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Newly Named NIGMS Director Jon Lorsch Talks About His Science and His New Job

Newly appointed NIGMS Director Jon R. Lorsch.
Newly appointed NIGMS Director Jon R. Lorsch.

Jon R. Lorsch knew it was coming but he still wasn’t prepared for the email explosion at his Johns Hopkins lab when the National Institutes of Health (NIH) announced on Monday that Lorsch would become the new Director of the National Institute of General Medical Sciences (NIGMS), starting this summer. “You can’t imagine how many emails I’ve gotten in the last few hours,” Lorsch reported by early afternoon. “It’s unbelievable.”

The email flood becomes believable when you realize that with its $2.4 billion budget, NIGMS is the primary federal funder for basic research in “cell biology, biophysics, genetics, developmental biology, pharmacology, physiology, biological chemistry, biomedical technology, bioinformatics, and computational biology,” according to the NIH press release. A significant portion of that funding supports the training of young scientists as well as programs to ensure diversity in the scientific workforce. For so many—from PIs to students— in basic research, the buck starts at NIGMS.

The new NIGMS director, at least on his first day in the public spotlight, sounded remarkably relaxed, excited, and reflective about his own life in science. Science started early. “I wanted to be a scientist since I was 4-years-old and a science teacher came to our classroom to show us a cow’s heart,” Lorsch explained. “I was fascinated with the chambers and how the blood moved through them. I vividly remember this. That’s when I knew.”

The son of a Harvard Business School professor, Jay Lorsch, and the retired news and media relations director for Williams College, Jo Procter, Lorsch grew up in Cambridge, MA, and took his first lab job in the tenth grade at the Boston Biomedical Research Institute. “I worked on myosin,” he said, “which sort of fits in with the cow heart.”

From the beginning, the lab world fit Lorsch’s temperament. He majored in chemistry and minored in biology at Swarthmore College, picking Harvard University in 1990 for graduate school and joining the lab of the legendary enzymologist Jeremy Knowles. But a few months on, Knowles was named Dean of Harvard’s Faculty of Arts & Sciences and Lorsch was summoned to his office to be told that as a newcomer, he’d been reassigned to Jack Szostak’s lab at Harvard Medical School. “He didn’t give me a choice,” Lorsch recalled with a laugh. “It was the best decision that anyone ever made for me in my life.”

Szostak, who would win the Nobel Prize in 2009 for his earlier discoveries about the role of telomerase in maintaining chromosome integrity, was already turning in a new direction to explore what is now called the RNA world. Szostak’s lab would pursue RNA in many directions, ranging from molecular folding to the origins of life on earth. But one of the first questions to be answered was whether RNA molecules could act as “ribozymes,” that is, as true enzymes, capable of catalyzing reactions in cells. Lorsch looked at one of these specially folded RNA peptides that Szostak called aptamers. The aptamer that Lorsch fished out of pools of random RNA sequences was identified by its ability to bind a site on vitamin B-12. In a second project, Lorsch “evolved” an ATP-binding aptamer into a ribozyme with the ability to act as a kinase, transferring a gamma-phosphoryl group from ATP to another RNA molecule. Those early days of RNA enzyme study were brought home recently to Lorsch when one of his Hopkins medical students who is doing a research elective sketched out plans to test an aptamer-based drug for medical use. “I said to him, ‘Wow. I was there in the early days of this.’ It’s been very gratifying for me to see that technology is finding its way into the clinics.”

For his postdoc, Lorsch wanted to combine his new background in RNA with his first interest in enzymology. He found that mix in the Stanford University lab of Dan Herschlag who was studying enzymes that modulated the structure of RNA, especially the DEAD-box proteins, a huge and ubiquitous family of RNA helicases active in nearly every RNA process.  “That’s where I got interested in protein synthesis and translation.” The DEAD-box protein that Lorsch chose to work on—eIF4A—is a eukaryotic initiation factor. “That’s how I became fascinated by this incredible complexity of eukaryotic translation and the initiation machinery, which has dozens of components—the ribosome, tRNAs, mRNAs, and initiation factors. Somehow they work together in this intricate machinery to find the right place to start protein synthesis, assemble the whole ribosome right there, and start going.”

Even after 13 years in his Hopkins lab untangling the factors at work in transcription initiation, Lorsch is undismayed by the complexity. “The idea that one day you could understand this in the way you can understand how a car works has always appealed to me,” he said. “If you want to fix something like a mechanic can fix a car, you have to be able to understand it at the same level that a mechanic understands how a car works.”

And yet in recent years, a larger complexity has started to appeal to him—the chance to have an impact outside his lab on science and its role in society. When NIH Director Francis Collins first called him in for a talk about the NIGMS directorship, Lorsch was already primed. “When I first met with Francis, he described NIGMS as the center of the center of NIH. I thought that was exactly right. The question-based research that NIGMS supports, I look on as the wellspring that feeds advances in medicine and technology. It’s essential to the nation that this wellspring stays healthy and flowing.”

Lorsch acknowledges that these are difficult times for American research funding and that at NIGMS, he could be facing a rough ride. “But challenges can be opportunities to make a major, positive impact,” he said.

But before he takes the NIGMS tiller this summer, Lorsch said that he has his preparation work cut out for him. First he must “learn all the ropes and all the wisdom” from NIGMS staff and its acting director Judith Greenberg. Equally important, Lorsch said, “I’m also going to be talking with the scientific community to find out their ideas and concerns. This has got to be a two-way conversation.”

Beyond watering the fields of basic discovery, NIGMS also tends to the futures of individual young scientists through training grants and support for programs to increase scientific workforce diversity. The educational power of NIGMS is central to the institute’s research mission, according to Lorsch. “It’s essential for the scientific process to have the best educated and the most diverse scientific workforce in the world.”

Taking the tiller at NIGMS will also require moving his family from Baltimore to the Bethesda area, he said. The selection and vetting process took months but on the Friday before the Big Announcement, Lorsch and his wife, Kirstie Saltsman, called a family meeting to break the news to their two daughters, 14 and 12. They were not overly pleased. “But then the next morning, my younger daughter came to me and said, ‘Alright, I’m writing up a list of terms and conditions for our new house,’” Lorsch reported. Her demands included certain room requirements, a “real” closet, and a trampoline. “I figured we’d turned a corner and it would be okay,” her father said with a sigh of relief.

Next comes NIGMS.

—John Fleischman

Created on Tuesday, March 27, 2013

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