Montague Phillips (chemist)

Montague Alexander Phillips
Montague Alexander Phillips (Chemist)
Montague Phillips in c.1954
Born1 December 1902
South London, UK
Died12 October 1972
Upminster, Essex, UK
NationalityUK
SiglumMaP
Alma materBattersea Polytechnic (BSc 1926)
London University (DSc 1942)
Known forSynthesis of sulphapyridine / M&B 693 (1937)
Thalidomide whistleblower (1967)
Scientific career
FieldsChemistry
Industrial Chemistry
Chemical Engineering
InstitutionsMay & Baker, Dagenham, UK

Montague Alexander Phillips (1 December 1902 - 12 October 1972) was an English industrial chemist and chemical engineer.

He is notable for the synthesis of the drug sulphapyridine in 1937, while working as a research chemist at May & Baker, Dagenham, Essex.[1] Sulphapyridine (also known as sulfapyridine, T693, M&B 693 and Dagenan) was an early antimicrobial/antibiotic[2] and the first effective treatment for pneumonia, meningitis and various other bacterial infections of humans and animals.[3] As such, it saved many tens of thousands of lives globally in the years before penicillin and other antibiotics became generally available.[4]

In the 1960s, Phillips was a key whistleblower in the thalidomide scandal.[5]

Education and qualifications

Phillips attended the John Roan School, Greenwich. At 18 he joined May & Baker, Battersea[6] as a laboratory assistant while taking evening classes at Battersea Polytechnic. He graduated with a Bachelor of Science (BSc) degree in Chemistry in 1926. In 1942 Phillips was awarded a Doctor of Science (DSc) degree by London University.[7]

In addition, Phillips was a Fellow of the Royal Institute of Chemistry (FRIC), Chartered Member of the Institution of Chemical Engineers (MICHemE), Chartered Chemical Engineer, Chartered Engineer (CEng), Fellow of the Royal Society of Medicine (FRSM) and Fellow of the Chemical Society (FCS).[8]

Synthesis of sulphapyridine

The drug Prontosil was introduced in 1935 by IG Farben, Germany as an antibacterial treatment for streptococci infections.[9] Later that year, Daniel Bovet at the Pasteur Institute, Paris determined that sulfanilamide was the active form.[10] These were the first of the so-called sulfa drugs and their advent represented a revolution in the treatment of infectious diseases through drug therapy. Within months, a number of other pharmaceutical companies began efforts to develop their own antimicrobials.[3]

In early 1936 the UK chemical company May & Baker commenced an extensive search for new sulfanilamide derivatives with useful antimicrobial properties. This project was initiated by Arthur Ewins (director of research) and carried out by chemists George Newberry and Montague Phillips. Since May & Baker lacked suitable facilities, animal testing was conducted through a collaboration with Lionel Whitby, then a clinical pathologist at the Bland-Sutton Institute of Pathology, Middlesex Hospital in London. Between May 1936 and November 1937 around 64 different sulfanilamide compounds were synthesised and evaluated.[11]

First sample of M&B 693 (Wellcome Collection)
First sample of M&B 693 (Wellcome Collection)

The synthesis of sulphapyridine was not planned but rather it was produced opportunistically due to the availability of aminopyridine, a chemical precursor. The first sample of sulphapyridine was created by Phillips on 2 November 1937. This comprised 10 grammes and was initially recorded in the May & Baker laboratory test log as T693. The log entry was also initialed by Phillips. The final synthesis step, which involved the removal of an acetyl group, was not straightforward. The standard technique, using hydrochloric acid, does not work in this particular case. Instead, Phillips devised a counter-intuitive approach using sodium hydroxide. A few grammes of the first sulphapyridine sample were delivered to Whitby for animal testing with the designation M&B 693.[12][13]

Sulphapyridine proved effective against pneumococcal, streptococcal, meningococcal, staphylococcal, and gonococcal infections in mice.[11] In December 1937 Richard Wien, a researcher at the Pharmacological Society in London undertook toxicity testing with positive results. Several scientists at May & Baker were the first humans to consume the drug and reported no ill effects. In March 1938 sulphapyridine was tested on a single hospital patient with advanced pneumonia who subsequently recovered.[14]

Clinical trials were carried out by Gladys Mary Evans and Wilfrid Fletcher Gaisford, physicians at Dudley Road Hospital in Birmingham. Between March and June 1938, 100 patients with lobar pneumonia were treated with sulphapyridine with a mortality rate of 8% versus 27% in the equal sized control group.[15]

May & Baker industrialised production of the drug and began marketing sulphapyridine in October 1938 under the trade name Dagenan.[16] Sulphapyridine became more commonly known as M&B 693 or more simply M&B in most countries, apart from the USA and Canada. It was also introduced and widely used in veterinary medicine.[17]

The effectiveness of sulphapyridine, particularly against pneumonia, attracted considerable newspaper attention and M&B 693 quickly became a household name around the world.[18] At the end of 1938 a license was granted for Merck to manufacture and distribute sulphapyridine in the USA. Patents for sulphapyridine were issued in the UK in 1939[19] and the USA in 1941[20] with Ewins and Phillips named as co-inventors. Ewins and Phillips were recommended for a Nobel Prize by Calcutta University in 1942 .[21]

M&B 693 played an important role during World War II in many Allied countries. It was widely used, sometimes prophylactically and routinely issued to military personnel as tablets. Sulphapyridine was also found to be effective as a topical antimicrobial in powdered form.[7] M&B 693 was famously used to treat Winston Churchill for pneumonia on two occasions.[22] Churchill expressed his thanks to Phillips with a signed photograph.[23]

By 1943 sulphapyridine was estimated to be saving 25,000 civilian lives per year in the USA[24] and a similar number in the UK.[25] A 2009 study by the National Bureau of Economic Research concluded that between 1937 and 1943 sulfa drugs reduced the mortality rate in the USA by 2 to 4 percent and increased life expectancy by 0.4 to 0.8 years. During this period, sulphapyridine was responsible for the majority of this trend.[26]

The development of other sulfa drugs and the mass production of penicillin after World War II led to a decline in the use of sulphapyridine. However, it was still in use in the USA for treating people with Duhring's disease until 1990.[27] As of 2025, sulphapyridine is still used in the UK in veterinary medicine for the treatment of mastitis in cattle.[28]

Later life

Phillips left May & Baker in 1947 after 20 years service and having attained the position of assistant chief chemist.[29] He took with him the original T693 sample bottle which he later donated to the Wellcome Collection, London.[30] Phillips worked as an independent chemical consultant until his death in 1972. He also campaigned against excessive profit margins on pharmaceuticals.[31]

Throughout his career Phillips published a large number of scientific papers relating to chemistry and chemical engineering. He was also named on several further patents, both while he was employed at May & Baker and later while acting as an independent consultant.

Phillips served in the ARP Reserve between 1939-45 and received the Civil Defence Medal.[8] He was elected as a councillor in the Essex Administrative County in the 1950s and 1960s. During the same period we was also a Technical Reconnaissance Officer in the Civil Defence Corps. In that capacity, he was interviewed on ITN television news in April 1963 about the Spies for Peace revelations concerning RSG-6.

Phillips received some recognition for his role in the creation of sulphapyridine during his lifetime.[32][7][23] However, his involvement was often minimised[33] or overlooked entirely.[34] He received no honours or awards for his work.[35] Whitby received a knighthood in 1945 and over time has come to be regarded as the key figure in the development of sulphapyridine.

Thalidomide whistleblower

In the 1960s Phillips was retained as a professional advisor by Kimber Bull & Co, the solicitors representing the families against Distillers during the thalidomide lawsuits. His wife had previously developed irreversible nerve damage (polyneuritis) from the use of thalidomide as a sleeping pill. During this period Phillips passed 10,000 Distillers documents that were obtained through legal discovery to the Sunday Times newspaper as part of their long-running investigation into the thalidomide scandal.[5][36]

Personal life

Phillips married Helena May Matilda Holland (1902-1980) in June 1927 in Lewisham, London.[37] They had one child.

References

  1. ^ "M & B 693". Illustrated London News. 22 Jan 1944. p. 90.
  2. ^ Sulphapyridine and other sulfa drugs have frequently been characterised as antimicrobials, synthetic antibiotics or simply as antibiotics by different authors.
  3. ^ a b Christensen, S. B. (2021). "Drugs That Changed Society: History and Current Status of the Early Antibiotics: Salvarsan, Sulfonamides, and β-Lactams". Molecules (Basel, Switzerland). 26 (19): 6057. doi:10.3390/molecules26196057. PMC 8512414. PMID 34641601.
  4. ^ Lesch, John (2007). The first miracle drugs: how the sulfa drugs transformed medicine. Oxford University Press. p. 160. ISBN 9780195187755.
  5. ^ a b Evans, Harold (2009). My paper chase: true stories of forgotten times. Little, Brown and Company. p. 361. ISBN 9780316031424.
  6. ^ May & Baker relocated from Battersea to Dagenham in 1936.
  7. ^ a b c "Polytechnic ex-student honoured". South Western Star. 27 March 1942. p. 3.
  8. ^ a b Who's Who of British Scientists. Longman. 1970. p. 640. ISBN 9780582114630.
  9. ^ Domagk, Gerhard (1935). "Ein Beitrag zur Chemotherapie der bakteriellen Infektionen". Deutsche Medizinische Wochenschrift. 61 (7): 250–253. doi:10.1055/s-0028-1129486.
  10. ^ "25 Years of Sulphapyridine". The Chemist and Druggist. 180 (4367): 452–454. 26 October 1963.
  11. ^ a b Whitby, Lionel (28 May 1938). "Chemotherapy of pneumococcal and other infections with 2-(p-aminobenzenesulphonamide) pyridine". Lancet. 231 (5987): 1210–1212. doi:10.1016/S0140-6736(00)89787-1.
  12. ^ Lesch, John (1997). The Inside Story of Medicines: A Symposium. American Institute of the History of Pharmacy. pp. 101–119. ISBN 9780931292316.
  13. ^ Whitby was out of the laboratory when the first sample of T693 was received by his team and was not actually involved in the first round of animal testing.
  14. ^ Lesch 2007, pp. 165–166.
  15. ^ Evans, G. M.; Gaisford, W.F. (2 July 1938). "Treatment of pneumonia with 2-(p-aminobenzenesulphonamide) pyridine". Lancet. 235 (5992): 14–19. doi:10.1016/S0140-6736(00)87996-9.
  16. ^ "The discovery of Dagenan". The Chemist and Druggist. 129 (3051): 107. 30 July 1938.
  17. ^ Lesch 2007, p. 193.
  18. ^ The number 693 was misinterpreted by some newspaper journalists at the time as signifying that May & Baker had created and evaluated that number of chemical compounds in the development of sulphapyridine. This was not the case as the test log and the sample identifiers related to chemical samples produced by a number of concurrent and unrelated projects at their Dagenham laboratory. May & Baker never corrected this misinterpretation. Rather, on at least one occasion it recounted the same narrative: "Letters to the Editor M. & B. 693 How It Was Discovered". Civil & Military Gazette (Lahore, Pakistan). 5 April 1940. p. 11.
  19. ^ "Inventions in the Chemical Industry". The Chemical Age. 44 (1136): 192. 5 April 1941.
  20. ^ "US Patent 2259222: Preparation of sulphanilamide derivatives". Google Patents. Archived from the original on 19 March 2025. Retrieved 18 March 2025.
  21. ^ "M and B Discoverer Among 20 New Fellows". Belfast News Letter. 19 March 1943. p. 6.
  22. ^ "Admirable M & B". Time. Vol. 43, no. 2. 10 January 1944. p. 75.
  23. ^ a b "Mr Churchill's Grattitude". The Scotsman. 30 Dec 1943. p. 4.
  24. ^ Lesch 2007, p. 160.
  25. ^ "How millions of lives are saved". Liverpool Evening Express. 7 July 1943. p. 2.
  26. ^ Jayachandran, Seema; Lleras-Muney, Adriana; Smith, Kimberly V (June 2009). "Modern medicine and the 20th century decline in mortallity:evidence on the imoact of sulfa drugs" (PDF). National Bureau of Economic Research. Working Paper Series. doi:10.3386/w15089. Archived from the original on 28 March 2025. Retrieved 28 March 2025.
  27. ^ "Sulfapyridine (oral route)". Mayo Clinic. Archived from the original on 19 March 2025. Retrieved 18 March 2025.
  28. ^ "VSDB: Veterinary Substances DataBase: Sulphapyridine". University of Hertfordshire. Archived from the original on 19 March 2025. Retrieved 18 March 2025.
  29. ^ "Personal". The Chemical Age. Vol. 58, no. 1500. 10 April 1948. p. 500.
  30. ^ "Original laboratory sample of 'M and B 693', England, 1938". Science Museum Group. Archived from the original on 19 March 2025. Retrieved 18 March 2025.
  31. ^ "Life-saving drugs: Britain held to randsom". The People. 2 January 1966. pp. 2–3.
  32. ^ Other May & Baker chemists and laboratory personnel also contributed to the synthesis of sulphapyridine in different ways. However, Phillips was the only member of May & Baker staff with hands-on involvement in the synthesis of sulphapyridine to be named on associated papers and patents. As director, Ewins deserved credit for instigating the project and persisting with it through over sixty fruitless trials.
  33. ^ "M and B Doctor to Sue". The People. 13 September 1964. p. 13.
  34. ^ "Omission on Drug Discovery". Times. 2 April 1965. p. 8.
  35. ^ "Why leave this genius out in the cold?". The People. 21 June 1964. p. 7.
  36. ^ Knightley, Phillip (25 August 1997). "A battle won late". Independent. Retrieved 18 March 2025.
  37. ^ England & Wales Marriages, 1837-2005, quarter 2, vol. 1D. General Register Office, Southport, England. 1927. p. 2284.
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