Thursday, March 26, 2015

The 'obstetric dilemma' hypothesis unraveled

Right now I'm giving this talk at the annual meetings of the American Association of Physical Anthropologists. Here's the link to Session 15. Costly and Cute: How Helpless Newborns Made Us Human, where you'll see the participants, their talk titles and abstracts. This symposium evolved out of a seminar at the School for Advanced Research back in the summer of 2014 when I was very pregnant and on the cusp of facing my own obstetric dilemma.


Let’s see how far we can unravel this epic hypothesis in 15 minutes or less. To start, here are the two most important seeds I hope to plant today in hopes that you’ll read up on these things further:  One. The obstetric dilemma is a hypothesis, not a fact. And… Two. The obstetric dilemma is an elegant idea, and would be an extraordinary example of human exceptionalism if true.  But the burden of proof is on it. So what is the obstetric dilemma hypothesis? In a nutshell…

We use it to explain at least these two observations, and often there are more: First, childbirth is difficult and risky. And, second, humans are born with only about 30% of our adult brain size, but for chimps it’s 40%.  Why? The “obstetric dilemma” hypothesis. Constrained by bipedalism, the human pelvis constrains gestation length and fetal brain and body growth, while making childbirth difficult and dangerous.  Which, put differently, is the hypothesis that the unique human pelvis uniquely impacts human parturition and life history. Here’s a good example of how the obstetric dilemma is often presented as a common fact, even in a book that aims to have us rethink old assumptions:

“You can’t give birth to large-brained infants and also walk on two legs trouble-free, no matter how hard you try.” Alright so, locomotion’s running the show, but does it deserve to? That is, does selection for bipedalism limit the birth canal from widening and relieving a laboring mother’s difficulty?

As of now, even taking a new dynamic approach over the old static one, like Anna Warrener and her colleagues do, there is no strong history of support for the idea that wide or women’s hips are costlier or less efficient than narrow or male’s hips. This is, at present, the best approach to the question of whether women are presently at an upper limit in pelvic dimensions that selection for bipedalism will allow. And although it does not test the obstetric dilemma directly, it demonstrates that our perspective on sexual dimorphism has been biased toward seeing female bodies as compromised compared to a male ideal. 

Relatedly, recent additions to the hominin fossil record have lifted us from the temptation to see a progressive march through time to arrive at our bipedal perfection. There are numerous reasons the hominin pelvis evolved over the last several million years, making it unlikely that our present anatomy is what is “required” for bipedalism as is so often phrased. We can only assume that the few pelvic specimens in the hominin fossil record are testament to the variable morphology that has worked both for bipedalism as well as childbirth over the last several million years. Still, if bipedalism isn’t limiting the birth canal and causing childbirth difficulty, what is? Or, asked another way, there is an explanation for why chimpanzees have it so much easier than we do. So what is it?

The answer could still be that selection for bipedalism is constraining the pelvis and it has not yet been demonstrated.  The biomechanics of pregnancy may adaptively constrain pelvic dimensions, along the lines of what Katherine Whitcome and colleagues described for the spine. Further, limitations to tissue strength and other such properties of soft tissues of the pelvic floor may constrain pelvic dimensions, especially during pregnancy or as a result of it. But it must be noted that pelvic prolapse occurs in cows and sheep, not just bipeds.   Other significant contributors to childbirth difficulty include, but are not limited to: position of the laboring woman, position of the fetus and the umbilical cord, function of the placenta, uterus and cervix, muscular and bodily weakness, slow labor progression, multiple fetuses, preeclampsia, gestational diabetes, and age at first birth, young or old. At present, our impressions of hellish human childbirth are biased to a degree by Hollywood as well as the medical industry. So we may have to place some heavy blame on culture for our having it so much harder than chimpanzees. However, the rise in c-section rates from 5% to around 30% over the last several decades is not entirely due to unnecaesareans, as there has been a concurrent secular increase in neonatal size in hospitals as well. And that recent trend may be best explained by work being done by Jonathan Wells and his colleagues…

Although the tight fit between fetus and mother’s pelvis may have occurred millions of years prior, agriculture has had a remarkable and perhaps the most dramatic effect. Agriculture’s influence on diet and overall health has affected both the development of the female pelvis and the growth of her fetus during gestation. Undernourished mothers can birth relatively large babies due to adaptive responses to protect fetal growth during pregnancy, and regardless of maternal condition, larger babies are associated with longer labors and higher incidences of medical interventions. It is highly likely that there was never more childbirth difficulty than there is now and in recent history.  Plasticity has been both a blessing and a curse. Okay, so if childbirth difficulty may be new and is due to a complex vortex of proximate and ultimate explanations, not due solely or largely to locomotor selection on birth canal size, then what about our being born with only 30% of our adult brain size? 

Could the obstetric dilemma explain our relative immaturity at birth?  Which is to say, does the human pelvis uniquely influence gestation length and fetal growth? 

Or are we born early to experience a rich period of stimulation and learning, crucial to the development of human cognitive and neuromuscular function as Portmann hypothesized? According to the extra-uterine spring hypothesis, the pelvis does not limit gestation and fetal growth, the benefits to life outside mother do. These two hypotheses for gestation length and fetal development have humans born early or underdeveloped. A third does not. 

When the energetic and metabolic costs of pregnancy and lactation are considered, gestation ends and the birth process is initiated when pregnancy reaches a critical point at which the mother can no longer support her growing fetus. Fetal energy demands (black circles) increase exponentially during gestation.  Maternal energy expenditure (grey squares) rises during the first two trimesters but reaches a metabolic ceiling in the third, as total energy requirements approach 2.0x basal metabolic rate.  Projected fetal energy requirements for growth beyond 9 months (dark, dashed line) quickly exceed the maximum sustainable metabolic rates for human mothers (horizontal, dashed line).  After parturition, infant energy demands increase more slowly, and maternal energy requirements while lactating do not exceed the maximum sustainable metabolic rates. The hormonal cascade that is involved in triggering human birth has been described by Peter Ellison’s metabolic crossover hypothesis. We suggested that although the data are far better for humans, this broad and more ultimate hypothesis that we called EGG likely applies to other species since, among placental mammals, maternal body size (a proxy for metabolism) is a good predictor of gestation length, fetal mass, and fetal brain mass as the work of Bob Martin and others work has demonstrated. Still, this doesn’t answer the question as to whether humans are born early or underdeveloped. But it doesn’t need to because folks have known for a while that ….

Human gestation is not short and seems to be even longer than expected for a primate of our body size. Relatedly, a human mother does not invest less in pregnancy than expected; she bears a large infant with a large infant brain for a primate of her body size. Humans are born with absolutely larger brains than other primates. How can we explain all this? Here’s one hypothesis:

[Text redacted to avoid spoilers. See abstract for Herman Pontzer's talk this morning here.]

One of the most common reactions to the EGG hypothesis and in defense of the obstetric dilemma is that …

… lactation is even costlier than gestation!



And this is coming, I think, from the point of view of lifetime life history theory where we assume that mammals maximize gestation length to put off lactation unless there is something adaptive about shortening gestation and sucking up those extra lactation costs. For many, this is assumed to be why we push gestation right up to pelvic limit. But then what’s adaptive about starting lactation early for all the other great apes which don’t gestate to the pelvic limit? Why not, instead, hypothesize that pregnant apes reach their EGG limit prior to their pelvic one and pregnant humans reach our EGG limit closer to our pelvic limit. In other words, our birth canal has been selected to be as adequately capacious but not as comfortable as theirs. Another common reaction to the EGG hypothesis has been…



… but the tight fit is too much of a coincidence to ignore. And I have a cheeky retort that involves my nostril and my finger, but kindly and seriously…Okay…




Well then let’s not ignore the other coincidences in other primates that clearly aren’t equipped with our bipedal pelvis. What explains their tight fits at birth? Could those explanations apply to humans? That would be the spirit of the EGG hypothesis which we have only modeled for humans so far but deserves to be tested by building the same model with other primates. Yet another common reaction I hear is…




… but why doesn’t the birth canal get bigger to make childbirth easier? And I’ve touched on this already in different ways. But another way to address this is…


It has. That we have sexual dimorphism in the bony dimensions of the birth canal and that everyone in here knows which one is male and which one is female speaks directly to the notion that the female pelvis (and not the male’s) has adapted to accommodate our relatively big babies. The adaptation works terrifically in a sort of no pain, no fitness gain kind of way. And this last common reaction I want to share is, again, all about that 30% of adult brain size at birth.

… but humans are clearly born premature!

 Well then, so are other primates and with and without a tight fit at birth, without habitual bipedalism, and without our level of encephalization. Comparing humans to altricial mammals (like carnivores, rodents, and lagomorphs) is arguably more poetic than scientific. Among anthropoids, Fragaszy and colleagues have described capuchins as relatively altricial too, given how they are only able to thermoregulate within a narrow temperature range, and have less postural control and locomotor ability just after birth compared to Old World monkeys and many platyrrhines with comparable available studies. It cannot be coincidence that neonatal capuchins have the smallest relative brain size (~50%) of all primates save for chimpanzees (~40%) and humans (~30%), meaning that they, like us, have more postnatal brain growth to accomplish compared to other primates. Now, for fun, let’s take humans out of the equation and marvel at chimpanzees instead…


Why are chimpanzees born with only 40% of their brain size when capuchins are born with 50%?! Among anthropoids, chimpanzee infants are even more helpless with their slow development and long period of dependency. For the first few months of their lives, chimpanzee infants are actively alert for only 10 percent of the day. As we’ve seen, it’s not their pelvis forcing them out early. It could be the extrauterine spring hypothesis; they’re born when they’re born to receive adaptive stimulation outside of the womb. But it could boil down to the fact that pregnant placental mammals can only grow a fetus up to a limit and then getting out there into the world is a wonderful thing for developing all there is to mammalian sociality as well. Given the trend toward greater altriciality among encephalized primates, capuchins, chimps, and humans might be better described as “less precocial” rather than singled out as somehow altricial. 

And maybe we drove ourselves to this state. Maybe we’re relatively helpless as infants because we can be, that is, because of the relaxed selection afforded by hominin caregivers. Apes are infant coddlers, and assuming our shared ancestors were too, this could have ramped up long ago, with meddling, manipulative parents and alloparents relaxing selection on infant independence, allowing them to evolve paddled feet, weak muscles, fat heavy bodies, and huge heavy heads. A scenario like this would push the origins of helicopter parenting back, potentially, into the Pliocene.



Many of our questions, even the most ultimate evolutionary ones, would be answered if we knew what triggered labor in humans and other primates. Ellison’s metabolic crossover seems to be the strongest hypothesis, but this is a research area that begs our attention. . Of course the clinical implications are significant but such knowledge would also shed light on why chimpanzees and many other primates and mammals give birth so far in advance of reaching a pelvic limit. If there is one labor trigger for all of us, how do we explain this variation in birth weight and gestation length in this large human sample? Is it metabolism and energetic throughput alone? Most probably not. It’s more likely that labor is a reaction to any number of stressors and included in that could be the size of the pelvis, but then this trigger would be a unique development in humans that would not explain the end of gestation in any species without a tight fit. Getting even more evolutionarily complex… if it all comes down to a fetal timer, then each and every species would have its specifically timed fetal timer to end gestation, and that, although not impossible, just doesn’t seem like a strong hypothesis when compared to a maternal metabolic and energetic constraint.


There is so much more to discuss, there are so many remaining questions, but I’ll end here and leave you with this: Without increasing ability to make nonhuman primate comparisons, there is little hope for knowing how bipedalism, adiposity, taillessness, encephalization, culture, etc. contribute to the evolution of pregnancy, childbirth, infancy, and how we parent and alloparent.  Live primate studies (and those of all placental mammals that pertain to these questions) are crucial if we are to explain how humans have such costly infants yet have much shorter inter-birth intervals than the rest of the hominoids. Without more detailed comparison we cannot know how costly our pregnancies and the resulting infants truly are. Primates that birth twins and practice cooperative breeding, like marmosets, hold great potential for answering many questions about reproductive physiology, metabolic limits and behavioral correlates. But for now, as far as the obstetric dilemma hypothesis goes, intense childbirth and intensive parenting are not so easily explained by bipedal pelvic anatomy. Gestation length, fetal growth, childbirth processes, and neonatal helplessness are all connected to the bipedal hominin pelvis one way or another, but whether they are fundamentally influenced by it is not an easy argument to make. The way I see it, as far as human evolutionary hypotheses go, the obstetric dilemma has gone from top dog to underdog. Support for the obstetric dilemma requires much deeper digging. And we anthropologists are great at that. Thank you.

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Wednesday, March 25, 2015

An experience in informed consent

Half a century ago, a number of expeditions were taken by US, South American, and European scientists into the hinterlands of the Amazon rainforest.  Most or all of the tribal groups they visited were near Catholic mission stations, where there was a lot of interaction, or people were interacting in other ways with the colonizers of the continent.

Napoleon Chagnon, then at the University of Michigan (and whom I knew as a graduate student and post-doc), with contributions from other investigators, made the Yanomami tribal group of the Amazon basin the most famous 'native' population in the world.  For many years Nap was the world's most prominent cultural anthropologist, probably succeeding Margaret Mead in that distinction. Indeed, he may still be.  His work was assertive, among other things driven by evolutionary theory about reproductive dominance and behavior in tribal human societies, and the aggression that went with that.  He was a pro-active rather than purely observational anthropologist.  This naturally raised opposition and contention, of which there has been an ample amount for decades.

Napoleon Chagnon and Yanomami headman, 1986; Chagnon photo, from the NYTimes

As well as cultural studies there were biomedical and in particular genetic studies of the many Yanomami villages.  The object was to test some ideas about the amount of mutation that arose and the persistence of genetic variation in tribal groups living under their kinds of conditions. Could the Yanomami social and reproductive structure, in particular group size, fragmentation, and dominance hierarchies, tell us anything about the way genetic variation had been maintained in our ancestral populations? The interest was not purely scientific, but more specifically was about the dangers we in the developed world faced as a consequence of our exposure to mutagens.  In particular, at the time, was concern over exposure to nuclear radiation from x-rays and the like, and fallout from nuclear bomb testing.

Yanomami.  Source: Wikimedia Commons, alto orinioco5


Jim Neel a world-leading geneticist at the University of Michigan was the primary biomedical/genetic investigator.  He was working on the health effects on survivors of the atomic bombs that had been dropped on Nagasaki and Hiroshima during World War II, and had a keen interest in these questions.  He was also my post-doc supervisor, and when years later he retired, he asked me and a couple of other investigators to be custodian of the DNA samples, and to analyze them as new technologies made that possible.  But in 2000, a book called Darkness in El Dorado by Patrick Tierney was published.  Tierney accused Neel and Chagnon (and others) of grievous abuses of the Yanomami, taking harmful advantage of the tribe for their own professional advancement. We've previously written about these issues here, and beginning here.

The late Jim Neel.  Source: Dept of Human Genetics, UMich

Major controversies have swirled around these accusations, and there is no need to go into them here. An available HBO film, Secrets of the Tribe, and several YouTube videos and published articles and stories can be easily found if you want to learn more.  The point is that after Darkness appeared, Yanomami and various advocates and spokespersons demanded the return of the blood samples, which had become symbolic of the outside interference so resented by the tribe.  This request for return has led to over ten years of interactions between us and the Brazilian government to find a way to ship the samples collected there back to them, safely, and free of legal entanglements about the samples and the work done in the tribal area.  This was not contentious negotiation, just a matter of the complex logistics (including biosafety, getting samples to Amazonia) and technical (liability issues) things to work out.

Well, finally, yesterday, the samples were shipped back to Brazil.  I hope they arrive on location without incident, and that the Yanomami are pleased.  We are relieved that at least this aspect of contention has passed.  It won't change any feelings of having been taken advantage of, perhaps, but it may help show at least respect and good intentions.

What is informed consent?
These samples were collected in complete compliance with the informed consent conditions of fifty years ago. But since various untoward things have happened to the Yanomami, what was at the time clearly a voluntary cooperation with the outside scientists (based on extensive filming), has been seen in retrospect as exploitive in various ways that include stimulating violence and even child sexual abuse.  Exploitation by unrelated outsiders, such as mineral prospectors, has apparently caused much harm, and the Indians, searching for whatever redress they can obtain, see the continuing presence of the blood samples at various US institutions as symbolic of their sufferings.  I was not involved in the collection of these bloods, and have never been to the Yanomami territory.  So I cannot comment about those grievances.

However, I was blamed for having the samples in my possession as caretaker and someone who could do further analysis of their genetics, as if guilty of the decades-earlier abuses simply by association with the blood samples.  My only work at the time had been to analyze the Yanomami demographic data (after they were collected, when I was a post-doc) jointly with Jim Neel.  But as caretaker of the samples I have been accused of nefarious acts, none of which I had committed. I'm glad those samples have been returned, in part because I hope it makes clear my good intentions, but also because, once requested, we had no right to retain them.

This contentious affair raises many questions about informed consent.  Above all, I think, is that informed consent never ends.  Subjects have, and should have, the right to withdraw from a study at any time and for any expressed reason. Indeed, we have no right to ask for a reason.  Being ticked off at the outside world is as good as just saying "Remove me from your study, please."

One must recognize that when data about a sample have been published or melded into a large data base, or distributed anonymously and analyzed by various groups, turned into a patented product, or in other ways already analyzed, that such results cannot be un-published.  This is probably particularly relevant to genetic studies because of their complex statistical analytic nature.  But beyond that, rights should belong to the study subject, unless quid pro quo's and the like have been arranged at the time of collection, when conditions of participation and so on should be clearly settled at the time.  Investigators often try by various subtleties to retain rights, or obtain consent, that one knows, realistically, are not understood adequately by the study subjects.  Once DNA is in our hands, the temptation to study whatever becomes possible to study is hard to resist.  After all, study subjects are not as a rule technically aware and/or the investigators have clear self-interest.

Anyone who thinks informed consent is usually truly 'informed' is kidding him or herself.  Even the investigators cannot know the benefits or risks that may be involved, because if they did the science would not be necessary.  Subjects may be ill or even desperate patients seeking treatment, or subjects may be offered compensation for their participation.  This doesn't mean there is any evil intent on either party's behalf.  Vague promises of follow-up of various kinds are often made, sincerely or naively, but are often not kept or are conveniently interpreted by both parties.

We know a lot more about informed consent now than in the 1960s, but still issues arise because both subject and investigator have clear self-interests but also because the science has become ever more complex.  Decisions about restrictions and restraints seem, to me personally, too often to rest with the investigators, and the power is largely in their hands.  Rationales for doing things in, say, other countries that can't be done here seem rather common.  These have been  difficult issues for many decades, especially after the eugenic era abuses.  The issues are likely to remain challenging.  There are no clear answers, but at least we think that withdrawal without needing to give a reason should always be allowed, unless the work has been done and makes it impossible, as noted earlier.

But at least some contentious samples have been returned.

Tuesday, March 24, 2015

Bordello U's

It is no secret that universities are now operating on the 'business' model.  This self-flattering term applies to all of their operations, not just their research component which has by now long been in bed with private interests and empire-building in regard to public funding sources.  It also applies to athletics, which is nothing new, though seemingly more out of control than ever.  Finally, it's swept like a pandemic across the academic sides of things as well.

A good treatment of this, from the UK perspective, is an essay by Marina Warner, "Learning my Lesson: The Disfiguring of Higher Education", in the March 19, 2015  issue of the London Review of Books.  She properly rakes the UK university system, which is much more centralized under government control than ours, over the coals.  She identifies the various venal takeovers that have been occurring. These include the denigration and diminution of subjects that might enlighten people's personal lives but don't pay in hard cash (the humanities, arts, literature, and so on).  Among much else, she notes the very fine buildings being erected on campuses, by prizewinning architects, largely for industry-related research.

The priorities are clear and they're no secret.  Faculty are being downgraded unless they're in the money subjects.  Tenure and promotion are based on bean-counting 'objective', and hence essentially material, evaluation methods.  Such numerology can be gamed, and is being gamed, such as by publishing more but more trivial papers, spending more of one's time writing grant applications, less attention to teaching, universities hiring low-paid Instructors to teach high-paying high-indebted students, while high-paid professors seek high-income grants.  Meanwhile, even higher-paid administrations are becoming ever more bloated, administrators' salaries inflated with helium far exceeding those of actual professors.

By now everyone knows what's going on.  Administrators of course control the power leverage. They may delude themselves about how important and vital they are, and how their 'objective' performance standards maintain quality and all that sort of puffery.  Of course, only in Lake Woebegone can everyone be above average (though all can claim to be).  Administrators cannot be expected to curtail their own power and salaries, because if they did, most would have to return to the (ugh!) demeaning work of actually teaching classes.

It's not just Europe--indeed, we started it
Warner's article is about the UK, but in the US we have these problems in spades and here, too, everybody knows it.  Indeed, it was Reagan, and the ensuing Reagan-Thatcher conspiracy against ordinary people, by which this whole process was initiated.  Much of the rest of Europe is following suit (we don't know whether universities in Asia, Africa, or the rest of the Americas still have their pants on or are dropping them for money as is happing in the European-US axis).

The US has worse issues that it is conveniently not doing anything serious about.  Europe doesn't have the Greek (fraternity and sorority) system.  Europe doesn't have the athletics problem.  A recent graphic making the rounds of the internet showed the highest-paid state employees in the US states, and 40 were university coaches with outrageous salaries.  Europe doesn't (yet) have the fancy-dorms-with-luxury-spas system we are building, which venally corrupt the idea of a serious-level education.  Why this (given its huge cost and the student-debt problem) doesn't disgust parents and lead them to insist that their kids go to more cost-conscious and educationally serious schools instead is unclear.  Maybe a spate of OpEd articles will lead them to that, and perhaps force universities to scale back their excesses.

That all that glitters, staggers, and cheers appeals to 18 year-old high-schoolers looking for a college is easy to understand, but puts the blame on the adults who lure them, and their high tuition, to their campuses.  What's the justification?  "Everybody else is doing it and if we don't do it we'll lose these students!"  Of course, we here at the universities are the profiteers, because the students bear the debt burden, often for decades after graduation....er, that is, whether with a degree or not when they leave, while we take home our nice paychecks.

Just because it's in our own backyard?
We ourselves have had academic careers, and anyone knows best the dirty laundry in their own backyard.  There is a tendency, especially if one cares about that backyard, to be excessively critical of it.  In our case, Penn State, where we have been for almost 30 years, is a fine example of the not-so-fine state of affairs. But while we do criticize our own institution, we do our best to take into account that it's the one we care most about.  Here were and are our fine colleagues and many wonderful students (including two of our own children).  Bloated though bureaucracies may be, including university administrations, this doesn't mean the people are individually bad or not helpful, and we've admired and been helped by many across the years.  But the above burdens have grown here, as elsewhere, and it is fair game to note that.

We here are not unique; indeed, if anything has bothered us it is that Penn State has not taken leadership in addressing the issues in more than a me-too fashion.  Worse, in our particular case, the Sandusky child-abuse scandal gave Penn State a huge silver platter on which to do real reforms, curbing athletics' over-reach and reestablishing serious academic standards; indeed, it's what our then-President promised we would do in response to Sandusky: rebalance 'academics' and athletics.  But what happened since was nothing of this sort, and the old ways are in full stride, and academic standards have not been raised.  We repeat that this is not just a local problem: it is widely and often recognized as a national one.

The problems are not unknown and indeed are widely written about.  Universities, being good, well-behaved bureaucracies, usually respond by acknowledging problems and setting up a committee or 'task force'.  That meets for a year or more and issues a report that claims major changes but is usually little more than safe rearranging of the deck chairs.  We need to stimulate industry-related research?  Build a building and call it Novelty Central, accessed via Creativity Road.  You likely know what we're describing.

Just reactionary?
Warner's article should be read by anyone who cares about the state of educational affairs and would like to know more about what is going on--hopefully to be made angry enough to join in the effort to do something about it.  Reform will be very difficult because there are too many prima donnas too well entrenched to be dislodged without a struggle.  But if there is no struggle, reform will come after we have fallen so far that serious consequences become palpable.

Of course, we could just be reactionaries, objecting nostalgically to changes that make universities unlike what we ourselves have known.  If this were not clearly a national problem on three major fronts, that might be the case.  We don't think it's reactionary to object to the luxurious life for students (and faculty) on campus at the clearly exploitive expense of heavily indebtedness is a reactionary position.  The national downward trend in our educational attainment relative to competing countries elsewhere is a legitimate reason to call for reform.  The edifying value of education for its own sake and to engender better citizenship, and the value of disinterested research (publicly open and not done for private gain) are well-established reasons to have a bastion of independent thinking as part of our national resource.

Whatever happens with online and other new-mode courses may or may not be good, but doesn't directly address the issues of (1) the national value-added gain of subsidizing education, (2) the value of independent knowledge, and (3) the motivation of an idealistic and dedicated faculty to live a modest but comfortable life rather than chasing personal wealth which, after all, they are free to do in the private sector.

Is it fair to title this post as we did?   Regardless of how tolerant you are of the changes, the days of the elbow-patched tweed jacket seem to be over.  But that change has left other holes in our educational culture that badly need to be patched.

Monday, March 23, 2015

Germline gene therapy: Frankenstein or Frankincense?

Science, like any other human enterprise, is largely reactionary.  People in established positions of influence like to have their own way but perhaps even more, like their ways to stay basically the same: change is threatening.  For that general reason, new ideas that promise to be transformative are often faced with reactionary opposition.

A few decades ago we had the recombinant DNA revolution.  Changing DNA in bacteria for experimental reasons was seen as a potential global threat: if recombinant bacteria escaped the lab, they could become a global pandemic disaster that would make malaria or the bubonic plague seem trivial by comparison.  Of course, those excited about the potential of the new method, for legitimate as well as venal reasons, pushed hard to be allowed to proceed.  After careful examination, various protections were imposed (like working with experimental strains of E. coli that could not really live outside of test tubes), but these were loosened or abandoned over time, as the threats never materialized.

There are still some rumblings about this, as for example, the recent controversy over labs refusing to desist from engineering dangerous flu viruses to see what changes were needed to enable them to transfer from person to person more easily (they originate now in animals).  The rationale is to anticipate such occurrences and develop preventive measures or vaccines etc.  This work is on-again-off-again, in response to governmental and other dictates, and then pressure from investigators to do this no matter what, and then back again, as the issues are batted back and forth, unresolved.

A few years ago there was the reaction to cloning, when it was done to make Dolly, the sheep in a lab in Scotland.  There are many issues about this process, both the sci-fi horrors of cloning armies of humans who are genetically unable to experience fear, and the fact that cloning from an adult's cell would make newborns more vulnerable to age-related diseases.  Human cloning is not allowed as yet, though there are some rather similar things going on in the in vitro fertilization world to select embryos without known disease-related genetic variants.  As we understand it, various types of cloning are widespread in agricultural animals.

Another example is the reaction to genetically modified organisms (GMOs) and their potential to make proteins that would turn out to be allergenic or in other ways harmful, or to damage ecosystems by altering pests infestations as well as inadvertently destroying insect pollinators, the enabling of large-scale monocropping, and so on.  This debate is ongoing, and widely publicized.  It has stimulated 'natural' foods, non-GMO containing foods, local sustainable agriculture, etc.  Some of the resistance was, in essence, not about personal health but about the way GMOs threaten local farmers around the world, deplete natural variability, threaten bees and other pollinators, and more.

Much of the opposition to these sorts of change is emotional and sociopolitical--but that is not a criticism, because people are emotional and sociopolitical.  And that applies to people on both sides of the debates: nobody can claim that the proponents of the new technologies are dispassionate and without self-interest and limited perspectives.

Human genetic engineering: a blessing like Frankincense?
There is now the beginning, or perhaps continuation, of a debate about human genetic engineering.  Should it be done?  What is it, exactly.  One recent discussion outlines the issues.  New technologies are being developed, one of which is called CRISPR, to engineer changes in specific genes in situ in cells.  This is being done in cell culture and experimental animals and plants, to see what the specifically transgenic effects on them are.  But the potential for genetic engineering to produce human babies that do not carry deleterious genes that there parent(s) may be known to carry hasn't been ignored--and, even better, the dangerous genes are removed from the population because when the babies themselves reproduce they only have the normal version to transmit to their children.

This is different from genetic engineering that tries to deliver therapy based on genetic methods to persons who are affected by genetically based diseases (like cystic fibrosis) or to deliver genetic changes to diseased tissues to counter the pathology.  Those approaches are struggling to live up to their widespread promise, but there is little opposition that we know of to their implementation.

The resistance to germ line gene therapy seems to be that engineering of specific heritable genetic changes could backfire and generate new pathologies, monsters, or other unexpected side effects if the methods, still yet unproven and undergoing testing in lab species, don't work as precisely as their proponents claim.

An old way wise men tried to bless the human future: Frankincense therapy

But the idea of germ-line and hence permanent fixes is not at all new.  It's a scientific analog, one might say, of the religious doctrine of the blessing conferred on humankind by the wise men one Christmas eve.  An effort to save our patrimony from much suffering.

Selective abortion, prenatal counseling, and even IVF are now used to prevent the birth of babies that carry known dangerous variants that one or both parents may be known to carry.  This has greatly reduced the incidence of thalassemia (a blood disease related to anemia) in Sardinia, and of Tay Sachs disease in Ashkenazi Jews, and there are likely many examples we just haven't heard about.  There are now two- and even recently three-parent IVF conceptions being constructed.

So this time, the reactionary response to a new idea does seem to be reactionary.  It isn't that there's no risk of horrible misadventures occurring if the new techniques fail, and it's fair enough to say this should be stopped cold until the techniques are reliable (or early enough tests available to do instantaneous aborting of dysgenic conceptuses).  But that is not the same as reacting to the idea of germ-line therapy in the first place as if it were new in concept.

To prevent Frankensteins?
There will, of course, be those who agree with all of this so far, but foresee the mis-use of the procedure by rogue elements or governments for example to create fearless soldiers, drones, slaves, and so on based on mass-scale genetic engineering of this type.  Or doing the same kind of thing to create super-plagues (e.g., to visit on enemies).  Rogue elements can be expected to arise here and there within governments (e.g., in intelligence services, military, or other agencies).

Blessing gone awry: Boris Karloff style

Dr Frankensteins would perhaps find willing employers in such places.  Some would be rogues. Some might offer their services to our enemies.  Some might engineer irresistible plague germs. Such elements always exist in society.  There is plenty of evidence to think that otherwise respectable scientists will be (or are) doing this covertly or will find ways, such as by leaving universities to set up companies, moving to more permissive countries, and so on, to do this and skirt regulations and restrictions.

It is also true that the same sorts of claims have been around for a long time. That the predicted disasters haven't occurred--yet--is no reason to relax vigilance.  After all, the Nazi 'scientists' and 'doctors' were among the leading professionals of their days.  And this sort of thing wasn't restricted to Germany in the 20th century: it was part of global eugenics thinking and actions taken against those deemed to be inherently (that is, genetically) inferior.  Only a newborn babe would be so naive as to think the same sort of mentality cannot be found among today's leading scientists.

But perhaps every blessing comes with a curse, and to gain the former we must guard against the latter.  While vigilance is never perfect, and risks always do exist, at least we should recognize the positive potential for removing dangerous genetic elements from human patrimony.