An ideal physician-scientist

David Gutmann's passion for research and clinical care unravels a complex genetic disorder

David H. Gutmann, M.D., Ph.D., is having the time of his life. And despite his passion for jazz, this time there’s not a saxophone in sight.

The source of Gutmann’s zeal is the School of Medicine’s newly formed interdisciplinary team unified by his scientific crusade: unraveling the mystery of brain tumors in children with neurofibromatosis (NF).

David H. Gutmann, M.D., Ph.D. (left), and postdoctoral researcher Biplab Dasgupta, Ph.D., examine mouse brain tumors in the lab.
David H. Gutmann, M.D., Ph.D. (left), and postdoctoral researcher Biplab Dasgupta, Ph.D., examine mouse brain tumors in the lab. “My mission is to make sure everybody knows about NF and that when my productive days are over, I can look back and say we made a little bit of a difference,” Gutmann says. “It’s going to take an army of experts and a lot of creative thinking to make individualized medicine a reality, and I’ll do whatever it takes to make that happen.”

Though most people have never heard of this genetic disorder, more than 100,000 Americans have one of the disease’s two forms — making it more common than cystic fibrosis, Huntington’s disease, hereditary muscular dystrophy and Tay-Sachs disease combined. Individuals with NF are predisposed to a variety of debilitating complications, including brain cancer.

In an ongoing effort to combat NF, Gutmann recently established the Washington University NF Center. The collaborative center aims to promote NF research, achieve significant breakthroughs in the diagnosis and treatment of nervous system tumors, while establishing the University as an international beacon for NF research.

According to Peter Bellermann, president of the National NF Foundation, Gutmann is without question one of the premier NF researchers in the world.

Fittingly, Gutmann became the only person to hold an endowed professorship dedicated to the disease when he was named the Donald O. Schnuck Family Professor of Neurology in 2001.

“David is unusual in that he is both highly respected as a basic scientist and as a superb clinician,” Bellermann says. “He also has an impish, devilish sense of humor that is absolutely irresistible and makes this serious and devastating subject easier to deal with both for his patients and for his fellow scientists.”

A passion for genetics

The conference room in Gutmann’s laboratory says a lot about him. The room is bathed in the blue and yellow colors of his beloved University of Michigan Wolverines, and above the entrance is a sign with Nike’s famous slogan: “Just Do It.”

David Gutmann; his wife, Robin; and daughter, Rebecca.
David Gutmann; his wife, Robin; and daughter, Rebecca.

Gutmann’s resolute determination is not reserved exclusively for Michigan sports. That same dedication has helped him fulfill his lifelong career dreams.

He confirmed his medical aspirations by spending a few high school summers helping the cardiovascular team at the Henry Ford Hospital in Detroit. Confident of his vocational calling, he enrolled in the University of Michigan’s combined undergraduate and medical degree program.

His experiences conducting laboratory research during his first few years of college were far more exhilarating than the seemingly endless strings of unrelated facts presented to beginning medical students.

So Gutmann and his academic advisor reached a compromise: He would only attend those classes that were absolutely essential, freeing him to simultaneously pursue a master’s degree in human genetics. A year later, he found himself so enchanted with genetics he decided to delay completion of his medical degree in order to first earn a doctoral degree.

In the early 1980s, the field was witnessing one of its first intellectual explosions, and the University of Michigan was home to several of its biggest names.

“It was a phenomenal time to be in training,” he recalls. “It was exciting to watch people shift from thinking about genes as if they were holy spirits to viewing them as having concrete qualities that could actually be studied and understood.”

Reluctantly, Gutmann fulfilled his oath to his father and his advisor and returned to medical school after his Ph.D. To his surprise, he loved it. Although the first two years had exclusively consisted of classroom work, he finally found himself working directly with patients as a third-year student.

David H. Gutmann

Titles: The Donald O. Schnuck Family Professor of Neurology, professor of genetics and of pediatrics; director of the Washington University NF Center; director of the NF Program at St. Louis Children’s Hospital; co-director of neurooncology at Washington University/Alvin J. Siteman Cancer Center.

Family: Wife, Robin, a clinical nurse in psychiatry at Barnes-Jewish Hospital; daughter, Rebecca, 16.

Hobbies: Reading, University of Michigan sports, listening to jazz music. “When I travel, I always make sure there’s a jazz concert I can go to.”

It didn’t take long for Gutmann to realize he wanted to specialize in neurology. Because diseases of the brain are so complex both to diagnose and treat, they presented unique opportunities to apply the scientific method to real life, combining Gutmann’s analytic, research-oriented mind with his devotion to patient care.

As a neurology resident at the University of Pennsylvania, he discovered that neurology afforded ample opportunity to exercise his genetic curiosity.

“The genetics of human disease kept haunting me,” he recalls. “I thought the early work on neurogenetics was absolutely fascinating and spent every moment I could with the genetics group at the Children’s Hospital of Philadelphia.”

As a chief resident, he helped establish a neurogenetics clinic where he spent his spare time characterizing physical and neurological abnormalities that run in families. The experience left him even more excited about genetic research.

While considering a research fellowship in genetics, his mentor recommended he talk to a young “upstart” named Francis Collins, M.D., Ph.D., who later became one of the world’s premier geneticists and leader of the national Human Genome Project.

Not only did Collins offer Gutmann a position, but he also handed Gutmann a project that ultimately redirected the trajectory of his career.

Collins was on the brink of discovering the gene responsible for NF, which meant Gutmann could not only help identify the gene, but he could also help launch investigations into the gene’s function.

“This was the second genetics explosion I had the fortune to be a part of,” he says. “I remember thinking, ‘this is as good as it gets!'”

Yet for Gutmann, it just keeps getting better.

Ultimate collaborator

With passion and creativity as his most treasured qualities, the offer to join Washington University’s faculty in its renowned collaborative environment was impossible to resist.

“There are so few barriers to creativity here, and everyone was extremely welcoming and enthusiastic,” he says. “That’s a delicious combination. For someone like me, Washington University is the ultimate candy store.”

Here, Gutmann honed in on what he thought was the most pressing problem in young children with NF: tumors in a type of support cell in the brain, called an astrocyte.

He began applying his genetic understanding of the disease to develop mouse models of astrocyte growth and abnormalities. Before long, he had laid the groundwork for pioneering research not only on NF but also on brain tumor development in other genetic disorders and in the general population.

Now Gutmann, also a professor of genetics and of pediatrics, has set his sights even higher, building a synergistic network of faculty from a range of disciplines to break down even more scientific barriers.

“David is one of the leading physician-scientists in the world studying NF and the biology of brain tumors,” says David M. Holtzman, M.D., the Andrew B. and Gretchen P. Jones Professor of Neurology, the Charlotte and Paul Hagemann Professor of Neurology and head of that department. “His work and his multidisciplinary approach epitomize the type of translational research and clinical care the University is building as part of the BioMed 21 initiative.”

This latest project also enables Gutmann to attract a new generation of scientists to NF research, which he embraces as a way to en-sure the field’s prosperity and as an opportunity to provide the same invaluable support and mentorship he received as a new School of Medicine recruit.

According to one such scientist, Joshua B. Rubin, M.D., Ph.D., Gutmann is responsible for the group’s formation and its infectious energy.

“What has kept this collaboration going is how much fun it is to work with David, particularly for a young faculty member like myself,” says Rubin, assistant professor of pediatrics, of neurology and of anatomy and neurobiology.

“He gets very excited, and is the most organized person I have ever met — if only he weren’t so fanatic about Michigan sports.”

For Gutmann, the opportunity to build such an inspired research consortium has been more rewarding than his own research accomplishments.

And it’s brought him one critical step closer to his personal holy grail.

“My mission is to make sure everybody knows about NF and that when my productive days are over, I can look back and say we made a little bit of a difference,” he says.

“It’s going to take an army of experts and a lot of creative thinking to make individualized medicine a reality, and I’ll do whatever it takes to make that happen.”