Making Modern Medical History
Kat - Modern medicine tends to revolve around drugs, but pharmaceutical companies are a relatively new invention (certainly compared to the Romans or Chaucer!). Professor Tilli Tansey, who works with Vivian Nutton at UCL, studies the more recent history of medicine. Hi, Tilli!
Tilli - Hi.
Kat - Let's start with looking at pharmaceutical companies which seems to be a very modern invention. What can you tell us about where these kinds of companies came from; about their history and how they've contributed to the medicine we have today?
Tilli - Modern pharmaceutical companies as we would recognise them - research-based industrial enterprises really started in the latter part of the nineteenth century. They came very largely from the German chemical industry and in this country the chemical industry was one of the models. Old fashioned chemical manufacturers were one of the models. Also a big influence was the beginning of biological therapies such as serum antitoxins which required laboratories, which required animals to be used in animal experiments and scientists - properly trained scientists who'd be doing the research work. That was really when what we would recognise as the pharmaceutical industry started developing in this country.
Kat - What about the regulation of these kinds of industries? You think in theory there's nothing to stop anyone saying, "I shall flog this, it makes you better." How about the history of regulation and protection against quackery?
Tilli - It wasn't just theory it was also in practise. The people could just think "we'll make this and flog it." Really well into the twentieth century it was happening. Suddenly in Britain quack sellers would go around market places, selling compounds. Often they would be long-gone if there were any problems. Even quite well-known brands were often contaminated, sometimes deliberately so. There was very little regulation. The main regulation - the poisons act and then simple marketing regulations like weights and measures. It wasn't until the 1920s, 1926 that there was the beginnings of regulations in this country with the Therapeutic Substances Act which just applied to four particular kinds of preparations: three biological preparations and Salvarsan, which was a medicine against syphilis - an arsenic compound. After that it wasn't until 1968 that the medicines act was passed in this country which came into being in 1971 where there was really formal legislation for all drugs. Before then there'd just been perhaps one or two: for example, penicillin. There was particular regulations about penicillin. Otherwise there was no whole-sale regulation in this country.
Kat - I guess, with the rise of the internet we're seeing almost again an alternative medicine industry springing up that is very difficult to regulate and counter to pharmaceutical companies and their tightly-regulated research.
Tilli - Yes, and it varies of course with pharmaceutical industries that have become global industries. Regulations differ from continent to continent, from country to country. International regulation is a big issue.
Kat - What do you think have been the main drivers of change in modern medicine? How have we gone from bloodletting and leeches to the very highly specialised technical medicine that we have today and lots and lots of different drugs that we have.
Tilli - You have to remember that medicine is not just drugs, although obviously they are the most obvious therapeutics that people think about. During the twentieth century what has really happened is a big explosion in medical knowledge, medical education becoming much more scientific-based, explosion of laboratory research which has then fed into clinical research and into clinical applications. That has really been the story throughout the twentieth century.
Kat - One of the things from cancer research - one of the things I find fascinating is how serendipity has led to a lot of really important discoveries so things like the discovery of platinum drugs for chemotherapy or the discovery of nitrogen mustards which were poison gas in the First World War and then we discovered that they were actually quite powerful ways to treat things like blood cancers and lymphomas. What are your favourite serendipitous discoveries?
Tilli - You've just mentioned one of them: platinum compounds. I think the platinum compounds story for chemotherapy really started from a chemist working in a lab in Michigan, looking at the effects of platinum compounds on cell growth/on microbial growth. From that going through to microbiologists with cell biologists to oncologists, looking at how platinum compounds, if they affected the growth of normal organisms, what would they do to abnormal growth, i.e. a cancer cell? Then the development - and this was particularly in this country - the development of platinum compounds and then some chemical testing. Platinum compounds were found to be almost wonder drugs because they did affect the solid tumours like tumours of the ovary and testes for which there were very little treatments beforehand. The big problem with the platinum compounds (and it had been a recognised problem with other chemotherapy and radiotherapy) where the platinum compounds in particular caused nausea and vomiting. So much so that even thought they were the only drugs for these foul cancers patients refused to take them because they got so sick. As an added little quirk of research and another serendipitous leap was that pharmacologists became particularly interested in developing anti-nausea and vomiting drugs because of the platinum compounds. Pharmacologists started working on what was then known as 5-HT receptor antagonists which really can counteract the nausea and vomiting in platinum compounds and also led to the development of drugs that could be used against other chemotherapy adverse effects. I think it's a wonderful story and it starts with a chemist interested in platinum compounds in a lab in Michigan.
Kat - It's fantastic and I love the way that in big medical discoveries - they do have to involve so many people over so long. You think what the Eureka moment must have been. It never seems like a Eureka moment at the time.
Tilli - Exactly and you've raised another important point: so many people. Modern medicine is a big scene. There are numerous players in it unlike the Roman medicine that my colleague, Vivian Nutton was talking about, with major doctors. Doctors played their part but there are scientists, technicians, a whole range of people now involved in the process of medical research.
Kat - It's certainly something that Cancer Research UK - the organisation I work for - we're trying to track down how we've discovered things in the past and tried to trace the relationships between people. Tell us about some of the ways that you're trying to gather together doctors and scientists to actually trace medical history as it's happening.
Tilli - What I do is, in my own work, I do quite a lot of tracing records and talking to people on a one-to-one basis. What I'm particularly developed at UCL is a process called a Witness Seminar. We get together a group of people who've been involved in particular discoveries or debates to actually ask them to sit around together to talk about what happened, why, what perhaps went wrong, some of the serendipity which we've talked about - to discuss this and to have the whole meting recorded. It's then transcribed and edited. In that way we're actually bringing together the whole group of people, sometimes who've never met each other to talk about particular advances and debates. The famous scientist, Sir Peter Medawar, Nobel Laureate, once wrote famously that the scientific paper is a fraud. We could chart the history of, say, the discovery of platinum compounds by looking at all the scientific papers but actually when you get people together they say that the scientific paper's so structured you can't get the stories behind the science. When you get people together it's like an open peer review. They can all talk together. They can disagree, they can stimulate memories and they can tell us about what happened, why things happened and the sub-stories that don't make it into the formal scientific literature.
Kat - I always think those are the most fascinating stories in science: the personal stories of how someone was in the lab late and then something weird happened and then it turned into an interesting discovery. What are the most interesting stories that have turned out from your Witness Seminars?
Tilli - Certainly, as we've just said the platinum compounds because we did actually get all those people we talked about - from the chemist all the way up to the pharmacologist developing anti-emetics in one room. They were quite stunned by it because they had never done that together. Another one which was a particular favourite was haemophilia, looking at changes in the treatment of haemophilia: particularly after the Second World War and how really it as people working in very primitive situations, almost huts at the back of labs in Oxford, working out the blood chemistry and how clotting factors evolved. This explained why some people don't clot when particular factors are not available. Then actually developing and manufacturing the factor to give to haemophiliacs. Of particular interest from that project which had never occurred to me and indeed most of the people at the meeting - it hadn't occurred to them - the importance of home freezers. When people had managed to manufacture factor VIII which is the commonest lesion for haemophiliacs, the commonest missing material. Factor VIII was frozen and then given to patients so they had to go to hospitals and the patients-haemophiliacs were mainly children. There was a great deal of disruption with schooling and they were labelled as invalids and had very disrupted lives. A very influential lady physician at the Royal Free Hospital, Katharine Dormandy, Katherine paid for home freezers - this was in the mid-60s when home freezers were very rare. If patients had a home freezer and if their freezer had an alarm on it - if the electricity supply was disrupted patients knew that their precipitate that was in the freezer was going to be damaged. If they had those freezers they could self-medicate. They didn't have to go to hospital. This made quite a revolution so they could live a normal life. It was almost a de-medicalisation of a condition and children could have normal schoolings. That made an enormous difference to patients' lives.
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