Spring 2008 — Vol. 61, No. 2

Ask Conrad Gilliam to recall the “Eureka moment” when he first hit upon the startling idea that mental disorders such as autism and schizophrenia might be triggered by networks of linked genes — networks that somehow distort normal brain functioning. The Clemson biochemistry graduate will surprise you by laughing out loud.

“I’m not really sure I can take credit for that insight,” says Gilliam, chairman of the University of Chicago’s Department of Human Genetics.

His news-making theory explores how heritable mutations affect the function of interacting groups of genes, or gene networks, rather than treating single genes as the targets for mutations that predispose individuals to mental illness.

“Although I’d been thinking about how genes regulate brain development for some time, I had been focusing on the actions of single genes, and had not really considered that it might be the concerted action of groups of genes that is disrupted to cause mental disorders like Alzheimer’s.

“But then I had a sudden flash during a lecture I attended at Princeton eight years ago. The lecturer was physicist Albert-Laszlo Barabasi, who studies networks — everything from social and computer networks to biochemical networks you find in organic systems. Barabasi is a very gifted thinker, and by the time his lecture ended that night, I was so intrigued that I couldn’t get out of my chair.”

At the time, Gilliam was already recognized as a world-class scientist who’d led research teams that successfully mapped genes linked to cystic fibrosis (at the University of London in the early 1980s) and Huntington’s disease (at Harvard University a few years later).

“Like many geneticists during the 1990s,” he says, “I’d been assuming that most central nervous system disorders were caused by genes acting alone … and that the mapping of the entire human genome [completed in 2003] would allow us to begin pinpointing the exact locations of these flawed genes, so that we could design therapies aimed at neutralizing them.”

But, he points out, that’s not what happened.

Instead, after Barabasi’s powerful lecture, Gilliam was forced to begin rethinking all of his assumptions about the process in which inherited genes contribute to mental illness. The result was a new scientific model in which brain disorders are caused by genes that act in concert, rather than alone.

Gilliam’s new approach to brain genetics has begun to open up a whole new layer of investigation that could eventually lead to a paradigm shift in the way the medical profession understands — and then treats — the phenomenon of mental illness.

“During the last few years, we’ve entered a new, unexplored region of genetics,” says Gilliam, who leads a team of a dozen scientists in a continuing quest to uncover the genetic networks responsible for brain disorders. Armed with some of the most powerful computers in the nation (located at the Argonne National Laboratory, near Chicago), Gilliam and his staff of geneticists and “bio-informatics” computer whizzes are making new discoveries almost daily, as they close in on the staggeringly complex genetics behind mental illness.

Gilliam says, “I’ve always been interested in how things work and why they work that way. I like to dig deeper and deeper, and I like to forget about everything else while I push through one layer after another.

“One morning at Clemson,” he recalls, “when I was working on my master’s degree in biochemistry, I came into the lab and pulled my lab book out of a desk drawer. As always, I started my day by writing the date at the top of the page.

“I wrote it down — December 25th — and then I looked at it for a moment, and I said, ‘Oh yeah, it’s Christmas!’ I was so caught up in the lab work that I’d completely forgotten what day it was!”

Born and raised in Aiken, the son of a chemical engineer, Gilliam arrived on the Clemson campus in 1969. Intent on becoming a veterinarian, he soon discovered that he wanted to “study something more on the cutting-edge of science.” Eventually he found the challenge he wanted in molecular biology — along with an inspiring mentor, professor Gary Powell, who taught “intro to biochem.”

“Dr. Powell taught what many students regarded as the toughest course at Clemson,” recalls Gilliam. “His course was extremely rigorous, very tough … but I liked that. I really enjoyed the challenge of working in the lab night after night, trying to understand these very complex processes that were going on at the molecular level.”

After earning Clemson bachelor’s and master’s degrees in biochemistry, Gilliam headed off to work on his Ph.D. at the University of Missouri. With his doctorate in hand, he spent several years working on gene-mapping projects related to cystic fibrosis and Huntington’s disease as a “post-doc” at London University and then Harvard. He signed on as a genetics professor at Columbia University in New York City in 1987. Seventeen years later, having become a national leader in his field, he was tapped to take over the human genetics program at the University of Chicago.

Gilliam has published more than 100 peer-reviewed articles in his field, while also racking up half a dozen different teaching and research awards. News of his research has been covered in New York Times, Nature, Science and a variety of professional and general interest media.

“For a geneticist who’s interested in mental disorders, this is a very exciting time,” he says. “The technology keeps getting better every day, and we’re now able to manage an astonishing amount of complexity.

“And for a scientist who enjoys digging through layer after layer of data, it just doesn’t get any better than that!”