Hal Kohn tells Joanne Thomson about investigating the unknown and the joy experienced when its secrets are revealed 

Harold (Hal) Kohn is Kenan Professor of Medicinal Chemistry at the University of North Carolina, Chapel Hill, US. His research group examines the mechanism of action of clinically approved and emerging drug candidates and designs and synthesises new therapeutic agents. Hal is a member of the Natural Product Reports editorial Board.

What inspired you to become a scientist? 

It was a combination of factors. Firstly, I was drawn to the order and logic that I found in chemistry. For me, this was particularly true of organic chemistry. I found that organic and bioorganic transformations could often be explained using a set of basic principles that made sense and, most importantly, that permitted predictions. This was empowering. A second factor was the unknown. So much in science has not been determined and each new finding typically raises more probing and relevant questions. Finally, science is very humbling. Often just when I believe I've 'got it,' the next experiment provides something new that challenges my notions. This has been particularly true with our studies at the chemistry-biology interface. Realising that your knowledge set is incomplete is a powerful catalyst to redouble your energies. Then you experience the joy of 'getting it' after all.

Why did you choose to focus on medicinal chemistry in particular? 

It was an evolution. My initial interests were in organic and bioorganic transformations, and I am particularly grateful to Professors Roy Olofson, Steve Benkovic and Ron Breslow for instilling an appreciation of reaction mechanisms. An earlier favourable undergraduate research opportunity in Raymond Counsell's medicinal chemistry laboratory at the University of Michigan also had a strong impact on my path. My own research group began to shift its focus when we began to consider the mechanism of action of the mitomycins, which are anticancer agents. After those studies, we examined other anticancer agents and such antibiotics as bicyclomycin. We found that basic studies on drug function permitted us to use our knowledge in mechanistic organic chemistry while gaining knowledge in biochemistry, pharmacology, and molecular biology.

What are you working on at the moment? 

Our current efforts focus on identifying the target (or targets) of lacosamide, a small molecule discovered in our lab. Lacosamide (Vimpat®) has been submitted, under the sponsorship of UCB Pharma, for regulatory approval in Europe and the United States for the treatment of epilepsy and diabetic neuropathy. Scientists have not fully determined exactly how lacosamide works, and only recently has information been reported on the pathways for its function. My laboratory, in collaboration with Professor Rihe Liu here at the University of North Carolina, has constructed a general protocol to search the brain proteome for the lacosamide targets. If successful, we believe that we can use this approach to study other medicinal agents. We also have an active program in drug discovery

In your view, what has been the most significant breakthrough in drug discovery in the last century?

Hard question. There have been so many important advances. I'd have to say, though, it has been the many research tools that allow us to identify and characterise macromolecular targets. There are numerous procedures in molecular biology, bioanalytical chemistry and spectroscopy that allow us to search and validate targets, thereby providing critical information of how drugs interact with their cognate receptors.

And which cure would you love to discover tomorrow? 

Candidly, any! To imagine developing a cure for a disease or disorder is simply breathtaking. I'd say most scientists would be proud to make such a contribution. My research is stimulated by understanding the drug-receptor interaction and structures, rather than the specific disease state. Having said this, our efforts with lacosamide have spurred additional studies on controlling (rather than curing) a series of neurological disorders.

You joined the Natural Product Reports editorial board earlier this year. What do you hope to bring to the journal? 

The evolution of science and the power of contemporary methods have required chemists to think on multiple levels, often with a wider perspective than in the past. NPR has had a wonderful reputation within the community and has made efforts to provide focused articles that bridge chemistry and pharmacology. I hope to contribute to these efforts and specifically bring to the readership articles that blend the chemistry of natural products and their pharmacology.

What do you do in your spare time? 

While in Chapel Hill, my garden and particularly my roses demand my attention. I enjoy reading, and my wife and I are basketball junkies, which is not unique at Carolina. Our children are spread throughout the States so we try to visit them and their families as often as we can.

What would you be if you weren't a scientist? 

I find history and politics mesmerising, so the thought of being involved in policy decisions has always been appealing.