While practicing medicine was the Palo Alto Medical Clinic’s main function, the group also interfaced with a sister organization: the Palo Alto Medical Research Foundation. Like the Clinic, the Research Foundation (now called the Research Institute) was the brainchild of Dr. Russel Lee, who envisioned it as a place where doctors in clinical practice could study ideas that occurred to them while treating patients. In 1950, Dr. Lee recruited Marcus Krupp, M.D., from the San Francisco Veterans Affairs Hospital to run the Research Foundation. Board certified in internal medicine, Dr. Krupp had spent much of his career doing laboratory work and research.

The Palo Alto Medical Foundation (PAMF) Research Institute today has dozens of scientists and staff members and a world-class facility on PAMF’s main campus. Its start was somewhat less glamorous. With a $90,000 donation from the Lucie Stern Foundation, a four-person research staff set up shop in a house that had previously belonged to a junk dealer near the Clinic on Channing Street. "We took that old house and made it into laboratories," Dr. Krupp said. "I had the little room just adjacent to the front porch, and my lab was behind that in the kitchen. The living room became the library. Upstairs there were two large rooms that we turned into labs."

Despite Dr. Lee’s initial intent, most Clinic doctors lacked time or interest to participate in basic research, the initial scientific studies used to make medical discoveries before they are turned into treatments for patients. So instead, Dr. Krupp recruited outside physicians, graduate fellows and Ph.D. scientists who were looking for full-time careers in basic research. "My feelings were very strong that the strength of any institution in research is in fundamentals. Fundamental research, if it is valuable, will be used and will provide the basis for some kind of approach to a diagnosis or a treatment, and that’s what it’s all about. Testing drugs doesn’t seem to me to be basic – it’s important, of course, because you can’t use a new drug until it’s been tested. But to do only that seemed to preclude new ideas, and I was interested in new ideas."

• Major Breakthroughs

Major Breakthroughs

Dr. Krupp ran the Research Foundation with relative autonomy. "I had told Russ early on that physicians in practice would not do much research. And he said, ‘Well, you do what you want.’ That’s what attracted me, and it became our motto all through that you invited people in to do research and you left them alone if they had a good idea, let them do their own thing. And if they didn’t, they were out," he said. Researchers had three chances to win grants for their ideas; if they failed a third time, they had 18 months to prove that the idea could succeed before being let go.

It didn’t take long for the Research Foundation to begin building an international reputation. Among its first researchers was Barend Hofstee, Ph.D., who created a mathematical method for charting the rate of enzyme reactions that is still used in biochemical laboratories today. As the organization’s prestige grew, so did its research staff and finances. Researchers were successful at obtaining private and public scientific grants, and several patients made generous donations. In 1956, the Research Foundation was one of 26 research organizations nationwide to receive a National Institutes of Health matching grant to fund the construction of new research facilities. With nearly $300,000 from the government and a comparable amount raised from donors, a larger Research Foundation building opened in 1958. Many researchers came and stayed for their entire careers, attracted by the fact that, unlike in an academic setting, there was no requirement for teaching and little outside interference.

Over the years, the research organization’s areas of focus have changed depending on the scientists it has employed. One mainstay has been bioengineering with emphasis on the physiology of the heart. In the 1970s, a team headed by Neil Ingels, Ph.D., invented a technique to monitor heart motion that has led to breakthrough discoveries about how the heart pumps blood and influenced treatment of heart disease, post-operative heart bypass care and mitral valve repair. Dr. Ingels, who joined the Research Institute in the 1960s, still works there today. Immunology and infectious diseases has been another longstanding division. Its chief, Dr. Jack Remington, is considered the world’s leading expert on toxoplasmosis, a parasitic infection that can cause severe complications for babies infected in utero and for patients with weakened immune systems.

Research has not been limited to the laboratory. In the 1960s, Anne Scitovsky conducted the country’s first scientific studies on medical expenses, using the Clinic’s patient records to assess how costs of care had changed since 1951. Her work was used on a national level in analyzing programs such as Medicare. Scitovsky later conducted research on the economics of AIDS care that led to the creation of the federal Ryan White program, which provides primary care, medications and support services to people living with HIV. "It resulted in dramatic improvement in the care available to people all over the country," said Dr. Philip Lee, who worked with Scitovsky on that research when he was head of the University of California, San Francisco’s Institute for Health Policy Studies. "It shows you how one person sitting down here in Palo Alto can have a huge impact."

Today the Research Institute is part of the Palo Alto Medical Foundation, and has four divisions: Cardiovascular Biology, Immunology and Infectious Diseases, Health Services Research and Clinical Research. Scientists study new methods for asthma care and sexually transmitted disease prevention; immune system molecules that might help treat disease; and the mechanisms used to transport fatty acids from the bloodstream to the cells, among other areas. In coming years, the organization may also make investments to study subjects becoming more important in medicine, such as health information technology and geriatrics. "The opportunity for applying basic knowledge in very constructive ways for patients is better than it has ever been," Dr. Philip Lee said.
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