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Autism Research: Progress and Promises

10/14/2010 4:45 PM 46
Gerald Fischbach, Scientific Director, The Simons Foundation

Description: "Imagine what it's like to go through life without understanding what people you are with are thinking," poses Gerald Fischbach. "You have no way of gauging whether they are angry, sad or happy." At the core of the group of disorders known as autism, says Fischbach, is damaged social cognition, a kind of prison of the mind. First defined in 1943, autism has not readily yielded its secrets to scientists, but in the past decade, says Fischbach, there has been "remarkable progress" in working out the disorder's likely causes and mechanisms.

As many as one in 100 people are now said to live with autism, up from one in 1000 a few years ago, but Fischbach believes the increasing numbers are more likely due to broadening public awareness and continually expanding definitions of the disorder, rather than an "epidemic." Research on this pervasive problem proceeds on several fronts: genetic risk factors, molecular mechanisms, and neural circuits, cognition and behavior. Fischbach notes a plethora of genetic approaches to autism but says, "We researchers feel we are on to something" focusing on a type of genetic change called a copy number variant.

Ordinarily, individuals inherit a gene from each parent, but sometimes this process goes awry, leading to variances in the number of copies of genes. Studies show that deletions in copy numbers that occur in a certain region of DNA correspond to a "big risk factor" for autism. But these clues are just the start, says Fischbach. Now researchers must begin "figuring out precisely which gene is at fault, and what it is doing in the nervous system."

Fischbach's Simons Foundation is assembling a research pool of families with autistic members to serve as a long"term resource for scientists investigating not just copy number variants, but also other disorders with autistic features, including Rett syndrome and Fragile X syndrome. McGovern Institute research is revealing the central role of the synapse in these disorders, and imaging work is helping to point out regions of the brain central to the performance of social tasks and possibly to autistic behaviors.

Fischbach hopes in the next decade science will figure out not just gene factors, but the neural circuitry at play in autism. Says Fischbach, "In the end, we need to develop theories and models to account for the link between genes and behavior It's not enough to say autism is a disorder of synapses, or of connections. Of course it is. We need more specific hypotheses about autism and how it relates to social behavior."

About the Speaker(s): Gerald D. Fischbach joined the Simons Foundation in early 2006 to oversee the Simons Foundation Autism Research Initiative. Formerly Dean of the Faculties of Health Sciences at Columbia University, and former Director of the National Institute of Neurological Disorders and Stroke at the N.I.H. from 1998"2001, Fischbach received his M.D. in 1965 from Cornell University Medical School and interned at the University of Washington Hospital in Seattle. He began his research career at the National Institutes of Health, serving from 1966 _ 1973. He subsequently served on the faculty of Harvard Medical School, first as Associate Professor of Pharmacology from 1973 _ 1978 and then as Professor until 1981. From 1981 _ 1990, Fischbach was the Edison Professor of Neurobiology and Head of the Department of Anatomy and Neurobiology at Washington University School of Medicine. In 1990, he returned to Harvard Medical School where he was the Nathan Marsh Pusey Professor of Neurobiology and Chairman of the Neurobiology Departments of Harvard Medical School and Massachusetts General Hospital until 1998.

Throughout his career, Fischbach has studied the formation and maintenance of synapses, the contacts between nerve cells and their targets through which information is transferred in the nervous system. He pioneered the use of nerve cell cultures to study the electrophysiology, morphology, and biochemistry of developing nerve _ muscle and inter"neuronal synapses. His current research is focused on roles that neurotrophic factors play in determination of neural precursor fate, synapse formation, and neuronal survival.

Fischbach is a member of the National Academy of Sciences, the American Academy of Arts and Science, the Institute of Medicine, and a fellow of the American Association for the Advancement of Science and a non"resident Fellow of the Salk Institute.

Host(s): School of Science, McGovern Institute for Brain Research at MIT

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