J. Michael Bishop, MD, UCSF chancellor emeritus and Nobel Prize laureate, was honored at a daylong science symposium June 7 in Genentech Hall on the UCSF Mission Bay campus. Bishop, 74, served as chancellor from 1998 through last June, leading UCSF into a period of expansive growth. He continues to head a research lab on campus, which he has done continually since coming to UCSF as a faculty member in 1968. In 1989, Bishop and UCSF colleague Harold Varmus, MD, shared the Nobel Prize for Medicine or Physiology for their discovery that cancers can arise when certain normal genes become abnormally altered oncogenes. The symposium, titled, “Critical Unsolved Problems in BioMedicine,” was jam-packed with scientific information, and with audience members from the UCSF community and beyond. Scientists wrapped their minds around four difficult questions of broad interest: Can We Eradicate Malaria?, How Do Cells Make Decisions?, How Do We Prevent [Cancer] Metastasis?, and How Does the Brain Represent the Outside World? During each of the four sessions, invited experts from universities nationwide presented a main talk on the topic and then were joined by UCSF scientists in a panel discussion and question-and-answer period. The moderators who introduced each session offered perspectives on Bishop’s contributions to UCSF.
Mike Bishop, chancellor emeritus, talks with biotechnology pioneer William Rutter, former professor and chair of the Department of Biochemistry and Biophysics at UCSF, at a reception following a science symposium held to honor the former chancellor.
Bishop’s AccomplishmentsUCSF Chancellor Susan Desmond-Hellmann, MD, MPH, kicked off the day by lauding her predecessor’s accomplishments. Desmond-Hellmann noted that Bishop presided over many key advances, including the re-establishment of the UCSF Medical Center under new leadership after the dissolution of the merger that created UCSF Stanford Health Care, the development of the Mission Bay campus, the first new research building constructed over the last 40 years on Parnassus Heights, a record-setting, $1.7 billion fundraising campaign, a successful initiative to hire more female faculty, a boost of support for public art on UCSF campuses, a new peak in funding from the National Institutes of Health (NIH), the creation of the multi-campus California Institute for Quantitative Biology (QB3), and the establishment of the UCSF Global Health Sciences Research program. “The most important thing for our campus is that Mike has retired as chancellor, but has not retired as a faculty member and a leader in science,” Desmond-Hellmann said. During a lunch in Bishop’s honor, it was announced that the collection of contemporary art on public display at the campus will be named the J. Michael Bishop Art Collection at Mission Bay. To establish a public art program, in 1999 Bishop committed one percent of the privately funded construction costs for new buildings.
Eradicating MalariaHaile Debas, MD, executive director of the UCSF Global Health Sciences program, moderated the scientific session on malaria. Spread by mosquito-borne parasites, the disease is a major cause of death in many countries. There were 247 million cases of malaria worldwide in 2008, according to the World Health Organization. Christopher Plowe, MD, MPH, professor and chief of the Malaria Section with the University of Maryland Medical School Center for Vaccine Development, provided a perspective on the history of malaria as a public health problem. Plowe outlined the waxing and waning of public health programs and the ebb and flow of the disease across the globe. Phil Rosenthal, MD, professor of medicine at San Francisco General Hospital, described how the major malaria parasite, Plasmodium falciparum, is becoming resistant to the current cornerstone of treatment, Artemisinin, normally used in combination with other drugs. Regarding the goal of eradication, Rosenthal noted that, “In every case where we have had good success, vaccines are the principal tool.” UCSF researcher Joe DeRisi, PhD, a leading molecular biologist who studies malaria -- including Artemisinin resistance -- emphasized that the timely development of innovative new treatment ideas, including ideas for vaccines, will require that more researchers begin working on aspects of malaria that remain poorly understood. Molecular biologists and other lab scientists must find out more about how the human immune response and the malaria parasite adapt to each other during the course of infection, DeRisi said. Richard Feachem, PhD, director of the Global Health Group at UCSF Global Health Sciences, said he is optimistic that efforts to combat malaria worldwide will not once again fall into neglect. However, he warned that the global economic crisis will cause nations to renege on their funding commitments in coming years and that this will require public health leaders to do more with less. Panelists anticipated greater success in controlling malaria, but none of the panelists said elimination of the disease was likely to occur over the next few decades.
How Cells Make DecisionsThe audience grew to standing-room-only size, bolstered by many graduate students, for the session on cellular decision-making. Marc Kirshner, PhD, a former colleague of Bishop’s at UCSF and now a faculty member at Harvard University, provided the introduction. Richard Losick, PhD, also of Harvard, described new insights into the seemingly miraculous capability of certain single-cell bacteria to adapt to their surroundings by forming organized, multicellular structures called biofilms -- living communities, complete with “cheaters” and “cooperators.” Biofilms form in natural and industrial systems, but also can play an important role in some diseases. Bacteria may form biofilms when stressed, and they may return to their separate, independent ways when conditions are more favorable. Studying the bacterium Bacillus subtilis, Losick found that these two distinct states – independent and communal – are both stable, thanks to molecular feedback loops. Chance events, a kind of statistical “noise,” can eventually help trigger the switch between the two states. To aid in the formation of biofilms, the bacteria use amino acids that are the mirror images of the amino acids that form human proteins. The bacterial amino acids have distinctively different biochemical capabilities. They guide the production of a type of protein fiber called “amyloid,” which plays a role in biofilm formation. Hamad El-Samad, PhD, from the joint UCSF/UC Berkeley Graduate Group in Bioengineering, described efforts to use computational methods to predict the behavior of complex biological feedback systems, such as those that guide biofilm formation. Jonathan Weissman, PhD, a Howard Hughes Medical Institute investigator at UCSF, described the self-propagating nature of amyloid fibers. Amyloid structures appear to play a role not only in the formation of biofilms, but also in other biological phenomena – including the development of human neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease.
Preventing MetastasisThe topic of the third session was cancer metastasis – the spread and re-growth of a tumor in a different tissue than the one in which it first arose. When cancer kills, metastasis is the ultimate cause in 90 percent of cases. The session was moderated by Harold Varmus, the collaborator with whom Bishop shared the Nobel Prize. Varmus, a former head of the NIH and currently the president of the Sloan-Kettering Memorial Cancer Institute, was recently tapped by President Barack Obama to head the National Cancer Institute, part of the NIH. Varmus, speaker Joan Massagué, PhD, chair of cancer biology and genetics at Sloan Kettering, along with two panelists from UCSF – cancer researchers Zena Werb, PhD, and Marc Shuman, MD – explained why metastasis has been an elusive target for decades. Different types of tumors favor the invasion of different tissues when they spread. Massagué discussed his lab team’s progress in identifying telltale marker molecules that might be used to predict which tissues are likely to be colonized by particular tumors. Similar studies may also lead to new ideas for targeting the metastatic spread of cancer. Shuman cited the need to learn more from the direct study of cancerous cells that have spread beyond a primary tumor, as well as the difficulty of doing so. Metastatic tissue may sometimes be obtained during autopsies, which today are seldom performed. Current methods of biopsying metastatic tissue normally do not justify the risk to the patient, Shuman said. Cells in established tumors do not represent a single clone – they are quite diverse. The study of circulating tumor cells has not yet yielded a way to identify which cells among them are responsible for metastasis. Werb explained that the body’s non-cancerous tissues, especially those bordering tumors, may help govern the spread of tumors. She also described how the immune system can both encourage and suppress tumor growth.
NeurosciencesMichael Stryker, PhD, from the Keck Center for Integrative Neuroscience at UCSF, introduced speaker Patricia Churchland, PhD, a philosopher from UC San Diego. Churchland is well-known among neuroscientists for treading far beyond the research realms they themselves explore in their own laboratories. Churchland described how she uses what is known about human biology and the nervous system as the basis for exploring how complex mental constructs might arise. She discussed her hypothesis for how morality might be formed as a result of biological mechanisms that foster attachment and trust. Keck Center scientist Loren Frank, PhD, described his research in animals showing how patterns of nerve-cell signal transmission appear to be established uniquely during different learning experiences. Frank’s experiments indicate that the repetition of an experience triggers the same pattern or nerve firing, and that the brain can also regenerate the same unique signaling pattern after the experience has passed – suggesting a link between the repetition of the firing pattern and the establishment of a memory. Michael Brainard, PhD, also a Keck Center researcher, studies how birds learn their songs. Brainard has traced successful song-learning back to a region of the brain known as the basal ganglia, which also plays an important role in the brain’s pleasure-generating reward system. Photos by Noah Berger
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