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.