A simple nervous system
Horvitz's work has influenced many areas of biology over the years, but neuroscience has always been a central interest. By hunting for genetic mutations that affect C. elegans behaviors, Horvitz has revealed much about the genetic control of brain function, including how neural circuits control specific behaviors and how behavior is modulated by environment and experience. Many of the chemical signals used by the worm's nervous system are also present in the human brain. For example, Horvitz showed that serotonin, a neurotransmitter implicated in the control of human mood and appetite, also regulates the movement of worms. This finding has led to several new genes that affect serotonin signaling, which could help to identify potential targets for human drug development.
Another major theme of Horvitz's work is cell death. Apoptosis, or cell death, is a central feature of human neurodegenerative disease. Horvitz has shown that cell death is often an active process, and that many of the genes that control the deaths of worm neurons have counterparts in the human brain. Understanding how these genes operate has provided new insights into normal brain development as well as the pathological processes involved in many brain disorders. His discoveries might lead to new treatments for certain retinal degenerative diseases as well as for Alzheimer's, Parkinson's and Huntington's diseases, stroke and traumatic brain injury. Horvitz has recently begun to study the genetic basis of aging, and one of his aims is to understand how aging drives the degenerative process in conditions such as Alzheimer's disease.
In October 2002, the Nobel Prize in Physiology or Medicine was awarded to Horvitz, Sydney Brenner, and John El Sulston "for their discoveries concerning genetic regulation of organ development and programmed cell death."
Searching for human disease genes In addition to his work on C. elegans, Horvitz also has a longstanding interest in human neurodegenerative disease. He was a principal member of the team that in 1993 identified the first gene to cause familial ALS (Lou Gehrig's disease), and in collaboration with colleagues at Massachusetts General Hospital he continues to work on the search for additional ALS genes.