After the recent Neuroscience Workshop on 26 and 27 April 2014, The LKCMedicine caught up with keynote speaker Professor Andrew Jackson to find out more about what inspired him to become a clinician-scientist driving basic research. Prof Jackson is Programme Leader at the Medical Research Council’s Human Genetics Unit and Honorary Consultant Clinical Geneticist at the University of Edinburgh. In May 2014, he was elected a Fellow of the UK’s Academy of Medical Sciences in recognition of his standing as one of the leading medical researchers in the UK.
The LKCMedicine: How did you get interested in research?
Andrew Jackson (AJ): Almost by chance. During my second year at medical school, I attended a lunch time talk about opting for an integrated BSc (Bachelor of Science), which allows you to take a year out from your medical course to do a research project. I joined a molecular biology laboratory and was fascinated. I was particularly excited by molecular biologists’ ability to harness processes that occur naturally to manipulate DNA. I also met clinical geneticists working in the lab next door and became interested in this specialty.
When I went back to my medical student training, I spent time, whenever I could fit it in, in genetics clinics to get to know more about the specialty. I completed my medical degree and junior doctor posts in internal medicine, obtained my MRCP (Membership of the Royal College of Physicians) and then applied for a fellowship from the Wellcome Trust to do a PhD in molecular genetics. Since completing my PhD, I’ve split my time between clinical work and research. Even during my specialist training in clinical genetics, I continued with my research, which was supported by a Medical Research Council-funded Clinician Scientist fellowship.
Now, most of my time is spent running a research group of 16 scientists, who study primordial dwarfism and a neuro-inflammatory condition called Aicardi-Goutieres syndrome. I also spend some of my time working as a clinical geneticist, seeing patients of all ages with diverse genetic disorders – from babies with congenital malformations to older adults with neurodegenerative conditions.
The LKCMedicine: How did you come to specialise in primordial dwarfism?
AJ: This really evolved out of my PhD. I started out looking for a molecular basis as to why some people develop smaller brains and I discovered the first gene locus for microcephaly and then moved on to identify the responsible gene. From there, I started looking at growth and body size because the two are interrelated. Primordial dwarfism causes extreme growth failure of the brain and body and individuals with the condition are often described as the smallest people in the world.
The LKCMedicine: What improvements to patients’ care has your research led to?
AJ: We can now better diagnose and manage patients with primordial dwarfism. Many patients and their families find it helps to have a definite diagnosis and explanation for their condition. Since we started work in this field, we have discovered 12 new genes that can lead to types of primordial dwarfism.
With that, we can also better tailor clinical management because different subtypes have different risk profiles. For example, 90 per cent of people with a particular subtype of primordial dwarfism have neurovascular abnormalities, with a high risk of brain aneurysms, necessitating regular MRI screening (and neurosurgical intervention), while people with other types of primordial dwarfism don’t need this.
The LKCMedicine: What advantages does being a clinician bring to bench-based research?
AJ: As a basic scientist, your exposure to clinical problems is limited, so spotting what discoveries could become clinically relevant is harder. As a clinician, you always have clinical problems at the back of your mind and are alert to findings that can have an impact on human health and disease.
Also, as a clinician conducting research, you bring two additional skills to the bench: one is a very broad knowledge and interest in science from your medical education; and the other is a strong ability to work as a team. As clinicians, we’re used to working with different specialists in multidisciplinary teams, each bringing a slightly different perspective to the table. This has helped me greatly in following questions about the conditions I study into new scientific areas.
The LKCMedicine: Is that the only role a clinician can play in research?
AJ: No, a clinician’s contribution to science can be many things: someone who is research-aware, who will refer patients to scientists to help gain new insights into diseases or enable these patients to take part in clinical trials; someone who is working with pharmaceutical companies to test new drugs and other interventions; or someone who works full time on research projects in a lab.
Just as there are many kinds of clinician-scientists, there are also many different kinds of research that we can contribute to, beyond the often mentioned translational research. For me, translational research risks becoming a linear concept, where it’s all about finding and pushing new molecules into treatments. Instead, real innovation may well come from taking a broader view. An example is the discovery of the low-density lipoprotein (LDL) receptor and how its role in familial hypercholesterolemia led to statins. Such bigger leaps in healthcare advances are usually underpinned by discovery. Another example has been the significant advances in treatment of cancer and inflammatory disorders with biologicals which couldn’t have happened without the development of monoclonal antibodies.
The LKCMedicine: With both science and clinical problems getting more complex, can clinician-scientists continue to straddle both effectively?
AJ: We need to have clinician-scientists who can speak the language of both basic scientists and doctors treating patients. We don’t need many but I believe they play an important role in biomedical science and the future of healthcare.
But becoming good at both requires passion and a strong commitment, as effectively you have to train in two very different fields. And along the way, you’ll have to make sacrifices, such as slower career progression. But there are advantages. There is huge variety in the job, it’s always an adventure and you have the hope at the end of the day of making a big difference to society.
The LKCMedicine: Thank you, Professor Jackson.