Gunther Stent, Generalist, Feted at 80 Chromosome Mystery Solved

Transcript MCB Spring 2005 • Vol. 8, No. 1 Newsletter for Members and Alumni of the Department of Molecular & Cell Biology at the University of California, Berkeley Gunther Stent, Generalist, Chromosome Feted at 80 Mystery Solved Neurologist Oliver Sacks, chemist Manfred Few sights are as awe-inspiring as a cell in Eigen and biologist Sydney Brenner were anaphase. Seen through the microscope, the among the scientific notables who gathered replicated chromosomes, having lined up in Koshland Hall on a sunny April Saturday neatly along the midline of the dividing cell to celebrate the life and work of Professor like a row of tiny X’s, are simultaneously Emeritus Gunther Stent. The rare congress of yanked apart. Each X splits into two sideways luminaries and Nobel-prizewinners from V’s careening in opposite directions, folded diverse fields was intended to represent at the middle like a running back receiving a Stent’s wide-ranging interests and contribu- flying tackle. It all happens in the blink of an tions over the course of his career, which has eye in a space smaller than a speck of dust. lasted more than half a century. The orderly segregation of chromo- Organizers Michael Botchan and David somes is absolutely essential to ensure that Weisblat originally wanted the symposium to Gunther Stent every cell has a complete set of genes. Errors coincide with Stent’s 80th birthday last year, in segregation can sometimes lead to cancer but coordinating the visits of so many top sci- or birth defects. Yet how every cell pulls this entists proved more challenging than expect- influenced by physicist Erwin Schrödinger’s off without a hitch nearly every time is poor- ed, Botchan says. In the end, the April 9 book What is Life?, which suggested that ly understood. symposium featured seven speakers who undiscovered laws of physics might be neces- continued on page 4 . spoke on subjects as diverse as genome sary to explain heredity. The book mentioned expression, free will and visual perception. Max Delbrück as a young physicist with Besides the many local friends, colleagues and interesting ideas along these lines. So Stent interested students who filled Cox wrote Delbrück to ask if he could join his lab Auditorium, former post-docs and graduate at the California Institute of Technology as a students of Stent’s turned up from around the postdoc. country. Throughout the day, Stent looked As Stent tells it today, he hardly knew radiant. “I was completely overwhelmed,” he what he was getting into. Delbrück was using said a week later in his office in LSA. bacteriophage to study the nature of genes, Stent was among the handful of pioneer- and when he offered the young Stent a posi- ing scientists whose work launched the disci- tion, he said: “Do you want to work on pline molecular biology after the second phage?” “Yes sir,” Stent replied, “that’s exactly world war. Having fled Nazi Germany in what I want to work on, but could you 1940, Stent went to school in Chicago and refresh my memory as to just what phage is later studied physical chemistry at the actually all about?” University of Illinois. But after graduate Collared: Dam1 rings bound to microtubules school, his interests turned to biology. Like (Courtesy of Stefan Westermann) many of his contemporaries, he was deeply continued on page 2 . Gunther Stent continued from page 1 Stent came to UC Berkeley as an he published more than 100 papers on the experiments of Oswald Avery, which demon- Assistant Biochemist in 1952, around which neurophysiology of the leech. strated DNA to be the genetic substance, as time DNA had just become generally accept- At the same time, Stent began to an example of premature science. Even ed as the chemical basis of heredity. At explore more deeply his longstanding inter- though in retrospect the implications of the Berkeley, he continued to study the nature of est in philosophical questions. He published experiment were clear, Stent argued it had genes and their expression through the use of articles such as “Molecular biology and little impact on genetics at the time and few DNA radio-labeling techniques in bacterio- metaphysics” (Nature 248, 779-781; 1974), people talked about its significance until phage and E. coli. He helped establish and and “Limits to the scientific understanding years later. But some scientists, including shape the Department of Virology in 1957 of man” (Science 187, 1052-1057; 1975). Nobel-prizewinning geneticist Joshua and the Department of Molecular Biology in Philosophical claims often provoke Lederberg, were annoyed by Stent’s article, 1964. He chaired that department from 1980 controversy, and Stent’s were no exception. saying they knew full well the implications of to 1986 and then served as the founding One article, “Prematurity and uniqueness in the work right away. The paper still touches chair of MCB, which subsumed molecular scientific discovery” (Sci Am. 227, 84-93; off philosophical arguments today, much to biology and biochemistry, until 1992. 1972), got him into hot water with col- Stent’s surprise. “I thought it was a simple In the late 1960’s, Stent’s interest began leagues because it described the classic 1944 point,” he says. to turn away from strictly molecular questions. He had decided that the really com- pelling problems—such as the structure of DNA and the genetic code— had all been solved. As Brenner told the audience at the symposium, Stent liked to say at the time that “molecular biology has such a great future behind it.” What grabbed his interest was neuroscience, and over the next 20 years Clockwise from top: Seymour Benzer and Gunther Stent during a break; Oliver Sacks prepares his talk; Dale Purves discusses the nature of vision with Jim Watson; Stent and Eric Wieschaus at lunch. 2 Philosophical differences were in evi- Other speakers included Princeton dence at the symposium as well. Noted University biologist Eric Wieshaus, who Berkeley philosophy professor John Searle, shared the 1995 Nobel Prize in Physiology or Ruthild Winkler-Oswatitsch, Manfred who has sparred with Stent on previous occa- Medicine for his work on embryonic devel- sions, devoted his talk to their disagreement opment, and Manfred Eigen from the Max over the nature of consciousness and free will. Planck Institute for Biophysical Chemistry in Eigen’s partner and frequent co-author, “The highest compliment one philosopher Göttingen and winner of the 1967 Nobel can pay another is to try to refute something Prize in Chemistry. Among the well-known took photographs throughout he says,” said Searle. “I’m now going to pay figures in the audience were science writer Gunther a compliment.” Horace Judson, author of The Eighth Day of The day’s wide-ranging and thought- Creation: Makers of the Revolution in Biology, the day and was kind enough to provide provoking talks, punctuated with humorous as well as James Watson and Seymour Benzer, anecdotes delivered in a roast-like manner, who, with Stent, were members of Delbrück’s copies to the Transcript. A sampling kept the audience well entertained. Brenner, “Phage Group” at Cold Spring Harbor Stent’s first postdoc in the early 1950’s and Laboratory in New York. winner of the 2002 Nobel Prize for his work The day was appreciated by young and appears below. on developmental genetics, discussed his old alike. “Biology in general should pay ideas about the relationship between more attention to his senior citizens,” said ‘genome’ and ‘phenome.’ Neurologist Oliver Professor Emeritus Harry Rubin. “It tends to Sacks, author of The Man Who Mistook His forget its history in the rush to be up to Wife for a Hat and Awakenings, described date.” At least on this day, history was clinical cases of brain lesions that suggest remembered. human consciousness is much more modular than it seems. Clockwise from right: Stent unwinds at the end of the day with Manfred Eigen; John Searle delivers his critique of Stent's ideas on free will; Stent converses with his former postdoc (of 50 years ago) Sydney Brenner. 3 . Chromosomes continued from page 1 Now a group of MCB researchers led by chromosome hangs on has been one of the the 10 components and showed that they David Drubin, Eva Nogales and Georjana big mysteries.” could form rings around microtubules in a test Barnes has opened a window to one of the The first hint of a solution came in 1998 tube. In the electron microscope, these look most perplexing aspects of chromosome seg- with the discovery of a protein called Dam1, something like curtain rings around a rod (see regation. In a paper published in January, mutations in which either cause the spindles image on page 1). The rings stabilize the they describe a remarkable ring complex that to break down or produce defects in segrega- microtubules, and, perhaps most strikingly, are attaches the segregating chromosomes to the tion ( J Cell Biol. 143, 1029-1040; 1998). able to slide along them in a manner sugges- microtubule fibers that lead to opposite poles Later, Iain Cheeseman, a former graduate tive of the way the entire kinetochore may of the cell. The rings appear to slide along the student in the Drubin/Barnes lab, showed slide along the crumbling microtubule during microtubule, keeping the chromosome con- that Dam1 was part of a 10-member complex anaphase. nected even as the microtubule disintegrates needed for microtubules to attach to the Work is now continuing to show how the and shortens rapidly during anaphase. kinetochore (reviewed in J Cell Biol. Dam1 ring fits into the whole kinetochore. “When I first saw the pictures, I 157,199-203; 2002).

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