17 February 2015

Behind enemy lines: a medic goes native among the scientists (Part Two)

Professor Mark Pallen

In my first post, I talked about my experiences as a medical student and a junior doctor, my growing interest in clinical research and how I decided I wasn't suited to front-line medicine or surgery.

This week, I'll be talking how how I progressed from being a house officer to life in laboratory medicine.

Specialist training in Medical Microbiology

I decided to look at laboratory medicine as a career choice—an option often termed “Pathology” within the UK system. When I asked for advice from the local microbiology professor, J. D. Williams, I was surprised to be offered a job as a temporary lecturer in Medical Microbiology at the London. And so, without much forward planning and a heavy dose of serendipity, I embarked on a career in microbiology.

Learning point:

  • Use your own initiative to make contact with people who can help shape your career. You make your own luck.

I started on a research project on serodiagnosis of tuberculosis, but soon realised that I would be better off combining clinical and research training. I learnt the basics of medical microbiology and discovered how easy it was to slip between academic and clinical work within a laboratory-based discipline.

I was surprised to learn that the clinical laboratory was still using animals in routine diagnosis: all tissue samples were being inoculated into guinea pigs as part of the diagnostic work-up for tuberculosis. When I asked the laboratory staff how this could be justified, they said that it probably couldn't, but would provide something that could be cut the next time the professor was asked to save something from his budget!

In a fit of righteous indignation, I then did my own audit of the use of guinea pigs for TB diagnosis and established that they made at best only a marginal contribution to patient management and their use could not be justified on grounds of cost, safety, and animal welfare. This became my first original research publication.

Learning point:

  • If something doesn’t seem right, marshal the evidence and then fight bad practice with the facts
  • Get your first research publication out as soon as you can, however modest it may be

Me as a trainee microbiologist at the Royal Free
Frustrated by the fact that I was being employed on a short-term contract at the London, in 1986 I set off for a new job at the Royal Free, first as Senior House Officer then as Registrar. I soon passed my MRCPath Part 1 examination and by early 1988 was ready to apply for the next rung up the ladder: a Senior Registrar position.

However, by then I had decided that I wanted to follow a clinical academic career path, which meant finding a post in which I could pursue an MD (a research degree, similar to a PhD in being awarded after thesis and viva, but aimed at medics interweaving research with clinical work). This meant getting a Clinical Lectureship with honorary senior registrar status.

I was looking to move out of London, so when I saw an advert for a job at Barts (the UK’s oldest hospital on its original site: founded 1123), my only thought was I might as well apply for interview practice, particularly as there was a strong internal candidate. Surprisingly, I was offered the job and continued my academic career in Professor Soad Tabaqchali’s department.

Learning point:

  • Don’t be put off by competition from internal candidates—they have most to lose and so will often be nervous, whereas the outsider can impress with a relaxed indifference.

The Medical Microbiology department at Barts at that time was a remarkable place, with a thriving academic research lab joined to a busy diagnostic lab. There was a wide variety of pioneering projects underway, harnessing the new power of molecular biology and recombinant DNA technology to the study of bacterial pathogens. In addition, there was a very relaxed and flexible approach to clinical duties, which left plenty of time for research.

I enthusiastically imbibed the research culture, which included regular trips to the Barley Mow pub. I worked alongside several remarkable non-clinical scientists early in their careers, including Brendan Wren, Chris Clayton, Pete Mullany and Harry Kleanthous. I became a devotee of the Apple Mac computer, which I used to produce attractive student handouts. I also learnt how to analyse protein sequences and run searches against protein databases and gained a reputation as the lab’s computer geek.

Learning point:

  • Seek out smart and interesting people as colleagues. Work somewhere with an exciting research vibe. As Jim Watson says: avoid boring people.

I learnt the value of computers in biology when Chris Clayton asked me to analyse some sequence he had generated from what he thought might, or might not, be the gene for urease from the recently discovered gastric pathogen Helicobacter pylori. I compared his sequences with the only other known urease sequence (which came from the jack bean plant) and was amazed to discover a remarkable degree of sequence conservation across such a vast evolutionary distance. This culminated in a brief but highly cited publication.

Learning point:

  • Find your own niche, where you can make a difference.

While at Barts, I developed my own MD project out of a clinical problem — how to diagnose diphtheria (and also how to avoid unnecessary scary false-positives). I developed the first polymerase chain reaction aimed at detecting the diphtheria toxin gene. I also continued my specialist training and so by 1992, I had passed the final part of my MRCPath examination and been awarded an MD. I was then promoted to Senior Lecturer and given an Honorary Consultant position (the first from my year at the London to get a consultant position).

Learning point:

  • If you want to climb the ladder quickly, work in one of the less competitive disciplines.

Parachuted behind enemy lines

Me as lab idiot at Imperial
Once I had got my MD and become a Senior Lecturer, I soon learned that the goal posts have shifted. To be taken seriously as a clinical academic it was becoming clear that you had to have a PhD, i.e. the very same qualification that scientists who were non-medics had.

Through Brendan Wren I had gotten to know Gordon Dougan, who had recently become a professor at Imperial College and was highly influential with the Wellcome Trust. Dougan had taken a look at the state of medical microbiology in the UK and was not impressed. He persuaded the Wellcome Trust to invest in a scheme that allowed medically qualified microbiologists to spend three years at the bench gaining a PhD and before I knew it I was being encouraged to apply to the scheme.

While it clearly represented an opportunity I could not refuse, I have to admit to being very uneasy about taking up a fulltime research fellowship in my mid-thirties. Once I arrived in the lab at Imperial, I went from being a (self-) important medic to being the lab idiot. It was harsh medicine, but it worked.

Learning point:

  • Sometimes you have to seize opportunities that might you uncomfortable in the short term, but pay off in the long term.

During the course of those three years, thanks to interactions not just with Dougan, but with others in his lab, including Gadi Frankel, Paul Everest, Jeannette Adu-Bobie and Gill Douce, I absorbed the mind-set of the professional and competitive scientist.

Ironically, just as I was deciding that I was now interested in exciting basic curiosity-driven research (my thesis was on how Salmonella responds to starvation stress) rather than dull old applied translational research, my supervisor Gordon Dougan was complaining about the artificiality of studying Salmonella infections in mice and stressing the need to study typhoid in humans!

Aside from doing enough research to gain a PhD, I did three more things while at Imperial:
  1. I wrote a series of articles for the BMJ introducing the medical profession to the newly emerging phenomenon of the Internet.
  2. My wife and I started a family.
  3. I led the Imperial College team to victory in University Challenge.

Learning point:

  • Research fellowships with no on-call commitment are a good time to start a family—only one source of sleepless nights, not two!

Appearing on University Challenge

By a twist of fate, items 2 and 3 clashed, in that the final rounds of the contest were scheduled to appear a week before our first child was due to be born. I sought advice from my old friend Brendan Wren, who advised me that I would have many chances to have children, but only one to win University Challenge and that I must broker a deal so that I could participate in the contest and still act as a companion to my wife in labour. And so the compromise was struck that my wife and I would stay with her parents in Newcastle-under-Lyme while the shows were being filmed in Manchester, so that if she did go into labour, I would be close by.

As it happened, we won our way through the quarter-final, semi-final and then the final itself (view on YouTube) and Emma Louise (born November 5 1995) didn't come until a week later!

Learning point:

  • Learn the art of creative compromise
  • Add a few quirky things to your CV to stand out from the crowd

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