There are various informal indicators that funders are losing enthusiasm for human whole genome sequencing. [. . .] If this turns out to be more than a few anecdotes or personal opinions, and is actually occurring, it's understandable and to be lauded. As we think we can truthfully claim, we have for years been warning of the dangers of the kind of overkill that genomics (and, indeed, other 'omics' fads) present: promise miracles and you had better deliver!
The same thing applies to evolutionary studies that seek whole genome sequences as well as to studies designed to use such data to predict individual diseases. There are too many variants to sort through, the individual signal is too weak, and too many parts of the genome contribute to many if not most traits, for genomes to be all that important--whether for predicting future disease, normal phenotypes like behaviors, or fitness in the face of natural selection.
The proper response to genomic complexity is of course not to throw ones hands up and go back to candidate gene studies, but to sequence lots and lots of genomes in full. This is what needs to happen, and falling sequencing costs mean this is what will happen, regardless of what Ken Weiss wants.
Note: Ken Weiss is "Evan Pugh Professor of Anthropology and Genetics at Penn State University". I can think of a few possibilities: (1) Weiss is sincere in believing medical science and evolutionary research would be better advanced with less whole genome sequencing; he's not malicious -- just short-sighted, unimaginative, and breathtakingly ignorant of the broader state of his supposed academic specialty. (2) Weiss is merely jealous that his colleagues are getting bigger grants than him, a frailty he could perhaps be forgiven. (3) "Anthropology and Genetics" professor Weiss, for some reason, prefers that human evolutionary and genetics research not advance.
Wednesday, February 17, 2010On archaic-modern admixture:
Racing to confusion
One of the most important and contentious subjects in today's American society is that of race, or is it ethnicity, or is it color, or ....? There are good, natural reasons to want to belong to a group, whatever name you use for it. It can give you a feeling and the protection of solidarity. It can help you form alliances. It can get you legal entitlement rights. It can be a path to status (high or low depending).
But the term race also has biological connotations, of genetic continuity, or even genetic inherency (if one thinks of traits like hair form or skin color). Viewed, as many have done, in evolutionary terms, natural selection will have favored better traits within the evolution of each race (whatever that is), and by the very same reasoning, must have also favored values of one race vs another. That's because natural selection picks what's 'best' at any given time, and it's unlikely that, relative to any societal value today, all groups (whatever they are) would have evolved to be identical today. That doesn't mean differences would be great, of course.
Race was central from Darwin's time through WWII in the form of eugenics, a scientific movement concerned with these evolutionary issues. The term was due to Darwin's cousin Francis Galton. Scientists, generally from the privileged parts of society, expressed long-standing concerns about the masses of the less-worthy (a concern Darwin's inspiration Thomas Malthus, and Darwin himself shared).
The Nazi regime used mass eugenics to justify its tyranny, but thousands of other people were incarcerated, sterilized, or even killed because of the supposed characteristics of their race -- that is, in what the Germans called racial 'hygiene', individuals were picked on because of the assumption that any member of a race had the traits of that race. That was not the whole story, of course. Individuals within a society who were its 'worst' were also picked out for similar treatment. Invoking Darwin and natural selection, eugenicists piously presumed to be able to help evolution along by deciding who shall thrive and who shall not, and trying to make policy accordingly.
An important question besides concern about having to pay to support the starving lower class was the threat seen coming from immigrants into the advanced European societies. Our best and most respected scientists viewed races as real, evolutionarily determined, biological categories. They were treated just like classical 'type' specimens in biology. Every person was assumed to be a member of a pure race, or someone admixed among pure races. This, of course, assumes there are, or were such things as pure races to be admixed from. And that assumption was certainly and explicitly made.
Mixing of different types was considered important. In its classical form, inbred marriages were not legal of individuals closer than first cousins. In the US there were even laws against two epileptics marrying. From a genetic and evolutionary perspective,too, it was natural to think that if members of two races mixed, their hybrid offspring would bear some of the genes--and hence traits--of their inferior-race parents. Inter-racial marriage was illegal. and believe it or not, how much mixture should be tolerated became a serious topic of interest.
In our age in which genetic ancestry estimation from DNA sequence is a major recreation (with some legal entitlement elements that may be quite serious), the subject is certainly alive and well in all of its senses. Immigrants now, as then, were viewed as a potential source for the degradation of society. Somebody had to bar the door! But what criterion would be used?
It's too big a subject to go into in this post, but Jennifer Wagner, a colleague of ours who is a lawyer currently writing a doctoral thesis on her specialty interest, human rights law and concepts of genetic ancestry, has provided a summary of some of the slippery legal (court-related) issues in regard to defining who can immigrate, who can become a citizen. That formalized the rather informal writings of eugenicists, and gave related policy the ability to be implemented. We'll put up Jen's guest post tomorrow, and it's worth checking back for, as she is very thoughtful and knowledgeable on this subject (among others!).
Posted by Ken Weiss at 5:33 AM
Tuesday, February 23, 2010
Eugenics continued -- its modern guises
We have mentioned eugenics in several recent posts (e.g., here and here), but it's a thorny subject worth pursuing more fully. Indeed, 'Deadly Medicine', an exhibit from the US Holocaust Museum, is at Penn State for the next few months, reminding us that eugenics was alive and well in the US before the Nazis put it into practice.
There are two faces of eugenics. One is the goal that parents have of not bearing undesirable children. Normally, that means children with serious disabling disease. It can be a noble wish and even a noble act. So long as abortion or in vitro fertilization (IVF) and embryo screening are considered morally acceptable options, and the suffering of the embryo or fetus is not considered to be great, genetic screening can achieve this end. Premarital screening also works, if couples can be dissuaded from marriage (or from child-bearing) if they could produce such offspring (and, indeed, an AP story reporting that many genetic diseases are in decline because of prenatal testing was widely published on Feb 17).
If two carriers of recessive alleles (genetic variants) that are potentially harmful have children, then 1/4 of their offspring would inherit the 'bad' allele from each parent and would be affected with the disease. Call the defective allele 'd' and the normal one 'D'. Each parent is a Dd genotype. Randomly picking one of the alleles from each parent gives a 1/2 chance of picking d from each, or 1/4 chance of picking d's from both. These are the classical proportions discovered by Mendel.
There are many single-gene diseases for which, if the 'd' alleles are known, parents can be screened to determine if they are at risk of producing a dd offspring. Not implanting such an embryo, or aborting such a fetus, prevents the birth of someone carrying the disease.
Tay-Sachs disease in the Jewish population, and serious anemias called Thalassemia, are examples of diseases that have actually been substantially reduced or even nearly eliminated by such screening programs.
The fact is that, like much else in life, the genes have many--often hundreds--of alleles, and only a few of them are known to be seriously harmful. Others confer lesser risk and for most of them we simply don't know. It's less clear about alleles whose effects are uncertain, with comparably complicated moral issues associated with aborting these if they're detected. Still, even those few that are known are clear.
Most of us these days would consider this not just acceptable but a good form of personal eugenics. Others, however, object morally to any abortion, to making God's decisions, or to labeling disabled people as somehow not fully human or not worth living. A whole field of 'disability studies' deals with these issues, and much is being written about the degree to which meaningful, valuable lives can be lived by those formerly considered unworthy--hence questioning blanket policies of aborting them. These are ways in which the morality of eugenics enters society.
Is there a place to draw the line as to what counts as disease? If we ever learn to evaluate a fetus's IQ from its genotype, would it be OK to abort 'stupid' fetuses? If so, should parents be allowed to determine the decision point on the IQ scale? What about, say, musical or athletic ability? What about engineering genes into an embryo to give it traits you want your children to have?
Most if not all the humans who have had their whole genomes sequenced have genotypes at some genes that are 'disease' genotypes. The discoverer of DNA structure, Jim Watson, is one. As someone has quipped, if his own technology had been available to his parents, in the current climate of personal eugenics, he would have been aborted!
What about sex? In some countries there is reportedly substantial prenatal testing and aborting of female fetuses, because sons are more valuable to the parents than daughters. Is that OK? As long as the parents, and not society, make the decision? Of course, this can have ramifications into succeeding generations, as males find it difficult to marry, creating a sort of pendulum effect as to which sex is more valued.
The fears of eugenics imposed by society, as was done in the first half of the 20th century, spook many people as we increasingly enter the genetic age in which the belief is strong that genes generally will predict one's traits, one's identity as a person. We might not impose gas chambers on people because of their group membership, but what about policy involving insurance, employment, access to education, and the like aimed at individuals? Or in the classical example, to screen potential immigrants? Will subtle or unsubtle pressure be imposed on those who would choose not to screen, on the grounds that their impaired offspring will be a burden on the health care system and hence on everyone? (That's a classic argument used by the original eugenics movement, and vigorously used in Germany to justify 'euthanasia' to countless thousands of 'defective' societal burdens)
These are issues we'll have to be facing in the future. And we don't need to raise the Nazi holocaust specter to see that they will be important. They involve both our concepts of genetic causation, our concepts of personal value, and in subtle ways our concepts of societal responsibility. There will be a great increase in the number of genetic variants that have high predictive power.
A lot of the eugenics movement in the last century, and even the rationale for the holocaust, was framed around evolutionary and Darwinian ideas. Nature eliminates the unfit, so why can't we help Nature out? If we don't, will our advanced medical and social-net system lead to the gradual pollution of the human gene pool? If so, it is not just the right of individual parents to decide, but society's, because society pays the bills economically and in terms of its abilities, for decreasing overall 'fitness'. These were the classic arguments. Is there a risk that renewed darwinian determinism--of some form specific to our time, not last century's, will lead society in similar directions?
These issues will not go away. But, in our next post, we'll raise important additional questions about what the impact of screening is in terms of the human gene pool, and what the impact on society of widespread personal eugenics might be. Posted by Ken Weiss at 6:14 AM
Friday, July 17, 2009
Francis Collins and the NIH
Francis Collins, long-time director of the US National Human Genome Research Institute (part of our National Institutes of Health), is reported to be President Obama's choice to be the next NIH director. This is a curious choice and it is receiving comment from both Nature and Science this week (not to mention many blogs), and for good reasons.
First, on the surface it suggests a complete and total victory for the genetic view of life. That might have been fine for the Genome Institute, but seems much less so for NIH overall, because many if not most problems in both medicine and public health are not about genes or genetic variation (though they involve them at least indirectly) but are about environments, many kinds of therapies, prevention, and so on. One doesn't have to ignore the fact that genetics is certainly fundamental to life, and that molecular biology will become increasingly important, to know that (for example) most common diseases have little to do with genetic variation in any sensible way. Forcing things through a genetic conceptual lens will distort them, and root them in glamorous technology rather than concept or accountability for results.
As director of NHGRI, Dr Collins did a lot of things that can be praised and others that can be criticized. First and foremost among the former, perhaps, are that he nobly and successfully struggled to keep genome sequence and variation data in the public domain. But he also directly or indirectly intimidated other NIH agencies to get into the genome game, or even to contribute to NHGRI efforts. That did, and still does, coopt funds that could be used for other things instead. Partly, Francis rode a fashion, partly an explosion of genuinely new and important knowledge, and partly the Washington money game.
The other issue is Dr Collins' brand of Christian fundamentalism. He says he had a conversion experience, and believes in a 'personal' God and he's written a book about it. In the US context, that has implications for policy, not all of them good (and not all of them Constitutional, perhaps). He has done medical missionary work in Africa, as we understand it, but we don't know what kind of missionary work. If it was out in the sweaty hinterlands where people really need help, then he deserves and should get all the praise that is available for being consistent with the basic Christian principles that not all Christians follow (to say the least).
But a personal God intervenes in the world, and that is inconsistent with all the precepts of science. For example, one never expects experiments to be affected by God (or by prayer). Does he, or should we, pray for God to cure a loved one's disease? Science rests on the assumption that the world is a strictly material place to be understood in terms of its universal laws (like gravity, chemistry, etc.). And Dr. Collins clearly asserts that religions should basically not make scriptural claims about the world, because science will show that they are wrong. But what, then, is a personal God? These seem like incompatible views, which can be worrisome for someone in a position of science leadership in our culturally cloven society.
And what about evolution? What are his views of human origins, and the genetic relationships we bear with other species? Was that process mechanical, or God-directed? It makes a difference in how we interpret our own variation (not to mention racial variation), the differential impact of the 'curse' of disease, and the relevance of animal models. If humans are not 'just' genes, is that because God made us unique? If so, should we be licensed to torture animals in research? We do have to say that the NHGRI did not get involved in religious entanglements during Dr Collins' stewardship, but it is certainly fair to ask these things, as they have potential policy implications--especially if a fundamentalist chunk of the country will expect it.
Like grilling of a prospective Supreme Court justice, one would like to know how all our health needs will be addressed, not just one particular component of them. That will be of interest to those who are not just in genetics. Likewise, the religious aspect of Dr Collins' life is at least potentially relevant in our society, especially because genetics is inextricably and properly understood in the context of evolution; regardless of his view on evolution, religious literalists may expect him to use religion to filter research and policy decisions.
Supreme Court justices sometimes play the political role desired by those who appointed them, which is a shame since courts should be as objective as possible in the realities of human society. But sometimes they surprise. Dr Collins could go either way -- who can say? He could use his Christian religious beliefs to foster all sorts of health improvements for the needy here and abroad, rather than (as most genetics does) for the privileged. He could help international medical services (like Doctors Without Borders), a kind of US contribution to a medical Peace Corps. Or, he could stay close to his genetics worldview, narrowing the field directly or by bureaucrats being intimidated or chameleon-like in their struggle for cuts of the NIH pie.
In fact, there is no danger whatever that genetics research is going to be neglected; there are far too many commercial, academic, and bureaucratic careers that depend on it. We need to support basic genetics, but, for cost reasons, that should be done through NSF not NIH. But if anything is to be neglected it would be the work on the therapeutic approaches to hundreds of truly, seriously genetic diseases, and much less on the huge genomics studies aimed at genetic prediction or common diseases (like the targets of GWAS and biobanks); those are public-health scale approaches yet quart size Cokes and fries, not genes, are the major public health problems.
How Dr Collins will do will be interesting to see.
Posted by Ken Weiss at 7:29 AM
Tuesday, May 18, 2010
Blame it on Darwin?
Ken took part in a panel discussion recently about Nazi medicine and eugenics. The three participants on the panel were a lawyer who has done work on the legalities of torture, a historian of Nazi Germany, and Ken, a geneticist with interest in ethical issues. The discussion was led by a moderator, also a historian of Nazi Germany. This was in conjunction with a traveling exhibit, "Deadly Medicine," (logo at left) from the US National Holocaust Museum, that had been here at Penn State, and most of the attendees had seen the exhibit.
This was the third in a series of discussions of the importance of eugenics in Nazi Germany. Previous speakers had talked about the extermination programs that started, with the full cooperation of German physicians, with the elimination of mentally or physically disabled infants and children, and expanded to include many other members of society. The latter part of the history is well-known to most of us, but the acquiescence of the medical system is less so.
This third evening started with a discussion of the history of eugenics and how it came to motivate the Nazis. Ken traced it back to Darwin, and the idea of survival of the fittest, which was quickly translated into the social arena (mainly not by Darwin but by others), reinforcing existing class-society ideas whereby the richest, smartest, most powerful are best for society, while having to maintain the poor and the ill is an endless resource burden on the stronger members of society. This burden not only seemed unfair (to the rich and smart and powerful), but the cost of support for the weak, ill, insane, or otherwise undesirables would be a permanent drag on a society that wished to be its best. Thus, in implementing government-driven eugenics (sterilization and eventually murdering the 'undesirables'), the Nazis believed -- or, rationalized -- that they were doing what was right for their country by culling the less fit. Germany would become the #1 country in the world. Deutschland uber alles!
Darwin's ideas, and a strict adherence to the view that human individual or 'racial' traits can be judged to have more or less value and, because of evolution, are inherent, led scientists to decide that whereas Nature had made those judgments in the past, we (the scientists) are the ones whose duty it is to make them in our scientific age. The historian on the panel agreed about the importance of the eugenics movement in Germany at the time, and added that for cultural reasons the medical system was especially well-situated (or unfortunately situated) to support the cleansing of society in this way. Doctors did a lot of the dirty work, signed off on even the worst horrors, and gave the stamp of respectability to much of what happened. This history is well-known, but perhaps less so to the younger generation, which is why the 'Deadly Medicine' exhibit was brought to Penn State, and why there were three different events discussing its meaning.
In any event, the panel moderator finally noted that Darwin's name had been mentioned a number of times during the evening, and asked whether it was fair to conclude that Darwin should be blamed for the Holocaust. Darwinism is still used as a justification for making value judgments about human traits, including races, and for justifying inequality as a natural state of Nature. This is in fact an idea that has been widely promulgated by the extreme right wing in the US, and by Creationists. Ken's response was that blaming Darwin for what people did with his ideas would be like blaming Benjamin Franklin for the electric chair. This of course won't diminish the blame the right wing and religious fundamentalists bestow on Darwin for all of society's ills, because this is an ideological struggle, not one based on facts -- and of course Darwin's real sin was claiming that humans were not created by God in their present form.
But still, there are many lessons to be learned from the eugenic age for us in our own genetic age. Evolution, too, is an idea that is out there and can't be undone. We are not likely to repeat the same horrors of the original eugenics age, but new genetic data and the belief that genes determine your nature, can easily be misused in our own new ways, and there is no guarantee that those ways will all be benign. Our society will face the issues related to this, such as confidentiality of genetic data, the use of such data in governmental monitoring of citizens, in policies related to insurance and in many other ways. Many investigators are analyzing data on human variation in ways that are, perhaps unintentionally, almost identical to the categorical ways our species' variation was treated a century and more ago. Ken has a couple of papers in press that point this out.
So, whether remembering history actually discourages people from repeating it or not, we think it's incumbent upon practitioners of genetics and anthropology, which of course has its own entangled past with the Nazi regime, to know the history of their disciplines, and to be aware that it wasn't all pristine.
Posted by Anne Buchanan at 5:38 AM
Still, thinking about it, while it's very newsy, there is nothing particularly scientifically important about the question from a genetic point of view. Yes, there could be traits found in Neandertals but not in our lineage. Bigger brow-ridges may be an example. But we vary among ourselves in important traits (like disease susceptibility), and clearly in many physical traits as our 'racial' variation shows. This may have a lot to do with genetics, case by case, but it has very little to do with species or admixture.
For these reasons, despite the genocentric focus of all the news, the really interesting questions are not genetic ones. They are cultural ones. What were the Neandertal and pre-modern populations like in size, behavior, environmental preferences, language, technologies, and so on? What were their mating patterns? When they saw each other, what kinds of relationships did the two groups have? If there was intermating, were there recognized kinship affiliations among the adjacent villages of the two groups? Did they share religious, body-decorating, food preparation and preference, and so on patterns?
It is these things, not genes, that could have been far more important in determining what happened. It is true that genetic differences, even in something like body smell, could have inhibited mating. But why do so many go so far out of their way to suggest things, than to try to find cultural explanations?
In part this is because genes mean grants, the news media eat it up, and they're the causes-du-jour of our time. It is possible, certainly, that there were genetic barriers (even our favorite self-promoting criterion of intelligence). But then to suggest that and yet see some intermating evidence, leads to forced explanations (such as, essentially, rape of Neandertals by aggressive, superior, violent 'moderns'). That, too, is catchy and may attract media as well as professional attention. But so far, it's not supported by any actual evidence beyond the imagination.
Again, right under our noses is the most fascinating question of all: how one human-like species completely displaced or replaced another. The Neandertals disappeared, if they were indeed more than a 'racial' group at the time. But before that, even more surprising if current views are close to correct, about 100,000 or fewer years ago, premoderns spread out of a spot somewhere near east Africa, and the long-established Homo erectus creatures disappeared.
It's difficult to imagine how these things happened, other than by accepting superficial, nearly evidence-free speculations. But in any case, those questions seem more interesting, and are certainly more challenging, than always focusing on genes.
Darwin and others worried that the protections of society would lead to the pollution of our gene pool. This was one of the motivating factors of the eugenic movement, as we discussed in a recent post. That movement aimed to remove the 'unfit' (in the Darwinian sense, but often equated to what scientists felt were undesirable in their local social sense).
This is all true and the paper referred to in the news story is a good and informative one that shows how genetic technology has made it possible to find some specific responsible genes, even if one can debate the strength of evidence for some of its examples. But as so often happens with media reports, there is a problem, and the story is misleading in that it seems to suggest that the molding effects of culture are recent (say, post-agricultural), or enumerable (only a few traits molded that way), or that this is a new discovery.
Instead, there is nothing whatever new about this except the identification of specific genetic examples. Once again, it's misleading media-hyperbole. A better understanding of human nature, and an antidote to eugenic-like thinking, or ethnocentrism with the problems that causes, would result from the realization that is not at all new to anthropology, that humans have always been, from the beginning of our divergence from common ancestry with chimps and other apes, the cultural species. From upright posture, to opposable thumbs, language, hairlessness, our physical helplessness relative to other species (no claws, fangs, wings, etc.), and so much else, this has always molded our way of life. As CL Brace, a leading anthropologist put it way back around 1970, culture was humans' ecological niche -- culture is why are here. Indeed that was offered as the reason there is only one human species here today--what was called the competitive exclusion principle in population ecology: only one species can occupy any given ecological niche.