Noted pharmacologist and addiction expert Avram Goldstein dies at 92

- By Rosanne Spector

Avram Goldstein

Avram Goldstein, 92, an emeritus professor of pharmacology at the Stanford University School of Medicine and one of the discoverers of endorphins in the late 1970s, died June 1 after a long decline.

Among his accomplishments, Goldstein helped orchestrate the medical school’s emergence in the 1950s as a powerhouse for medical research by recruiting its faculty and shaping its curriculum, wrote a pharmacology textbook, founded a journal, organized California’s first major methadone program and made breakthrough discoveries in his lab about how narcotic drugs work in the brain.

As a 35-year-old assistant professor at Harvard in 1955, Goldstein accepted an offer to chair Stanford’s pharmacology department and hire new faculty for a research-oriented medical school that the university planned to build on its sprawling campus in Palo Alto. At that time, the medical school was based in San Francisco and focused training on preparation for medical practice — as did most medical schools of the day. Goldstein recruited other leading scientists to Stanford, notably by telling famed biochemist Arthur Kornberg, MD, that if he liked his current department at Washington University in St. Louis so much, “Fine — bring them all.” Stanford’s medical school moved to the Palo Alto campus in 1959, and its newly arrived faculty spent decades in the middle of the revolution in molecular biology that followed on the discovery of DNA.

“Stanford Medical School, as we know it today, is the result of Avram Goldstein's leadership and vision,” said Dean Philip Pizzo, MD. “He has left an endurable mark on the institution and the generations of individuals he worked with and trained. Of course his name will forever be associated with Stanford because of the professorship in his name — but more so because of the impact he had on individuals and our communities, locally and globally.”

Goldstein was born July 3, 1919, in New York City to Israel and Bert Goldstein and had a younger sister, Vivian. Growing up in Manhattan during the skyscraper-building boom and the Great Depression, he attended the progressive Walden School. The son of a prominent rabbi and Zionist, Goldstein became an atheist in childhood and dedicated his life to science. He was admitted to Harvard at age 15 but deferred college for a year and worked on a kibbutz in Palestine (although later, as an adult, he did not participate in Jewish life). After graduating from Harvard in 1940 and Harvard Medical School in 1943, he served in the U.S. Army in Colorado during World War II, treating soldiers returning from Europe. Goldstein’s first wife, Naomi Friedman, died in a car accident in 1946. He married Dora (Dody) Benedict, who would become a distinguished pharmacologist and Stanford professor herself, in 1948. During 62 years of marriage, they raised four children, and spent sabbatical years in Edinburgh, Copenhagen and Cambridge, England.

While department chair (1955-70), Goldstein studied the effects of caffeine in human subjects, founded the journal Molecular Pharmacology (1965), wrote Biostatistics (1967) and co-authored the textbook Principles of Drug Action (1968). In 1969, wanting to do socially meaningful work, he began studying opiates such as morphine and heroin at a time when these drugs were ravaging American cities but nobody understood their effects in the brain. Goldstein announced to his lab staff one day, “We’re going to switch all the research we’re doing, quit the microbial stuff ... and apply for new grants to work on opiates.” He developed the methodology for studying how molecules bind to opiate receptors in the brain, a key step in the search for the endorphins.

In the 1970s Goldstein worked doggedly to isolate and identify the chemical structure of an endorphin receptor and then the endorphin itself. At one point his lab spent four years turning tons of pig pituitaries into 2 micrograms of purified endorphin. (He posted on the wall of the lab the sheet music for He Shall Purify from Handel’s Messiah.) The molecule he thus discovered was one of the major endorphins, which he named dynorphin because of its high potency. However, he lost the friendly competition to discover the first endorphins (the enkephalins).

Simultaneously with his lab research, Goldstein worked directly with heroin addicts in San Jose, where he organized California’s first major methadone clinic in the early 1970s. He wanted to learn about the realities of heroin addiction and to measure scientifically the effectiveness of methadone treatment. Over the years, Goldstein advised officials on drug policies, generally advocating a public-health, harm-reduction approach. He helped develop urine tests that identified returning Vietnam veterans addicted to heroin so they could receive treatment before being discharged. Goldstein’s book Addiction (1994; 2001) explained drug addiction, from biology to government policy, for a broad audience. He consulted for biotech industry in Silicon Valley, serving as scientific advisor to several companies. Thus his work ran the spectrum from basic research to real-world, applied science. These came together in 1974 when Goldstein established the Addiction Research Foundation next door to Stanford, housing lab research, human-subjects research and treatment of heroin addicts.

Biochemist and Nobel laureate Paul Berg, PhD, who was among the faculty who came to Stanford from Washington University with Kornberg, saw Goldstein as a man who acted on what he believed, and persisted even when the going was tough. “He’d never take no for an answer,” said Berg, who remembers Goldstein’s recruiting visits to St. Louis, including one especially persuasive encounter when he pulled out a floor plan showing one floor was completely open, saying they could do anything they wanted with it.

Goldstein also led the design of the school’s new curriculum taking effect in 1959, which aimed to cover the required ground but to remain flexible enough to maximize opportunity for students to do whatever interested them the most. Students were allowed to take a large number of electives, and they were given lab space of their own. And, contrary to the national trend, which was toward reducing the time spent in medical school, Stanford extended the time from the standard four years to five.

“Avram was a tough mentor in the sense that he had high expectations and standards — but he was also exceedingly fair. I regard it as an incredibly lucky stroke that I ended up stumbling into his lab,” recalled Charles Weitz, MD, PhD, a professor of neurobiology at Harvard Medical School who from 1984-88 was a graduate student in the Goldstein lab, which was a formal, serious place. “Clearly, being in his lab was the formative thing that influenced how I think about science and how I train people in my lab now.”

Weitz said Goldstein taught students how to be objective about their work. “What that really means is you have to disentangle your hopes for a result from what the data were actually telling you. This is more difficult than it sounds.”

Goldstein’s colleagues remember him as a man who not only spoke out about his convictions, but acted on them.

“He was courageous and was an activist — that was his personality,” said Berg. “He was in the forefront of every progressive movement — during the Vietnam War uproars on campus, he led student protests.” He also fought hard to set up the methadone clinics, said Berg, which were not welcomed by the community. “He did not just sit back and watch things go by. If he was stymied, he’d fight very hard to get what he thought was right.”

Goldstein embraced the California lifestyle, driving a convertible and holding lab meetings at home by his swimming pool. He was passionate about piloting small airplanes — even moonlighting as an instrument flight instructor and writing several books about flying. He loved opera, and was fascinated by southwest American Indian cultures.

He won the Benjamin Franklin Medal in Life Science (1980) and major awards in pharmacology. He was elected to the National Academy of Sciences and its Institute of Medicine. He published more than 360 research articles.

In the 1970s, Goldstein was treated for lymphoma, one of the first patients to receive radiation, and recovered fully. However, he was confined to a wheelchair in his last decade, after a spinal-cord injury, and relied on his longtime caregiver Mara Passi. He is survived by his children, Margaret Wallace of Longmont, Colo., Daniel Goldstein of Port Townsend, Wash., Joshua Goldstein of Amherst, Mass., and Michael Goldstein of San Francisco; and five grandchildren. He was pre-deceased by his sister, Vivian Olum, in 1986, and his wife, Dora, in October 2011.

Both the family and Stanford’s medical school are planning memorials.

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