The Pew Charitable Trusts

Jack Keene was born in Florida, one of four children. His father worked in early computers for the RAND Corporation, and the family moved numerous times. Keene finished high school in Redlands, California, and entered University of California, Los Angeles (UCLA), later transferring to University of California, Riverside. There he majored in biology, inspired and mentored by Carlton Bovell. Next he entered Helen Whiteley’s lab at the University of Washington for a PhD in microbiology and immunology. While in graduate school he married. During his postdoc in Robert Lazzarini’s lab at the National Institutes of Health (NIH) he learned classical sequencing, scientific discipline, and high standards. He loved the NIH, where he met many important scientists, had good funding, and found congenial the atmosphere at the NIH generally and in Lazzarini’s lab in particular. Keene accepted an assistant professorship at Duke University. There he worked on negative-strand RNA virology until he won the Pew Scholars award. Wolfgang Joklik, the chairman of Keene’s department, became a very good mentor and friend. Keene studied how RNA virus works in autoimmune patients, using antibodies to study virus-host interactions; then cell components; eventually cell proteins. The work has engendered five publications so far, with five more coming, dealing with RNA-binding proteins. Keene obtained a patent on an autoimmune test kit, a patent he licensed to Duke and on which he consults; and he shares the royalties with his lab. He says the Pew Scholars award brought him notoriety, more academic work, and funding he was able to save for a low point. In five or ten years Keene hopes to understand basic principles of development of the human organism from fertilization to death. In his second interview Jack Keene expands on his biographical information. He worked summers in Missouri at relatives’ farms; worked at the US Salinity Laboratory while he was in graduate school; played guitar and sang, but only privately; took up the American Civil War as a hobby. His wife is an artist; she worked at the Smithsonian Institution while Keene was at the NIH; they have two grown children and some grandchildren. Making an easy transition to an assistant professorship at Duke University and interested in what proteins interact with regulating regions, Keene sequenced vesicular stomatitis virus, which is associated with rabies, Ebola, and influenza. Wolfgang Joklik, the department chairman, became his mentor and good friend; he helped Keene obtain grants, including the Pew Scholars award, using which Keene discovered RNA recognition motif (RRM). This led to work on binding specificity. Finding the multibinding of specific sequences has led to Keene’s post-transcription theory and in turn to a coordination theory of RNA operons. Keene muses throughout the interview on a number of subjects. He found at least the first Pew meetings perhaps excessively luxurious, but he enjoyed the intellectual talk and the chance to get to know such famous scientists as Joshua Lederberg, Daniel Tosteson, Gerald Weissman. He discusses his own lab management; teaching students to write; evidence-based reasoning; funding’s outsized role in competition for students and for the rush to publish. He says that science cannot be proved, only disproved; that truth equals functional truth. While on the Pew Scholars Program advisory committee he looked for imagination and passion in applicants. For a while he was department chairman but had to delegate his chairman duties in order to teach and run his lab. In fact, two subsequent Pew Scholars came from his lab. A merger of departments created the Center for RNA Biology for him. Keene considers his discovery of the binding motif a major contribution to biochemistry. Having found the protein that regulates growth control messages, he switched to working in that area. Fen-Baio Gao, his student, got the protein to bind with brain RNAs; from that they discovered that translation activated RNAs into proteins, and this became the early core of the operon regulon model. Because this work was considered “odd,” it was hard to find funding, so he used some Pew money. Scott Tenenbaum, his postdoc, used microarrays for in vivo testing, a major turning point. Keene’s theory was hard to communicate and unpersuasive, but finally Keene got an in vivo hypothesis article published. The operon was discovered in mammals in Keene’s lab and later proved in yeast in Patrick Brown’s lab. Keene is now working on exosomes, microscopic particles that pass RNA operons among cells; this is a new direction, not yet credible, he says. Keene concludes his interview with more general musings. He points out that there have been no RNA operon publications in Science. He believes that the NIH should spread funding around among investigator-initiated projects, not give blocks of money to large but often-unsuccessful projects like development of an AIDS vaccine. He talks about science ethics and the public trust; who should decide funding; and a lack of science understanding among citizens. He says that guidelines, oversight, and interest are needed on the part of the National Science Foundation’s outreach requirements; his own project was rejected. For assigning value to scientists and their work he compares the European system with the American. Projects these days are often too big and have too many authors, so young scientists are not recognized. Keene gives his opinions on innate genius versus luck; careerism versus professionalism; personal responsibility; and the importance of morals in rearing children. Keene believes that his work is extremely important. He reiterates his belief that truth equals functional truth.

Susan J. Birren spent time in New York and Washington, D.C., though grew up mostly in Kentfield, California, just north of San Francisco, the second youngest of four siblings.  Her father was a lawyer, and then an administrative law judge, for the National Labor Relations Board; her mother studied art and worked as a designer in the garment industry until she had children, after which she became a professional artist.  Her family did much together—camping, sailing, hiking, and general playing—and Birren was an avid reader and enjoyed exploring nature.  Academics came easily and she had a clear interest in science and mathematics throughout her early schooling; a female chemistry teacher in high school, with a master’s degree, proved somewhat influential.

Birren applied to two schools only for college and undertook her undergraduate career at the University of California, Berkeley.  Initially interested in studying mathematics, she decided to switch to biochemistry for her major and had the opportunity to work with Edward E. Penhoet, who later became one of the founders of Chiron Corporation.  She worked on isolating opsins from a halobacterium, a high-salt bacterium, but, more importantly, she fell in love with lab life and lab culture and benefitted from being mentored by Penhoet.  From Berkeley she moved on to the University of California, Los Angeles working with Harvey R. Hirschman on the transcriptional regulation of the metallothionein gene; while there, Kathryn L. Calame also served as a mentor.  Birren decided to remain in California for her postdoctoral work, moving into the lab of David J. Anderson at the California Institute of Technology, studying the differentiation of neural crest cells.  From there she went on to a faculty position at Brandeis University looking at the functional development of neurons.

During the interview Birren was candid about being a working mother and dealing with a chronic medical condition.  At the end of the interview she discusses gender issues in science; administrative duties; the grant-writing process; balancing career and family; the issue of patents; creativity in science; and the role of serendipity in her work.  The interview concludes with thoughts on teaching the history of science; the process of conducting scientific research; setting the national scientific agenda; the role of the scientist in educating the public; and the role of the Pew Scholars Program in the Biomedical Sciences on her work.

Anthony Brown was one of two sons of a father in the Royal Navy and a mother of Armenian descent who spoke several languages. The family lived in a number of places primarily on the south coast of England. Brown attended Cranleigh School, where his interest in science evolved past the “inevitable chemistry set.” The British system of education required that he study three related subjects, so he reluctantly gave up history. At the University of Cambridge he found chemistry dull but liked genetics and the history and philosophy of science. He decided to spend his third year in genetics. Two laboratory experiences and a brief foray into the “real world” convinced Brown he wanted to do science, so he entered a PhD program at the University of Edinburgh.

Degree in hand, Brown spent two postdoctoral years in Pierre Chambon’s lab at the Institute for Genetics and Cellular and Molecular Biology in Strasbourg, France, and three years in Harold Varmus’ lab at University of California, San Francisco. At this point he was ready for his own lab and was being recruited by the Imperial Cancer Research Fund (ICRF) in London, England. He sought competing offers and found Cornell University’s superior. Brown says science in the United States has better funding, access to more graduate students, and a smaller teaching load. His work is moving toward developmental biology; he hopes in future to understand differentiation pathways better. He likes a smaller lab, giving him some trainees and workers but not requiring ceding of control. He says the Pew meetings have given him the opportunity to learn about areas he would not otherwise have investigated, with the result that he is now working on developmental biology as well as the molecular biology of cancer. Brown finds the conflict between religion and science, as represented by Genesis and DNA, fascinating; his only religious connection is musical.

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