Some people go fly fishing to put their day-to-day cares aside, enjoy the outdoors and maybe even achieve some level of peace. Others go fishing and come back with a business plan. HHMI investigator Robert Tjian belongs to the latter group.

For more than 15 years, the biochemist at the University of California, Berkeley, has gone angling for salmon and trout all over the globe with his friend David Goeddel, a gene-cloning pioneer. In 1989, on a fishing trip in northern California, Goeddel told Tjian that he wanted to start his own biotech company and he asked his pal to join him.

At first, Tjian wasn't particularly interested. "I could see it would be a lot of work," he recalls. "I also didn't want to do it unless it was going to be different from [biotech giant] Genentech; there was no way you could compete with Genentech."

Still, he kept mulling it over. When Goeddel asked him again in the spring of 1991—while fishing on Christmas Island, 1,300 miles south of Hawaii—Tjian made up his mind. "I said, okay, it's now or never." It was during a third fishing excursion the following September, on Alaska's Tularik River, that the pair committed to the launch. That November, after enlisting biochemist Steven McKnight from the University of Texas Southwestern Medical Center at Dallas as a third partner, they founded a company to propel research on gene expression—Tjian and McKnight's specialty—into the clinical realm.

The San Francisco-based firm, which the founders named Tularik, would pursue what was then a bold new approach: hunting for small molecules that could squeeze their way into cells and block or enhance the transcription of genes coding for disease-related proteins. Drugs based on such molecules would offer a major advantage over biotech drugs made of larger proteins: Patients could take them as pills instead of injections.

Tularik's first year was a whirlwind. Aside from honing the company's technological plan of attack, the founders had to raise money, hire the right people and build new labs from scratch. Tjian took a sabbatical from teaching but kept up his research activities at the university. As it turned out, securing money was relatively easy. "As soon as people found out Dave was a founder, it was kind of a no-brainer," says Tjian, who chairs Tularik's scientific advisory board.

Most biotech start-ups focus on one major product and go public within three years. Tularik, however, took a maverick route, chasing 10 to 20 promising drug candidates at once and going public only in late 1999. Right now, the firm has four drugs in early-phase clinical trials—three to treat several different cancers and the fourth to work against cytomegalovirus. It's also pursuing more than 50 other leads, targeting disorders such as rheumatoid arthritis, diabetes and obesity.

The company still faces an upstream battle. It may be several years before Tularik finally gets a drug on the market, but the partners are confident that their efforts will prevail. "Goeddel, McKnight and I all have the same philosophy," says Tjian. "We don't mind working hard and taking risks."

—Ingfei Chen

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Reprinted from the HHMI Bulletin,
June 2002, pages 26-30.
©2002 Howard Hughes Medical Institute