Lives of the fellows

Denis John Bauer

b.6 August 1914 d.10 February 2001
PhD Cantab(1938) MB BChir(1943) MA(1962) FRCPath(1964) MRCP(1964) FRCP(1978)

John Bauer discovered the first effective antiviral agent methisazone (Marboran) and, if that was not enough, discovered acyclovir (Zovirax), the first antiviral to have a real impact on clinical medicine and to be a commercial success. He also discovered the antiviral action of Flavans against rhinoviruses but these have not reached the market. Despite these achievements he did not get the general renown that he deserved. He was not a good speaker although he wrote clearly, nor was he a self publicist. He was awkward in his personal relationships, with a hint of intellectual arrogance, which probably held him back.

He was a brilliant student obtaining first class honours in both parts of the natural science tripos from Trinity College, Cambridge. He then took his PhD in the physiology department before proceeding to his medical degree. He did his clinical work at University College Hospital in London. After qualification he soon joined the Wellcome Research Laboratories. At first he worked on yellow fever vaccine and then investigated hepatitis viruses under F O MacCallum [Munk's Roll, Vol.X, p.310], helping to distinguish between infectious hepatitis (hepatitis A) and serum hepatitis (hepatitis B).

In 1947 he started work looking for antiviral compounds. He was one of very few medical scientists who thought this a realistic endeavour. From the start he set himself the task to find selective chemotherapeutic agents; at first he sought to find enzymes that were present only or in greater abundance in viral infected tissues.

His first sniff of success came from investigating the thiosemicarbazones synthesized by George Hitchings, his colleague from B W & Co USA, for activity against pox viruses in vitro and in vivo. Later with the chemist Peter Sadler of the Courtauld Institute he tested a whole range of thiosemicarbazones before settling on methisazone as the most promising to take forward for extensive trials.

In his laboratory work Bauer ensured the highest standards and devised quantitative tests so the activity of competing compounds could be assessed accurately by determining the ED50. He also expressed the results of his assays in molar terms because of course the interesting point is which compound is more active molecule for molecule. Finally, he was always keen to do tests in vivo, in order to show that a candidate compound was active in an actual infection, in a living animal. He also set his face against random screening for antivirals, preferring to have some reason for searching amongst a group of compounds.

In 1963 a major trial of methisazone for the prevention of smallpox was set up by Bauer in India, and proved a resounding success. The drug was also shown to be effective if given early enough in the treatment of the complications of vaccinia immunization. This work brought Bauer recognition. Thus he was elected MRCP in 1964. However methisazone was not a commercial success because it came at a time when WHO were launching their highly successful programme to eradicate smallpox. It was nonetheless an important milestone in antiviral chemotherapy, showing that it was feasible.

His discovery of the antiviral activity of acyclovir occurred in 1974 when at the request of Howard Schaeffer, from B W & Co USA, he looked at the activity of 9-(2-hydroxyethoxy)methylguanine. Just a month after the request he had a result from an experiment in which a monolayer of cells infected with herpes virus of type 1 or type 2 were almost completely protected. His technician Nick Oliver famously wrote in his note book 'very active; investigate further'. This stained Petri dish deserves a place comparable to Fleming's famous penicillin plate in the history of antimicrobial chemotherapy. Indeed in some respects it is more remarkable because the chemists thought such compounds might be active and they also had the backing of a superb biochemist and enzymologist Trudy Elion, who shortly after the discovery was able to elucidate its mode of action. The result was when the work was published finally in Nature four years later after substantial 'further investigation' he was not the lead author. His peers recognised his outstanding achievements when they elected him an honorary member of the British Society for Antimicrobial Chemotherapy.

Outside medicine, John had wide interests. Probably music was his first love, for he was an accomplished musician, sufficiently talented to have contemplated a career as a classical pianist. He was also a knowledgeable botanist, keeping in his office a range of exotic plants. He had an amazing talent for languages and spoke all the major European languages, including Hungarian, Finnish and Russian. He even accepted the challenge of one of his clinical colleagues and learnt Welsh.

He was a very private man and kept his home life quite distinct from his work.

John Beale

(Volume XI, page 41)

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