Many consider the discovery of penicillin the single greatest medical achievement of all time. Subsequent to its discovery in 1928, penicillin and other antibiotics have significantly reduced illness and death from infectious diseases. But as antibiotic resistance grows, new answers must be found.
Enter Jeffrey Stein, president and CEO of Trius Therapeutics. Trius Therapeutics is a biotechnology company focused on the discovery and development of innovative antibiotics to treat life-threatening infections. Trius is currently collaborating with William Fenical and his science team at Scripps Institution of Oceanography, UC San Diego to discover new antibiotics from marine microorganisms.
While the richest source of antibacterial drugs in use today are derived from a single order of terrestrial bacteria - actinomycetales – this source has been virtually tapped out as a resource, Stein said. The rate of discovery of effective antibiotics has not kept pace with the ability of pathogenic bacteria to develop resistance.
“But the recent discovery by the Fenical laboratory of a new group of marine actinomycetales, and the demonstration that they produce structurally unique antibiotic molecules, provides an exciting opportunity to develop effective new drugs,” said Stein.
The collaboration between Trius and the Fenical lab is funded by the federal Defense Threat Reduction Agency (DTRA), committed to investing in basic research enabling the U.S. to better address future threats. Under this contract, “Trius is using proprietary screening technologies to discover antibiotics with activity against specific, drugable targets in pathogenic bacteria and then applying structure guided medicinal chemistry to improve those molecules for drug-like properties,” said Stein. The molecules used will be drawn from Dr. Fenical’s extensive marine natural product libraries.
Stein says he set his sights at age eight on a postgraduate education from Scripps Institution of Oceanography. But he probably couldn’t have guessed that he might one day have a shot at helping to transform the face of modern medicine. As a child, he describes himself as being “completely focused” on attending Scripps. After all, one of his heroes, the surf legend Ricky Grigg, was a Scripps graduate student at that time and eventually became a professor of oceanography at the University of Hawaii.
“I always figured I would follow a similar path. As an eerie coincidence, when I started as a graduate student at Scripps there was an old surfboard hanging in the rafters above my office door in the marine biology building. It turned out to be Ricky Grigg’s former surfboard,” Stein said.
Despite not knowing where his career would take him, what became quickly evident was that Stein marched to the beat of his own drum. Even during the days of his doctoral program at Scripps Oceanography from 1985 to 1991, with marine biologist Horst Felbeck as his advisor, he experienced a slightly different graduate education. He was a virtual entrepreneur within the Felback laboratory, seeking and obtaining his own funding for research that was outside the mainstream.
“I was allowed free rein and Horst was enormously supportive, even when my research strayed well outside the boundaries of what was being pursued by the rest of the Felbeck laboratory,” Stein said. “I doubt that I could have thrived in a more structured environment.”
But thrive he did and after receiving a Ph.D. in marine biology in 1991, Stein conducted postdoctoral research at Caltech and then moved quickly into the biotech industry, with positions at the Agouron Institute and Diversa Corporation before founding his first biotech company, Quorex Pharmaceuticals in 1999. Now leading Trius Therapeutics, Stein is patiently waiting to experience the joy of moving a research project from the bench to the marketplace. The lead program at Trius has entered Phase Three clinical development where it is being tested in hundreds of patients with severe bacterial infections.
Stein’s is a path divergent from that of his surfing hero and the mainstream of Scripps students but he believes it’s still very much in keeping with a common sense of mission.
“Although my career path has certainly diverged from Ricky’s, it has followed a step-wise progression toward becoming a biotech CEO,” he said. “What has remained unchanged, however, is a focus on scientific exploration. This is why it is so gratifying to reconnect with Scripps on this important project.”
--Wendy Hunter Barker
Class: 1991
Advisor: Horst Felbeck
Thesis: Molecular Genetics and Biochemistry of Ribulose-1,5-bisphosphate Carboxylase/Oxygenase in the Endosymbiont of the Hydrothermal Vent Gastropod Alivnoconcha hessleri
Current Occupation: President and CEO of Trius Therapeutics, San Diego, Calif. (Trius recently went public on the NASDAQ exchange where it is listed under the symbol TSRX.)