J. B. S. Haldane

2.1. Early life and education

John Burdon Sanderson Haldane was born on November 5, 1892, in Oxford, England. His father was John Scott Haldane, a distinguished Scottish physiologist, scientist, and philosopher, known for his work on respiration. His mother, Louisa Kathleen Trotter, was a Conservative of Scottish ancestry. His only sibling, Naomi Mitchison, became a notable Scottish writer. The Haldane family was aristocratic and secular, with a lineage that Haldane later claimed could be traced back to Robert the Bruce.

Haldane's childhood was steeped in scientific inquiry. He learned to read at the age of three, and at four, after injuring his forehead, he famously asked the physician if the bleeding was "oxyhaemoglobin or carboxyhaemoglobin?". From the age of eight, he assisted his father in their home laboratory, where he began his lifelong practice of self-experimentation. He and his father often served as their own test subjects, notably in investigations into the effects of poison gases. In 1901, at the age of eight, his father took him to the Oxford University Junior Scientific Club to hear a lecture on Mendelian genetics, which had recently been rediscovered. Though he found the lecture "interesting but difficult," it profoundly influenced him, setting the stage for his most significant scientific contributions in genetics.

His formal education began at Oxford Preparatory School (now Dragon School), where he earned a scholarship to Eton College in 1904. At Eton, he endured severe bullying from senior students, which he attributed to his perceived arrogance. This experience fostered a lasting disdain for the English education system, though he still managed to become captain of the school. In 1906, at 13, he volunteered for his first scientific research, assisting his father in studying decompression and "bends" in deep-sea divers aboard HMS Spanker. This research, published in The Journal of Hygiene in 1908, laid the groundwork for Haldane's decompression model.

Haldane pursued mathematics and classics at New College, Oxford, graduating with first-class honors in both mathematical Moderations (1912) and Greats (1914). Despite his intention to study physiology, his plans were interrupted by the outbreak of World War I. Notably, his only formal biology education was an incomplete course in vertebrate anatomy, yet he would go on to teach and conduct groundbreaking research in the field. His first technical paper, on hemoglobin function, was co-authored with his father and published in 1912.

2.2. World War I service

With the outbreak of World War I, Haldane volunteered for the British Army, commissioned as a temporary second lieutenant in the 3rd Battalion of the Black Watch in August 1914. He served as a trench mortar officer, a role he described as "enjoyable" due to the opportunity to "kill people," which he regarded as a "respectable relic of primitive man." He was promoted to temporary lieutenant in February 1915 and temporary captain in October 1915.

His service included combat in France, where he was wounded by artillery fire and sent back to Scotland to instruct recruits in grenade use. In 1916, he joined the war in Mesopotamia (modern-day Iraq), where he was severely wounded by an enemy bomb. He was then sent to a hospital in India, where he spent the remainder of the war, using his time to study Urdu and Indian culture. He returned to England in 1919, retaining his rank of captain. His commanders described him as "the bravest and dirtiest officer in my Army" and "mad" and "cracked" due to his ferocity and aggressive, often reckless, behavior in battles. His wartime experiences significantly shaped his worldview, contributing to his later embrace of socialism. He even managed to write scientific papers and poetry from the front lines, famously stating he was "the only officer to complete a scientific paper from a forward position of the Black Watch."

2.3. Academic career

Following his military service, Haldane returned to academia, despite his unconventional educational background in biology. From 1919 to 1922, he served as a Fellow at New College, Oxford, teaching and researching physiology and genetics. During his first year, he published six papers on respiration physiology and genetics.

In 1923, he moved to the University of Cambridge, where he accepted a newly created readership in biochemistry, teaching there until 1932. His work at Cambridge focused on enzymes and the mathematical aspects of genetics. While a visiting professor at the University of California, Berkeley in 1932, he was elected a Fellow of the Royal Society.

From 1927 to 1937, Haldane also worked part-time at the John Innes Horticultural Institution in Surrey, where he was officer in charge of Genetical Investigations. His contributions were credited with making John Innes "the liveliest place for research in genetics in Britain." He served as the Fullerian Professor of Physiology at the Royal Institution from 1930 to 1932. In 1933, he became Professor of Genetics at University College London, where he spent the majority of his academic career. In 1936, he became the first Weldon Professor of biometry at University College London. During World War II, he moved his team to the Rothamsted Experimental Station in Hertfordshire from 1941 to 1944 to avoid bombings. He also became editor of the Journal of Genetics in 1933, a position he held until his death.

2.4. Life in India

In 1956, Haldane left University College London and moved to India, joining the Indian Statistical Institute (ISI) in Calcutta (now Kolkata) in the biometry unit. He cited multiple reasons for this significant life change. Officially, he protested the Suez Crisis, stating that he considered the British government's actions to be "violations of international law." He also believed that India's warm climate would benefit his health and that the country aligned with his socialist ideals. In his 1958 article "A passage to India," he elaborated that he preferred Indian food and saw better opportunities for scientific research that did not require expensive equipment like electron microscopes or cyclotrons, preferring facilities akin to those used by Charles Darwin or William Bateson, such as gardens and pigeon lofts, which were more accessible in India.

His decision was also influenced by personal circumstances; his wife, Helen Spurway, had been dismissed from the university for being "drunk and disorderly," leading to Haldane's resignation. Upon moving to India, he declared, "Sixty years in socks is enough," and adopted Indian attire, never again wearing socks.

Haldane was deeply interested in inexpensive research methods and actively engaged with Indian biology. He observed local bird species like the yellow-wattled lapwing, advocated for cowpea as a model for plant genetics, and studied the pollination of Lantana camara. He lamented that Indian universities often forced biology students to drop mathematics, a subject he considered crucial. He also took an interest in floral symmetry.

In January 1961, a controversial incident occurred when he invited Canadian science fair winners, Gary Botting and Susan Brown, to a banquet. When they declined due to a prior engagement, Haldane, misunderstanding the situation, went on a much-publicized hunger strike to protest what he perceived as a "U.S. insult." This led to a confrontation with ISI director P. C. Mahalanobis, and Haldane resigned from the ISI in February 1961. He then moved to a newly established biometry unit in Bhubaneswar, the capital of Odisha (then Orissa), where he continued his work.

Haldane became an Indian citizen in 1961, embracing Hinduism and becoming a vegetarian. He saw India as "the closest approximation to the Free World," appreciating its diversity and the freedom to criticize the government, even if responses were slow. He famously stated, "I also happen to be proud of being a citizen of India, which is a lot more diverse than Europe, let alone the U.S.A, the U.S.S.R or China, and thus a better model for a possible world organisation."

2.5. Personal life

Haldane's personal life was as unconventional as his scientific and political careers. He was married twice. In 1924, he met Charlotte Franken, a journalist. Their relationship became a public scandal when Haldane was named as co-respondent in her divorce suit. To facilitate her divorce, Haldane openly admitted to adultery, which led to his formal dismissal from Cambridge by the Sex Viri, a disciplinary committee, in 1925 for "gross immorality." However, prominent intellectuals like G. K. Chesterton and Bertrand Russell defended Haldane, arguing against university interference in a professor's private life, and his ouster was revoked in 1926. He married Charlotte Franken that same year. They separated in 1942 and divorced in 1945. Later that year, he married Helen Spurway, his former PhD student. He also had an affair with Dorle Soria, founder of Angel Records.

Haldane famously boasted, "I can read 11 languages and make public speeches in three; but am unmusical. I am a fairly competent public speaker." He had no children of his own, but he and his father significantly influenced his sister Naomi's children, three of whom became biology professors.

Inspired by his father, Haldane frequently engaged in self-experimentation, often exposing himself to considerable danger to gather data. He drank dilute hydrochloric acid to study blood acidification, enclosed himself in an airtight room with 7% carbon dioxide (which caused a "violent headache"), and suffered crushed vertebrae from an experiment on elevated oxygen saturation. His decompression chamber experiments resulted in perforated eardrums for him and his volunteers, which he humorously noted allowed one to "blow tobacco smoke out of the ear in question, which is a social accomplishment."

His uninhibited behavior often made him unpopular among colleagues. At Cambridge, his eccentricities, such as bringing a gallon jar of urine from his laboratory to dinner, annoyed senior faculty and even derailed a potential fellowship offer from Trinity College, Cambridge.

2.6. Later life and death

In the autumn of 1963, while attending scientific conferences in the United States, Haldane began experiencing abdominal pains. He returned to London for a diagnosis and was found to have colorectal cancer, undergoing surgery in February 1964. During his hospital stay, he was approached for a BBC documentary on eminent scientists. Instead of a filmed interview, Haldane provided a self-obituary, famously beginning, "I believe that I am one of the most influential people living today, although I haven't got a scrap of power." He also penned a comic poem, "Cancer's a Funny Thing," mocking his incurable disease, which reflected his consistent irreverence. The poem was published in the New Statesman in February 1964.

Despite the initial success of his surgery in London, his symptoms reappeared after he returned to India in June 1964. Indian doctors confirmed his condition was terminal in August. He wrote to John Maynard Smith on September 7, stating, "I am not appreciably upset by the prospect of dying fairly soon. But I am very angry [at the English doctor who performed the operation]."

Haldane died on December 1, 1964, in Bhubaneswar, India. On the day of his death, the BBC broadcast his self-obituary. In accordance with his will, his body was donated for medical research and instruction at the Rangaraya Medical College in Kakinada. He explicitly stated in his will: My body has been used for both purposes during my lifetime and after my death, whether I continue to exist or not, I shall have no further use for it, and desire that it shall be used by others. Its refrigeration, if this is possible, should be a first charge on my estate.
His post-mortem was performed by Vissa Ramachandra Rao, and his skeleton and organs are now on public display in the Haldane Museum, located in the pathology department of Rangaraya Medical College.

3.1. Population genetics and evolutionary theory

Haldane was one of the three principal architects of the mathematical theory of population genetics, alongside Ronald Fisher and Sewall Wright. His work was crucial to the modern evolutionary synthesis of the early 20th century, which reconciled Darwinian evolution with Mendelian inheritance. He mathematically demonstrated how natural selection could operate on Mendelian traits, thereby re-establishing it as the central mechanism of evolution.

Between 1924 and 1934, he published a seminal series of ten papers titled "A Mathematical Theory of Natural and Artificial Selection." In these papers, he derived expressions for the direction and rate of change of gene frequencies and analyzed the complex interactions between natural selection, mutation, and migration. These theoretical insights were summarized in his influential 1932 book, The Causes of Evolution.

One notable prediction from his 1924 paper concerned the rate of natural selection in peppered moth evolution. He theorized that in a sooty environment like Manchester, where industrial melanism was observed, the fertility of the dominant (melanic) moths would need to be 50% greater than that of the recessive (grey) forms for the observed change in frequency to occur. He predicted that the dominant form could go from 1% to 99% in just 48 generations, with a majority appearing in 13 generations. This mathematical prediction, initially considered improbable for natural selection, was later experimentally confirmed by Bernard Kettlewell in the 1950s and further validated by Michael Majerus in the 2000s.

3.2. Genetics and human biology

Haldane's pioneering work in human genetics included the development of the first methods using maximum likelihood for estimating human linkage maps. He also pioneered methods and provided the first estimates for human mutation rates, notably calculating a rate of 2 × 10^-5 mutations per gene per generation for the X-linked haemophilia gene in his 1932 book The Causes of Evolution.

He was instrumental in establishing human gene maps for haemophilia and colour blindness on the X chromosome. His collaboration with his sister, Naomi Mitchison, and Alexander Dalzell Sprunt led to the first demonstration of genetic linkage in mammals, published in 1915. This paper, "Reduplication in mice," was famously written from a front-line trench during World War I. He also demonstrated linkage in chickens in 1921 and, with Julia Bell, in humans in 1937.

At the John Innes Horticultural Institution, Haldane developed complex linkage theory for polyploids and expanded the understanding of gene-enzyme relationships through biochemical and genetic studies of plant pigments.

3.3. Biochemistry and physiology

Haldane's contributions extended to biochemistry and physiology, building on his father's legacy. His first publication, co-authored with his father, was on the mechanism of gaseous exchange by haemoglobin in The Journal of Physiology. He subsequently investigated the chemical properties of blood as a pH buffer and explored various aspects of kidney function and excretion mechanisms.

In 1925, collaborating with George Edward Briggs, Haldane derived a new interpretation of enzyme kinetics, now known as the Briggs-Haldane equation. This work refined the earlier Michaelis-Menten kinetics by basing the derivation on the quasi-steady state approximation, which assumes that the concentration of intermediate enzyme-substrate complexes remains constant. This provided a more general and accurate understanding of enzyme action, and most current models of enzyme kinetics use the Briggs-Haldane derivation.

3.4. Origin of life

Haldane made a significant contribution to the understanding of the origin of life with his "primordial soup theory," introduced in his 1929 article "The Origin of Life" in The Rationalist Annual. He described the primitive ocean as a "vast chemical laboratory" where inorganic compounds, under solar energy and an anoxic atmosphere containing carbon dioxide, ammonia, and water vapour, could have given rise to a variety of organic compounds, forming a "hot dilute soup." These molecules would then react to produce more complex compounds, eventually leading to cellular components. He hypothesized that an "oily film" might have enclosed self-replicating nucleic acids, forming the first cells.

Haldane also proposed that viruses could have been intermediate entities between the prebiotic soup and the first cells, suggesting that prebiotic life might have existed in a "virus stage for many millions of years." While initially dismissed as "wild speculation," his idea gained empirical support with the Miller-Urey experiment in 1953. This "Oparin-Haldane hypothesis" (named also for Alexander Oparin, who independently proposed a similar idea in Russian in 1924) has since become a cornerstone in the study of abiogenesis. Haldane himself acknowledged Oparin's priority upon learning of his earlier work.

3.5. Key biological concepts and theories

Haldane either coined or significantly advanced several fundamental biological concepts and terms:

• Haldane's principle: Outlined in his essay "On Being the Right Size", this principle states that an animal's size often dictates its necessary bodily equipment. For example, small insects can absorb oxygen by simple diffusion, while larger animals require complex oxygen pumping and distributing systems.
• Haldane's sieve: In 1927, Haldane proposed that newly arisen dominant mutations are much more likely to be fixed by selection than recessive ones because selection acts primarily on heterozygotes. This implies that adaptation from new mutations in large, outcrossing populations should predominantly occur through the fixation of non-recessive beneficial mutations.
• Haldane's rule: Proposed in 1922, this rule states that if, in the first generation of hybrids between different animal species, one sex is absent, rare, or sterile, that sex is the heterogametic sex (the one with different sex chromosomes, e.g., XY in humans).
• Haldane's dilemma: Articulated in 1957, this concept describes a limit on the speed of beneficial evolution, suggesting a "cost of natural selection" in terms of the number of selective deaths required for a new allele to spread through a population. This idea remains a subject of debate in evolutionary biology.
• Haldane-Muller principle: In 1937, with Hermann Joseph Muller, Haldane showed that in genetically stable populations, the reduction in population fitness due to mutation is equal to the total mutation rate per individual, regardless of the harmfulness of individual genes.
• He also coined the term "darwin" as a unit of evolutionary change.

3.6. Malaria and sickle-cell anemia

Haldane was the first to recognize the evolutionary link between human genetic disorders and infectious diseases. While studying human mutation rates, he observed that mutations affecting red blood cells, such as thalassemias, were prevalent in tropical regions where malaria was endemic. He hypothesized that these genetic traits, specifically the sickle cell trait in its heterozygous form, conferred a selective advantage by protecting individuals from malarial infection.

He introduced this hypothesis at the Eighth International Congress of Genetics in Stockholm in 1948. In a technical paper published in 1949, he made a prophetic statement: "The corpuscles of the anaemic heterozygotes are smaller than normal, and more resistant to hypotonic solutions. It is at least conceivable that they are also more resistant to attacks by the sporozoa which cause malaria." This became known as "Haldane's malaria hypothesis." His prediction was later confirmed by Anthony C. Allison in 1954, specifically for the case of sickle-cell anemia, demonstrating how a seemingly deleterious genetic condition could be maintained in a population due to its protective effect against a deadly disease.

3.7. Technological and scientific foresight

Haldane possessed remarkable foresight regarding future scientific and technological developments. He is credited with coining the terms "clone" and "cloning" in his 1963 speech "Biological Possibilities for the Human Species of the Next Ten Thousand Years" at the Ciba Foundation Symposium on Man and his Future. He envisioned the possibility of producing a clone from a single fertilized egg, similar to the concept in Aldous Huxley's Brave New World. While he discussed the potential for cloning "superior individuals" and those who "excelled in a socially acceptable accomplishment," he also cautioned against cloning "the wrong people" like Adolf Hitler, reflecting a complex and at times controversial view on eugenics.

His 1924 essay Daedalus; or, Science and the Future posited the concept of in vitro fertilisation, which he termed "ectogenesis" (artificial development outside the body). He saw ectogenesis as a tool for creating "better individuals." This work significantly influenced Aldous Huxley's Brave New World and showcased Haldane's early engagement with transhumanist ideas.

Beyond biology, Haldane also proposed the concept of a hydrogen economy. In a 1923 talk in Cambridge titled "Science and the Future," he foresaw the exhaustion of coal as a power source in Britain and suggested a network of hydrogen-generating windmills, marking the first proposal for a hydrogen-based renewable energy economy. He also suggested concepts such as cis-acting and trans-acting regulation, coupling reaction, and molecular repulsion.

4.1. Socialism and Marxism

Haldane became a committed socialist during World War I, a transformation influenced by his experiences in the trenches. He later became an open supporter of the Communist Party of Great Britain, joining in 1942. A pragmatic dialectical-materialist Marxist, he frequently contributed articles to the Daily Worker. His writings often explored the social implications of science and advocated for social justice and economic reform. In his essay "On Being the Right Size", he humorously applied biological principles to political systems, suggesting that while nationalization might be feasible in large states, a completely socialized British Empire or United States was as improbable as an elephant performing somersaults.

In 1938, he enthusiastically proclaimed, "I think that Marxism is true." He remained a staunch communist through World War II, even considering standing for Parliament as a Communist Party candidate. However, his views on the Soviet Union would evolve significantly.

4.2. Criticism of Soviet Union and Lysenkoism

Haldane's relationship with the Soviet Union and its scientific policies, particularly Lysenkoism, was complex and evolved over time. Initially, he showed some understanding of the Soviet geneticists' debates, writing in 1941 that the controversy between academic scientists like Nikolai Vavilov and those seeking practical results like Trofim Lysenko was conducted "not with venom, but in a friendly spirit." He expressed hope for a "synthesis of these two contrasted points of view" within Soviet genetics.

However, by the end of World War II, Haldane became an explicit critic of the Soviet regime, particularly as the political suppression of genetics and the persecution of geneticists under Lysenkoism became undeniable. He found Lysenkoism's anti-Darwinian stance and the political interference in science incompatible with his commitment to scientific integrity and human rights. He left the Communist Party in 1950. Despite his eventual disillusionment with the Soviet system, he maintained a nuanced view of figures like Joseph Stalin, describing him in 1962 as "a very great man who did a very good job."

Haldane was also controversially accused by authors like Peter Wright and Chapman Pincher of having been a Soviet GRU spy codenamed "Intelligentsia."

4.3. Views on science and society

Haldane held strong views on the relationship between science, society, and culture. He was a vocal advocate for scientific popularization and rationalism, believing that scientific understanding was crucial for societal progress. Arthur C. Clarke credited him as "perhaps the most brilliant science populariser of his generation."

His ideas on eugenics were complex and, from a modern perspective, controversial. While he envisioned technologies like ectogenesis and human cloning as tools for creating "better individuals" or those with "socially acceptable accomplishment," this perspective aligns with historical eugenic thought that has been widely criticized for its potential to infringe upon individual rights and promote discriminatory practices. His advocacy for these technologies, even with his caveats, highlights the need for critical analysis of the social implications of scientific advancements.

Haldane was also a sharp critic of established institutions and figures he perceived as anti-scientific or irrational. He engaged in a notable intellectual dispute with C. S. Lewis, accusing Lewis and his Ransom Trilogy of a "complete mischaracterisation of science, and his disparagement of the human race." Haldane even wrote an essay titled "More Anti-Lewisite," a pun on the poison gas and its antidote, to critique Lewis's arguments for the existence of God. He also authored a children's book, My Friend Mr. Leakey (1937), which featured fantastical elements and later editions were illustrated by Quentin Blake.

5.1. Scientific legacy and impact

Haldane's scientific legacy is profound, particularly in the fields of genetics and evolutionary biology. His mathematical framework for population genetics, developed alongside Fisher and Wright, laid the theoretical foundation for the modern evolutionary synthesis, which remains the cornerstone of evolutionary biology. His work demonstrated how Mendelian genetics could explain Darwinian natural selection, providing a quantitative basis for evolutionary change.

His contributions to human genetics, including gene mapping for conditions like hemophilia and color blindness, and his pioneering estimates of human mutation rates, were foundational for the field. The Oparin-Haldane hypothesis on the origin of life remains a central concept in abiogenesis research. His insight into the evolutionary link between genetic disorders and infectious diseases, particularly his hypothesis on sickle-cell anemia and malaria resistance, was a major breakthrough in understanding human adaptation.

Beyond these specific discoveries, Haldane's interdisciplinary approach, his willingness to challenge conventional wisdom, and his emphasis on the mathematical rigor of biological phenomena influenced generations of scientists. Prominent figures like Peter Medawar called him "the cleverest man I ever knew," and James Watson described him as "England's most clever and eccentric biologist." According to a Cambridge student, "he seemed to be the last man who might know all there was to be known," underscoring his polymathic intellect.

5.2. Awards and honours

Haldane received numerous accolades throughout his career in recognition of his significant scientific achievements:

• He was elected a Fellow of the Royal Society in 1932.
• The French Government conferred upon him the National Order of the Legion of Honour in 1937.
• He received the Weldon Memorial Prize in 1938.
• He was awarded the Croonian Medal by the Royal Society in 1946.
• In 1952, he received the prestigious Darwin Medal from the Royal Society.
• He was awarded the Huxley Memorial Medal of the Anthropological Institute of Great Britain in 1956.
• The Linnean Society of London honored him with the Darwin-Wallace Medal in 1958.
• He received the Feltrinelli Prize from the Accademia Nazionale dei Lincei in 1961.
• He also received an Honorary Doctorate of Science, an Honorary Fellowship at New College, Oxford, and the Kimber Award of the National Academy of Sciences in the United States.

5.3. Criticism and controversy

Haldane's life was not without its share of criticism and controversy. His unconventional personal life, particularly the scandal surrounding his first divorce and his public admission of adultery, led to his temporary dismissal from Cambridge, though this decision was later reversed due to widespread academic protest. His eccentric behaviors, such as bringing a jar of urine to a formal dinner, also made him unpopular among some colleagues.

His strong political affiliations, particularly his support for the Communist Party, drew significant scrutiny, especially during the Cold War era. While he eventually criticized the Soviet regime and Lysenkoism, his initial defense of Soviet genetics and his continued admiration for figures like Joseph Stalin even after leaving the party, remained contentious. Furthermore, accusations of his having been a Soviet spy, codenamed "Intelligentsia," have been made by authors like Peter Wright and Chapman Pincher, though these claims remain debated.

His views on eugenics, particularly his discussions of using technologies like cloning and ectogenesis to create "better individuals," are also a source of modern criticism. While he approached these topics from a scientific perspective of human improvement, such ideas are now often viewed with caution due to their historical association with discriminatory practices and potential infringements on human rights.

5.4. Cultural impact and popularization

Haldane was a gifted communicator who excelled at popularizing science for a broad audience. His essays, collected in volumes such as Possible Worlds and Other Essays (1927) and Science and Everyday Life (1940), made complex scientific concepts accessible and engaging. His 1924 essay Daedalus; or, Science and the Future was particularly influential, predicting future scientific advancements and inspiring works like Aldous Huxley's dystopian novel Brave New World, which incorporated Haldane's ideas on artificial reproduction. Haldane and Huxley were close friends from childhood.

His wit and distinctive personality also contributed to his cultural impact. He was parodied by Aldous Huxley as the obsessive self-experimenter "Shearwater" in his novel Antic Hay (1923). Haldane's memorable quotes, often blending scientific insight with humor and philosophical depth, continue to be widely cited.

His legacy is also honored through academic institutions. The Haldane Lecture at the John Innes Centre, where he worked, and the JBS Haldane Lecture of The Genetics Society are named in his honor, recognizing his enduring influence on genetics and biology.