Interview with Sir Philip Cohen

by David Bradley

Position: Royal Society Research Professor; Director, Wellcome Trust

Biography Born July 22, 1945, Edgware, Middlesex, England

B.Sc. at University College, London; 1963-1966. Ph.D. at UCL under Michael Rosemeyer, 1966-1969. Postdoc with Edmond Fisher, Seattle, Washington, as a Science Research Council NATO fellow. Recent awards: The 1999 Pfizer Award for Innovative Science, Honorary D.Sc. from the University of Strathclyde. Named by the Institute of Scientific Information as the third most highly cited UK-based scientist of the 1990s.

Research interests The reversible phosphorylation of proteins catalyzed by protein kinases and protein phosphatases is the principal mechanism by which intracellular functions are regulated by extracellular signals. A third of all proteins in mammalian cells are now thought to contain covalently bound phosphate, and protein kinases, protein phosphatases, and their regulatory subunits are likely to account for about 3 percent of all human gene products.

Abnormal protein phosphorylation is a cause or consequence of major diseases, such as cancer, diabetes, and rheumatoid arthritis, and an increasing number of hereditary disorders resulting from mutations in the genes encoding particular protein kinases and phosphatases. Some of the major drugs that will be developed over the next few decades are likely to be specific inhibitors of these enzymes. For example, cyclosporin, the drug that prevents tissue rejection after organ transplantation, acts as an immunosuppressant by inhibiting a calcium-dependent protein phosphatase that was identified and characterized in my laboratory in the early 1980s. Several inhibitors of receptor tyrosine kinases are well advanced in human clinical trials for the treatment of different cancers.

What was the seminal event that pushed you into your line of research?

There were two things. The first was going to my first-ever scientific conference as a Ph.D. student, which was held in a monastery on the island of St. Georgio off the Venetian waterfront, and hearing Edmond Fisher (a 1992 Nobelist) give three lectures on proteins. The second key event was during my third year as a graduate student at University College, London, when Bill Whelan from Miami offered to write a letter of support for me to Fisher, whom he knew personally. It took four attempts to get an acceptance from Fisher, though!

What do you enjoy about your work?

The excitement of discovering something no one has discovered before. I also get a kick from the contribution the life sciences here are making to the local economy. When I came to the department 28 years ago, there were about 30 to 40 people in the field of biomedical science. There are some 1,600 today, which has completely turned around the whole makeup of the town.

Are there aspects you would change?

If I had the money (and the space), I would recruit a lot more support staff to whom I could delegate the major administrative responsibilities.

What was your best experiment?

I was doing bench work up until about ten years ago, so I would think my discovery of the calcium-binding protein calmodulin as one of the protein components of a protein-kinase involved in glycogen metabolism. It was something that had been missed by many prominent researchers simply because of technical flaws in their experiments that didn't allow for the small size of the protein.

How did the experience increase your maturity as a scientist?

The things you find most exciting are those that are unexpected. A lot of people miss key discoveries because they are aiming for a goal rigidly and fail to see the little discoveries on the side as they're heading for that goal. The ability to spot the unexpected is really what science is all about. That particular discovery helped me realize this.

Who was your most influential teacher?

Edmond Fisher, undoubtedly. In the 1950s, he and Edwin Krebs really created this whole area of research. He essentially taught me how to discover something exciting.

How would you best like to be remembered?

I hope I'm too young to answer this question. Although it would be nice to be remembered for something I am yet to discover - the pathway that led to a drug to replace insulin for treating diabetes, perhaps.

What is your advice to a Ph.D. student or a medical student entering research?

Don't go into it unless you're really excited about discovery and unless you're really driven to do this above all else. It has to be a hobby!

In what areas do you think you need advice yourself?

I need to be more diplomatic and patient. I don't suffer fools gladly. When I see people frittering their time away - Ph.D. students, for instance, who think it's okay to take six weeks off a year and then wonder why they need an extra six months to complete and write up their dissertation - it annoys me.

What would you be if not a scientist?

Many moons ago, I might have hoped to have been a chess or cricket professional. Although these days I would probably be a restaurateur.

Which scientist from history would you like to meet?

American physiologist Earl W. Sutherland, Jr., who started the whole field of cell signaling research, and whom I am sad to have missed meeting.

What would you ask him?

He wrote a wonderful autobiography that answers many questions. But I would probably ask him why he started drinking because he killed himself through cirrhosis of the liver. You'd think someone that successful somehow wouldn't do that.

What was the greatest scientific discovery of the last century?

It would have to be not the discovery of the structure of DNA, but the discovery by Avery that DNA is the genetic material. The Watson-Crick work was just the icing on the cake and may have been worked out by others fairly soon.

What will be the great discoveries of this century?

It is impossible to predict, but the basis of memory and behavior and how the brain works still requires some big insight. I also think we are really going to see many really specific drugs being developed soon against proteins in cell signaling processes.

How has the Internet influenced what you do?

You may be surprised to learn that I have never used it. I rely on my three secretaries to extract anything I might want from it for me. I have never yet sent an email directly. My secretaries retrieve and filter all my incoming emails. I simply do not want to see memos from the department safety officer and the like.