Kenneth Callow
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Robert Kenneth Callow, FRS (15 February 1901 – 12 April 1983) was a British
biochemist Biochemists are scientists who are trained in biochemistry. They study chemical processes and chemical transformations in living organisms. Biochemists study DNA, proteins and Cell (biology), cell parts. The word "biochemist" is a portmanteau of ...
. He worked at the
National Institute for Medical Research The National Institute for Medical Research (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 became part of the new F ...
(NIMR, Medical Research Council) in Hampstead and Mill Hill, where his work on
steroids A steroid is an organic compound with four fused rings (designated A, B, C, and D) arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter mem ...
included contributions to the isolation and characterisation of
vitamin D Vitamin D is a group of structurally related, fat-soluble compounds responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, along with numerous other biological functions. In humans, the most important compo ...
, 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. Cortisol is converted by the action of the enzyme corticosteroid 11-beta-dehydrogenase ...
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 Harp ...
(now Rothamsted Research) until 1971.


Early life and education

Kenneth Callow was born on 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. Situated on the county border with Berkshire, it is south of Wallingford and north-west of Reading. It had a population of 3,187 in ...
, 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 The City of London School, also known as CLS and City, is a Private schools in the United Kingdom, private day school for Single-sex education, boys in the City of London, England, on the banks of the River Thames next to the Millennium Bridge, ...
(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 Christ Church (, the temple or house, ''wikt:aedes, ædes'', of Christ, and thus sometimes known as "The House") is a Colleges of the University of Oxford, constituent college of the University of Oxford in England. Founded in 1546 by Henry V ...
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 Alkaloids are a broad class of naturally occurring organic compounds that contain at least one nitrogen atom. Some synthetic compounds of similar structure may also be termed alkaloids. Alkaloids are produced by a large variety of organisms i ...
and attempting to isolate
taxine Taxine alkaloids, which are often named under the collective title of taxines, are the toxic chemicals that can be isolated from the yew tree. The amount of taxine alkaloids depends on the species of yew, with ''Taxus baccata'' and '' Taxus cus ...
, a toxic alkaloid of
yew Yew is a common name given to various species of trees. It is most prominently given to any of various coniferous trees and shrubs in the genus '' Taxus'': * European yew or common yew (''Taxus baccata'') * Pacific yew or western yew ('' Taxus ...
. 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 structurally related, fat-soluble compounds responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, along with numerous other biological functions. In humans, the most important compo ...
. 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,
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 boo ...
and
Dorothy Crowfoot Dorothy Mary Crowfoot Hodgkin (née Crowfoot; 12 May 1910 – 29 July 1994) was a Nobel Prize-winning English chemist who advanced the technique of X-ray crystallography to determine the structure of biomolecules, which became essential for ...
to discuss possible structures, which contributed to bringing a team together. X-ray crystallography demonstrated that
sterol A sterol is any organic compound with a Skeletal formula, skeleton closely related to Cholestanol, cholestan-3-ol. The simplest sterol is gonan-3-ol, which has a formula of , and is derived from that of gonane by replacement of a hydrogen atom on ...
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, scientific nomenclature: rachitis (from Greek , meaning 'in or of the spine'), is a condition that results in weak or soft bones in children and may have either dietary deficiency or genetic causes. Symptoms include bowed legs, stun ...
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 Olive ...
). 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
steroid A steroid is an organic compound with four fused compound, fused rings (designated A, B, C, and D) arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes t ...
s 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 ) is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This includes ...
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 The adrenal cortex is the outer region and also the largest part of the adrenal gland. It is divided into three separate zones: zona glomerulosa, zona fasciculata and zona reticularis. Each zone is responsible for producing specific hormones. I ...
as well as by the
gonads A gonad, sex gland, or reproductive gland is a mixed gland and sex organ 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, ...
. 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, ...
, 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 Air force, air and space force of the United Kingdom, British Overseas Territories and Crown Dependencies. It was formed towards the end of the World War I, First World War on 1 April 1918, on the merger of t ...
in 1940. He became an armaments officer and spent much of the war in the NW Frontier area of India (
Waziristan Waziristan (Persian language, Persian, Pashto, Ormuri, , ) is a mountainous region of the Pakistani province of Khyber Pakhtunkhwa. The Waziristan region administratively splits among three districts: North Waziristan, Lower South Waziristan Dis ...
, now in Pakistan) defusing unexploded bombs. He was mentioned in dispatches for activity in the relief of Datta Khel. Later in the war he worked for the Inter-Services Research Bureau, a cover name for
Special Operations Executive Special Operations Executive (SOE) was a British organisation formed in 1940 to conduct espionage, sabotage and reconnaissance in German-occupied Europe and to aid local Resistance during World War II, resistance movements during World War II. ...
(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. Cortisol is converted by the action of the enzyme corticosteroid 11-beta-dehydrogenase ...
from naturally occurring steroids. (
Merck & Co Merck & Co., Inc. is an American Multinational corporation, multinational pharmaceutical company headquartered in Rahway, New Jersey. The company does business as Merck Sharp & Dohme or MSD outside the United States and Canada. It is one of the ...
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 university located in Ibadan, Oyo State, Nigeria. Initially founded as the University College Ibadan in 1948, it maintained its affiliation with the University of London. In 1962, it became an independe ...
, 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 sisal fiber is ...
plant, and its availability made it a suitable commercial source.
Glaxo GSK plc (an acronym from its former name GlaxoSmithKline plc) is a British multinational pharmaceutical and biotechnology company with headquarters in London. It was established in 2000 by a merger of Glaxo Wellcome and SmithKline Beecham, wh ...
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 mainland Afro-Eurasia. After bees spread naturally throughout Africa and Eurasia, humans became responsible for the c ...
, 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 people, Irish prince and c ...
,
Isle of Man The Isle of Man ( , also ), or Mann ( ), is a self-governing British Crown Dependency in the Irish Sea, between Great Britain and Ireland. As head of state, Charles III holds the title Lord of Mann and is represented by a Lieutenant Govern ...
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 ''Obi ...
'' 1984 vol 30 pp 91–116. *Obituary, Robert Kenneth Callow, ''
The Lancet ''The Lancet'' is a weekly peer-reviewed general medical journal, founded in England in 1823. It is one of the world's highest-impact academic journals and also one of the oldest medical journals still in publication. The journal publishes ...
'', 30 April 1983, p. 1000. *Obituary, Dr R.K. Callow, ''
The Times ''The Times'' is a British Newspaper#Daily, daily Newspaper#National, national newspaper based in London. It began in 1785 under the title ''The Daily Universal Register'', adopting its modern name on 1 January 1788. ''The Times'' and its si ...
'', 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 20th-century British biochemists 1901 births 1983 deaths Fellows of the Royal Society