One on one with… Jan Karlseder
Jan Karlseder, holder of Salk's Donald and Darlene Shiley Chair, studies the complex relationship between aging and telomeres, the protective ends of chromosomes, as well as such aging-related diseases as cancer.
A professor in Salk's Molecular and Cell Biology Laboratory, Karlseder, along with his team, has discovered that the relationship between telomeres and cancer extends much further than previously believed. Their research has explained the process by which a class of anti-cancer drugs known as mitotic inhibitors kills cells: exposure to mitotic inhibitors causes telomeres to lose their protective function, and the cells respond with stress signals that eventually lead to the death of cancer cells. Karlseder believes that continued research into the telomeres' functions within cells will lead to an ability to influence the aging process and, as a result, to the restriction of cancer cell growth.
A recent discussion with Karlseder reveals how, in the lab as well as his personal life, he pursues "the bigger picture" by addressing the smallest details.
Your grandfather was a scientist in Austria. Did that influence your decision to go into science?
Yes, definitely. He was a botanist who studied alpine plants. He used to take me and my brother into the forest and tell us about all the plants. It instilled in us a curiosity about the natural world, and both my brother and I still love the outdoors. It also gave us a do-it-yourself mentality. My brother, who still lives in Austria, is a serious mushroom hunter and brews his own schnapps. The schnapps varieties are actually really good.
Your grandfather lived a long, healthy life and stayed active until the very end. Why do some people get so lucky?
These things are very circumstantial. Good genes, probably. He didn't exercise rigorously, but he stayed active walking and gardening. One thing about my grandfather was that stress was unknown to him. He had the attitude that if something couldn't get done today, it could wait until tomorrow. Nearly every day, he drank a glass of the local white wine, for which that area of Austria is famous. But really, it's impossible to know.
But your research is helping us to understand aging?
We're learning a lot about how our cells and organs age. Telomeres control a lot more than just the number of times a cell divides. They play a role in arranging chromosomes in a certain order so that they can talk to each other. It's very well-controlled, certainly not random, so there must be a mechanism behind this process. If we can identify this mechanism, then I think we'll be able to address the often coordinated onset of age-associated diseases. I have terrific people working in my lab, and we've shown that the deeper we dig, the more we realize how these very localized processes affect the entire cell and therefore the organ and after that the organism. There's always a bigger picture.
Away from your lab, you spend a lot of free time working on Land Cruisers. What is the attraction?
The attraction came about after moving to San Diego. I fell in love with the southwestern desert and the Mexican desert, and I wanted to explore these areas. I met some others who shared that interest, and the general agreement was that if you don't want to break down out there you must have a Toyota Land Cruiser. If you look at the wildest continents of the world, such as Africa and Australia, you don't see too many Jeeps; you do see a lot of Land Cruisers. They are very durable trucks. So I bought a Land Cruiser and I drove it to Mexico. And of course it broke down. That was because it was old and I didn't know what I was buying. That's when I decided that if I was going to do this, I needed to know a whole lot more about these vehicles. I met a good guy, a sort of hobby mechanic, and we became friends and started working on them together, rebuilding engines, taking transmissions apart and such.
How many Land Cruisers have you built?
Just for my use, at least six. I have one right now that's a diesel. Diesels have become our specialty. They get much better gas mileage, which is important when you're traveling through the remote areas of the desert. And the diesel engines are usually more reliable, too. But they're difficult to get. They were never sold in the U.S. You could get them in Canada for a while but not now. I just put an Australian diesel engine in my 1996 Land Cruiser. Over the past 11 years, I think I've logged about 100,000 miles in Baja.
What was your most harrowing moment?
I took a trip with my brother and a friend. We were going to try a new route from the Pacific Ocean to the Sea of Cortez, and it was through some really high mountains. We had two vehicles, and at one point we overlooked a big rock, and the Toyota Tundra got hung up. That ripped out the rear axle and tore the driveshaft in two. So, there we were in the middle of absolute nowhere, high in the mountains, and we didn't know what we were going to do. We thought about piling all of our stuff into the one vehicle and just driving away, leaving the Tundra. But then we took some time to put up some shade—it was scorchingly hot—and think about the problem, and we decided, "Hey, we can fix this." We had a few tools with us, but some sockets were missing, so I ended up driving to Loreto, which was six hours away. When I got back, we lifted up the rear of the truck and tried to push the axle into place, but it was too heavy. So we put the truck in front wheel drive and drove backward, doing our best to center the truck over the axle. Then we managed to rig up something to bolt it into place. It was on that trip that we discovered the most important tool of all: a really big hammer. We used that to fix the driveshaft. It was a little unbalanced when we were done but it got us back to San Diego without a hiccup. You know, you can work yourself out of a lot of problems if you have at least a remote idea of what you're doing.
What keeps you going back to Baja California?
It is absolutely beautiful there, completely deserted. You have a 1,200-mile stretch of land that no one has spoiled. In many places there is not a single person around, and there probably hasn't been a single person around in a month. It's incredibly peaceful. You can sit on a beach and just think. No email, no cell phones. You know that no one's going to bother you. It's very relaxing.
Do you think about science when you're there?
All the time. You get a distance, you know. And sometimes you actually get some very good ideas just sitting on the beach.