Philip D'Arcy Hart

Philip Montagu D’Arcy Hart, CBE, (June 25, 1900 - July 30 2006) was a British medical researcher and pioneer in tuberculosis treatment.

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He came from a notable Jewish family, [1] being a grandson of Samuel Montagu, 1st Baron Swaythling.

Hart was educated at Clifton College, near Bristol, and Gonville and Caius College, Cambridge, where he read medicine. He moved to University College Hospital medical school, London, for his training in clinical medicine, qualifying as a physician in 1925. He obtained an MD by thesis in 1930. At that time UCH boasted an unusual number of distinguished clinician-scientists. Hart thrived in the academic atmosphere and became a consultant in 1934. Such posts at London teaching hospitals were unpaid; the holder was expected to set up a private medical practice to make a living. Hart did not find this arrangement congenial, being left no time for research. He abandoned a secure career in clinical medicine in 1937 to join the Medical Research Council for a working life of medical research and its administration.

His particular interest was in tuberculosis, which in the first part of the 20th century was as grave a problem in western countries as it remains today in the developing world. He had spent a year working with René Dubos at the Rockefeller Institute in New York immediately after becoming a consultant. However, his first work for the MRC was in south Wales, investigating pneumoconiosis, a disabling and potentially fatal disease of coal miners. It was not at the time clear whether this was a condition distinct from silicosis or that coal dust (as distinct from silica dust caused by rock mining) could cause any pathology. The issue had financial implications, because if coal dust was harmful, those affected were entitled to industrial injury benefit from the state. Hart's group was able to show that the prevalence of the condition increased as one moved further west in the south Wales coalfield, and that this correlated with the hardness of the coal and hence with the amount of dust generated in extracting it.

The pneumoconiosis unit closed early in the second world war and Hart was transferred to the tuberculosis research unit in London, becoming its head from 1948 until he retired in 1965. The unit had many achievements, at first relating primarily to the control of the disease in the UK but later in many parts of the world. Perhaps the work of which Hart was most proud was the demonstration by controlled clinical trials, at a time when such trials were novel and their necessity much debated, of the efficacy of streptomycin in treating tuberculosis - the first effective non-surgical treatment for this disease.

Better known is the massive trial of bacille Calmette-Guérin or BCG as a vaccine in thousands of schoolchildren, which demonstrated induction of strong and persistent protection and has been the basis of public health policy. (Universal BCG vaccination delivered through schools has been replaced with targeted vaccination for individuals at greatest risk.) Unfortunately the efficacy of BCG varies widely among countries, and the UK finding cannot everywhere be successfully applied.

The tuberculosis research unit was based at the old National Institute for Medical Research in Hampstead, north London, where there were no facilities for laboratory work on tuberculosis. Hart set up such facilities at the future site of the institute in Mill Hill. When the new institute opened, it included state-of-the-art facilities for safe handling of mice infected with tuberculosis.

When he retired in 1965 he moved full time to Mill Hill with a research grant from the MRC. At the same time he shed his advisory and administrative commitments so that he could concentrate on laboratory work, taking up ideas he had had no time to explore while head of an MRC unit.

So began a period of impressively productive research, which continued until Hart had passed his 100th birthday. His aim had been to study a group of surface-active substances which had the property of affecting the growth of the tubercle bacillus only when it was growing in living cells. Though Hart was able to obtain further information about these compounds, he was unable to determine how they worked. Largely as a result of his persistence, the investigation has recently been restarted.

Meanwhile Hart had discovered a fundamental property of the Mycobacterium tuberculosis growing within cells: its ability to interfere with the normal mechanisms by which phagocytic cells destroy ingested micro-organisms. At a morphological level this was manifested as a failure of phagosomes containing live (but not dead) bacilli to fuse with potentially bacteriolytic lysosomes.

In collaboration with the electron microscopist John Armstrong, Hart developed electron and light microscopical methods to quantify this failure to fuse, and investigated the ability of various mycobacterial and other substances to affect it. The particular natural product or process of the Mycobacterium tuberculosis that accomplishes this interference with the host cell remains unknown but is still being investigated. It is clearly of fundamental importance in understanding how the Mycobacterium tuberculosis survives in its host to cause tuberculosis.

Though his mind remained characteristically acute, Hart suffered in his later years with increasing deafness and poor vision, as well as with neurological problems affecting his mobility. It was this physical deterioration that forced him to abandon work in the laboratory and retire - for a second time - in 2002.

Hart enjoyed books and films and plays; his comments and criticisms were always enlightening. Physical disabilities eventually limited his enjoyment of foreign travel, except for visits to his son and his family in the United States. Mobility problems also curtailed his fly-fishing, a difficult art at which he had been successful.

An important aspect of Hart was his socialism. He was active in the Socialist Medical Association, which in the 1930s supported the setting up of a system very similar to the National Health Service as established in 1947. Tuberculosis was a problem, especially in industrial towns, and of great interest to the society. There was no effective treatment and it was this, as well as general dissatisfaction with a system in which access to treatment was so inequitably distributed among the population, which led Hart to leave clinical medicine in favour of research.

He is survived by his wife, Ruth, and their son, Oliver.

• http://bmj.bmjjournals.com/collections/century/data/darcy.htm

• http://www.jem.org/cgi/content/full/203/9/2047

Obituaries

• http://www.iuatld.org/upload/home_news/hart_uk_199.pdf

• http://www.guardian.co.uk/obituaries/story/0,,1860651,00.html

• http://news.independent.co.uk/people/obituaries/article1221277.ece

• http://www.ilep.org.uk/?niid=222&id=13