April 2002

The Virtual Cell

With human cells distilled into digital models, testing the effectiveness of a new drug could be as simple as typing a few lines into a computer.

By Gary Taubes

When Harley McAdams was a few years shy of 60, he became a biologist. He had spent two decades of his working life as a systems engineer at AT&T's Bell Laboratories, and four years at Lockheed Missile and Space in Sunnyvale, CA, working on data systems architecture for military satellites. In 1994, however, he took to attending biology seminars at Stanford University, where his wife, Lucy Shapiro, was chair of the developmental biology department. McAdams had his epiphany while listening to an eminent geneticist describe the complex biological circuitry that turns genes on and off in yeast. To the uninitiated, the diagram of this system was vaguely reminiscent of a plate of spaghetti, with various arrows and stop and go signs attached. To McAdams, it looked like nothing more than an electric circuit, with the kinds of feedback loops and regulatory and control mechanisms that constituted the meat and potatoes of his systems engineering work.

After the lecture, says McAdams, he and his wife made a deal. He would teach her Boolean algebra, the mathematical logic of computer circuitry, and in return she would teach him genetics. And so they spent the next year, or at least the nights and weekends, educating each other, until the day McAdams claimed that he could apply the rules of electrical circuitry-along with the computer modeling techniques engineers typically use to analyze and design such circuitry-to a genetic circuit. By so doing, McAdams was able to provide an understanding of how the genetic system worked that went far beyond what biologists had managed to achieve. "At one point, he just walked out of Lockheed and started working at home," says Shapiro. "I nearly had a heart attack."

By 2000, McAdams and Shapiro had published a seminal paper in the journal Science on the application of systems engineering to biology, and McAdams had acquired his own biology laboratory at Stanford University School of Medicine and funding from the U.S. Defense Advanced Research Projects Agency (DARPA) to pursue biological research. Even Shapiro began to view herself and her work in an entirely different light. "Now if somebody asks me what I do for a living," she says, "I say I am a biological systems engineer."

Shapiro and McAdams can be considered among the more senior members of the avant-garde of a revolution in biology, in which the immediate goal is to create computer simulations-styled after systems engineering-of the regulatory mechanisms of genes and, eventually, entire cells, tissues and organs. These simulations will allow researchers to do biology experiments "in silico," inexpensively and remarkably quickly. Ultimately, researchers will use such computer simulations to identify new drug targets and to design and screen new drugs that will lead to entirely new treatments-if not cures. "It's just a wholly new way of doing biology," says Jim Anderson, who directs a new program to fund such research at the National Institutes of Health.