Sleep Evolved Before Brains. Hydras Are Living Proof.

The hydra is a simple creature. Less than half an inch long, its tubular body has a foot at one end and a mouth at the other. The foot clings to a surface underwater — a plant or a rock, perhaps — and the mouth, ringed with tentacles, ensnares passing water fleas. It does not have a brain, or even much of a nervous system.

And yet, new research shows, it sleeps. Studies by a team in South Korea and Japan showed that the hydra periodically drops into a rest state that meets the essential criteria for sleep.

On the face of it, that might seem improbable. For more than a century, researchers who study sleep have looked for its purpose and structure in the brain. They have explored sleep’s connections to memory and learning. They have numbered the neural circuits that push us down into oblivious slumber and pull us back out of it. They have recorded the telltale changes in brain waves that mark our passage through different stages of sleep and tried to understand what drives them. Mountains of research and people’s daily experience attest to human sleep’s connection to the brain.

But a counterpoint to this brain-centric view of sleep has emerged. Researchers have noticed that molecules produced by muscles and some other tissues outside the nervous system can regulate sleep. Sleep affects metabolism pervasively in the body, suggesting that its influence is not exclusively neurological. And a body of work that’s been growing quietly but consistently for decades has shown that simple organisms with less and less brain spend significant time doing something that looks a lot like sleep. Sometimes their behavior has been pigeonholed as only “sleeplike,” but as more details are uncovered, it has become less and less clear why that distinction is necessary.

It appears that simple creatures — including, now, the brainless hydra — can sleep. And the intriguing implication of that finding is that sleep’s original role, buried billions of years back in life’s history, may have been very different from the standard human conception of it. If sleep does not require a brain, then it may be a profoundly broader phenomenon than we supposed.

Recognizing Sleep

Sleep is not the same as hibernation, or coma, or inebriation, or any other quiescent state, wrote the French sleep scientist Henri Piéron in 1913. Though all involved a superficially similar absence of movement, each had distinctive qualities, and that daily interruption of our conscious experience was particularly mysterious. Going without it made one foggy, confused, incapable of clear thought. For researchers who wanted to learn more about sleep, it seemed essential to understand what it did to the brain.

And so, in the mid-20th century, if you wanted to study sleep, you became an expert reader of electroencephalograms, or EEGs. Putting electrodes on humans, cats or rats allowed researchers to say with apparent precision whether a subject was sleeping and what stage of sleep they were in. That approach produced many insights, but it left a bias in the science: Almost everything we learned about sleep came from animals that could be fitted with electrodes, and the characteristics of sleep were increasingly defined in terms of the brain activity associated with them.

This frustrated Irene Tobler, a sleep physiologist working at the University of Zurich in the late 1970s, who had begun to study the behavior of cockroaches, curious whether invertebrates like insects sleep as mammals do. Having read Piéron and others, Tobler knew that sleep could be defined behaviorally too.

She distilled a set of behavioral criteria to identify sleep without the EEG. A sleeping animal does not move around. It is harder to rouse than one that’s simply resting. It may take on a different pose than when awake, or it may seek out a specific location for sleep. Once awakened it behaves normally rather than sluggishly. And Tobler added a criterion of her own, drawn from her work with rats: A sleeping animal that has been disturbed will later sleep longer or more deeply than usual, a phenomenon called sleep homeostasis.

Tobler soon laid out her case that cockroaches were either sleeping or doing something very like it. The response from her colleagues, most of whom studied higher-order mammals, was immediate. “It was heresy to even consider this,” Tobler said. “They really made fun of me in my early years. It wasn’t very pleasant. But I sort of felt time would tell.” She studied scorpions, giraffes, hamsters, cats — 22 species in all. She was convinced that science would eventually confirm that sleep was widespread, and in later studies of sleep, her behavioral criteria would prove critical.

Those criteria were on the minds of Amita Sehgal at the University of Pennsylvania School of Medicine, Paul Shaw (now at Washington University School of Medicine in St. Louis) and their colleagues in the late 1990s. They were part of two independent groups that had begun to look closely at the quiescence of fruit flies. Sleep was still largely the domain of psychologists, Sehgal says, rather than scientists who studied genetics or cell biology. With respect to mechanisms, from a molecular biologist’s perspective, “the sleep field was sleeping,” she said.

However, the neighboring field of circadian clock biology was exploding with activity, following the discovery of genes that regulate the body’s 24-hour clock. If molecular mechanisms behind sleep could be uncovered — if a well-understood model organism like the fruit fly could be used to study them — then there was the potential for a revolution in sleep science as well. Flies, like Tobler’s cockroaches and scorpions, could not be easily hooked up to an EEG machine. But they could be observed minutely, and their responses to deprivation could be recorded.

With Less and Less Brain

In January 2000, Sehgal and her colleagues published their paper asserting that flies were sleeping. That March, Shaw and colleagues published their parallel work confirming the claim. The field was still reluctant to admit that true sleep existed in invertebrates, and that human sleep could be usefully studied using flies, Shaw says. But the flies proved their worth. Today more than 50 labs use flies to study sleep, generating findings that suggest that sleep has a set of core features present across the animal kingdom. And biologists did not stop with flies. “Once we showed that flies slept,” Shaw said, “then it became possible to say that anything slept.”

The sleep that researchers studied in other species was not always similar to the standard human variety. Dolphins and migrating birds can send half their brain to sleep while appearing awake, researchers realized. Elephants spend almost every hour awake, while little brown bats spend almost every hour asleep.

In 2008, David Raizen and his colleagues even reported sleep in Caenorhabditis elegans, the roundworm widely used as a model organism in biology laboratories. They have only 959 body cells (apart from their gonads), with 302 neurons that are mostly gathered in several clusters in the head. Unlike many other creatures, C. elegans does not sleep for a portion of every day of its life. Instead, it sleeps for short bouts during its development. It also sleeps after periods of stress as an adult.

The evidence for sleep in creatures with minimal nervous systems seemed to reach a new high about five years ago with studies of jellyfish. The Cassiopea jellies, about four inches long, spend most of their time upside down, tentacles reaching toward the ocean surface, and pulsating to push seawater through their bodies. When Michael Abrams, now a fellow at the University of California, Berkeley, and two other graduate students at the California Institute of Technology asked if Cassiopea might sleep, they were continuing the line of inquiry that Tobler had followed when she studied cockroaches, investigating whether sleep exists in ever simpler organisms. If jellyfish sleep, that suggests sleep may have evolved more than 1 billion years ago and could be a fundamental function of almost all organisms in the animal kingdom, many of which do not have brains.