sign in sign up
<<
Home , James Watson

obituary Thomas Steitz 1940–2018

t was in December 1989, as an time I was not aware of Tom’s interests in undergraduate student at Zagreb the ribosome, I wrote to Tom and expressed IUniversity, that I first came face to face my interest in joining his group—where with Thomas Steitz: he was looking at me else to go for superb, state-of-the-art from a Research News article published structural and the conviction to in , “The structure of the ‘second tackle the impossible? The letter I received genetic code’” (Waldrop, M.M. Science as a reply was a revelation: without an 246, 1122; 1989). The article reported that interview, Tom offered me the position and Tom’s group at Yale had determined the mentioned among several other projects first structure of a complex between tRNA in his group “studies of the components of and the enzyme responsible for linking it to the synthesis machinery, including the correct amino acid, tRNA synthetase. the ribosome.” Both Tom and Peter Moore, Because my application to Yale for graduate a professor of Chemistry at Yale who had school had just been rejected a few months devoted his entire career to studying the earlier, I could not imagine then that six ribosome, were keen to pursue the project years later, my career would bring me to together, and I knew I had come to the right Tom’s laboratory, where we would share place. On a personal level, the ‘chemistry’ five intense and scientifically exciting was also right—Tom and I got along very years working on the structure of the large well. He had a charismatic presence, with ribosomal subunit. his white chin-curtain beard, and he could The sad news that Thomas Steitz passed appear intimidating because of his tendency away in early October of this year spread Credit: Yale University, Michael Marsland to talk slowly and deliberately, raising his quickly through the scientific community, voice when somebody tried to interject. He as it tends to do when a field loses one of was an impressive personality to be sure, its trailblazers. Tom was a true pioneer That December in 1989 was not the first but despite his drive, his sharp wit and his and a maverick in the field of structural time I marveled at research results from uncompromising commitment to high biology, and he pushed the boundaries of Tom’s laboratory. A few years earlier, trying standards in science, he was never arrogant the types of biological problems that could to understand the mechanism of DNA in his demeanor. On the contrary, Tom had be investigated. His scientific contributions replication, I found that the Steitz lab had a charming and very amiable personality. are now part of every undergraduate also provided the first structural insights I could talk to him easily, about a range of textbook. After hearing of into the mechanism of DNA polymerase and topics from science to sports and politics. Tom’s passing, colleagues asked me in had revealed the two-metal-ion mechanism On the day of my first visit to the lab, there disbelief whether it was true, but at the same of phosphoryl transfer that subsequently was a party, and Tom happily joined the time we all were aware that Tom’s scientific was shown to apply to all DNA and RNA crowd of students who got together that legacy will live on. polymerases. Later on, during the early evening and chatted along. Thomas Steitz was born in Milwaukee 1990s, with great interest, I followed Tom’s In September 1995, I joined Tom’s lab, in 1940. He studied chemistry at Lawrence research focusing on the key and within a few months after purifying College as an undergraduate and then involved in the expression and maintenance ribosomes from a number of species, helped pursued his PhD studies at Harvard of genetic information. His group published by Peter Moore’s technician Betty Freeborn, University with William Lipscomb. There, seminal results in that time period, including I managed to reproduce sheets of thin he also met his future wife, fellow scientist structures of the CAP transcription factor crystals of the large ribosomal subunit Joan Argetsinger, who was at the time a in complex with DNA; the lac repressor, from the halophilic archaeon Haloarcula PhD student in the lab of . a protein that was considered a paradigm marismortui, which had been reported The two were equally brilliant scientists, for understanding transcriptional control; almost a decade before by the Yonath and Joan herself later became one of the the RecA protein, which is involved in group. Then began the quest to find ways most prominent figures in the field of RNA homologous recombination; and HIV to improve the crystals and calculate the biology. Tom and Joan next moved together reverse transcriptase, the key enzyme phases that would ultimately allow us to to the Medical Research Council Laboratory involved in viral replication. visualize the structure. Tom was in the of in Cambridge, England, As I was approaching the end of my middle of it all, and he was extremely excited where Tom joined the laboratory of David PhD studies in in 1994, I started by the progress. However, the crystals were Blow for his postdoctoral studies. In 1970, investigating possible laboratories to pursue notoriously difficult to handle: they were Tom established his own group at Yale and my postdoctoral studies. From the time of thin, and attempts to derivatize them with later became Sterling Professor of Molecular my undergraduate interest in understanding heavy atoms yielded inconsistent results, Biophysics and Biochemistry and Investigator the expression of genetic information, thus suggesting problems with crystal of the Howard Hughes Medical Institute. In I had dreamed of investigating the structure packing. Tom provided critical comments 1990, his research accomplishments were of the ribosome, which I considered one that kept us on the right track and recognized with one of the highest honors of the key problems in biology. However, prevented us from getting trapped in partial in science when he became a member of the I was unsure of where and how to pursue interpretations of the crystallographic National Academy of . this formidable problem. Although at that data. This philosophy was typical for him:

Nature Structural & Molecular Biology | VOL 25 | DECEMBER 2018 | 1065–1066 | www..com/nsmb 1065 obituary

Tom’s mission to understand the most fundamental problems in biology resumed on many other fronts. Over the years, his research group contributed vastly to the understanding of RNA polymerases, including solving structures of complexes with a transcriptional repressor, DNA substrate and RNA transcript that have explained the opening of the transcription bubble and the processivity of the elongation complex. In the years that followed, our work on the structure of the large ribosomal subunit and Tom’s career-long contributions to structural biology were widely recognized as important milestones in the field: Tom and Peter went on to receive the Rosenstiel Award in basic biomedical research, and the people who worked on the project— Jeffrey Hansen, Poul Nissen, Peter Moore, Thomas Steitz and myself—shared the Newcomb Cleveland Prize of the American Association for the Advancement of Science with the group of Harry Noller. Tom later also received the Keio Medical Science Prize, the Gairdner International Award and Thomas Steitz (right), sitting next to the author (left), Zurich, 2006. Credit: Nenad Ban the George E. Palade Award, and in 2009 he shared the in Chemistry with Ada Yonath and Venkatraman keep your eye on the final goal, and do Our results finally enabled us to see Ramakrishnan. On the day after the not settle for anything less. We achieved what the active site of the ribosome was carefully choreographed Nobel Banquet, a major breakthrough in understanding made of. Tom, Peter, Poul, Jeff and I tried a large picture on the front page of the the nature of crystal disorder, an unusual to rotate the crystallographic map of the Swedish newspaper showed Sweden’s Crown case of twinning, and by the end of 1997 ribosome by using a computer that was Princess sitting between Tom and Venki, we were able to calculate the first maps of underpowered for the task. It kept skipping enjoying the meal. In a small footnote on the large ribosomal subunit. At that stage, until it luckily froze at just the right moment the same page, the newspaper also featured Poul Nissen from Denmark joined Tom’s to provide us with the perfect view. Tom a photograph of the American president, lab, and we combined forces toward the was elated, eyes shining and barely able and I felt that for a moment the world was goal of determining the high-resolution to contain his excitement. It was one of in its right order. structure of the ribosome. The crystals those defining moments when nature gives Tom’s view was that to fully understand were still frequently twinned, but, aware up one of its secrets. For the next several the chemical basis of biological processes, of the problem, we found a systematic way months, we remained rooted in front one had to capture the involved molecules to perform screening. Jeffrey Hansen, who of the workstations, in my case literally, in a functional complex and visualize joined the project at a later stage, managed because a ruptured Achilles tendon kept them at high resolution. Pursuing this to decrease the frequency of twinning by me immobilized. Tom had to undergo eye vision over many decades, Tom’s group changing the conditions under which the surgery during that time and was forced contributed monumental discoveries crystals were prepared for freezing before to lie face down for a while. This setback that changed structural biology and the crystallographic data collection. did not keep him from working on the understanding of . He will be missed as The next several years were very exciting; manuscript, face down. The high-resolution a scientist by everyone who has ever read there were new discoveries and strategies to structure was published in the summer his papers or heard him talk. By those of us discuss daily. Peter shared his encyclopedic of 2000 and had major implications who knew him personally as a colleague or knowledge of the ribosome field, and Tom for understanding the of life, mentor, he will be missed also as a shared his vast experience in structural because it revealed that the active dear friend. ❐ biology. We were also facing considerable site of the ribosome is made entirely competition, and everybody was tense, of ribosomal RNA. Nenad Ban trying to be as efficient as possible. Tom’s lab continued with seminal Department of Biology, Institute of Molecular Biology Nevertheless, when I mentioned to Tom that discoveries that advanced understanding of and Biophysics, ETH Zurich, Zurich, Switzerland. I was planning to take a few days off to go the mechanism of peptide-bond formation e-mail: [email protected] hiking with my friends, the same evening, he catalyzed by the ribosome. However, in sent me a detailed description of his favorite spite of the breakthroughs in understanding Published online: 26 November 2018 hiking trail. That’s how Tom was. the chemical basis of protein synthesis, https://doi.org/10.1038/s41594-018-0163-0

1066 Nature Structural & Molecular Biology | VOL 25 | DECEMBER 2018 | 1065–1066 | www.nature.com/nsmb