Professor Sir Christopher Dobson on the importance of fundamental science in understanding the underlying cause of diseases to develop novel treatments

August 19, 2018

Prof Sir Chris Dobson is renowned for his groundbreaking work into neurodegenerative diseases, such as dementia, which are rapidly becoming commonplace in ageing populations. He is the John Humphrey Plummer Professor of Chemical and Structural Biology at the University of Cambridge, and Master of St John’s College. Prof Sir Dobson is a Fellow of the Royal Society and a foreign associate of the National Academy of Sciences. He is also one of the founders of the interdisciplinary Centre for Misfolding Diseases at the University of Cambridge. He was an undergraduate and graduate student in chemistry at the University of Oxford and has previously held academic positions at Harvard University, MIT and Oxford. Prof Dobson's research group investigates the nature and properties of protein molecules, especially the phenomenon of protein misfolding, which can cause serious diseases such as Alzheimer’s, Parkinson’s and Type 2 diabetes. This forms the foundations for developing strategies for the cure and prevention of these debilitating illnesses.

In this interview, he shares his journey into science with us, and leaves us with the hope for a dementia-free future.

 

“Some people feel that fundamental science is not the most efficient way to solve really practical problems. However, advances in the applied sciences come out of progress made in fundamental science”

 

What fascinates you about science, and why should people study it? How can we encourage the new generation to choose to study and practise science?

 

Science enables us to make discoveries that can make a real difference to people’s lives. Studying science enhances our understanding of ourselves and of the world. Science also has an innate value in furthering human knowledge and allows us to try to find the answers to fundamental questions that we all ask ourselves, such as how life began or how our brains work.

For the first time in history, the current generation has the tools and methodology to address the major issues facing the world. Developments for example in computer technology, methods of communication and gene sequencing now enable us to tackle extremely complex challenges in better and faster ways. My generation was only able to identify the potential of many of these techniques, but in the last two decades or so they have become usable in new and powerful ways. We can now hope to eliminate many diseases, prevent food shortages and combat climate change. Members of the younger generation have the tools to make discoveries which have eluded us in the past. This is a truly exciting prospect and must be pursued as vigorously as possible! In order to encourage younger people to take up studying the sciences, more inspirational teachers are needed and this issue must be addressed as a vital aspect of educational policy.

 

Where do we lose people when it comes to engaging with science? Do you think there is a communication problem between the scientific community and society? Do you personally take part in outreach activities?

 

There is an inherent fascination about science amongst most young people. However, we do not always communicate effectively the future potential of studying science as a career. There was also a phase when science had a very negative image in society, being associated with nuclear weapons, environmental pollution and the accidental creation of frightening new diseases. This created an element of fear around the whole subject and many people began to avoid the sciences rather than embrace them. As practitioners of science, we must show people how and why science is a force for good in the world.

There are definitely communication problems in science, and often members of the scientific community have been too self-contained. It is vital to be able to explain the significance of one’s research to the general public in relatively simple terms. Everyone must be able to relate to the research that we do by understanding how it can make an impact on their lives. The story of the discovery of penicillin is a well-known historic example, although most people don’t realise the huge scientific effort that was needed to make its use possible. Conveying such information about current scientific issues in a comprehensible manner will focus people’s attention towards the exciting and valuable nature of scientific research. Though the engagement of scientists with the general public is getting better, it is still challenging to convey ideas at the right level. We need to explain what we are trying to achieve through our research, why we approach specific problems in  particular ways, and what is the value of our ultimate successes.

I give a number of talks at schools and to the public more generally to help in this task,  and I mainly discuss the questions my research group is addressing and the importance of overcoming them. I also give talks to many student societies on 'Why science is a wonderful thing to spend one’s life doing'. I would very much enjoy the time to engage in even more such activities as they are often very rewarding experiences.

 

How did you get into science? Did your parents have a major impact on your interest and were you interested in any other careers as well? What was your family background and childhood like?

 

I became involved in science by chance. Both my parents were very intelligent but had to leave school at the age of 14 because of the financial challenges at the time. My father then joined the army as a private soldier at the outbreak of the war and later became an officer. As a result, my family moved around a lot, but I was lucky to have gone to a series of good schools. My parents always encouraged me to do well in my school work in all subjects. I had really inspirational science teachers at my secondary school, and it was they who opened my eyes to what studying science could do. And then I was lucky to go to Oxford University, where I had great lecturers who sustained my enthusiasm. I’ve also had the good fortune to have been able to work on problems which have turned out to be very interesting!

I didn’t have any clear career plans in my mind when I was at school. I chose to do chemistry at university, because I found it interesting and was quite good at it. My journey into an academic career then happened very naturally when I started my doctorate and became fascinated by research. It wasn’t a pre-ordained plan and I had thought about other careers, but in rather abstract terms. One which interested me was architecture because you can change people’s lives though buildings and each structure bears your mark, and is your personal contribution. It is like science in that respect. I was also really interested in being a farmer when I was much younger, but I don’t think I would have been a very good one!

 

Throughout your career, you have been associated with elite universities and have carried out path breaking research. Do you feel that excellence in research is always connected to elite universities? Is the quality and impact of research at less-prominent universities lower?

 

I have been privileged to be associated with four great institutions of higher education: Oxford, Harvard, Cambridge and MIT. What all these well-known universities have in common are inspiring colleagues, highly motivated students and a very intellectually stimulating environment in which to work. I have always tried to provide my students and collaborators with a great working environment. And their ideas and enthusiasm have enabled us to tackle complex problems.

Nevertheless, it is of course possible to conduct outstanding research at universities which aren’t as high-profile. One has to work slightly differently, perhaps, and within a different set of constraints, and the choice of research challenges may need more strategic thinking to make the most of the resources that are available. It certainly doesn’t prevent one from doing great work, as any study of the history of science shows, and certainly not from enjoying the thrill of discovery and the excitement of teaching.

 

When it comes to getting more women into the sciences, do you feel having more female role models will help?

 

I feel very strongly that science would benefit enormously from the involvement of more women. In my experience, there is no difference in aptitude and ability for research between men and women. Not only the scientific community but also society in general should do everything possible to encourage more women to practice science.

In my own research group, I don’t treat men and women any differently, and there is no difference in their achievements or their ability to get jobs or to succeed in their careers, whether they remain in science or not.

 

In the most general sense, what do you work on in the moment, and why and how does your research benefit humanity?

 

My group studies the nature and properties of protein molecules.  We started by exploring the way that these molecules, the most abundant of all biomolecules in living systems, fold up into their functional states. We then became interested by chance in what happens if proteins do not fold correctly. It turns out that protein misfolding can cause serious diseases such as Alzheimer’s, Parkinson’s and Type 2 diabetes. These disorders, and the exploration of ways to combat them, has become a very prominent topic for discussion in the past decade. However, progress in medicine cannot generally be made unless the underlying origins and causes of disease are fully understood. Only then can we hope to develop effective means of combating them.

Protein Misfolding diseases are now frighteningly common. There are, for example, about 40 million people currently afflicted by dementia, the main form of which is Alzheimer’s disease, and this number is set to rise to at least 100 million in the next 20-30 years because of our increasing ageing populations. Unfortunately, these diseases aren’t yet fully understood, making them very difficult to treat. In my research group, we focus on generating this understanding at the molecular level.  We have recently acquired dedicated space for our activities in the Centre for Misfolding Diseases (CMD) at the University of Cambridge. It is a newly established research centre, which brings together people from different academic disciplines including physics, chemistry, mathematics, biology and engineering. An interdisciplinary and collaborative approach is needed to try to tackle multifaceted problems such as neurodegenerative disorders.

 

What made you want to go to academia as opposed to industry? What is the beauty of the academic world? How does research in fundamental science compare to that in applied science?

 

I think it was because I felt that academia would allow me to focus on the fundamental ideas behind scientific problems and work independently on those topics which interest me. I never really considered anything other than research, and academic research was a natural progression from my doctoral studies. I don’t really know how I would have performed if I had gone to industry, but I hope I would have been able to contribute just as effectively but, perhaps in a different way, to the important problems facing the world

Some people feel that fundamental science is not the most efficient way to solve really practical problems. However, advances in the applied sciences come out of progress made in fundamental science. I think that fundamental researchers ought to be more vocal in explaining the applicability of their work. For example, turning again to the history of medicine, we can see that little progress in combating any disease was ever made until its causes and origins were understood. Unless we understand the basics behind complex processes, such as those giving rise to disease, applied sciences cannot translate this work into meaningful solutions for the good of humanity. People often say that fundamental science is less important, or even that there is not much left to discover. This is completely untrue, and new technologies and solutions cannot arise unless we make progress in understanding better the scientific principles behind them.

Although I work in academia, I have had many important interactions with scientists in industry. Links between fundamental and applied science are vital to translate ideas into the products needed for the modern world.

 

Have you ever had entrepreneurial ventures spring out of your research? If so, how did it happen?

 

Yes, entrepreneurial ventures have arisen out of our research, and indeed I am one of the founders of a company set up to find therapeutic solutions to protein misfolding diseases. Indeed there are increasing opportunities to convert research ideas into products to benefit society. Our venture arose because we realised that our enhanced understanding of our academic work on disorders such as Alzheimer’s disease provided a new opportunity to develop drugs against these currently incurable and highly debilitating conditions.

In the CMD which I mentioned earlier, there is substantial space that is dedicated to transforming ideas and concepts into viable solutions for treating diseases. These activities spring out of the desire to bring our research to the point where it can really benefit humanity.

 

How do you deal with failure, and stay motivated? If there is one thing you could change about you, what would it be?

 

Failure is part of academic research. The important thing is what one learns from failures. On a mundane level, if a research paper is not accepted for publication, we examine the reviewers’ comments in detail and often realise that some more data are needed, or we may have overlooked a particular possibility. By addressing critical comments rather than ignoring them, we can publish a much better paper and sometimes make a new discovery. So, apparent failures can generate success in unexpected ways.

 

However, more generally, working in science means there will always be setbacks and projects which don’t work out. Persistence in scientific research is critical, as the failure of a project to develop as one expects often means that the fundamental principles on which it is based are not correct. Carrying out additional work can result in a real discovery that changes the way we think about a problem. It is incredibly exciting for students to keep on working with a project and then make a real discovery. Dealing with apparent failure is very often the way to eventual success.

 

How important are good advisors, teachers and mentors? How have your contributions as an advisor changed over time?

 

It is very important to try to create an environment where people can do their best and succeed. Towards this aim, good teachers and mentors are crucial. They need to make their students feel that their ideas are important and worth pursuing.

At the CMD, we have a large number of people at different stages of their careers, from faculty members to early career academics, collaborators and students. We encourage everyone to work together  and to support each other. My contribution as an advisor has changed over time as I have become more senior. My students work very independently, but I hope they always know that they have my support when they need it. If they face a problem they cannot solve by themselves, I do my best to help them and we try to overcome the problem together. The CMD also has regular group retreats, where everyone gets together and we all share our ideas and what we are working on. There are also regular research seminars, group meetings, project meetings and one-on-one meetings, which all contribute to the progress of all involved.

I don’t believe that there is a fixed rule about how many times I see my students. I try to help my students, postdocs and colleagues to do the research they want to do, in the way they think best. They know much more about their specific projects then I do. Indeed, they don’t let me into the lab as they think I would wreck all the equipment!

 

What do you think is the next big breakthrough/idea in science?

 

I think it has to be in the treatment of dementia. If nothing is done perhaps ten percent of the world’s population would be affected by neurodegenerative disease. Thus far, there hasn’t been a successful drug for Alzheimer’s disease because of a lack of understanding of its fundamental causes. I feel the next big breakthrough will be the realisation that such a disease is potentially treatable, and is not beyond the power of science. Fifty years ago cancer was often untreatable, but nowadays there are an increasing number of ways to diagnose and treat it effectively.  I am convinced that the same will be true of neurodegenerative diseases, particularly with the increasing power of scientific methodologies and understanding.

Indeed, in the CMD we are working to develop drugs to reduce the risk of the onset of these diseases, much as statins work to reduce the risk of heart disease. And we are also working to develop ways of preventing disease from spreading and progressing if it develops. And perhaps if we are fortunate we will find ways of alleviating the symptoms and restoring sufferers to normal health.

 

More information on Professor Dobson and the Centre for Misfolding Diseases can be found here.

 

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