change a baby’s diaper because you know they’ll soil themselves, and they can’t be left that way. Perhaps there’s a fixed amount of sympathy for people who shit themselves because they don’t know any better, literally or metaphorically. I’ve got to deal with the former right now, so maybe I’m not having any of the latter anymore.

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CATEGORIZED UNDER: Creationism
MORE ABOUT: Creationism

The first, second, and third nations

By Razib Khan | July 11, 2012 10:47 pm

By now you’ve probably read about the paper which reports that there seem to have been three waves of humans migrating into the New World prior to the arrival of Europeans. A major aspect of this result is that it does not emerge out of a vacuum, but rather comes close to settling an old question in linguistics. The late Joseph Greenberg generated a series of audacious phylogenies of languages of the world. Greenberg’s attempts received mixed reviews. It seems that there is little controversy about some of his classifications of African languages, but linguists of American native dialects rejected his division of the languages of the New World into three broad families, Eskimo-Aleut, Na-Dene, and Amerind. Eskimo-Aleut is rather self-evident. Na-Dene encompasses a group of languages in northwest North America, along with some significant outliers such as Navajo. Amerind seems to roughly be a grab-bag of everything else. The linguistic trichotomy also lent itself to a narrative of three migrations. L. L. Cavalli-Sforza gave his support to Greenberg’s framework in The History and Geography of Human Genes, and it seems most non-linguists are particularly congenial toward his tendency of ‘lumping.’ In contrast, linguists remain more skeptical ‘splitters,’ at lease those who have a more ethnographic disciplinary bent. Geneticists have not always supported Greenberg’s suppositions. For example, many of the members of the same group which authored this paper implicitly put the kibosh on the attempt to construct a unified linguistic family which spanned the Andaman Islanders and the Papuans.

The method of the paper was relatively straightforward, assuming you are already somewhat familiar with the statistical genetic esoterica which was unveiled a few years ago by this group and others. Basically you take genetic data in the form of hundreds of thousands of SNPs, and you test the patterns of variation in that data across populations against explicit models of demographic history, represented visually by phylogenetic trees. You can see here that the sampling was relatively thick, except for the United States. Chalk this up to politics. I’ve been hearing about this particular problem in relation to this paper for over a year now. Not having asked any of the members of the group directly I obviously am going off hearsay, but the lack of American samples is most definitely not a feature. It’s a bug. In the supplement they also note that they couldn’t get Na-Dene data from another research group. Almost certainly that’s because of bioethical issues and legal contractual constraints.

Despite all this drama, the scientific isn’t too hard to understand. Aside from the nifty statistics one problem is that many of these native groups have European and African admixture, but there are workarounds to that (e.g., just pull out genomic segments which are indigenous, and use those). The outcome is neatly visualized in the figure below:

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Creative bacterial destruction

By Razib Khan | July 11, 2012 12:00 am

To the left is a panel from a new paper in PLoS Genetics, Selection-Driven Gene Loss in Bacteria. The y-axis is selection, so above 0 represents a positive selection coefficient, and below a negative one. The lineages above the x-axis then are more fit against the baseline wild type (selection coefficients above 0.01 can be considered rather strong, with 0.08 very strong). The top-line result of this paper is that 11 out of 55 deletion constructs in bacterial lineages seem to result in increased fitness. This is rather weird if you are viewing it from a homocentric perspective, or more ecumenically, a multicelluar organismic perspective. If you add copies of a gene the result is not always good because of dosage effects (Down Syndrome is an extreme case of this on the smallest chromosome). If you delete whole regions of the genome the results are usually disastrous.  This comports with common sense. If you break something it isn’t usually a good thing. It was there for a reason.

But this heuristic may not be applicable to bacteria. Or, more precisely, when you remove the large set of parameters which constrain the adaptive landscape of multicellular organisms, you may be exploring an evolutionary space with somewhat different rules. If someone reported that 25% of deletions in a multicellular organism resulted in increased fitness I’d probably be curious if there was a basic human error somewhere along the way generating this crazy proportion. But fast-breeding and genomically economically designed bacteria may not be governed by the same expectations.

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CATEGORIZED UNDER: Genetics, Genomics

The world I knew

By Razib Khan | July 10, 2012 8:24 pm

There’s something about this 1995 single from Collective Soul, The World I Know, which is redolent to me of the Pacific Northwest.* Yes, it’s precious, but the Pacific Northwest is a bit precious. The land of misty mornings, SWPLs, and strong coffee. The shadows alternating with colorized high key lighting common in these alter-rock videos from the mid-90s does neatly parallel some of the scenery which you encounter in the geography of that region. It was only through happenstance that my family moved to the land of big trees when I was on the cusp of puberty, but it was where I matured as a person. Living outside the Northwest now I regularly identify as a Northwesterner, and I certainly miss some of the perks of that region, though I could do without the feeling that I’m walking around in a cloud forest scene in a fantasy novel all the time. ’till we see each other again, on 47th and Division.

* I am aware that CS is not a “Seattle band.”

CATEGORIZED UNDER: Blog
MORE ABOUT: Northwest

A history of science blogging

By Razib Khan | July 10, 2012 8:00 pm

Bora Zivkovic has what is basically a short history of science blogging up. I was one of those who was there at the beginning, and I honestly can’t say that he left anything of great relevance out of the narrative. In normal circumstances I don’t think much about what I do, I do. But one thing I will add: blogging isn’t some exotic and peculiar aspect of science anymore, many labs use WordPress as a content management system. Blogs as they were 10 years ago aimed out, toward the populace. Today the info-ecological niches what we would have called blogs fill are much more diverse. Some blogs basically exist to update lab members and interested researchers on their publications and journal club. I add these to my RSS even though I’m not a member of the lab and don’t participate in the journal club because they’re educational to me (e.g., gc bias). Imagine, if you will, that R. A. Fisher had had a blog at Rothamsted. Though this is an opportunity to point you to the R.A. Fisher Digital Archive in case you don’t know about it. We live in rich times for the infovore.

Oh, and in the interests of social media whoring:

CATEGORIZED UNDER: Blog
MORE ABOUT: Blogs, science blogs

Toward healthier gestations

By Razib Khan | July 10, 2012 7:44 pm

Neuroskeptic has a post up, The Coming Age of Fetal Genomics:

So they don’t. Instead, they buy a $100 test kit, they each provide a small blood sample and send it off to one of the companies offering fetal genome testing. At the testing lab, they can separate out the mother’s DNA from that of the fetus, both of which are present in the mother’s blood. By comparing the fetal genome to the mother’s and father’s, it’s easy to spot de novo mutations. If a certain gene doesn’t match either the mother or the father’s sequence, it’s mutated.

A few days later the results are back. There are several mismatches detected. Most are benign – they’re not predicted to have any biological effects. But there’s one, a deletion of a few thousand bases in a gene involved in brain development. This deletion is predicted to raise the risk of epilepsy and autism from 1% to 10% apiece. The parents now have a decision to make. The mutation is a one off, it’s not inherited. If they conceive again… roll the dice again… and it’ll be gone. Do they terminate?

Like the adverts say, “Some people disagree with this, but we say there’s only one person who really matters: your baby.”

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CATEGORIZED UNDER: Culture, Personal Genomics

More on jobs & Ph.D.s

By Razib Khan | July 10, 2012 1:01 am

First, I’m sure that the blue-collar readers of this weblog are thinking “cry me a river.” Yes, American scientists (perhaps excluding engineers, and to a lesser extent pharmaceutical researchers) are generally Left-liberal, but the collapse of the American working class due to globalization is something that they fixate on only as part of a broader political vision, along with other concerns. But when it comes to tenure-track jobs, the end is nigh! Consider that the woman who seems to have “wasted” a neuroscience Ph.D. in yesterday’s Washington Post article now has a job in academic administration. This is the sort of failure that manual laborers and factory workers alike would probably kill for.

But in any case, some more posts for you. Reader Miko reflects on searching for a job, Mike the Mad Biologist keeps doing his thing, and fellow Discover blogger Julianne on Subtleties of the Crappy Job Market for Scientists:

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CATEGORIZED UNDER: Culture
MORE ABOUT: Science

The privileges and burdens of a novel inversion

By Razib Khan | July 10, 2012 12:22 am

There’s two papers in Nature Genetics on the 17q21.31, and variation of haplotypes of inversions in world wide populations. Here’s a part of the discussion from the first paper:

In conclusion, we propose that the ancestral H2′ haplotype arose in eastern or central Africa and spread to southern Africa before the emergence of anatomically modern humans…Approximately 2.3 million years ago, the inversion rearranged to what we now refer as the direct orientation haplotype (H1′). This haplotype spread throughout the Homo ancestral populations in the African continent, virtually replacing the H2′ haplotype and becoming the predominant haplotype. We note that both the Denisova and Neandertal sister groups are predicted to have H1′ haplotypesThese early haplotypes were much simpler in their duplication architecture, similar to the patterns seen in great apes. We find that the more complex duplication architectures are particularly enriched in populations that migrated out of Africa. On the basis of sequence at the duplication loci, we estimate that the H2-specific duplication event occurred approximately 1.3 million years ago. Independent of the H2 duplication, the H1-specific duplication event occurred much more recently, approximately 250,000 years ago. Notably, we did not observe this haplotype in any of the African or Asian populations studied, suggesting that it may have been lost in these groups as a result of genetic drift. The H2D haplotype has risen to frequencies of 10–25% in European populations with virtually no genetic variation, suggesting an extremely recent and rapid expansion of this haplotype. High-coverage sequencing of more individuals along with fecundity data will likely shed further light on whether the high frequency of the haplotype-specific duplication in Europeans is due to selection or the effects of demographic history specific to this locus.

H2D individuals are susceptible to disease. If there is a fitness gain, there is also a loss. Despite his eugenical enthusiasms W. D. Hamilton ultimately gave up on the idea because he admitted it was difficult to predict what was beneficial and what is deleterious. Context matters. The distribution of haplotypes in this region seems to reflect echoes of deep pre-“Out of Africa” history in our species.

CATEGORIZED UNDER: Human Genetics, Human Genomics

Two pulses of white admixture in American slaves?

By Razib Khan | July 9, 2012 11:54 pm

I noticed today an interesting paper in Genetics by Simon Gravel, Population Genetics Models of Local Ancestry. As indicated by the title this is a general paper where the method is the main course. But, there was an interesting empirical result which I want to highlight:

Comparing the ancestry variance from the African-American data to those predicted by the demographic models, we find that the pulse model predicts a genealogy variance of 0.0005, whereas the variance in the model with two distinct pulses is 0.002. The total variance in the African-American sample is 0.0047, of which we infer that 0.0041 is due to genealogy variance (using the method described in Appendix 3). Thus the model with two pulses of migration is again more realistic than the single pulse model; the fact that it still underestimates the variance can be due to a combination of factors that have not been modeled: our demographic model may be underestimating low level, very recent migration because of the parameterization as two discrete pulses of migration, and both population structure and errors in ancestry assignment may be adding to the observed variance.

To the left is a screenshot which represents a slice of the technical meat of the paper. Most people aren’t going to be able to penetrate this. So how to evaluate? The author presents an empirical prediction. I’ve read a bit about American slavery, a few years back, and I don’t recall any mention of two pulses. This isn’t too surprising, as there wasn’t that much cliometrics. But if this is attested in the literature it would certainly increase my confidence in the utility and power of the method of the paper. By their fruits you shall know them!

More generally, this sort of analysis of phased data sets is obviously the future. A more detailed topography of genomic variation is going to open up a huge window onto the human past.

MORE ABOUT: Genomics

The genetic map of Britain

By Razib Khan | July 9, 2012 11:38 pm

Update: A commenter noted that North England and Southwest Wales have different shape points. This is clear in the original PDF when I increased resolution. So ignore my comment about Brythonic Celtcs.

End Update

A few weeks ago I heard about the project to create a genetic map of Britain. Actually, I knew a bit about this because they’ve been publishing a few papers here and there over the years. But there is now an an exhibit up at The Royal Society Summer Science Exhibition 2012. My attention was drawn to this because British tabloids kept pushing headlines like “Cornish genetically different from other English!” I emailed one of the scientists associated with the project, Peter Donnelly, but he never got back to me. So I figured I would post anyway. Looks like they’re using thousands of samples at 600,000 SNPs. When they get a paper out it should be neat. On the other hand the map leaves a little to be desired. The clusters are clear, but what’s the genetic distance between the clusters in a relative sense? How were the cut-offs devised? I’m sure there are reasonable answers, but it’s all rather opaque at this point.

Nevertheless, I do want to point out two things. First, Anglo-Saxon England rather jumps out at you does it not? Second, the similarity between southwest Wales and northern England is explicable. The northern English region was associated with the Brythonic Celtic kingdom of Rheged, and later the southern portion of historical Strathclyde. These were the cousins of the Welsh, not Gaels like the Scots, but Britons. This is evident in the name Cumbria, it has the same root as Cymry, the ethnonym of the Welsh for themselves.

CATEGORIZED UNDER: Anthroplogy
MORE ABOUT: British Genetics

Selection of and in groups

By Razib Khan | July 9, 2012 9:45 pm

Eric Michael Johnson has an excellent round-up of and commentary upon recent debates about “group selection” (also, a decent primer on the basics). If there is one major issue I might take with the narrative outlined, it is the idea that E. O. Wilson has made a recent about-face in regards to group selection, going from a skeptic to a believer. In Defenders of the Truth: The Sociobiology Debate Ullica Segerstrale pointed out that this was obviously not the case even in Wilson’s grand book Sociobiology. If you don’t accept this, David Sloan Wilson seems to implicitly confirm Segerstrale’s position in his semi-autobiographical book Evolution for Everyone. Finally, I’ve heard it from acquaintances at Harvard that it was an open secret that E. O. Wilson was skeptical of the “Hamiltonian orthodoxy” ascendant in evolutionary biology and ecology. The controversy over the notorious paper, The evolution of eusociality, was years in the making. From what I gather many of Wilson’s colleagues at Harvard were skeptical that he comprehended the depths of the mathematics which he promoted to support his more intuitive empirically informed skepticism of the power of inclusive fitness. It isn’t an unheard of sin for an eminent empiricist to go shopping for a theoretician to add some luster to his logic, but it does frame the reason that some of Wilson’s colleagues seem so irritable about the whole affair.

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CATEGORIZED UNDER: Evolution
MORE ABOUT: Social Evolution
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This blog is about evolution, genetics, genomics and their interstices. Please beware that comments are aggressively moderated. Uncivil or churlish comments will likely get you banned immediately, so make any contribution count!
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