I
n a windowless room near the western edge of Vancouver, Canada, a team of researchers trains microscopes on dishes of tiny worms about the size of a comma in 12-point font. Some of the worms squirm atop a sticky, jelly-like platform of nutrients that is saltier in some places than in others. Others endure vibrations as a machine periodically taps the sides of their dishes.Typical roundworms of this species, known scientifically as Caenorhabditis elegans, move toward salt — a sign of food — and crawl backward when they sense reverberations. But these roundworms crawl away from salt and often seem to ignore the knocks on their dishes. The strange behavior suggests that a mutation the worms have — in a top autism gene called PTEN — is harmful. “It might seem a little funny at first to study, say, tapping a dish with worms in it,” says Troy McDiarmid, a former graduate student in the lab of Catharine Rankin, a behavioral neuroscientist at the University of British Columbia in Canada. “But that ends up being a really good readout” of the role autism-linked genes play in learning and behavior.
Most animal research on autism involves mice. As fellow mammals, mice are relatively closely related to people, but there’s still debate about whether the behaviors of autism mouse models accurately mirror those of autistic people. And yet, in the past 20 years, some autism researchers have turned to even simpler animals, such as roundworms, fruit flies and zebrafish, for their investigations. In 2000, just one published autism
study used zebrafish or roundworms, and four focused on fruit flies. In 2020, those numbers had risen to 29 studies for zebrafish, 30 for fruit flies and 8 for roundworms.
So how could a fish or a fly, let alone a roundworm, be the source of insights into a condition that involves language and complex cognitive skills? Autism researchers who work with these animals are careful not to overhype their possibilities. Their nervous systems are small and lack complex brain structures, and their genes are regulated differently from those in mammals. Yet the basic mechanisms by which cells function have a remarkable continuity across animals, as do the structure and function of many genes. Seemingly simple animals also may show complex behaviors: Flies have social networks; fish swim in sync with others of their kind; worms pick up on chemical signals from other worms to help them find food.
The major value of these model organisms is practical: They are relatively cheap and easy to maintain, with short generation times, and straightforward to manipulate genetically. So researchers can use them for rapid-fire testing of drugs or to get a quick read on the effects of mutations, as well as for exploratory work that would be too costly and time-consuming in mice. “You can do a lot of wonderful things in C. elegans,” Rankin says.
These animals have helped link new genes to autism, sort out harmful from benign mutations, show how multiple autism-linked genes interact, and uncover neural circuits involved in sensory and social function. “Working on simple critters is an essential part of the information pipeline,” says James Rand, a retired molecular biologist who worked at the Oklahoma Medical Research Foundation in Oklahoma City.