When you think of true pioneers in research and development for the treatment of infectious diseases, Dr. Dennis Mitchison is sure to come to mind. Born on September 6, 1916, Dr. Mitchison has had a long career dedicated to treating tuberculosis. After qualifying in Medicine from University College in 1943, he began his career in Pathology at the Brompton Hospital at the time that the first clinical trial with a randomised intake between treatment of pulmonary tuberculosis with streptomucin or with bed rest alone was run. He then continued his life-long interest in the treatment of TB, participating in the clinical trials organized by the Medical Research Council’s Tuberculosis Research Unit. In 1946, he was appointed as Director of a new MRC Unit on Drug Resistance in Tuberculosis at the Royal Postgraduate Medical School. He worked closely with Wallace Fox, Director of the MRC Tuberculosis and Chest Diseases Research Unit on developing effective, affordable and short-course treatments for TB. 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. He established specialist TB laboratories in Kenya, Uganda, Tanzania and Zambia as well as a central laboratory in Hong Kong. He has published in excess of 400 papers. After his retirement in 1985, he continued working first at the Royal Postgraduate Medical School, Hammersmith, and now at St. George’s University of London.
Recently, we had the privilege to chat with Dr. Dennis Mitchison to learn about his life and get his views on tuberculosis and the state of research and development for new TB drugs. We will post excerpts from this interview in several parts. Below please find part one of our interview with Dr. Mitchison:
Dr. Mitchison, what inspired you to get involved in the fight to stop TB?
Nothing inspired me. It happened just purely by luck. Serendipity is the right word. It happened because I always have wanted to do research, but not necessarily in TB. I wanted to do research as much as anything because my family has a number of eminent scientists in it in the past. I was following the family tradition. The Haldanes, my mother’s side of the family, are an example. J.B.S. Haldane really pioneered respiratory physiology and did an awful lot of things and was a very eminent person in his own right, and others. That was why I got started in research. It just happened that the first job I took was at the Brompton Hospital in London, which was one of the two first clinical centers in the first streptomycin trial. So it’s purely fortuitous.
If you were going to look back on your career, what are you most proud of?
Well, you know, I’ve been involved in a team effort. Quite a lot of people were active members of this team, though many of them are no longer available either from death or illness. This was a team of British Medical Research Council units of which the leadership really was from Wallace Fox who is now very ill and now longer able to participate. I’m probably one of the few surviving people from that team.
The part that we played on the laboratory side was first of all to design and implement the new laboratories in a number of developing countries – four laboratories in east Africa to be precise. We got a big laboratory in Hong Kong going, and so on. Part of the work was just getting the laboratory basis of these trials going.
But the other side, which was in a sense just as, and probably more, important, was to understand the theoretical reasons why drug treatment works or fails. This started initially with understanding what is drug resistance, how do you measure it and what are its implications for treatment. I mean that’s a very big subject that took something like 20 years to get all the answers to, and we still don’t have all the answers.
Then there is the other fundamental question, why does it take so long for treatment to work in TB? This is still one of the most important questions in modern drug development. I was one of the very first people to try and look at conditions that slowed down or stopped tubercular bacilli from growing and the effect those had on exposure to the different drugs.
Why do you feel that TB is such a problem globally still today?
I think it is a problem simply because there are a large number of people who get infected and who get the disease. I think it’s about 1.8 million or something like that, who die every year from the disease. So although it’s not quite as dangerous a condition as it used to be, it still is dangerous. I think we still have a long way to go before we can properly use the knowledge that’s come from the development of effective drug treatment.
So in other words, you’re saying that we actually know more than we’re able to implement at the moment?
I think that is certainly true. You know, after all, in 1985 there were a series of papers published, first of all from Singapore, which was part of the network that was associated with the British Medical Research Council. They are the prototype studies for modern TB treatment, and it’s from those studies in Singapore that we derived the treatment regime for tuberculosis that is being used today in the DOTS program of The World Health Organization. It’s taken this long, you see, for it to actually be used in the majority of countries. And still, not all countries are using it. So that’s a significant time lag.
Stay tuned to hear more from Dr. Dennis Mitchison on the state of research and development for new TB drugs and his take on the impact that regulation has had on scientific progress in this area…