From Telomeres to the Origins of Life
NOBELIST Jack Szostak shifted his focus from telomeres to the origins of life.
By CLAUDIA DREIFUS, Published: October 17, 2011
BOSTON — The October night before he learned he had won the 2009 Nobel Prize in medicine, the biochemical researcher Jack W. Szostak says he slept like a log.
“I wasn’t going to lose a night’s sleep because of work I’d done in the 1980s,” Dr. Szostak, 58, said with a laugh during a recent two-hour interview at his laboratory at Massachusetts General Hospital. “It was old work.”
That “old work,” for which he had already won the Lasker Prize, was to help identify the nature and biochemistry of telomeres, the tips at the ends of chromosomes. Understanding them may be the key to unlocking the mysteries of cancer and cell aging. An edited version of our conversation follows.
Was telomere research your life’s work?
It was somewhat of a side project. Before I began working on telomeres, I’d been studying DNA recombination. What do cells do when they see a broken piece of DNA? Cells don’t like such breaks. They’ll do pretty much anything they can to fix things up. If a chromosome is broken, the cells will repair the break using an intact chromosome. That process is called recombination. And that’s what I was looking at.
Now, telomeres: They are the ends of chromosomes, the caps, and they don’t recombine. One day in 1980, I heard Liz [his colleague Elizabeth H. Blackburn] at a conference talking about how telomeres behaved. It was the contrast between the DNA she was working with and the material I was studying that caught my attention. I wanted to understand what was going on. So I wrote Liz right afterward.
What did you discover together?
We figured out what was going on at normal chromosome ends. We figured out the underlying biochemistry and showed that lots of different organisms use that biochemistry. We figured out that there was an enzyme, telomerase, that adds DNA to the ends of chromosomes to balance out the DNA that is naturally lost as cells grow.
Afterward, as people in the field began to see how important it was, telomere research just took off. It became clear that the loss of DNA from telomeres might have something to do with aging. Subsequently, it’s turned out that in almost all cancers, telomerase is turned on so those cells grow indefinitely. Of course, it’s very nice that work we did so long ago turned out to be important! But the truth is my work has gone off in several different directions.
What do you study now?
The origins of life. In my lab, we’re interested in the transition from chemistry to early biology on the early earth. Let’s go back to the early earth — let’s say probably some time within the first 500 million years. And let’s say the right chemistry that would make the building blocks of life has happened and you have the right molecules with which you can spark life. How did those chemicals get together and act something like a cell? You want something that can grow and divide and, most importantly, exhibit Darwinian evolution. The way that we study that is by trying to make it happen in the lab. We take simple chemicals and put them together in the right way. And we’re trying to build a very, very simple cell that might look like something that might have developed spontaneously on the early earth. (See also: http://tinyurl.com/3rkhk5j)