About CSci

  • Professor Stephen Holgate
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Professor Stephen Holgate
Featured Profile: 
At A Glance
Licensed Body: 
South East
First Degree: 
Works For: 
Southampton University Hospital Trust, Medical Research Council
Burning Ambition: 
To cure asthma. I’d love to see major breakthrough that would make major difference to patients.
To understand the nature of complexity. To understand better how things in the natural world interrelate. We’re spent the last 50 years reducing things to individual components, but knowing how things interrelate is the biggest challenge we have- both in medicine and in the wider natural world.
Big Picture
When you were a child, what did you want to be when you grew up? 
A scientist. My mother and father used to be distracted by me asking them science-related questions all the time. All of my relatives used to complain about it!
Who or what inspired you to become a scientist? 
I’m from the North of England and I went to school in the silk spinning town of Macclesfield in Cheshire. Every morning I used to go on a steam train to school and pass a company called ICI Pharmaceuticals, which later became Astra Zeneca. One day people from this drug company came to careers day at my school and really impressed me. This early experience was very influential in my life. Also, a distant relative of mine was Christopher Addison who in the early 20th century helped found the Medical Research Committee (the precursor to the MRC) because the then Prime Minister, David Lloyd George, wanted to find the cause of tuberculosis. Addison was a Professor of Anatomy at the University Sheffield. Mentioning his name may have helped get me into medical school, because he went on to be Chairman of the MRC! I never met him but he was quite an interesting character who aspired towards wanting to discover the underlying causes of diseases. He was a major person in the family.
What do you love about your job and being a “scientist”? 
It’s waking up every morning looking forward to new challenges wherever they come from, not just in science, but helping others dealing with complex issues around complicated diseases. For example, at the moment I’m part of a group working on ME (chronic fatigue syndrome). We had a big conference for people doing work in this area and you could see where breakthroughs were going to happen. The conference was not so much about science as building relationships and confidence in a cross-disciplinary way
What would you change? 
What qualifications did you take at school? 
I did A-levels in biology, chemistry, and physics.
Why did you choose your first degree subject? 
I received a BSc degree in Biochemistry in 1968 (Imperial) and completed my medical degree at the Charing Cross Hospital Medical School in 1971. The Charing Cross Hospital Medical School, based in Trafalgar Square, was small and only accepted about 50 students per year.
Do you have a Masters or PhD? If not, was it difficult to demonstrate Masters-level equivalence in order to achieve CSci? 
I completed my training in general and internal medicine in London Postgraduate hospitals (UCL Institute of Neurology in Queen Square where I was lucky enough to work with Michael Kremer, an extremely good clinician, and then the Royal Brompton Hospital where I did cardiology and chest diseases). Next I moved to Salisbury Hospital where I worked as a Medical Registrar. I moved to Southampton between 1975 to 1980 during which time I completed specialist training in respiratory medicine and obtained my MD thesis on the subject of ß-agonist resistance of human airways. Then I did a two-year post-doctoral fellowship with Dr K. Frank Austen at Boston, US before returning to Southampton in 1980 when the Medical School was new.
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.
Would you say you have a good standard of living/ work-life balance? 
Yes, I think so. Others may not think so… but I love work so much.
What do your friends and family think about your job? 
I think they love it. In different stages I’ve had to be away and my family’s had to give things up. I have a wonderful wife who has supported me over the years – I can’t speak more highly of her. I’m very lucky to have four children who are healthy and highly educated. We all have a lot of fun together.
What kind of hobbies or extracurricular activities do you do to relax? 
Gardening, walking and travelling.
Why did you choose to apply for CSci and what do you value most about being a Chartered Scientist? 
I think multidisciplinarity is something in science that’s so important and we need a common qualification that binds everyone together. CSci clearly is designed to do that. It’s about recognition by individual bodies of a certain standard. It not only generates a qualification that says something about professional skills and competencies…it also says something about others who have a similar qualification at a similar level. Multidisciplinarity is terribly important in this new, complicated world in which we live and CSci really does that more than anything else. Being part of Science Council Science in Health Group I’ve seen all these different organizations come together which has been quite liberating. It’s important to remember that no single person’s got the answer. You did need to have views coming from different directions
What is the value of professional bodies? 
The good side of professional bodies is that they generate standards of one form or another and aspire to maintain competencies. The bad side of professional bodies is they tend to be rather individual, which can be inhibitory. I see this especially in the fields of medicine, where you have many different professional bodies for different specialties but where people are all doing similar jobs. My own personal view is that we shouldn’t have them all…we should have one body perhaps with different divisions. A good example is The Academy of Medical Sciences which cuts across all these disciplines. There’s room for more collaboration and less of these individual organizations. I’d like to see these colleges merging and speaking with a single voice.
How important is CPD? What do you think of the revalidation process in ensuring that CSci is a mark of current competence? 
CPD is fine as long as it doesn’t remove aspiration. Sometimes it becomes a box-ticking exercise which becomes boring. If you have to do a lot of drudging then you lose the sparkle of wanting to improve your own professional activities. CPD can be too blunt an instrument.
Advice & Reflection
What words of wisdom would you give someone interested in getting into your field? 
First, to try and find individuals within your sphere of contacts who you respect and look up to and to try and harness their interest in you as an individual so you’ve got someone who will help you in you career development. Second, anything that’s worth doing will be difficult. Don’t always take the easy route. Sometimes to change direction you have to be brave and courageous. Those are attributes that can’t be gained through degrees and professional bodies. To get mixed experience increases one’s confidence and doesn’t come from linear thinking and progression.
How important is the mentoring process in your field and to you personally? 
Hugely important. People aren’t clear about this. They confuse mentoring with supervision. They are not the same. Mentoring is about aspirational people who are able to help you through difficult decisions outside of your professional interest. There’s not enough of that – we need more.
How would you define “professionalism”? 
Professionalism is a particular code of conduct which maps onto your professional interests. It’s the ability to be confident in your relationships with people which enables you to be influential and to make progress and talk a common language but is bound by a series of important limitations so one doesn’t step outside of your competencies. It’s difficult because people do tend to exaggerate. Professionalism is knowing where your limitations are, maintaining the highest skill base you can, and being humble when you don’t know the answers.
What would you do differently if you were starting out in your career now? 
I don’t think I would. These things come together as a list of coincidences…those coincidences have turned out to be rather nice.
What would you like people to remember about your life as a scientist? 
That I was prepared to listen and take on difficult challenges and continue even if prevailing opinion was against me!
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