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Theodore T. Puck

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Theodore T. Puck NATIONAL ACADEMY OF SCIENCES THEODORE THOMAS PUCK 1 9 1 6 — 2 0 0 5 A Biographical Memoir by DAVID PATTERSON Any opinions expressed in this memoir are those of the author and do not necessarily reflect the views of the National Academy of Sciences. Biographical Memoir COPYRIGHT 2009 NATIONAL ACADEMY OF SCIENCES WASHINGTON, D.C. THEODORE THOMAS PUCK September 24, 1916–November 6, 2005 BY DAVID PATTERSON HEODORE PUCK WAS ONE of those rare scientists who es- Tsentially created a new discipline, somatic cell genetics. His work made possible much of modern mammalian cell molecular genetics. He devised the first practical method to accomplish single-cell plating of mammalian cells with a high (indistinguishable from 100 percent in some cases) plating efficiency (1955). What is not so widely recognized are his contributions to the more technical aspects of this discipline; for example, he and his colleagues designed and built the first really practical CO2 incubators for growing mammalian cells as individual colonies (1962,2). The incubators we all currently use, although technologically much different from Ted’s original design, are based on the principles that he established. Ted’s lab was still building incubators when I arrived in 1971, and in my experience these incubators worked bet- ter than anything available to this day. He recognized early on the importance of devising well-defined, and hopefully completely defined, growth media for mammalian cells. He was certainly not the first to come to this realization, but he and his colleagues, especially Richard Ham and Gordon Sato, were among the most successful (Ham 1965; Barnes and Sato, 1980). One result of these studies was Ham’s F10 B IO G RAPHICAL MEMOIRS and later Ham’s F12 media, which are still widely used. He established and characterized the Chinese hamster ovary cell line K1 (CHO-K1), which remains a mainstay of modern mammalian cell genetics and is widely used in academic labs and in many biotechnology companies because of its favor- able growth characteristics and ease of use for many different kinds of experiments (Puck, 1985). These innovations were critical for the success of somatic cell genetics. Shortly after devising the single-cell plating technique, Ted and his colleagues determined the mean lethal dose of X irradiation required to kill mammalian cells (1956,2). This experiment is widely recognized as one that revolutionized the field of radiation biology. It is also recognized as having a revolutionary effect on the use of radiation to treat cancer. Another early contribution involved the definitive proof that humans have 6 chromosomes. Clearly this was first shown by Tjio and Levan, but their results were not easily accepted (Tjio and Levan, 1956); for example, in 1958 a suggestion was made that humans could have 6, 7, or 8 chromosomes, and that Caucasians and Japanese might differ in this regard (Kodani, 1958). Ted’s immediate recognition of the outstand- ing nature of Tjio and Levan’s cytogenetic work led him to invite Tjio to join the laboratory, where they made important contributions firmly demonstrating that 6 is indeed the cor- rect number of human chromosomes (1958,1). He organized a seminal meeting in 1960 in Denver that established the Denver system of chromosome classification that is the basis for the methods still used today (1960,2). Ted and his colleagues developed the first practical method for isolating auxotrophic mutants of CHO-K1 cells (1967,2; 1968). His laboratory was one of the first to use somatic cell hybridization to map genes onto human chro- mosomes and the first to identify different complementa- tion groups among auxotrophic mutants with the same THEODORE THOMAS PUCK 5 nutritional requirements (glycine in this case) (1969,1,2). His laboratory was also one of the first to apply techniques of molecular biology to extend the resolution of mapping human chromosomes theoretically to any degree of resolu- tion desired (1982). He was one of the first to recognize the relationship between structural components of the cell and regulation of gene activity, a phenomenon he called “gene exposure” (Ashall et al., 1988). He also devised what may be the most sensitive assay for mutation using mammalian cells in existence (1997, 2002). He looked upon this as one of his most important scientific endeavors, one that he continued to pursue until his death. Ted was elected to the National Academy of Sciences in 1960 and the Institute of Medicine in 197. He garnered numerous awards in his life, including the Lasker Award in Health Science in 1958, a Distinguished Professorship of the American Cancer Society in 1966, the E. B. Wilson Medal of the American Society for Cell Biology in 198, the Bonfils- Stanton Foundation Award in Science in 198, and many others. Unfortunately he was never awarded the Nobel Prize, which I and many others are convinced he deserved. Ted was born in 1916 in Chicago. He remained in Chi- cago—with the exception of a one-year stay in Gary, Indiana, during his childhood—throughout his education, including his Ph.D. training with James Franck, a Nobel laureate in physics, at the University of Chicago. Early in his life he and his brother Bernard helped their father install asbestos insulation. At that time the dangers of asbestos were not known. Tragically his brother died of mesothelioma, a form of lung cancer provoked by exposure to asbestos fibers. Ted credits his brother’s death, which occurred after he started working on cancer, with giving him a more personal stake in his research. This experience probably also contributed to Ted’s lifelong interest in environmental mutagens. Indeed, 6 B IO G RAPHICAL MEMOIRS he was working on methods to detect environmental muta- gens until he died. His goal was to develop a rapid, accurate, inexpensive, and simple method for detecting environmental mutagens so that exposure to them could be eliminated or minimized. Ted was a dedicated family man who was extremely proud of the accomplishments of his wife, Mary, who coauthored many publications on sex chromosome disorders with Arthur Robinson. They were married at the Taos Pueblo in New Mexico, and had a home in Santa Fe, where his wife now resides. He was especially proud, and rightly so, of his three daughters, all M.D.s: Jennifer, Stirling, and Laurel. He died of complications from a fall on November 6, 2005. James Franck had a major influence on Ted’s career. Ted used to tell us that during World War II, he had been recruited (it seemed more like drafted to him at the time) to work on the Manhattan Project and that Professor Franck not only advised against it but made sure that Ted was not forced to work on the project. Franck, who was involved in the Manhattan Project, eventually chaired a committee that issued what became known as the Franck Report, the official title being “Report of the Committee on Political and So- cial Problems Manhattan Project ‘Metallurgical Laboratory’ University of Chicago, June 11, 195” (http://www.dannen. com/decision/franck.html). In this report the committee, which also included Leo Szilard (see below), urged the demonstration of the atom bomb at an uninhabited site rather than its use against Japan and predicted the arms race that later occurred. Since this was a classified report, it is not likely that Ted knew about it until later, but one can- not help but speculate that Ted’s relationship with Franck helped shape his lifelong interest in the role of science in human society. THEODORE THOMAS PUCK 7 During World War II, Ted stayed at the University of Chi- cago, where he worked in the laboratory of O. H. Robertson in the Department of Medicine on problems related to aerosols and the spread of bacterial and viral infections through the air and on dust particles. He was also a member of the Com- mission on Air-borne Infections, Army Epidemiological Board, Office of the Surgeon General, and his work had relevance to the war effort. In this capacity he was remarkably produc- tive, publishing over 0 manuscripts. This period heightened his interest in biological sciences, and he applied for and obtained a postdoctoral fellowship in the laboratory of Max Delbruck at the California Institute of Technology, where he developed his interest in genetics and in the application of physical principles to biological problems. He remained in Delbruck’s lab for only one year. At that point he was suc- cessfully recruited to establish and chair the Department of Biophysics at the University of Colorado Medical School. He remained affiliated with the University of Colorado for the rest of his life. He continued his work on bacteriophage until 195, publishing 1 papers, many of which made important contributions to understanding of phage-host interactions. At that point his career shifted into mammalian cell tissue culture and somatic cell genetics. At this point I would like to comment on Ted’s relation- ship to Leo Szilard because this is a matter of some sensitiv- ity. It is true that the nature of Szilard’s involvement in the development of the feeder layer technology for single-cell growth of mammalian cells is a matter of some discussion, with the exact nature of the contribution being somewhat unclear (199; Marcus et al., 2006). What is often overlooked in these discussions of events in and around 195 and 1955 is that the evidence shows that Ted retained a deep respect and admiration for Szilard; for example, Szilard won the 1960 award as Humanist of the Year from the American Humanist 8 B IO G RAPHICAL MEMOIRS Association. Ted presented the award to Szilard on behalf of the association and wrote an eloquent article extolling Szilard’s scientific accomplishments as well as his accomplish- ments as a humanitarian (1960,1).
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