The Unz Review: An Alternative Media Selection
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CRISPR associated protein

CRISPR associated protein

When I first started writing on the internet in the early aughts times were different. Preimplantation genetic diagnosis (PGD) was more science fiction than a topic which touched the realm of reality. Yes, there was screening for a handful of classic recessive diseases, and somewhere Leon Kass was reflecting upon human dignity being undermined by the very idea of PGD with all the clarity of Martin Heidegger ruminating upon Being. But really this was a speculative period, when we were test driving arguments, positions, and talking points. I believe most of us understood that we were rehearsing for the true battles which would erupt at the center of modern civilization with the rise of biological engineering.

The era of test-driving arguments is over when you see articles by Gina Kolata about real people in The New York Times. Ethics Questions Arise as Genetic Testing of Embryos Increases:

On the spot, Ms. Baxley, 26, declared she would not let the disease take another life in her family line, even if that meant forgoing childbirth. “I want it stopped,” she said. The next day, her boyfriend, Bradley Kalinsky, asked her to marry him.

But the Kalinskys’ wedded life has taken a completely unexpected turn, one briefly described on Monday in The Journal of the American Medical Association Neurology. Like a growing number of couples who know a disease runs in the family, they chose in vitro fertilization, and had cells from the embryos, created in a petri dish with her eggs and his sperm, tested first for the disease-causing gene. Only embryos without the gene were implanted. The Kalinskys are now parents of three children who will be free of the fear of GSS.

The subject of the story is still likely to die at some point during or before her 50s. And, that process of death may span as much as two decades. So the disease, and the couple’s choice to have children, is not without consequences which are less than optimal. But the bottom-line for me is that the decision made here was fundamentally a noncontroversial pro-life act. In the face of the darkness of a potential terminal diagnosis this woman and her husband have brought forth life, and as a new father I truly know in my bones the joy of that as I never would have before. But this isn’t a human interest piece, much of the article is given over to the vague and to be expected platitudes from ethicists. There is “trouble.” The implications are “unsettling.” To me these sorts of talking points have all the power of “think of the children” as an argument against interracial marriage. You can see where they’re coming from, and it’s nowhere substantive.

I assume that professional ethicists not constantly being interviewed by high profile journalists have opinions which aren’t easily condensed into one sentence triteness. Or perhaps more fairly that’s just what gets distilled from a long interview. But I’m rather sick and tired of ethicists being “troubled,” and also fed up with reductio ad absurdum arguments. At one point Kolata paraphrases one of her sources as saying: “Eliminating embryos with such genes is essentially saying someone like Ms. Kalinsky should never have been born.” What does that even mean?

To truly get to the heart of these questions we have to ask deep philosophical questions about the nature of one’s own existence, being, and identity. Obviously that’s not appropriate fare for The New York Times, which seems to be cautious about treading beyond its core milquetoast mildly liberal reading audience. The sorts who are self-satisfied in their unexamined enlightenment received from on-middlebrow. But PGD and the assorted technologies of the mass applied biology of the first few decades of this century will force us as a society to elucidate once more what we truly believe the good life is. What is the life worth living? Is it truly just the lives which parents deign worth living? Society? Gods on high? These are the real questions which strike at the heart of the matter, and the sooner we get to them, the sooner we’ll achieve our unsatisfying resolutions.

• Category: Science • Tags: Bioethics 
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At 9 weeks
Credit: Ed Uthman

A new opinion piece in The New England Journal of Medicine is titled A New Era in Noninvasive Prenatal Testing. It is free, so I commend you to read the whole thing. But this is the key section, “A new, noninvasive prenatal test is poised to change the standard of care for genetic screening. Cell-free fetal DNA (cfDNA) testing requires only a maternal blood sample, can be performed as early as 9 weeks of gestation, and outperforms standard screening tests for trisomies 21, 18, and 13 in high-risk populations.” Nine weeks is of course still in the 1st trimester.

While 60 percent of Americans support the legality of 1st trimester abortions, only 30 percent support the legality of those in the 2nd, and it is in that trimester that the abortion of a fetus with a trisomy abnormality now occurs because the various prenatal tests are at this stage. Mind you, I understand that despite what the public says a larger share of parents who receive “positive” results in that trimester abort the pregnancy than might be expected based on surveys about the legality of the practice. But, there is probably considerable room on the margin for the class of those who would opt for this if the results arrived in the 1st trimester.

And of course trisomy tests are just the beginning. Whole genome sequencing of 2nd trimester fetuses is now possible, and it seems very likely that in the next few years they’ll move all the way to the 1st trimester. At that point the genetic analysis of 1st trimester fetuses will be routinized and be a simple consumption good. The ultimate question is what are we going to do with all that information? This is not hypothetical, speculative, or blue sky. It’s almost a reality.

• Category: Science • Tags: Bioethics, Prenatal Screening 
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Obsession. I’ve been obsessed with many things in my life, from specific women to sundry topics. But I’ve never known obsession until I had a child. Perhaps others are not like me, but the monomaniacal need to know as much as you can about your future child as soon as possible gripped me early on. Even today I want to know as much about her as I can. This is why I had her genotyped at two months, and this is why I plan to have her whole-genome sequenced as soon as it is feasible. This doesn’t mean that I put much stock in the power of individual prediction. Rather, even if the returns are marginal even the smallest tidbit of knowledge about my child is precious to me.

This is why I’m left scratching my head when I see pieces which moot concerns about whole-genome sequencing of fetuses. Obviously some people will go for it, and some people will not. It won’t be very cheap, nor will it frankly tell you that much on a per base pair basis as a function of the cost. But it will tell you something, and depending on the coverage (ergo, how accurate the sequence is going to be at the end of the day) you keep the information you get. Imagine, for example, that it would cost $5,000 for 10X coverage. Would you go for it? I would. Why? How much does the average American car cost? $30,000 dollars. A car is very useful, but it’s a depreciating asset. A genome will never depreciate, it won’t degrade. In fact, as more research gets done its utility will only increase! If people are willing to pay >$5,000 for a high end gaming box, and not be perceived as crazy, why should genophiles be seen to be wild-eyed weirdos?

Of course the natural objection is that I’m discussing a problem which doesn’t exist. I wish this were so, but there’s a whole bioethics industry whose bread & butter is to trade in flimsy and specious reasoning, which might appeal to politicians who are will to purchase specious reasoning for purposes of their demagoguery. For example, As Prices for Prenatal Genome Sequencing Tests Fall, Researchers Worry About Consequences for Families in a Real-Life ‘Gattaca’:

Donley and her fellow investigators cited three specific areas of concern. The quality and quantity of information in existence, and the changing definition of “normal”, may lead to an increase in the number of pregnancy terminations.

They also worry that, after the child is born, genome sequencing could have implications on raising children. For example, if parents are already aware from the time of their child’s birth of little Billy’s predicted low IQ score , it may cause them not to push him to do well in school, even if the prediction is incorrect.

Donley and her team also point out that a parent’s right to know in order to better inform their reproductive choices may conflict with children’s rights to not know.

But researchers also point out that genome sequencing would be futile for a while. For 90 percent of genes their function remains unclear, so sequencing would be unclear and of relatively little use. Researchers believe that , in the present tense, specialized genetic testing, like the kind currently in use, would hold more utility for future parents than genome testing.

The National Institute of Health fellows suggest that doctors elaborate a plan about just what kind of information may be given to parents. They also say that the child’s right to not know should not be breached, except in special circumstances. Professional societies, like the American Medical Association, should coach the public on the difference between genome tests and current genetic testing. And, of course, they say that more data is needed to coach both professional organizations and the public.

First, the main issue I always have in regards to “the children” is the context is that we as a society give broad liberties to parents to behave bizarrely and thoroughly embarrass, mortify, and “fuck up” the lives of their children. Some parents even tell their daughters that they’re “dirty sluts” and they should stay away from boys, lest they tempt them. Other subcultures expel young boys to make polygamy feasible. Of course bioethicists need something to do, and we’re not going to solve all the world’s problems by ignoring genomics. But a lot of the “concerns” just make me laugh, they’re so picayune and vague. The child might know something which might not be totally “true”! It’s all terrifying, in a verbose academic sort of way.

As for phenotypic prediction, who exactly are these parents who won’t invest in a child who may have difficulties? Sure, they exist, but I’m pretty sure they’re not the ones who will pony up for prenatal sequencing! Rather than not investing in a child a natural weakness in one domain may actually be a reason to invest more in that child! Yes, some parents do “think of the children.” Most parents who are involved and learn their child has a learning disability don’t give up on the child. They try proactively allow that child to overcome their extra barrier.

Finally, who does the AMA think they’re going to be fooling? Oh yeah, they’ll explain the difference between a whole-genome sequence and just using a SNP-chip. Most doctors don’t have the time or inclination for this sort of thing. That’s why there are genetic counselors. And since most people are not too bright some level of paternalism is perhaps warranted, but this is information we’re talking about, not cyanide. I think the threshold for paternalism when it comes to an individual’s own information, or that of their children, should be set very high. Here what they are implicitly suggesting is that a priestly class of information librarians should dole out their nuggets of wisdom when they think it is prudent. Reflect on that.

You can find original paper which the piece above was based on online, Prenatal Whole Genome Sequencing – Just Because We Can, Should We?. Frankly a lot of it is anodyne concern about public health confusions. I would say that where the authors focus on “trained professionals” I would put the onus on more sophisticated automatic analytics. There’s going to be lots of money to be made on mass-marketed genetic interpretation software, and for the truly well-off I’m sure firms such as 23andMe would be willing to provide the services of a professional statistical geneticist who would be able to do a deeper consultation.

Since the authors are so scared of how ignorant the public is one obvious solution would be to make parents take a test as to their scientific knowledge in this domain. I have more confidence in my own abilities to interpret my genetic data than any licensed professional who would be there to collect hundreds of dollars per hour to explain my results to me (I’m sure I’m not the only one a little irritated when my M.D. alludes to some genetic issue, allows me to elucidate in more detail, and then collects the fee from the insurance company for listening to me). This way you’d have a paternalistic track and a non-paternalistic track. Mind you, when it comes to information I don’t think this sort of paternalism does any good, but this may be an option that we have to fall back on.

Then there’s the concern about genetic determinism and free will. Here’s some relevant passages:

Wilfond and Kathleen Nolan call extemporaneous, where the independent market, professional practice, and legal and consumer forces determine utilization. Conversely, in the evidentiary model, new technologies are adopted after an examination of the underlying normative considerations that arise from their use

It is clear they prefer the “evidentiary” model. This does not make me happy. I am a priestless person, and I decide what my norms are. I don’t take kindly to a reemergence of medical paternalism in the 21st century, where the professionals you are paying decide what is, and isn’t, right for you, sometimes behind your veil of ignorance. Then there’s this section:

We are concerned that the technology could (1) change the norms and expectations of pregnancy in ways that complicate parental autonomy and informed decision-making, (2) exacerbate the deleterious role that genetic determinism plays in child rearing, and (3) undermine children’s future autonomy by removing the option of not knowing their genetic information without appropriate justification.

Abortion is a totally different debate, and I’m confused and irritated that they’re trying to bring this into the prenatal sequencing discussion. Of course that’s bound to rile people up, though perhaps that’s the intent. Second, we don’t have enough genetic determinism in our culture! Actually, “genetic determinism” is a word like “anti-choice” or “pro-abortion.” People who believe in the power of genes to shape outcomes are rarely determinist, rather, that’s a term of aspersion which critics make recourse to. As Steven Pinker has noted if you say that half the variation of the trait is genetic, you will be called a determinist, even if it is obvious that the other half is non-genetic (this has happened to me). I subscribe to the philosophy implied from The Nurture Assumption and Selfish Reasons to Have Kids. Micromanaging the environment of your child is unlikely to have longer term effects, so you should relax a little. As for the free will aspect, are we back to St. Augustine and Pelagius? Is this really appropriate for a discussion in bioethics? I hope this journal has a decent impact factor to justify such a strange tack.

In the end it is simple: be very careful when you suggest that the free choice of parents should be curtailed for the ‘greater good.’ There are cases where this does need to occur, but you better have strong grounds to stand on, because I’m apt to be vicious if you get between me and my obsessions. This isn’t child’s play, this is my child.

Via Dr. Daniel MacArthur.

• Category: Science • Tags: Bioethics, Personal Genomics, Prenatal Screening 
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As they say, read all about it. I’m rather ambivalent. 23andMe has a business rationale to go in this direction, so I don’t begrudge them their decision. The problem, at least from a legal perspective, is that they’re providing medical advice at least implicitly. And I think this medical direction is really where the big money is in any case. There’s no angle standing on principle.

But, I still believe that on a deep level regulatory agencies don’t “get it.” Our own genotype and genome is going to be a cheap commodity in the next few years. Services like Promethease will proliferate to provide people open source information. Is openSNP going to the FDA anytime soon? The main reason that firms like 23andMe will go through regulatory hurdles is that they are, or aim to be, legitimate public entities. In other words this is an artifact of our institutions. Mind you, 23andMe et al. will probably always have slicker user interfaces, and there’s some value in that. But that doesn’t entail FDA oversight, does it?

The shift toward automation and computation are real ones, and I have a difficult time how seeing regulation developed in the 20th century is going to be relevant. There is a doctor shortage in this country. The number of graduates from medical schools is not keeping up with population growth, or a shift toward a population which consumes more health care. For regulatory reasons professionals like nurses can’t provide all the services that a full M.D. can, and I see no expectation that the medical professionals of the USA will welcome more competitors. So technology is the way to go in increasing productivity. If doctors don’t go into general practice because there’s no money in that, perhaps there’ll be an app for that?

I’m not imagining some magic bull algorithm. Rather, I’m assuming that the quantified self and more powerful artificial diagnostics will be able to take care a lot of the “low hanging fruit.” Personal genomics is part of this, though obviously not the totality of it.

• Category: Science • Tags: Bioethics, FDA 
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An interview with paleoanthropologist Chris Stringer:

This raises one more question: Could we ever clone these extinct people?

Science is moving on so fast. The first bit of Neanderthal mitochondrial DNA was recovered in 1997. No one then could have believed that 10 years later we might have most of the genome. And a few years after that, we’d have whole Denisovan and Neanderthal genomes available. So no one would have thought cloning was a possibility. Now, at least theoretically, if someone had enough money, and I’d say stupidity, to do it, you could cut and paste those Denisovan mutations into a modern human genome, and then implant that into an egg and then grow a Denisovan.

I think it would be completely unethical to do anything like that, but unfortunately someone with enough money, and vanity and arrogance, might attempt it one day. These creatures lived in the past in their own environments, in their own social groups. Bringing isolated individuals back, for our own curiosity or arrogant purposes, would be completely wrong.


I do find it curious that Chris used the term “creatures.” This probably not intentional, or with serious conscious intent, but Neadertals and Denisovans are creatures I think the ethical issues are strongly mitigated. After all, chimpanzees are used in medical experiments. I assume that the woolly mammoth will be the first extinct complex organism which is resurrected. But what if they’re human???

Stalin purportedly wished to create ape-human super-soldiers. What if it is true that Neandertals were, and would be, far stronger on a per unit basis than humans? Can you imagine: “unleash the Neandertal brigade!” More optimistically, what if Neandertals lacked social intelligence, but exhibited very strong aptitudes in the visuo-spatial sciences? Neandertals had average cranial capacities which were larger than modern humans.

• Category: Science • Tags: Bioethics, Neandertal, Neandertal genomics 
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An interesting comment:

“If you add copies of a gene the result is not always good because of dosage effects (Down Syndrome is an extreme case of this on the smallest chromosome).” [From my post, -Razib]

As a father of a child with Down syndrome, I would take exception to this comment. First DS, is not “bad” – my daughter is an amazing and wonderful person, and her DS is part of that wonderful person. She is one of the most amazingly positive things that has ever happened in my life. So I have a hard time reconciling that with your “extremely bad” synopsis.

Second, DS is not an at all extreme case – it is rather run of the mill. It is so minor of a variant that it is survivable and very common place (1 in 733 births). People with DS lead full, productive and meaningful lives. That is not extreme, it is mild. Extreme would be being born inside out or having no chance of surviving 72 hours.
Please don’t add to the misconceptions around Down syndrome. Most of us parents, siblings, and self-advocates find this to be both untrue and unhelpful.

I feel to some extent that the commenter is engaging in a few rhetorical tricks (e.g., contrasting Down Syndrome with diseases which result in mortality within a few days of birth). But his point is well taken. I think it is useful because it smokes out some presuppositions about the nature of the world and the values we hold. The sketchy statistic is that 90% of couples who receive a positive result for Down Syndrome opt to kill their fetus (the shift toward older mothers though means that the number of children growing up with Down Syndrome is not declining nearly as much as you’d think). But in the media you see many more pieces such as George F. Will’s: Jon Will’s gift (for the record, Will is an agnostic). There seems here a disjunction between how people act, and what people say. Or, perhaps more accurately what people don’t say.

One tack would be address Brad, the commenter, head on. I might point out that Down Syndrome can be bad, even if his daughter is a joyful and happy person who brings nothing but good into his life. But I don’t want to argue on the details of one specific case here. I suspect most readers will accept that I don’t think that just because I believe Down Syndrome is a disease I mean to imply that the lives of people with the disease are totally bereft of happiness, or that they are without value. That’s a caricature which only leads to fruitless and symbolic discussion, which plays out mostly for public consumption, and is not getting to the heart of the issue.

And the heart of the issue is that I believe that humans flourish best when they are beautiful, intelligent, and healthy. Some people deny that beauty and intelligence are anything but social constructs. But I bet a survey of progressive and enlightened women who might accept such propositions at face value, but who are in need of sperm donors, would indicate that no matter what people say for their peers to align with social norms they believe that beauty and intelligence are heritable, and their preference would reveal that they value these traits (individuals looking for sperm donors tend to value intelligence, height, and athleticism in the potential biological fathers). As far as health, as Brad’s comment suggests that’s a somewhat subjective proposition. Many of us have allergies. Are we diseased? I’m a very happy person who brings great joy to some people, but I do have this common autoimmune disease. Additionally, I’d also be happy to get rid of it. To address Brad more specifically: his daughter’s Down Syndrome is not a necessary condition for her being a wonderful and amazing person. I wish she did not have Down Syndrome.

All of this naturally opens us up to the “slippery slope” rebuttal. I think that’s a useless argument and I’m going to ban you if you bring it up. I don’t want to create a clone race. Being tolerant of a reasonable range of genetic and phenotypic diversity does not mean that one should be equanimous to the birth of people with karytotype abnormalities. I’m sure at some point someone will use the term “karyotype diversity” in more than a technical sense. It’s keeping with the spirit of the age, but it’s a farce. Diversity is not strength when that diversity is diversity of disease. Heart disease, congenital defects, disfigurements, obesity, and mental retardation are not strengths. They are all tragedies of various degrees.

The point of this post was to forthrightly admit and assert what I think are values which most of the human race holds implicitly. These values to some extent have been silenced because of the unfortunate fact that the Nazi regime took these intuitions and warped them to perverse and inhumane purposes. But I do not think that the world we have today is the “best of all worlds”, I think we can do better, as individuals, and as a society. It is doubtful we can abolish disease, but we can make a dent it in. It is doubtful that we can all be as svelte and fit as we wish, but we can aim toward such a goal. Unfortunately we do not cultivate our minds to the extent we would like, but we can agree that it is a goal worth pursuing and elevating.

In sum, humans differ, and that difference is not always a strength. The tall, handsome, and intelligent, have traits which most people feel to be superior. There is inequality. We can not abolish inequality, but we can increase the basal level of human quality of life. This may seem like an abstract digression, but it is not. In the near future we will have a much better sense of our mutations, and those of our potential offspring. Our values will guide our actions. Let’s have a frank and honest discussion about them.

Image credit: Tolgrenn

• Category: Science • Tags: Bioethics, Down Syndrome 
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In the comments:

And yes, species concepts are much more fuzzy in many cases. Were mice to hold their own Olympics, they might well have learned (if slightly furry) discussions about whether musculus/domesticus/castaneus should compete in the same events, and if so, which events molossinus or other hybrid individuals should compete in. As humans, we dodge that bullet by having no closely enough related species to confuse the issue. The difference between us and a chimp is well defined. If Neanderthals were still around, that would be a different matter.

What happens is a nation (e.g., China?) reconstructs a Neandertal individual from the sequence in the public domain as well as segments from living human beings. Do they get to compete as power-lifters? This might seem like a crazy question, but I’m not totally unconvinced that it will be just academic within our lifetime. Genetic modification is likely to become ubiquitous within a generation.

Image credit: Wikipedia

• Category: Science • Tags: Bioethics 
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The New York Times has an article up on a new I.O.C. ruling on who can compete as a woman. Basically they look at testosterone levels. This seems a different tack than cases where women were banned from competing as women because they had a male karytoptype (AIS). This article came on my radar because I had already read this op-ed from about a week ago, You Say You’re a Woman? That Should Be Enough. This sentence jumped out at me:

Second, when it comes to sex, sports authorities should acknowledge that while science can offer evidence, it cannot dictate what evidence we should use. Scientifically, there is no clear or objective way to draw a bright line between male and female.

What do people think of this assertion? I’m aware of intersex individuals. But if we start to assert that dioecy is just a “social construct” then let’s revisit species concepts. I’m sure there are some farmers and loggers who might assert that one can’t draw objective bright lines between populations. Distinctions between male and female in most species is much more clear and distinct than various taxonomic categories.

• Category: Science • Tags: Bioethics, Sex 
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Evolution’s winner. Real headline.

In the mid-2000s two British biologists of some public note attempted to revive or resuscitate the good name of eugenics, Richard Dawkins and Armand Leroi. My own suspicion is that this emerges in part from a implicit cultural history in the British Isles in regards to eugenics: in those nations,* unlike in the USA or Germany, eugenics was generally conceived of in the positive rather than negative sense. By this, I mean that a disproportionate amount of thought was given to the procreation of the favored, rather than coercive restriction of the unfit. This is exemplified by R. A. Fisher, the co-founder of both evolutionary genetics and statistics, who worried about the high mortality rate of the British elite during World War I. Fisher himself went on to have eight children, a situation which occasionally left him in financial distress, as would be predicted from standard Malthusian assumptions (see R.A. Fisher: The Life of a Scientist).

But despite the best efforts of Dawkins & Leroi, eugenics is still a swear word. For example, a few months ago Chris Mooney was accused of being a eugenicist because of the nature of his arguments in The Republican Brain. Of course there’s a difference between the word, and the reality. Idiocracy had an implicitly eugenical moral. And there are dating sites like Good Genes:

Our mission is to help Ivy Leaguers and similarly well-educated graduates and faculty find others with matching credentials. We introduce people who enjoy sharing thoughts, opinions and quality time.

Apparently good genes do not entail web design skills which post-date 1997. In any case, “good genes” has been obviated by the emergence of social networks, where people can sort and segregate to their hearts’ delight. And of course there is a copious social science on the strong racial and ethnic preferences of people dating. In particular, this preference seems to be much stronger in females, as one would predict from behavioral ecology (i.e., women are looking for “good genes” because they have a smaller number of potential reproductive opportunities).

Finally, there’s the famous statistic that 90 percent of couples who receive a positive test for Down Syndrome choose to terminate the pregnancy. That is, they request the doctors kill the fetus. This datum is at the heart of a recent Ross Douthat column, Eugenics, Past and Future. I appreciate Ross’ take though I disagree on the details and normative implications. He at least attempts not to be trite or trivialize the matter. Many conservative critics of eugenics are more interested in using the term as a cudgel against liberals, while liberals abhor eugenics the term, but dismiss the eugenical implications of individual freedoms which they defend (the abortion & crime argument being an exception). Douthat is clearly against eugenics, but he draws up real statistics and cutting edge science which attests to its reality in our time.

In particular he is putting the focus on non-invasive forms of prenatal testing. I do think that he overestimates the power of individual prediction broadly in the near term (and possibly the long term). Though there are many traits, like height, which are highly heritable, they’re so genomically diffuse that you have to screen from a wide range of embryos before you pick the “right” one. And that assumes you can adduce a good correlation between genotype and phenotype. But, there will be some immediate yield when it comes to large effect genetic abnormalities.

We can have theoretical discussions about genetics and ethics, but the real phenomenon which aggravates me about people who act Very Serious is that this is a domain which manifests not through discussion, but action. If you read the articles about “test tube babies” from the 1970s you notice how frightened everyone was, and contrast it with the banality of in vitro fertilization now. The past is not always prologue to the present, but if we have such high abortion rates of fetuses with Down Syndrome via amniocentesis and CVS, it is totally reasonable to assume that the rates will increase even higher with widespread and nearly obligate screening.

I’m not a pro-choice absolutist. In fact, I don’t even believe in rights, as such. I’m generally predisposed toward stronger restrictions on post-1st trimester abortions on the grounds which pro-life people would recognize. But, I also think we do need to open the possibility toward restrictions on 1st trimester abortions in some circumstances if feasible, because I do not believe children are a parental consumption good. In other words, becoming a parent is not an increment of individual utility in toto. The child is going to be a member of a community, to which they will have responsibilities, and from whom they will derive benefits.**

We did choose to go through CVS testing when my daughter was in utero. And I plan to have some form of non-invasive screening performed for our next child. That’s a personal choice. When I explain my rationale to people often I get standard-issue ignorant repugnance. My main annoyance is that it’s an unthinking reflex in a world already saturated with artifice. We need to have a serious conversation about the limits of individual self-actualization when it comes to the potential lives of other human beings who are integral elements of society. But, in the interests of candid realism I am very uninterested in the stories of people like George F. Will (who is, by the way, an agnostic) about the value of their Down Syndrome son. George F. Will is a man of means. I’d like to see how a struggling lower middle class family manages. There are many more of them. This is a frankly base consideration, but such are the things which constitute a life lived in the real world.

* Britain is home to three nations, England, Scotland, and Wales.

** My concern about sex-selective abortion is as much a consideration of a well balance society as it is about sex-bias.

• Category: Science • Tags: Bioethics, Down Syndrome, Personal Genomics, Testing 
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Nature has a Peopling the planet issue out that is worth reading. Lots of the features are free to the public, but Chris Stringer’s comment is not. Though there is some science in the comment, a lot of it is about normative concerns. Not what is, but what should be. Or, more precisely what should be the values we hold dear, rather than the reality of the world as it is. But this bit caught my attention: “Already I’m reading blogs that speculate about whether some groups are less ‘modern’ than others, and I fear that such discussions endanger the considerable progress promised by palaeogenetic research.” Well, I know Chris drops in on this blog now and then, so I hope he’s not talking about little old me!

Though more seriously, there are two issues where I want to dissent from Chris (or at least what I think he meant). I don’t know what he meant by “discussions endanger the considerable progress promised by palaeogenetic research,” but it sounds like he’s talking about what palaeogenetic research may imply for things which are not palaeogenetic research. At this point I think we should really start being more thorough about separating the is from the ought. Like the visually accessible aspects of astronomy paleogenetics appeals to something deep within us on a level which is more transcendent than the real and concrete achievements of civil engineering. But I don’t think palaeogenetics teaches us any deep moral lessons anymore than the Bible does; in other words, it does not tell us anything we don’t already know. Moral human equality has little to do with human identity. Where to place readers of this weblog, who seem to be superior in general intelligence, but generally less gifted than the average in terms of social wisdom? Humans are diverse. We know that. Science will simply add nuance and depth to that understanding.

The second point extends upon the first: why fixate on the DNA that unites us? If the squid were understood to be sentient, would we deny it it is dignity because of low DNA sequence identity? I hope not. If the machines ever think, and demand that they should be due their proper rights, then we should entertain that proposition. Frankly, if an entity has reached the level of self-awareness to demand basic “human” rights, then that seems grounds to grant those rights on the spot! One of the most annoying aspects of Blade Runner for me is that it was hard to sympathize with the protagonist due to his vicious profession, of hunting down humans who were stripped of their humanity (replicants). I wouldn’t be surprised if uplift were possible in the near future. If it is, then why not? We’ve always speculated what animals would tell us if they could talk. Then let them talk!

A few years ago we barely thought Neanderthals were human. Many scholars speculated that they lacked language. Now we know most of us have Neanderthal ancestry. Are we less than we were? Obviously not. There’s no magic threshold of human. And there’s no magic threshold of modern. I come not to offer simple answers, but to repudiate clear and distinct measures of modernity and humanity, which lull us into the delusion that we don’t need to wrestle with what makes us humane and what separates us from the “beasts.”

• Category: Science • Tags: Bioethics 
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There’s news about the Woolly Mammoth cloning attempts again. This gets floated every few years, and nothing has come of it…yet. I assume with enough money and time invested it will come to fruition. And whoever invests their time and energy and gets a successful return will probably get really famous, really quickly. But I’ve recently been thinking of a more practical application of cloning: reproducing enormous numbers of individuals who are mostly replicates of John von Neumann.*

To get a sense of why, see this Steve Hsu post. You can read about how much of a genius von Neumann (he was a source for Dr. Strangelove), but his legend is even larger in the oral history of mathematical science. There are still individuals alive who knew von Neumann personally, and they continue to maintain the memory of his preternatural mind.

My argument for cloning von Neumann in large numbers has a practical rationale: the world needs genius to maintain complex human civilization. John von Neumann certainly qualifies as a genius. And we need more than one, as it is likely that there is a random element to the expression of his particular brilliance.

* von Neumann is buried in Princeton, so partially degraded DNA would have to be extracted from his grave. One can also utilize DNA from his daughter, who is still alive.

• Category: Science • Tags: Bioethics, Cloning 
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Get ready for PGD, the acronym for preimplantation genetic diagnosis. We don’t really talk about “test tube babies” anymore. It’s “IVF,” and as American as apple pie (OK, perhaps as Israeli as falafel). Here’s the Ngrams result:

It’s just not that big of a deal anymore. But take a look at the order articles in The New York Times. There was a day that peopel were very worried about what “test tube babies” entailed. The end of the world as we know it? If that happened I don’t see anymore complaining.

The Globe & Mail in Canada has a very long piece on PGD, Unnatural selection: Is evolving reproductive technology ushering in a new age of eugenics? I do think it is ushering in a new age of eugenics, though it doesn’t go by that name. Many of the issues I’ve brought up on this weblog, such as the incentive for governments which fund national healthcare to take a deep interest in sifting through the range of future taxpayers and consumers of services, are explored. My basic instinct here is much more libertarian than most people. As a practical matter I’m rather close to a maximalist in terms of the amount of latitude I think parents should be given in selecting the nature of their offspring. But, I’m not a libertarian in an absolute philosophical sense, and I think a broader discussion in a society where the state and majority have coercive power over individuals is warranted.

There are two minor technical angles that I do want to bring up though:

– PGD seems to be ideally tailored already for people who marry their cousins. It would be relatively good at screening for the many recessive diseases which are common in the children of cousins. Also, it might even be able to reduce the fraction of runs of homozygosity through judicious selection. So, in the near future Muslim nations might be major consumers of PGD (Muslims as a whole are moderately anti-abortion, but they take a much more pragmatic line on these issues than the Roman Catholic church).

– PGD for trait selection runs into some statistical genetic difficulties. But, I wonder if perhaps PGD for decreased mutational load might be useful? With high coverage full genome scans could not one ascertain with good precision which genes have been subject to inherited or de novo deleterious mutations? It is generally assumed that loci where there is a major deleterious mutation masked by a normal functional copy still induce some fitness drag on the individual. The range in outcomes in siblings may be part of the natural variation in the mutational load. Parents may be tempted to lop off the asymmetrical-faced end of this.

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A comment below clarified my thinking in one particular area: is widespread genetic screening going to result in a reconsidering of the idea of ‘engineering’ society? I realize now that in a comparative scenario this is ridiculous. The majority of healthcare expenditure is near the end of life, not the beginning. In 17 years the last of the Baby Boomers will turn 65. The looming costs are rather straightforward. And it’s not just an issue in the United States, the whole worlds is going gray.


How do we handle this sort of sociological challenge? One solution lies in increased economic productivity through innovation. This is great if you can get it. But another was option is obviously something like a milquetoast form of Logan’s Run.* Governor Dick Lamm was reputed to have said “we have a duty to die.” But not to be churlish, I observe that at 77 years of age now Lamm himself continues to be active and full of life (he made the comments when he was 50).

I’ve also been thinking about this issue because of a radio series on learning to live with “early onset” Alzheimer’s. Upon further reflection I realize that I don’t think I would want to “learn to live” with such a disease. Yes, such things are easy to say now. But perhaps it is best that we start to consider these issues as early as possible, both individually, and as a society. At the end of the day many of us would say that the point of living is to live a good life, not to just live.

* The option of allowing in large numbers of immigrants is a short term solution, the source nations for migration are themselves aging.

• Category: Science • Tags: Bioethics, Eugenics 
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In earlier discussions I’ve been skeptical of the idea of “designer babies” for many traits which we may find of interest in terms of selection. For example, intelligence and height. Why? Because variation on these traits seems highly polygenic and widely distributed across the genome. Unlike cystic fibrosis (Mendelian recessive) or blue eye color (quasi-Mendelian recessive) you can’t just focus on one genomic region and then make a prediction about phenotype with a high degree of certainty. Rather, you need to know thousands and thousands of genetic variants, and we just don’t know them.

But I just realized one way that genomics might make it a little easier even without this specific information.

The method relies on the phenotypic correlation between relatives. Even before genomics, and genetics, biometricians could generate rough & ready predictions about phenotypic values based on parental values. The extent of the predictive power depends upon the heritability of the trait. A trait like height is ~80-90% heritable. That means that ~80-90% of the variation in the population of the trait is due to genes. The expected value of your height is strongly conditional upon the heights of your parents.

That’s all common sense. What does this have to do with genomics? Simple. You are 50% identical by descent with each parent. That means half your gene copies come from your mother and half from your father. You can’t change that unless you’re a clone. But, because of the law of segregation and recombination you are not necessarily 25% identical by descent from each grandparent! The expectation is that you’re coefficient of relatedness is 25%, but there is variation around this. A given parent either contributes their own paternal or maternal homologous chromosome. There’s a 50% chance that you’re going to inherit one or the other across your chromosomes, of independent probability. You have 22 autosomal chromosome pairs (non-sex chromosomes), so there’s a strong chance that you won’t be equally balanced between your opposite sex paternal and maternal grandparents (e.g., you have more genes identical by descent from your paternal grandfather than paternal grandmother).* Second, recombination is also going to generate new combinations. In the generation we’re concerned about this will work against the dynamic we’re relying on, by swapping segments across homologous chromosomes from the parents’ mother or father.

The ultimate logic here is to select for zygotes or gametes which are biased toward the grandparents with phenotypic values which you are interested in. To give a concrete example, if you have a parent who is moderately tall, whose own father was very tall, while the mother was somewhat short, and you want the tallest possible child, you’ll want to select zygotes with the most gene content identical by descent with the tall grandparent. The point isn’t to pick specific genetic variants, you don’t need to know that. All you know is that the tall grandfather probably had genes which resulted in a predisposition toward being tall. So just make sure that the grandchild has as much of that grandparent “in them.”

I still don’t know if this is going to be cost effective in the near term. But I began to think of it because in the near future I’ll be checking the genotype of a child who has a full pedigree of 1,000,000 SNPs of their parents and grandparents.

* Modeling it as a binomial, about 1 in 7 cases will have the expected 11 chromosomes from a focal grandparent. The standard deviation is more than 2 chromosomes. You need to have about 100 zygotes to expect to get any individuals who are 5 chromosomal units away from the expected value (i.e., the individual is 10-15% instead of 25% one grandparent, or 35-40%). Obviously you need more to be assured of getting zygotes of that value. And I neglected recombination, which would work against this, by swapping genomic regions….

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I’ve mentioned this before, but I thought I’d pass on the latest report on MaterniT21, the prenatal noninvasive Down Syndrome test. Currently it has a $235 copay for women with insurance. As of now only a few percent of the ~5 million pregnancies in the USA are subject to amnio or c.v.s. This procedure may result in the screened proportion going from ~1 percent to ~50 or more percent (though the firm that is providing this can only process ~100,000 tests per year as of now). I stumbled upon this after doing a follow up on my post, Would you have your fetus genetically tested? Interestingly the proportions who would get tested doesn’t differ that much between demographics.

And the outcomes can sometimes surprise. A story in the Columbus Dispatch relates the story of a couple who kept their daughter, who tested positive for Down Syndrome. They had originally decided that if the tests came back positive the would terminate. In contrast, the nurses relate that one strongly anti-abortion couple at the beginning of the process seems to have terminated. Right now 1 in 700 pregnancies result in Down Syndrome.

• Category: Science • Tags: Bioethics, Down Syndrome 
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For several days I’ve gotten referrals from message board discussions about the case of Trent Arsenault. Trent is a “free sperm donor” (see the link for the details). For various financial reasons he can’t adhere to all the regulations which sperm banks are subject to. I don’t dismiss the concerns out of hand, but I object to the idea that this sort of project is a rational and useful allocation of regulatory time and money. I find one section of a Reuter’s piece illuminating:

Arsenault gets himself screened every six months for that entire list of diseases but cannot afford the specific FDA-approved tests he is supposed to undergo within seven days of each sperm donation, at a cost of $1,700, he said.

The stringent, costly testing regimen is the main reason sperm banks charge hundreds of dollars for their services, says Sherron Mills, executive director of the Pacific Reproductive Services in San Francisco.

Rates there range from $425 to $600 or more per insemination, and any woman who finds such a sum too onerous to pay is probably unable to afford routine costs associated with being a parent, Mills said. “Once you have kids, it costs every bit as much every month,” she said.

Really? Is this the logic that we see in broader society? I make enough references to Idiocracy that it’s obvious that I think our society needs to have a frank discussion about variation in fertility rates across the income and education range (people, especially women, who invest in human capital through education tend to delay childbearing and have fewer offspring than those who do not). But is the discussion going to start with banning the activities of someone like Trent Arsenault? The only long term solution may be the marketing of “sperm donation kits,” available to consenting adults who meet each other by whatever means they choose.

• Category: Science • Tags: Bioethics 
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I have discussed the reality that many areas of psychology are susceptible enough to false positives that the ideological preferences of the researchers come to the fore. CBC Radio contacted me after that post, and I asked them to consider that in 1960 psychologists discussed the behavior of homosexuality as if it was a pathology. Is homosexuality no longer a pathology, or have we as a society changed our definitions? In any given discipline when confronted with the specter of false positives which happen to meet statistical significance there is the natural tendency to align the outcome so that it is socially and professionally optimized. That is, the results support your own ideological preferences, and, they reinforce your own career aspirations. Publishing preferred positive results furthers both these ends, even if at the end of the day many researchers may understand on a deep level the likelihood that a specific set of published results are not robust.

This issue is not endemic to social sciences alone. I have already admitted this issue in medical sciences, where there is a lot of money at stake. But it crops up in more theoretical biology as well. In the early 20th century Charles Davenport’s research which suggested the inferiority of hybrids between human races was in keeping with the ideological preferences of the era. In our age Armand Leroi extols the beauty of hybrids, who have masked their genetic load through heterozygosity (a nations like Britain which once had a public norm against ‘mongrelization’ now promote racial intermarriage in the dominant media!). There are a priori biological rationales for both positions, hybrid breakdown and vigor (for humans from what I have heard and seen there seems to be very little evidence overall for either once you control for the deleterious consequences of inbreeding). In 1900 and in 2000 there are very different and opposing social preferences on this issue (as opposed to individual preferences). The empirical distribution of outcomes will vary in any given set of cases, so researchers are incentivized to seek the results which align well with social expectations. (here’s an example of heightened fatality due to mixing genetic backgrounds; it seems the exception rather than the rule).

Thinking about all this made me reread James F. Crow’s Unequal by nature: a geneticist’s perspective on human differences. Crow is arguably the most eminent living population geneticist (see my interview from 2006). Born in 1916, he has seen much come and go. For those of us who wonder how anyone could accept ideas which seem shocking or unbelievable today, I suspect Crow could give an answer. He was there. In any case, on an editorial note I think the essay should have been titled “Different by nature.” Inequality tends to connote a rank order of superiority or inferiority, though in the context of the essay the title is obviously accurate. Here is the most important section:

Two populations may have a large overlap and differ only slightly in their means. Still, the most outstanding individuals will tend to come from the population with the higher mean. The implication, I think, is clear: whenever an institution or society singles out individuals who are exceptional or outstanding in some way, racial differences will become more apparent. That fact may be uncomfortable, but there is no way around it.

The fact that racial differences exist does not, of course, explain their origin. The cause of the observed differences may be genetic. But it may also be environmental, the result of diet, or family structure, or schooling, or any number of other possible biological and social factors.

My conclusion, to repeat, is that whenever a society singles out individuals who are outstanding or unusual in any way, the statistical contrast between means and extremes comes to the fore. I think that recognizing this can eventually only help politicians and social policymakers.

You can, and should, read the whole thing. Let’s make it concrete. Imagine the following trait with two distributions (i.e., two populations):

– Mean = 100 and 105 (average value)
– Standard deviation = 15 (measure of dispersion)
– Let’s assume a normal distribution

Let’s plot the two distributions:

Observe the close overlap between the two distributions. Most of the variance occurs within both sets of populations. Now let’s impose a cut-off of about ~130 on the curves:

Now the similarity between the two curves is not as striking. As you move to the tails of the distribution they begin to diverge. In other words, the average of the two populations is pretty much interchangeable, but the values at the tails differ. Now let’s move the cut-off to 145:

The difference is now even more stark. Let’s compare the ratios of the area under the curve for the two populations as defined by the cut-offs:

Value at 100 = 1.26 (any given individual in the blue population is 1.26 times more likely to be above 100 than in the red population)
Value at 130 = 1.83
Value at 145 = 28

A major caveat: quantitative traits are only approximately normally distributed, and there tends to be a “fat tail” dynamic, where deviation from the normal increases as one moves away from the mean. Concretely, this means that the ratios at the tails are probably not quite as extreme, as there are more individuals in all populations at the tails than you’d expect.

What does this entail concretely? As Crow noted above if you sample from the tails of the distribution then very modest differences between groups become rather salient. Consider long distance running. To be successful in international competitions one presumably has to be many, many, standard deviations above the norm. One can’t be a 1 out of 100, or 1 out of 1,000. Rather, presumably one should be 1 out of hundreds of thousands, at a minimum. This would be the fastest ~100,000 or so people in the world (out of 7 billion). With this in mind, we should not be surprised a priori at the success of the Kalenjin people of Kenya in this domain. They may have both the biological and social preconditions which allow their distribution of talent to be moderately above that of the human norm. Even a marginal shift can make a huge difference at the tails. 1 out of 100,000 is 4.26 deviation units above the mean. Increasing the mean of a population by half a standard deviation units (e.g., if 100 is the mean, 15 is the standard deviation, then for the population with the higher mean you’d be at 107.5) results in a disproportion in ratio of above 8:1 at 4.26 units (as measured in the first population). This is modest, about 1 order of magnitude, but consider possible gene-environment correlations and synergies that might ensue when you have a critical mass of very fast individuals. This could amplify the effect of a difference in distributions on a single variate (more importantly I suspect, consider that virtuosity in many domains requires an intersection of aptitudes many units deviated from the norm across many traits).

In the early 2000s James F. Crow was responding to the Human Genome Project. As has been thoroughly covered elsewhere human genomics has probably underwhelmed in terms of outcomes 10 years out. But it is often the case that with new technologies we overestimate the short-term change which they will effect and underestimate their long-term consequences. I believe with the rise of mass genomics, a radical increase in population coverage and full genome sequencing, we may finally start to adduce the underpinnings of quantitative traits. We already have indirect methods, but I believe that by 2020 we will have direct means at our disposal. We’ll have a good sense how deeply humans are commensurable on a population genetic level. I doubt it will change much in our values, but it may entail some rhetorical adjustments.

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I don’t give much thought to chimeras, so this editorial in Nature took me unawares (OA): The legacy of Doctor Moreau:

Innumerable mice and other animals have been engineered in past decades to express a human gene and model specific aspects of human disease. They rarely inspire disgust, because they still resemble their own species. But further advances in genetic and stem-cell technologies mean that researchers could, in theory, create animals with quintessentially human characteristics or behaviours. The sight of an animal with shiny, furless ‘human’ skin, for example — exceptionally useful for research into skin disorders — could evoke disgust similar to that created by Moreau’s beast folk, even though the animal itself might be perfectly comfortable. One of the biggest horrors — although technically unlikely — could be a self-aware monkey, a creature with human thought trapped in the body of an animal, unable to express itself.

Perception, the ‘optics,’ matters. I think there are going to be serious issues if chimeras resemble humans. It’s just too good for video not to trigger outrage. More subtle hybridizations which are less phenotypically salient though….

• Category: Science • Tags: Bioethics 
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In the comments below, John Howard asks in relation to me releasing my genotype into the public domain: “I’m curious if this means you give permission to be cloned, or for someone to reproduce with you, by making gametes from your genome. Do you think other people have the right to do that?” I’ll be honest that I laughed when I first saw this comment. My genome is not magical. If someone wants to make more of me (and I can see why they’d want to do that), I probably wouldn’t mind. My siblings are versions of me diluted by a factor of 1/2, if you want to think in terms of blending analogies. But the biggest issue is this: identical twins already share very concordant genomes, and no one would presume that one twin should have a right to a say in the use of the genome of the other twin. Then again, John Howard runs a website, “Dedicated to stopping genetic engineering of human beings, and preserving individual conception rights for all people. All people should be created equal, by the union of a woman and a man.”

Now, imagine that identical twins did not exist. How would you feel about the idea of someone with a nearly identical genome? I think people would be very disturbed by the concept, and I’m sure philosophers would cook up all sorts of bioethical conundrums. But since identical twins do exist, we understand that the whole phenomenon is pretty banal after the first blush of novelty. Genes are not magic. They’re a start. Fear not DNA. It is not the alpha & the omega.

• Category: Science • Tags: Bioethics, Genetics, Genomics, Twins 
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Slate has a piece up, Pregnant Pause: Who should pay for in vitro fertilization?. What might the objection to the bolded section be?:

Roughly 10 percent of couples experience infertility, a rate possibly accelerated by the increasing average age of prospective mothers. This demographic trend of older mothers is encouraging (since higher maternal age is a powerful predictor of financial security and the child’s future social and educational attainment), but the odds of successful spontaneous pregnancy are lower. And so women increasingly turn to fertility treatments such as ovarian hyperstimulation, which forces the ovaries to pump out more eggs per cycle and increases the risk of having twins or triplets, and IVF, in which fertilized eggs, or embryos, are implanted in the uterus directly. Almost one in 80 newborns in the United States owes his existence to IVF.

In any case, if there is mandatory insurance coverage for IVF that would seem to have obvious social consequences in terms of the decision-calculus that women make. The magnitude of the trade-offs shift….

• Category: Science • Tags: Bioethics 
Razib Khan
About Razib Khan

"I have degrees in biology and biochemistry, a passion for genetics, history, and philosophy, and shrimp is my favorite food. If you want to know more, see the links at"