Denis Mitchison

Family

Mitchison was born in 1919, the son of the Labour politician Dick Mitchison and his wife, the writer Naomi (née Haldane). His uncle was the biologist J.B.S. Haldane and his grandfather the physiologist John Scott Haldane. His younger brothers are the zoologists Avrion Mitchison and Murdoch Mitchison.

In 1954 Denis Mitchison's mother wrote the fantasy book Graeme and the Dragon, in which the protagonist is her grandson, Denis's son Graeme Mitchison.

Education

He was educated at the Dragon School, Oxford and Abbotsholme School, going on to Trinity College, Cambridge where he studied Natural Science obtaining a 1st class degree and a senior scholarship. He then changed to Medicine, qualifying from University College in 1943 and did postgraduate training in Pathology.

Brompton Hospital

His first job in Pathology was at the Brompton Hospital at the time that the first clinical trial with a randomised intake between treatment of pulmonary tuberculosis (TB) with streptomycin or with bed rest alone was run.

Medical Research Council

Mitchison then continued his lifelong interest in the treatment of TB participating in the clinical trials organised by the Medical Research Council's Tuberculosis Research Unit (MRC TRU) with Director Philip D'Arcy Hart).

Following the decisive importance of drug-resistant tubercle bacilli in treatment, he was appointed in 1964 as Director of a new MRC Unit on Drug Resistance in Tuberculosis (later changed to MRC Unit for Laboratory Studies of Tuberculosis) at the Royal Postgraduate Medical School. He then worked closely with Dr Hart at the MRC TRU and later with Wallace Fox, Director of the MRC Tuberculosis and Chest Diseases Research Unit on developing effective treatment for TB at a cost sufficiently low to be affordable in developing countries.

Research

The framework of this work was a series of clinical trials in the UK and in larger numbers in East Africa, India, Hong Kong, Singapore and Czechoslovakia. This work passed through two stages; the first dealt with the problem of drug-resistant tubercle bacilli, which was solved by the use of regimens incorporating 2, 3 or 4 different anti-tuberculosis drugs. The second phase, starting with a publication in 1970, dealt with the shortening of the treatment period from at least 12 months to 6 months by the use of rifampicin and pyrazinamide in so-called "short-course" regimens. These short-course regimens are the basis of current standard therapy with 2 months of 4 drugs (rifampicin, isoniazid, pyrazinamide and ethambutol) followed by 4 months of rifampicin and isoniazid.

He established specialist TB laboratories in Kenya, Uganda, Tanzania and Zambia as well as a central laboratory in Hong Kong.

Publications

He published about 250 papers dealing with (1) factors slowing the growth of tubercle bacilli that might account for the lengthy duration of treatment, including the first paper on the effects of anaerobic culture; (2) with Jean Dickinson on post-antibiotic effects to account for the success of intermittent drug dosage; (3) the curious characteristics of attenuated South Indian strains of TB; (4) the response to treatment when the strains were initially resistant to the drugs allowing identification of the action of individual drugs.

Post-retirement

After his retirement in 1985, he continued working first at the Royal Postgraduate Medical School, Hammersmith and then at St George's, University of London. With Dr Amina Jindani and colleagues in South Africa, he developed the technique of measuring the early bactericidal activity of drugs, which is now standard practice as the initial step in the phase II of clinical development of new drugs. He also introduced the concept of the 8-week phase II study with the proportion of patients obtaining negative sputum culture at 8 weeks, a standard assessment in most such studies. More recently he developed (with Dr Geraint Davies and the South African MRC) a new type of phase II 8-week study using modelling of counts of TB in sputum during treatment. He has done work on several new anti-TB drugs and participated in clinical trials on high dosage rifamycins.