Cystic Fibrosis

A friend of mine once had an encounter with a fairly prominent geneticist* who thought that there was only one clear example of heterozygote advantage in humans – sickle-cell.  Of course that is not the case: we know of a number of genetic malaria defenses that work in similar ways – alpha-thalassemia, beta-thalassemia,  G6PD deficiency, Melanesian ovalocytosis, etc.  Not all such are malaria defenses: cystic fibrosis has some advantage, nature unclear, but it’s not malaria resistance.

CF is mostly a European disease, particularly in northern Europeans and their diaspora. The gene frequency for CFTR mutations is around 2%, mostly one mutation, delta-508. It’s easy to show that CFTR mutations have some sort of heterozygote advantage, although that same fairly prominent geneticist didn’t think this had been established.  Realize that the input of new mutations per generation is insignificant. Without any advantage in carriers , the frequency of mutated CFTR genes should slowly decline, since the mutation used to be lethal in homozygotes and is still very, very unpleasant.  The rarer these mutant alleles get, the slower the decline, since a smaller fraction of them run into each other.

But if you run time backward, the frequency should increase more and more rapidly.  If there was no advantage in carriers, a frequency of 2% today implies a frequency of 50% 1200 years ago. Takes a code of several lines to show this!

The scenario is ridiculous.  This would require a super-tight bottleneck, in which Europe was first wiped out and then refounded by a population of 2 about 1200 years ago, but that never happened – although it might seem reasonable to some young geneticists.  When John Hawks and I talked about the genetic impact of the big population expansion in the Neolithic, which greatly increased effective population size, I remember a person like that saying that we didn’t really know that there was a large ( >> 10,000) population in Pharaonic Egypt. I guess he thought that Paul Bunyan built the Pyramids.  By the way, another very prominent geneticist, upon hearing our idea,  asked “Why would there be more mutations with a larger population?”  I got a million of ‘em!

I think I don’t know what the advantage was.  This puts me ahead of many people, including Wikipedia, because they think that it’s a cholera defense.  It may well protect against cholera in carriers, but that’s not why it became common, because cholera was never seen in any part of Europe until 1817.  Better to know nothing than to know what ain’t so. The people who proposed that in Nature weren’t stupid – they had evidence that it protected against cholera in vitro.  They were merely deeply ignorant of history. Which is stupid.

* although I have never quite been able to figure out what he is famous for.  I have another,  much funnier anecdote about him, by the way.

 

 

 

 

 

 

 

 

 

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At Least Erroneous in Faith

A large collection of prominent geneticists has published a group letter to the New York Times Book Review endorsing a negative review of Nicholas Wade’s “A Troublesome Inheritance: Genes, Race, and Human History.” They speak of “Wade’s misappropriation of research from our field…” The list of signers includes an impressive group of geneticists and others, claiming special expertise in their field. This deserves some thoughtful evaluation.

The last half century of population genetics has been more or less dominated by neutralism, a model of genetic change that postulated, in its strong and common form, that population differences are a passive reflection of histories of gene flow and genetic drift. In human genetics, especially, selection has been of little interest. The idea of group differences being products of natural selection is abhorrent to many. The reaction to recent models of selection in humans recalls a common quotation whose origin is murky but is often attributed to a Victorian lady, reacting to news of Darwin’s theory of evolution by natural selection: “My dear, I trust that it is not true; but if it is, let us pray that it may not become widely known.”

The authors and signatories of the letter number 144. Surely they must speak with authority on this matter of Wade’s incorrect thought about their field? In the last few years evolution by natural selection has been appearing in the literature in various ways. There is a sea change coming in evolutionary biology. My immediate associations are with Brian Charlesworth, Francisco Ayala, Michael Lynch, Russell Lande, Michael Rose, Steven Frank, H. Allen Orr, Peter Visscher, Nick Barton, and Bernard Crespi come to mind. I am no expert in this domain, and I mean no slight to folks who didn’t immediately jump into my head, in particular the lot who write about evolutionary medicine. Interesting that none of these are signatories of the letter. H. Allen Orr in particular is curiously absent since he wrote the only sensible negative review of Wade’s book I have seen.

There may be an interesting background to this inquisition. I suggest starting with a reread of Geoffrey Miller’s editorial in the Economist in 2009. He discusses the hype and high hopes of medical breakthroughs from the Human Genome project, the collapse of that hope (continuing since the 2009 article) and the rich harvest of knowledge of human history and human evolution that the project has produced. Some of this harvest is unwelcome, especially because it led to the resurgence of the study of evolution by natural selection. Does this new direction threaten the revenue stream from agencies like the Wellcome trust and NIH? I remember a conversation with a colleague several years ago about something I had written. “Of course you are right,” he said, “but you know you are peeing in the swimming pool.”

I am especially curious about how Gregory Clark has managed to escape the wrath of the righteous guardians of “our field.” His brilliant economic history of the UK from medieval times up to 1800 is the most inflammatory book I have read in years. He proposes that Darwinian natural selection essentially bred a new version of humans, a version adapted to a stable society with courts and contracts, low time preference, aversion to violence, and middle class values. I have spent some time around economists and I hear none of them whining about Clark’s book, calling him a racist, and all the stuff a geneticist would get. How does he do it?

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Powerful Stuff

I was thinking again about that Denisovan allele of EPAS1 that plays a big role in Tibetan altitude adaptation.  Considering modern humans, it has only been found in Tibetans (high frequency) and in the Chinese (couple of percent).  The preferred model  in the paper is that it entered the common ancestors of Tibetans and Han, rising to high frequency among the Tibetans because of its advantage.  I doubt this: the authors are clinging to a claim of a recent split in a previous publication of theirs – but the idea that the modern Tibetans are a fusion of a Han-like population with a long-established  group of  Tibetan hunter-gatherers seems more likely to me. So the few copies of the high-altitude EPAS1 allele among the Chinese are probably a result of recent gene flow, possibly from the Tibetan empire (618-841) that controlled parts of China, or from ethnic Tibetans identifying as Chinese.

This allele has some pretty powerful effects on the hypoxia response, which is there for a reason.  The usual evolutionary rule is that change is bad: even though the Denisovan allele confers a big advantage at high altitude, the odds are that it is disadvantageous at low altitude.  This would explain why it is rare in China and apparently unknown in Japan. This would also explain why it never made it to the Andes –  even though there might have been a copy or two in the long-ago East Asian ancestors of the Amerindians, who have a bit of Denisovan admixture admixture  (at least, I think they do – interesting if that isn’t the case) , it would most likely have been lost in Beringia. Along the same lines,  altitude adaptations probably never managed to travel from Ethiopia to Tibet, which is why they have different approaches to altitude adaptation today.

It is therefore no surprise that this EPAS1 allele does not exist in Melanesians, even though they have 25 times as much Denisovan ancestry as mainland East Asians.

At low altitude, it was likely disadvantageous in Denisovans as well.  Probably it was only found in Denisovans who lived at fairly high altitude, or that had recently migrated from a high-altitude area.  Which suggests that Denisovans in Denisova Cave had recent ancestors living at high altitude.

The introgression was most likely to be successful in an area where it conferred advantage, which suggest that admixture probably occurred  in or near the Tibetan plateau. When you think about it,  anatomically modern humans would have more trouble than average displacing archaics from areas for which they had special adaptations not possessed by AMH – so Denisovans may have lingered longer in Tibet and neighboring high-altitude areas, affording greater opportunities for gene flow.  This was especially the case when the local environmental challenge could not be solved by ancient technology – you can deal with cold through better clothes, but people weren’t quite up to oxygen masks 40,000 years ago.

As I have said before, Denisovans might have persisted longer in Sundaland because of resistance to local infectious disease – same principle.

 

 

 

 

 

Posted in Altitude adaptations, Denisovans, Genetics | 18 Comments

Biology and Human Capital

I don’t pretend to be an economist.  If I had been, I’m sure that I too would have been unable to see the big real-estate bubble back in 2008, even though crazed Californians  were flipping houses all around my neighborhood.

Nevertheless, I am trying to think useful thoughts about the biological aspects of human capital. Wiki says that human capital is ” the stock of competencies, knowledge, habits, social and personality attributes, including creativity, cognitive abilities, embodied in the ability to perform labor so as to produce economic value. ” I’m down with that, although I’d choose to to take a separate look at creativity.

That stuff is all learned – babies don’t know much – but people vary in how easily they learn things. There are also cognitive ceilings,  such that you can’t really understand a subject beyond a certain complexity.  This can bite pretty hard when you run into it, as Luis Alvarez once said: ” The world of mathematics and theoretical physics is hierarchical. That was my first exposure to it. There’s a limit beyond which one cannot progress. The differences between the limiting abilities of those on successively higher steps of the pyramid are enormous. I have not seen described anywhere the shock a talented man experiences when he finds, late in his academic life, that there are others enormously more talented than he. I have personally seen more tears shed by grown men and women over this discovery than I would have believed possible. Most of those men and women shift to fields where they can compete on more equal terms. “

Or perhaps you could understand those things, but it would take more time than you have (say longer than a human lifetime) or more energy and dedication than you have.  I would guess that there is also a practical limit on how many things you can know  – because of time, if nothing else. That too must vary between individuals. John von Neumann absorbed info pretty easily – a professor of Byzantine history, at one of his Princeton parties, was dismayed to find that  John knew more about the subject than he did.

You might compare the human capital situation to soil fertility.  Some people are cheaper to educate than others (Ramanujan!), and the practical limit of education is not the same for everyone. An observational fact, not something that absolutely had to be the case, is that the payoff for educational investment plateaus:  we have a lot more ways of spending on education than we did in 1940, but the grandkids of people who took the Iowa Basic Tests in 1940 score about the same as the oldsters did.  Spending on education is like pushing a rope: past a fairly low point, nobody knows how to further improve things by spending more money. Although, to be fair,  the universe of proposed improvement methods is a narrow one.  I’ve never even heard an educationist suggest caffeinating the hell out of students – certainly worth trying.

At the upper end of the IQ distribution, people can learn things rapidly. High-school freshmen in in the Study of Mathematically Precocious Youth (SMPY), who had tested in the top one-hundredth of one percent, managed to get a median score of 727 out of 800 on an AP Biology exam (95th  percentile) after an intensive three-week course.  Of course, to be fair, they averaged 52nd percentile before they even took it, even though they had not previously studied biology.

That’s an extreme example, of course, but it shows how far up is in this business.

On the other end of the spectrum, there seem to be plenty of kids who just don’t get algebra II.   By which I mean that they can’t get algebra II:   many suggest getting rid of the NEA, or supplying them with sufficiently magical teachers, or some other currently fashionable education nostrum,  just has to work.

It doesn’t have to work.

Even if you came up with a scheme that worked – which nobody has – it would have to be practical, affordable, and nontoxic, which rules out many possibilities.

Moreover, the fraction of kids that don’t get algebra II varies a lot between populations.  Generally, such racial /ethnic ‘gaps’ seem to bother people a lot more than randomly-distributed incompetence, of which we also have plenty.  Note: that SMPY sample was about half Ashkenazi Jewish, although for some reason they never seem to have published anything about that.

If economists absorbed the results of psychometrics and genetics,  they would have a reasonable start on the biological influences on human capital.  I say this realizing that other personality factors matter, not just intelligence – but A. we don’t have good measures and B. intelligence is genuinely important.  If Brad Delong did this, he would not find low per-capita GDP in Kenya such a mystery, or economic success in South Korea.  But he won’t, of course. There are more important things than figuring stuff out.

If economists took those results into account, they’d be mighty skeptical of the current enthusiasm for Pre-K.

In thinking of the long-run, they’d have to think about heritability and natural selection, which they sure don’t now. Considering those issues, it’s pretty obvious that what we now consider an efficient way of running an economy has disastrous long-term consequences for human capital formation.

 

 

 

 

 

 

 

 

 

Posted in Economics, Education | 192 Comments

Washukanni

Mitanni, controlling northern Syria and southeastern Anatolia, was a major player in the Bronze Age Near East from 1500 BC-1300 BC.  They contended and negotiated with the Hittites and the Egyptian New Kingdom.

Most of the population seems to have spoken Hurrian, but there are traces of something very different in their ruling class.  We have preserved diplomatic correspondence (cuneiform tablets last!)  showing that the rulers of Mitanni swore by Mitra, Varuna, Indra, and Nasatya.  There are other hints: names of the ruling class often make sense in Sanskrit.  Kikkuli of Mitanni’s horse conditioning manual has some Indo-Aryan words (aika, tera, panza, satta). Etc.  The semi-educated guess is that Indo-Aryans, as early charioteers, were hired by Mitanni as mercenaries and eventually grabbed the reins of power.   After, of course, making a wrong turn at Albuquerque: North Syria is quite a ways from the known stomping grounds of the Indo-Aryans.

There’s likely an interesting story here, but we are missing almost all of it, because we have never found Washukanni, the Mitanni capital. If we did, we’d probably find lots of cuneiform tablets – as we have other capital cities of that era, such as Boğazköy.

Washukanni was probably somewhere in the Khabur triangle.  Which brings me to the present, and possible near future: if we end up occupying that area, it’d be nice if we could manage a little digging on the side.  We just need to start embedding archaeologists into the infantry.

 

 

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Secondary Crops

There are weeds that gradually came to resemble the crop they infested.  When they were recognizably different  from the crop species, people pulled them up or separated out their seeds – automatically selecting for weeds that loo0ked more and more like the original crop.   Some of  the traits acquired are those we actually desire in a crop plant, such as larger seeds that don’t drop off spontaneously – and so in some cases, a weed became a  new crop.

Rye probably started out a a weed in wheat and barley fields.  It was originally a perennial, but that didn’t work very well in cultivated fields, so it evolved into an annual, like wheat and barley.  It  was hardier than wheat, and tolerated poorer soils, so it eventually became the main crop east of the Rhine and north of Hungary.

Oats has a similar origin: it does best in areas with cool, wet summers, like Scotland.

It seems to me that there may be some social parallels: bandits turning into governments, alchemists into chemists, Galenic doctors into almost-scientific medicine.

 

 

 

 

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501 (c)(3) : The Adventure Begins

The Dark Lords of the IRS have proclaimed that West Hunter Incorporated has Federal tax-exempt status. Contributions, including various forms of real property,  are deductible.  For details, write gcochran9@comcast.net.

West Hunter’s purpose is the advancement of education and science in anthropology and evolution.  That means this blog, scientific and popular articles, books, talks, and research projects.  Depending on resources, possible projects might include a search for  effective nootropics (possibly inspired by some of the Ashkenazi mutations),  cloning  a super-Neanderthal, or breeding the Kwisatz Haderach.

Robert Heinlein, in Methuselah’s Children, imagined the Howard Foundation.  Founded by Ira Howard, who made a pile in the California Gold Rush but died young (of old age!) and childless,  the foundation bribed people with unusually long-lived ancestors into marrying people with similar backgrounds, thus selectively breeding for longevity. This was written in 1941, when many people still knew that such things were possible.

You can imagine a similar foundation that breeds for intelligence: Cyril Kornbluth did, as background for The Marching Morons.  But today, there’s no such thing. Any attempt would be denounced, even if utterly non-coercive and completely successful.

Nobody’s thinking about the long run, the big issues.  Well, hardly anybody.

 

 

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