Prof. David Clemmer of Indiana University has a theory about art and science.
“The best scientists are artists, and they have an intuitive side that leads them to the answer,” he said. “You’d be surprised how much science is actually in an artist. Both involve a process of trial and error, as well, where they learn and then they leap forward with new things.”
David Clemmer knows of what he speaks. A former music major who plays several instruments, he is also an analytical chemist and a pioneer in the development of ion mobility mass spectrometry (MS). Ion mobility detects minute amounts of compounds based on the rate at which their ions migrate through an electric field. This breakthrough, coupled with specialized software, has enabled the analysis of sample ions differentiated not only by their mass, but also by their size, shape and charge. This has opened new doors of discovery for researchers around the world.
Prof. Clemmer has dedicated most of his career to developing tools that help us understand the structures of complex molecular systems. For him, that includes proteins as they emerge into the gas phase from solvent during the electrospray process in mass spectrometry, as well as large mixtures of proteins that come out of the proteomes of organisms in different physiological states.
“In the attempt to study these things, we’ve developed new mass spectrometers,” he explained. “We were the first group to develop a nested ion-mobility time-of-flight measurement. That's where the time-of-flight mass spectrum is nested within the individual windows of the ion-mobility separation.
By Clemmer's estimate, he and his team have developed a dozen different configurations of mass spectrometers with ion-mobility mass spectrometry. The technology was first made commercially available in 2006 as part of the Waters SYNAPT HDMS system.
Clemmer's innovations give researchers “the capability to see ions that you really can’t see any other way if you’re using a typical ion source like electrospray or MALDI,” he explained. “And so that allows you then to reach way down into the noise of the spectrum and see tiny signals that you just wouldn’t perceive otherwise. The fact that the mobility measurement can be done in milliseconds is really quite elegant, because it fits in between the seconds to minute timescales of an LC separation and microsecond timescales necessary for time of flight analysis. So you get this additional dimension about the structure of the ion without any additional cost of experiment time.”
These innovations seem a long way from Alamosa, the small town in southern Colorado where David Clemmer grew up, dreaming of becoming a professional musician or competitive runner before his scientific interests grew.
“I attended a small college in my hometown called Adams State College,” said Clemmer, “and I was very lucky to have a husband and wife team – Kay and Jan Watkins – as my English teacher and my first college chemistry teacher. They sort of sheltered me and took me through my undergraduate work.”
That early mentoring prepared Clemmer to move on after graduation to The University of Utah, where he earned his Ph.D in Chemistry under Prof. Peter Armentrout.
“I was really lucky to meet Peter Armentrout,” says Clemmer. “He’s just a force of nature, and has a tremendous passion to do science. We ran reactions in a mass spectrometer involving transition metal ions when I was his student.”
That passion proved contagious as David Clemmer traveled to Japan to work on neutrals at the Himeji Institute of Technology with Prof. Kenji Homma before venturing to Northwestern University to work on carbon clusters with Prof. Martin Gerald.
Clemmer has now spent 18 years on the Chemistry faculty of Indiana University, where he holds the Robert & Marjorie Mann Chair and serves as Associate Dean for the Sciences. Along the way, he has published more than 175 papers and received several awards, including the Fresenius Chemistry Award, and the American Association for the Advancement of Science recently awarded him with the distinction of Fellow.
Outside of the laboratory and the classroom, Clemmer leads an active life with his wife and three daughters. An avid runner, he has completed 14 marathons. Music continues to be a big part of his life.
“I play the guitar and the mandolin, and I’m working on the cello,” he said. “I have a collaboration right now with a friend in Colorado named Don Richmond, who’s the owner of Howling Dog Records. He and I are co-writing my first album.”
Clemmer believes the physical and mental stimulation of running and music contributes to his scientific work. Another key to his success is timing.
“There are things that come together at the right time that make technology viable,” said Clemmer. “In our case, the computer had just gotten fast enough to nest a mass spectrum within the mobility distribution, the way we did it. At the same time that we were doing that, Mike Bowers and Martin Gerald had just developed techniques to calculate collision cross-sections for ions, and so the ability to measure mixtures of ions and then calculate the collision cross-sections for trial geometries made it possible to learn about the structures of these ions in an entirely new way.”
Clemmer has had the pleasure of seeing his innovations put to a broad range of scientific purposes.
“I’m always amazed to see what people use nested ion mobility time-of-flight mass spectrometry for,” he said. “People have used it in very complicated mixture analysis to do very high-throughput proteomics or glycomics experiments. This is an instrument that can be applied to any chemical problem where you’re monitoring structure and mass, so it stretches from the small molecules all the way out to these very large protein complexes that people like Albert Heck at Utrecht and Carol Robinson at Oxford are beginning to measure.”
Like his music, Prof. Clemmer sees his scientific work as the product of influences and collaboration.
“I’ve been lucky enough to be a couple hours south of Purdue, and Graham Cooks and Scott McLuckey have been very interesting colleagues to be near,” Prof. Clemmer noted. “And then early on in my career, I studied a system that Fred McLafferty cared about at Cornell, and Fred has been a very interesting collaborator through the years. I pay careful attention to Evan Williams’ work at Berkeley, and I’ve always liked Joe Loo’s work. And Vicky Wysocki’s work. One of my very big influences has been Julie Leary at UC Davis.”
This intellectual ferment energizes his work in the classroom and the laboratory.
“What’s so special about a laboratory is that you really do have the chance to just be surprised, or have everything you thought you knew about something disrupted for a while. And that’s a really interesting feeling that I enjoy. I think most scientists get addicted to that feeling.”