Volume 92 Issue 11 | pp. 10-13
Issue Date: March 17, 2014

Cover Stories

Trailblazer And Mentor

The 2014 Priestley Medalist has pioneered the field of bioinorganic chemistry and shepherded legions of students to careers in chemistry
Department: Science & Technology, ACS News
News Channels: JACS In C&EN
Keywords: Stephen Lippard, Priestley Medal, bioinorganic

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.

Lippard talks about his scientific research.
Credit: American Chemical Society

Over the years Lippard has surely come to pick out the varying facial expressions exhibited by bright potential graduate students, 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 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.

Credit: Rick Friedman
Credit: Rick Friedman

“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 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 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. 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 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 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.

Lippard with his wife, Judy; sons Joshua (far left) and Alex (far right); and daughter-in-law, Sandra, in July 2012.
Credit: Courtesy of Stephen Lippard
Lippard with his wife, Judy; sons Joshua (far left) and Alex (far right); and daughter-in-law, Sandra, in July 2012.
Credit: Courtesy of Stephen Lippard

“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 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 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 to double-book him.

“Steve’s science is his number one achievement,” Koch points out, “but a close second would be his students and postdocs.” Indeed, Lippard has mentored more than 100 graduate students, 170 postdocs, and countless undergraduates in his years at MIT and Columbia. Many of these students now hold prominent positions in academia, industry, and government.

“He’s trained a number of really outstanding people, and that’s not an accident,” Berg points out. “The thing that characterizes Steve is that he has incredibly high standards, first and foremost for himself but also for the people that work with him.”

Lippard communicates without 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 Bioinorganic Chemistry’ textbook. It was a pleasure to work with him, but if I was getting behind schedule, I would hear about it.

Lippard’s sabbaticals have helped him broaden his scientific expertise.
Lippard’s sabbaticals have helped him broaden his scientific expertise.

“At one point he was pushing me to get things done over the weekends. Around that time we got a new fax machine for my office. It was programmable, so I thought, ‘Aha! I’ll outsmart him.’ So I programmed the machine to send him a fax at 7 o’clock on Sunday morning with some materials for the book. Of course, I got into work Monday 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 corrections or seeing Lippard pull out a white glove to go over the bench tops on lab cleanup day.

Chuan He, a University of Chicago chemistry professor who earned his Ph.D. in 2000 after working in the Lippard lab, says the thing he finds most striking about Lippard’s former students and postdocs is that they work in so many different areas. Some are organometallic chemists, some study metals in physiology, some work in neuroscience. Taking an unusual path himself, He studies epigenetics.

“None of us compete with each other because we all work on very different things,” He says. “That tells you something about Steve. He doesn’t only teach his students and postdocs what he knows. He delivers a strong message that you need to go to the frontier of science and pick interesting problems. He taught us to not be limited by our own knowledge. He prepared us to be fearless, with himself as an example.”

Credit: Courtesy of Stephen Lippard
Credit: Courtesy of Stephen Lippard
Credit: Courtesy of Stephen Lippard
Credit: Courtesy of Stephen Lippard

Lippard posing with a molecular model circa 1970 (top) and receiving a 2004 National Medal of Science (above).

Amy C. Rosenzweig, a Northwestern chemistry professor who finished her doctoral work with Lippard in 1993, says that as a mentor he was incredibly supportive. When she was a first-year graduate student, Rosenzweig approached Lippard with an ambitious project: She wanted to determine the structure of methane monooxygenase, the multisubunit enzyme that converts methane to methanol.

“These days it wouldn’t be such 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 could for the project, even though the fellow was based in Sweden. Then Lippard flew the collaborator to MIT to work with her. Lippard 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 present the work, which was eventually published in Nature.

Rosenzweig’s success is exemplary of something else Lippard has become known for: training successful women in chemistry. “It’s amazing,” says Helen Sunshine, who earned her Ph.D. in 1975 after working in Lippard’s lab and is now the chief of the Office of Scientific Review at the National Institute of General Medical Sciences. “If you look at his total Ph.D. output, it’s 40% women. And the interesting thing about this is that it’s been that right from the beginning.” Among the first 10 Ph.D.s Lippard graduated, Sunshine notes, four are women.

Sunshine gave birth to two children during her time as a graduate student in Lippard’s lab. Starting a family could have been career-ending for many women in chemistry at that time. But not for Sunshine. “When I told Steve I was pregnant with my first child, he asked me, ‘What are you going to do?’ ” she remembers. “I looked at him and said, ‘I’m planning to continue and finish my degree.’ He said, ‘Then I will do whatever I can to help you.’ And he did.”

Anne-Frances Miller, a chemistry professor at the University of Kentucky who did not study with Lippard but knew him when she was a postdoc at MIT, says Lippard has a track record of giving women high-risk, high-reward projects. “The projects that really go beyond everybody’s expectations are the ones that can allow us to stand out and then command a position at a fabulous institution,” Miller notes. “Somebody’s got to take a risk on students and give them something that is going to produce a splash.

“He pushes the women as hard as he pushes the men,” Miller adds. “This is important for women to be able reach their full potential. I fear that in groups where they don’t get pushed, it’s because the boss doesn’t necessarily trust them with his best ideas.”

Lippard says of his track record of training women, “I am sex-blind when it comes to talent and people working in my lab. I have never treated the women any differently than the men.”

For many years, Lippard’s colleagues and former students have nominated him for the ACS Award for Encouraging Women into Careers in the Chemical Sciences. He has never won. So when Lippard celebrated his 70th birthday in 2010, the women he had mentored as graduate students, postdocs, and visiting scholars presented him with their own award: The Cold Iron Award, named after Lippard’s favorite Rudyard Kipling poem. The inscription recognizes Lippard for “more than 40 years of inspiring, training, promoting, and encouraging women in chemistry and steadfast support of their career advancement.”

Although Lippard has been a critical source of support for many of his former students, the major source of support in his own life has been his wife, Judy, who passed away last year after a battle with cancer. “I think a lot of what he accomplished was helped by the amazing support his wife, Judy, gave him,” Sunshine says.

Watch Lippard speak about his scientific research at http://cenm.ag/lippard.

“I was unbelievably lucky to have Judy,” Lippard agrees. “It takes a special kind of person to be married to a scientist. I tell my students, ‘When you pick your partner be sure they understand the part of your life that’s going to be your passion for discovering the unknown and creating new things. Science doesn’t work a 40-hour week. It can’t stop on Friday afternoon at 5 o’clock if that experiment is percolating. Sometimes you just can’t stop yourself from going in on Saturday morning or at midnight or on Sunday to see what’s happening.’ It takes a very special partner to live with someone that lives that type of life.”

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