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From a veterinary degree to FRS
  1. Elizabeth Simpson

Abstract

Elizabeth Simpson's distinguished scientific career was recently recognised by her election as a Fellow of the Royal Society. It started with a veterinary degree, and has hinged on her curiosity to find out how things worked

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AS a child, I was interested in how complex living things worked – animals and people – and decided that becoming a vet provided more scope. I regretted giving up English at A level, but became increasingly drawn into chemistry and physics as well as biology – how living things worked clearly depends on the laws of gravity and mass action, as well as the neat pleating of intestines and the complex pattern of the circulatory system.

Route to the Royal Society: the timeline of Professor Simpson's career

I was lucky to be offered a place to study veterinary medicine at Cambridge, unique at the time for the compulsory three-year science degree before starting clinical studies. We studied physiology and pathology alongside basic science students and those reading human medicine. I became hooked on hypothesis-based accounts of how organs worked, and what happens to them when things go wrong – infections, for example, or cancer.

My interest in pathology increased during the clinical years, starting with a year of veterinary parasitology, microbiology and studies of postmortem material, including histopathology. I found it intriguing to analyse histological images, then a hazard a guess at how things got to look like that, but I was not satisfied when this couldn't be tested.

Solid foundations

Our surgical and medical skills were built on basic science foundations, and I enjoyed my clinical studies, including seeing mixed practices in England, Scotland and Scandinavia.

I had a relatively short time after qualifying to work under supervision before going to Canada, where I started my own practice in the backwoods of New Brunswick. Work with small animals was mixed with horses and also included wild animals (raccoons and seals). I learned fast and became a skilful surgeon – operations sometimes being carried out on kitchen tables in isolated homesteads. When treatment was not effective or practical and the animal had to be put down, I usually asked if I could carry out a postmortem examination, and I persuaded the local human hospital pathology department to process selected tissues for histopathology.

Looking at those histology slides raised further questions, and confirmed my wish to get further training in pathology. I returned to Cambridge to a post of university demonstrator, under the guidance of a wonderful pathologist, Dr Arthur Jennings.

During the following three years, I became increasingly dissatisfied with proposing best-guess scenarios for observations on biopsy and postmortem material. I wanted to test whether those accounts were verifiable, particularly in cases where the immune response appeared to play an important role – tuberculosis, Johne's disease and cancer. Why did tumours with significant lymphocytic infiltrations generally have a better prognosis? Was this related to the immune response against transplants?

It was to address that question that I joined the research lab of Sir Peter Medawar, director of the National Institute for Medical Research (NIMR) in London. My world was transformed by that experience, and the excitement of working in a cutting-edge lab-oratory with hugely gifted and imaginative scientists. At first I felt out of my depth, but I learned to ask questions and contribute to discussions, to design and carry out experiments.

I contributed to making new discoveries in immunology, which at that time was burgeoning with advances of relevance for understanding rejection responses to transplants, tumours, and, in the case of auto-immunity, self components. I was awarded a fellowship to work at the National Institutes of Health (NIH) in the USA, and was subsequently invited to return as a junior group leader at the Medical Research Council's (MRC's) Clinical Research Centre in Harrow. This gave me the impetus and freedom to address questions about T cell responses to transplants in new ways, by adding the in vitro methods for generation and measurement of cytotoxic T cells that I'd developed at NIH. I chose a genetically tractable system in which to explore this, based on the ability of female inbred mice to reject skin grafts from males of the same strain in which expression of the target antigens must be controlled by genes on the Y chromosome. That work took me into the genetics of sex determination as well as transplantation.

Peer review

In addition to the laboratory work, research scientists are asked to provide reviewers' reports for grant applications and papers submitted to journals for publication, part of the peer-review process crucial for evaluating new proposals and examining evidence for new findings. Reviewers must argue their critical points cogently, with pointers towards what might have been included or is needed. Reviewers who are helpful in that way are identified for membership of research grant funding committees and editorial boards.

I was asked to join the editorial boards of several journals, and to become a member, and then chairman, of the MRC's Cell Board Grants committee. After completing my four-year term, I joined an equivalent Biotechnology and Biological Sciences Research Council (BBSRC) committee, followed by membership of the Wellcome Trust infections and immunity panel. Subsequently, I chaired the Cancer Research Campaign's project grant committee and became a member of Cancer Research UK's scientific and strategy committees.

I followed this by contributing to the work of the Wellcome Trust in selecting clinical fellowship candidates for PhD training and postdoctoral research. This exposed me to research across very broad subject areas, including basic and clinical research by human and veterinary clinicians. I also became chairman of a Wellcome Trust veterinary fellowship scheme for improving entry of veterinary graduates into research, a need identified in the influential Selborne Report in 1997, and not yet met.

Family and other interests

What happens to other interests, including family, during a research career? In many ways it is easier to manage in an academic environment, which allows some flexibility for organising time. A research lab runs with input from the group head, postdoctoral fellows, PhD students and research assistants. The group head obtains funds for the research and steers the ship, with significant input from the fellows and increasingly from PhD students as they progress with their research projects.

The presence of good postdoctoral fellows makes it easier for a group head to take parental leave, but they tend to spend a minimum of time away, as the work of so many people turns on them. When my daughter was born I was out of the lab for a few weeks, but during that time held lab meetings at home.

At the postdoctoral stage it is generally not a good idea to spend more than a few months away – science moves fast. Babies are also remarkably versatile creatures with great powers of adaption, especially if introduced to other caring adults and children at an early age.

Having a child during the time studying for a PhD puts strains on the student – the project makes progress with their own benchwork and, when new to that, time in the lab is not always efficiently spent, so progress can be slow. A new baby slows it down even further, but some candidates manage. There really are no rules about when it is best to have children.

‘One does not go into scientific research to become rich, but nor is poverty likely’

How about other interests – the ones developed at school and university – skiing, sailing, hiking and other sports? And music, theatre, literature, art – what chance do they have when career choices are made? My daughter learned to ski when she came with me to scientific meetings in ski resorts; she swam in the South China Sea on our way to my sabbatical in Canberra; I taught her and her cousins to sail during our summers in Maine, when I was attached to the Jackson Laboratory in Bar Harbor as a visiting academic. When we were at home she came with me to concerts, opera, art exhibitions and the theatre – easy in London – and for us hiking was a treat enjoyed when we stayed with friends in Scotland.

My research group transferred to Hammersmith Hospital in 1994 to help found the MRC's Clinical Sciences Centre, of which I became deputy director in 1999. That move increased collaborations with clinical scientists in the hospital, now part of Imperial College, London. During the 10 years leading up to my formal retirement in 2004, our research reached a successful conclusion in using HY-specific T cell clones isolated in vitro to identify and clone the Y chromosome genes responsible for eliciting graft rejection in vivo, and we discovered that selected HY peptides could be used to induce transplantation tolerance, a finding that has clinical implications. Our work also created a set of useful biological tools for setting up model experiments to address both basic and translational questions relevant for better understanding of responses to transplants, tumours and autoantigens.

One medicine

One does not go into scientific research to become rich, but nor is poverty likely – neither of which I would have found comfortable. My career motivation has been curiosity to find out how things worked, one question leading to another. Had that not been satisfying, unlike my basic science colleagues, I always had professional qualifications to fall back on – clinical skills may become rusty, but, like riding a bike, you don't lose them. I was fortunate in finding a rich seam of research questions and obtaining support to explore them, leading to good publications. The quality of these and my broader involvement in science funding and administration led to my election as Fellow of the Academy of Medical Sciences in 1999 and Fellow of the Royal Society this year, as well as being elected an honorary Fellow of the Royal College of Veterinary Surgeons. I was awarded an OBE in 2002.

My science-related work is now largely focused on helping to select medical and veterinary candidates for postgraduate training. The threat of newly emerging diseases, many of them zoonoses, can only be tackled by the combined efforts of those with training in microbiology, parasitology, epidemiology and pathology. The training in whole animal physiology and pathology received by vets and medics is a fantastic starting point for specialist research training in these important areas, and nothing would please me more than to see more veterinary graduates coming forward into the broad world of ‘one medicine’.

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