J. B. S. Haldane

John Burdon Sanderson Haldane (; 5 November 18921 December 1964), nicknamed "Jack" or "JBS", was a British scientist known for his works in physiology, genetics, evolutionary biology, and mathematics. With innovative use of statistics in biology, he was one of the founders of neo-Darwinism. 
Haldane's article on abiogenesis in 1929 introduced the "primordial soup theory", which became the foundation for the concept of the chemical origin of life. He established human gene maps for haemophilia and colour blindness on the X chromosome, and codified Haldane's rule on sterility in the heterogametic sex of hybrids in species. He correctly proposed that sickle-cell disease confers some immunity to malaria. He was the first to suggest the central idea of "in vitro" fertilisation, as well as concepts such as hydrogen economy, cis and trans-acting regulation, coupling reaction, molecular repulsion, the darwin (as a unit of evolution) and organismal cloning. In 1957 he articulated Haldane's dilemma, a limit on the speed of beneficial evolution which subsequently proved incorrect. He willed his body for medical studies, as he wanted to remain useful even in death. He is also remembered for coining the words "clone" and "cloning" in human biology, and "ectogenesis". With his sister, Naomi Mitchison, Haldane was the first to demonstrate genetic linkage in mammals. Subsequent works established a unification of Mendelian genetics and Darwinian evolution by natural selection whilst laying the groundwork for modern evolutionary synthesis and thus helped to create population genetics.
Haldane was a professed socialist, Marxist, atheist and humanist whose political dissent led him to leave England in 1956 and live in India, becoming a naturalised Indian citizen in 1961. 
Arthur C. Clarke credited him as "perhaps the most brilliant science populariser of his generation". Nobel laureate Peter Medawar called Haldane "the cleverest man I ever knew". According to Theodosius Dobzhansky, "Haldane was always recognized as a singular case"; and to Michael J. D. White, "the most erudite biologist of his generation, and perhaps of the century."
Biography.
Early life and education.
Haldane was born in Oxford to John Scott Haldane, a physiologist, scientist, a philosopher and a Liberal, and Louisa Kathleen Trotter, a Conservative and descended from Scottish ancestry. During the First World War, he served with the Black Watch in France and Iraq. His younger sister, Naomi Mitchison, became a writer, and his uncle was Viscount Haldane and his aunt the author Elizabeth Haldane. Descended from an aristocratic and secular family of the Clan Haldane, he would later claim that his Y chromosome could be traced back to Robert the Bruce.
He grew up at 11 Crick Road, North Oxford. He learnt to read at the age of three, and at four, after injuring his forehead he asked the doctor, "Is this oxyhaemoglobin or carboxyhaemoglobin?". From age eight he worked with his father in their home laboratory where he experienced his first self-experimentation, the method he would later be famous for. He and his father became their own "human guinea pigs", such as in their investigation on the effects of poison gases. In 1899 his family moved to "Cherwell", a late Victorian house at the outskirts of Oxford with its own private laboratory.
His formal education began in 1897 at Oxford Preparatory School (now Dragon School), where he gained a First Scholarship in 1904 to Eton. In 1905 he joined Eton, where he experienced severe abuse from senior students for allegedly being arrogant. The indifference of authority left him with a lasting hatred for the English education system. However, the ordeal did not stop him from becoming Captain of the school. He studied mathematics and classics at New College at the University of Oxford and obtained first-class honours in mathematical moderations in 1912 and first-class honours in Greats in 1914. He became engrossed in genetics and presented a paper on gene linkage in vertebrates in the summer of 1912. His first technical paper, a 30-page long article on haemoglobin function, was published that same year, as a co-author alongside his father.
Career.
His education was interrupted by the First World War during which he fought in the British Army, being commissioned a temporary second lieutenant in the 3rd Battalion of the Black Watch (Royal Highland Regiment) on 15 August 1914. He was promoted to temporary lieutenant on 18 February 1915 and to temporary captain on 18 October. He served in France and Iraq, where he was wounded. He relinquished his commission on 1 April 1920, retaining his rank of captain. For his ferocity and aggressiveness in battles, his commander called him the "bravest and dirtiest officer in my Army."
Between 1919 and 1922 he was a Fellow of New College, Oxford, where he researched physiology and genetics. He then moved to the University of Cambridge, where he accepted a readership in Biochemistry and taught until 1932. From 1927 until 1937 he was also Head of Genetical Research at the John Innes Horticultural Institution. During his nine years at Cambridge, Haldane worked on enzymes and genetics, particularly the mathematical side of genetics. He was the Fullerian Professor of Physiology at the Royal Institution from 1930 to 1932 and in 1933 he became full Professor of Genetics at University College London, where he spent most of his academic career. Four years later he became the first Weldon Professor of Biometry at University College London.
In 1924, Haldane met Charlotte Franken. So that they could marry, Charlotte divorced her husband, Jack Burghes, causing some controversy. Haldane was almost dismissed from Cambridge for the way he handled his meeting with her. They married in 1926. Following their separation in 1942, the Haldanes divorced in 1945. Later that year he married Helen Spurway.
Haldane, inspired by his father, would expose himself to danger to obtain data. To test the effects of acidification of the blood he drank dilute hydrochloric acid, enclosed himself in an airtight room containing 7% carbon dioxide, and found that it 'gives one a rather violent headache'. One experiment to study elevated levels of oxygen saturation triggered a fit which resulted in him suffering crushed vertebrae. In his decompression chamber experiments, he and his volunteers suffered perforated eardrums. But, as Haldane stated in "What is Life," "the drum generally heals up; and if a hole remains in it, although one is somewhat deaf, one can blow tobacco smoke out of the ear in question, which is a social accomplishment."
In India.
In 1956, Haldane left University College London, and joined the Indian Statistical Institute (ISI) in Kolkata, India, where he headed the biometry unit. Officially he stated that he left the UK because of the Suez Crisis, writing: "Finally, I am going to India because I consider that recent acts of the British Government have been violations of international law." He believed that the warm climate would do him good, and that India shared his socialist dreams. The university had sacked his wife Helen for being drunk and disorderly and refusing to pay a fine, triggering Haldane's resignation. He declared he would no longer wear socks, "Sixty years in socks is enough." and always dressed in Indian attire.
He was keenly interested in inexpensive research. He wrote to Julian Huxley about his observations on "Vanellus malabaricus", the yellow-wattled lapwing. He advocated the use of "Vigna sinensis" (cowpea) as a model for studying plant genetics. He took an interest in the pollination of "Lantana camara". He lamented that Indian universities forced those who took up biology to drop mathematics. Haldane took an interest in the study of floral symmetry. In January 1961 he befriended Gary Botting, 1960 U.S. Science Fair winner in zoology (who had first visited the Haldanes along with Susan Brown, 1960 U.S. National Science Fair winner in botany), inviting him to share the results of his experiments hybridising "Antheraea" silk moths. J.B.S., his wife Helen Spurway, and Krishna Dronamraju were present at the Oberoi Grand Hotel in Kolkata when Brown reminded the Haldanes that she and Botting had a previously scheduled event that would prevent them from accepting an invitation to a banquet proposed by J.B.S. and Helen in their honour and had regretfully declined the honour. After the two students had left the hotel, Haldane went on his much-publicized hunger strike to protest what he regarded as a "U.S. insult." When the director of the ISI, P. C. Mahalanobis, confronted Haldane about both the hunger strike and the unbudgeted banquet, Haldane resigned from his post (in February 1961), and moved to a newly established biometry unit in Odisha.
Haldane took Indian citizenship; he was interested in Hinduism and became a vegetarian. In 1961, Haldane described India as "the closest approximation to the Free World." Jerzy Neyman objected that "India has its fair share of scoundrels and a tremendous amount of poor unthinking and disgustingly subservient individuals who are not attractive." Haldane retorted:
When on 25 June 1962 he was described in print as a "Citizen of the World" by Groff Conklin, Haldane responded:
Personal life.
Haldane wed twice, to Charlotte Franken in 1926 and Helen Spurway in 1945.
Death.
Shortly before his death from cancer, Haldane wrote a comic poem while in the hospital, mocking his own incurable disease. It was read by his friends, who appreciated the consistent irreverence with which Haldane had lived his life. He died in Bhubaneshwar, India on 1 December 1964. The poem first appeared in print on 21 February 1964 issue of the "New Statesman", and runs:
The poem ends:
Haldane died on 1 December 1964 in Bhubaneswar. He willed that his body be used for medical research and teaching at the Rangaraya Medical College, Kakinada.
Scientific contributions.
Following his father's footsteps, Haldane's first publication was on the mechanism of gaseous exchange by haemoglobin, and he subsequently worked on the chemical properties of blood as a pH buffer. He investigated several aspects of kidney functions and mechanism of excretion.
Genetic linkage.
With his sister Naomi Mitchison, Haldane started investigating Mendelian genetics in 1908, used guinea pigs and mice, publishing "Reduplication in mice" in 1915 the first demonstration of genetic linkage in mammals, showing that certain genetic traits tend to be inherited together (as was later discovered, because of their proximity on chromosomes). As the paper was written during Haldane's service in the First World War, James F. Crow called it "the most important science article ever written in a front-line trench". He was the first to demonstrate linkage in chickens in 1921, and (with Julia Bell) in humans in 1937.
Enzyme kinetics.
In 1925, with G.E. Briggs, Haldane derived a new interpretation of the enzyme kinetic law of Victor Henri in 1903, better known as the 1913 Michaelis–Menten equation. Leonor Michaelis and Maud Menten assumed that enzyme (catalyst) and substrate (reactant) are in fast equilibrium with their complex, which then dissociates to yield product and free enzyme. By contrast, at almost the same time, Donald Van Slyke and G. E. Cullen treated the binding step as an irreversible reaction. The Briggs–Haldane equation was of the same algebraic form as both of the earlier equations, but their derivation is based on the quasi-steady state approximation, which is the concentration of intermediate complex (or complexes) does not change. As a result, the microscopic meaning of the "Michaelis Constant" ("Km") is different. Although commonly referring to it as Michaelis–Menten kinetics, most of the current models typically use the Briggs–Haldane derivation.
Haldane's principle.
In his essay "On Being the Right Size" he outlines Haldane's principle, which states that the size very often defines what bodily equipment an animal must have: "Insects, being so small, do not have oxygen-carrying bloodstreams. What little oxygen their cells require can be absorbed by simple diffusion of air through their bodies. But being larger means an animal must have complicated oxygen pumping and distributing systems to reach all the cells." The conceptual metaphor to animal allometry has been of use in energy economics and secession ideas.
Origin of life.
Haldane introduced the modern concept of abiogenesis in an eight-page article titled "The origin of life," in the "Rationalist Annual" in 1929, describing the primitive ocean as a "vast chemical laboratory" containing a mixture of inorganic compounds – like a "hot dilute soup" in which organic compounds could have formed. Under the solar energy the anoxic atmosphere containing carbon dioxide, ammonia and water vapour gave rise to a variety of organic compounds, "living or half-living things". The first molecules reacted with one another to produce more complex compounds, and ultimately the cellular components. At some point a kind of "oily film" was produced that enclosed self-replicating nucleic acids, thereby becoming the first cell. J. D. Bernal named the hypothesis "biopoiesis" or "biopoesis", the process of living matter spontaneously evolving from self-replicating but lifeless molecules. Haldane further hypothesised that viruses were the intermediate entities between the prebiotic soup and the first cells. He asserted that prebiotic life would have been "in the virus stage for many millions of years before a suitable assemblage of elementary units was brought together in the first cell." The idea was generally dismissed as "wild speculation". Alexander Oparin had suggested a similar idea in Russian in 1924 (published in English in 1936). The hypothesis gained some empirical support in 1953 with the classic Miller–Urey experiment. Since then, the primordial soup theory (Oparin–Haldane hypothesis) has become prevalent in the study of abiogenesis.
Malaria and sickle-cell anemia.
In 1949, Haldane proposed that genetic disorders in humans living in malaria-endemic regions provided a phenotype with immunity to blood-borne haemophiles. He noted that mutations expressed in red blood cells, such as sickle-cell anemia and various thalassemias, were prevalent only in tropical regions where malaria has been endemic. He further observed that these were favourable traits for natural selection which protected individuals from receiving malarial infection. This idea was eventually confirmed by Anthony C. Allison in 1954.
Population genetics.
He was one of the three major figures to develop the mathematical theory of population genetics, along with Ronald Fisher and Sewall Wright. He thus played an important role in the modern evolutionary synthesis of the early 20th century. He re-established natural selection as the central mechanism of evolution by explaining it as a mathematical consequence of Mendelian inheritance. He wrote a series of ten papers, A Mathematical Theory of Natural and Artificial Selection, deriving expressions for the direction and rate of change of gene frequencies, and also analyzing the interaction of natural selection with mutation and migration. Haldane's book, "The Causes of Evolution" (1932), summarised these results, especially in its extensive appendix.
His contributions to statistical human genetics included: the first methods using maximum likelihood for the estimation of human linkage maps; pioneering methods for estimating human mutation rates; the first estimates of mutation rate in humans (2 × 10−5 mutations per gene per generation for the X-linked haemophilia gene); and the first notion that there is a "cost of natural selection". At the John Innes Horticultural Institution, he developed the complicated linkage theory for polyploids; and extended the idea of gene/enzyme relationships with the biochemical and genetic study of plant pigments.
Political views.
Haldane became a socialist during the First World War; supported the Second Spanish Republic during the Spanish Civil War; and then became an open supporter of the Communist Party in 1937. A pragmatic dialectical-materialist Marxist, he wrote many articles for the "Daily Worker". In "On Being the Right Size", he wrote: "while nationalization of certain industries is an obvious possibility in the largest of states, I find it no easier to picture a completely socialized British Empire or United States than an elephant turning somersaults or a hippopotamus jumping a hedge."
Haldane has been accused by authors including Peter Wright and Chapman Pincher of having been a Soviet GRU spy codenamed "Intelligentsia".
In 1938, he proclaimed enthusiastically that "I think that Marxism is true." He joined the Communist Party of Great Britain in 1942. He was pressed to speak out about the rise of Lysenkoism and the persecution of geneticists in the Soviet Union as anti-Darwinist and the political suppression of genetics as incompatible with dialectical materialism. He shifted his polemic focus to the United Kingdom, criticizing the dependence of scientific research on financial patronage. In 1941 he wrote about the Soviet trial of his friend and fellow geneticist Nikolai Vavilov:
By the end of the Second World War Haldane had become an explicit critic of the regime. He left the party in 1950, shortly after considering standing for Parliament as a Communist Party candidate. He continued to admire Joseph Stalin, describing him in 1962 as "a very great man who did a very good job".
Social and scientific views.
Human cloning.
Haldane was the first to have thought of the genetic basis for human cloning, and the eventual artificial breeding of superior individuals. For this he introduced the terms "clone" and "cloning", modifying the earlier "clon" which had been used in agriculture since the early 20th century (from Greek "klōn", twig). He introduced the term in his speech on "Biological Possibilities for the Human Species of the Next Ten Thousand Years" at the "Ciba Foundation Symposium on Man and his Future" in 1963. He said:
Ectogenesis and "in vitro" fertilisation.
His essay "Daedalus; or, Science and the Future" (1924) introduced the term ectogenesis for the concept of what is later known as "in vitro" fertilisation (test tube babies). He envisioned ectogenesis as a tool for creating better individuals (eugenics). Haldane's work was an influence on Huxley's "Brave New World" (1932) and was also admired by Gerald Heard. Various essays on science were collected and published in a volume titled "Possible Worlds" in 1927. His book, "A.R.P. (Air Raid Precautions)" (1938) combined his physiological research into the effects of stress upon the human body with his experience of air raids during the Spanish Civil War to provide a scientific account of the likely effects of the air raids that Britain was to endure during the Second World War.
Criticism of C.S. Lewis.
Along with Olaf Stapledon, Charles Kay Ogden, I. A. Richards, and H. G. Wells, Haldane was accused by C. S. Lewis of scientism. Haldane criticised Lewis and his Ransom Trilogy for the "complete mischaracterisation of science, and his disparagement of the human race". Haldane wrote a book for children titled "My Friend Mr Leakey" (1937), containing the stories "A Meal With a Magician", "A Day in the Life of a Magician", "Mr Leakey's Party", "Rats", "The Snake with the Golden Teeth", and "My Magic Collar Stud"; later editions featured illustrations by Quentin Blake. 
Hydrogen-generating windmills.
In 1923, in a talk given in Cambridge titled "Science and the Future", Haldane, foreseeing the exhaustion of coal for power generation in Britain, proposed a network of hydrogen-generating windmills. This is the first proposal of the hydrogen-based renewable energy economy.
Scientists.
In his "An Autobiography in Brief", published shortly before his death in India, Haldane named four close associates as showing promise to become illustrious scientists: T. A. Davis, Dronamraju Krishna Rao, Suresh Jayakar and S. K. Roy.
Awards and honours.
Haldane was elected a Fellow of the Royal Society in 1932. The French Government conferred him its National Order of the Legion of Honour in 1937. In 1952, he received the Darwin Medal from the Royal Society. In 1956, he was awarded the Huxley Memorial Medal of the Anthropological Institute of Great Britain. He received the Feltrinelli Prize from Accademia Nazionale dei Lincei in 1961. He also received an Honorary Doctorate of Science, an Honorary Fellowship at New College, and the Kimber Award of the US National Academy of Sciences. He was awarded the Linnean Society of London's prestigious Darwin–Wallace Medal in 1958.
Legacy.
The Haldane Lecture at the John Innes Centre, where Haldane worked from 1927 to 1937 is named in his honour. The JBS Haldane Lecture of The Genetics Society is also named in his honour.
Haldane was parodied as "the biologist too absorbed in his experiments to notice his friends bedding his wife" by his friend Aldous Huxley in the novel "Antic Hay" (1923). 