The tale of Sherlock’s greatest foe

All medical progress depends on the unreasonable doctor or researcher

Prof Dame Sheila Sherlock (1918-2001) almost single-handedly established hepatology as a speciality in Britain. In the 1940s, she trained as a research fellow with Sir John McMichael at the Hammersmith Hospital in London and made her name with her work on percutaneous liver biopsy, then an experimental procedure. The endocrinologist Sir Richard Bayliss, who worked at the hospital in the late 1940s, told Sherlock’s biographer, Prof Om P Sharma, about her methods of patient recruitment:

“One morning I went to do a ward round. We went to the male ward and there were my six patients all lying flat in bed without a pillow. I said, ‘what are these patients doing without any pillows?’ and Sister said, ‘Sherlock came and lumbar punctured them at 7.30 this morning.’ So I said, ‘really! What did she do that for?’ Horowitz, the houseman, spoke up and said, ‘she is interested in knowing the normal level of ammonia in the cerebro-spinal fluid because she thinks that there is some relationship between the encephalopathy of liver failure and the ammonia level.’ So I went down to see Sheila and she pulled the whole, ‘you know, you are relatively new here. This is what happens, this is what I do. Don’t be such a silly old fogey.’”

Sharma (a distinguished chest physician and friend of Sherlock’s husband, Dr Geraint James) vigorously defended her, arguing that hospitals in those days did not have research ethics committees, that patients were generally very willing to help out with research, and that “what is appropriate in one era is often deemed inadmissible in a later one”. Many others were not quite so forgiving. Malcolm Watson, who was McMichael’s houseman in the early 1950s, had grave misgivings about his chief’s experiments with cardiac catheterisation: “One of his patients was told, ‘we are going to do some tests to see how your ulcer is getting on’. The McMichael team then spent half a day catheterising him in arm veins, and to the superior vena cava, to the hepatic vein, for sampling the effects of medication. It seemed highly dishonest, if not illegal.”

Sherlock’s nemesis arrived in the form of Maurice Pappworth, a Liverpool-born, London-based general physician. He made his living from private practice and by running courses coaching candidates for the clinical part of the MRCP. The Royal College of Physicians regarded such coaching as bad form and an unfair gaming of the examination, and pointedly denied Pappworth the fellowship. He first publicly criticised Sherlock in a letter to The Lancet in 1957, questioning the ethics of her “challenge diet”. Sherlock had published a paper in the journal describing the effects of large doses of ammonium chloride and high-protein diet given to 65 patients with liver disease: This “challenge” often precipitated encephalopathy. Pappworth asked: “Who can condone the giving of a noxious substance to a sick man, knowing that it will cause severe harm?” Sherlock was unperturbed, and replied in the letters pages of The Lancet: “Until some more convenient test is available, challenge diets of protein and ammonium chloride will continue to hold a valuable place in the patient’s management and for his ultimate good.” One wonders how such a “challenge” could guide clinical management.

But Pappworth didn’t give up. In 1967, he published a book called Human Guinea Pigs, in which he described over 200 cases of unethical research practices in the US and Britain, including experiments on children, prison inmates and people with intellectual disability. Ironically, the two countries who most flouted the 1947 Nuremberg Code on Human Experimentation were the two main prosecutors at Nuremberg. The book provoked a furore, and the academic medical establishment was outraged. Many in that establishment believed that Pappworth’s campaign was driven by sour grapes: Earlier in his career, he had interviewed unsuccessfully for several teaching hospital consultant posts, including one at the Hammersmith. He suspected his lack of success was due, at least in part, to anti-Semitism; after one unsuccessful interview, he was told by a local medical grandee: “No Jew could ever be a gentleman.”

In 1959, Sheila Sherlock became Professor of Medicine at the Royal Free Hospital in London, the first woman to be appointed to a full chair of medicine in Britain. Between then and her retirement in 1983, she built up an internationally-renowned liver unit, picking up along the way a Damehood and Fellowship of the Royal Society. Maurice Pappworth was ultimately vindicated by the establishment of ethics committees and much tighter regulation of clinical research. The Royal College of Physicians finally granted him the fellowship in 1993, a year before his death, and 57 years after passing the MRCP. The occasion, wrote Sir Christopher Booth in Pappworth’s obituary for the British Medical Journal, was “greeted with spontaneous applause”.

Sheila Sherlock and Maurice Pappworth were more alike than either would have cared to admit. Both were difficult, prickly, and fearless; both left an enduring legacy.