How do you describe your job when you meet people at a party?
I tell people I’m a practicing medical doctor or clinician and interested in the causes of complex diseases. It’s because of that interest that I’m keen on pursuing the underlying mechanisms of disease with the hope of pursuing diagnosis and treatment. In my case, I’m specifically concerned with asthma, allergies and air pollution
What is ‘cutting-edge’ about your work?
suppose being able to use human disease cells and tissues to be able to discover novel therapeutic targets against which to direct new treatments. The main issue is that we can reproduce the disease in the test tube.
What are the biggest implications your work will/could have in the future?
I think the major breakthroughs will come if we can identify new targets and then develop treatments towards them. A very important objective for my team is to get industry involved. Industry’s role is to discover the drugs, but without the targets they don’t know what to develop the drugs for. It’s all about translation really, which is where my whole area of research is oriented. One example is a gene called ADAM33. This was the first new asthma gene to be discovered in the year 2000 and published in Nature. We’ve spent the last nine years trying to understand what ADAM33 does in asthma. We know it’s involved in proliferating the vasculature and the muscle in the airways. It goes some way to help explain why people have asthma have too much muscle tissue and blood vessels in their airways which then causes the airways to contract too much and too easily as well as serving to enhance inflammation. Another breakthrough we’ve had was made by studying lining cells from the airways. We showed that in asthma they couldn’t defend themselves against common cold viruses due to a deficiency in a protein called Interferon Beta which is involved in the defense of all human tissues against virus infections. We’ve developed a treatment which replaces Interferon Beta with the hope of reducing and preventing virus-related asthma attacks.
Describe some of the highlights of your average day.
Just taking this last example, we’ve been giving Interferon Beta by inhalation to mild asthmatics and shown that it switches on all antiviral pathways. It’s a major highlight when you’re able to measure that a treatment is actually working. Another example from circa 1993. We were the first people to give an antibody which blocks the allergic reaction of asthma. That is one of the first really new biologic treatments in asthma benefiting thousands of patients with a severe disease across the world. That first experiment was groundbreaking in a way that we didn’t realize at the time. I’m just back from a trip to visit Merck in Boston and Novartis in Switzerland. They both realize that they need to develop new asthma treatments. A highlight for me in my work is the recognition that we need to get a better relationship going between industry and academia to get some of these new treatments developed. We need to work in different ways and aspire to cure disease rather than just suppressing it.
Describe briefly how your career has progressed to date.
Getting my B.Sc. in biochemistry was really the thing that motivated me to go into the science base of medicines in 1968. In addition to that, I’ve had some wonderful mentors, people who I looked up to and who inspired me to make links and discoveries in science. After my stints at UCL’s Institute of Neurology and the Royal Brompton hospital, I moved to the lovely city of Salisbury (close to Southampton) to do a registrar’s job. I worked at Salisbury District Hospital, which used to be an American hospital during World War II, but was taken over by the MRC after the war. It was here that I met Dr David Tyrrell, who first discovered the common cold virus. He used to infect students with viruses as part of his research. When we came together it was obvious we should find out why the common cold leads to the worsening of asthma. We developed some diagnostic tests very early on in my career (mid-1970s). In 1978 I took my family to Boston to work at Harvard (The Robert Brigham Hospital). That experience was inspiring from the scientific point of view but also the personal and family point of view. When you’re away from home comforts you look at life in a different way, and feel more adventurous. When I came back to England in 1980 with my wife and two small children, we’d changed a lot but the country hadn’t. It was that that inspired me to pursue an academic career – I wanted to change things – and I had the courage to do that after being away
How is your job cross-disciplinary?
When you’re a clinician and see patients you begin to understand what the problems are. Unfortunately there are no simple answers to a lot of these conditions. I recognize that you need to bring in particular expertise to tackle them. Only if you can communicate across the divide can real progress be made. My area of asthma should have been cured years ago – everyone thought it was simple. Industry has had a go at it for the last 50 years and only been partially successful. It’s all about drawing on the right expertise, including basic scientists, clinicians, physiologists who can measure outputs, pharmacologists for drug effects, and people working in industry. Also important in all of this are funding bodies and charities (i.e. patient based charities and research councils). They bring in levels of support without which we’d be nowhere
How well is your job compensated? What is the starting salary for your field, and how much can this be expected to rise?
I am paid as a consultant physician which is fine.
How do you see your field developing over the next 5-10 years?
I see a cure in sight. There’s now a recognition that we need to cooperate more to make progress…what people thought was going to be easy has turned out to be much more complicated. Asthma is not a single disease. We’ve got to get clinicians and scientists to work towards identifying what the subtypes are and then targeting those subtypes…progress has started to be made but it has only just started.
What’s the most unexpected thing about your job?
I suppose, from my personal point of view, one of the things that I’ve got the most enjoyment from has also been my greatest surprise. I was asked to be chair of one of the MRC’s four research boards (Population and Systems Medicine Board). This was quite an amazing opening of my scientific vision. The Board deals with all medical research in Britain, and with all diseases outside of neuroscience, infectious diseases, cancer and molecular activities. We look at diseases primarily associated with the heart, lungs, bones, arteries and skin etc. After starting out in a narrow field, within a rapid period of time I gained an interface with a wide body of scientists. It makes you appreciate how important it is to develop the right interfaces between different specialties and fields. There’s this tendency to become too specialized but working on the board has made me realize how important collaboration is.
What’s the biggest achievement of your career so far?
My greatest achievement has been realizing that asthma is both an inflammatory and an airway remodelling condition. It used to be treated to with broncho-dilators (which dilate the muscle), but a large part of my work has been to demonstrate that a special type of inflammation is the main cause of asthma, which acts on the smooth muscle to cause the airways to contract. All of my publications have been in this area. Also, discerning that the common cold virus causes acute worsening of asthma, which we were the first to discover in 1995. We found the underlying cause and now we’re working on a new treatment.
