Growing up in the 1950s and 1960s in West Hartford, Conn., Carla Shatz was a self-described “science nerd” — an unorthodox descriptor for a girl at that time. Her mother, an artist, and her father, an aeronautical engineer, encouraged her to follow her interests, however. “They were pretty amazing people,” Shatz recalls. “They gave me an important piece of advice: Don’t worry what other people think of you. I think I was a little less susceptible to peer pressure as a result.”
Shatz went to Radcliffe College, then the “sister” school of Harvard University, where she majored in chemistry, but also followed another early passion of hers: design. Courses with perceptual psychologist Rudolf Arnheim and with biochemist George Wald, who had won a Nobel Prize for his work on how the eye converts light to a neural signal, got Shatz interested in the science of vision. Her Chemistry advisor suggested that she work on her honor thesis with Harvard neurophysiologists David Hubel and Torsten Wiesel, who were investigating how the brain processes visual information coming from the eyes (work for which they would win a Nobel Prize in 1981). Shatz found the work irresistibly fascinating. After graduating from Radcliffe in 1969, she decided to become a neurobiologist.
Shatz won a Marshall scholarship to the University College London to study physiology, and then returned to Hubel and Wiesel’s lab for her doctoral studies. In 1976, she became the first woman to receive a PhD in neurobiology from Harvard University. “I didn’t realize that I was pioneering anything at that time,” she recalls. “I also didn’t realize until later that there had been a really serious discussion at Harvard about whether to allow a woman to the program. They were worried a woman might go off and get married and have kids.”
After Harvard, Shatz was hired by Stanford University Medical School, where she established another milestone for her gender: She became the first woman in the basic sciences at the medical school to receive a tenured professorship. Once she had her own lab, Shatz set out to expand on the work of her mentors, Hubel and Wiesel, but she was soon making groundbreaking discoveries of her own. At the time, it was believed throughout the neuroscience community that the visual system in the mammalian brain was hardwired until the animal was born, at which point experience “fine-tuned” the system’s neural connections. Shatz showed, however, that the eye sends neural signals to the brain very early in development — long before the animal can see or even born. She also demonstrated that this in utero spontaneous neural activity comes in highly synchronized neural “waves” that help prune and strengthen connections in the brain’s visual system. “It’s sort of a rehearsal for post-natal life, in this case for vision,” says Shatz.
In 1992, Shatz moved to the University of California, Berkeley, with her then-husband, who was also a neuroscientist. While there, she began a series of experiments that led to even more remarkable discoveries. One of the most important of these was the finding that MHC (major histocompatibility) Class I genes are needed for the synaptic remodeling that helps the developing brain tune up its circuits in preparation for visual input. This finding was a huge surprise, says Shatz, for at the time, MHCI proteins were well known for their role in the immune system, but were not believed to be expressed by neurons.
“When we sent the paper to Nature, we got a nice note back telling us we must have made some fundamental mistake in our lab,” Shatz recalls. But she wasn’t deterred. “I told the guys in my lab not to get discouraged,” she says. “I knew we weren’t wrong.” Shatz sent the paper to the journal Neuron, which accepted it. That study redefined the field of neuroimmunology.
In 2000, Shatz returned to Harvard Medical School to chair the neurobiology department — the first woman to do so. More groundbreaking discoveries followed, including the finding that MHCI molecules interact in the brain with another molecule that was also previously thought to exist only in the immune system: a receptor called PirB. After developing a mouse model that lacked PirB, Shatz demonstrated that synaptic plasticity in the visual cortex was far greater than normal, not only during critical periods of development but also during adulthood. Her lab also reported that these “knockout” mice performed better at learning and memory tasks. Even after the knockout mice were given strokes, they regained their ability to perform the tasks more quickly and more fully than normal mice with strokes. Shatz and her lab also discovered that if they removed PirB receptors from the brains of mice with Alzheimer’s, the animals did not develop the disease. These and other findings have opened entire new avenues of research into the treatment of stroke, Alzheimer’s, and other devastating brain diseases.
Much of this later work was conducted at Stanford, where Shatz returned in 2007 to run Bio-X, an interdisciplinary institute that encourages collaboration among biomedical and life science researchers, clinicians, engineers, physicists, and computer scientists. “We’re trying to break down the silos that exist between departments and across school borders,” says Shatz. “It’s very stimulating and rewarding.”
Shatz has received numerous honors and awards during her career, including memberships in the National Academy of Sciences, the American Academy of Arts and Sciences, the Institute of Medicine and the Royal Society of London. She has also served in many leadership roles within the scientific community, including as president of the Society for Neuroscience during 1994-1995. Over the years, Shatz has mentored and trained many graduate and postdoctoral students who are now recognized leaders in neurobiological research at academic institutions around the world.
Shatz is a lifelong skier and opera enthusiast. She engages in both activities whenever she has the chance. Science, however, remains her major focus, for Shatz finds it as fascinating today as she did as a child growing up in Connecticut. “Right now, I’m working so hard and loving it so much, I don’t have time for much else,” she says.