The Genetic Revolution: The Importance of Flies and Worms

It seems remarkable that within 50 years of the discovery of the double helical structure of DNA, the genetic code was deciphered, recombinant DNA technology was devised, and the nucleotide sequences of the entire genomes of man, mouse, the fruit fly (Drosophila), the nematode (C. elegans), yeast, and many other organisms were determined. The discovery of thousands of genes represents one of the great achievements of science, yet the functions of most genes remain unknown. Eventually, it will surely be found that some of these genes are involved in psychiatric or neurological diseases. A tremendous opportunity exists to explore the functions of these genes by various means, including mutation or RNA interference. The latter method depends on the use of double-stranded RNA, or oligoribonucleotides, to temporarily destroy the corresponding species of mRNA, thereby resulting in a temporary mutant phenotype.

Comparative genomics has shown that Drosophila and C. elegans have many genes for proteins involved in neural information processing that are similar to genes found in humans. Thirty-eight genes that bear some similarity to genes thought to be involved in human neurological diseases have been found in Drosophila, including parkin, β-amyloid precursor-like protein, presenilin, tau (involved in frontotemporal dementia with parkinsonism), and neuroserpin (involved in familial encephalopathy) (1); some genes have also been found in C. elegans. There are many advantages to studying such genes in Drosophila or C. elegans, since many genetic techniques are available that can be used to investigate the functions of proteins, whereas similar studies in the mouse would be too time consuming or expensive to be feasible. For example, to find compounds that enhance memory in humans, hundreds of thousands of compounds are being screened currently in Drosophila by Timothy Tully of Cold Spring Harbor Laboratory.

Thus, the revolution in molecular genetics has created tremendous opportunities to do research that surely will lead to fundamental advances in knowledge of normal and pathological processes in psychiatry and neurobiology. But only in the human can one explore the psychological and social factors that influence behavior.