Alzheimers

The amyloid-beta peptide forms insoluble clumps in the brains of patients with AD, and may be responsible for neuronal death (the amyloid hypothesis) . There have been many efforts to treat Alzheimers, most based on the dominant amyloid hypotheses. None have worked.

For quite a while, some have suspected that pathogens might be the primary cause of AD, but the idea has never been very popular with the funding agencies, or with most medical researchers. For example, there was some evidence that HSV-I increases Alzheimers risk, but there was a common objection: since healthy oldsters often have HSV-I in the brain, it can’t be the cause. In much the same way, many MDs said that h. pylori couldn’t be the cause of duodenal ulcers or stomach cancer, since it is found in large numbers of healthy people. It is the cause, though. Most people carrying the tuberculosis germ don’t get sick either – but nobody gets tuberculosis without it. In recent decades I think that few MDs say that therefore Mycobacterium tuberculosis is not really the cause of tuberculosis. Why don’t they? – the ‘logic’ is the same. I leave that as an exercise for my readers.

Some disease syndromes almost have to be caused by pathogens – for example, any with a fitness impact (prevalence x fitness reduction) > 2% or so, too big to be caused by mutational pressure. I don’t think that this is the case for AD: it hits so late in life that the fitness impact is minimal. However, that hardly means that it can’t be caused by a pathogen or pathogens – a big fraction of all disease syndromes are, including many that strike in old age. That possibility is always worth checking out, not least because infectious diseases are generally easier to prevent and/or treat.

There is new work that strongly suggests that pathogens are the root cause. It appears that the amyloid is an antimicrobial peptide. amyloid-beta binds to invading microbes and then surrounds and entraps them. ‘When researchers injected Salmonella into mice’s hippocampi, a brain area damaged in Alzheimer’s, A-beta quickly sprang into action. It swarmed the bugs and formed aggregates called fibrils and plaques. “Overnight you see the plaques throughout the hippocampus where the bugs were, and then in each single plaque is a single bacterium,” Tanzi says. ‘

If this new picture turns to to be correct, some combination of fighting & preventing the relevant pathogens, perhaps combined with methods of removing excessive amyloid buildup, would probably be fruitful.

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Bad Teacher

I just read “The Battle For Room 314”, Ed Boland’s account of a year teaching at a NYC high school. Boland had been an admissions officer, done fundraising for nonprofits – but wanted to DO GOOD, and of course go broke in the process.

The dean of the Harvard graduate school of education praises it, as does the former head of the Ford Foundation. So you know it’s a bad book. Sheesh, Boland only taught for a year, and he wasn’t particularly successful. He didn’t have great personal force, couldn’t control the kids, didn’t realize when they were lying to him. Came to hate them. But I didn’t expect to learn anything about educating kids- I wanted to see what page the educrats are on lately, just I have a green chili cheeseburger every ten years or so just to see if they’re still nasty.

Apparently they haven’t learned a thing. Certainly Boland hasn’t, other than than finding out that he likes being paid enough to live on in New York, in a job where people won’t call him a ‘turd burglar’.

He recommends Pre-K and school integration [works in Berkeley, right? no? they must not be liberal enough!] . He thinks poverty is the root of educational failure. He’s so dumb that he talks about the educational magic distilled by Finland and South Korea. The idea that being Finnish or Korean has anything to do with it is beyond his imagination.

What possible observation or event, up to and including Ragnarok, could ever make him come to any other conclusion? He learned nothing, understood nothing, denied everything he saw or experienced.

Sure, we have an intractably low-functioning underclass – two of them now! – but we also have a crazy overclass, and that’s worse. We have a problem.

Posted in Book Reviews, Education | Tagged | 142 Comments

Economists and biology

Naturally, economists know a lot about human biology and evolution, just as civil engineers have to know about the properties of timber, concrete and steel. They have a good grounding in psychometrics, behavioral genetics, and quantitative genetics – how else could they do their job? Populations vary in traits that play key roles in economic activity and growth – in intelligence, asabiya, savings propensity, etc – you have to be aware of that variation, else whole continents would be economic mysteries. In the same way they know that those observed differences are a product of selection – which means economic historians think seriously about psychometric changes over time and their consequences, such as the Industrial Revolution. That kind of analysis helps predict where modern economic institutions can be successfully introduced, and where they cannot.

Yet even Jove nods. Sometimes even tenured professors make serious errors on fairly elementary topics. Like anyone else who has made a mental typo, they welcome polite correction.

Deirdre McCloskey has a new book out: Bourgeois Equality: How Ideas, Not Capital or Institutions, Enriched the World. I’m sure that there are many good things in it. But McCloskey makes a significant error in talking about genetics. “Know also a remarkable likelihood in our future. Begin with the sober scientific fact that sub-Saharan Africa has great genetic diversity, at any rate by the standard of the narrow genetic endowment of the ancestors of the rest of us, the small part of of the race of Homo sapiens that left Mother Africa in dribs and drabs after about 70,000 BCE…. Any gene-influenced activity is therefore going to have more African extremes. The naturally tallest people and the naturally shortest people, for example, are in sub-Saharan Africa. The naturally quickest long-distance runners are in East Africa. The best basketball players descend from West Africans. In other words, below the Sahara the top end of the distribution of human abilities – physical and intellectual and artistic – is unusually thick. …

The upshot? Genetic diversity in a rich Africa will yield a crop of geniuses unprecedented in world history. In a century or so the leading scientists and artists in the world will be black – at any rate if the diversity is as large in gene expression and social relevance as it is in, say, height or running ability. ”

So by this argument that the most cold-tolerant Africans must be more cold-tolerant than Eskimos: but they’re not. The most altitude-tolerant Africans must be more altitude-tolerant than Tibetans – but they’re not. McCloskey is thinking that a turn to free markets will make Africa rich, and that will give educational opportunities to Africans now denied them – but a fair-sized mostly-African population already lives in the United States, a population that is already much more prosperous than sub-Saharan Africans. How are they doing? How many geniuses are they producing?

The whole argument is flawed. Overall genetic variation is mostly in neutral loci. By itself it tells you nothing about any particular trait. Europeans do have less overall genetic variation than sub-Saharan Africans (~20% less), but they show more variation in hair color and eye color than Africans.

Essentially every domesticated species has less genetic variation than its wild progenitor. Dogs have less genetic variation than wolves. So, does this mean that the tallest wolf is taller than any dog? No – the tallest Great Danes are taller than any wolf. The heaviest mastiffs are heavier than any wolf. Chihuahua are the smallest. Greyhounds are faster than wolves (by a little).

Thoroughbred horses have little genetic variation – their effective population size is under 100. Tarpans, the wild ancestor of domesticated horses, are extinct, but there certainly are horse breeds with much more genetic variation than Thoroughbreds. But they’re slower.

What matters is the frequency of alleles that influence a trait, not overall genetic diversity. If, for example, the variants that tend to boost educational achievement (some of which were found in the just-released Nature study) were on average less common in sub-Saharan Africans than in Europeans – says 5% less common – Africans would tend to do less well in school. Like they actually do. Now Africa is a big place, and some groups are genetically quite distinct from others. Bushmen are genetically more distant from the Bantu than the Bantu are from Chinese. Some African populations might have experienced selective pressures that were more (or less) favorable for intelligence than others. Is there evidence, either in test scores or cultural accomplishment (better than any test), that some African populations may have smarts comparable with, or better than, people in Switzerland or Holland or Scotland?

No. There is no such evidence.

How many real geniuses out of African populations – people like Fermat, or Riemann, or Gauss, or Laplace? Newton? Maxwell? Gibbs? None. How many of the top 1000 mathematicians in the 20th century were of sub-Saharan ancestry? One, perhaps?

McCloskey’s prediction of an efflorescence of African genius is based on an incorrect understanding of how quantitative traits work. It’s also in that interesting, ever-popular class of theories that are contradicted by everything that has ever happened in the history of the world.

Posted in Economics, Genetics | 122 Comments

Public intellectuals, pundits, and all that

In principle, public intellectuals should have something interesting to say, ideally not just interesting because ridiculous or incredibly stupid. The ideal P.I. might have a special area of expertise and apply that to current events and questions, or whatever struck his fancy.. He might have a wide range of interests and make connections that others can’t see. He might be smart, or independent minded, or both. It would be nice if he had a decent predictive track record, better than a dart board. He should be stubborn enough to resist currently fashionable errors.

As for ideology, that’s a poor substitute for understanding how things actually work.

In my opinion, elegant prose isn’t very important.

He probably does all this for $25 dollars a day and expenses, mostly gasoline and whiskey. That’s about all he’s going to get, because there’s not much demand for analysts, as opposed to cheerleaders.

If most PIs are schlockmeisters, that’s because of popular demand. Bullshit walks.

I invite nominations: either a P.I. that is actually good-for-something (if you can find one), or give an amusingly damning quote for one of the vast majority of vile drones.

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You don’t need a weatherman

This is very nice, very interesting new paper out by Yair Field, Evan Boyle et al: they present a new method that can detect human adaptation over the past couple of thousand years. And there is some, of course. They found strong signs of selection at lactase and HLA, and in favor of blond hair and blue eyes. This new method (SDS, Singleton Density Score) can also detect signs of polygenic selection, and they found that selection for increased height ‘has driven allele frequency shifts across most of the genome’.

They found evidence for selection acting on other polygenic traits: favoring increased infant head circumference, increased female hip size, and later sexual maturation in women.

You can do a million cool things with this method. Since the effective time scale goes inversely with sample size, you could look at evolution in England over the past 1000 years or the past 500. Differencing, over the period 1-1000 AD. Since you can look at polygenic traits, you can see whether the alleles favoring higher IQs have increased or decreased in frequency over various stretches of time. You can see if Greg Clark’s proposed mechanism really happened. You can (soon) tell if creeping Pinkerization is genetic, or partly genetic.

You could probably find out if the Middle Easterners really have gotten slower, and when it happened.

Looking at IQ alleles, you could not only show whether the Ashkenazi Jews really are biologically smarter but if so, when it happened, which would give you strong hints as to how it happened.

We know that IQ-favoring alleles are going down (slowly) right now (not counting immigration, which of course drastically speeds it up). Soon we will know if this was true while Russia was under the Mongol yoke – we’ll know how smart Periclean Athenians were and when that boost occurred. And so on. And on!

Feel free to mention some of the theories (distilled horseshit, mostly) that are likely to bite the dust, between SDS and aDNA.

“The pace has been so rapid that humans have changed significantly in body and mind over recorded history.”

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Post-Columbian Evolution – Holes

At this point, we have some decent examples of post-Columbian evolution, genetic changes in New World populations after 1492. There is evidence for selection for increased fertility in Quebec, along with increased mutational load due to relaxed selection. Something similar must have occurred in American colonial populations.

I think that the Amish are probably becoming plainer, thru the boiling-off process – which can’t be a common mechanism, because it requires very high fertility, enough to sustain a substantial defection rate.

HbS (sickle-cell) gene frequency has almost certainly decreased significantly among African-Americans – a simple model suggests by about half. There has probably been a decrease in other expensive malaria defenses.

There are a couple of recent papers that touch upon genetic changes that were caused by Old World diseases. Among Mestizos, there’s an excess of European ancestry at 1p36 and 14q32, and an excess of African ancestry at 6p22 (HLA region). Another paper, which looked at contemporary and ancient DNA among an Amerindian population from the northwest coast of North America, found a particular HLA-DQA1 variant went from 100% in pre-Columbian remains to 32% today, a far bigger change that you would see just from admixture. I think we’re talking about smallpox, although not that alone.

In principle, if you had an immune gene that defended against an Old World pathogen that didn’t cross into America, Amerindians would have gradually accumulated nonfunctional variants, just from mutational pressure. the percentage of people with such mutations in any particular immune defense gene would not be very high (not in only 500 generations) but since there are many such genes, the fraction of Amerindians with at least one such hole in their immunological armor might have been significant. Probably this would have been more of a problem in the Caribbean islands, where the Taino seem to have just melted away… Presumably most such holes are gone now in surviving populations, but you might be able to identify them in pre-Columbian DNA.

I see where some Kraut is saying that we now know that human evolution is continuing. I think that’s been an obvious conclusion for almost 160 years.

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the cards fall

People are doing GWAS studies on alleles that influence educational achievement – IQ alleles, more or less – and are finding some. Once you find them, the natural question is how the frequencies of those vary in different populations. Do populations that test low on IQ have fewer plus alleles than those that test high?

This can get complicated, at least if the populations you’re comparing are highly divergent. If they are, the set of education alleles in one pop might be significantly different than the set in the other. Pygmies are like this with height: they share many of the alleles that affect height in Europeans, but also have some of their own. Of course, the most divergent human populations, Pygmies and Bushmen, are few in number and have no significant diasporas.

If all you want to know is the source of population differences, you can easily get around this: look at a mixed population and see how IQ varies with the degree of admixture.

Next question: what would be the implications of various possible results? Suppose that GWAS hits and admixture studies suggest that population ancestry did not matter. Every population is equal in genetic potential for intelligence. That would be a surprise – things sure don’t look that way. It would suggest that a potent and unknown environmental influence(s) was responsible for observed differences. I doubt this outcome a whole lot, but it’s a big universe.

Next possibility: the distribution of IQ alleles predicts what we already see. Those populations that test low have correspondingly low frequencies of plus alleles. Things are the way they look – no real surprises.

Last: things are mostly the way they look, but at least one population does a lot worse (or better) than you would expect from their measured IQ-allele frequencies. I think if you had done this 100 years ago there would have been some anomalies of this sort – populations with serious iodine shortages would have had anomalously low scores. If we hadn’t known about iodine shortages and their consequences, this kind of result would have hinted at it.

Next question: what would the impact of such results be?

For option 1: we would start looking hard for that indumbnifying environmental influence. We would want to be able to turn it off – or on.

Option II and III: Much would be explained. But the results would be almost entirely rejected. How many minds would be changed? Hardly any. You’d have to know a fair amount about genetics to even appreciate the evidence. No matter how sound the result, various bastards will emit a fog of lies about it – not many people would be able to see through that fog, and even fewer would want to. I know of a couple of cases in which people who were disinclined to believe in the results of twin studies came to accept them after GCTA results – extrapolating from that example, results like II or III would change the minds of hundreds of people worldwide.

This doesn’t mean that there would never be any consequences. There would eventually be practical applications of such a result, and the people working those applications would know and understand it.

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