Oral History Spotlight

George Poste:
Embracing Complexity

George Poste is a big picture guy. He believes that progress in science and medicine requires understandings of complex wholes, and that reductionism is foolhardy. “With reductionism,” he says, “you delude yourself into thinking that you can understand a complex system by analyzing its parts, but you can’t.” Poste’s appreciation for big picture thinking has been reinforced by adventures in cancer research, drug discovery, genomics, and biosecurity, but it first came to him through exposure to the traditional practices of an older world.

George Poste grew up in rural Sussex, in the south of England, during the postwar period, a time of austerity and reconstruction. The life of the local community was ordered by the natural rhythms of farming. His father was a mechanic, “a keen practical intellect” who made his living servicing farm machinery and vehicles.

Poste observed that veterinarians also played critically important roles in the farm economy, and in the course of their work confronted “a diverse set of intellectual challenges.” Veterinarians are trained to diagnose and treat ailments of many different kinds — equine, bovine, porcine, ovine, caprine, and so on. It seemed to the boy that their practice was far more demanding than that of the village physician.

In 1954, Poste came to a branching point — the Eleven Plus exam that stratified primary school students on the basis of intellectual ability. He took the exam a year early, but still scored in the top 5 percent, which put him on the university track. Some time later, he began accompanying local veterinarians on their rounds. He wanted to acquire their big picture perspective on health and illness.

At the age of eighteen, he went off to the University of Bristol with a plan to study clinical veterinary medicine. He was not surprised to find that “veterinary students had the highest entrance qualifications, and the medics, dentists, and vets all went to the same classes.”

At the time, biomedicine was being rebuilt on molecular foundations. Poste feels “fortunate to have been there at the beginning, to get training in molecular biology.” He became particularly interested in cancer — studies of retroviruses and oncogenes had begun to reveal the complexities of tumor biology.

Poste completed his veterinary training in 1966, but rather than going into clinical practice, he went on to earn a PhD in virology at Bristol in 1969. He then accepted a position as a lecturer in the field at the University of London’s Royal Postgraduate Medical School.

Two years later, he took a sabbatical at the Roswell Park Cancer Institute in Buffalo, New York. “I’m the only guy who ever went to Buffalo not knowing that it snows there,” he laughs. The institute had recruited a stellar multidisciplinary group composed of molecular geneticists, cell biologists, immunologists, and pharmacologists. Poste found it a uniquely stimulating environment: “There was a great intellectual nucleus and I was trying to absorb everything like a sponge.” The sabbatical visit turned into a permanent tenured appointment at the State University of New York.

Then, out of the blue in 1981, Poste received a call from a headhunter representing a “major research firm.” It turned out to be the Philadelphia pharmaceutical house, Smith, Kline & French. “I had never thought about going into industry,” says Poste. “I had a typically insular, academic view of the world, and by this time I was a full professor. But I went through the interviews, and only an idiot would come away unimpressed by what I saw and the ambitious plans that the company had to participate in the then emerging new domain of biotechnology.”

SmithKline had recently introduced the world’s first blockbuster drug, the anti-ulcer histamine blocker cimetidine (Tagamet), one of the inventive payoffs of James Black’s pioneering work in “rational drug design.” Bryce Douglas, the company’s senior vice president of R&D, recognized the potential of molecular biology to advance this novel mode of drug discovery and development. He encouraged Chairman Henry Wendt and CEO Bob Dee to invest heavily.

Douglas recruited Stanley Crooke, who had built Bristol- Myers Squibb’s oncology program, as president of R&D, and Poste as vice president of research — two people he believed had the background and the will to innovate. “This was sophisticated strategic planning,” says Poste. “The molecular revolution was underway, and Bryce wanted SmithKline to be part of it.”

Still, it was a struggle to bring molecular biology into an organization steeped in pharmaceutical chemistry. Poste remembers: “It was a pretty traumatic time. Stan Crooke and I literally tore the place apart. We imposed radical change.” And, he admits, “It wasn’t always done optimally or with adequate consideration.” It was a difficult time for the company’s powerful marketing group, too. “Sales people understand existing markets,” says Poste, “but they have a harder time with disruptive technologies.”

Battles ensued. Poste was convinced, for example, that recombinant DNA technology would revitalize SmithKline’s vaccine business, but on three separate occasions, factions in the company’s executive suite pushed to sell it off. “I laid down in front of it each time,” says Poste, “and I’ve got the scars on my back to prove it. But I was right — vaccines now have profit margins that equal pharmaceuticals.”

Crooke left in 1988 to start his own company, Isis Pharmaceuticals, and Poste took over as president of the R&D division. In the 1990s, as part of a forward-looking executive cadre, he helped to devise a “grand plan” for the company. It was an early vision of “personalized medicine.” Poste anticipated an integrated program of genomics-based drug discovery, companion diagnostics, and healthcare informatics.

In 1993, he spearheaded SmithKline’s landmark $125 million deal for rights to develop drugs, vaccines, and diagnostics from gene sequences identified by the pioneering genomics company, Human Genome Sciences. It was a bold move. The company recouped its investment by subleasing access to the sequence data, but the integrated healthcare framework wasn’t realized. “It was premature,” says Poste, “and the company reverted back to the standard pharma model.”

In retrospect, Poste sees the episode as a lesson in biological complexity and big picture pharmacology: “You need to work from the bottom up, you need the genes, but you also need a top-down understanding of the system. So, we missed a lot of things.” Two decades later, molecular medicine is still moving into terra incognita. The “personalization” of medicine is still in its infancy.

In 2000, SmithKline merged with Glaxo Wellcome, and Poste was ready to step out. He had by this time received high honors from his country of origin — he had been elected a Fellow of the Royal Society and received the Order of Commander of the British Empire from Queen Elizabeth — and he had helped shepherd more than thirty new drugs to market.

In his “retirement,” Poste planned to shuttle between his three favorite cities — San Francisco, San Diego, and Scottsdale, Arizona — serving biotech enterprises as a director and consultant. After 9/11, however, his expertise became vital to the US Department of Defense. For two years, he traveled regularly to Washington, DC to chair the agency’s Defense Science Board Bioterrorism Task Force (and he continues to advise on matters of national security).

In 2003, Michael Crow, president of Arizona State University, asked Poste to help the school set up a life sciences innovation center, the Biodesign Institute, that would merge the best of university and industry research styles. Some on campus felt the two approaches were antithetical. Poste didn’t. He accepted the invitation.

He implemented what he calls a “3M” approach as the core organizing principle in the Biodesign Institute’s multi-investigator, multi-institution, multi-million dollar research projects. “Just as in industry,” Poste explains, “projects are led by teams and the matrices of ever-fluid, ever-shifting assemblies of skills needed at any given time to tackle specific problems.”

In 2009, Crow asked Poste to lead another new program, the Complex Adaptive Systems Initiative (CASI), to drive 3M projects on a larger scale across the university’s research units. CASI seeks multidisciplinary solutions to pressing problems as they emerge from within complex sociotechnical systems — financial crises, food and water shortages, pandemics, bioterrorism, cyber warfare, and the complex potential effects of climate change, for example. For a big picture guy, CASI is an ideal environment.

Poste chalks up much of his professional success to luck, and the fact that he never worked for anyone who viewed him as a competitor: “Every single person I‘ve worked for has been gifted. None felt threatened by my talents.” He also acknowledges the stimulating influence of creative and insightful colleagues at Bristol, Roswell Park, SmithKline, and Arizona State.

Beyond good fortune and good friends, he recognizes the importance of three fateful personal decisions: “To go to university, to come to the United States, and to go into industry. Those choices led me to a very enjoyable and successful life.” Finally, Poste cites his natural inquisitiveness, inherited from both of his parents. “I still have a voracious appetite for knowledge,” he says. “My kids joke that when they try to nail the coffin shut, my hand will shoot out and they’ll hear, ‘Wait a minute, there’s one more thing I want to know.”

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Telling the story of biotechnology