Sulphonamides and saving Churchill

It seems that Churchill, a pillar of the ruling class, born in Blenheim Palace, may well have owed his life to this less-exalted area of East London. 

Dagenham has other claims to fame: the Becontree estate, at one time, the largest area of public housing in the world; the Ford Motor Company, which, at its peak, employed 40,000 workers in a plant boasting its own steel foundry and deep water port; and it has also been the source of a long line of footballing talent including such luminaries as Sir Alf Ramsey, Jimmy Greaves, Terry Venables, Bobby Moore, Martin Peters and John Terry. But, more importantly for this story, Dagenham was the home of May & Baker (M & B), a company founded in 1834 in Battersea in SE London as a manufacturer of fine chemicals, and which moved to Dagenham in 1934. It was here that they developed the sulphonamide ‘M & B 693’, claimed to have saved Churchill’s life. 

In December 1943, Churchill flew to Tunis in North Africa on an exhausting trip that had already included Tehran and Cairo and planned to continue to Italy. In Tunis he complained of a sore throat and later developed a fever. A portable X-ray machine allowed his doctor Charles Wilson (later Lord Moran) to diagnose pneumonia, recording in his diary, ‘It means we can begin giving him M & B straight away’. In his war memoirs, Churchill states ‘The M and B…. did the work most effectively. There is no doubt that pneumonia is a very different illness from what it was before this marvellous drug was discovered.’ The drug referred to is generally said to have been the sulphonamide M & B 693. 

The first sulphonamide was Prontosil, a red azo dye discovered by Gerhard Domagk at Bayer in Germany while pursuing the mistaken hypothesis that coal tar dyes, which bind preferentially to bacteria, could be used to treat bacterial infections in the body. Domagk reported Prontosil’s efficacy against the streptococci causing puerperal and scarlet fevers in 1935 and had patented his discovery 3 years earlier. Later work, however, at the Institute Pasteur established that the Prontosil molecule was in fact a pro-drug – one that is metabolised in the body to generate its active constituent – in this case, sulphanilamide. Sulphanilamide acts as a competitive inhibitor of dihydropteroate synthase, an enzyme involved in the production of folic acid, an important coenzyme involved in the biosynthesis of purines and pyrimidines. Humans and other mammals get their folate from dietary sources and are therefore less affected by the drug’s action. 

As a result of the French work, Bayer was unable to protect its discovery since the active component, sulphanilamide, was a relatively well-known compound and the subject of an earlier, expired patent of 1909. Thus a promising field of research was open to all, including May & Baker, who started a programme under the direction of Dr Arthur Ewins in 1936. This followed a familiar but laborious course of synthesising numerous sulphanilamide derivatives and testing their clinical efficacy: a procedure for which they recruited Dr Lionel Whitby from London’s Middlesex Hospital. On 2 November 1937 the aminopyridine derivative of sulphanilamide, compound number 693, was made and later shown to be effective in the treatment of pneumonia. In the following 6 years of research, 3000 compounds were synthesised and May & Baker found a further five sulphanilamide derivatives with useful therapeutic activity. 

Somewhat surprisingly, in view of the efforts now expended conferring suitably impressive names on new drugs, the laboratory name M & B 693 persisted. Some attempt was made to give it a little more cachet when, in the 1940s in ‘Notes on M & B Specialities’ , M & B 693 sported the additional designation of ‘Dagenan’, presumably in misspelt homage to the town, but this was short-lived and in subsequent editions the name reverted to just M & B 693. 

As with so many things, the Churchill story is slightly more complex than is often told. In 1943, Churchill was in his seventieth year and in what can fairly be described as a stressful job. He was overweight, a heavy smoker and drinker (and, one presumes, a stranger to the gym). He was clearly vulnerable and had had an earlier bout of streptococcal pneumonia in February 1943. According to a recent account of the February infection (Journal of the Royal College of Physicians of Edinburgh 2017; 47, 388–94), based on the unpublished war diary of a nurse attending him, he was prescribed sulphathiazole (also known as M & B 760) rather than M & B 693. The same authors have also published an account of Churchill’s December, more serious, pneumonia where, based on other unpublished sources – an autobiography and a war diary, they state that Churchill was in fact given sulphadiazine in Tunis, a drug introduced by American Cyanamid in 1940. This may change an oft-repeated story, though it remains that both Churchill and his doctor refer in their published accounts of the episode to ‘M & B’ (without designating a particular number). Whatever the truth in this instance, M & B 693 undoubtedly saved many lives in the course of its use, since with the introduction of sulphonamides in the early 1940s, mortality from streptococcal pneumonia fell from 40% to 10%. 

Though Ford remain in Dagenham in a much reduced presence, the May & Baker factory has gone. The company had become a wholly owned subsidiary of Poulenc Frères, later Rhône Poulenc, in the 1920s and ended its life in Dagenham in 2013 as Sanofi Aventis. The name lives on however in ‘May & Baker Nigeria’ and in a Dagenham-based football team playing in the Eastern Counties League, from whose ranks, who knows, another Bobby Moore may emerge.