Combinatorial Chemistry: Doing It Nature's Way

Chemists usually analyze the properties of molecules one compound at a time. But that's not how nature does it. The immune system, for example, responds to diseases by turning out billions of antibodies and screening the whole lot to find one that works. Setting out to mimic the body's strategy, Peter Schultz pioneered a new "combinatorial" chemistry that is sweeping the most advanced labs and is widely used to search for drugs and other biologically active materials.

Not content to excel in academia, Schultz, 44, has also been busy founding companies: Affymax (1988), to hunt for new drugs; Symyx Technologies (1994), to develop advanced materials; SyrrX (2000), to sell protein structures to drug companies.

Today, as director of the Novartis Research Foundation's new Genomics Institute, Schultz is boning up on genetics. But he also keeps one foot planted in pure science. His lab at the Scripps Research Institute, where he starts his day by 5 a.m., uses combinatorial methods to study everything from nanotechnology to organ regeneration. His scientists have invented 80 new amino acids and used them to make proteins seen nowhere in nature, and they are trying to create an artificial bacterium with two extra bases in its DNA and five unnatural amino acids in its proteins. "The question is," says Schultz, "Why are there only four bases in our DNA and only 20 amino acids in our proteins? What would life look like if God had worked on the seventh day and made a few more?" If anyone can answer that question, Schultz can.

--By Unmesh Kher