Nobel Effort

As a chemistry major at Lawrence University working in the rudimentary labs of Stephenson Hall, Thomas Steitz ’62 had never even heard of a protein structure.

It was beyond his imagination that one day he would be world renowned in the field of molecular biology and win the world’s most prestigious science award — the Nobel Prize. His decades-long, groundbreaking research revealed the structure and function of the large subunit of the ribosome, which transforms encoded DNA information into proteins central to virtually every life function.

In the predawn dark of October 7, a 5:20 a.m. phone call awoke Steitz at his Branford, Conn., home before his alarm clock could. While most calls at odd hours bring bad news, this particular one brought a celebratory, life-altering message, courtesy of the Royal Swedish Academy of Sciences in Stockholm: Steitz had been named one of three recipients of the 2009 Nobel Prize in chemistry.

“He apologized for calling me so early and I said, ‘Well, that’s alright. I was going to get up in 20 minutes and go to the gym anyhow,’” said Steitz, who in turn received congratulations from each member of the Nobel Committee. “He said, ‘I don’t think you should do it today, you’re going to be too busy. In 20 minutes, your phone is going to ring off the hook.’ Boy, was he right!”

Since 1970, Steitz has taught at Yale University, where he is the Sterling Professor of Molecular Biophysics and Biochemistry and professor of chemistry and a Howard Hughes Medical Institute investigator. He shares the 2009 Nobel honor — and its $1.4 million prize — with Venkatraman Ramakrishnan of the Medical Research Council Laboratory of Molecular Biology in Cambridge, England and Ada E. Yonath of the Weizmann Institute of Science in Rehovot, Israel.

Working independently, all three were cited for their fundamental research on the crucial role of ribosomes, which serve as protein factories inside all living cells.

The award recognized more than 30 years of bulldog determination to solve a mystery at the core of basic biology. Using X-ray crystallography to determine the three-dimensional structure of biological molecules, Steitz was able to map the position of each of the more than 100,000 individual atoms that make up the ribosome, a massive complex of proteins and RNA material. His research has found that a step in the synthesis of bacterial proteins is a reaction initiated by RNA that many antibiotics typically inhibit. An understanding of the structural basis of the function provides possibilities for the development of new antibiotics.

While the structure of thousands of molecules is known, Assistant Professor of Chemistry Kimberly Dickson said the size of the molecule Steitz mapped is on a completely different scale. “If for comparison purposes we said most known structures were the size of a typical car, the structure Dr. Steitz solved would be of a molecule the equivalent size of Youngchild Hall,” Dickson explained.

Steitz likened his investigation of the ribosome to scaling Mount Everest: “We knew it was doable in principle but we did not know if we would ever get there.”

But in true dedicated-scientist fashion, Steitz said the thrill of finally seeing that long elusive ribosome trumped winning the Nobel Prize. “That’s what I really wanted to do,” he said.

“Seeing the structure of the ribosome and seeing how it is put together after pursuing it was extraordinarily exciting,” said Steitz. “I wish I had taken notes of the journey so I could remember everything better. I never saw anything so exciting. The Nobel Prize is exciting, but in a different way.”

President Jill Beck hailed Steitz’ achievement as “a tremendous affirmation for the quality of education that our faculty offer our students and the research relationships that develop between faculty and students, during their time with us.”

If not for the suggestion of the mother of his high school friend and eventual Lawrence classmate, Alex Wilde ’62, Steitz might never had found his way to Lawrence in the fall of 1958. Her suggestion to apply for a scholarship at Lawrence turned his attention away from the University of Wisconsin system campuses. He not only applied for a scholarship, but received one that covered his full tuition.

“As soon as I visited, I realized that’s where I wanted to go,” recalled Steitz, a Milwaukee native who graduated from Wauwatosa High School. “All I had to do was visit. And after I got there, I never thought anything except this was the place to be.”

Lawrence Professor Emeritus of Chemistry Robert Rosenberg, who served as Steitz’ academic advisor and mentor, said his prize pupil arrived on campus with an extra active inquisitive gene.

“Tom was very inquiring. He was a curious person, much more so than most students, always questioning and always eager to learn,” said Rosenberg, who retired from Lawrence in 1991 and now serves as an adjunct professor of chemistry at Northwestern University. “I am very proud of Tom and very lucky to have had him for a student. I was walking on air when I learned he had won the Nobel Prize.”

Steitz’ journey to scientific celebrity started humbly enough in Stephenson Hall, where the floor in the analytic lab creaked and the balances shook whenever someone walked in the room. Before then-Lawrence President Douglas Knight ordered a broom closet turned into a lab, there was only one small room for student research.

“That may be why Tom made the decision to do his undergraduate research at Argonne,” said Rosenberg, who regularly returns to campus for Reunion Weekend.

Steitz spent the fall term of his senior year on the Associated Colleges of the Midwest-sponsored off-campus study program at the Argonne National Laboratory in suburban Chicago.

Today, with its state-of-the-art facilities, including the renamed Steitz Hall, Lawrence boasts a vibrant student research program of its own, including independent study projects during the academic year and a burgeoning summer program supported in part by the Excellence in Science Fund and a variety of grants from public and private funding agencies, including the National Institutes of Health, National Science Foundation, Research Corp. and the Merck-AAAS Undergraduate Science Research Program.

What Stephenson Hall may have lacked in amenities in its day, it more than made up for with devoted faculty, none more so than Rosenberg.

“He was the one who really inspired me to pursue science and chemistry and biochemistry. It’s not that others didn’t have influence, but he was really the pivotal person,” Steitz said of Rosenberg. “He talked about bonding; I’d never heard of bonding; orbital, I’d never heard of orbital or how one could use this to understand light absorption and color.

“He had a style — if you asked him a question, he would ask you a question, to make you think about how to answer questions,” he added. “And so that style of teaching not only got the information across, which he did very effectively, but it also taught you how to think.”

Since Steitz’ undergraduate days at Lawrence, the complexity of the knowledge base of the biochemistry field has exploded exponentially, along with sweeping advances in technology and instrumentation. When he began his research, there was only one known protein structure and he read every single paper in the entire field.

“Now I can’t even read the table of contents of a journal that’s talking about structures,” Steitz said. “And the topics are so incredibly diverse that it’s very hard, even for me to comprehend them.”

What hasn’t changed is the kind of close, personal mentoring that Rosenberg provided. It remains a fundamental component of the Lawrence teaching model today. Dickson, a biochemist who includes the structures Steitz discovered as part of her own classes, sees Steitz’ Nobel Prize as a validation of Lawrence’s mission.

“As a scientist, you don’t get anything more prestigious than a Nobel Prize,” said Dickson, whose own research involves trying to understand the biological activity of proteins that are involved in cancer and amyotrophic lateral sclerosis (ALS). “An honor like that demonstrates that the investment we make in our students through individualized learning can really pay off. Our philosophy, our actions and our hearts are in the right place to help our students succeed.”

In his article “Science at Liberal Arts Colleges: A Better Education?” Nobel Laureate and former president of the Howard Hughes Medical Institute Tom Cech noted that small liberal arts colleges produce approximately twice as many doctoral graduates as baccalaureate institutions and the top liberal arts colleges vie with the nation’s very best research universities in their efficiency of production of eventual science Ph.D.s., accounting for three of the top six and 11 of the top 25 institutions in the United States in terms of producing undergraduates who complete doctorates in science and engineering.

David Hall, an associate professor of chemistry specializing in the ways rhinoviruses activate immune cells and exacerbate asthma, points to the long Lawrence tradition of faculty establishing personal relationships with students as one of the reasons behind numbers like those cited by Cech and the ultimate recognition earned by Steitz.

“The kind of close, mentoring relationships Lawrence is known for allow the faculty member and student to motivate and challenge each other to learn, understand, ask questions and solve problems at a high level,” said Hall. “As our knowledge base grows, the ability to think critically and synthesis information becomes all the more important.”

Steitz credits those critical thinking skills imparted by Rosenberg and others and his exposure to the interdisciplinary approach of Freshman Studies during his undergraduate days at Lawrence for providing a broad and solid foundation for his future endeavors.

“Life is one step after another step and it is hard to ask how important the roots are, except they got you on the right path,” he said of his time at Lawrence. “I took an anthropology course, a philosophy course, and certainly I wouldn’t have taken a religion course if it wasn’t required. I could understand the scholarship of religion and anthropology and philosophy and put those all together and understand how people’s understanding of the world developed.

“Those courses transformed the way I think about the world,” he added. “It gave me an appreciation about how to think about answering questions. I found as a graduate student at Harvard, I didn’t know about things as well as my fellow students who had been to large universities — our courses were not as detailed, so I didn’t know as many facts as they did — but in retrospect, I was able to think about things perhaps a little better than they were, because that’s what I was taught how to do, how to put things together, how to integrate information. I think that has been an important contributor all along.”

The magnitude of Steitz’ Nobel achievement is manifesting itself in interesting ways on campus. On a recent take-home exam for her molecular biology class, Dickson included a structural model of a ribosome that included a caricature of Steitz embedded in it. She asked her students to describe the work of art with respect to its molecular significance and its far-reaching accomplishments in science.

“Our students recognize we have many very successful alumni, but I think they were a little stunned to find out we have one on this level of success,” said Dickson. “At the very least, Dr. Steitz’ Nobel Prize has planted the seed and they’re starting to realize that this could happen to them at some point in the future. They recognize that Lawrence is providing them with the tools to be successful in any career, not just the sciences, because we teach them how to think.”

In his research laboratory at Yale, Steitz annually oversees a team of approximately 20: five or six graduate students, one or two undergraduates, as many as a dozen post-doctoral fellows and several technicians. While still awaiting his first graduate student from Lawrence, he doesn’t expect his new-found fame to significantly raise his popularity.

“Obviously it puts me on the ‘I want to check this person out’ list, but there are so many things that are important for a student to evaluate,” said Steitz, an old-school professor who still prefers chalk and blackboard in the classroom. “There’s too much information, not enough thinking when PowerPoint is involved.”

During his graduate days at Harvard University, and later as research fellow at the Medical Research Council Laboratory of Molecular Biology in Cambridge, England, there were Nobel Laureates in his midst who were inspiring figures to him long before they received their recognition.

“They were inspirational individuals who happened to have a Nobel Prize, rather than I was inspired because they had a Nobel Prize,” said Steitz.

As for his own stature as a potential role model for future scientists, Steitz sees his work, not his reward, as the best inspiration.

“People who do good science and interact with students can be inspirational,” he said. “I might inspire somebody else. I hope so.”

For Hall, one of the most inspiring aspects of Steitz’ Nobel Prize was the mutual admiration expressed between student and professor.

“I was thrilled, as I am sure all faculty were, to hear Professor Rosenberg speak with pride about an advisee who had graduated 47 years earlier,” said Hall. “That kind of long-term connection with a student is why many of us become teachers. His comments reminded me of one of my favorite movies, “Mr. Holland’s Opus.” Fifteen years after I started teaching undergraduates, I have already shared deep moments of pride myself as former students have matriculated from graduate schools. In this age of social networking, I am extraordinarily fortunate to be able to share in their successes years after they have left the safety of the Lawrence bubble. Their success after Lawrence is a tremendous source of pride and inspiration to keep up my own research and teaching.”

For today’s students who are contemplating careers in the sciences, the fundamental motivation, in Steitz’ view, comes down to something as basic as genuinely wanting to ask and answer questions.

“They should be doing things that excite them, taking courses or interacting with faculty who address questions and issues that they’re interested in,” said Steitz. “What I see happening, certainly with Yale graduates and I think it is nationwide, is that bright students are being motivated by Wall Street and money.

“I think that’s extraordinarily unfortunate for them and for the country because they do things that frankly are boring, but they make a lot of money. I think they should be doing things that excite them. I think it’s unfortunate that so many students these days are motivated by money, rather than pursuing things that interest them and stimulate their curiosity.”

A “retired” saxophonist who as an undergraduate took advantage of Lawrence’s Conservatory of Music to play in the band and the orchestra — “The music school was extraordinarily important to me. I crossed over College Avenue all the time” — Steitz once considered music as his career choice before settling on science.

“I thought, well I can do science and do music on the side, but I can’t do music and do science on the side,” he said. “To make a living in music is very difficult, you have to be the top of the top of the top. Science has the great advantage in that there are lots of opportunities in it. Students should go into science because it excites them and then take courses that excite them with faculty who excite them.”

Whether by premonition or sheer good fortune, Steitz is on sabbatical from his teaching responsibilities for the 2009-10 academic year. In recent years, he routinely has traveled 100,000 miles or more annually to deliver lectures. This year, he luckily had the foresight to keep his appointment schedule to a minimum in November and December.

A good thing, too. Once his prize was announced, there was a steady stream of interview requests from journalists and writers around the world, a visit to his Yale office by a public television film crew from Sweden, a December reception at the White House with President Obama and other Nobel laureates and of course the grandiose Nobel Prize medal-awarding ceremony in Stockholm.

“The most fun part is having contact with people whom I haven’t had contact with for years to decades, old friends, former roommates. It’s been very nice,” he said. “I run into people in town and at the gym, all over the place, that come up and talk to me.

“I feel uncomfortable being a celebrity, to tell you the truth,” he added. “It’s not something I would seek for itself, but it has its giggles.”