Peter Huttenlocher, MD, 1931-2013

August 19, 2013

A pioneering neuroscientist and highly respected pediatric neurologist, Peter Huttenlocher, MD, professor emeritus and former section chief of pediatric neurology at the University of Chicago Medicine, died in Chicago of pneumonia and complications of Parkinson's disease on Aug. 15, 2013. He was 82.

Huttenlocher was known internationally for his clinical skills, his research on pediatric neurological disorders and especially for a set of four groundbreaking studies on synaptic density and neural plasticity in children. Beginning in 1979, he became the first to describe the rapid increase in the connections between neurons in a child's developing brain, followed by gradual "pruning" of little-used connections.

He later mapped out the timetables for this process in three specific regions of the brain and correlated the timing of synapse generation -- the creation of new neuron-to-neuron connections -- with the acquisition of cognitive skills associated with that part of the brain. These discoveries made a significant impact on early childhood education, emphasizing the benefits of early introduction of certain subjects, such as learning a second language and musical training, to take advantage of periods of high neural plasticity.

"It would be hard to think of another discovery that is so central to our understanding of pediatric neurology," said his friend and colleague, 2000 Nobel laureate Eric Kandel, MD, the University Professor and Kavli Professor of Brain Science in the Department of Neuroscience at Columbia University and senior investigator at Howard Hughes Medical Institute.

"There was the suggestion, based on animal studies, that humans might assemble these connections between neurons after birth. But no one was thinking about young children subsequently losing those connections," Kandel said. "We now know how absolutely crucial synaptic pruning is to mental development and that defects in this system can lead to severe cognitive deficits."

Huttenlocher made major contributions to a variety of fields. Working with University colleagues in psychology, he studied the cognitive effects of focal brain injuries and the role of synapse generation in a child's recovery from brain damage. He was an early authority on the diagnosis and treatment of children with Reye's syndrome and helped organize a nationwide study looking at the suspected connection between this disease and aspirin use.

In 1987, with support from a grateful patient's family, he launched the first clinic in the United States for children with tuberous sclerosis, a rare neurologic disorder. He also did important research on seizure disorders, one of which, Alpers-Huttenlocher syndrome, was named after him and Bernard Alpers.

"Peter Huttenlocher was a rare triple threat," said colleague Susan Levine, PhD, Rebecca Anne Boylan Professor in Psychology and a member of the Committee on Education at the University of Chicago. "His research was known and respected worldwide and highly cited. He was a fabulous and devoted physician, absolutely committed to his patients. And he was a role model for medical students, in the classroom and the clinic."

His legacy includes the many medical students, residents and neurology fellows he helped to train at Yale University and the University of Chicago.

"I will always be grateful to him for being such a fine teacher and, in particular, for teaching by example," said Bruce Beutler, MD, a 1981 graduate of the University of Chicago Pritzker School of Medicine and a 2011 Nobel laureate. "I remember him as extremely compassionate and considerate, both to patients and their parents, and to the house staff and students. From him, I first learned how children, and particularly infants, are almost like a different species. They must be examined for neurological function using entirely different tests and evaluation criteria than adults."

Beutler recalled Huttenlocher's interest in Reye's syndrome, which was alarmingly common when he was in medical school. "I remember such a patient: a boy who had been treated with aspirin when he had chickenpox and developed a severe encephalopathy," he said. "Peter seemed deeply moved by that particular case. I remember him calling out to the comatose child by name, hoping for a response."

Peter Richard Huttenlocher was born on Feb. 23, 1931, in Oberlahnstein bei Koblenz, Germany. His father, Richard, was a chemist. His mother, Else, an opera singer, ran afoul of the Nazi party and had to leave Germany shortly before World War II.

Huttenlocher and his brother, Dieter, moved to the United States in 1949. He quickly learned English -- even though he was well past the critical period for learning a foreign language -- and earned his bachelor's degree, summa cum laude, in philosophy from the University at Buffalo in 1953.

He met his wife, Janellen Burns, who would become a highly respected cognitive psychologist, when they were freshmen in college. "He was tall and handsome and he just started following me around," she recalled. "I soon learned that he was this incredibly kind, fair fellow, the kindest man on the planet."

After graduation, they both began advanced studies at Harvard University; he in medicine, she in psychology. They married in June 1954.

Huttenlocher earned his MD, magna cum laude, from Harvard Medical School in 1957. After an internship at Harvard's Peter Bent Brigham Hospital, he completed his residency at Boston Children's Hospital and Massachusetts General Hospital (MGH), followed by research fellowships at the National Institutes of Health and MGH. He was an assistant professor in pediatric neurology at Harvard from 1964 to 1966, followed by eight years at Yale University Medical School. In 1974, he moved to the University of Chicago as a professor of pediatrics, adding neurology in 1976. He stayed for almost 30 years, shifting to emeritus status in 2003.

He published extensively, more than 80 papers in leading journals plus dozens of book chapters, on a wide variety of topics related to brain development and neurologic disease in children. In 2002, he published Neural Plasticity: The Effects of Environment on the Development of the Cerebral Cortex, a book that synthesized his landmark research on synapse generation and pruning and placed it in context. He received a number of honors for his discoveries and served on regional and national study sections and committees for many organizations, including the National Institutes of Health, the Easter Seals research foundation, the March of Dimes and the National Tuberous Sclerosis Foundation.

Many of Huttenlocher's fundamental discoveries grew out of encounters with his patients. His interest in the blossoming and pruning of neural synapses in the normal young brain, for example, was triggered by the sparse, poorly connected neurons he examined from patients with fatal, neurologic defects.

"Paradoxically, in our early studies, the findings in the normal population were more interesting than the abnormal population," he wrote in a 1999 essay about this project. So he shifted the focus from diseased cells to normal neurons, the control group.

Over the next 20 years, he and colleagues performed autopsies on the brains of about 50 people, mostly infants and young children who had died unexpectedly, but also a few adults, one of them age 90. Using an electron microscope to count each synapse, they showed that synaptic density was low at birth, about 2,500 connections per neuron. It increased rapidly to levels 50 to 60 percent above adult levels, and then gradually declined, falling to typical adult values.

This happened at different paces in different brain centers. In the auditory cortex, crucial for learning language and music, synaptic density peaked early, about 3 months old, then tapered to adult levels by age 12. In the visual cortex, density peaked at 8 to 12 months, and then declined to adult levels by about age 12. In the frontal cortex, important for higher-order thinking, synaptic density peaked at around 3 years of age and slowly declined into the middle teen years.

His discoveries have had a significant effect on current thinking about education.

"It heightened our awareness of the importance of the early years," Levine said. "It was just one piece of the puzzle, but it was the piece based on solid, quantifiable, consistent evidence, meticulously gathered at the cellular and subcellular level. Peter's work had a huge impact on how we think about the underlying neural basis of learning."

Huttenlocher also had many interests outside of medicine. He played the flute, and his plum torte was legendary. He also built a cabin for the family in the woods of western Massachusetts, with a bridge across a nearby creek.

He was "a deeply engaged appreciator of classical music and German Expressionist art, a tireless caretaker of homes, yards and woodlands, and a baker of cakes and fruit pastries," said his daughter Anna. "He built us little castles and doll houses.".

Huttenlocher is survived by his wife, Janellen, PhD, the William S. Gray Professor Emeritus of psychology at the University of Chicago; three children, Daniel, PhD, dean and vice provost of the new Tech Campus at Cornell University, Anna, MD, a professor of medical microbiology & immunology and pediatrics and director of the MD/PhD program at the University of Wisconsin, and Carl, the founder of Myriad Asset Management Ltd; and four grandchildren, Eric, Jason, Annika and Kaia.

A memorial service is planned for 2 p.m. Saturday, Sept. 28, at Montgomery Place, 5550 S. Shore Drive, Chicago. In lieu of flowers, donations may be sent to the Tuberous Sclerosis Association (http://www.tuberous-sclerosis.org/) or the Parkinson's Disease Foundation (http://www.pdf.org/).