Genework

“The Unselfish Gene” by Johnjoe McFadden, in The Guardian (May 6, 2005), 119 Farringdon Rd., London EC1R 3ER, England.

For decades, scientists have been in hot pursuit of the genes for this and that—for heart disease, autism, schizophrenia, homosexuality, criminality, even genius. For the most part, they’ve come away empty-handed. As a result, many are turning to “an entirely new way of doing biology: systems biology,” says McFadden, a professor of molecular genetics at the University of Surrey, England.

Scientists studying the cell’s metabolic pathways picked up some early clues that something was amiss in their search for isolated genes. The metabolic pathways are like a network of roads that transport food to enzymes, which assemble the useful molecules into more cells. Biotechnologists seeking to engineer the cells to produce certain types of new cells found their efforts hindered by genes that appeared to be controlling the whole network’s operation. Striking back, the scientists engineered the genes to prevent them from taking control. But it didn’t matter: The metabolic pathways swiftly went back to business as usual.

Geneticists were also frustrated and puzzled by the many genes that had no apparent function at all. Take the “prion gene,” which mad cow disease turns into a pathogenic brain-destroying protein. What does this gene normally do? “The standard way to investigate what a gene does is to inactivate it and see what happens,” McFadden writes. Yet when geneticists did that to the prion gene in mice, nothing happened: The mutant mice were perfectly normal. But a functionless gene isn’t really a “gene” at all, as the entity is conventionally understood, for it is invisible to natural selection.

Instead of having a single major function, McFadden writes, most genes “probably play a small part in lots of tasks within the cell. . . . So the starting point for systems biologists isn’t the gene but rather a mathematical model of the entire cell. Instead of focusing on key control points, systems biologists look at the system properties of the entire network. In this new vision of biology, genes aren’t discrete nuggets of genetic information but more diffuse entities whose functional reality may be spread across hundreds of interacting DNA segments.” Instead of a single gene’s being responsible for schizophrenia, for example, the condition “may represent a network perturbation generated by small, almost imperceptible, changes in lots of genes.”

To pursue this new vision, systems biology centers “are popping up in cities from London to Seattle.” Unlike traditional biol­ogy departments, these centers generally have on staff not only biologists but physicists, mathematicians, and engineers. “Rath­er like the systems they study, systems biology centers are designed to promote inter­activity and networking.”