John “Iain” Glen
The Albert and Mary Lasker Foundation
The Albert and Mary Lasker Foundation has awarded its three annual prizes, regarded as the United States’s most prestigious biomedical research awards, to four researchers in fields including genetics and anesthetic drug development. The Laskers often precede a Nobel Prize in Physiology or Medicine: Since the awards were founded in 1945, 87 Lasker laureates have later gotten the call from Stockholm.
The basic research prize is shared by Michael Grunstein of the University of California, Los Angeles, and C. David Allis of The Rockefeller University in New York City, who investigated the histone, once considered to be inert packing material for DNA. It is now recognized as an essential component in gene regulation.
Joan Argetsinger Steitz of Yale University won the special prize for her discoveries in RNA biology, as well as her work in mentoring and advocating for women in science.
John “Iain” Glen, a Scottish veterinary-anesthesiologist now retired from AstraZeneca, the biopharmaceutical company headquartered in Cambridge, U.K., won the clinical award for development of propofol. One of the most widely used drugs for inducing anesthesia, propofol is administered some 60 million times per year in the United States.
The laureates will receive their prizes and honorariums of $250,000 for each category at a ceremony in New York City on 21 September.
Science chatted with Glen about winning the Lasker, the decadelong journey to develop propofol, and how testing the drug involved mice balancing on tightropes. This interview has been edited for clarity and brevity.
Q: How did you go from growing up on a small farm in Scotland to developing a new drug for anesthesia?
A: When I was growing up, I helped out in the fields and with the animals—cows, pigs, sheep, hens. I was always quite keen on working alongside animals. My first career choice was to be a farmer, but our farm was too small for me to make a living. So, I went after my second choice, veterinary medicine. I studied at Glasgow University, became a practicing animal surgeon, then in 1968 I became the first person in the U.K. to earn a diploma in veterinary anesthesia.
Q: When did you make the switch to studying anesthesia drugs for humans?
A: One day, I saw an ad in the paper. What was then called Imperial Chemical Industries was looking for a veterinary or medical anesthetist to join their team looking for new drugs. They wanted someone who knew how anesthetics affected animals to help them run trials with lab animals and be able to understand how [the drugs] might translate into affecting humans. Many species have the same kind of broad, physical reactions to anesthetics.
Q: Where did the idea of using propofol as an anesthesia-inducing agent come from?
A: There’s a Catch-22 when it comes to anesthetics. In order for a drug to get into the brain, it needs to be a fat-soluble compound. But if a compound is fat-soluble, then it becomes very difficult to get it into water-based solutions that can be injected into the veins. Fortunately, in the early 1970s, a technique was developed to combine these fat-soluble compounds with a chemical called a surfactant to get them into water. This allowed us to go back and look through all the promising compounds we’d previously passed over because they weren’t water-soluble. One of those was propofol.
Q: How did you know it was the right compound for the job?
A: We saw propofol as having the most attractive effects—it was potent, it took effect quickly, and it didn’t cause tissue damage like other drugs being used at the time. Plus, we would do a series of animal tests for each compound: first mice, then rabbits, then cats, and then sometimes pigs or monkeys. I remember knowing it was special when I saw how quickly the animals recovered after they woke up. A whole pen of pigs could be out cold one moment, and then digging into their food the next. We had mice walking on little rods like tightropes, and they regained their balance 3 minutes after waking up from propofol.
Q: How did you make sure propofol was safe to use in humans?
A: For each new formulation, we would do pharmacology and toxicology studies in animals, and then we would do several rounds of clinical trials in patients. It took us four different formulations and 13 years before we developed a drug that was safe and could be sold on the market.
Q: Did any of the roadblocks make you feel like giving up?
A: Our clinical trials with the first formula we tested weren’t very successful. Our division had a vote on whether or not to shut down the project altogether. Luckily, we voted five to four to continue working on propofol. And at one point, management was trying to push a formula out to market too early, and I knew it would be likely to cause an anaphylactic reaction in patients. I was very disappointed by that decision. The negative reactions came out in clinical trials anyway, so they weren’t able to get that version out the door.
Q: Propofol has been on the market for almost 30 years. How does it feel getting the award now?
A: It’s quite surprising. I was delighted when I got the call. But so many people worked on the drug, and so many anesthesiologists are working with it every day to treat patients, it really feels like a big team effort. I almost feel like the drug should be getting the award, not me.
Q: You call yourself a “drug hunter.” What kind of skills and personality to do you need to do that work?
A: You need tenacity. Drug hunting can be quite a lonely business. It’s like when you’re plowing the first furrow in a big, stony field. You can feel quite lonely and hopeless when you’re doing it, but if you plant enough seeds, sometimes you end up with a bountiful harvest.