David Uehling

Briefly describe your job.

My job is to discover compounds that work for cancer. The hypothesis is that if you affect a biological target with a small molecule, it will positively impact the growth of the cancer cell. I design compounds that fit into the “lock” of the protein target; the better the fit is, the better we think the modulation of the target will be.

What education and work experience is required for your job?

Medicinal chemists have a basic foundation in organic chemistry as an undergraduate degree. Most of us then get a master's degree or PhD in synthetic organic chemistry. We learn how to synthesize complicated organic molecules. We do many different types of reactions, but we had our training in all the different techniques we use on a daily basis in school. Even though instrumentation becomes more sophisticated and the methods become more efficient, we basically still use the same types of techniques and principles.

For example, we have instruments that perform silica gel chromatography, which is used to purify compounds. When I was in grad school, we did this all manually. Nowadays, we have instruments that we can use to purify compounds. We can load a machine, and walk away and do something else, which makes it more efficient, but the basic principle is still the same.

Why did you choose this career?

I chose to be a medicinal chemist because I like to make compounds, but I like to make them for a specific reason: to help human health. So I thought, not only is this a job that is going to be enjoyable, it's going to force me to learn all the time. When you're a medicinal chemist, you need to learn a lot of biology as well as chemistry. We're always on a steep learning curve. To me, it's always fun and satisfying to be able to learn all these things and be able to talk to biologists. And of course, helping people is always the ultimate goal.

What is your favourite part of this job?

Medicinal chemists get to design compounds. We get a lot of satisfaction from making compounds or a new substance; it's a fun part of the job. What makes medicinal chemistry as a general field is that we put our compounds into biologists' hands and let them test the compounds in various biological assays. We get data back that tells us whether or not our compound is doing what we intended it to do. Getting that feedback from the biologists makes this job very special and enjoyable. When you see compounds working well, when you get more and more potency, it's a success for all the chemists.

We work in a very interdisciplinary environment, with focus on teamwork. Usually the chemists divide up a lead molecule to work on different parts to improve. When we get good data back, everyone gets very excited.

Please describe a typical workday.

Typically, chemists will come into their office area and receive data about their compounds. They'll think about what compounds they need to make that day, and how to make them. They'll go into their lab, get their chemicals together, and start running reactions. A lot of it is tedious; it's not easily automated, even though our equipment is getting better and better. A typical day includes nursing a reaction along, then seeing if the reaction worked, and then trying to isolate the product. Once we do that, chemists characterize the product and decide whether or not it is what they wanted.

There are also a lot of meetings we have to attend. I, personally, attend a lot of meetings with collaborators we're working with. They have various ideas and projects they want to work with us on, so we need to evaluate whether or not we think the projects would be good for us to work on.

Chemists also need to read a lot of literature in order to understand the projects we work on.

What advice would you give to high school or undergraduate students who are interested in this career?

Take lots of science courses. Get a strong background, but don't become too specialized too quickly. If you have a chemistry degree, that can take you in a lot of possible directions. You have many options for many different branches of science in the future.

What kind of challenges are there in your job?

Making the compounds is the first challenge. When you decide to make a compound, you have to read the literature, synthesize it, and then make it. Often, the first time we try it doesn't work, so we have to go back. Then the challenge is figuring out whether or not the compounds will be active in our tests: first the enzyme assays and then seeing if it crosses the cell membrane. The next challenge is finding whether or not it can get into an animal and whether or not it has good pharmacokinetics. A huge challenge is finding out whether or not the compounds will be safe. Sometimes, the compound will be toxic to the animals, and we can't know until we test it on the animals.

Every step of the way, we need to decide how far back we should go to improve the compound. A constraint of resources is also a huge challenge.

Approximately how long does it take for a team to develop a compound that passes all of these tests and is developed into a drug humans can use?

If you have a project where the target is well validated, the team could be expected to come up with a suitable compound every two to three years. That's just after the project has become strongly validated. Add another one to two years to get the project off the ground. Conservatively speaking, maybe every four to five years for a compound to get to the clinical testing phase.

The standard attrition rate for a compound that is tested in humans that actually becomes a drug is around five to 10 per cent. Maybe around one out of 20 compounds becomes a marketed drug.

What related areas are there in this field?

Organic chemistry is about problem solving. People who are trained in organic chemistry or synthetic organic chemistry can branch off into biology or biochemistry. Chemistry is a more fundamental science; we always say that it's much easier for a chemist to learn and study biology than it is for a biologist to learn chemistry. Once you become a strong synthetic chemist, you could go into biology, biochemistry, or even medicine, and do very well.

Building a molecule is sort of like solving a puzzle. Having that problem-solving training would be useful for many different jobs.

How do you feel your job is contributing to the battle against cancer?

Medicinal chemists are absolutely necessary in the battle against cancer. One big part of cancer research is trying to understand how to prevent it, but there are many cancers that can't be prevented. For those people, there have to be new drugs that are better than the current drugs. We are the ones who investigate these drugs.

Are there any resources that you would direct students who are interested in your career to?

The best resources are talking to people who work for drug companies and people who have been a part of successful projects. People give lectures, or they also have stories on the Internet. You can look at well known drugs that have been discovered for cancer in the last 10 years, and do research on how they were discovered.