Editing J. B. S. Haldane (section)

== Scientific contributions ==

Following his father's footsteps, Haldane's first publication was on the mechanism of [[gaseous exchange]] by haemoglobin in ''[[The Journal of Physiology]]'',<ref name=haldane1912 /> and he subsequently worked on the chemical properties of blood as a pH buffer.<ref>{{cite journal |last = Davies |first = HW |author2 = Haldane, JB |author3 = Kennaway, EL |title = Experiments on the regulation of the blood's alkalinity: I |journal = The Journal of Physiology |year = 1920 |volume = 54 |issue = 1–2 |pages = 32–45 |pmid = 16993473 |pmc = 1405746 |doi = 10.1113/jphysiol.1920.sp001906 }}</ref><ref>{{cite journal |last = Haldane |first = JB |title = Experiments on the regulation of the blood's alkalinity: II |journal = The Journal of Physiology |year = 1921 |volume = 55 |issue = 3–4 |pages = 265–75 |pmid = 16993510 |pmc = 1405425 |doi = 10.1113/jphysiol.1921.sp001969 }}</ref> He investigated several aspects of [[kidney function]]s and mechanism of excretion.<ref>{{cite journal |last = Baird |first = MM |author2 = Haldane, JB |title = Salt and water elimination in man |journal = The Journal of Physiology |year = 1922 |volume = 56 |issue = 3–4 |pages = 259–62 |pmid = 16993567 |pmc = 1405382 |doi = 10.1113/jphysiol.1922.sp002007 }}</ref><ref>{{cite journal |last = Davies |first = HW |author2 = Haldane, JB |author3 = Peskett, GL |title = The excretion of chlorides and bicarbonates by the human kidney |journal = The Journal of Physiology |year = 1922 |volume = 56 |issue = 5 |pages = 269–74 |pmid = 16993528 |pmc = 1405381 |doi = 10.1113/jphysiol.1922.sp002009 }}</ref>

=== Genetic linkage ===

In 1904, [[Arthur Dukinfield Darbishire]] published a paper on an experiment attempting to test [[Mendelian inheritance]] between [[Japanese house mouse|Japanese waltzing]] and albino mice.<ref>{{Cite journal|last=Darbishire|first=A. D.|date=1904|title=On the Result of Crossing Japanese Waltzing with Albino Mice|url=https://www.jstor.org/stable/2331519|journal=Biometrika|volume=3|issue=1|pages=1–51|doi=10.2307/2331519|jstor=2331519}}</ref> When Haldane came across the paper, he noticed that Darbishire had overlooked the possibility of genetic linkage in the experiment. Having sought advice from [[Reginald Punnett]], a professor of biology at the University of Cambridge, he was ready to write a paper, but only after an independent experiment.<ref name=":3" /> With his sister [[Naomi Mitchison|Naomi]] and a friend one year his senior, Alexander Dalzell Sprunt, he started the experiment in 1908 using [[guinea pigs]] and [[mouse|mice]]. By 1912, the report was ready.<ref name=":8" /> The paper was entitled ''Reduplication in mice'' and published in the ''[[Journal of Genetics]]'' only in December 1915.<ref name="haldane1915">{{cite journal|last=Haldane|first=J. B. S.|author2=Sprunt, A. D.|author3=Haldane, N. M.|year=1915|title=Reduplication in mice (Preliminary Communication)|url=https://www.ias.ac.in/article/fulltext/jgen/005/02/0133-0135|journal=Journal of Genetics|volume=5|issue=2|pages=133–135|doi=10.1007/BF02985370|s2cid=22245638}}</ref> It became the first demonstration of [[genetic linkage]] in [[mammal]]s, showing that certain genetic traits tend to be inherited together (this was later discovered to be due to their proximity on chromosomes).<ref name="Dronamraju-Recollections" /> (Between 1912 and 1914, genetic linkage had been reported in the fruit fly ''[[Drosophila melanogaster|Drosophilla]]'',<ref>{{Cite journal|last1=Morgan|first1=T. H.|last2=Lynch|first2=Clara J.|date=1912|title=The Linkage of Two Factors in Drosophila That Are Not Sex-Linked|journal=Biological Bulletin|volume=23|issue=3|pages=174–182|doi=10.2307/1535915|jstor=1535915|doi-access=free}}</ref> [[Bombyx mori|silk moth]],<ref>{{Cite journal|last=Tanaka|first=Yoshimaro|date=30 April 1913|title=Gametic coupling and repulsion in silkworm, Bombyx Mori|url=https://eprints.lib.hokudai.ac.jp/dspace/handle/2115/12515|journal=The Journal of the College of Agriculture, Tohoku Imperial University, Sapporo, Japan|language=en|volume=5|issue=5|pages=115–148}}</ref> and plants.<ref>{{Cite journal|last=Bridges|first=Calvin B.|date=1914|title=The Chromosome Hypothesis of Linkage Applied to Cases in Sweet Peas and Primula|journal=The American Naturalist|language=en|volume=48|issue=573|pages=524–534|doi=10.1086/279428|doi-access=free|bibcode=1914ANat...48..524B }}</ref>)

As the paper was written during Haldane's service during World War I, [[James F. Crow]] called it "the most important science article ever written in a front-line trench".<ref name=":3">{{cite journal|last1=Crow|first1=JF|date=1992|title=Centennial: J. B. S. Haldane, 1892–1964|journal=Genetics|volume=130|issue=1|pages=1–6|doi=10.1093/genetics/130.1.1|pmc=1204784|pmid=1732155}}</ref> Haldane recalled that he was the "only officer to complete a scientific paper from a forward position of the Black Watch".<ref name=":4" /> As was Haldane, Sprunt had joined 4th Battalion [[Bedfordshire Regiment]] at the start of World War I, and was killed at the [[Battle of Neuve Chapelle]] on 17 March 1915.<ref>{{Cite web|title=A D Sprunt|url=https://www.iwm.org.uk/memorials/item/memorial/14590|access-date=8 August 2021|website=Imperial War Museums|language=en}}</ref> It was upon this news that Haldane submitted the paper for publication, in which he remarked: "Owing to the war it has been necessary to publish prematurely, as unfortunately one of us (A. D. S.) has already been killed in France."<ref name="haldane1915" /> He was also the first to demonstrate linkage in [[chicken]]s in 1921,<ref>{{cite journal|last=Haldane|first=JB|year=1921|title=Linkage in poultry|url=https://zenodo.org/record/1448275|journal=Science|volume=54|issue=1409|page=663|bibcode=1921Sci....54..663H|doi=10.1126/science.54.1409.663|pmid=17816160}}</ref> and (with [[Julia Bell]]) in humans in 1937.<ref>{{cite journal|last1=Bell|first1=J.|last2=Haldane|first2=J. B. S.|date=1937|title=The Linkage between the Genes for Colour-Blindness and Haemophilia in Man|journal=Proceedings of the Royal Society B: Biological Sciences|volume=123|issue=831|pages=119–150|bibcode=1937RSPSB.123..119B|doi=10.1098/rspb.1937.0046|doi-access=free}}</ref>

=== Enzyme kinetics ===

In 1925, with [[George Edward Briggs|G.{{nbsp}}E. Briggs]], Haldane derived a new interpretation of the [[enzyme]] kinetic law of Victor Henri in 1903, better known as the 1913 [[Michaelis–Menten kinetics|Michaelis–Menten equation]].<ref>U. Deichmann, S. Schuster, J.-P. Mazat, [[A. Cornish-Bowden]]: ''Commemorating the 1913 Michaelis–Menten paper "Die Kinetik der Invertinwirkung": three perspectives.'' In: ''FEBS Journal.'' 2013, {{doi|10.1111/febs.12598}}</ref> [[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<ref>{{Cite journal  
 | last1 = Van Slyke
 | first1 = DD
 | last2 = Cullen
 | first2 = GE
 | title = The mode of action of urease and of enzyme in general
 | journal = Journal of Biological Chemistry
 | volume = 19 
 | pages = 141–180
 | year = 1914| issue = 2
 | doi = 10.1016/S0021-9258(18)88300-4
 | doi-access = free
 }}</ref> 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" (''K<sub>m</sub>'') is different. Although commonly referring to it as Michaelis–Menten kinetics, most of the current models typically use the Briggs–Haldane derivation.<ref>{{cite journal |last = Briggs |first = GE |author2 = Haldane, JB |title = A Note on the Kinetics of Enzyme Action |journal = The Biochemical Journal |year = 1925 |volume = 19 |issue = 2 |pages = 338–9 |pmid = 16743508 |pmc = 1259181 |doi = 10.1042/bj0190338 }}</ref><ref>{{cite journal |last = Chen |first = W. W. |author2 = Niepel, M. |author3 = Sorger, P. K. |title = Classic and contemporary approaches to modeling biochemical reactions |journal = Genes & Development |year = 2010 |volume = 24 |issue = 17 |pages = 1861–1875 |doi = 10.1101/gad.1945410 |pmid = 20810646 |pmc = 2932968 }}</ref>

=== Haldane's principle<!--'Haldane's principle' redirects here--> ===

In his essay ''[[On Being the Right Size]]'' he outlines '''Haldane's principle'''<!--boldface per WP:R#PLA-->, 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."<ref>{{cite book|title=Dictionary of Scientific Principles|last=Marvin|first=Stephen|publisher=John Wiley & Sons|year=2012|isbn=978-1-118-58224-4|location=Chicester|page=140}}</ref>

{{anchor|Haldane's principle}}

=== Haldane's sieve ===

In 1927, Haldane pointed out that because selection mainly acts on heterozygotes, newly arisen dominant mutations are much more likely to be fixed, than are recessive ones,<ref>{{cite journal |last=Haldane |first=J. B. S. |year=1927 |title=A mathematical theory of natural and artificial selection, part V: selection and mutation |journal=Proceedings of the Cambridge Philosophical Society |volume=28 |issue=7 |pages=838–844 |doi= 10.1017/S0305004100015644|bibcode=1927PCPS...23..838H |s2cid=86716613 }}</ref> a mechanism now called ''[[Haldane's sieve]]''.<ref>{{cite journal |title=Adaptation and evolution in Heliconius: a defense of neoDarwinism |first=John R. G. |last=Turner |journal=Annual Review of Ecology and Systematics |volume=12 |pages=99–121 |date=1981 |issue=1 |doi=10.1146/annurev.es.12.110181.000531 |bibcode=1981AnRES..12...99T }}</ref><ref>{{cite journal |title=Mating system, Haldane's sieve, and the domestication process |first1=Joëlle |last1=Ronfort |first2=Sylvain |last2=Glemin |journal=Evolution |volume= 67 |issue=5 |pages=1518–1526 |date=2013 |doi= 10.1111/evo.12025|pmid=23617927 |s2cid=33466120 }}</ref> This leads to the expectation that adaptation from new mutations in large outcrossing populations should primarily proceed via fixing non-recessive beneficial mutations.

=== Origin of life ===
{{further|Prebiotic soup}}

In 1929, Haldane introduced the modern concept of [[abiogenesis]] in an eight-page article entitled "The Origin of Life" in ''The Rationalist Annual'',<ref name=lazcano>{{cite journal |last1 = Lazcano |first1 = A. |title = Historical development of origins research |journal = Cold Spring Harbor Perspectives in Biology |date = 2010 |volume = 2 |issue = 11 |pages = a002089 |doi = 10.1101/cshperspect.a002089 |pmid = 20534710 |pmc = 2964185 }}</ref> 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 event|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-replication|self-replicating]] nucleic acids, thereby becoming the first cell. [[John Desmond Bernal|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".<ref name=lazcano /> The idea was generally dismissed as "wild speculation".<ref>{{cite book |last = Fry |first = Iris |title = The Emergence of Life on Earth: A Historical and Scientific Overview |year = 2000 |publisher = Rutgers University Press |location = New Brunswick, N.J. |isbn=978-0-8135-2740-6 |pages = 65–66, 71–74 |url=https://books.google.com/books?id=6KoRvUeUUuEC }}</ref>

[[Alexander Oparin]] had suggested a similar idea in [[Russian language|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 the foundation in the study of abiogenesis.<ref>{{cite web |last = Gordon-Smith |first = Chris |title = The Oparin–Haldane Hypothesis |url=http://www.simsoup.info/Origin_Landmarks_Oparin_Haldane.html |access-date = 18 February 2014 |url-status = live |archive-url=https://web.archive.org/web/20140226225142/http://www.simsoup.info/Origin_Landmarks_Oparin_Haldane.html |archive-date = 26 February 2014 |df = dmy-all }}</ref><ref>{{cite web |title = The Oparin–Haldane Theory of the Origin of Life |url=http://www.chem.ox.ac.uk/vrchemistry/chapter26/page10.htm |publisher = Department of Chemistry, University of Oxford |access-date = 18 February 2014 |url-status = live |archive-url=https://web.archive.org/web/20150923202551/http://www.chem.ox.ac.uk/vrchemistry/chapter26/page10.htm |archive-date = 23 September 2015 |df = dmy-all }}</ref><ref>{{cite journal |last = Lazcano |first = A. |title = Historical development of origins research |journal = Cold Spring Harbor Perspectives in Biology |year = 2010 |volume = 2 |issue = 11 |pages = a002089 |doi = 10.1101/cshperspect.a002089 |pmid = 20534710 |pmc = 2964185 }}</ref>

Although Oparin's theory became widely known only after the English version in 1936, Haldane accepted Oparin's originality and said, "I have very little doubt that Professor Oparin has the priority over me."<ref>{{cite journal|last1=Miller|first1=Stanley L.|last2=Schopf|first2=J. William|last3=Lazcano|first3=Antonio|date=1997|title=Oparin's "Origin of Life": Sixty Years Later|journal=Journal of Molecular Evolution|volume=44|issue=4|pages=351–353|bibcode=1997JMolE..44..351M|doi=10.1007/PL00006153|pmid=9089073|s2cid=40090531}}</ref>

=== Malaria and sickle-cell anemia ===

Haldane was the first to realise the evolutionary link between genetic disorder and infection in humans. While estimating the rates of human mutation in different situations and diseases, he noted that mutations expressed in red blood cells, such as [[thalassemia]]s, were prevalent only in [[tropical regions]] where deadly infection such as malaria has been [[Endemic (epidemiology)|endemic]]. He further observed that these were favourable traits (heterozygous inheritance of [[sickle cell trait]]) for natural selection that protected individuals from receiving malarial infection.<ref>{{cite journal |last = Sabeti |first = Pardis C |author-link=Pardis Sabeti |title = Natural selection: uncovering mechanisms of evolutionary adaptation to infectious disease |journal = Nature Education |year = 2008 |volume = 1 |issue = 1 |page = 13 |url=http://www.nature.com/scitable/topicpage/natural-selection-uncovering-mechanisms-of-evolutionary-adaptation-34539 |url-status = live |archive-url=https://web.archive.org/web/20150109143615/http://www.nature.com/scitable/topicpage/Natural-Selection-Uncovering-Mechanisms-of-Evolutionary-Adaptation-34539 |archive-date = 9 January 2015 |df = dmy-all }}</ref> He introduced his hypothesis at the Eighth International Congress of Genetics held in 1948 at Stockholm on a topic "The Rate of Mutation of Human Genes".<ref>{{cite journal|vauthors=Bengtsson BO, Tunlid A|date=July 2010|title=The 1948 international congress of genetics in Sweden: people and politics|journal=Genetics|volume=185|issue=3|pages=709–15|doi=10.1534/genetics.110.119305|pmc=2907196|pmid=20660651}}</ref> He proposed that genetic disorders in humans living in [[malaria]]-endemic regions provided a condition ([[phenotype]]) that makes them relatively immune to malarial infections. He formalised the concept in a technical paper published in 1949 in which 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."<ref>{{cite journal|last1=Haldane|first1=J. B. S.|year=1949|title=The rate of mutation of human genes|journal=Hereditas|volume=35|issue=S1|pages=267–273|doi=10.1111/j.1601-5223.1949.tb03339.x|doi-access=free}}</ref> This became known as "Haldane's malaria hypothesis", or concisely, the "malaria hypothesis".<ref>{{cite journal|vauthors=Lederberg J|date=September 1999|title=J. B. S. Haldane (1949) on infectious disease and evolution|journal=Genetics|volume=153|issue=1|pages=1–3|doi=10.1093/genetics/153.1.1|pmc=1460735|pmid=10471694}}</ref> This hypothesis was eventually confirmed by [[Anthony C. Allison]] in 1954 in the case of [[sickle-cell anemia]].<ref>{{cite journal |last = Allison |first = AC |title = The distribution of the sickle-cell trait in East Africa and elsewhere, and its apparent relationship to the incidence of subtertian malaria |journal = Transactions of the Royal Society of Tropical Medicine and Hygiene |year = 1954 |volume = 48 |issue = 4 |pages = 312–8 |pmid = 13187561 |doi = 10.1016/0035-9203(54)90101-7 }}</ref><ref>{{cite journal |last = Hedrick |first = Philip W |title = Resistance to malaria in humans: the impact of strong, recent selection |journal = Malaria Journal |year = 2012 |volume = 11 |issue = 1 |page = 349 |doi = 10.1186/1475-2875-11-349 |pmid = 23088866 |pmc = 3502258 |doi-access = free }}</ref>

=== Population genetics ===
{{further|Modern synthesis (20th century)}}

Haldane 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 synthesis (20th century)|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]].<ref>{{cite journal|last=Haldane|first=JB|year=1990|title=A mathematical theory of natural and artificial selection—I. 1924|journal=Bulletin of Mathematical Biology|volume=52|issue=1–2|pages=209–40; discussion 201–7|doi=10.1007/BF02459574|pmid=2185859|s2cid=189884360}}</ref><ref>{{cite journal|last=Haldane|first=JB|year=1959|title=The theory of natural selection today|journal=Nature|volume=183|issue=4663|pages=710–3|bibcode=1959Natur.183..710H|doi=10.1038/183710a0|pmid=13644170|s2cid=4185793}}</ref> 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 (ecology)|migration]]. The series consists of ten papers published between 1924 and 1934 in journals such as ''[[Biological Reviews]]'' (part II), ''[[Mathematical Proceedings of the Cambridge Philosophical Society]]'' (parts I and from III to IX), and ''[[Genetics (journal)|Genetics]]'' (part X).<ref name=":10">{{Cite journal|last=Haldane|first=J. B. S.|date=1990|orig-year=1924|title=A mathematical theory of natural and artificial selection—I|url=https://www.blackwellpublishing.com/ridley/classictexts/haldane1.pdf|journal=Bulletin of Mathematical Biology|language=en|volume=52|issue=1–2|pages=209–240|doi=10.1007/BF02459574|pmid=2185859|s2cid=189884360}}</ref><ref>{{Cite journal|last=Haldane|first=J. B.|date=1934|title=A Mathematical Theory of Natural and Artificial Selection Part X. Some Theorems on Artificial Selection|journal=Genetics|volume=19|issue=5|pages=412–429|doi=10.1093/genetics/19.5.412|pmc=1208491|pmid=17246731}}</ref><ref>{{Cite journal|last=Bodmer|first=W. F.|date=2017|title=A Haldane perspective from a Fisher student|url=http://link.springer.com/10.1007/s12041-017-0825-4|journal=Journal of Genetics|language=en|volume=96|issue=5|pages=743–746|doi=10.1007/s12041-017-0825-4|pmid=29237882|s2cid=33409033}}</ref> He gave a set of lectures based on this series at the [[University of Wales]] in 1931, and they were summarised in his book, ''[[The Causes of Evolution]]'' in 1932.<ref name=":9">{{Citation|last=Sarkar|first=Sahotra|title=Haldane as Biochemist: The Cambridge Decade, 1923–1932|date=1992|url=http://link.springer.com/10.1007/978-94-011-2856-8_4|work=The Founders of Evolutionary Genetics|series=Boston Studies in the Philosophy of Science|volume=142|pages=53–81|editor-last=Sarkar|editor-first=Sahotra|place=Dordrecht|publisher=Springer Netherlands|doi=10.1007/978-94-011-2856-8_4|isbn=978-0-7923-3392-0|access-date=7 August 2021}}</ref>

His first paper on the series in 1924 specifically deals with the rate of natural selection in [[peppered moth evolution]]. He predicted that environmental conditions can favour the increase or decline of either the dominant (in this case the black or [[Melanism|melanic forms]]) or the recessive (the grey or [[wild type]]) moths. For a sooty environment such as Manchester, where the phenomenon was discovered in 1848, he predicted that the "fertility of the dominants must be 50% greater than that of the recessives".<ref name=cook50/> According to his estimate, assuming 1% dominant form in 1848 and about 99% in 1898, "48 generations are needed for the change [for the dominant to appear]... After only 13 generations the dominants would be in a majority."<ref name=":10" /> Such mathematical prediction was considered improbable for natural selection in nature,<ref name=":8" /> but it was subsequently proven by an elaborate experiment (named [[Kettlewell's experiment]]) that was performed by an Oxford zoologist [[Bernard Kettlewell]] between 1953 and 1958.<ref name="kett1955">{{cite journal|last1=Kettlewell|first1=H B D|year=1955|title=Selection experiments on industrial melanism in the Lepidoptera|journal=Heredity|volume=9|issue=3|pages=323–342|doi=10.1038/hdy.1955.36|doi-access=free|bibcode=1955Hered...9..323K }}</ref><ref name="kett56">{{cite journal|last1=Kettlewell|first1=Bernard|year=1956|title=Further selection experiments on industrial melanism in the Lepidoptera|journal=Heredity|volume=10|issue=3|pages=287–301|doi=10.1038/hdy.1956.28|doi-access=free|bibcode=1956Hered..10..287K |authorlink=Bernard Kettlewell}}</ref><ref name="kett58">{{cite journal|last1=Kettlewell|first1=Bernard|year=1958|title=A survey of the frequencies of ''Biston betularia'' (L.) (Lep.) and its melanic forms in Great Britain|journal=Heredity|volume=12|issue=1|pages=51–72|doi=10.1038/hdy.1958.4|doi-access=free|bibcode=1958Hered..12...51K |authorlink=Bernard Kettlewell}}</ref> Haldane's prediction was proven further by a Cambridge geneticist [[Michael Majerus]] in his experiments conducted between 2001 and 2007.<ref name="Cook2012">{{cite journal|author=Cook, L. M.|author2=Grant, B. S.|author3=Saccheri, I. J.|author4=Mallet, James|year=2012|title=Selective bird predation on the peppered moth: the last experiment of Michael Majerus|journal=Biology Letters|volume=8|issue=4|pages=609–612|doi=10.1098/rsbl.2011.1136|pmc=3391436|pmid=22319093}}</ref>

His contributions to statistical human genetics included: the first methods using [[maximum likelihood]] for the estimation of human [[linkage map]]s; pioneering methods for estimating human mutation rates; the first estimates of [[rate of mutation|mutation rate]] in humans (2 × 10<sup>−5</sup> mutations per gene per generation for the X-linked [[haemophilia]] [[gene]]); and the first notion that there is a "cost of natural selection".<ref>{{cite journal|last=Haldane|first=J. B. S.|year=1935|title=The rate of spontaneous mutation of a human gene|journal=Journal of Genetics|volume=31|issue=3|pages=317–326|doi=10.1007/BF02982403|s2cid=34797487}}</ref> He was the first to estimate the rate of human mutation in his 1932 book entitled ''The Causes of Evolution''.<ref>{{Cite journal|last=Nachman|first=Michael W.|date=2004|title=Haldane and the first estimates of the human mutation rate|journal=Journal of Genetics|volume=83|issue=3|pages=231–233|doi=10.1007/BF02717891|pmid=15689624|doi-access=free}}</ref> At the [[John Innes Horticultural Institution]], he developed the complicated linkage theory for polyploids;<ref name="jic.ac.uk" /><ref>{{Cite journal|last=Haldane|first=J. B. S.|date=1930|title=Theoretical genetics of autopolyploids|url=http://link.springer.com/10.1007/BF02984197|journal=Journal of Genetics|language=en|volume=22|issue=3|pages=359–372|doi=10.1007/BF02984197|s2cid=46262752}}</ref> and extended the idea of gene-enzyme relationships with the biochemical and genetic study of plant pigments.<ref>{{Cite journal|last=Crow|first=James F.|date=1985|title=JBS Haldane-an appreciation|url=http://link.springer.com/10.1007/BF02923548|journal=Journal of Genetics|language=en|volume=64|issue=1|pages=3–5|doi=10.1007/BF02923548|s2cid=34693589}}</ref><ref name=":3" />