Lessons from Tom Steitz, surveyor of molecular empires (1940-2018)

The ribosome is one of the most important and complicated molecular machines ever devised by evolution. Functioning as the factory and assembler for making proteins from RNA, it is as important as DNA itself and is found in every life form on planet Earth. If we find life on another planet, along with some form of DNA, it is almost certain to contain some kind of ribosome.

Tom Steitz, Venki Ramakrishnan and Ada Yonath won the Nobel Prize for chemistry in 2009 for cracking the structure of the ribosome. I was saddened to hear that Steitz passed away a few days ago. Incidentally, his demise comes after Venki Ramakrishnan published his memoir on his ribosome odyssey, a journey that both starred and owed a lot to Tom Steitz.

Over more than two decades, Steitz, Ramakrishnan, Yonath and others used laborious techniques to carefully obtain more complicated and better structures of this beast of a molecule. And a beast it certainly was; the 40S subunit of a eukaryotic ribosome contains 1900 nucleotides and 33 proteins. While protein crystallography is now routine, solving the structure of a multiprotein assembly like the ribosome is incredibly daunting even now, and is a tribute to both the perseverance and the creativity of these scientists. Crystallography is the ultimate example of marathon running in science, something that at its highest levels can easily take a decade and long hours in the lab. Even before he attacked the ribosome, Steitz had already established a reputation as one of the world's top crystallographers, doing a detailed study of the enzyme hexokinase for instance. Among other findings, his work revealed that the ribosome is composed mainly of RNA rather than proteins; another boost for the RNA world theory for the origins of life.

I have fond memories of Steitz from my time as a postdoc at the University of North Carolina, Chapel Hill. In 2010, a year after he won the prize, he was a visiting lecturer at UNC. Four or five of us had a chance to sign up for a private breakfast with him in a small room at the faculty club. There wasn't a trace of ego in Steitz's interactions with us, but what I remember best was his unending curiosity regarding each of our research projects (not surprisingly, he was particularly interested in some cryo-EM work a colleague of mine was doing). It was clear that Seitz was no prima donna, but a scientist's scientist who was not resting on his laurels but seeking new adventures.

The New York Times has a good obituary of Steitz that showcases many of his qualities. After his PhD he trained at the famed MRC Laboratory of Molecular Biology, an institution started by Watson, Crick, Perutz and others that has produced more than fifteen Nobel Laureates. The article talks about the atmosphere in the institute, where Nobel laureates sat next to graduate students during tea and lunch in the cafeteria and constantly talked science. One thing that struck Steitz was how much time they spent talking about experiments rather than doing them; later he realized that they were basically enforcing a process of ruthless elimination on the experiments by discussing them beforehand, so that they would pursue only the most promising ones. That's a good lesson.

I remember another MRC-related anecdote that Steitz told us during our breakfast eight years ago; he was constantly surprised how the famous scientists at the MRC asked seemingly stupid or simple questions whose answers were not as obvious as we think. For instance, he remembers Max Perutz asking everyone what a eukaryote was; the question led to an unexpectedly fascinating discussion about the molecular differences between eukaryotes and prokaryotes. Steitz emphasized to us how important it is to keep on asking simple questions and setting our egos aside, a lesson that many of us sadly don't imbibe.

Steitz's wife Joan is an equally eminent biologist in her own regard. She was awarded a Lasker Prize this year and has done much to advance RNA science in addition to serving as a role model for women in science. When Steitz was looking for a faculty position he was offered one at Berkeley, but they declined to offer Joan - a protégé of James Watson - one, so Steitz turned down the job, and the couple moved to Yale where both of them acquired prestigious positions.

Tom Steitz was a scientist's scientist and an honorable man who did much to advance progress in molecular biology and the cause of honest, sound science. He will be missed.