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Robert Kenneth Callow, FRS (15 February 1901 – 1983) was a British biochemist. He worked at the
National Institute for Medical Research The National Institute for Medical Research (commonly abbreviated to NIMR), was a medical research institute based in Mill Hill, on the outskirts of north London, England. It was funded by the Medical Research Council (MRC); In 2016, the NIMR b ...
(NIMR, Medical Research Council) in Hampstead and Mill Hill, where his work on steroids included contributions to the isolation and characterisation of
vitamin D Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group are vitamin D3 (c ...
, and the synthesis of
cortisone Cortisone is a pregnene (21-carbon) steroid hormone. It is a naturally-occurring corticosteroid metabolite that is also used as a pharmaceutical prodrug; it is not synthesized in the adrenal glands. Cortisol is converted by the action of the enz ...
from naturally occurring steroids. After he retired from the NIMR in 1966 he worked on insect pheromones at
Rothamsted Experimental Station Rothamsted Research, previously known as the Rothamsted Experimental Station and then the Institute of Arable Crops Research, is one of the oldest agricultural research institutions in the world, having been founded in 1843. It is located at Har ...
(now Rothamsted Research) until 1971.


Early life and education

Kenneth Callow was born 15 February 1901 in
Goring-on-Thames Goring-on-Thames (or Goring) is a village and civil parish on the River Thames in South Oxfordshire, England, about south of Wallingford and northwest of Reading. It had a population of 3,187 in the 2011 census, put at 3,335 in 2019. Goring ...
, Oxfordshire, England. His father, Cecil Callow (1865–1912), was an electrical engineer. Kenneth's mother, Kate Peverell (1868–1955), became the head of the Peverell household in Gateshead in 1885 after her parents died, when she was 17 years old with two younger sisters. After 1891 she moved to London. In 1896 she married Cecil Callow. Kenneth attended
City of London School , established = , closed = , type = Public school Boys' independent day school , president = , head_label = Headmaster , head = Alan Bird , chair_label = Chair of Governors , chair = Ian Seaton , founder = John Carpenter , special ...
(1911–1919), on a scholarship after his father died in 1912. He was awarded a senior science scholarship in 1916, that allowed him to continue at school. In 1919 he went up to Christ Church, Oxford as an exhibitioner, to study chemistry. For part II chemistry his supervisor was
Nevil Sidgwick Nevil Vincent Sidgwick FRS (8 May 1873 – 15 March 1952) was an English theoretical chemist who made significant contributions to the theory of valency and chemical bonding. Biography Sidgwick was born in Park Town, Oxford, the elder of two ...
, FRS. After a time at
British Celanese British Celanese was a chemical company based in England. Formed in 1916, it survived as an independent company until 1957 when it became a subsidiary of Courtaulds. History The origins of the company lie with two brothers, Henri and Camille ...
(1924–1927) he returned to Oxford as a Research Scholar of Christ Church, synthesising alkaloids and attempting to isolate taxine, a toxic alkaloid of yew. He submitted his D.Phil. thesis in 1929.


Vitamin D

In 1929 he was invited by R.B. Bourdillon at NIMR in Hampstead to join him in work on
vitamin D Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group are vitamin D3 (c ...
. The structure of vitamin D was unknown at that time, and the structure of steroids in general was a matter of debate. A meeting took place with
J.B.S. Haldane John Burdon Sanderson Haldane (; 5 November 18921 December 1964), nicknamed "Jack" or "JBS", was a British-Indian scientist who worked in physiology, genetics, evolutionary biology, and mathematics. With innovative use of statistics in biolog ...
,
J.D. Bernal John Desmond Bernal (; 10 May 1901 – 15 September 1971) was an Irish scientist who pioneered the use of X-ray crystallography in molecular biology. He published extensively on the history of science. In addition, Bernal wrote popular book ...
and Dorothy Crowfoot to discuss possible structures, which contributed to bringing a team together. X-ray crystallography demonstrated that sterol molecules were flat, not as previously proposed by
Adolf Windaus Adolf Otto Reinhold Windaus (; 25 December 1876 – 9 June 1959) was a German chemist who won a Nobel Prize in Chemistry in 1928 for his work on sterols and their relation to vitamins. He was the doctoral advisor of Adolf Butenandt who also won ...
. In 1932 Otto Rosenheim and Harold King published a paper putting forward structures for sterols and bile acids which found immediate acceptance. The loose association between Bourdillon, Rosenheim, King and Callow was very productive and led to the isolation and characterisation of vitamin D. At this time the policy of the MRC was not to patent discoveries, believing that results of medical research should be open to everybody. The team working on vitamin D included Bourdillon, a physical chemist with a medical degree; T.C. Angus, a physician; F.A. Askew, a chemist; Hilda Bruce, a biologist, Kate Fischmann, a biologist, J. St.L. Philpott, a physical chemist, and T.A. Webster, a biologist.


Collaborative work

Callow became involved with a variety of problems related to the work on vitamin D, including the claim that
rickets Rickets is a condition that results in weak or soft bones in children, and is caused by either dietary deficiency or genetic causes. Symptoms include bowed legs, stunted growth, bone pain, large forehead, and trouble sleeping. Complications ma ...
was produced by the action of certain cereals. This was shown to be due to interference with calcium absorption (working with
Hilda Bruce Hilda Margaret Bruce (5 April 1903 – 2 November 1974) was a British zoologist, best known for her discovery of the Bruce effect, a pheromonal behaviour observed in many rodent species. Her work on the control of fertility earned her the Oliv ...
). He also worked closely with Alan Parkes who was working on the physiology of reproduction, and C.W. Emmens.


Steroids

In the 1930s Callow became interested in the structure and action of
sex hormones Sex hormones, also known as sex steroids, gonadocorticoids and gonadal steroids, are steroid hormones that interact with vertebrate steroid hormone receptors. The sex hormones include the androgens, estrogens, and progestogens. Their effects a ...
and identifying steroids in urine. In a 1936 paper, written with Frank Young, a footnote states "The term steroids is proposed as generic name for the group of compounds comprising the sterols, bile acids, heart poisons, saponins and sex hormones." Callow claimed that this was the first use of the term "steroids". He showed that
androgen An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This in ...
s were excreted in the urine in similar amounts in men, women and eunuchs, which at the time was surprising. His conclusion was that these substances were produced by the adrenal cortex as well as by the
gonads A gonad, sex gland, or reproductive gland is a mixed gland that produces the gametes and sex hormones of an organism. Female reproductive cells are egg cells, and male reproductive cells are sperm. The male gonad, the testicle, produces sper ...
. This conclusion was supported by findings made jointly with A.C. Crooke, working at the London Hospital, that patients with
Cushing's syndrome Cushing's syndrome is a collection of signs and symptoms due to prolonged exposure to glucocorticoids such as cortisol. Signs and symptoms may include high blood pressure, abdominal obesity but with thin arms and legs, reddish stretch marks, a ...
, caused by a tumour of the adrenals, had very high levels of androgenic substances in the urine.


War service 1940 – 1945

Despite being in a reserved occupation, he joined the
Royal Air Force The Royal Air Force (RAF) is the United Kingdom's air and space force. It was formed towards the end of the First World War on 1 April 1918, becoming the first independent air force in the world, by regrouping the Royal Flying Corps (RFC) an ...
in 1940. He became an armaments officer and spent much of the war in the NW Frontier area of India (
Waziristan Waziristan (Pashto and ur, , "land of the Wazir") is a mountainous region covering the former FATA agencies of North Waziristan and South Waziristan which are now districts of Khyber Pakhtunkhwa province of Pakistan. Waziristan covers some . ...
, now in Pakistan) defusing unexploded bombs. He was mentioned in dispatches for activity in the relief of
Datta Khel Datakhel () or Datta Khel is a town in North Waziristan district of Khyber Pakhtunkhwa, Pakistan. It is part of Datta Khel Tehsil of North Waziristan district. Overview and history Datakhel is located around 41 km South West of near by to ...
. Later in the war he worked for the Inter-Services Research Bureau, a cover name for
Special Operations Executive The Special Operations Executive (SOE) was a secret British World War II organisation. It was officially formed on 22 July 1940 under Minister of Economic Warfare Hugh Dalton, from the amalgamation of three existing secret organisations. Its pu ...
(SOE), an organisation responsible for sabotage in enemy-occupied territory, with A.G. Ogston, under the leadership of E. Gordon Cox, applying plant and medical chemistry, and developing unusual equipment.


Cortisone

In 1945 he returned to the NIMR, and worked with
John Cornforth Sir John Warcup Cornforth Jr., (7 September 1917 – 8 December 2013) was an AustralianBritish chemist who won the Nobel Prize in Chemistry in 1975 for his work on the stereochemistry of enzyme-catalysed reactions, becoming the only Nobel l ...
on a commercially attractive way of synthesising
cortisone Cortisone is a pregnene (21-carbon) steroid hormone. It is a naturally-occurring corticosteroid metabolite that is also used as a pharmaceutical prodrug; it is not synthesized in the adrenal glands. Cortisol is converted by the action of the enz ...
from naturally occurring steroids. ( Merck & Co had a long and complex synthesis from bile acids, the only known source of cortisone in quantity.) One possible source was sarmentogenin, found in extracts of arrow poisons (heart poisons) from
Strophanthus ''Strophanthus'' is a genus of flowering plants in the family Apocynaceae, first described as a genus in 1802. It is native primarily to tropical Africa, extending to South Africa, with a few species in Asia from southern India to New Guinea and ...
seeds, but there was confusion about which species. During the course of this work Callow went to Nigeria at the invitation of
Ibadan University The University of Ibadan (UI) is a public research university in Ibadan, Nigeria. The university was founded in 1948 as University College Ibadan, one of many colleges within the University of London. It became an independent university in 1962 ...
, for six months with R.D. Meikle, a botanist from the
Royal Botanic Gardens, Kew Royal Botanic Gardens, Kew is a non-departmental public body in the United Kingdom sponsored by the Department for Environment, Food and Rural Affairs. An internationally important botanical research and education institution, it employs 1,10 ...
, to collect arrow poison material. '' S. sarmentosus'' was found to contain sarmentogenin but it was not easy to cultivate or to produce in sufficiently large quantities. Another possible source was hecogenin from '' Agave sisalana'', a plant native to Mexico, grown commercially in Kenya. This was a less direct way of producing cortisone, but the successful extraction and purification of hecogenin from the
sisal Sisal (, ) (''Agave sisalana'') is a species of flowering plant native to southern Mexico, but widely cultivated and naturalized in many other countries. It yields a stiff fibre used in making rope and various other products. The term sisal may ...
plant, and its availability made it a suitable commercial source.
Glaxo GSK plc, formerly GlaxoSmithKline plc, is a British multinational pharmaceutical and biotechnology company with global headquarters in London, England. Established in 2000 by a merger of Glaxo Wellcome and SmithKline Beecham. GSK is the tent ...
Laboratories cooperated with Cornforth and Callow to devise a production process for cortisone from hecogenin. In this case the work done by NIMR staff was patented and sold to Glaxo Labs. Callow was elected as a Fellow of the Royal Society (FRS) in 1958.


Honeybee pheromones

Callow became interested in the structure and action of "queen substance," produced by the queen
honeybee A honey bee (also spelled honeybee) is a eusocial flying insect within the genus ''Apis'' of the bee clade, all native to Afro-Eurasia. After bees spread naturally throughout Africa and Eurasia, humans became responsible for the current cosm ...
, after hearing a talk by Dr. Colin G. Butler on honeybee behaviour at NIMR. Queen substance controls queen-rearing by honeybees, as well as being the sex pheromone attracting drones to a queen on her nuptial flights. Callow isolated and identified this as 9-oxodec-''trans''-2-enoic acid in 1959. This work led to a general interest in the biochemistry of insects. After he retired from the NIMR in 1966, Callow joined the staff at Rothamsted Experimental Station in the insecticide department. Using a
mass spectrometer Mass spectrometry (MS) is an analytical technique that is used to measure the mass-to-charge ratio of ions. The results are presented as a '' mass spectrum'', a plot of intensity as a function of the mass-to-charge ratio. Mass spectrometry is us ...
, he carried out work in the field of insect pheromones until 1971.


Editorial and other work

Kenneth Callow was a member of the editorial board of the
Biochemical Journal The ''Biochemical Journal'' is a peer-reviewed scientific journal which covers all aspects of biochemistry, as well as cell and molecular biology. It is published by Portland Press and was established in 1906. History The journal was established ...
from 1946 until 1953. Later he was chairman of Biological and Medical Abstracts Ltd. He was a member of the Council of the Bee Research Association from 1962 to 1974, being chairman 1963–68, and later Vice-President.


Personal life

In his work on oestrone he was assisted by Nancy Newman (1913–1989), whom he married in 1937. He was the father of John Callow (1944–2000) a merchant navy officer and arboriculturalist, and "Mo" Callow (Mo Laidlaw), an ergonomist at Bell Northern Research in Ottawa from 1978 to 1987. He died 12 April 1983 in
Maughold Maughold (also known as Macaille, Maccaldus, Machalus, Machaoi, Machella, Maghor, Mawgan, Maccul, Macc Cuill; died c. 488 AD) is venerated as the patron saint of the Isle of Man. Tradition states that he was an Irish prince and captain of a ban ...
,
Isle of Man ) , anthem = "O Land of Our Birth" , image = Isle of Man by Sentinel-2.jpg , image_map = Europe-Isle_of_Man.svg , mapsize = , map_alt = Location of the Isle of Man in Europe , map_caption = Location of the Isle of Man (green) in Europe ...
where he had moved in 1980, in pursuit of his Manx ancestors. His grandfather Edward Callow wrote a history of the Isle of Man: ''From King Orry to Queen Victoria'', Elliot Stock, 1899.


Notes


References

* Complete bibliography, in Albert Neuberger, ''Biographical Memoirs of Fellows of the Royal Society'' 1984 vol 30 pp 91–116. *http://rsbm.royalsocietypublishing.org/content/30/92.full.pdf Albert Neuberger, ''
Biographical Memoirs of Fellows of the Royal Society The ''Biographical Memoirs of Fellows of the Royal Society'' is an academic journal on the history of science published annually by the Royal Society. It publishes obituaries of Fellows of the Royal Society. It was established in 1932 as ''Obitua ...
'' 1984 vol 30 pp 91–116. *Obituary, Robert Kenneth Callow, ''
The Lancet ''The Lancet'' is a weekly peer-reviewed general medical journal and one of the oldest of its kind. It is also the world's highest-impact academic journal. It was founded in England in 1823. The journal publishes original research articles, ...
'', 30 April 1983, p. 1000. *Obituary, Dr R.K. Callow, ''
The Times ''The Times'' is a British daily national newspaper based in London. It began in 1785 under the title ''The Daily Universal Register'', adopting its current name on 1 January 1788. ''The Times'' and its sister paper '' The Sunday Times'' (f ...
'', London, 22 April 1983, p. 14. *http://www.heritagepontiac.ca/rkc-biog.htm Transcription of handwritten notes by R.K. Callow, for biographer. {{DEFAULTSORT:Callow, Kenneth British biochemists 1901 births 1983 deaths Fellows of the Royal Society