Norman Heatley | |
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Born | Woodbridge, Suffolk, England | 10 January 1911
Died | 5 January 2004 92) Oxford, England | (aged
Nationality | English |
Education | Saint Felix School; Westbourne House School; Tonbridge School |
Alma mater | St John's College, Cambridge |
Known for | Penicillin |
Scientific career | |
Fields | Biology, biochemistry |
Institutions | Lincoln College, Oxford University |
Norman George Heatley OBE (10 January 1911 –5 January 2004) was an English biologist and biochemist. [1] He was a member of the team of Oxford University scientists who developed penicillin. [2] [3] Heatley developed the back-extraction technique for efficiently purifying penicillin in bulk.
He was born in Woodbridge, Suffolk, and as a boy was an enthusiastic sailor of a small boat on the River Deben, an experience which gave him a lifelong love of sailing. He attended school at Westbourne House in Folkestone, followed by Tonbridge School, then went on to St John's College, Cambridge, where he studied Natural Sciences, graduating in 1933. His doctoral research in Cambridge led to a PhD in 1936, and he then moved to the University of Oxford, where he became a fellow of Lincoln College and joined a team working under Howard Florey that included Ernst Chain. [4]
Alexander Fleming had first discovered penicillin by accident in 1928, but at that time believed it had little application. When Florey and his team recognised the potential of the discovery for combating bacterial infection, they faced the problem of how to manufacture penicillin in sufficient quantities to be of use. Heatley, although the junior member of the team, possessed a natural gift for ingenuity and invention. It was he who suggested transferring the active ingredient of penicillin back into water by changing its acidity, thus purifying the penicillin. [5]
Heatley recorded these trials, carried out on eight mice in May 1940, in his diary:[ citation needed ]
"After supper with some friends, I returned to the lab and met the professor to give a final dose of penicillin to two of the mice. The 'controls' were looking very sick, but the two treated mice seemed very well. I stayed at the lab until 3:45 a.m., by which time all four control animals were dead."
On returning home, he realised that in haste and darkness, he had put his underpants on back to front, and noted this in his diary too, adding "It really looks as if penicillin may be of practical importance." In order to conduct tests on human patients, even more of the drug had to be produced, and again it was Heatley who realised that the most effective vessel for this purpose was something like the porcelain bedpans in use at the Radcliffe Infirmary. These were in short supply because the ongoing World War II, so Heatley designed a modified version which was manufactured in the Potteries. With the help of these, the Oxford laboratory became the first penicillin factory, and subsequent tests on humans proved the efficacy of the new treatment. Even so, it was very difficult to produce enough for sustained treatment. [4]
In December 1940, a 43-year-old police constable, Albert Alexander, was accidentally scratched by a rose thorn on his mouth and was succumbing to septicaemia. Alexander was admitted to the Radcliffe Infirmary, where various conventional treatments all failed, and his case was brought to Florey and Heatley's attention. [6] Having previously tried penicillin only on mice, Heatley was concerned about the side effects large doses of penicillin might have. A patient in a terminal condition with nothing to lose was needed as a human volunteer, and Constable Alexander met this requirement. On 12 February 1941, Alexander was given an intravenous infusion of 160 mg (200 units) of penicillin. Within 24 hours, Alexander's temperature had dropped, his appetite had returned and the infection had begun to subside. However, owing to the instability of penicillin and the wartime restrictions placed on Howard Florey's Laboratory, only a small quantity was available, and although Florey and colleagues extracted any remaining penicillin from Alexander's urine, they had run out by the fifth day and Alexander died a month later. [6] [7] Florey and his team thereafter decided to work only on sick children, who did not need such large doses of penicillin, until their methods of production improved. [8]
Eventually, Heatley and Florey travelled to the United States in 1941 because they wanted to produce about one kilogram of pure penicillin, and persuaded a laboratory in Peoria, Illinois, to develop larger-scale manufacturing of it. In Peoria, Heatley was assigned to work with Dr. A.J. Moyer. Moyer suggested adding corn-steep liquor, a by-product of starch extraction, to the growth medium. With this and other subtle changes, such as using lactose in place of glucose, they were able to push up yields of penicillin to 20 units per millilitre. But their cooperation had become one-sided. Heatley noted, "Moyer had begun not telling me what he was doing." [9]
Florey returned to Oxford that September, but Heatley stayed on in Peoria until December; then for the next six months, he worked at Merck & Co. in Rahway, New Jersey. In July 1942, he returned to Oxford and was soon to learn why Moyer had become so secretive. When he published their research results, he omitted Heatley's name from the paper, despite an original contract which stipulated that any publications should be jointly authored. Fifty years on, Heatley confessed that he was amused, rather than upset, by Moyer's duplicity. Later he was to learn that financial greed had led Moyer to claim all the credit for himself. To have acknowledged Heatley's part of the work would have made it difficult to apply for patents, as he did, with himself as sole inventor. [4]
As Sir Henry Harris put it succinctly in 1998:[ citation needed ]
"Without Fleming, no Chain or Florey; without Florey, no Heatley; without Heatley, no penicillin."
Yet while Fleming, Florey and Chain jointly received the Nobel prize for their work in 1945, Heatley's contribution was not fully recognized for another 45 years. It was only in 1990 that he was awarded the unusual distinction of an Honorary Doctorate of Medicine from Oxford University, the first given to a non-medic in Oxford's 800-year history. [10] He was appointed an Officer of the Order of the British Empire (OBE) "For services to scientific research", in the 1978 Birthday Honours. [11] [12]
Heatley died on 5 January 2004 at his home, 12 Oxford Road, Old Marston, near Oxford.[ citation needed ]
He was cremated in a cardboard coffin after a funeral service at St Nicholas's Church, Marston, on 15 January 2004. Heatley was survived by his wife, Mercy, and four children, Rose, Chris, Jonathan and Tamsin. [4]
Heatley's former home on Oxford Road now bears a commemorative blue plaque, erected in his honour in 2010 by the Oxfordshire Blue Plaques Board. [11] Heatley is also mentioned alongside Florey and Chain, on another blue plaque, on the Sir William Dunn School of Pathology building on South Parks Road, Oxford.
After Heatley died in 2004, Oxford University established a Norman Heatley Postdoctoral Award for researchers showing excellent ingenuity and problem-solving skills. [11] Heatley's papers are archived within the Wellcome Collection in London. [13]
Sir Alexander Fleming was a Scottish physician and microbiologist, best known for discovering the world's first broadly effective antibiotic substance, which he named penicillin. His discovery in 1928 of what was later named benzylpenicillin from the mould Penicillium rubens has been described as the "single greatest victory ever achieved over disease". For this discovery, he shared the Nobel Prize in Physiology or Medicine in 1945 with Howard Florey and Ernst Chain.
Penicillins are a group of β-lactam antibiotics originally obtained from Penicillium moulds, principally P. chrysogenum and P. rubens. Most penicillins in clinical use are synthesised by P. chrysogenum using deep tank fermentation and then purified. A number of natural penicillins have been discovered, but only two purified compounds are in clinical use: penicillin G and penicillin V. Penicillins were among the first medications to be effective against many bacterial infections caused by staphylococci and streptococci. They are still widely used today for various bacterial infections, though many types of bacteria have developed resistance following extensive use.
Howard Walter Florey, Baron Florey, was an Australian pharmacologist and pathologist who shared the Nobel Prize in Physiology or Medicine in 1945 with Ernst Chain and Sir Alexander Fleming for his role in the development of penicillin.
A mold or mould is one of the structures that certain fungi can form. The dust-like, colored appearance of molds is due to the formation of spores containing fungal secondary metabolites. The spores are the dispersal units of the fungi. Not all fungi form molds. Some fungi form mushrooms; others grow as single cells and are called microfungi.
The year 1940 in science and technology involved some significant events, listed below.
Marston is a village in the civil parish of Old Marston about 2 miles (3 km) northeast of the centre of Oxford, England. It was absorbed within the city boundaries in 1991. It is commonly called Old Marston to distinguish it from the suburb of New Marston that developed between St. Clement's and the village in the 19th and 20th centuries. The A40 Northern Bypass, part of the Oxford Ring Road forms a long north-west boundary of the village and parish and a limb, namely a distributary, of the Cherwell forms the western boundary.
Sir Ernst Boris Chain was a German-born British biochemist and co-recipient of the Nobel Prize in Physiology or Medicine for his work on penicillin.
Sir Edward Penley Abraham, was an English biochemist instrumental in the development of the first antibiotics penicillin and cephalosporin.
The history of penicillin follows observations and discoveries of evidence of antibiotic activity of the mould Penicillium that led to the development of penicillins that became the first widely used antibiotics. Following the production of a relatively pure compound in 1942, penicillin was the first naturally-derived antibiotic.
Albert Neuberger was a British Professor of Chemical Pathology, St Mary's Hospital, 1955–1973, and later emeritus professor.
Reserve Constable Albert Alexander was the first patient to be treated with injections of penicillin.
Kevin Brown has been Trust Archivist and Alexander Fleming Laboratory Museum Curator at St Mary's NHS Trust, subsequently Imperial College Healthcare NHS Trust, since 1989, having set up the archives service for St Mary's Hospital, Paddington, London, England, in 1989 and having established the museum in 1993.
The Sir William Dunn School of Pathology is a department within the University of Oxford. Its research programme includes the cellular and molecular biology of pathogens, the immune response, cancer and cardiovascular disease. It teaches undergraduate and graduate courses in the medical sciences.
The discovery of penicillin was one of the most important scientific discoveries in the history of medicine. Ancient societies used moulds to treat infections and in the following centuries many people observed the inhibition of bacterial growth by moulds. While working at St Mary's Hospital in London in 1928, Scottish physician Alexander Fleming was the first to experimentally demonstrate that a Penicillium mould secretes an antibacterial substance, which he named "penicillin". The mould was found to be a variant of Penicillium notatum, a contaminant of a bacterial culture in his laboratory. The work on penicillin at St Mary's ended in 1929.
Robert Hugh Jackson OBE MC was a British paediatrician most notable for his campaign to introduce childproof packaging to medicine.
Kenneth Bryan Raper was an American mycologist.
Andrew J. Moyer was an American microbiologist. He was a researcher at the USDA Northern Regional Research Laboratory in Peoria, Illinois. His group was responsible for the development of techniques for the mass production of penicillin. This led to the wide scale use of penicillin in World War II.
Dr Frank Ralph Batchelor, known as Ralph, was a British biochemist and businessman.
A state microbe is a microorganism used as an official state symbol. Several U.S. states have honored microorganisms by nominating them to become official state symbols. The first state to declare an Official State Microbe is Oregon which chose Saccharomyces cerevisiae as the Official Microbe of the State of Oregon in 2013 for its significance to the craft beer industry in Oregon. One of the first proponents of State Microbes was microbiologist Moselio Schaechter, who, in 2010, commented on Official Microbes for the American Society for Microbiology's blog "Small Things Considered" as well as on National Public Radio's "All Things Considered".
Mary Ethel Florey, Baroness Florey was an Australian doctor and medical scientist. Her work was instrumental in the discovery of penicillin. She was part of the team that ran the first trials on penicillin and first administered the drug in a human trial. Part of her research has been summarized in a four volume book on antibiotics published from 1952 to 1960.
(1990 Oxford: an Honorary Doctorate in Medicine, the first given to a non-medic in Oxford's 800-year history and, in Heatley's view, 'an enormous privilege, since I am not medically qualified')