September 15, 2023 | PERSPECTIVES, NEWS | Interview by Konoha Tomono Duval
Before coming to CC, Professor Amy Dounay spent eight years as a medicinal chemist at the pharmaceutical company Pfizer. While there, she led several chemistry teams searching for psychiatric and neurodegenerative drugs. At CC, she has studied African Sleeping Sickness, antibiotics, and new approaches to teaching chemistry. With Third Week of Organic Chemistry 1 on the horizon, we met to talk about drug discovery, facing decade-long projects and the challenges of science in the pharmaceutical industry.
Back and Forth from Chemistry to Biology
When people think about medicine and pharmaceuticals, many might first picture biology and medical school. How does chemistry fit into the drug discovery process?
“Drug discovery teams have a lot of specialists working together. As a medicinal chemist, my role was to help design the structure of molecules and then synthesize the ones that could be potential future drugs. These are usually large teams of chemists, doing design and synthesis [of the molecules] as well as computational chemists who use molecular models to help decide what a good structure might be.
We make these compounds, and we hand them off to the biologists for testing. They’ll see if [the molecules] have the desired pharmacological activity. And then we’ll feed it back into our design to address any shortcomings.
Among the biologists, there are pharmacologists who help us figure out what biochemical pathways, what receptors or what enzymes might be good targets for us to interfere with or activate. It’s a pharmacologist trying to find out what are the right biological targets. And then the chemists figure out what are the right small molecules that can interact with that target.
The part that I worked on would be called the Discovery Stage. Discovery is preclinical, so you test the compounds before you put them into humans. This can last anywhere from a few years to a couple of decades, depending on how successful [your research] is and how well understood the biological processes are. There are ongoing projects like Alzheimer’s disease where we still don’t really understand what it takes to have an effective Alzheimer’s drug.”
Science and Profit in the Drug Industry
How did you feel, going into a problem where you might not see results for maybe a decade?
“What you have to anticipate working on these projects is that many people spend their entire career and never work on a project that produces a successful drug. That doesn’t mean that it wasn’t useful and productive science.
What I experienced a number of times was that the company would make business decisions to discontinue a project even when the science was successful and moving forward. They’d say this project was interesting but we don’t think it will have a big enough payoff from the business side. Having been through that cycle a few times, you realize that that’s part of how the business operates, but it is definitely a point of frustration as a scientist.”
Once you’d moved out of drug discovery [at Pfizer], did your options for research open up?
“Definitely. In academia, that’s where there’s much more opportunity to work on other things. When I first started here, I was working on African Sleeping Sickness. There wasn’t a big investment from pharma companies, but there’s a big medical need. More recently, I’ve been working on antibiotic drug discovery. Again, there’s a big medical need, but not a huge industry investment.”
Buttons and Failure
Do you have any favorite books on chemistry?
“One of them is Napoleon’s Buttons [Napoleon’s Buttons: How 17 Molecules Changed History, by Penny Le Couteur and Jay Burreson]. Each chapter talks about a different molecule, and it asks how its structure works in each case.
Another is Failure [Failure: Why Science is So Successful, by Stuart Firestein]. It gets to this idea, that the whole drug discovery paradigm is built on the premise that most projects are going to fail. But a few things will work, and you need that mindset if you are going into the industry.”
And the few that succeed are worth it for all of those that fail?
“Yes, and there’s learning that happens in the failures. Even if you spend a whole career in drug discovery without a successful drug on the market, you’ve still contributed to helping advance the science.”