Imagining a World Without Mendel

Review of

Disputed Inheritance: The Battle over Mendel and the Future of Biology. By Gregory Radick. Chicago: University of Chicago Press. 2023. xii+ 630 pp. ISBN 978-0-226-82272-3 (paper).

How We Get Mendel Wrong, and Why It Matters. By Kostas Kampourakis. Boca Raton: CRC Press. 2024. xxi + 226 pp. ISBN 978-1-032-45690-4 (paper).

I am a reformed Mendelian. I left the cult when I came to realize that Mendel himself never had two laws called Segregation and Independent Assortment. That was Thomas Hunt Morgan’s reframing of Mendel. Prior to Morgan, the first decade-and-a-half of Mendelians referred to something nebulous and singular, Mendel’s Law. It generally went something like this: A trait is controlled by a pair of elements, only one of which is passed on to offspring, and one element of a pair can sometimes suppress the effect of the other.

But that leaves out chromosomes, polygenic inheritance, crossing-over, co-dominance, pleiotropy, epistasis, developmental plasticity, mtDNA, epigenetics, microbiomes, indeed most of genetics. Which in turn raises the question, are Mendel’s Laws the rule or the exception? The attempt to make Mendel seem relevant to an understanding of human genetics has indeed always proved vexing. There are genes making enzymes and blood antigens, but having B-negative blood or the ability to taste phenylthiocarbamide seem unlikely to have been major factors in the adaptive divergence of the hominin lineage, much less in the extinction of Neanderthals. Of course, there are also genes causing rare genetic diseases, but they are less relevant to a general understanding of human heredity simply by virtue of being rare. In 1940, infamously, the fruitfly geneticist Alfred Sturtevant suggested that the ability to roll one’s human tongue was a Mendelian trait.  By 1956, he acknowledged being embarrassed by it, but it proved too pedagogically valuable to discard so readily. The Mendelian gene, for all its heuristic value, is surprisingly elusive in human biology.

Gregory Radick is a historian of biology, whose excellent 2016 book on early studies of ape cognition, The Simian Tongue, is itself of considerable interest to readers of this journal. Radick wants to call our attention to W. F. R. (Raphael) Weldon, a geneticist at the base of the Mendelian intellectual tree, who maintained that the emerging concept of a gene was meaningless, for a gene (whatever it may be) is actually a complex and context-dependent unit. Weldon’s untimely death in 1906, argues Radick, left the more complex gene without a defender, and left subsequent Mendelian discourse on a much more simplistic (and conveniently easily politicized) track. That track was defined by William Bateson, who was so into Gregor Mendel that he named his first son (who later became an eminent anthropologist) after him.

Convergently, philosopher and biology educator Kostas Kampourakis has written several books on genetics and evolution, and trains his sights on Mendelism as well. As a historian, Radick is more focused on the past; Kampourakis, on the other hand, is more interested in the future. Both books are at pains to dismantle the myth of Mendel. The founding myth of genetics is that of the solitary genius, working to discover the basis of heredity in the cloistered confines of his monastery, disconnected from mainstream science; then deducing the rules of particulate genetic transmission by quantifying his results; and summarizing them in two Laws, Segregation and Independent Assortment (Dagher 2014).  He understood before anyone else that a genetic factor is responsible for a visible character, and it enters the next generation probabilistically. Alas, his work went unnoticed and thus unappreciated until 35 years later, when it was noticed, and belatedly constituted the foundation of our understanding of heredity – albeit with most of our understanding of heredity as exceptions. There have been, naturally, some geneticists who have pushed back in various ways against the reductive Mendelian fallacies at the center of 20^th century genetics: notably, from center-left to far-left: Sewall Wright at Chicago, Conrad Waddington at Edinburgh, Richard Lewontin at Harvard, and Trofim D. Lysenko in Moscow.

Kampourakis highlights Mendel’s education and connectedness within the community of scholars, especially with Carl Nägeli, a Swiss experimental botanist. Mendel himself was interested in genetics only insofar as it related to hybridization, and he knew that his results were not particularly generalizable. Moreover, the 20^th century was well underway before anyone at all was talking about two laws, Segregation and Independent Assortment. Kampourakis also paints with broader strokes than Radick, whose book is primary research in the history of science, with the depth and focus that comes with that territory. Both books are readable, and tell familiar and unfamiliar stories in readily understandable ways. Radick’s book is devoted in nearly its entirety to the machinations of William Bateson in promoting and elevating a particular vision of Mendel’s work.  Radick’s denouement is an experiment in counterfactual science history: What if Raphael Weldon hadn’t died in 1906, but had lived to challenge Bateson’s binary, essentialist “Mendelian gene” with a more fluid concept – a “Mendelian gene” that could be upregulated and downregulated, interact with other genes, and whose products could engage in a complex set of cellular, physiological, and ontogenetic processes, eventually resulting in a phenotype? 

Much has been written on just why Mendel’s work was ignored. It focused exclusively on heredity, when biologists still combined heredity and development, which later became disengaged after the development of the cell theory. It was also a paper about hybridization, not genetics. He didn’t follow it up. It was in German. And it was about peas. Today we casually accept (and teach) that reproduction in peas is the same as it is in humans, but that is actually only true from the perspective of cells. And even then, only very abstractly. Moreover, if you try to show your students videos of both species reproducing, you may well find the perspective of lawyers, in which reproduction in peas and people is very different, more important than the perspective of cells.

When I was in graduate school, some people followed an old rumor in questioning whether Brother Gregor fudged his data, on the grounds that his reported numbers were somehow too close to the ratios he was deducing. I always thought that was a weird argument; but to me what was weirder was that Mendel reported on seven traits, each of which turned out to be on a different one of the seven pea chromosomes. God must have really wanted him to come up with a Law of Independent Assortment.

Whatever laws he may have discovered, and whatever he may have done to discover them, the fact remains that Mendel was adopted as an icon by the fledgling field of genetics early in the 20^th century. Students of heredity brandished him as their standard-bearer and mythic founder in much the same way as their recent precursors in natural history had adopted Darwin (Meloni 2016). Their main difference would be that Darwin’s insight was recognized in his time, while Mendel’s was not. A more sinister convergence is that both sets of theories were readily appropriated in ways that we identify retrospectively as evil: Social Darwinism (Hofstadter 1944) and social Mendelism (Teicher 2022).

We don’t talk as much about social Mendelism. But the tunnel vision of seeing the world from the perspective of cells and meiosis and fertilization eventually led Mendelism to accumulate a lot of baggage over the course of the 20^th century. The gene for wrinkled seeds had hardly a fraction of the effect on people’s lives that the gene for feeblemindedness had. The Mendelian gene for beta-globin (dysfunctional in sickle-cell anemia) and the gene for hexosaminidase A (dysfunctional in Tay-Sachs Disease), which are both very real, lie on one side of the ledger.  On the other side are the genes for intelligence, altruism, and xenophobia, which aren’t real, or at least aren’t real in the same way.

A British geneticist named David Heron put it this way in 1912, critical of the American genetical obsession with a gene for this and a gene for that, especially when it came to psychological traits: “Mendel defectiveness seems for these American investigators to be a far more serious problem than mental defectiveness!” (p. 54, emphasis in original).

Obviously we don’t want to throw out the baby with the bathwater. So what is at stake with baby Gregor? On one side of the moral ledger are Mendel and his laws. On the other side of the ledger is the take-home lesson from the very first English textbook on the subject, called Mendelism: namely, that education is bunk, and “the creature is not made, but born” (Punnett 1905:60).  On that same side is the “unit-character fallacy,” identified by cautious geneticists a century ago as the problem of mapping a single gene onto a single noun – such as thalassophilia, an ostensibly genetic explanation for the Phoenicians’ love of the sea, by an incautious but nevertheless very influential geneticist. On that same side is also the idea that somehow you are, or are built from, nothing but the summation of your genes, the intellectual stimulus that eventually got the Human Genome Project rolling in the 1990s. And on that side as well is the idea that people can be naturally sorted into discrete binaries, like wrinkled and round peas.

So maybe taken as a whole, Mendelism wasn’t that great of a way to think about biological heredity in the first place, has run its course, and should be re-thought for the 21^st century. Maybe binary Mendelian genes are simply special cases in a real world of chromosomes, RNA, pleiotropy, and epigenetics that sometimes even manages to mimic Lamarckism. Both books converge on a common theme: How can we teach human genetics differently and better? For a human genetics seminar, a science studies class, or just to rethink some of those undergraduate lectures, the two books will pair very well.

What might replace the Mendelian genes as units of inheritance? The physical elements that actually do the cellular work of segregating and recombining – namely, the chromosomes. There aren’t 20,000 independently segregating genetic elements in a human cell, only 23. The segregating units aren’t the genes, but blocks of genes. And within those segregating and recombining units lie units of transcription, embedded within complex patterns of DNA, whose products may themselves be biochemically active (i.e., as RNA), or may help produce other biochemically active molecules in turn (i.e, as proteins). The biochemical activity can be upregulated or downregulated by direct interaction with the environment (i.e., epigenetically) or by mutation. And out of this often qualitative cellular business somehow emerge quantitative phenotypes, for phenotypes are problematic, not automatic. And what gets downplayed in such a treatment? Those bits of phenotypic difference that automatically represent genotypic difference – that is to say, genes for things. Those rare diseases, like the pea examples, which are special cases.

Together, what these books demonstrate is that there is a major change in the offing about how we should teach the most basic facts about heredity, from centering abstract binary elements to instead centering the actual cellular and biological systems involved in genetic transmission. Viva la revolución!

 

References

Dagher, Zoubeida R. (2014) The relevance of history of biology to teaching and learning in the life sciences: The case of Mendel’s laws. Interchange 45: 205–216. https://doi.org/10.1007/s10780-015-9241-y.

Heron, David. (1913) Mendelism and the Problem of Mental Defect. I. A Criticism of Recent American Work. London: Dulau.

Hofstadter, Richard (1944) Social Darwinism in American Thought. Philadelphia: University of Pennsylvania Press.

Meloni, Maurizio. (2016) Political Biology: Science and Social Values in Human Heredity from Eugenics to Epigenetics. London: Palgrave Macmillan.

Punnett, Reginald C. (1905) Mendelism. London: Macmillan.

Sturtevant, A. H. (1940) A new inherited character in man. Proceedings of the National Academy of Sciences, USA 26: 100-102.

Sturtevant, A. H. (1965) A History of Genetics. New York: Harper and Row.

Teicher, Amir (2020) Social Mendelism: Genetics and the Politics of Race in Germany, 1900–1948. New York: Cambridge University Press.

Epigenetics as epiphenomenal

               There is an interesting intellectual war going on right now, between scientist/author Siddhartha Mukherjee and molecular geneticists.  It was precipitated by Mukherjee’s recent article in The New Yorker on the wonderful world of epigenetics.

               Geneticist Jerry Coyne  objected stridently to the New Yorker essay. Now, Coyne is one of those people who thinks that a real scientist should not be able to tell a human from an ape, and has chastised me in the past for being able to.  Such people are either deaf, dumb, and blind, or else they don’t think that the choice to privilege genetic relations (which make it hard to tell humans from apes) over ecological relations (where it is really, really easy to tell humans from apes) requires a justification.   In fact, in the 1960s, G. G. Simpson demanded such a justification, and never got one. Historians like Marianne Sommer, Joel Hagen, and Michael Dietrich have been writing about it.

               Mukherjee is responding to his critics.  Anyway, since I already knew that Coyne is apparently not very good at confronting his intellectual prejudices, I thought it might be a good time to reconsider just what is at stake intellectually in this epigenetics business. I talked about this a little in my Annual Review of Anthropology article a few years ago.  But actually it’s a nice example of how understanding the science can be helped by asking the lawyerly question “Cui bono?” (who benefits?).  And further, it helps to show that this isn’t a controversy of biology, but of biopolitics.

               Point #1: Human genetics is invariably biopolitical. To see this point, you must grapple with the history of human genetics.  Not the history as told by scientists, the time-line approach that begins, “Once upon a time there was Archibald Garrod...” – but the history as told by historians.  That’s the history that looks at what scientists said to the public, and at the associated social relations.  The twentieth century, after all, began with eugenics and ended with “genohype” – which no sensible geneticist wants to defend today.

               And we nearly span the century when we compare the concluding statement of the first textbook of Mendelism (1905) with the director of the Human Genome Project’s comment to Time Magazine in 1989. First, the eponymous Reginald C. Punnett, remembered in science today for his square:

“As our knowledge of heredity clears and the mists of superstition are dispelled, there grows upon us with an ever increasing and relentless force the conviction that the creature is not made but born.”

               Ummm, WTF?  Granted, genetics was important enough to him to write a book about, but the message that “the creature is not made but born” is certainly not its central message.  Its central message is about how the creature gets born – not that the facts of birth are the only important things about it.

               Compare James Watson: “We used to think our fate was in the stars.  Now we know, in large measure, our fate is in our genes.”

               Now, I know, throwing out Watson quotes is hardly even fun any more, and nobody in science really believes him.  But let me just remind you that he knows more about DNA than you do, and he has a fucking Nobel Prize.  What have you got?

               What these two thoughts have in common, 84 years and a whole lot of data and theory apart, is their biopolitics.  They are saying something very important, and it’s not about fruitflies, nor is it about the ABO blood group.  It’s about your lot in life.  It’s about who you are, and what you can aspire to become. And it’s a fairly pessimistic note, if your origins are humble: You can never transcend you ancestors. Read it:

The creature is not made, but born.

Our fate is in our genes.

Your personal development is strictly limited by your ancestry.

Now, that is a message that resonates far beyond genetics.  It is familiar to readers of 1994's The Bell Curve, for instance, whose authors were a psychologist and a political theorist.  It is there in the 19^th century political writings of Arthur de Gobineau.  It is also familiar to readers of pre-modern geneticists, such as August Weismann and Francis Galton.

         

            What is interesting in the present context is the broad opposition to that pessimistic statement, and the alternative scientific venues for studying how the creature is indeed made, our fates are not in our genes, and we can become different from our ancestors.

     

              One such venue, which was popular in the late 19^th and early 20^th centuries, was the inheritance of acquired characteristics, often known as Lamarckism. This of course petered out with the suicide of Paul Kammerer in the 1920s, but has never been entirely buried. Bipedalism, after all, was a behavioral choice made by our ancestors, for which we no longer have a choice.

               Another venue for studying how we are made is culture, which eventually superseded eugenics as the favored mode of improving society in the 20^th century.

               And still another is human adaptability.

               So over the course of the 20^th century, we actually learned that, despite the biopolitical rhetoric of geneticists, there were in fact several significant ways in which you could become different from your ancestors and not necessarily be limited by them.

              The scientistic rhetoric turned once again with the Human Genome Project in the 1980s. To get that program off the ground, molecular geneticists groomed the public with sound-bites like James Watson’s.  Then (like the eugenicists of the 1920s) they embarked on a wildly successful public education program, to convince taxpayers that three billion dollars to sequence the human genome would be the best three billion dollars we ever spent.

               And a wave of purple scientific prose flowed in its wake.  Remember “Mapping the Code”?  That’s still my favorite mixed metaphor.  And “Mapping our Genes”? And “The Human Blueprint”? And “The Book of Man”?  How about “The Code of Codes”?  (I still don't know what that actually means, except that it is vaguely evocative of Jesus as "King of Kings," and of The Godfather, as "capo di tutti capi".)  Remember how the Human Genome Project was the most important scientific revolution since Galileo and we were going to know what it meant to be human and cure all genetic diseases and stuff?

               Ah well, the important thing is, they got the money.  So what if the public transiently believed that your DNA code was the most important thing about you? Hey, it's just a hypothesis.  And it might be true, right?

   

               Let’s now answer the question “Cui bono?”  Who benefits by having the educated public misbelieve that your DNA code is the most important thing about you?  Two principal groups – just as in the 1920s.  First off, the one percent – those now favored by nature, not merely by avarice or luck or unscrupulousness - and who are inclined to try and give their own kids a financial leg up in this dog-eat-dog world, rather than redistribute the wealth in the form of public goods and services that might permit others to compete more fairly in that world.

               And second, the molecular geneticists – the ones now studying the most important thing about you.  Your DNA code.  In fact, anything’s DNA code.  It’s also The Frog Blueprint and The Book of Frog.  That is Point #2: It is in the interests of the molecular geneticists to have you believe that everything important about you lies in the field of molecular genetics.

               That is a significant convergence of interests with the one percent.  Back to history.

              By the late 1930s, the developmental geneticist C. H. Waddington was distinguishing between the kind of information in a human cell that distinguishes one person from another (genetic) and the kind of information that distinguishes one cell type from another, with identical DNA sequences (epigenetic).  Waddington’s  reputation had been all but eclipsed in genetics, when Stephen Jay Gould revived him in evolutionary biology, specifically in the call for an evolutionary science of organismal form, rather than the reductive evolutionary science that was normative in the 1980s.

               Epigenetics is a label for the non-reductive study of heredity.  You are no longer just your ancestors’ DNA sequences, but also their methylation and transcriptional regulation patterns.  But more significantly, your genetics is far more conservative than your epigenetics.  Your “epigenome” is responsive to the environment; that is to say, it adapts.  And it does so far more rapidly and directly than your genome does.

               That extends our list of alternative scientific venues for studying your non-DNA-sequence-based self just a bit.  In addition to the study of possible Lamarckian inheritance, culture, and human adaptability, there is now epigenetics.  In other words, the significance of epigenetics lies in its biopolitical role as a reaction against the genetic determinism, or hereditarianism, that accompanied the Human Genome Project.

              There is, in fact, a lot more at stake than just transcription factors.  The smart geneticists already know that.

               Waddington, it turns out, was a very smart one.  He was a broad intellectual, and actually wrote a book about art at the end of his life.  I don’t think he was that big of a Marxist, as Mukherjee suggests, although he was certainly left of center politically, and was instrumental in getting the famous University of Edinburgh science studies program going (known as the “strong programme”).

              Waddington’s biology was also always very well-informed anthropologically.  When he and his wife visited New York they always stayed with Margaret Mead.  Why? Because Waddington’s BFF from college days at Cambridge was Mead’s third husband, Gregory Bateson.  (Waddington’s daughter is a distinguished Cambridge social anthropologist.)  The major influence on Bateson and on Waddington was not the philosopher Marx, but the philosopher Alfred North Whitehead, also very much the anti-reductionist, but a bit more spiritual.

               At least I think so.  He may have been less impenetrable in person. He’s fucking tough in print.  

               Gregory Bateson’s 1936 ethnography Naven acknowledges some influence of Waddington and Whitehead in a footnote.