INTERVIEW

Charles Scriver

Interviewed by Rabiya S. Tuma

Posted October 26, 2001 · Issue 113

Background

Biography
Charles Scriver, winner of this year's ASHG Award for Excellence in Human Genetics Education, describes himself as an almost extinct species, a clinician scientist. A pioneer in the field of modern biochemical genetics, Scriver has lived nearly all of his life in Montreal, where he received both his undergraduate and graduate degrees from McGill University, and has been a faculty member in pediatrics since 1961. He has been a research scientist since the late 1950s, is senior editor of The Metabolic and Molecular Basis of Inherited Disease, and during all of that time has continued to see patients with metabolic disorders, some of whom he has treated for 40 years.

What event led you into research?

I thought I would follow the excellent role model of my parents - that I would be an academic physician who practiced medicine and saw patients. But the world has changed since their days, and my mentors, who were extraordinary people at McGill, suggested that maybe I needed something that would be special and make me attractive if I wanted to be on the faculty at McGill.

I had no idea what that would be. As Yogi Berra says, predictions are difficult, especially with the future.

As a pediatric resident [Harvard's Children's Medical Center], a colleague, Irwin Schafer, and I saw at 1 A.M. on a Sunday morning in the emergency room, a young man, a boy, who had deafness. He was in for viral meningitis. When we did all our own lab work, which is what we did in those days, we found he had hematuria [red blood cells in the urine]. That began the inch-wide, mile-deep examination.

Several months after meeting this young man, I went to England and started working in Charles Dent's laboratory. I learned to do chromatography myself. And I made a discovery. Pure chance. We found that the patient had a disorder of proline metabolism. It was the first patient to ever be discovered with hyperprolinemia.

In one of the really great moments for anybody in science, I can recall the place and the moment when the insight came, which at the time was a totally new concept. They had no animal quarters in those days, so I decided to test the major model organism that I was familiar with. Without the approval or an ethics committee or a six-month review, I arranged with a colleague to infuse me with proline and I would collect the blood and the urine. In my very first experiment on myself, I had support for the hypothesis. So I was very excited and forever after I was hooked on science.

Do you practice medicine at all?

Not in the usual way. In 1960, I came back to McGill as the chief resident in pediatrics. I did not enjoy that lofty appointment as much as I think I would have if I hadn't discovered the joy of science.

I was very blessed with my next major mentor, Alan Ross [chair of pediatrics at McGill], who gave me the appointment as chief resident and my faculty appointment, which I've had ever since. [Ross] recognized that I was not happy doing only clinical work and he allowed me time to go and visit my colleagues at Harvard, to write the paper that described hyperprolinemia. That was the beginning of my career.

In our day, if you were a clinician scientist, [the American Society for Clinical Investigation] was the mountain peak you wanted to be on when you were presenting. By some fluke my abstract got on the plenary session. And I gave this description of a shared transport system discovered through a child with hyperprolinemia, and corroborated through experiments on myself and other people.

How did your colleagues react to the fact that you tested it on yourself?

Nobody cared about that in those days, we were doing it all the time. What they were amused with was the innocence and naivete with which I presented my results to this very sophisticated audience. It was not a very complex talk compared to other talks in the plenary session. But it was interesting and several people came up afterwards and said "Hey that's a whole new idea, transport systems, like enzymes?"

If transporters weren't known, what sparked that idea?

I was lucky enough to read Hal Christianson's review in the Annual Review of Biochemistry on transporter systems. I read it on a train going from Montreal to Edmonton and on to Calgary. There were about half a dozen people working on transport systems at the time. I thought "Oh, this is a good time to get into a narrow field."

I was given a job at McGill in 1961 as Canada's first biochemical geneticist. My chief [Ross] said, "I'll let you do something that no one else is doing at the moment," which is an enormous gift from a mentor. He put me up for a Markle Scholarship, which allowed me five years of protected academic environment.

I should explain also the importance of support like that. I was sent to England on a traveling McLaughlin Fellowship, founded in the early 1950s. I was one of the early people to get one, and it changed my life.

[These days], universities sometimes have their own protection systems. There are competitive fellowships and studentships, provided by societies, like ASHG. In Canada, the Canadian Medical Hall of Fame is announcing awards to six young scientists - the new McLaughlin Fellowships as it were.

I've been describing myself as an almost extinct species, the clinician scientist - people who do clinical work and see patients and what they see drives the next experiment that they do, as I described with the patient Frances.

Why is the clinician scientist becoming an extinct species?

Because the clinician is not protected in the way that I described. There has been a generation of very, very good people who are trained in hard-core biological science, which the medical person has not been trained in correspondingly. Therefore when the clinician scientist comes to write a grant and it goes to a panel that is inhabited by hard-core scientists, they say this guy is innocent, he doesn't compete with these other people.

What was your best experiment?

I have no idea.

I can't answer that because what I observe is an incremental life. Whatever we are celebrating with this award, which I am very grateful for, I think represents continuous committed effort with incremental achievement and growth. A coral reef is made up of millions of tiny organisms all added up together. I don't see any great meteor or sky rocket in what I have been doing, but I do see a lot of interaction, give and take, and sustained effort that ultimately achieved something.

What are the qualities of a successful researcher?

They must be willing to work hard. My joke is that now that I am retired, I'm down to full time. That is one of the things that makes it a full-time career of its own and very hard to fit into a clinical career at the same time.

Imagination, to recognize an interesting observation or hypothesis when you are looking at it.

The other side of all of this about self and career is the relationship between people. I have been blessed with a family that tolerates what I do. I met my wife when I was 15 and I lived close enough to the university that I could be home for supper every night. And everything that I did was with colleagues, wonderful people from all walks of life and a variety of interests. I have very few papers on which my name is first. Most of the papers have two or more names and all of the names on the paper reflect an input, without which it would have been an unsuccessful set of observations, or at least a different paper.

What are your scientific plans for the next five years?

First and foremost, to keep alive and reasonably healthy.

This year I was supposed to prepare a paper on hereditary metabolic diseases and the aging patient. But I decided that what I really wanted to think about was what is the aging process. Why do we age? How do we age and what do we learn from inborn errors of metabolism and that process? I am looking forward to thinking about those things and seeing more activity in that area.

I want to take The Metabolic and Molecular Basis of Inherited Disease and put it on the Web. It will become a continuous book on the Web and updateable, allowing new material to be introduced.

The third thing is the treatment of phenylketonuria (PKU). It is the flagship illustration that you can bother about genetic disease and you can do something about it. When I graduated from medical school there was no teaching about genetic diseases because it was something you could do nothing about. The treatment of PKU transformed that outlook.