GORDON LITHGOW was in Switzerland, doing a postdoctorate in industry, when he read of the first genetic mutation shown to prolong life. It was Dr. Thomas E. Johnson’s age-1, and it increased the lifespan of the tiny worm C. elegans by nearly 70%. “I was a microbiologist looking around for the next big thing,” Dr. Lithgow said. “And I realized that absolutely nothing was known about aging. It was Tom Johnson’s paper that proved something could be done.” Soon Dr. Lithgow, who is from Scotland, was working with C. elegans in the Johnson lab. Various labs began to produce discoveries about the genetics of longevity that, in his words, “set the grass on fire.” In Dr. Tom Johnson’s lab, Dr. Lithgow was part of a group that showed that long-lived mutants were resistant to heat stress. Now, in his Ellison-supported research at the Buck Institute for Age Research, Dr. Lithgow is working to extend that insight by finding drugs, rather than genes, that enhance worms’ stress resistance. Such compounds will be tested to see if they extend lifespan. As part of this process, the Lithgow team is developing an automated system to allow high throughout screening (HTS) of whole, albeit microscopic, worms. “Normally, you’re sitting at the microscope moving worms individually from one agar plate to another with a platinum wire,” Dr. Lithgow said. “If you’re doing lifespan research, you’re trying to assess whether a worm is alive or dead. You’re probing it with a platinum wire – it if moves, it’s alive, if not it’s dead. It’s incredibly time consuming.” C. ELEGANS (Caenorhabditis elegans) With the new system, he said, “instead of looking at a hundred worms in one survival experiment, you’ll be looking at hundreds of thousands at a time.” And instead of screening one compound a week, as used to be done, researchers will be able to screen thousands, including various concentrations and combinations. Such testing allows different patterns to emerge, he said. “The same antioxidant at different concentrations can have opposite effects. That’s something we wouldn’t have known the way we used to test things.” The new system is based on combining off-theshelf technology: an automated worm sorter, fluorescent dye, and a microtiter plate reader. “Fluorescent SYTOX dye is taken up when the worms die,” Dr. Lithgow said. “A worm glowing is a dead worm.” As of early 2005, the lab was refining the system. Dr. Lithgow got his start in science as a birdwatcher, a member of Britain’s Young Ornithologists Club. In school, he said, he had “extremely average grades,” was slightly dyslexic and weak on memorization. (“This will not surprise people who know my work in aging,” he jokes.) His strengths – which he described as curiosity and logical thinking – became more important as he got into research. Although he was the first in his family to go to college, “my parents somehow managed to fool me into thinking it was something you would do.” He wanted to study biology, he said, “but unemployment was sky-high in Scotland, and how many jobs are there for biologists? My teacher convinced me to do microbiology because there are always jobs in the food industry and” – here his accent buzzes into a burr – “brewing.” He didn’t get back to whole animals until C. elegans. As head of a lab, Dr. Lithgow, who is 42, says his job is “trying to keep the money coming in and the papers going out.” He is married to Dr. Julie Andersen, also a Buck Institute scientist. They have a young son and, he says, a shared interest in oxidative stress.