Switching Sides

Carl Zimmer

One day in 1788, students at the Hunterian School of Medicine in London were opening a cadaver when they discovered something startling. The dead man's anatomy was a mirror image of normal. His liver was on his left side instead of the right. His heart had beaten on his right side, not his left.

The students had never seen anything like it, and they rushed to find their teacher, the Scottish physician Matthew Baillie, who was just as stunned as they were. "It is so extraordinary as scarcely to have been seen by any of the most celebrated anatomists," he later wrote.

His report was the first detailed description of the condition, which came to be known as situs inversus and is thought to occur in about 1 in 20,000 people. Baillie argued that if doctors could figure out how this strange condition came to be, they might come to understand how our bodies normally tell the right side from the left.

Over two centuries later, the mystery of left and right still captivates scientists. "I know what it is, you know what it is, but how does the embryo learn what it is?" asked Dominic P Norris, a developmental biologist at the University of Cambridge in England. Now Norris and other scientists are beginning to answer that question. They have pinpointed some of the steps by which embryos' organs develop on the left or right. And their research may do more than simply solve an old puzzle.

Mutations that cause situs inversus can lead to a number of serious disorders, including congenital heart defects. Deciphering the effects of mutated genes could lead to diagnoses and treatments for those conditions.

Biologists have pinpointed a single spot where this symmetry breaking starts: a tiny pit called the node, on the embryo's midline. The interior of the node is lined with hundreds of tiny hairs, called cilia, which whirl round and round at a rate of 10 times a second. These whirling cilia are tilted, pointing away from the head. The tilt is essential to their ability to divide the body into left and right. Recently Kathryn V Anderson and her colleagues at Memorial Sloan-Kettering Cancer Center disabled genes required to tip the cilia in the node. As they report in the journal Development, that mutation led to some mouse embryos' developing a mirror-image anatomy.

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