Current Issue About Edge Past Issues

WHEN PROFESSOR EMERITUS WERNER KALOW returned to Berlin after the Second World War he had job offers from both the department of pathology and the department of pharmacology at his university. Though he was fascinated by both disciplines, his decision to choose pharmacology arose from extraordinary circumstances — the pharmacology department, which had been bombed, was temporarily housed in the American-occupied part of Berlin, while the pathology department remained in the Russian-occupied area of the city.

Almost 60 years later, Kalow is a world-renowned researcher in the field he chose by happenstance, known for bringing pharmacology and genetics together into a subspecialty called pharmacogenetics.

Very early in his career Kalow became involved in a study investigating why some patients who receive a normally safe local anesthetic drug experience fatal side effects. Ultimately he found that some people have a genetic defect that causes variability in the activity of a blood enzyme called cholinesterase, which makes the drug deadly for them while for everyone else it is entirely benign. Spurred on by this knowledge, he dedicated his research to a relatively unexplored area of pharmacology — the study of how genetic variations affect drug metabolism and drug safety.

Kalow worked in Philadelphia after leaving Germany and during those years he met Professor Ken Ferguson, then chair of U of T’s Department of Pharmacology, at a scientific meeting. Ferguson invited him to visit the university in 1951 and later offered him a permanent position. Other than a brief stint in industry, Kalow has been at U of T ever since, serving as chair from 1966 to 1977 and formally retiring in 1982 though he is still very active in the department.

His research initially examined the differences in drug metabolism among individuals but a discovery in 1982 expanded his focus to differences among whole populations. During a study that tested how a group of student volunteers metabolized a sedative drug he noticed a striking variation in some students’ results. “I thought it was a mistake,” he recalls, “until I realized all of the affected students were Chinese.” This discovery led him to publish the first comprehensive
investigations of interethnic differences in drug metabolism.

More recently Kalow has developed a test, now in worldwide use, that uses caffeine metabolism as an indicator of enzyme activity that affects people’s ability to safely take certain drugs. Another ongoing project, one he says he is personally proud of, has eliminated the need for studies using twins to determine how much genetics contribute to variations in drug metabolism.

In 2001, his achievements were honoured when he received the prestigious Killam Prize, a $100,000 award that recognizes outstanding lifetime research contributions in the natural sciences, health sciences and engineering.

At 85, Kalow still makes it to his office almost every day, and will use the Killam Prize money to continue his research. “I’ve worked for 20 years on pension, so I’m very happy to get a little bit of extra money,” he says.

In addition to the Killam, Kalow has received numerous honours for his research achievements including the Canadian Society of Anesthetists’ Research Recognition Award, the American Society for Clinical Pharmacology and Therapeutics’ Oscar B. Hunter Memorial Award in Therapeutics and the Drug Information Association’s Distinguished Career Award. In 1995 the Werner Kalow Lectureship was established at U of T in honour of his contributions to pharmacogenetics and drug safety.

Kalow’s 1962 book, Pharmacogenetics, represented the first systematic study of the emerging subspecialty, heightening its profile and making Kalow a recognized expert in the field. Since then, he has published more than 300 scientific papers and several other books. And while he is one of the most highly cited authors in his field, Kalow is modest about his achievements. “I had some new ideas.”

Denis Grant, chair of pharmacology at U of T and director of the university’s Institute for Drug Research, is quick to laud Kalow’s leadership role. “Werner Kalow is one of the true ‘fathers of pharmacogenetics.’ He has seen the specialty grow from a niche area of scientific research into one of the hottest research fields from the perspectives of both drug development and commercialized genomics.”

Kalow recently served as main editor of Pharmacogenomics, released in May 2001. The subject of this last book is Kalow’s current interest. Knowledge of the human genome, he argues, has transformed the field of pharmacogenetics and will ultimately allow researchers to design drugs that are tailor-made for people’s unique genetic code.

“We hope for individualized medicine and individualized drug choice based on a patient’s genes. So of course we can apply that to abnormal drug effects or to the choice of a drug, which will be most efficient for that patient,” he says. “While pharmacogenetics was most concerned with drug safety, the future will be more concerned with drug efficacy.”

Kalow says he is excited about the new avenues of pharmacological inquiry opened up by genome studies and plans to continue his research as long as he is able. And while he’s officially been retired for 20 years, he says he doesn’t have much time for hobbies. “My work is my hobby!”

University of Toronto Office of the Vice-President, Research and Associate Provost