Editing J. B. S. Haldane (section)

=== 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>