biomedical factors in feature The ‘Three Strikes’ Concept of Autism Interviewed by Judy Chinitz Gorman; Edited by Dr. Ian Lipkin and Dr. Mady Hornig

Since the 1980s, Dr. Ian Lipkin has investigated the links between strikes principle in children. A unique opportunity to do so infection, immunity and brain disorders. In 1995, Dr. Mady emerged in 2000 when they were invited to join the faculty of the Hornig introduced him to screenwriter and Emmy Award-winning Mailman School of Public Health by Dr. Ezra Susser, a pioneer art director, Portia Iversen and her husband, movie producer in birth cohort research. In conjunction with the Norwegian In- Jonathan Shestack, the founders of CAN (Cure Autism Now). stitute of Public Health, the team began a unique autism research Impressed by their dedication, and concerned with the initiative, the ABC Project: Gene-environment Interactions in an overall lack of awareness of the significance of this public health Autism Birth Cohort (www.abc.columbia.edu). problem, Lipkin became an advocate for autism research. As the the ABC project involves collecting 100,000 samples of first chair of the scientific advisory board ofC AN, he recruited a umbilical cord blood from a random population of Norwegian distinguished group of neuroscientists and physicians, and helped infants, along with biological samples from their mothers, begin- develop grant mechanisms to bring new investigators to the field. ning at the 17th week of pregnancy. Samples also are taken from He also began to shift his laboratory’s efforts to autism research. their fathers. By following the infants’ natural histories over years, Hornig’s investigations into the importance of brain-immune recording physical and behavioral anomalies, rigorously diagnos- interactions in the development of neuropsychiatric illness also date ing and characterizing a subset of autism cases and controls, and back to the early 1980s with work on the combined modulation comparing their genetic materials, the team has an excellent op- of brain function by immune and central nervous system factors. portunity to identify both the biomedical markers that may make Intrigued by the concept that the immune system often is responsive children susceptible to autism and the environmental factors that to environmental stressors, she hypothesized that variations in the may tip the scales: , bacteria, toxins such as mercury or individual’s genes and maturational state, combined with these PCBs, psychosocial stress, or combinations thereof. stressors, were important to health outcomes. they can compare the DNA of children who develop autism Lipkin and Hornig use animal models and epidemiologic to those who do not to better understand heritable risks, and approaches to dissect potential causes of neurodevelopmental measure levels of messenger RNAs and proteins to learn when disorders and to test potential strategies for early diagnosis, various genes important for brain development are turned on prevention and treatment. Their work has led to the “three and off. Identification of specific patterns of gene expression can strikes” concept of neurodevelopmental disorders such as autism, provide tools for diagnosis at birth and insights into the causes of whereby genetic susceptibility (strike one), environmental trig- different subtypes of disorders that may lead to gers (strike two) and the timing of exposure during periods of new strategies for prevention or treatment. vulnerability for the developing nervous system (strike three) Lipkin brings to this program what he describes as a “peace result in disease. This concept integrates , microbiology, dividend” from his work in biodefense research: exciting new developmental biology and toxicology, and explains why efforts techniques for rapid, sensitive detection of infection and disor- that focus on only one of these disciplines have not been successful. dered immunity, and high throughput molecular investigations. After demonstrating the biological plausibility of the three In the near future, Lipkin and Hornig, in collaboration with strikes paradigm in animal models of neurodevelopmental dis- Drs. Margaret Bauman and Timothy Buie, both at Harvard Uni- orders involving infection, autoimmunity and toxicant exposure, versity’s Massachusetts General Hospital, will publish research on Lipkin and Hornig began to search for ways to explore the three the relationship of the -mumps-rubella vaccine to autism.

Authors Dr. W. Ian Lipkin is the Jerome L. and Dawn Greene professor of epidemiology, and professor of Neurology and Pathology in the Mailman School of Public Health (MSPH), and College of Physicians and Surgeons at in New York.

Dr. Mady Hornig is an associate professor of epidemiology at MSPH and director of translational research in the Greene Laboratory.

Judy Chinitz Gorman is the parent of two sons, one of whom has autism. She holds a master’s in special education and is currently pursuing another in nutrition.

Autism Advocate FIFTH EDITION 2006 45