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Haldane — a force of nature

2017; Elsevier BV; Volume: 27; Issue: 9 Linguagem: Inglês

10.1016/j.cub.2017.03.041

1879-0445

Brian Charlesworth,

Nutrition, Genetics, and Disease

J.B.S. Haldane was one of the towering figures of twentieth-century biology. He made numerous contributions to genetics, evolutionary biology, biochemistry and physiology, displaying an uncanny ability to apply mathematical methods to answer important biological questions. Many of these contributions, especially his work on population genetics, still influence contemporary researchers. His wide-ranging intellect and prodigious memory, together with his lucid and concise style of writing, made him an outstanding populariser of science, as well as an author of several serious scientific books. His larger-than-life personality, summed up by Boris Ephrussi’s quip “Ce n’est pas un homme, c’est une force de nature”, and his Marxist politics attracted a level of public attention that is very unusual for a scientist. Krishna Dronamraju’s book is the latest biography of Haldane. Dronamraju is especially well qualified for this purpose, since he was one of the graduate students who worked with Haldane after his move to India late in life, and has edited several collections of Haldane’s writings, as well as a book on Haldane’s contributions to modern biology. The book is organised in an unusual way, with chapters dealing with different facets of Haldane’s life rather than following a strict temporal sequence. It therefore reads like a collection of essays, with a good deal of repetition between chapters. Indeed, there are several instances of repetition within chapters, and other signs of a lack of careful editing, as well as a very sketchy index. This is a pity, since the book contains a wealth of information about Haldane’s life, both personal and scientific, illustrated with numerous photographs, and documented with extensive notes at the end of each chapter. Here, I will briefly summarise a few of the topics covered by Dronomraju. To people living in the 21st century, the account of Haldane’s background as a scion of the Scottish minor aristocracy on his father’s side (very little is said about his mother, Louisa née Trotter, other than that she was a strong Imperialist and Conservative) seems to relate to another world. Dronamraju does not mention that, like many Scottish names, Haldane is of Scandinavian origin. The little-known German play based on Alfred Bicknell’s Life of Alfred, King of the Anglo-Saxons, with incidental music by Joseph Haydn, has a chorus of Danes celebrating a massacre of Anglo-Saxons, with the words “Triumph, Triumph, Triumph dir Haldane” (Triumph…for you, Haldane). It is tempting to suppose that Haldane’s large size and ferocious temperament reflected Norse ancestry. Haldane’s father, John Scott Haldane, was a prominent Oxford physiologist, after whom the ‘Haldane effect’ of oxygen on the retention of CO2 by haemoglobin was named, and his uncle, Lord Haldane, was a leading Liberal politician. Young Jack Haldane grew up in a highly privileged environment, but one in which intellectual activities, especially scientific ones, were predominant. One cannot avoid the impression that, despite his conversion to left-wing political views, his behaviour throughout life reflected the self-confidence and sense of entitlement that characterises the British upper classes. Conventionally enough, Haldane was sent to Eton, which he loathed, in part because his evident mental superiority isolated him from his peers. From an early age, he assisted his father with physiological experiments, even including work on decompression of divers, which prefigured his important research on diving physiology for the Royal Navy during World War II. This work involved exposing himself and several associates to very dangerous conditions, resulting in a severe back injury to Haldane. Haldane’s courage, not to say reckless disregard of danger, was also displayed during his frontline career in the British Army in World War I, which Dronamraju describes only briefly. Haldane early developed an interest in genetics — according to Dronamraju, this started during his time at Eton, and he published his first genetics paper in 1915 in collaboration with his sister Naomi and A.D. Sprunt (who was killed in action), describing linkage in mice for the first time. Haldane was characteristically very proud of the fact that he was “the only officer to complete a scientific paper from a forward position of the Black Watch” (p.16). His 1919 paper on his mapping function (which relates genetic map distance to recombination frequency under the assumption of no interference) was a pioneering contribution, which was only superseded by formulae based on more realistic assumptions many years later. Somewhat later, in 1922, he published his famous paper on ‘Haldane’s Rule’, using data on interspecific crosses to show that it is usually the heterogametic sex that suffers inviability or sterility in interspecific crosses; this raised questions of causation that are still being studied by researchers in evolutionary genetics. Haldane’s early postwar scientific career involved an appointment in physiology at Oxford, followed in 1922–1933 by a readership in biochemistry at Cambridge under Gowland Hopkins, who led what was then the world’s foremost biochemistry institute. From Dronamraju’s account, it is unclear why Haldane was appointed to this post, but he was clearly a great success, contributing importantly to theories of enzyme kinetics, summarised in his 1930 book Enzymes. During this period, Haldane’s 1924 meeting with the journalist Charlotte Franken led to the infamous ‘Sex Viri’ scandal, in which he was cited as co-respondent in her divorce case, leading to his conviction for immoral behaviour by the (unintentionally comically named) Sex Viri committee of Cambridge University, and dismissed from his post. He successfully appealed to a higher tribunal of the university, and was reinstated. Charlotte became Haldane’s first wife, and was responsible for encouraging him in engaging in his popular science activities, which seem to have been quite lucrative. (It is a sad reflection on our society that fame and fortune mostly come to popularisers of science, rather than to those who toil at the scientific coalface.) Her influence also led Haldane to embrace Marxism, and to join the Communist Party in the late 1930s. However, their relationship became increasingly strained, and they divorced in 1945. Haldane’s exposure to biochemists led him to develop an interest in the basis of the relations between a gene and the phenotypic effects of its mutant alleles. His part-time appointment in 1927 at the John Innes Horticultural Institution allowed him to foster research by Rose Scott-Moncrieff and others on the genetics of the production of anthocyanins by plants, which helped to establish the concept that, in the words of Beadle and Tatum in their seminal 1941 paper on metabolic mutants of Neurospora, “the development and functioning of an organism consist essentially of an integrated system of chemical reactions controlled in some manner by genes”. One chapter of Haldane’s 1941 book New Paths in Genetics was devoted to this topic, which eventually led to the idea that genes specify the sequences of polypeptides, and to the genetic code. Of course, many others in the 1930s, notably Sewall Wright, helped to develop the notion that genes controlled enzymes, as had Garrod’s earlier work on human genetic disorders of metabolism, so that this was by no means Haldane’s most original contribution to science. The most important was probably his series of nine papers A mathematical theory of natural and artificial selection, which started in 1924 and ended in 1932. These were mainly concerned with the dynamics of allele frequency changes caused by selection in large populations. It seems likely that, as stated by William Provine in The Origins of Theoretical Population Genetics, Haldane’s interest in this subject was stimulated by conversations in the early 1920s with Harry Norton, a mathematician and fellow member of Trinity College, who had published calculations of the time taken for selection at a single genetic locus to change the frequency of the allele favoured by selection, in an appendix to the 1915 book on mimicry by R.C. Punnett. Norton, however, failed to publish much of his work, until his monumental 1928 paper on selection in an age-structured population. Dronomaraju (p.89) quotes from correspondence in 1950 between Norton’s sister and Haldane, in which she asks Haldane to ensure proper recognition for Norton’s work; in fact, Haldane had explicitly mentioned Norton in two of his papers. Dronomaraju’s account of this work is rather dry — I feel he could have done a better job of making it clear to the general reader why it has been felt to be so important by the evolutionary biology community. This is because Haldane’s models of selection finally laid to rest the view that selection is not an effective agent of evolutionary change, which was widely held in the early 20th century (in his first two papers, he seems to have been unaware of Fisher’s 1922 paper on related topics). Haldane showed that even a rare, selectively favourable allele that arises in a large population at a very low initial frequency can spread to a high frequency, over a period of time that is only a relatively small multiple of the inverse of the strength of selection on the allele. This fails to hold only for completely recessive mutations in a randomly mating population. It would probably have been fatal to the theory of evolution by natural selection if it had turned out that the time for spread was of the order of the inverse of the initial frequency of the mutation. Instead, Haldane showed that it is usually dependent only on the logarithm of this frequency. Not surprisingly, Haldane became a strong proponent of the neo-Darwinian interpretation of evolution, expressed in his 1932 classic The Causes of Evolution, which brought together a wide range of facts from general evolutionary biology and genetics, and related them to the population genetics theory of the day. This makes Haldane’s attitude to the suppression of genetics in the Soviet Union and its satellites, as a result of the influence of T.D. Lysenko on Stalin, so puzzling, especially in view of his outspokenness on many other issues. Despite his friendship with the great plant geneticist Nikolai Vavilov, who was arrested in 1940 and starved to death in jail in Saratov in 1943 (not in Siberia, as stated by Dronomraju), Haldane refrained from making public criticisms of the repressive activities of the Soviet government. These activities became widely known in 1948, as a result of a session of the All-Union Academy of Agricultural Sciences, in which Lysenko made a lengthy speech denouncing ‘Weismannist–Mendelist–Morganist’ genetics, followed by wholesale dismissals of geneticists from their posts. This speech, and the ensuing lengthy report of the proceedings of the session, was translated into English. In contrast to Haldane, H.J. Muller, a former Marxist, published several denunciations of Lysenko’s activities, and resigned from the Soviet Academy of Sciences, as did Sir Henry Dale, a former President of the Royal Society. Haldane remained a member of the Academy until his death. As Dronamraju says (p.290), “the silence was deafening”. Although Haldane was clearly uncomfortable with Lysenko’s doings, and eventually resigned from his post at the Communist newspaper The Daily Worker, in his self-taped 1964 obituary for the BBC he made the bizarre statement “In my opinion, Lysenko is a very fine biologist and some of his ideas are right”. Although this book could have been put together much better, it does provide solid information about the life of one of the most important and interesting scientists of the past century. It makes it clear why, like everyone I have known who was acquainted with Haldane, Dronamraju is overwhelmed with admiration for his abilities, despite his often difficult behaviour. Haldane’s contributions to biology will be remembered long after his personal and political foibles are forgotten.