Tag: Genetics and Darwin

Final Thoughts on Genetic Science

I highly recommend this essay by Matthew Cobb in the New York Review of Books.  It is a wonderfully succinct and admirably clear account of the current state of genetic science–and of the technical, moral, economic, and political issues that follow from what we can now do to genes.

I want to get down here some final reactions to the Mukherjee book, reactions also spurred by reading the Cobb essay.

  1.  Back to Down syndrome as a way of thinking about natural selection.  Mukherjee points out that natural selection works at the level of phenotype (the features of the organism), not at the level of genetics.  That is, natural selection works for or against what genes produce, but has no way of intervening in genes directly.  That’s why recessive traits can continue to exist despite their not leading to fitness.  But the case of Down syndrome is even weirder.  Down syndrome is a mutation, a random genetic event.  There are no carriers–although if a woman with Down syndrome has a child, the chances are about 50% that her child will have Down syndrome.  Males with Down syndrome are generally infertile, although now there have been some cases of Down syndrome males having children.  In sum, the actual incidences of Down syndrome persons having children are very low, but the former belief that Down syndrome came with infertility has now been disproved.

No matter.  The bigger point is that Down Syndrome, in the vast majority of cases and certainly throughout most of evolutionary history, has not been passed down from parent to child via genetic inheritance the way sickle cell anemia is.  Rather, Down syndrome is the result of a mutation.  But–and this is the remarkable thing–it is a mutation that, while random, occurs with a fairly regular probability that can be predicted.  About 1 in 1000 for a mother aged 20; about 3 in 1000 for a mother aged 45.  The regular process of creating human children predictably produces Down syndrome babies even though each of those events is random, just like each individual coin flip.  So here we have natural selection undermined by a stubborn, apparently ineradicable, mutation.  There is no way to argue that natural selection chooses Down syndrome, because Down syndrome persons do not reproduce (except in very rare cases).  But natural selection, which can only work through reproduction, also fails to eliminate Down syndrome because another naturally occurring phenomenon–a random, but still regular, mutation–over-rules natural selection.  My point is only that natural selection is not the only game in town; it doesn’t completely rule which mutations persist and which don’t.  Another blow to Darwinian reductionism.

2.  One fascinating thing about the history Mukherjee tells is that “the gene” was posited as a theoretical necessity before there was any proof of its actual, material existence.  Like the unobservables in physics, the gene was needed to explain certain phenomena even when the techniques needed to locate the gene did not exist.

3.  Eugenics are usefully defined by Mukherjee as any attempt to eliminate certain genes from the gene pool.  Early 20th century eugenics–both in the US and Germany–(like natural selection) worked at the level of features, of the phenotype.  Newgenics (as some people are calling 21st century eugenics) works at the level of the gene.  Again, we need to be precise.  We can eliminate the existence of Down syndrome persons if prenatal testing leads to the universal termination of fetuses with Down syndrome.  But we can’t eliminate the mutation that causes Down syndrome so long as there is human reproduction.  We can, if embryos are produced artificially, eliminate Down syndrome by controlling the reproductive process to such an extent that the mutation does not occur.  We can, however, eliminate hemophilia because it is a “one gene syndrome,” not a mutation, and targeted gene therapies can kill off that gene in its carriers.  Whether that elimination would be permanent is unclear–since presumably future mutations could bring it back.  But, at least theoretically, if an entire population was fully genetically tested, then the hemophilia gene could be eliminated in every one who possessed it. It is this fact, that we have now acquired the technical prowess for that kind of targeted gene therapy, that is at the heart of Cobb’s essay.

4.  Mukherjee’s definition (from Victor McKusick) of illness: “relative incongruence between a genotype and an evironment” (449).  Which means there are always two possibilities: working on the “patient” or working on the environment.  Disability activists often tell us that we don’t think often enough or creatively enough about amending the environment.  A reminder of old leftist arguments about psychiatry.  What proves I am crazy–and not this society in which I have to live?  As Mukherjee puts it:  “A child with a high-functioning form of autism may be impaired in this world, but might be hyperfunctional in another–one in which, say, the performance of complex arithmetic calculations, or the sorting of objects by the subtlest gradations of color, is a requirement for survival or success” (449).

5.  Cobb, more than Mukherjee, considers the dangers attached to the privatization of techniques developed by and even genes uncovered by the new genetic science.  Here we are back on Chris Newfield territory, the way in which public resources are used to produce knowledge which is then privatized.  In Newfield’s account (in Unmaking the University [Johns Hopkins University Press, 2016]), the so-called public/private partnerships and the offices of “technology transfer” so lauded on today’s campuses are just a colossal rip-off.  A disproportionate share of  the risk and cost of research (the vast majority of which, after all, never bears any monetizable fruit) is borne by the university, but then, when a commercially viable result is produced, private corporations swoop in to license or patent it–and to begin to produce it for profit.  It is the scientific equivalent of the banks relying on the government to cover its losses (through the Federal Reserve and bail-outs) while they get to keep all their profits.  And this way of thinking about the issue doesn’t even touch the larger issues of a) our totally broken patent system which has allowed impossibly vague and far-reaching “ownership” of fundamental ideas and techniques that haven’t even been connected to actual production of anything yet and b) how privatization (as we have seen in spades with big pharma) leads to differential access to therapies that were developed on the public dime.  So everyone pays the first time around (through tax payer subsidies of research) and then the fortunate (those with enough disposable income) get to pay again the second time around, when they actually avail themselves of the results of that research.  Cobb tells us how Berkeley and MIT are engaged in a nasty patent fight over gene therapy–about which university’s scientists got there first and, hence, have the right to patent it.

6.  It’s a complex world out there.  The complexities of the genetic system are only matched by the complexities of political and social realities.  One thing comes through loud and clear in the scientific story: complexity is a short-term, but not a long-term, barrier.  Problems get solved.  Everything hopeful or fearful (often both) prophets of genetic science told us would someday be possible is just about at hand.  Things are generally more complicated than first imagined.  Nature is actually not all that elegant.  It’s more of a Rube Goldberg machine than some sleek Maserati.  Natural selection, like Donald Rumsfeld, has to work with the army it has, the materials at hand.  Plus (as I keep insisting) it doesn’t utterly rule the roost, so there are various compromises along the way.  But science really does seem up to the challenge of figuring it out.  Complexity itself is not going to prove a shelter for the romantics who cringe at the thought of full, disenchanted explanations.  Individual variation is a more hopeful shelter.  The introduction of chance–through mutation, incomplete penetrance, environmental differences and the like–still suggests limits to our predictive powers when it comes to saying what trajectory any individual’s life will take (even when we have a full map of his or her genetic makeup).  Still, science’s doggedness is impressive–and contrasts strongly with our inability (in the social sciences) to make much sense of our political and social realities.  Our lack of command over those scenarios seems more obvious every day.  John Dewey’s optimistic belief that the ways science has increased our comprehension of nature would be mirrored by a corresponding increase of our comprehension of society seems the least credible feature of his pragmatism. The advances made by genetic science wouldn’t be half as scary if we had any reason to be confident that we had the political capability of handling and controlling this new knowledge.  But just about everything we witness in our everyday world leads to exactly the opposite conclusion.  Neither the scientists nor the polis seems up to the task of using this knowledge either wisely or well.


Gene Regulation—and Darwinian Fundamentalism

Turns out that regulation is biological and genetic as well as political.  One major functions of genes is to regulate, mostly in the form of on and off signals.  It is genes that have the job of activating immune system responses to external microbes—and then to shutting off those responses once the threat is defanged.  Hence, over-reactive immune systems are results of the off switch not being pulled, whereas immune system deficiencies occur because the on button does not get pushed.  The body, too, can overdo things, can push past limits best left intact.

Immune system responses are obvious cases where genes are activated by environmental triggers.  There are other fairly obvious environmental factors—like adequate nutrition.  More mysterious is “incomplete penetrance”—i.e. the fact that two organisms can possess the same gene, but it only expresses itself in one of them.  Such is the case, for example, for women who carry a gene highly associated with breast cancer.  But only highly associated; that gene does not result in 100% of the women who possess it eventually getting breast cancer.  More like 60%.  (Incomplete penetrance, then, is one way harmful genes do not get eliminated through natural selection.)

Mukherjee sums up what genes do with the three “R”s: regulation, replication, and recombination.  To which he then adds a fourth: repair.  It’s the replication part that gets most of the press: cloning and all that.  But it’s regulation and recombination that makes straight-forward genetic engineering and simple-minded Darwinian fundamentalism equally pipe dreams.  There’s just way too much slippage in the process, too large an element of chance along with environmental factors that would be difficult to control even if we understood them completely.

Hemophilia offers a good example of why a simple fitness story doesn’t work.  The gene that causes can be carried by the mother, but only expresses itself in male progeny.  Therefore, because the gene is recessive in women, natural selection doesn’t get the opportunity to eliminate it.  Even though there is no way to link hemophilia to fitness, it persists.

Furthermore, while hemophilia is one of those diseases that can be linked to a specific gene, there are lots of conditions and abilities—smell is one good example—that are the product of multiple genes, often in the dozens, sometimes over one hundred.  Natural selection can’t zero in on a defective gene in such cases, plus mucking around in such complex systems often has bad side effects.  The complexity of human biology, in other words, works against any simplistic understanding of natural selection.  Features of the human organism are just too inter-related to make targeted elimination of specific features possible in many, many (although not all) instances.

In addition, there are the benefits of diversity itself.  The trouble with Darwinian fundamentalism is that it takes the ranking approach to human behavior and personality and capabilities—as if it were the AP ranking of college basketball teams.  The “fittest”—absolute superlative—is what emerges from evolution.  But that’s nonsense.  There are multiple possible ways of surviving to the point of reproduction.  Evolution, at best, eliminates those that can’t survive until reproduction.  It does not optimize; it does not only select the best.  The “good enough” survive as well.

And the survival of that diverse range is crucial because a diverse gene pool is the vast reserve army by which a species arms itself against environmental change.  An over-specialized species, ill equipped to adapt to change, will not survive in the long run.  Far from needing the fittest, evolution needs the diverse, a whole range of types and variants.

To switch the focus to emphasizing how evolution selects a wide range instead of “the fittest” is to understand why evolution is not destiny nor even an indicator of set limits.  New environments will call forth new adaptive behaviors—and a rich gene pool will ensure that such adaptions are possible.  Not for everyone perhaps, but for some.   Not to mention that the complexity of the system lays itself open to new interactive patterns, along with innovative recombinations and the development of regulative responses to new triggers.  Of course, translating from a specific genetic make-up to behavioral patterns and capabilities is very difficult.  Such a holistic vision of human functioning–arising out of the base of genes–is still far beyond our analytic abilities.

Natural selection, in short, is not the conservative’s dream of a Hobbesian competition of all against all.  It is not just that humans, quite obviously given their extra-long immaturity, cannot survive except in mutual aid societies; it is also because the elimination of all diverse others would quickly lead to the extinction of the species.  To put it in the bluntest terms: if I only worked to ensure the survival of my genes—and not those of anyone else—I would be murdering the species. A purely selfish gene will not see too many generations.