Kenneth Callow | |
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Born | Goring-on-Thames, Oxfordshire, England |
Robert Kenneth Callow, FRS (15 February 1901 – 1983) was a British biochemist. He worked at the National Institute for Medical Research (NIMR, Medical Research Council) in Hampstead and Mill Hill, where his work on steroids included contributions to the isolation and characterisation of vitamin D, and the synthesis of cortisone from naturally occurring steroids. After he retired from the NIMR in 1966 he worked on insect pheromones at Rothamsted Experimental Station (now Rothamsted Research) until 1971.
Fellowship of the Royal Society is an award granted to individuals that the Royal Society of London judges to have made a 'substantial contribution to the improvement of natural knowledge, including mathematics, engineering science and medical science'.
Biochemists are scientists that are trained in biochemistry.
The National Institute for Medical Research, 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);
Kenneth Callow was born 15 February 1901 in Goring-on-Thames, 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 (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, FRS.
Goring-on-Thames is a village and civil parish on the River Thames in South Oxfordshire, England, about 5.5 miles (8.9 km) south of Wallingford and 8 miles (13 km) north-west of Reading. The name of Goring is first seen in the Domesday Book of 1086 as Garinges. It appears as Garingies in a charter once held in the British Museum. It means "Gara's people". Goring has a railway station on the main line between Oxford and London. Most land is farmland, with woodland on the Goring Gap outcrop of the Chiltern Hills. Its riverside plain consists of the residential area, including a high street with a few shops, public houses and restaurants. Nearby are the village's churches – one dedicated to St Thomas Becket has a nave built within 50 years after the saint's death, in the early 13th century, and a later bell tower. Goring faces the smaller Streatley across the Thames. The two villages are linked by Goring and Streatley Bridge.
The City of London School, also known as CLS and City, is an independent day school for boys in the City of London, England, on the banks of the River Thames next to the Millennium Bridge, opposite Tate Modern. It is a partner school of the City of London School for Girls and the City of London Freemen's School. All three schools receive funding from the City's Cash. It is a member of the Headmasters' and Headmistresses' Conference (HMC).
Christ Church is a constituent college of the University of Oxford in England. Christ Church is a joint foundation of the college and the cathedral of the Oxford diocese, which serves as the college chapel and whose dean is ex officio the college head.
After a time at British Celanese (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.
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.
Yew is a common name given to various species of trees.
In 1929 he was invited by R.B. Bourdillon at NIMR in Hampstead to join him in work on vitamin D. 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 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. In 1932 Otto Rosenheim and Harold King published a paper putting forward structures for sterols and bile acids which found immediate acceptance. [1] The loose association between Bourdillon, Rosenheim, King and Callow was very productive and led to the isolation and characterisation of vitamin D. [2] 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.
Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and multiple other biological effects. In humans, the most important compounds in this group are vitamin D3 (also known as cholecalciferol) and vitamin D2 (ergocalciferol). Cholecalciferol and ergocalciferol can be ingested from the diet and from supplements. Only a few foods contain vitamin D. The major natural source of the vitamin is synthesis of cholecalciferol in the skin from cholesterol through a chemical reaction that is dependent on sun exposure (specifically UVB radiation). Dietary recommendations typically assume that all of a person's vitamin D is taken by mouth, as sun exposure in the population is variable and recommendations about the amount of sun exposure that is safe are uncertain in view of the skin cancer risk.
John Desmond Bernal 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 was a political supporter of communism and wrote popular books on science and society.
Dorothy Mary Crowfoot Hodgkin was a British chemist who developed protein crystallography, for which she won the Nobel Prize in Chemistry in 1964.
Callow became involved with a variety of problems related to the work on vitamin D, including the claim that rickets was produced by the action of certain cereals. This was shown to be due to interference with calcium absorption (working with Hilda Bruce). He also worked closely with Alan Parkes [3] who was working on the physiology of reproduction, and C.W. Emmens.
Rickets is a condition that results in weak or soft bones in children. Symptoms include bowed legs, stunted growth, bone pain, large forehead, and trouble sleeping. Complications may include bone fractures, muscle spasms, an abnormally curved spine, or intellectual disability.
In the 1930s Callow became interested in the structure and action of sex hormones and identifying steroids in urine. In a 1936 paper, written with Frank Young, [4] 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 androgens 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. This conclusion was supported by findings made jointly with A.C. Crooke, working at the London Hospital, that patients with Cushing's syndrome, caused by a tumour of the adrenals, had very high levels of androgenic substances in the urine.
A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes which alter membrane fluidity; and as signaling molecules. Hundreds of steroids are found in plants, animals and fungi. All steroids are manufactured in cells from the sterols lanosterol (opisthokonts) or cycloartenol (plants). Lanosterol and cycloartenol are derived from the cyclization of the triterpene squalene.
An androgen 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 the embryological development of the primary male sex organs, and the development of male secondary sex characteristics at puberty. Androgens are synthesized in the testes, the ovaries, and the adrenal glands.
Situated along the perimeter of the adrenal gland, the adrenal cortex mediates the stress response through the production of mineralocorticoids and glucocorticoids, such as aldosterone and cortisol, respectively. It is also a secondary site of androgen synthesis. Recent data suggest that adrenocortical cells under pathological as well as under physiological conditions show neuroendocrine properties; within the normal adrenal, this neuroendocrine differentiation seems to be restricted to cells of the zona glomerulosa and might be important for an autocrine regulation of adrenocortical function.
Despite being in a reserved occupation, he joined the Royal Air Force in 1940. He became an armaments officer and spent much of the war in the NW Frontier area of India (Waziristan, now in Pakistan) defusing unexploded bombs. He was mentioned in dispatches for activity in the relief of Datta Khel. [5] Later in the war he worked for the Inter-Services Research Bureau, a cover name for Special Operations Executive (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.
In 1945 he returned to the NIMR, and worked with John Cornforth on a commercially attractive way of synthesising cortisone 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 seeds, but there was confusion about which species. During the course of this work Callow went to Nigeria at the invitation of Ibadan University, for six months with R.D. Meikle, a botanist from the Royal Botanic Gardens, Kew, to collect arrow poison material. [6] 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 plant, and its availability made it a suitable commercial source. [7] [8] Glaxo Laboratories cooperated with Cornforth and Callow to devise a production process for cortisone from hecogenin. [9] 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.
Callow became interested in the structure and action of "queen substance," produced by the queen honeybee, 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, he carried out work in the field of insect pheromones until 1971.
Kenneth Callow was a member of the editorial board of the Biochemical Journal 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.
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, Isle of Man 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.
Cholesterol is an organic molecule. It is a sterol, a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell membranes.
Cortisone is a pregnane (21-carbon) steroid hormone. It is one of the main hormones released by the adrenal gland in response to stress. In chemical structure, it is a corticosteroid closely related to cortisol. It is used to treat a variety of ailments and can be administered intravenously, orally, intra-articularly, or transcutaneously. Cortisone suppresses the immune system, thus reducing inflammation and attendant pain and swelling at the site of the injury. Risks exist, in particular in the long-term use of cortisone.
Royal jelly is a honey bee secretion that is used in the nutrition of larvae, as well as adult queens. It is secreted from the glands in the hypopharynx of nurse bees, and fed to all larvae in the colony, regardless of sex or caste.
Percy Lavon Julian was a research chemist and a pioneer in the chemical synthesis of medicinal drugs from plants. He was the first to synthesize the natural product physostigmine, plus a pioneer in the industrial large-scale chemical synthesis of the human hormones progesterone and testosterone from plant sterols such as stigmasterol and sitosterol. His work laid the foundation for the steroid drug industry's production of cortisone, other corticosteroids, and birth control pills.
Sir John Warcup Cornforth Jr., AC, CBE, FRS, FAA was an Australian–British chemist who won the Nobel Prize in Chemistry in 1975 for his work on the stereochemistry of enzyme-catalysed reactions, becoming the only Nobel laureate born in New South Wales.
The Upjohn Company was a pharmaceutical manufacturing firm founded in 1886 in Kalamazoo, Michigan, by Dr. William E. Upjohn, an 1875 graduate of the University of Michigan medical school. The company was originally formed to make friable pills, which were specifically designed to be easily digested. These could be "reduced to a powder under the thumb", a strong marketing argument at the time.
Stigmasterol – a plant sterol (phytosterol) – is among the most abundant of plant sterols, having a major function to maintain the structure and physiology of cell membranes. In the European Union, it is a food additive listed with E number E499, and may be used in food manufacturing to increase the phytosterol content, potentially lowering the levels of LDL cholesterol.
Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Different molecular forms of bile acids can be synthesized in the liver by different species. Bile acids are conjugated with taurine or glycine in the liver, and the sodium and potassium salts of these conjugated bile acids are called bile salts.
Laboratorios Syntex SA was a pharmaceutical company formed in Mexico City in 1944 by Russell Marker to manufacture therapeutic steroids from the Mexican yams called cabeza de negro and Barbasco. The demand for barbasco by Syntex initiated the Mexican barbasco trade.
CYP27A1 is a gene encoding a cytochrome P450 oxidase, and is commonly known as sterol 27-hydroxylase. This enzyme is located in many different tissues where it is found within the mitochondria. It is most prominently involved in the biosynthesis of bile acids.
Diosgenin, a phytosteroid sapogenin, is the product of hydrolysis by acids, strong bases, or enzymes of saponins, extracted from the tubers of Dioscorea wild yam, such as the Kokoro. The sugar-free (aglycone) product of such hydrolysis, diosgenin is used for the commercial synthesis of cortisone, pregnenolone, progesterone, and other steroid products.
Cholesterol 7 alpha-hydroxylase also known as cholesterol 7-alpha-monooxygenase or cytochrome P450 7A1 (CYP7A1) is an enzyme that in humans is encoded by the CYP7A1 gene which has an important role in cholesterol metabolism. It is a cytochrome P450 enzyme, which belongs to the oxidoreductase class, and converts cholesterol to 7-alpha-hydroxycholesterol, the first and rate limiting step in bile acid synthesis.
The Marker degradation is a three-step synthetic route in steroid chemistry developed by American chemist Russell Earl Marker in 1938–40. It is used for the production of cortisone and mammalian sex hormones from plant steroids, and established Mexico as a world center for steroid production in the years immediately after World War II. The discovery of the Marker degradation allowed the production of substantial quantities of steroid hormones for the first time, and was fundamental in the development of the contraceptive pill and corticosteroid anti-inflammatory drugs. In 1999, the American Chemical Society and the Sociedad Química de México named the route as an International Historic Chemical Landmark.
In enzymology, a cholestanetriol 26-monooxygenase (EC 1.14.13.15) is an enzyme that catalyzes the chemical reaction
Jenapharm is a pharmaceutical company from Jena, Germany. Founded in 1950 in East Germany, the company focused from the beginning on the production and development of steroids. Due to the economic circumstances of the Eastern Bloc, the company initially used a unique process of steroid synthesis starting from hog bile, however this method was abandoned a decade later in favor of total synthesis. Initially the company produced a wide range of generic steroids, including corticosteroids, but later on it focused on anabolic steroids, estrogens and progestins.
Hilda Margaret Bruce 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 Oliver Bird Medal.
Cholesterol total synthesis in chemistry describes the total synthesis of the complex biomolecule cholesterol and is considered a great scientific achievement. The research group of Robert Robinson with John Cornforth published their synthesis in 1951 and that of Robert Burns Woodward with Franz Sondheimer in 1952. Both groups competed for the first publication since 1950 with Robinson having started in 1932 and Woodward in 1949. According to historian Greg Mulheirn the Robinson effort was hampered by his micromanagement style of leadership and the Woodward effort was greatly facilitated by his good relationships with chemical industry. Around 1949 steroids like cortisone were produced from natural resources but expensive. Chemical companies Merck & Co. and Monsanto saw commercial opportunities for steroid synthesis and not only funded Woodward but also provided him with large quantities of certain chemical intermediates from pilot plants. Hard work also helped the Woodward effort: one of the intermediate compounds was named Christmasterone as it was synthesized on Christmas Day 1950 by Sondheimer.
Robert Benedict Bourdillon MC AFC DM CBE was a British World War I pilot and medical researcher.