How did you get interested in Medicinal Chemistry?
The power of chemistry to create novel matter always fascinated me. As a kid, I witnessed an epilepsy patient having a seizure while on vacation in Spain, and that left a lasting impression on me. When I realized that new molecules might have the power to heal, I became fascinated in the potential of medicinal chemistry.
Where and when did you obtain your PhD diploma?
I obtained my PhD in 1990, in Prof. Pierre Vogel’s group in Lausanne, Switzerland. I developed total syntheses of rare sugars: Fun chemistry, intellectually challenging, and that prepared me well for the next step in my career.
Where did you have your postdoc position?
With Prof. Peter Schultz, at Affymax in Palo Alto, California. It was a start-up company by then, and I had a great time. We were surrounded by brilliant people, pursuing new ideas by mixing techniques of biology and chemistry with printing technology. What a lesson it was! The company was at the research edge in combinatorial libraries, which was a fancy new development at that time: printing DNA on chips, or using phage display to produce gigantic peptide libraries created fascinating opportunities. My project was to develop catalytic antibodies to lower the energy of activation of thermodynamically disfavoured reactions. That was an ambitious goal, and despite all efforts, impossible reactions remained... impossible.
Where do you work at the moment and what is your current position?
I work in the Novartis Institute for Biomedical Research in Basel, Switzerland, and have a double role: leading a research group, and serving as president of both EFMC and of the Division of Medicinal Chemistry and Chemical Biology of the Swiss Chemical Society.
Novartis is a great company to work for, science-oriented and supportive of the scientific community in general.
What are your current research interests?
My research group is developing clinical imaging agents to facilitate the development of our drug candidates. Imaging helps with diagnosis and monitoring of disease progression, but also answering questions that cannot be easily addressed otherwise, such as: Does a drug reach its target and occupy it long enough to have an effect? What is the most effective and safe clinical dose? This is very helpful information for our clinicians, and when it helps bring a drug faster to the patients, it is well worth the effort. There is also an artistic dimension to the images we generate, and that makes it even more interesting.
What do you like most in your job?
Its intellectual diversity, the people I work with, and the fact that I will never know everything and must keep learning all the time.
What do you consider your biggest achievement in your scientific carrier?
When we tested our first development compound in treatment-resistant epilepsy patients and... yes, it worked! There is no bigger satisfaction than seeing years of research transform into a therapy. It feels like a miracle happened when a new molecule created in a medicinal chemistry lab proves to work in the clinic and restore health.
Which scientist do you admire the most and why?
I still remember reading, as a child, the “Stories of Uncle Paul”, a cartoon that introduced me to the life of Alexander Fleming and Louis Pasteur, and many other wonderful scientists and admirable minds. I loved these stories, and I suspect this is one reason I became interested in science. There are of course many admirable scientists, past and present. They all have in common dedication, a sense of innovation, curiosity and an acute sense of observation, and a knack for finding gold nuggets in mountains of data.
Which field of medicinal chemistry do you consider the most promising in the future?
This is an interesting question, and my belief is that medicinal chemistry will become even more diverse. Low molecular weight compounds will remain a major source of new treatments in the future. Other areas, including synthetically optimized biologics, will expand our options. There is much to gain by exploiting the chemical biology – medicinal chemistry continuum. Better chemical tools will help improve target selection; new modalities will allow developing novel therapeutic approaches. Imagination and innovation should have no limits.
What would you guess to be the next major breakthrough in medicinal chemistry?
It is hard to say, as the claims around the potential impact of new techniques in drug discovery are often exaggerated. I tend to believe that innovation is incremental and that we will continue to develop the power of medicinal chemistry by constantly challenging ourselves, exploring new technologies and ideas. Over the years, multiple innovations have contributed to this progress, such as computer-assisted drug discovery, new synthetic methods and screening technologies, chemically optimized biologics or target identification technologies. The human body is complex and we need a broad variety of approaches. The next major breakthrough is always a drug that shows a real impact on patient’s lives, whatever form it takes.
What would you like to ask from other medicinal chemists?
To stay passionate, curious and creative, to be supportive of their team and community, to trust themselves and have fun in research, but never forget the ultimate objective of what we do: create tools to improve our understanding of disease, and drugs to help people live a better and healthier life. This is something we can really be proud of.