From Telomeres to the Origins of Life

It was somewhat of a side project. Before I began working on telomeres,I’d been studying DNA recombination. If a chromosome is broken,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 ageing. Subsequently,it’s turned out that in almost all cancers,telomerase is turned on so those cells grow indefinitely.

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.

How far have you gotten?

Maybe I can say we’re halfway there. We think that a primitive cell has to have two parts. First,it has to have a cell membrane that can be a boundary between itself and the rest of the earth. And then there has to be some genetic material,which has to perform some function that’s useful for the cell and get replicated to be inherited. The part we’ve come to understand reasonably well is the membrane part. The genetic material is the harder problem; the chemistry is just more complicated. The puzzle has been understanding how a molecule like RNA can get replicated before there were enzymes and all this fancy biological stuff,protein machinery,that we have now in our cells.

You’ve now been working on this problem for a quarter of a century. Do you ever grow weary of it?

No. No. Because this isn’t a monolithic question where there’s nothing interesting until you get to the end. In fact,the question breaks down into maybe a dozen smaller questions. Each has interesting parts. Eventually it will all fit together.

For instance,we’ve made progress on the question of how you make a primitive cell membrane. Others had showed how a common clay mineral,montmorillonite,might have played a role in helping to make RNA. Our lab showed how it could help membranes to form and bring the RNA into the membrane.