Portal de Periódicos da CAPES

Open to Scientific Opportunity

2009; Wiley; Volume: 2; Issue: 4 Linguagem: Inglês

10.1111/j.1752-8062.2009.00125.x

1752-8062

Elaine Musgrave,

Conferences and Exhibitions Management

Throughout his distinguished career, Nobel Laureate J. Michael Bishop, MD, has shown himself open to new challenges. Following his resignation this June as chancellor of the University of California, San Francisco (UCSF), he has looked forward to devoting more time to his UCSF research laboratory, which focuses on the genetic basis of cancer, and to the additional challenge, he says, of “getting back to reading a few novels.” During his more than 10 years of service as chancellor as well as during his previous decades as UCSF faculty member, Dr. Bishop's opportunities for leisure have been rare. Under his tenure as chancellor, UCSF has embarked upon many ambitious projects, including the UCSF Mission Bay campus, scheduled for completion in 2020 but already the site of productive research; a foundation, UCSF Global Sciences, supporting educational programs worldwide; collaboration with UC Berkeley and UC Santa Cruz in the California Institute for Quantitative Biosciences (QB3), a state-funded enterprise; and the launch of UCSF's Clinical and Translational Science Institute (CTSI), the largest federally-funded clinical and translational research center in the country. Dr. Bishop has also overseen significant institutional efforts in strategic planning, diversity outreach, work-life balance, and fundraising. The whole spectrum now of research design, research funding, and higher education in the biomedical sciences, be it PhD or professional—all of that happened here during my time. Reflecting on the strides UCSF has made in clinical and translational research during his time as chancellor, the 2003 National Medal of Science recipient takes a longer look at the institution's legacy in this area, a history reaching back to the beginning of the 20th century. As director of UCSF's G. W. Hooper Research Foundation, Dr. Bishop uses the work of his predecessors to illustrate how UCSF research has translated into concrete advances in health care. The foundation's first director, George Hoyt Whipple, identified vitamin B12 as a therapy for pernicious anemia, a discovery for which he and fellow researchers won a Nobel Prize. Another early director, Karl F. Meyer, participated in research that solved the California canning industry's botulism problem. In more recent years, research at UCSF identified surfactin as essential in neonatal care and the institution also played an important role in the development of recombinant DNA. “We’re not new to this game by any stretch of the imagination,” Dr. Bishop says. To sustain this rich legacy of innovation, UCSF continually adapts its organization and curricula to respond to developments in bio-medical research and practice. His work in the 1970s to develop the Program in Biomedical Sciences was a natural extension of his belief that departmental divisions are, as he says, “artificial boundaries.” That program was one of the first biomedical graduate programs to eliminate departmental borders in favor of a larger entity that took a unified approach to curriculum planning and faculty recruitment. Clinical departments also discovered significant benefits in the program's partnership. Dr. Bishop explains, “by doing joint hires between the clinical department and the program, the clinical departments were able to hire first-rank PhD scientists for whom one of the principal courtesies is accessibility to good graduate students.” The most recent innovation in UCSF's educational and research mission is a movement toward graduate coursework designed to foster translational research. Dr. Bishop reports that “graduate students have, of their own accord, certainly here and I think elsewhere, begun to request curricula that alert them to opportunities in true translational research, in research that actually has a mission, with a disease … as the target of that mission.” At UCSF, a concrete curriculum is taking shape, devised, Dr. Bishop says, “for PhD students who normally might just think about molecular biology or genetics or nanotechnology or whatever, but who actually wanted to be taught—not only exposed to but be taught about—the opportunities to apply their research interests to a problem in human biology or human disease.” For Dr. Bishop, UCSF's support of clinical and translational research spans “the whole spectrum now of research design, research funding, and higher education in the biomedical sciences, be it PhD or professional—all of that happened here during my time,” he says, “and I’ve done what little I can as chancellor to certainly encourage and foster it.” Ideally, Dr. Bishop says, “the administration does what it can to foster [change] and support it and see that quality control is exercised,” but the change itself “comes up from the ranks, from a widespread revelation or epiphany.” Dr. Bishop's commitment to this administrative flexibility and support derives from his own training, which defied traditional boundaries. It was only when he started receiving job offers that he found himself associated with a discipline—he says, “I was apparently a microbiologist”—and he began his medical training without knowing that biomedical research was an available career path. A graduate of a small liberal arts college where, at the time, research opportunities were virtually nonexistent, he credits his medical school colleagues with his introduction to the very concept of research. He did not find the research environment at Harvard Medical School particularly welcoming, but he was struck by the way research permeated the institution. “The value of research was what came across in the curriculum, the underpinning of what doctors learned to do and what physicians did in their daily practice,” he says. Research, he adds, was “portrayed as a very noble enterprise and a very human enterprise, too.” A year of from medical school and a pathology fellowship at Massachusetts General Hospital in Boston allowed him to “tinker” in the laboratory and read. Returning to medical school convinced he would finish his MD program and become a researcher, Dr. Bishop persuaded the Harvard Dean of Students to let him do just one clinical clerkship and spend the rest of the year on research. “Most of the people I talked to thought I was committing professional suicide,” he recalls, but his performance in that one clerkship earned him a coveted internship and residency in internal medicine at Mass General. We should be funding research across the spectrum according to opportunity, according to rigorously perceived opportunity. Despite what he describes as “a boot-straps sort of entry” into the world of biomedical research, once there Dr. Bishop thrived, finding his way to the National Institutes of Health (NIH) for a postdoctoral position and then moving to UCSF. He brought his research on poliovirus to San Francisco, but new discoveries and colleagues led him in unexpected directions. Ultimately, a team led by Dr. Bishop and then postdoctoral researcher Harold Varmus—later to direct the NIH from 1993–1999—identified the origin of src, an oncogene (cancer-causing gene) responsible for Rous sarcoma virus in chickens. Demonstrating that normal cells contain genes with the potential to become cancerous, this research earned Drs. Bishop and Varmus the 1989 Nobel Prize in Physiology or Medicine. “We were working with a very primitive assay,” Dr. Bishop says. Given that the undertaking was so diffcult, he says that people wonder why his team took such pains to do the work. “We bothered,” he insists, “because we thought we were answering a really important question, and we thought we could get a first answer this way, and we could—we did.” Since that momentous discovery, Dr. Bishop says, “the field has been propelled, as is usually the case in science, tremendously by technological advances.” Through subsequent research as well as administrative and advisory positions—he has served, for example, as the chair of the National Cancer Advisory Board— he has had the opportunity to observe and critique the logistics of performing and funding scientific research. Uninterested in semantic discussions about funding, he is grateful that the NIH chose to join the clinical and the translational in its Clinical and Translational Science Awards rather than debate about which term to invoke. He sees these types of research as belonging to one continuum and states emphatically, “We should be funding research across the spectrum according to opportunity, according to rigorously perceived opportunity.” Nevertheless, Dr. Bishop of ers no pat answer to the question of whether scientific research is adequately funded today. “The usual metric,” he points out, “is how many scientists are eligible to do the work versus how many are funded, or how many meritorious grant requests does an agency have as compared to how many they can fund,” but that evidence can be misleading. “There's a certain herd instinct in science,” Dr. Bishop notes, “and so a given number of grants on a given subject might well represent a true surfeit of what's necessary to keep that subject moving at an appropriate rate.” It is, however, a source of concern to him that federal funding for scientific research is dwarfed by what the pharmaceutical and cosmetic industries spend. More federal money could be invested in research, but how much?“I’ve never seen an adequate algorithm for it,” he says. “The essence of it is opportunism: you do need to have enough fungible money around so that you can move on something when it breaks.” To achieve this goal, Dr. Bishop says, the NIH needs more flexibility in its allocation of funds. The NIH's grant award process is “sluggish,” he says, and while attempts have been made to energize that process, commitment to peer-review necessarily requires a significant time investment. Nonetheless, there could be opportunities for the NIH to perform small-scale experiments modeled on the successes of other federal institutions. “You’d like to have a modest investment in something like DARPA [the Department of Defense's Defense Advanced Research Projects Agency],” he says, “where decisions can be made on wild ideas and quick feasibility studies done.” Dr. Bishop says he wants accountability in the grant process but worries that it is especially dificult now for scientists, particularly young scientists, to enjoy the freedom to innovate and use their grant funds to do risky projects. In a different era, Dr. Bishop recalls, that is precisely what he did. When he moved to California in the late 1960s, he had a grant to research poliovirus; when his interests changed, he used his grant money to begin work on Rous sarcoma virus. “By the time I had to write my renewal application, no one gave a damn. I was now doing gang-buster stuf on cancer viruses. That's what mattered. I changed the title of my grant and never looked back.”