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Thoughts for International Clinical Trials Day

20 May 2019

Anton Chekhov's life was cut short by tuberculosis in 1904. To mark International Clinical Trials Day, Prof Neil Stoker wonders how the then-incurable disease may have affected Chekov's creativity and worldview, and reflects on the medical advances made by clinical trials since.

The Three Sisters and the Fourth Horseman

The stage is set at the Almeida Theatre

Last week I exited a performance of The Three Sisters by Chekhov at Islington’s Almeida Theatre.  The theatre was originally built in 1833 for the Islington Literary and Scientific Society, and had housed a laboratory, library and lecture theatre.  Discussion of politics and religion were not allowed, something I think Chekhov might have approved of.

I was enjoying the fresh night air after the stifling atmosphere of the play.  My first Chekhov, and possibly, I thought, my last. Although the production was excellent, sitting through three hours of other people’s misery felt like an exercise in endurance.

I’d been taken by a friend with whom I had a mutual enjoyment of the perpetual gloom of Arkady Renko in Martin Cruz Smith’s series of novels. But while she actively sought out Chekhov, it appeared that the chord he touched in her was not shared by me.

However, like much great art, the play has stayed with me and rattled round my head, and I wondered about its meaning for Chekhov.  If it was, as was suggested to me, about the pointlessness of life, the inevitability of disappointment, the insanity of our dreams, and the realisation that nothing changes and the only purpose of life is to endure, it had certainly succeeded. 

Then I found that the playwright had spent almost half his short life suffering from tuberculosis.  He became a doctor at the age of 24, so would have understood what it meant that he had just started coughing up blood.  

The Three Sisters was written 1901, just three years before his death, and I wondered how it must have affected him, to be living his entire adult life with a disease that he knew was killing him slowly, and for which there was no effective cure.  I could see a narrative in his plays where people were not just struggling with the imperfections of their own and others’ natures, but with arbitrary, relentless and invisible killers that made any apparent worldy success futile.

Monday 20 May is marked as International Clinical Trials Day, with the day marking the first recorded clinical trial in 1747, for the treatment of scurvy at sea. The fact that we can now treat tuberculosis effectively, owes a huge debt to clinical trials.  TB was the biggest killer in the UK in the early 20th century, and in 1901, the same year as The Three Sisters appeared, there were the first stirrings of our Medical Research Council (MRC). A Royal Commission was appointed ‘to Inquire into the Relations of Human and Animal Tuberculosis’, and this group eventually became the MRC.  Then, in the 1960s, the MRC was involved in carrying out landmark clinical trials, that gave us the foundations for the effective TB treatment programmes we have today, with 6 months of multiple drug chemotherapy. TB became curable. 

Clinical trials are the main tool we use for ensuring that all the medicines we use are safe and effective.  I’d argue that they are even more important for dealing with infectious diseases than with non-infectious ailments, because inappropriate treatment not only affects the patient, but also the rest of us if antibiotic resistance develops. We are currently enjoying the benefits of antibiotics, but sitting at the edge of a precipice where they are no longer of any use. Clinical trials are a major tool in our arsenal for slowing down this looming catastrophe. 

I have spent the past few months working with a team involved in clinical trials for treating highly resistant strains of Mycobacterium tuberculosis, and for shortening the treatment time for non-resistant strains. I already knew that these trials take time and are expensive, but I’ve become more aware of their phenomenal complexity, how many people are involved, and how committed these people are to getting clear and reliable answers as to whether new treatments are genuinely better, or are no better than the dreams of the characters in the play. 

With the benefit of the treatment that came from clinical trials, I pondered, Chekhov might have lived another 44 years.  And his plays just might have a become a little lighter, and a little more fun.

Neil Stoker is working in the UCL Centre for Clinical Microbiology at the Royal Free Hospital  They are partners in clinical trials for treatment of tuberculosis funded by the TB Alliance
ORCID ID; neilstoker.com; @neil_stoker


References
https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/deaths/articles/causesofdeathover100years/2017-09-18
https://www.theguardian.com/books/2013/mar/01/anton-chekhov-lifetime-lovers-play
https://www.british-history.ac.uk/vch/middx/vol8/pp45-51
https://en.wikipedia.org/wiki/Anton_Chekhov
https://mrc.ukri.org/about/what-we-do/history/