The future will be genetically engineered


If the film Rise of the Planet of the Apes had come out a few years later I believe there would have been mention of CRISPR. Sometimes science leads to technology, and other times technology aids in science. On occasion the two are one in the same.

The plot I made above shows that in the first five years of the second decade of the 20th century CRISPR went from being an obscure aspect of bacterial genetics to ubiquitous. Friends who had been utilizing “advanced” genetic engineering methods such as TALENS and zinc fingers switched overnight to a CRISPR/Cas9 framework.

As I’ve said before the 2010s are the decade when “reading” the genome becomes normal. We really don’t know what the CRISPR/Cas9 technology is capable of. It’s early years yet. With that, First Human Embryos Edited in U.S.. Technically they’re single celled zygotes. The science itself is not astounding. Rather, it is that the human rubicon has been passed in the United States. As indicated in the article there has been some jealousy about what the Chinese have been able to do because of a different cultural and regulatory framework.

There are those calling for a moratorium on this work (on humans). I’m not in favor or opposed. Rather, my question is simple: if CRISPR/Cas9 makes genetic engineering cheap, easy, and effective, how exactly are we going to enforce a world-wide moratorium? A Butlerian Jihad?

Note: I know that people are freaking about humans + genetic engineering. But most geneticists I know are more excited about the prospects of non-human work, since human clinical trials are going to be way in the future. Over 20 years since Dolly it’s notable to me that no human has been cloned from adult somatic cells yet.

Origin of modern humanity pushed back 260,000 years BP (?)


The above figure is from a preprint, Ancient genomes from southern Africa pushes modern human divergence beyond 260,000 years ago. The title and abstract are pretty clear:

Southern Africa is consistently placed as one of the potential regions for the evolution of Homo sapiens. To examine the region’s human prehistory prior to the arrival of migrants from East and West Africa or Eurasia in the last 1,700 years, we generated and analyzed genome sequence data from seven ancient individuals from KwaZulu-Natal, South Africa. Three Stone Age hunter-gatherers date to ~2,000 years ago, and we show that they were related to current-day southern San groups such as the Karretjie People. Four Iron Age farmers (300-500 years old) have genetic signatures similar to present day Bantu-speakers. The genome sequence (13x coverage) of a juvenile boy from Ballito Bay, who lived ~2,000 years ago, demonstrates that southern African Stone Age hunter-gatherers were not impacted by recent admixture; however, we estimate that all modern-day Khoekhoe and San groups have been influenced by 9-22% genetic admixture from East African/Eurasian pastoralist groups arriving >1,000 years ago, including the Ju|’hoansi San, previously thought to have very low levels of admixture. Using traditional and new approaches, we estimate the population divergence time between the Ballito Bay boy and other groups to beyond 260,000 years ago. These estimates dramatically increases the deepest divergence amongst modern humans, coincide with the onset of the Middle Stone Age in sub-Saharan Africa, and coincide with anatomical developments of archaic humans into modern humans as represented in the local fossil record. Cumulatively, cross-disciplinary records increasingly point to southern Africa as a potential (not necessarily exclusive) ‘hot spot’ for the evolution of our species.

These results in the outlines were actually presented at a conference. I saw it on Twitter and don’t remember which conference anymore. But this is not entirely surprising.

First, much respect to Mattias Jakobsson’s group for breaking through the Reich-Willerslev duopoly. Hopefully this presages some democratization of the ancient DNA field as expenses are going down.

Second, notice how in most cases ancient DNA shows that modern reference populations turn out to be admixed. This was the problem with much of Eurasia, and why using modern genetic variation to make inferences about the past totally failed.

I am entirely convinced that the genome from Ballito Bay dating to ~2,000 years does not carry the Eurasian inflected East African admixture. The Mota genome implies that Eurasian admixture did not come to eastern Africa much before 4,500 years ago. There needs to be a much deeper big picture analysis of the archaeology of Africa and the genetic information we have to get a sense of what happened back then…but, it seems likely that the Bantu migration has over-written much of the earlier genetic variation.

The fact that ancient genomes always show that our current populations are admixed makes me wonder if the Ballito Bay sample itself is admixed from more ancient populations. That is, if we found a genome from 20,000 years ago, would it be very different from the Ballito Bay samples? The relatively thick time transect from Europe indicates that turnover happens every 10,000 years or so. Australian Aborigines seem to have been resident in their current locations for ~50,000 years, but this seems the exception, not the rule. Do we really think that the ancestors of the Bushmen were living in southern Africa for five times as long as Australian Aborigines?

Another curious aspect of this paper is that it suggests the effective population size of Bushmen is smaller than we might have thought, and they’re somewhat less diverse than we’d thought. That’s because East African (with Eurasian ancestry) gene flow increased heterozygosity, as well as inferred effective population sizes. I’ve mentioned this effect on statistics before. Unless you have a true model of population history (or close to it) your assumptions might distort the numbers you get.

There is another aspect to this preprint mentioned glancingly in the text, and a bit more in the supplements: they seem to only be able to model Yoruba well if you assume that they themselves are a mix of “Basal Humans” (BH) and other African population which gave rise to East Africans and “Out of Africa” populations. Note that the BH seem to diverge from other human populations before the ancestors of Southern Africans like the Ballito Bay sample. That is, BH could push the diversification of the ancestors of modern humans considerably before 260,000 years before the present.

The possibility of deep structure in the Yoruba is pretty notable because they’ve been the gold standard in many human population genetic data sets as a reference population. But this is not result of deep structure is not entirely surprising. For years researchers have been hinting at confusing results in relation to the possibility of Eurasian back-migration. Perhaps the deep structure was confounding inferences?

The authors themselves are quite cautious about their dating of the divergence. It’s sensitive to many assumptions, and in particular the mutation rate being known and constant over time. But I think it’s hard to deny that this is pushing back the emergence of modern humans beyond what we know today. The earliest anatomically modern humans are found in Ethiopia 195,000 years ago from what I know. As I said, I’m convinced that the ancient genome has shown that modern “pristine” populations have some serious admixture. But I’m not as convinced about any specific point estimate, because that’s sensitive to a lot of assumptions which might not hold.

Finally, first a quick shout out to the blogger Dienekes. As early as ten years ago he anticipated the basic outlines of these sorts of results in the generality, if not the details. We really have come a long way from popular science declaring that all humans descend from a small group of East Africans who lived 50,000 to 100,000 years ago. The real picture was much more complex.

Also, I have to admit I considered titling this blogspot “Wolpoff’s revenge.” As in Milford Wolpoff. The reason being that we’re getting quite close to territory familiar to the much maligned multi-regionalist model of modern human origins.

Note: These findings should make us less surprised perhaps by a “modern” human migration before the primary one out of Africa.

The nadir of genetics in the Soviet Union

A fascinating excerpt in Slate from How to Tame a Fox (and Build a Dog), :

This skepticism of genetics all started when, in the mid-1920s, the Communist Party leadership elevated a number of uneducated men from the proletariat into positions of authority in the scientific community, as part of a program to glorify the average citizen after centuries of monarchy had perpetuated wide class divisions between the wealthy and the workers and peasants. Lysenko fit the bill perfectly, having been raised by peasant farmer parents in the Ukraine. He hadn’t learned to read until he was 13, and he had no university degree, having studied at what amounted to a gardening school, which awarded him a correspondence degree. The only training he had in crop-breeding was a brief course in cultivating sugar beets. In 1925, he landed a middle-level job at the Gandzha Plant Breeding Laboratory in Azerbaijan, where he worked on sowing peas. Lysenko convinced a Pravda reporter who was writing a puff piece about the wonders of peasant scientists that the yield from his pea crop was far above average and that his technique could help feed his starving country. In the glowing article the reporter claimed, “the barefoot professor Lysenko has followers … and the luminaries of agronomy visit … and gratefully shake his hand.” The article was pure fiction. But it propelled Lysenko to national attention, including that of Josef Stalin.

Sometimes it is easy to believe that the period in the Soviet Union under Stalin or in China under Mao or in Germany under Hitler, to name a few, were aberrations. But I think that’s the wrong way to look at it. The story of how Lysenko became influential hooks into so many historical tropes and psychological instincts of our species that we should be wary of it.

There have been great scholars without requisite qualifications. Ramanujan and Faraday come to mind. But great scholars are exceptional people. They are not average.

To be a scientific intellectual today

George Busby has put up note about changes in his career path, Meditation on the Caltrain. I took offense to this section:

On top of this, there was the burgeoning realisation that no one actually reads the academic papers that I write. This is no moot point: writing papers is the main purview of a research scientist, and the central way we both communicate our results and measure success. However, compared to the proportion of the world’s population who can read, the number of people that had sat down to ingest my latest, dense, and fascinating (to me at least) treaty on the population genetics of Africa, three years in the making, was minuscule. The words of a colleague rang in my head: “99.9% of scientific papers just don’t get read”.

His most recent paper, Admixture into and within sub-Saharan Africa, was great. I meant to blog it, but got busy with other things. To be frank the fact that someone like George Busy is having trouble in the academic market is sobering. He has produced good and prominent work, and has been attached to groups which have some prominence. Of course grant approvals and job prospects have a stochastic element. But his experience shows that talent and good work is just a necessary, not sufficient, condition.

It looks like Busby will land in Silicon Valley with one of the two companies that do a lot of work on ancestry. Good for him. I think it does behoove those of us with intellectual pretensions to wonder what we’re doing out in the world. And, it also behooves academics to wonder what they’re doing with their job security. Sometimes it is important to tell the truth and explore topics even if people don’t care, or don’t want to listen. Otherwise, why fund anything that’s not practical with the public fisc?

The misrepresentation of genetic science in the Vox piece on race and IQ

I don’t have time or inclination to do a detailed analysis of this piece in Vox, Charles Murray is once again peddling junk science about race and IQ. Most people really don’t care about the details, so what’s the point?

But in a long piece one section jumped out to me in particular because it is false:

Murray talks about advances in population genetics as if they have validated modern racial groups. In reality, the racial groups used in the US — white, black, Hispanic, Asian — are such a poor proxy for underlying genetic ancestry that no self-respecting statistical geneticist would undertake a study based only on self-identified racial category as a proxy for genetic ancestry measured from DNA.

Obviously the Census categories are pretty bad and not optimal (e.g., the “Asian American” category pools South with East & Southeast Asians, and that has caused issues in biomedical research in the past). But the claim is false. In the first half of the 2000s the eminent statistical geneticist Neil Risch specifically addressed this issue. From 2002 in Genome Biology Categorization of humans in biomedical research: genes, race and disease:

A debate has arisen regarding the validity of racial/ethnic categories for biomedical and genetic research. Some claim ‘no biological basis for race’ while others advocate a ‘race-neutral’ approach, using genetic clustering rather than self-identified ethnicity for human genetic categorization. We provide an epidemiologic perspective on the issue of human categorization in biomedical and genetic research that strongly supports the continued use of self-identified race and ethnicity.

A major discussion has arisen recently regarding optimal strategies for categorizing humans, especially in the United States, for the purpose of biomedical research, both etiologic and pharmaceutical. Clearly it is important to know whether particular individuals within the population are more susceptible to particular diseases or most likely to benefit from certain therapeutic interventions. The focus of the dialogue has been the relative merit of the concept of ‘race’ or ‘ethnicity’, especially from the genetic perspective. For example, a recent editorial in the New England Journal of Medicine [1] claimed that “race is biologically meaningless” and warned that “instruction in medical genetics should emphasize the fallacy of race as a scientific concept and the dangers inherent in practicing race-based medicine.” In support of this perspective, a recent article in Nature Genetics [2] purported to find that “commonly used ethnic labels are both insufficient and inaccurate representations of inferred genetic clusters.” Furthermore, a supporting editorial in the same issue [3] concluded that “population clusters identified by genotype analysis seem to be more informative than those identified by skin color or self-declaration of ‘race’.” These conclusions seem consistent with the claim that “there is no biological basis for ‘race'” [3] and that “the myth of major genetic differences across ‘races’ is nonetheless worth dismissing with genetic evidence” [4]. Of course, the use of the term “major” leaves the door open for possible differences but a priori limits any potential significance of such differences.

In our view, much of this discussion does not derive from an objective scientific perspective. This is understandable, given both historic and current inequities based on perceived racial or ethnic identities, both in the US and around the world, and the resulting sensitivities in such debates. Nonetheless, we demonstrate here that from both an objective and scientific (genetic and epidemiologic) perspective there is great validity in racial/ethnic self-categorizations, both from the research and public policy points of view.

From a 2005 interview:

Gitschier: Let’s talk about the former, the genetic basis of race. As you know, I went to a session for the press at the ASHG [American Society for Human Genetics] meeting in Toronto, and the first words out of the mouth of the first speaker were “Genome variation research does not support the existence of human races.”

Risch: What is your definition of races? If you define it a certain way, maybe that’s a valid statement. There is obviously still disagreement.

Gitschier: But how can there still be disagreement?

Risch: Scientists always disagree! A lot of the problem is terminology. I’m not even sure what race means, people use it in many different ways.

In our own studies, to avoid coming up with our own definition of race, we tend to use the definition others have employed, for example, the US census definition of race. There is also the concept of the major geographical structuring that exists in human populations—continental divisions—which has led to genetic differentiation. But if you expect absolute precision in any of these definitions, you can undermine any definitional system. Any category you come up with is going to be imperfect, but that doesn’t preclude you from using it or the fact that it has utility.

We talk about the prejudicial aspect of this. If you demand that kind of accuracy, then one could make the same arguments about sex and age!

You’ll like this. In a recent study, when we looked at the correlation between genetic structure [based on microsatellite markers] versus self-description, we found 99.9% concordance between the two. We actually had a higher discordance rate between self-reported sex and markers on the X chromosome! So you could argue that sex is also a problematic category. And there are differences between sex and gender; self-identification may not be correlated with biology perfectly. And there is sexism. And you can talk about age the same way. A person’s chronological age does not correspond perfectly with his biological age for a variety of reasons, both inherited and non-inherited. Perhaps just using someone’s actual birth year is not a very good way of measuring age. Does that mean we should throw it out? No. Also, there is ageism—prejudice related to age in our society. A lot of these arguments, which have a political or social aspect to them, can be made about all categories, not just the race/ethnicity one.

Risch is not obscure. In the piece the author observes that Risch ‘was described by one of the field’s founding fathers [of the field] as “the statistical geneticist of our time.’

2005 is a long way from 2017. Risch may have changed his mind. In fact, it is probably best for him and his reputation if he has changed his mind. I wouldn’t be surprised if Risch comes out and engages in a struggle session where he disavows his copious output from 2005 and earlier defending the utilization of race as a concept in statistical genetics.

Also, genotyping is cheap enough and precise enough that one might actually make an argument for leaving off any self-reported ancestry questions. It’s really not necessary. This isn’t 2005.

But that section in the Vox piece is simply false. The existence of Risch refutes it. Vox is a high profile website which serves to “explain” things to people. The academics who co-wrote that piece are very smart, prominent, and known to me. I don’t plan on asking them why they put that section in there. I think I know why.

There will be no update to that piece I’m sure. It will be cited widely. It will become part of what “we” all know. Who I am to disagree with Vox? This is journalism from what have been able to gather and understand. The founders of Vox are rich and famous now. Incentives matter. There are great journalists out there  who don’t misrepresent topics which I know well. But the incentive structure is not to reward this. More often storytellers who tell you the story you like to be told are rewarded.

As for science and the academy? I am frankly too depressed to say more.

The population genetic structure of Sicily and Greece


By total coincidence a paper came out yesterday, Ancient and recent admixture layers in Sicily and Southern Italy trace multiple migration routes along the Mediterranean (I blogged about the topic). It’s open access, and it has a lot of statistics and analyses. I’d recommend you read it yourself.

You see the Sicilian and Greek populations and their skew toward the eastern Mediterranean. But in the supplements they displayed some fineSTRUCTURE clustering, and at K = 3 you see that Europe and the Middle East diverge into three populations. What this is showing seems to be: 1) in red, those groups least impacted by post-Neolithic migration 2) in blue, Middle Eastern groups characterized by the fusion between western & eastern Middle Eastern farmer which occurred after the movement west of the ancestors of the “Early European Farmers” (who gave rise to the red cluster), who were related to the western Middle Eastern farmers 3) the groups most impacted by Pontic steppe migration.

The authors confirm what I reported over two years ago on this blog: mainland and island Greeks are genetically distinct, probably because the former have recent admixture from Slavs and Slav-influenced people. And, many Southern Italians resemble island Greeks.

One has to be careful about dates inferred from genetic patterns. For example:

Significant admixture events successfully dated by ALDER reveal that all Southern Italian and Balkan groups received contributions from populations bearing a Continental European ancestry between 3.0 and 1.5 kya

The beginning of folk wanderings in the Balkans which reshaped its ethnographic landscape really dates to the later 6th century, when the proto-Byzantines began to divert all its resources to the eastern front with Persia, and abandoned the hinterlands beyond the Mediterranean coast in Europe to shift its focus toward the Anatolian core of the empire. The Slavic migrations were such that there were tribes resident in the area of Sparta in the early medieval period. Presumably because they were not a seafaring folk they don’t seem to have had much impact on the islands.

Such an early period in the interval though can not be the Slavs. What can it be? I suspect that that there are signals of Indo-European migrations in there that are being conflated due to low power to detect them since they are rather modest in demographic impact. The islands such as Sardinia, Crete and Cyprus had non-Indo-European speakers down to the Classical period.

Overall it’s an interesting paper. But it needs a deeper dig than I have time right now.

The Orantes has not mixed much with the Tiber


In a moment of weakness I decided to read some of Mary Beard’s SPQR: A History of Ancient Rome. I say weakness because I want to wean myself off of excessive reading of Roman history, as in terms of inferential utility I’ve long reached diminishing returns. But I quite enjoy the topic, and so here I am.

The author is an excellent writer as well as a scholar, and I quite enjoyed Roman Triumph, so I am entirely not surprised that SPQR has me hooked. Some of my correspondents have exhibited some disdain toward it because of Beard’s attempts to draw some connections to present day mores and values from that of Rome, presumably with a progressive bent.

Myself, this does not bother me. I don’t come into reading about Rome as an ignorant, so I can sort that from the nuggets of fact and positivistic interpretation. In any case, I think of it rather like how Islamic philosophers viewed Aristotle through their own religio-cultural lens. Obviously this was an issue that caused resistance to the transmission of Aristotle to the Christian West, but ultimately it did not stop what was inevitable. At the end of the day it was more about Aristotle than the glosses.

Though I highly recommend SPQR (I’m halfway through), that’s not the point of this post. Going along I kept thinking about the section on the Etruscans. The Rasena. Their origins have a genetic connection that is clouded and uncertain right now. I would like to dig deeper into this issue in the future; no doubt some day it will be cleared up. But that day is not this day.

Modern Italians have more “Indo-European” admixture than they do “Middle Eastern”

Rather, I want to address the idea that modern Italians are genetically a distinct people from ancient Roman Italians. Because on that score we have the answers. Ultimately the idea that this is even a debate goes back to Juvenal:

It is that the city is become Greek, Quirites, that I cannot tolerate; and yet how small the proportion even of the dregs of Greece! Syrian Orontes has long since flowed into the Tiber, and brought with it its language, morals, and the crooked harps with the flute-player, and its national tambourines, and girls made to stand for hire at the Circus. Go thither, you who fancy a barbarian harlot with embroidered turban….

These comments are rooted in the reality that Rome during Juvenal’s period was quite a cosmopolitan city, with large numbers of Greeks and people from the Eastern Mediterranean who were Hellenized to various degrees (in the early 3rd century Rome was ruled by a family of Hellenized Syrians). We know this because we have plenty of observations and complaints, and there are a plethora of inscriptions and graffiti in the new languages.

In the 19th and early 20th century the ascendency of Nordic racial theories about the origins of white supremacy across the world presented a problem. The Mediterranean peoples had been in decline for centuries, and were perceived to be Orientalized and inferior. Yet in the past they had achieved greatness which Northern Europeans were attempting to emulate. How could a racially inferior people have created such excellence?

A simple explanation for this condition for Victorians and their Continental fellow travelers was one of racial degradation. The ancient Romans were in this telling fundamentally a different people than modern Romans, with the latter being derived from migrants from the eastern Mediterranean who had arrived during the period of the Empire.

Though most of the racially derogatory elements are gone form this narrative, it is still strongly persistent in public consciousness. Being a Cavalli-Sforza nerd (there is such a thing), I have a copy of Consanguinity, Inbreeding, and Genetic Drift in Italy, and there was data in it which made me skeptical of wholesale replacement in the middle 2000s. Then there was Peter Ralph and Graham Coop’s 2013 paper, The Geography of Recent Genetic Ancestry across Europe, which reported lots of deep regional structure across Italy.

This is important because it suggests a local stability to the demographic character of the regions for a long time. Probably earlier than the period of the Roman Empire. Though one can imagine scenarios of demographic replacement which would produce this result, they’re generally less parsimonious than the model whereby modern Italian population structure maintains the general outline it had at the beginning of the Iron age.

Finally, over the past seven years I have done a lot of analysis and manipulation of tens of thousands of Europeans and Middle Easterners in relation to their genetic data for personal and professional reasons. Some patterns jump out at you, and some subtle tendencies come into the foreground. It is pretty clear that Italians are not a transplanted Middle Eastern population (though there is some recent non-Italian ancestry; Sicilians often have minor components of clear North African ancestry as well as small percentages of Sub-Saharan heritage, which I think is almost certainly due not to Greek and Roman cosmopolitanism, but the legacy of the Arab emirate which existed on the island for a few centuries).

But now I have realized probably the best illustration of this. The Reich lab has been generating a massive genotype dataset over the past five years on the Human Origins Array. And not only do you have modern populations, but you have ancient ones (from ancient DNA). The PCA plots in their papers make what I’m saying above pretty clear.

I’ve modified the PCA plot from Genomic insights into the origin of farming in the ancient Near East. Notice where various Italian groups and Greeks are. I’ve also labeled the Druze; they are almost certainly an excellent representation of Near Eastern Syrians from 2,000 years ago. They have been endogamous for nearly 1,000 years in the Lebanese highlands, and don’t have admixture that is more common in Syrian Muslims from the lowlands.

Notice that the most of the Greeks are shifted further toward Northwestern Europeans than Southern Italians. I say most, because I’ve had access to a larger data set of Greeks, and it becomes clear that a minority of Greeks cluster more with Southern Italians, and the majority have a minority admixture element from a Northern European population. This is Slavic ancestry that arrived after the middle of the 6th century, when the East Roman state basically abandoned most of the Balkans to focus on maintaining control over Constantinople, Salonika, and the Peloponnese.

Northern Italians are shifted toward Sardinians and Spaniards. The Sardinians are important, because we now know that they are the closest modern Europeans to the agriculturalists who arrived from the eastern Mediterranean during the early Neolithic. This population, “Early European Farmers” (EEF), once dominated most of the continent. But ~5,000 years ago migrations from the steppe brought a new element which replaced and assimilated them in Northern Europe.

But in Southern Europe their genetic legacy remains strong and to a great extent dominant. Iberia and the Italian peninsula have been impacted by the migrations out of the steppe, with Sardinia the least so. In the smaller plot above you can see that the early Neolithic individuals are close to the Sardinians, with mainland Italians being shifted toward other populations.

The Northern Italians in particular show some influence from Northern European populations. Some of this may be gene flow through diffusion due to proximity, but the Alps are a rather formidable barrier. Rather, I suspect it reflects episodic migration. I generally do not weight the Lombards too highly as a major influence. Rather, I suspect that it is a combination of Gaulish settlement in the Po river valley, and early impacts from the Indo-Europeans who arrived in the Italian peninsula.

The Southern Italian shift toward the Middle East probably does indicate some gene flow, but it is important to remember that this was also Magna Graecia, so there is probably a Greek element here similar to what occurs among those Greeks without Slavic admixture (please note that Byzantine Greek rule also persisted in Southern Italy up until the Norman conquest ). And if you look at how they relate to the Neolithic samples, they exhibit a lot of shift on the plane toward the steppe populations, parallel to the Levantines. In other words, a lot of the change since the Neolithic in Southern Italy is attributable to the influence of the steppe migration, not Roman era gene flow from Syrians.

I will probably do some formal analysis at some point so that the numbers can get out there now that there are so many ancient genotypes available too. But really this shouldn’t be a discussion anymore.

Addendum: You may be asking, if there are so many literary comments about non-Italians during the Roman Empire in Italy, where did they go? I think the big thing to remember is that there is an ascertainment bias toward what we know in urban areas. There is a high likelihood that urban areas were population sinks, which could not maintain themselves without constant migration.

The end of insurance (some if it)

Unless you’ve been sleeping under a rock you are aware that the cost of sequencing has been going down. Less clear to many is that genotyping has also been declining. At last year’s ASHG some physicians were talking about SNP-chips in the range of the low tens of dollars.

Right now most diseases for most people who buy health care are accounted for by the standard issue SNP-chips. If you have a rare mutation not on the chip, or are of a minority ethnic group not well ascertained by the chip, well, tough luck. My point is that chips probably have a near term future.

And that’s what’s at the heart of this piece in The New York Times, New Gene Tests Pose a Threat to Insurers:

So Ms. Reilly, 77, a retired social worker in Ann Arbor, Mich., applied for a long-term care insurance policy. Wary of enrolling people at risk for dementia, the insurance company tested her memory three times before issuing the policy.

But Ms. Reilly knew something the insurer did not: She has inherited the ApoE4 gene, which increases the lifetime risk of developing Alzheimer’s. “I decided I’d best get long-term care insurance,” she said.

I think the headline will mislead many people because when we hear “insurance” in relation to health, we assume health insurance. But long-term care insurance and life insurance are both relevant to health, and both of these have a major issue now with asymmetric information.

Many people are declaring that health insurance is over once everyone gets sequenced. I don’t think that’s necessarily true. The minority of the population that has a highly penetrant Mendelian disease may be in trouble without legal protection. But most disease variance is not going to be due to Mendelian disorders. Rather, people have risks based on family history and polygenic scores and lifestyle. And, a substantial proportion of disease and illness remains and will remain random.

With all that said, it’s not going to be a pretty picture when pockets of the insurance industry collapse. With greater knowledge comes the reckoning that we as a society have to make about the values who hold to be true.

When conquered pre-Greece took captive her rude Hellene conqueror


When I was a child in the 1980s I was captivated by Michael Wood’s documentary In Search of the Trojan War (he also wrote a book with the same name). I had read a fair amount of Greek mythology, prose translations of the Iliad, as well as ancient history. The contrast between the Classical Greeks and the strangeness of their mythology was always something that on the surface of my mind. The reality that Bronze Age Greeks were very different from Classical Greeks resolved this issue to some extent, as the mythos no doubt drew from the alien world of the former.

Though Classical Greeks were very different from us (e.g., slavery), to some extent Western civilization began with them, and they are very familiar to us for this reason. Rebecca Goldstein’s Plato at the Googleplex was predicated on the thesis that the ancient Greek philosopher had something to tell us, and that if he was alive today he would be a prominent public speaker.

I’m going to dodge the issue of Julian Jaynes’ bicameral mind, and just assert that people of the Bronze Age were fundamentally different from us in a way Plato was not. And that difference is preserved in aspects of Greek mythology. Though it is fashionable, and correct, to assert that Homer’s world was not that of Mycenaeans, but the barbarian period of the Greek Dark Age, it is not entirely true. Homer clearly preserved traditions where citadels such as Mycenae and Pylos were preeminent. Details such as the boar’s tusk helmets are also present in the Iliad. His corpus of oral history clearly preserved some ancient folkways which had fallen out of favor.

But aesthetic details or geopolitics are not what struck me about Greek mythology, but events such as the sacrifice of Iphigenia. Like Abraham’s near sacrifice of his son, this plot element seems to moderns cruel, barbaric, and unthinking. And though the Classical Greeks did not have our conception of human rights, they had turned against human sacrifice (and the Romans suppressed the practice when they conquered the Celts) on the whole. But it seems to have occurred in earlier periods.

The rupture between the world of the Classical Greeks and the strange edifices of Mycenaean Greece were such that scholars were shocked that the Linear B tablets of the Bronze Age were written in Greek when they were finally deciphered. In fact many of the names and deities on these tablets would be familiar to us today; the name Alexander and the goddess Athena are both attested to in Mycenaean tablets.

Preceding the Mycenaeans, who  emerge in the period between 1400-1600 BCE, are the Minoans, who seem to have developed organically in the Aegean in the 3rd millennium. This culture had relations with Egypt and the Near East, their own system of writing, and deeply influenced the motifs of the successor Mycenaean Greek civilization. The aesthetic similarities between Mycenaeans and Minoans is one reason that many were surprised that the former were Greek, because the Minoan language was likely not.

Mycenaean civilization seems to have been a highly militarized and stratified society. There is a reason that this is sometimes referred to as the “age of citadels.” Allusions to the Greeks, or Achaeans, in the diplomatic missives of the Egyptians and Hittites suggests that the lords of the Hellenes were reaver kings. In 1177 B.C. Eric Cline repeats the contention that a fair portion of the “sea peoples” who ravaged Egypt in the late Bronze Age were actually Greeks.

So when did these Greeks arrive on the shores of Hellas? In The Coming of the Greeks Robert Drews argued that the Greeks were part of a broader movement of mobile charioteers who toppled antique polities and turned them into their own. The Hittites and Mitanni were two examples of Indo-European ruling elites who took over a much more advanced civilizational superstructure. While the Hittites and other Indo-Europeans, such as the Luwians and Armenians, slowly absorbed the non-Indo-European substrate of Anatolia, the Indo-Aryan Mitanni elite were linguistically absorbed by their non-Indo-European Hurrian subjects. Indo-Aryan elements persisted only their names, their gods, and tellingly, in a treatise on training horses for charioteers.

Drews’ thesis is that the Greek language percolated down from the warlords of the citadels and their retinues over the Bronze Age, with the relics who did not speak Greek persisting into the Classical period as the Pelasgians. Set against this is the thesis of Colin Renfrew that Greek was one of the first Indo-European languages, as Indo-European languages began in Anatolia.

The most recent genetic data suggest to me that both theses are likely to be wrong. The data are presented in two preprints The Population Genomics Of Archaeological Transition In West Iberia and The Genomic History Of Southeastern Europe. The two papers cover lots of different topics. But I want to focus on one aspect: gene flow from steppe populations into Southern Europe.

We know that in the centuries after 2900 BCE there was a massive eruption of individuals from the steppe fringe of Eastern Europe, and Northern Europe from Ireland to to Poland was genetically transformed. Though there was some assimilation of indigenous elements, it looks to be that the majority element in Northern Europe were descended from migrants.

For various reasons this was always less plausible for Southern Europe. The first reason is that Southern Europeans shared a lot of genetic similarities to Sardinians, who resembled Neolithic farmers. Admixture models generally suggested that in the peninsulas of Southern Europe the steppe-like ancestry was the minority component, not the majority, as was the case in Northern Europe.

These data confirm it. The Bronze Age in Portugal saw a shift toward steppe-inflected populations, but it was not a large shift. There seems to have been later gene flow too. But by and large the Iberian populations exhibit some continuity with late Neolithic populations.  This is not the case in Northern Europe.

In The Genomic History Of Southeastern Europe the authors note that steppe-like ancestry could be found sporadically during early periods, but that there was a notable increase in the Bronze Age, and later individuals in the Bronze Age had a higher fraction. Nevertheless, by and large it looks as if the steppe-like gene flow in the southerly Balkans (focusing on Bulgarian samples) was modest in comparison to the northern regions of Europe. Unfortunately I do not see any Greece Bronze Age samples, but it seems likely that steppe-like influence came into these groups after they arrived in Bulgaria, which is more northerly.

Down to the present day a non-Indo-European language, Basque, is spoken in Spain. Paleo-Sardinian survived down to the Common Era, and it too was not Indo-European. Similarly, non-Indo-European Pelasgian communities continued down to the period of city-states in Greece.

These long periods of coexistence point to the demographic equality (or even superiority) of the non-Indo-European populations. The dry climate of the Mediterranean peninsulas are not as suitable for cattle based agro-pastoralism. This may have limited the spread and dominance of Indo-Europeans. Additionally, the Mediterranean peninsulas were likely touched by Indo-European migrations relatively late. Much of the early zeal for expansion may have already dissipated by them. The high frequency of likely Indo-European R1b lineages among the Basques is curious, and may point to the spreading of male patronization networks, and their assimilation into non-Indo-European substrates where necessary. R1b is also found in Sardinia, and in high frequencies in much of Italy.

The interaction and synthesis between native and newcomer was likely intensive in the Mediterranean. For example, of the gods of the Greek pantheon only Zeus is indubitably of Indo-European origin. Some, such as Artemis, have clear Near Eastern antecedents. But other Greek gods may come down from the pre-Greek inhabitants of what became Greece.

Ultimately these copious interactions and transformations should not be a great surprise. The sunny lands of the Mediterranean attracted Northern European tribes during Classical antiquity. The Cimbri invasion of Italy, Galatians in Thrace and Anatolia, the folk wandering of Vandals and Goths into Iberia, are all instances of population movements southward. These likely moved the needle ever so slightly toward convergence between Northern and Southern Europe in terms of genetic content.

In relation to the more general spread of Indo-Europeans, I believe there are a few areas like Northern Europe, where replacement was preponderant (e.g., the Tarim basin). But I also believe there were many more which presented a Southern European model of synthesis and accommodation.