Degrees of Wrinkledness

Perhaps​ you too have planted a hydrangea in your garden, its blossom as blue as blue can be while still in its pot from the nursery, only to watch its colour muddy and turn ever pinker as the plant’s roots sink into alkaline soil. This is an example of the way the visible character of an organism can be modified by its immediate environment – in this case, soil pH. Many other instances are even more striking. The spine of the translucent water flea Daphnia shortens and ultimately disappears if it is bred for generations in polluted water, only for the long spines to reappear in the offspring of spineless Daphnia removed to clean water. There are examples from human biology as well. Ogden syndrome, a disease that can result in heart arrhythmia, large eyes, wrinkled skin and even death in infants, is linked to a mutation in the gene NAA10. But quite a number of healthy people also carry this mutation, suggesting that the micro-environment of the carrier’s genes probably plays an important role in the highly variable manifestation and severity of symptoms, which range from barely noticeable to fatal.

None of this will be news to most biologists, especially in the age of evo-devo (evolutionary developmental biology) and the new epigenetics, which studies the way genes are switched on or off by biochemical signals from the organism’s internal and external environments. But Gregory Radick, a historian of science at the University of Leeds, thinks that paying closer attention to such examples would help the rest of us rethink our assumptions about genetic determinism. He wants us to stop talking about ‘genes for’ this or that trait or using such metaphors as ‘it’s in the DNA’ to describe some ancestral and unalterable trait of a person or institution, and he wants us to guard against genomic hype, whether it’s the fantasies of ancestral identity bound up with 23andMe or promises that the discoveries of genes for schizophrenia or cardiovascular disease are just around the corner. The reality, Radick insists, is a lot more complicated, and if we had a better appreciation of that reality, we might come to see other things differently too. We might, in particular, be more sceptical of claims made about robust genetic differences between groups – not least regarding race.

The cure Radick proposes for knee-jerk genetic determinism is a large dose of history. Why did we – not just laypeople but also many biologists – embrace genetic determinism in the first place? And why has our faith in the doctrine not been eradicated by the eugenic policies it has inspired, from mass sterilisation in the US to mass murder in Nazi Germany? Just as Freud thought that he could cure neuroses by helping patients work through their memories of the event that triggered them in the first place, Radick hopes that by tracing genetic determinism back to its origins and exhibiting the force of the arguments against it – not adequately addressed then or now – he can free us from our illusions. More than that, he wants us to imagine a counterfactual history in which the course of science took a different direction, in which the countervailing evidence to what became the genetic orthodoxy was fully acknowledged.

Radick begins, as do most histories of modern genetics, in the 1850s, with the experiments of Gregor Mendel on peas in the garden of the monastery at Brünn (now Brno in the Czech Republic). Mendel had studied at the University of Vienna, but his interests were shaped at least as much by his farming background and the aim of the abbot of the monastery to improve local breeds of everything from sheep to apples in order to boost the regional economy. Mendel knew from horticulturalists that traits such as flower and seed colour could be changed by hybridisation, and set out to investigate the stability of the hybrid form when it is bred over many generations, a question of obvious interest to breeders. He selected easily observable trait differences in his cross-breeding experiments with garden peas (Pisum sativum): round or wrinkled seeds; yellow or green seed colour; purple or white flowers. Taking great care to keep his self-fertilising stock as pure as possible, so he could be confident that, for example, the green-seeded peas reliably produced only green seeds and yellow-seeded ones only yellow, he proceeded to hybridise them and keep track of their traits over generations. The result, when you cross green and yellow-seeded peas, is that you get on average three yellows (dominant) to one green (recessive) in the next generation. Mendel knew nothing about genes or chromosomes, but reasoned that if the pollen and egg of the parent plant each contributed equally to the offspring trait, his results could be explained by assuming that all combinations – YY, GG, YG, GY – were equally probable, but that YY, GY and YG would all manifest as yellow-seeded peas because yellow was a dominant trait. Only the double GG, with a one-in-four probability of occurring, would manifest as green.

Mendel was modest about his ‘law’, qualifying it as the ‘law for Pisum’. But his followers soon threw such caution to the wind, and it is the Mendelians whom Radick has in his sights, first and foremost William Bateson (1861-1926) of Cambridge. The bulk of the book is given over to the controversy that raged between Bateson and W.F.R. Weldon (1860-1906) of University College London and later Oxford, and between their allies, over the interpretation and implications of Mendel’s results for inheritance in all organisms. Bateson and Weldon had met as students at Cambridge, and although Bateson was the one with a Cambridge pedigree (his father was master of St John’s College), at first he happily accepted Weldon as his guide to the study of morphology, which was all the rage in the 1880s. But he came to chafe at Weldon’s professional successes and perceived condescension; he later remarked that he’d been made to feel like Weldon’s ‘bottle-washer’. It can’t have helped that while Weldon sailed from fellowship to lectureship to university chair, Bateson was stuck in a sinecure at St John’s (in charge of the kitchen) until he was eventually named to a Cambridge professorship in 1908, the first such position in the new science of genetics. Whatever the personal origins of their rivalry, it soon flared into an acrimonious professional disagreement over how to think about inheritance.

The dynamics of debate between Bateson and Weldon – played out in person at meetings of the Royal Society and the British Association for the Advancement of Science as well as in correspondence and learned journals – favoured a thrust-and-parry style of argument that sharpened points of difference. As in a duel, the two opponents enlisted seconds, allies who made sure that a key article was rushed into print or held up in committee, who raised objections after talks and added their own arguments and evidence to the record. The allies on both sides included quite a few women, early graduates of Oxbridge women’s colleges, but the agonistic, masculine language of the debate was the scientists’ own. Although it was no longer necessary to forbid insults and fisticuffs at meetings of scientific societies, as the 1699 regulations of the Académie Royale des Sciences had, the controversy over Mendelism did get nasty at times. Weldon felt guilty about it; Bateson apparently did not.

What were they fighting about? Bateson had become Britain’s foremost champion of Mendelism. All that mattered, he argued, was the genetic material (though everyone was pretty foggy as to what exactly that might be) contained in parental gametes. The transmission of traits to the next generation followed Mendelian patterns, as well-distinguished dominant and recessive characters combined in straightforward fashion, more or less independent of each other and of physiological and environmental factors. Weldon objected that ancestry, sometimes even distant ancestry, mattered too, and that there was far more variability in the data than the strict Mendelians acknowledged. Not only were many species exquisitely sensitive to environmental conditions in terms of which characters they manifested and to what extent (recall the hydrangeas and the water fleas), but there was a spectrum of gradations, rather than the clear-cut categories required by Mendelian accounting. When Weldon repeated Mendel’s pea experiments, he discovered all manner of shades between unambiguously yellow and green seeds, as well as variable degrees of wrinkledness and roundness. Where Mendelians like Bateson insisted on discrete characters inherited in predictable proportions, Weldon saw continuous characters which defied Mendelian ratios and were demonstrably modified or suppressed altogether by slight changes in ambient conditions.

This is​ a summary of some 250 footnote-packed pages, the core of Radick’s book. The archives for this episode in the history of biology are almost too rich: sheaves of correspondence among the protagonists, minutes of meetings, committee reports, Weldon’s unpublished manuscripts. Radick recounts every twist and turn of the debate, and his account of the Bateson-Weldon stand-off is surely definitive, whatever queries might be made of his interpretations. Parts of the story have been told before: Francis Galton’s brilliant visualisations of mathematical ideas, such as the quincunx that generated a normal curve by ricocheting a bunch of balls randomly down a pegboard; Darwin’s ill-fated theory of pangenesis; the founding of the journal Biometrika by Weldon, Galton and Karl Pearson to bring statistical thinking to biology; the popularisation of the Mendelian message by Charles Davenport and other eugenicists (to baleful effect). Radick weaves these familiar elements into his account to show the ways in which biology was becoming more professional, and international, at the end of the 19th century.

Young researchers could now undertake their apprenticeships at marine zoological stations in Naples, Plymouth and Virginia, where they learned to merge traditional field observation with new kinds of laboratory experimentation and became members of international networks. A typical day for Weldon at Plymouth consisted in measuring 160 crabs; Bateson spent a steamy Virginia summer studying the acorn worm, which lives in the seabed. Biologists of their generation investigated a range of plant and animal species, from snails and moths to peas and poppies, and this emboldened them to ask big questions about inheritance and the emergence of new species.

The teeming detail of Radick’s book baffles efforts to plot a straight-line narrative. I suspect this effect is a deliberate attempt to allow the reader to experience the uncertainty and messiness of real science in the making. He insists that the outcome of his story was contingent, in the same way that the outcomes of elections and military battles depend on a tangle of factors too numerous to list and too complicated in their interactions to predict. But what is a truism in most kinds of history – that events turn out as they do for contingent reasons – is disputed in the history of science. Almost all history of science is winners’ history. The last proponents of geocentric astronomy or phlogiston may no longer be dismissed as irrational or pigheaded, but their evidence and arguments receive considerably less attention from academics than those of their ultimately successful opponents. And almost no one suggests that the likes of Tycho Brahe or Joseph Priestley ought to have won, however sympathetically their reasons for resisting Copernicus or Lavoisier might be reconstructed. Radick is more radical. Everyone now knows that Bateson and the Mendelians won in the end. Radick wants us to imagine that it could have and should have turned out differently, had all the evidence and arguments been weighed and had Weldon not died prematurely in 1906, aged 46.

In the final part of the book, Radick tries to make this counterfactual history plausible. He musters all the protests from the Mendelian camp (what about the successful application of Mendelism to breeding? What about Lysenkoism, according to which hereditary material could be modified by changes to the parent organism’s body, and which became Soviet doctrine under Stalin? What about the subsequent triumphs of genetics?) and tries to knock them down one by one. Some of his rebuttals are persuasive, others less so. It’s true that successful applications of a theory do not mean it is correct (geocentric astronomy was still used for navigation at sea long after the triumph of heliocentrism); and the fact that the Soviet Union later rejected Lysenkoism does not, of course, make Lysenko’s own rejection of Mendelian genetics any more defensible. More interesting are Radick’s observations as to which scientific data do and do not get remembered, and which phenomena do and do not get investigated. Many people will remember from school biology lessons that blue-eyed parents will have only blue-eyed children, because being blue-eyed is a recessive trait. Yet a study in 1918 showed that 12 per cent of the children of blue-eyed parents had brown eyes. How reliable was the study? It’s hard to know, because once Mendelism had carried the day there was no motivation to put one of its most useful examples to the test.

Still more intriguing is the progress of research on what are known as ‘norms of reaction’. The German biologist Richard Woltereck advanced the idea in 1909, based on his experiments on the water flea Daphnia. He noted that different varieties of a species might, when exposed to environmental changes, react in a range of ways. Some varieties might hardly change; others might exhibit changes dramatic enough to suggest that a new species was emerging. Later research showed that even monoclonal organisms – ones with identical genotypes – might exhibit different degrees of phenotypical plasticity. Had anyone wanted to follow it up, here lay a clue as to why the Batesonian and Weldonian factions had obtained such divergent results in their experiments on the impact of environmental modifications: depending on the norm of reaction of the organism in question, the impact of environmental changes can vary considerably. Although norms of reaction never entirely disappeared from biology (Richard Lewontin made much of them in his attacks on what he perceived to be the ideological basis of genetic determinism in the 1980s), they receded into the background until recent work in epigenetics revealed the huge importance of changes within the genome, as it reacts nimbly to cues at every level from the cellular to the environmental. In the metaphorical language that has always saturated the science of inheritance, the genome may turn out to be less like a computer program and more like an organ of perception. This isn’t so much a nature versus nurture story as a complete rejection of all three parts of Galton’s opposition, including the ‘versus’. It’s much, much more complicated.

Radick thinks Weldonian pedagogy might heighten appreciation of this complexity and has tried to test his hypothesis in his biology classes at Leeds and elsewhere. He admits that the results so far have been modest; and, at least at Leeds, none of the biology students wanted to sign up for the alternative course. He’s well aware of the tyranny of the textbook, especially of those seductively simple Mendelian matrices. As Thomas Kuhn pointed out in The Structure of Scientific Revolutions (1962), science textbooks do much more than teach students what is worth knowing (and, implicitly, what is not); they also teach what it means to know by providing models of problems successfully solved – ‘paradigms’, in Kuhn’s term. These models are invariably oversimplified, by the standards both of the history of science and of what the students will encounter if they go on to more advanced training (and even more so if they try to apply what they’ve learned to practical ends). But encumbering these models with the complexity and variability that would make them more realistic would destroy their paradigmatic character: every new particular reduces generality.

As a historian, Radick is a connoisseur of particulars and committed to contingency. But it is worth reflecting on which domains of inquiry reward scrupulous attention to variability and which do not. The Scottish physicist James Clerk Maxwell, whom Radick quotes for his witty riposte to Galton that if heredity was destiny, then belief in free will must be predetermined too, observed that Galileo had been lucky to begin his inquiry with the fall of heavy bodies rather than turbulence. Free fall is a phenomenon in which one big cause (gravity) overwhelms many little ones (air currents, friction, viscosity, shape etc) in determining the trajectory of a falling body. By neglecting all the little causes, Galileo was able to extract a simple mathematical relation that was a decent fit to observation and that required no more than the mathematics then available (Euclidean geometry). In contrast, turbulence phenomena exhibit no such hierarchy of big and little causes, as Maxwell was all too aware. In the familiar example, a tiny perturbation in the turbulent system of the world’s weather – the flapping of a butterfly’s wings – can trigger a mighty storm many thousands of miles away. As a result, climate models are monsters of complexity, taxing the most powerful supercomputers to their limits. Had Galileo begun with the weather, physics would still be in its infancy. The question of whether or not variability and complexity matter in science may not have a one-size-fits-all answer: it depends on which discipline and what kinds of phenomenon are at issue.

Mendel seems to have practised a strategy of simplification so extreme that subsequent researchers, starting with Weldon, have wondered whether he cooked his numbers: the data were simply too good to be true. Radick has a more charitable explanation. Recall those spectral shades fanning out between yellow-yellow and green-green pea seeds, and imagine that it wasn’t a biologist trying to classify them unambiguously as yellow or green but a fashion writer bent on capturing every tint and hue – chartreuse, apple green, olive, lime – and you get some idea of the kind of discretionary judgments Mendel would have had to make in order to sustain his strict binary classification. Or he might simply have discarded in-between colours, in the way scientists (and scholars) occasionally exclude outliers from their data as glitches or flukes. Sometimes a clear signal emerges from the noise after judicious pruning, but sometimes the pruning inadvertently exaggerates or even creates the signal.

Viewed at a distance of more than a hundred years, during which research has revealed the nature of chromosomes, the existence and structure of DNA, the mechanisms by which genes code for the manufacture of proteins, intra-genomic regulation and a great deal more besides, the Bateson-Weldon debate about the way inheritance works doesn’t seem so decisive. The Mendelism they fought over is not the genetics of today. Radick quotes the philosopher of science Evelyn Fox Keller, who was trained in physics and molecular biology, to the effect that there’s almost nothing left in the annals of contemporary genetics of the old view of stable genes inexorably determining specific characters. Yet he believes that the genetic determinism of the Mendelians persists nonetheless, at least in public discourse, and that revealing its history and teaching biology in light of that history will strip us of our illusions.

If only. Long before Mendel planted his peas or Bateson and Weldon squared up to each other, ideas about inheritance had seeped into the collective consciousness. Obsessive interest in lineages and bloodlines neither began nor ended with snobbish characters in Victorian novels; humans have been attentive to inherited traits ever since they began domesticating plants and animals some fifteen thousand years ago. The practice of breeding anticipates and shadows the science of inheritance every step of the way, from Darwin’s instructive conversations with pigeon fanciers to Mendel’s interest in improving pea strains to Galton’s brief for eugenics as an extension of breeders’ insights to humans. Whether it was Bateson preaching the new Mendelian science to American horticulturalists eager to increase grain yields or Weldon poring over the twenty-volume General Stud Book of Race Horses to work out the patterns of inheritance governing chestnut coats, breeding was everywhere. Its vocabulary of thoroughbreds and mongrels, pedigrees and sports, was common currency among all those who fancied flowers or dogs or horses.

Fascination with inheritance overflows genetics. Plumping for nurture over nature just highlights another side of inheritance, once to do with wills and entailed estates and now talked about in terms of privilege and nepo babies. Metaphors of inheritance have burrowed deeper still into our ways of thinking. The pun in Radick’s title, Disputed Inheritance, depends on them. Perhaps we can be cured of talking about ‘genes for’, but it will take much more than therapeutic history and revised biology curricula to dislodge inheritance from its place in our imaginations.