RICK FRIEDMAN
COVER STORY
TRAILBLAZER AND MENTOR The 2014 Priestley Medalist has pioneered the field of BIOINORGANIC CHEMISTRY and shepherded legions of students to careers in chemistry BETHANY HALFORD, C&EN BOSTON
VISITORS TO Stephen J. Lippard’s office
should be prepared for a test. Upon entering the tidy, bright room on the fourth floor of the chemistry building at Massachusetts Institute of Technology, one can’t help but notice the colorful painting of a periodic table that hangs adjacent to the doorway. An inorganic chemist to his core, Lippard says he likes the artwork for the wild hues that color the elements. But, he adds, the artist had taken some liberties with Mendeleev’s masterpiece; there are mistakes. Then he will invite you to find them. Over the years Lippard has surely come to pick out the varying facial expressions exhibited by bright potential graduate stu-
dents, seasoned chemistry luminaries, and panic-stricken reporters when faced with this challenge. After all, his eye for detail is practically legend among bioinorganic chemists, having led him to insights on the molecular workings of metalloenzymes, cancer drugs, and the human brain. And his ability to read people and motivate them has helped him successfully guide hundreds of undergraduates, graduate students, and postdocs to standout careers in chemistry. It is these attributes—Lippard’s pioneering scientific research in bioinorganic chemistry and human health, as well as his masterful mentoring—that have garnered him the 2014 Priestley Medal, the CEN.ACS.ORG
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highest honor bestowed by the American Chemical Society. Whether a visitor rises to the periodic table painting challenge or stumbles, Lippard, a gracious host, might then extend an invitation to join him in a tipple from the bottle of Jack Daniel’s he keeps in the cupboard. Shots are taken from 30-mL beakers, of course. Although Lippard has been studying chemistry for more than 50 years, it was not always clear that he would be a scientist. As an undergraduate at Haverford College, Lippard studied English and intended to go to medical school. But he found chemistry’s call irresistible.
MIT to join the faculty, where he is currently the Arthur Amos Noyes Professor of Chemistry. He also spent a decade, from 1995 to 2005, as the department head. For 30 years, Lippard served ACS as an associate journal editor. His name first appeared on the masthead of Inorganic Chemistry in 1983. In 1989, he left that post to become an associate editor of the Journal of the American Chemical Society, a position he stepped down from in late 2013.
COURTESY OF STEPHEN LIPPARD (BOTH)
“Chemistry is unique in that it has both an artistic side and a quantitative side,” Lippard says of his chosen field. “A synthetic chemist has to put together molecules and think of ways of synthesizing things. It’s the same way a musician puts together different melodies and orchestrates different instruments. At the other end of the spectrum are chemists who develop highly mathematical insights. Not everybody can be a chemist.” “Steve was an outstanding student,” remembers Colin F. MacKay, one of Lippard’s chemistry professors at Haverford. “He had high intellectual ability, but that wasn’t the end of it. He was very organized and had a very strong work ethic.” HAVERFORD HAS A distinguished
A MODEL CHEMIST Lippard posing
visitors program, where dignitaries and scholars in the arts, sciences, and humanities visit the campus and interact with the students. In particular, Lippard recalls being strongly influenced by Francis P. J. Dwyer, a visitor from Australian National University. “He worked on medicinal inorganic chemistry, which I didn’t know anything about,” Lippard remembers. “I was so fascinated by his work that I was thinking of going to Australia to work with him.” But it was not to be. Dwyer died unexpectedly of a heart attack, and Lippard had to look elsewhere. “I decided that what I needed to do was to get a sound education in inorganic chemistry,” he says. In 1962, the year Lippard graduated from Haverford, the first ACS Award in Inorganic Chemistry was given to F. Albert Cotton, who was a professor at MIT at the time. “I visited Al, and we hit it off,” Lippard says. So he decided to undertake his graduate studies with Cotton. Lippard’s doctoral thesis focused on rhenium oxo complexes and metal-metal bonded clusters, problems of pure inorganic chemistry. But he was always thinking about how he might combine inorganic chemistry and biology. “It looked like a really wonderful area where one could do a lot of things,” he says. Lippard began his career as a chemistry professor at Columbia University in 1966. He rose through the ranks, becoming a full professor in 1972. In 1983, he returned to
with a molecular model circa 1970 (left) and receiving a 2004 National Medal of Science (above).
VIDEO ONLINE
how this miraculous drug that was discovered serendipitously really works,” Berg says. “I think that both in terms of understanding the basis for drug action and also bringing deep chemical thinking to analysis of metal ion-nucleic acid interactions, he’s been tremendously influential.” “HE’S WORKED on many different
Many students of inorganic chemistry have come to know the Lippard name through his work with chemistry texts. He spent 22 years as editor of the popular series “Progress in Inorganic Chemistry,” and he coauthored the textbook “Principles of Bioinorganic Chemistry,” which is still popular 20 years after its publication. “He’s one of a small group of people who are really the founding fathers of bioinorganic chemistry,” says Jeremy M. Berg, Lippard’s “Principles of Bioinorganic Chemistry” coauthor and director of the University of Pittsburgh’s Institute for Personalized Medicine. Berg points to Lippard’s early work with the cancer drug cisplatin. “He brought chemical skills to bear on understanding
Watch Lippard speak about his scientific research at http://cenm.ag/lippard. CEN.ACS.ORG
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areas and impacted many, many investigators,” says Harry B. Gray, a bioinorganic chemistry professor at California Institute of Technology. In addition to Lippard’s pioneering work on tumor reduction by platinum drugs, Gray says, “his work on redox metalloenzymes has been groundbreaking, particularly his research on the structures and mechanisms of methane monooxygenase.” That enzyme uses an iron center to convert methane to methanol, a feat chemists would love to replicate. “Many of my contributions relied upon an important collaborator to teach me things I didn’t know,” Lippard points out. “I’m a very problem-directed person. I’m not a technique-directed person. So I would reach out to different people to learn different methodologies. “I decided toward the end of the 1990s that I wanted to work on neuroscience,” Lippard says. His connection to the chemistry of the brain is more than just an intellectual pursuit. It’s personal. In 1973, his oldest son, Andrew Mark Lippard, died
COVER STORY
COURTESY OF STEPHEN LIPPARD
from an acute toxic encephalopathy, a neurological disorder. He was seven years old. But it wasn’t until the late 1990s, Lippard says, that the area of molecular neuroscience had moved far enough along that he felt he might be able to contribute something as a chemist. “So I did what I always do when I want to get into something new,” he says. “I went on sabbatical.” He traveled to Nobel Laureate Roger Tsien’s lab at the University of California, San Diego. Ever since his time with Tsien, Lippard has been active in an area he calls metalloneurochemistry. His work here has included the development of optical sensors that can be used to determine concentrations of biologically important metal ions in neurons. The research has helped scientists understand how zinc and nitric oxide serve as signaling agents in biology. LIPPARD HAS MADE his mark on so many
ambiguity, Berg says. “He’s very direct, but it’s to his students’ benefit. They learn how to do well because they had to do well and push themselves when working with him. I certainly found the same thing myself working with him on the ‘Principles of
and there was a voice mail message on my machine left at 7:03 Sunday morning from Steve saying, ‘Just got your fax. Where are you?’ I learned very quickly that trying to fool him was not going to work.” “He’s a driven scientist who still works with the intensity of an assistant professor trying to get tenure,” says Thomas V. O’Halloran, a chemistry professor at Northwestern University who did his doctoral studies with Lippard in the 1980s. “He has a great ability to sense the best ways to work with people.” Lippard is the sort of mentor you don’t want to disappoint, his former students and postdocs say. And they all have a story, whether it’s getting back a lab report covered in red FAMILY PORTAIT Bioinorganic Chemistry’ textbook. corrections or seeing LipLippard with his It was a pleasure to work with him, pard pull out a white glove Judy; sons but if I was getting behind schedule, wife, to go over the bench tops Joshua (far left) and I would hear about it. on lab cleanup day. Alex (far right); and “At one point he was pushing me Chuan He, a Univerdaughter-in-law, Sandra, in July 2012. sity of Chicago chemistry to get things done over the weekends. Around that time we got a new professor who earned his fax machine for my office. It was Ph.D. in 2000 after workprogrammable, so I thought, ‘Aha! I’ll outing in the Lippard lab, says the thing he smart him.’ So I programmed the machine finds most striking about Lippard’s former to send him a fax at 7 o’clock on Sunday students and postdocs is that they work in morning with some materials for the so many different areas. Some are organobook. Of course, I got into work Monday metallic chemists, some study metals in
areas of science that he often gives three or four talks at an ACS national meeting, says Stephen A. Koch, an inorganic chemistry professor at Stony Brook University, SUNY, who has spent several years as a program chair for the ACS Division of Inorganic Chemistry. Lippard’s talks are often in different divisions, Koch notes, so program chairs have to be careful not STEVE LIPPARD BY THE NUMBERS to double-book him. “Steve’s science is his number one achievement,” Koch points out, The time he gets up on Lunch in the “but a close second would be Tuesdays and lab’s tearoom his students and postdocs.” Thursdays to overlooking the Indeed, Lippard has menrun 4 miles. On circular patch of tored more than 100 graduSundays, he grass known to MIT ate students, 170 postdocs, runs 6. students as the dot. and countless undergraduates in his years at MIT and Columbia. Many of these students now hold prominent positions in academia, industry, and government. Number Total Approximate number “He’s trained a number of really of courses number of of lobsters served outstanding people, and that’s not an he years he over the years at accident,” Berg points out. “The thing needed to spent as his biennial lab that characterizes Steve is that he has complete associate feast on Martha’s incredibly high standards, first and an English editor Vineyard. foremost for himself but also for the major at for an people that work with him.” Haverford ACS Lippard communicates without College. journal.
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38,000 Approximate number of papers he has collected as reference material.
850 Number of publications from the Lippard lab.
48 Number of years he has played the harpsichord.
physiology, some work in neuroscience. pard’s lab. Starting a family could have been him for the ACS Award for Encouraging Taking an unusual path himself, He studies career-ending for many women in chemWomen into Careers in the Chemical Sciepigenetics. istry at that time. But not for Sunshine. ences. He has never won. So when Lippard “None of us compete with each other be“When I told Steve I was pregnant with my celebrated his 70th birthday in 2010, the cause we all work on very different things,” first child, he asked me, ‘What are you going women he had mentored as graduate stuHe says. “That tells you something about to do?’ ” she remembers. “I looked at him dents, postdocs, and visiting scholars preSteve. He doesn’t only teach his students and said, ‘I’m planning to continue and finsented him with their own award: The Cold and postdocs what he knows. He delivers ish my degree.’ He said, ‘Then I will do whatIron Award, named after Lippard’s favorite a strong message that you need to go to ever I can to help you.’ And he did.” Rudyard Kipling poem. The inscription the frontier of science and pick interesting Anne-Frances Miller, a chemistry prorecognizes Lippard for “more than 40 years problems. He taught us to not be limited by fessor at the University of Kentucky who of inspiring, training, promoting, and enour own knowledge. He prepared us to be did not study with Lippard but knew him couraging women in chemistry and steadfearless, with himself as an example.” when she was a postdoc at MIT, says Lipfast support of their career advancement.” Amy C. Rosenzweig, a Northwestern pard has a track record of giving women Although Lippard has been a critical chemistry professor who finished her dochigh-risk, high-reward projects. “The source of support for many of his former toral work with Lippard in 1993, says that projects that really go beyond everybody’s students, the major source of support in his as a mentor he was incredibly supportive. expectations are the ones that can allow us own life has been his wife, Judy, who passed When she was a first-year graduate stuto stand out and then command a position away last year after a battle with cancer. “I dent, Rosenzweig approached Lippard with an ambitious project: She A WORLD OF EXPERIENCE Lippard’s sabbaticals have helped him broaden his wanted to determine the structure scientific expertise. of methane monooxygenase, the multisubunit enzyme that converts methane to methanol. 1979: MRC Laboratory of 1972: University of 2005: Stanford “THESE DAYS IT wouldn’t be such
University, Palo Alto, Calif., with Keith O. Hodgson, where he continued studies of methane monooxygenase.
Molecular Biology, Cambridge, England, with Aaron Klug, where he investigated platinum cancer drug binding to nucleosomes.
Göteborg, Sweden, with Bo G. Malmström, where he learned biochemistry, isolating cytochrome c oxidase from beef heart and obtaining its Mössbauer spectrum.
a big deal, but 20 years ago doing a crystal structure of this kind of enzyme was very difficult,” Rosenzweig says. “Steve had not done any macromolecular crystallography up to that point. But he let me go after this.” Lippard did everything he could to support her, Rosenzweig says. He found her the best collaborator he 1988: Technical University of 1998: University of 2012: National Cancer Institute, Munich, with Wolfgang A. could for the project, even though California, San Diego, Bethesda, Md., with Michael M. Herrmann, where he focused the fellow was based in Sweden. with Roger Tsien, where Gottesman and Yves Pommier, where on organometallic chemistry Then Lippard flew the collaborator he formulated his he explored the properties of and began work on to MIT to work with her. Lippard metalloneurochemistry monofunctional platinum complexes, “Principles of Bioinorganic program. such as phenanthriplatin. Chemistry” with Jeremy Berg. sent Rosenzweig to Japan to collect data when it was necessary, and he also sent her to Sweden to work on the project. He sent her to conferences to at a fabulous institution,” Miller notes. think a lot of what he accomplished was present the work, which was eventually “Somebody’s got to take a risk on students helped by the amazing support his wife, published in Nature. and give them something that is going to Judy, gave him,” Sunshine says. Rosenzweig’s success is exemplary of produce a splash. “I was unbelievably lucky to have Judy,” something else Lippard has become known “He pushes the women as hard as he Lippard agrees. “It takes a special kind of for: training successful women in chemispushes the men,” Miller adds. “This is imperson to be married to a scientist. I tell my try. “It’s amazing,” says Helen Sunshine, portant for women to be able reach their students, ‘When you pick your partner be who earned her Ph.D. in 1975 after working full potential. I fear that in groups where sure they understand the part of your life in Lippard’s lab and is now the chief of the they don’t get pushed, it’s because the boss that’s going to be your passion for discoverOffice of Scientific Review at the National doesn’t necessarily trust them with his best ing the unknown and creating new things. Institute of General Medical Sciences. “If ideas.” Science doesn’t work a 40-hour week. It you look at his total Ph.D. output, it’s 40% Lippard says of his track record of traincan’t stop on Friday afternoon at 5 o’clock if women. And the interesting thing about ing women, “I am sex-blind when it comes that experiment is percolating. Sometimes this is that it’s been that right from the beto talent and people working in my lab. I you just can’t stop yourself from going in ginning.” Among the first 10 Ph.D.s Lippard have never treated the women any differon Saturday morning or at midnight or on graduated, Sunshine notes, four are women. ently than the men.” Sunday to see what’s happening.’ It takes a Sunshine gave birth to two children durFor many years, Lippard’s colleagues very special partner to live with someone ing her time as a graduate student in Lipand former students have nominated that lives that type of life.” ◾ CEN.ACS.ORG
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