It is not every day that a scientific society gives its top award to a scientist who already has a top award named after herself. This December 6 at its Annual Meeting in San Francisco, the ASCB will bestow the E.B. Wilson Medal, its highest scientific honor, on Mina J. Bissell, the namesake of the Mina J. Bissell Award presented since 2008 in Portugal by the University of Porto’s Graduate Program in Areas of Basic and Applied Biology. The Wilson medal is an actual medal, struck in honor of one of the founders of modern cell biology. The Bissell Award is a small metal sculpture, a ring set with moveable rectangles, which change the award’s shape depending on where it’s standing. This seems entirely fitting for Bissell, who turned cancer biology on its ear by demonstrating the importance of context in cell biology, especially in her exploration of the 3-D microenvironment’s effects on gene expression, tissue differentiation, and tumor fate.
Now in her fifth decade of a research career that shows no indication of slowing, Bissell is a Distinguished Scientist in the Life Sciences Division at the Lawrence Berkeley National Laboratory (LBNL) and a member of the faculty in five graduate programs at the University of California, Berkeley (UC Berkeley). Her publications list is staggering, her honors list overflowing (including the American Cancer Society’s Medal of Honor and an Honoris Docteur Causis from the Pierre and Marie Curie University in Paris). She has served both as ASCB President and as the chair of ASCB’s Women in Cell Biology Committee.
But it is Bissell’s controversial insistence that physical context matters in cells and her demonstrations that the extracellular matrix (ECM) was integral to breast tissue remodeling and to breast cancer progression that are being honored with the Wilson medal, according to Susan Lindquist of the Whitehead Institute. A former E.B. Wilson medalist herself, Lindquist wrote in support of Bissell’s nomination that, “In the past 20 years, she has revolutionized biologists’ view of the importance of external cues in controlling programs of gene expression and differentiation in normal tissue morphogenesis and in breast cancer. Her creative work forged a new frontier in cell biology, transforming our understanding of the role of extracellular matrix, the three-dimensional cellular microenvironment. She has fundamentally changed our understanding of the forces of tumor biology, and the ways in which tumor cells themselves influence their environment.”
Of Bissell, another previous E.B. Wilson medal winner (and previous ASCB President), Elaine Fuchs of Rockefeller University and the Howard Hughes Medical Institute declared, “She put the field of the microenvironment on the map and was the major instigator for the creation of two Study Sections at the NIH in this area. Her contributions to the field of tumor biology and the relevance of her work to normal regulatory mechanisms and cancer are indeed paradigm-shifting.”
Valerie Weaver, who is now at the University of California, San Francisco, was a new postdoc at the Canadian National Research Council when she first heard Bissell speak in Ottawa on the role of the ECM in mammary cell differentiation. Weaver decided on the spot that this was the topic she wanted to work on and Bissell was the PI she wanted to work with. Weaver relocated her postdoc to UC Berkeley and the Bissell lab in 1994. “I ended up spending five very influential years working under Mina’s direct mentorship during which I studied the role of stromal-epithelial interactions and tissue architecture in breast morphogenesis and cancer,” Weaver recalled. “This experience working with Mina…changed the trajectory of my research and left an indelible imprint on my scientific perspective and world view that have proved critical for my scientific success.”
But beyond Bissell’s scientific impact, Weaver wrote, “It is only now that I am an established scientist and I am more frequently thrust into leadership positions that I can truly appreciate the full measure of Mina’s impact on today’s cell biology research community.” Bissell’s influence extends well beyond her field, Weaver believes. “Her larger gift is that she inspires others to participate and take on new challenges through her own passion and dedication and also by her fearless and uncompromising leadership.“
Mina Bissell was born in Tehran, Iran, into a well-to-do, well-educated family. She excelled in science, emerging from high school as the top student of the year. She won an undergraduate scholarship education to Bryn Mawr in 1959 but transferred to Radcliffe/Harvard, graduating in chemistry in1963. She was accepted into the Microbiology and Molecular Genetics program at Harvard University, taking her doctorate in 1969, one of three women in the graduate school’s class of 200. After postdocs at Harvard and UC Berkeley, she was hired as a staff biochemist at LBNL in 1972. In a 2009 interview, Bissell recalled that, “When I interviewed for my first job at LBNL, I was three months pregnant, but it did not show and I didn’t see any reason to announce it. Then, when I showed up to start the job four months later, and was obviously pregnant at seven months, I was fired on the spot! I was told that pregnant women didn’t belong.” An older colleague interceded, offering to take Bissell into his lab. Bissell rose steadily in the Life Science Division at LBNL, reaching Senior Staff by 1976. In 1988, she became Director of Cell & Molecular Biology. In 1992, she became Director of the entire division.
Yet through the 1980s, Bissell’s papers were controversial, especially her hypothesis that there was a “dynamic reciprocity” between the ECM and the cell itself with signals passing in an interactive loop from ECM through the cytoskeleton to the nucleus to the chromatin where changes in expression would in turn affect the ECM. Later Bissell would describe some of the hostility she encountered in a 2009 interview with reporter Gina Kolata of the New York Times. Bissell recalled handing a new paper to a colleague visiting her office at LBNL. “He took the paper and held it over the wastebasket and said, ‘What do you want me to do with it?’ Then he dropped it in.”
But the scientific tide was turning as Bissell’s experiments yielded startling results. According to Fuchs, “In the 80s, she provided some of the more dramatic evidence of the significance of ‘context’ by showing that a potent oncogene such as Rous sarcoma virus (RSV) does not form tumors in chick embryos despite the activity of PP60 src (Dolberg and Bissell, 1984). Yet isolated cells plated on 2D cultures become mass transformed overnight. She showed that even in chickens, wounding is required for RSV to form tumors and her laboratory was the first to identify TGFβ as the culprit in wounding.” Bissell also championed 3D cell culture as the only way to replicate the complicated spatial arrangements in breast tissue or tumor architecture.
Bissell continues a rigorous speaking schedule that has included, by her calculation, over 130 named or distinguished lectures since 1980. She kicked off 2016 with a talk at the Indian Institute of Science, Education, & Research in Pune, India, and will be winding the year down next December in San Francisco when she receives her E.B. Wilson Medal and gives her lecture on December 6. Meantime Bissell continues as a tireless mentor. At last count, Bissell reports that of her former postdocs and grad students, two are now deans, 25 are tenured professors, 18 are assistant professors, 18 are in senior biotech positions,12 are PIs, plus numerous lab managers, educators, two patent attorneys, and one science editor. Here once again, the Bissell context is everything.