Peter Nowell, the Gaylord Harnwell Professor of Pathology and Laboratory Medicine, doesn't take himself too seriously. That casual attitude perhaps explains how he was able to do the research that last September won him the Lasker Award, American medicine's most prestigious honor.
The Lasker Award-winning researcher believes that serendipity can still be an important research tool.
Photo by Candace diCarlo
Nowell had not set out to deliberately discover the "Philadelphia chromosome," a genetic defect that plays a key role in the development of a common form of leukemia. Instead - as is the case with a great number of significant discoveries - he was just experimenting with a new technique for preparing cancerous cells for examination in the late 1950s when he and a partner stumbled across the defective chromosome.
Since that time, American medicine has gotten a great deal more sophisticated and medical researchers increasingly specialized. But even in this environment, Nowell, who shared the award with two others, including adjunct faculty member Alfred G. Knudson Jr., a geneticist at Fox Chase Medical Center, still feels that there is room for the unexpected to play a role in advancing medical knowledge.
Q. What was the atmosphere like when you realized that you had discovered a chromosome that could be traced to the development of leukemia?
A. Well, the atmosphere was not particularly excited. I joined this department in the middle '50s, and [the researchers here] were all working on some aspects of cancer, but in those days, we really knew nothing about the fundamental nature of cancer.
I was looking at some leukemic cells, inadvertently treated them so we could see the chromosomes and see them dividing, and I knew nothing about that.... And then I hooked up with this graduate student at Fox Chase [Cancer Center], David Hungerford, who was trying to do a thesis on human chromosomes and didn't have any material.
He spotted this little chromosome in one form of [chronic] leukemia - we had already looked at some of the acute forms and hadn't seen anything that jumped out. In this case, every cell had it, and it was there in every typical case [of the disease]. So that argued both for one, a genetic change as being important in the development of this form of cancer, and two, that tumors might indeed arise from a single cell in which such a change occurred.
Now, a lot of people didn't want to believe that at the time, because they preferred that cancer should result from changes that did not involve the genetic material of the cell, because it would be easier to reverse - you could just manipulate the environment and make the cell grow normally. So a lot of people were willing to dismiss this as something of an epiphenomenon-
Q. A freak of nature?
A. Yeah, maybe it was just something that occurred as this tumor was developing, and it really didn't have a critical role in the initiation of the tumor.... And I wasn't particularly concerned, because it made sense to me, and so I just kept on working.
Q. In other words, few people accepted your theory until the technology for analyzing chromosome and gene structure improved?
A. Yes, that's true. [Our research] was published in 1960, and it was 10 years [after that] before some techniques were developed...which permitted people to identify individual chromosomes and actually see much smaller changes when a piece has been moved from one place to another.
And then we had to wait another 10 years, until around 1980, when the people who thought all tumors were due to viruses, which was wrong, had developed the molecular techniques that then allowed a lot of people to go and look at these chromosome changes that we could see under a light microscope and actually pull out the specific genes involved.
That was the good news. The bad news was that as we and others did this over the next decade, it turned out that there were 20 or 30 or 50 different genes just producing different kinds of leukemia.
Q. So it looks like cancer researchers will have plenty of work to keep them busy.
A. I think even more importantly, it suggests things positive for the future of the population as a whole. We now have all this information, and cancer researchers, whether they're using gene-therapy approaches or immunological approaches or other kinds of chemical approaches, will be able to target this gene or that gene and actually better control this kind of cancer or that kind.
The downside is that it's going to be incremental, it's not going to be one single treatment that's going to do all cancer. So I think what's going to happen over the next several decades is that you're going to see incremental improvement in our ability to diagnose and control different kinds of cancer.
Q. Would you say that having a sense of humor helps speed your work along?
A. I would say that having a sense of humor helps survival in general. Unfortunately, to make it today with the multiple bureaucratic and other pressures, you have to have some of that [serious intensity and compulsive focus]. Fortunately, I [began] in an era when it was a relaxed, easy environment. I was lucky early and had some serendipitous observations, so in that sense, it was easier for me to maintain a sense of humor. But an awful lot of the successful researchers today are extremely narrow, extremely focused.
Q. You mean it's not possible anymore to stumble across something?
A. Oh, it still is. I think this is something that we all recognize, that serendipity plays a major role in biological progress. That's why I tell people who are starting in the game to keep at least three or four different lines of investigation going, because the one that pays off is the one you don't think will. As my old chief used to say, the real trick is to keep going out on different limbs and then decide how far out to go before you go back to the trunk of the tree, which is the main area you're interested in.
Q. What other advice do you offer researchers starting out?
A. I think particularly in the context of this campus, I certainly advise people to establish linkages with other labs. This is why I've been able to do as much as I have with a very small laboratory and very limited skills. Again, it's one of the ways of keeping multiple options open and multiple lines going so that something works.
Q. So I take it you regard the institutional initiatives to establish interdisciplinary institutes across schools as a good thing?
A. Absolutely. As an excuse to get out of the chairmanship of pathology, I did take on the leadership of the Cancer Center initially for a couple of years, and then jumped out of that too. But I think that was a very good model, which has been built on. I think this new Abramson unit within the Cancer Center is just going to reinforce and expand on it.
Q. What was your own reaction to the news of the Lasker Award?
A. I was surprised, because I thought I was past it. I thought they were more appropriately giving most of the awards these days to people using the newer techniques, but it was pleasant to see this recognized. And for me, it was really icing on the cake, because I've had an extraordinarily satisfying, enjoyable career. And I hope that the younger people can find their careers half as enjoyable.
Originally published on January 28, 1999