Zebrafish on drugs

In the November 21 Proceedings of the National Academy of Sciences, Peterson et al. describe a screen for chemicals that can be used to interfere with, and time, developmental events in zebrafish (Proc Natl Acad Sci USA 2000, 97:12965-12969). Zebrafish eggs were arrayed three to a well in 96-well plates, along with one of 1,100 synthetic small molecules. The developing embryos were screened once a day for three days for defects in the central nervous system, the cardiovascular system, pigmentation, or ear development, with one person capable of screening approximately 400 compounds a day. Approximately 2% of the compounds were generally lethal or caused widespread necrosis, but approximately 1% of the compounds affected a specific aspect of one system under study. Peterson et al. demonstrated the utility of such probes by adding and washing away a particular chemical at different times, thus determining that a critical stage for ear development occurs between 14 and 26 hours post-fertilization. Further insight may come from isolation of the proteins targeted by the chemicals, using procedures such as affinity chromatography.