Growing knowledge on the margins

Michelle Meyer and Chris Chabris have a long piece in Slate, Why Psychologists’ Food Fight Matters, which covers the argument about replication within psychology. Many readers may have followed the controversy closely, but if you have not then I highly recommend the piece. As Meyer and Chabris suggest this is a general problem in much of science. Arguably it is even more of a problem in biomedical science, since the efficacy (or lack thereof) of drugs and treatments is a more short term life and death matter. But obviously social science is not irrelevant to this world; results can have highly fraught normative consequences.

The general problem is that the ultimate aim of science is to model the world through a process of discovery of robust regularities and then refinement of those general principles. To make an analogy with economic growth theory, the normal workaday science is like classical growth in a Smithian framework. You have parameters which are eventually are maximized (e.g., land), as our knowledge reaches a saturating point with the principles we have at hand. The way to fame, and a critical aspect of science, is what is often termed a “paradigm shift,” which is analogous to the invention of a new technology which changes the fundamental parameters of the game in terms of what seems possible. People find entrepreneurs much more interesting than the CEO of a mature corporation. The latter are fundamentally more like bureaucrats than entrepreneurs, though some can construct a different life narrative. But corporations which execute economies of scale and result in gains in marginal efficiency are a critical part of the ecosystem. Similarly, the corrective and incremental aspects of science are just as important in the grand picture as revolutionary theories and results. But glory goes to the latter.

Decency on the internet, 20 years on

Recently I was curious about what people were saying about the internet in 1994. I stumbled upon this article in The New York Times, Smut Ban Backed for Computer Net. Even the title strikes me as quaint. This seems to be describing an early version of the Communication Decency Act of 1996. Signed by Bill Clinton and unanimously overturned by the Supreme Court. From the article:

The measure, attached without any debate to a sweeping proposal to overhaul the nation’s communication laws, would levy fines as high as $100,000 and prison terms up to two years on anyone who transmits material that is “obscene, lewd, lascivious, filthy or indecent.”

No one disputes that sex is abundant on the Internet, where magazines like Playboy offer nude pictures at no cost and electronic bulletin boards share information on a wide variety of practices, from masochism to French kissing.

For instance, by clicking an electronic mouse on the Playboy menu, a person can summon up color pictures of the latest Playboy model. Playboy, in a provocative move to enter the age of high technology, is asking for women to apply for a future portfolio called “Women of the Internet.”

Much more explicit fare, in text and pictures, can be found in other locations. One site on the World Wide Web, called “For Your Eyes Only,” offers the likes of the Leather and Fetish Community Outreach and quick access to on-line forums devoted to bondage, domination, submission and masochism.

When Europa was admixed

Raptus_EuropaeI’ve mentioned the preprint Ancient human genomes suggest three ancestral populations for present-day Europeans several times, but I thought that I would highlight that there has been a substantial revision as of April 5th. One section I think points to possible future results, and where we are now. The authors conclude (before the methods): Three questions seem particularly important to address in follow-up work. Where did the EEF obtain their WHG ancestry? Southeastern Europe is a candidate as it lies along the path from Anatolia into central Europe. When and where the ancestors of present-day Europeans first acquire their ANE ancestry? Based on discontinuity in mtDNA haplogroup frequencies, this may have occurred ~5,500-4,000 years ago in Central Europe. When and where did Basal Eurasians mix into the ancestors of the EEF? An important aim for future work should be to collect DNA from additional ancient samples to illuminate these transformations As is clear from their results to a first approximation to be genetically European entails ~20 on the order of 10 percent ANE ancestry. If the admixture in most of Europe dates to 5,500 to 4,000 years ago, then it is possible that the basic historical framework which serves as the backdrop for the Epic of Gilgamesh was contemporaneous with the emergence of populations which we would recognize as European! I am rather doubtful as to the power of ancient myths rooted in the Bronze Age to give us deep insights about prehistory, mostly because the myths themselves are often sprawling enough that they can be “fit” to a host of diverse scenarios. But, it does suggest that it is possible that Greek myths which date back to the Bronze Age may actually be somewhat informative, even if by chance, of the origins of the peoples and places of antiquity.

We are all relatively recently admixed (OK, most)

Racially admixed
Racially admixed

In the comments below in regards to mixed-race children:

“Designer baby”? How about “genetic experiment”? Like sitting all day long, eating lots of sugar, etc., mixed race offspring are biological experiments we are doing on ourselves that very seldom happened among our ancestors in the environments of evolution. Ideological certainty notwithstanding, we don’t know what most of the biological consequences, good or bad, for mixed-race descendants are going to be.

On the one hand there is some truth in this is, insofar as contact between populations which are very genetically divergent was likely to be a rare event in the past. That is because even minimal gene flow between populations can homogenize between population genetic differences (population genetic theory usually gives 1 migrant per generation). Sustained contact between populations genetically and physically different to a magnitude which we would term racial probably required very specific events, such as trans-continental migrations, or the opening of virgin land due to deglaciation and demographic expansion from differing directions.

But, there are two caveats, a general and a specific. A general caveat is that those periods of contact were very important. This is trivially obvious when you consider the expansion of a recently African derived population over Eurasia and Oceania ~50,000 years ago, replacing earlier Homo lineages in less than 10,000 years. But there is a second critical point which has started to become evident over the past few years, and that is that it seems likely that the majority of populations extant today are the outcome of admixture events between rather isolated lineages which were genetically and physically distinct. I’ve posted on this before in a broad sense. But for Dr. Calvin Greene, and I suspect the reader below, this is probably the paper of relevance in terms of what they care about: Ancient human genomes suggest three ancestral populations for present-day Europeans. In short most of the world’s “races” are the products of admixture events in the range of 5,000 to 10,000 years ago.

Note: I use the image of Vendela Krisebom because she is the product of ancient and recent admixture.

Why siblings can produce offspring with each other

Parents may have been siblings
Parents may have been siblings
Last year I mentioned in passing accounts of the “Colt” family in Australia. Though the press has sensationalized them as an “incest cult,” it does seem that many of the individuals of this family are the products of sexual relations between first degree relatives (e.g., sibling or parent-child). I noted that of the children placed in foster care the one who is known to likely have been the product of out-breeding was the one who quickly began to flourish. In contrast many of the other children exhibited a variety of illnesses which likely had a genetic disposition. With all that said, please note that these first degree relatives could indeed produce offspring. This should give us a general sense that the deleterious recessives which presumably will be unmasked at high frequencies in these cases can’t be that numerous within the genome of a given individual, or the fertility of first degree crosses would be far lower.

Though there has been earlier work in this area a new preprint on arXiv, An estimate of the average number of recessive lethal mutations carried by humans, attempts to infer the average load per person using an incredibly extensive Hutterite pedigree. In the results they infer that there is fewer than 1 deleterious lethal per person in the human population. They admit with extensive caveat that this is likely a low bound, but it is probably in the right range (e.g., another result gives a figure greater by a factor of two). With such a low frequency it isn’t implausible that two individuals would lack deleterious lethal alleles altogether. One result which surprised me was the relatively low power of selection to purge genetic load even across many generations of inbreeding (something that you see most powerfully in selfing plant lineages). Of course just because someone lacks lethal mutations does not imply that they lack all alleles which express in recessive phenotypes and are deleterious. Additionally, heterozygote masking of the recessive phenotype is often incomplete due to partial dominance (at least in Drosophila). So inbreeding of near kin can still result in very serious pathologies, even if they don’t result in early mortality.

Mixed-race babies are ‘designer babies’?

Engineered for cuteness
Engineered for cuteness
Apparently the only fertility clinic in Calgary, Canada, a city of 1 million, won’t countenance the conception of mixed-race children. Here are the details:

Calgary’s only fertility centre, which has made headlines for requiring that patients receive only sperm from donors of the same ethnicity, is a medically respected clinic but one with conservative views.

The private clinic, known as the Regional Fertility Program, got wide attention last week after a Caucasian female patient complained that she had been told she could only get sperm from white donors.

She said that unlike other clinics, the Calgary clinic will not take patients who deal with surrogacy agencies. The clinic also long resisted taking gay patients, she added.

“I deal with a lot of fertility clinics. They are certainly the most conservative. That is their choice to a certain extent as long as it is a private service.”

Officials at the clinic didn’t reply to an interview request Monday, but administrative director Calvin Greene told the Calgary Herald that it is better to raise children who ressemble their parents.

“A child of an ethnic background should have the ability to be able to identify with their ethnic roots,” Dr. Greene said.

The patient who went public with her complaint about the clinic’s policy is a single woman who is considering in-vitro fertilization.

“I’m not sure that we should be creating rainbow families just because some single woman decides that that’s what she wants,” Dr. Greene said about her.

Dr. Greene said that his stance is consistent with the spirit of Ottawa’s Assisted Human Reproduction Act, which discourages doctors from helping create “designer babies.”

First, I have to admit that this isn’t that strange when you hear people always talk about ‘multi-cultural’ families when they really mean multi-racial. I’m in a multi-racial family personally, not a multi-cultural one. This is a slip of the tongue in our colloquial speech that has always made me uncomfortable. People aren’t born with their culture, they’re inculcated with it. It’s the majority sentiment for people to be more comfortable with people who look like themselves, but there’s no reason to make this a metaphysical or ontological issue, unless you are a racialist of some sort.

Second, this is a private clinic, so depending on how funds are allocated (Canada having literally socialized medicine) that’s their prerogative. But reading between the lines though it seems that assisted reproduction in Canada is not as widely distributed in availability as in the United States. As is clear from the above passage it isn’t simply people who don’t share this clinic’s views on race (or race-mixing) who might have problems. There have been many criticisms of the relatively lax oversight of assisted reproduction in the United States, but this shows the other side. By making it common and widely available people whose preferences don’t align with the attitudes of a given clinic have a wide array of choices. Rather than getting offended and being angry temporarily we need to be on guard against those who would interfere in one of the most private and important decisions a person might ever make.

Update: The policy isn’t on their website anymore. Show some courage! All across the internet people are Offended and asserting that this is NOT OK. The major issue I have with this is that most people prefer people of their own race in the mating game, and, most people select sperm donors who do reflect their own racial background. This isn’t just the retrograde, but the majority sentiment. The issue is that people don’t think that this should be imposed as a norm anymore. Obviously when you become a licensed professional you have particular obligations. But rather than enforcing the most up-to-date understanding of social policies to the most picayune details I believe that the best way to go is making these sorts of services widely available from an array of providers. That way there’s a minimum of imposition.

Update: The clinic claims it discontinued the policy a year ago. The website had not been updated, and the doctor who gave the quote about “Rainbow Families” was speaking in his personal capacity.

Three continents come together in Cuba

Eva Mendes, "Eva Mendès 66ème Festival de Venise (Mostra)" by nicolas genin - originally posted to Flickr as Eva Mendès 66ème Festival de Venise (Mostra). Licensed under CC BY-SA 2.0 via Wikimedia Commons.
Eva Mendes, “Eva Mendès 66ème Festival de Venise (Mostra)” by nicolas genin – originally posted to Flickr as Eva Mendès 66ème Festival de Venise (Mostra). Licensed under CC BY-SA 2.0 via Wikimedia Commons.

One of the most interesting aspects of human genomics over the past 10 years or so to me is that it has uncovered that in the Caribbean the Amerindian population was not totally exterminated, but rather its genetic legacy has persisted via females. The most sophisticated paper in this area is probably Reconstructing the Population Genetic History of the Caribbean. But there are other papers, and today PLOS Genetics came out with Cuba: Exploring the History of Admixture and the Genetic Basis of Pigmentation Using Autosomal and Uniparental Markers. The downside of this paper is that they use “Ancestrally Informative Markers,” rather than dense SNPs. This limits what you can do (though the authors do look at specific SNPs of functional significance). More specifically 128 AIMs. But the upside of this paper is its massive sample size. 1,019 individuals from all provinces of Cuba.

There are many results in the paper, but I would like to highlight one aspect: the 55% of sample respondents that identified as “white” almost all had non-European ancestry. This goes back to a discussion I had with readers years back about admixture among white Cubans, who are the dominant community in the United States. Like most Latin American “whites,” and unlike American “whites,” the non-European ancestry in Cubans does seem non-trivial from what I’ve seen. These results would seem to confirm that. The main questions that come to mind in regards to skepticism would be how much of this is due to admixture in Europe (e.g., Spain and the Canaries), and, how precise are these AIMs? I’d have liked to see the AIMs on a European population. Look at the fraction of African and Amerindian ancestry I suspect that these results are valid, but I’m not sure how noisy the inferences are.

The mtDNA and Y results are harder to quibble with, and they’re striking. “The analysis of mtSNPs indicates that 34.5% of the mtDNA haplotypes have Native American ancestry, 38.8% African ancestry, and 26.7% Eurasian ancestry.” And for the Y: “Most of the haplotypes are of Eurasian ancestry (81.8%), while 17.7% have African ancestry and only two haplotypes are of Native American ancestry.” This is in line with what you see in the rest of Latin America, but the disjunction is still sobering.

Citation: Marcheco-Teruel B, Parra EJ, Fuentes-Smith E, Salas A, Buttenschøn HN, et al. (2014) Cuba: Exploring the History of Admixture and the Genetic Basis of Pigmentation Using Autosomal and Uniparental Markers. PLoS Genet 10(7): e1004488. doi:10.1371/journal.pgen.1004488

Mind the residual!

a_man_of_sizeOne of the important things to remember in life is that even after accounting for “all factors” often you can’t account for much. By “life” I do not mean mathematics or physics, two domains where this does not hold. In biology by contrast this is something you always have to keep in mind. I like to say that genes matter, but they’re not everything. As a specific illustration, an old friend with a background in elegans research observed that even with isogenic lines with controlled environmental conditions you can only account for half the variation in some traits which are clearly biologically caused. In plainer language, if you have inbred genetically homogeneous organisms in uniform conditions you’re still going to have variation because of randomness. A side effect of the mysterious aspect of all this is that the “environmental” component is often totally outside of our control (at least conscious).

I’ve been thinking a little about this because of the divergent developmental paths of my two children. To a good approximation my son is in the interval of one to two standard deviations above the norm in size, while my daughter is one to two standard deviations below.* To our knowledge there hasn’t been any difference in environmental input, and they began life at about the same weight and length. The divergence began within the first few weeks, as he gained an inordinate amount of weight in his first week. Height is a quantitative trait which looks to be about 80 to 90 percent heritable in Western societies. That means that 80 to 90 percent of the variation within the population can be accounted for in variation of genes in the population. I suspect many people would be surprised by such a wide range in size in offspring despite the high heritability of height, but correlation in height for full siblings is only ~0.50.

Let’s assume that our offspring end up one standard deviation above and below the norm in adult.** What’s the probability of this, assuming these two particular parents? Well, the mid-parent expected value is ~1/3 above the mean. Therefore my son is ~2/3 standard deviation units above expectation, and my daughter is ~1 & 1/3 below. The probability that my son would be as long as he is is about ~25% (i.e., 25 percent chance his particular length, or longer). For my daughter’s height I get 9%. So the chance of having two children which are this far apart in size is about 2%, 1 out of 50. It’s not common, but, it’s not exactly vanishingly rare.

This sort of insight can be extrapolated to any quantitative trait. Imagine for example that a couple has a tall, intelligent, and good looking offspring. The chance of replicating this is not particularly good.*** It is the nature of things for there to be diversity within families. From what I know about height and intelligence the variation within families for quantitative traits is probably about the same as the variation within the population (in standard deviation units).  Of course the average within families may differ a great deal from the average within the population, but  that is a different issue altogether.****

* Averaging over time, and also taking into account imprecision at this age in measurement.

** I have yet to find a correlation statistic for predicting infant/toddler height to adulthood. Please tell if you know. More precisely the “double from height at age two” is an expected value. I want the error.

*** Yes, I’m aware of the genetic correlation between these traits, but it’s not incredibly high.

**** I know of a family where one brother became a Rhodes Scholar, while the other went on to graduate from a moderately selective private college. In another family the second brother wouldn’t be too shabby, but he was labelled the “dumb one.”

The cultural wasteland sans intellectual propery

Aeneas Flees Burning Troy
Aeneas Flees Burning Troy
I found the old edition of The New Republic under Marty Peretz a bit too smug, not being as heterodox or unpredictable as it fancied itself. But the new Chris Hughes owned version does make me miss the old TNR sometimes. It’s now predictably liberal, a more high-toned and moderate sibling of The Nation. Not that there’s anything wrong with that, but that space is more consumer driven (i.e., people want to confirm their priors), and it would have been nice if a billionaire like Hughes would be more open to looking at viewpoints in a genuinely original manner. That being said the Hughes owned TNR has expanded their cultural coverage in interesting directions. But sometimes the results are uneven. This piece cross-posted from The New Statesman, Bored With Hollywood Blockbusters? Blame Digital Piracy, seems to be very close to trolling.

The author makes some valid points, in particular the ad hoc nature of many arguments for the principled usage of file sharing. But the headline itself is grossly misleading. The domination of comic themed blockbusters at the movies, with thin plots and zero characterization, derives from many factors. The international consumer market (read: China) in media is obviously the biggest driver of the change. The rise of the lowest common denominator popcorn film is a function of the expanding nature of the audience which Hollywood feels it needs to satisfy. Headline aside, there is also the argument that free music downloads is driving musicians into penury. My question to this is when has the modal musician ever not been economically marginal? Back in the days of CDs some musicians became very wealthy, but it was still a winner-take-all game. Probably more hard hit by the collapse of revenues in the music industry has been the ancillary employment around the music itself. And these arguments in favor of intellectual property always strike me as peculiar because they often don’t grapple with the historical reality that intellectual property rights have been absent for almost the whole of human history, and somehow humans did produce works of great artistry.

To be fair the author has a whole book, Freeloading, in which he expounds on this topic. There might be more there than can be distilled into a magazine piece. But let’s take the author’s argument at face value, that creativity will be abolished by the lack of enforcement of intellectual property.* Is that disastrous in all domains? It looks as if piracy has resulted in a recession of the porn industry. What if all porn production ceased today. Wouldn’t the “back catalog” suffice? There are only so many things you can do in porn, so a lot of the new production must be driven by “enthusiasts” who are looking for the next new star. But is this the standard consumer of porn? I suspect most individuals are not particular discerning in what they whack off to, certain preconditions being met. Similarly, in music we have Beethoven, Ella Fitzgerald, the Beatles, Nirvana, and N.W.A. Is something in the future going to be that much better? In fiction there is also an enormous back catalog. The vast majority of Victorian fiction is out of print, and there may even be no extant copies. What a waste. But how many ways can you tell a story? You get the picture.

My point with this thought experiment is to suggest that human creativity exists to fulfill particular urges, on the part of both producers and consumers, and any particular institutional scaffold around the process of production and consumption is a historical contingency. Going back to the headline of the TNR piece, the early 1980s saw the collapse of “New Hollywood” for reasons of capitalism. The rise of superhero films in the teens of the 21st century is simply the next stage in this process. I suspect in the future if you want to produce novel high concept art you are unlikely to be able to do so via the conventional capitalist means of production. And why would we be surprised by that? The production of high art in the past was often underwritten by elites, from Virgil’s Aenied to Beethoven’s symphonies. As for low mass art, that will always have an audience, so capitalism will suffice.

* A minor sidenote not acknowledged in this piece is that the heyday of file sharing in the 2000s is in abatement due to the emergence of services such as Netflix and Spotify, which can provide streaming for a modest fee. Of course the fees on a per unit basis are not particular high, and so may have the same effect.