If that’s true, sleep in humans, rodents,
and other vertebrates is a highly evolved
behavior—one adapted to each organism’s
needs and lifestyle. Gleaning insights into
its basic function from those species could
be difficult. Earlier evolving creatures, with
fewer cell types, less complicated molecu-
lar pathways, and simpler behaviors may
reveal sleep in its most fundamental form.
So, some sleep researchers have turned
to invertebrates such as fruit flies and
roundworms—and most recently to
sponges and another early-evolving group,
placozoans. Already, their work is driving
home two key new insights: that sleep’s
benefits extend far beyond the brain, and
that muscles, the immune system, and the
gut can all have a say in when and how
sleep occurs. That work “might change our
focus from studying sleep’s role in complex
cognitive processes to how it impacts ba-
sic cellular function,” says Alex Keene, a
neurogeneticist at Texas A&M University,
College Station.
A new picture of what controls sleep
might also lead researchers to new treat-
ments for sleep disorders, says Amita
Sehgal, a neuroscientist at UPenn’s Chrono-
biology and Sleep Institute. “The hope is
that what we learn will be relevant to un-
derstanding why some people can’t sleep
and also how disrupted sleep might affect
their health and performance.”THE EARLIEST STUDIES of sleep defined it
by how it changes human behavior: We lie
down, close our eyes, remain motionless,
and become oblivious to the outside world.
Also obvious are the consequences of skip-
ping sleep: We lose our ability to function,
struggling to focus in a meeting or dozing
off at the wheel.
By the 1950s and ’60s, researchers were
converging on a definition of sleep based
on polysomnography, a combined measure
of brain activity, eye movement, and muscle
tone that became a gold standard. Neuro-
scientists figured out how to capture
brain activity from electrodes on the sur-
face of the head and discovered that hu-
man sleep has two major stages: rapid eye
movement (REM), a more active stage in
which dreaming occurs; and non-REM,
defined by slow, synchronous waves of
electrical firing.
Behavioral and physiological tests have
revealed how varied sleep can be in the
animal world. Cows and other large graz-
ing mammals sleep standing up. Some ma-
rine mammals sleep while swimming and
some seabirds catnap while flying, letting
one half of the brain doze while the other
keeps working. Bats sleep about 20 hours a
day; wild elephants as few as two. Most of
the animals studied with electrical record-
ing techniques have at least two stages of
sleep, though the brain activity characteriz-
ing these stages can vary. The color changes
of the octopus as it sleeps suggest it, too,
has several sleep stages.
By the turn of the 21st century, evidence
of sleep outside mammals prompted re-
searchers to start to work down the animal
tree of life to evolutionarily older species.
They had to confront the question of how
to define sleep in these simpler species. A
sleeping jellyfish looks a lot like a wakingone, after all, and is nearly impossible to
outfit with electrodes. Researchers must
instead recognize where and when simple
creatures seek respite and find a behavior
that ceases when they sleep. Studies must
also poke or otherwise bother the animals
to make sure they are unresponsive—and
to see whether being forced to stay awake
has consequences.
In 2017, Michael Abrams and two other
California Institute of Technology graduate
students devised such tests for Cassiopea,
known as the upside-down jellyfish be-
cause it tends to stay near the shallow sea
floor, pulsing with its tentacles pointing up
so more light reaches the photosynthetic
microorganisms it relies on for energy. The
students observed that at night, this motion
slowed from 60 pulses per minute to 39.
To see whether the jellyfish were really
asleep, they built a false bottom to the
aquarium and lowered it—essentially “pull-
ing the rug out” from under the creatures.
At night, the groggy jellyfish were slower
to react and swim to the new bottom than
in the day. And when the team disturbed
the jellyfish by pulsing currents of water
over them, the animals were less active the
next day—as if having to recuperate from
sleep loss. Finally, the drug melatonin,
an over-the-counter sleep remedy, slowed
their pulses to nighttime speeds. All this
without a real brain: Jellyfish have a ring
of nerve cell clusters around the rim of
their bells.
Recently, researchers caught another
brainless creature napping: Hydra vulgaris,
a stationary freshwater relative of jellyfish.
Taichi Itoh, a chronobiologist at Kyushu
University, and colleagues filmed these
centimeter-long animals as they wiggled
their tentacles during 12-hour periods of
light and dark in the lab. In the dark, the
hydra were less active. Other researchers
probing sleep in simpler animals have also
adopted definitions based on behavioral
changes such as reduced responsiveness.
More recently, however, a few are advo-
cating a shift to molecular criteria such as
whether an organism has genes that are
part of sleep-promoting pathways in mam-
mals and other species known to sleep. For
example, Itoh’s team reported last year that
more than 200 genes changed their activ-
ity in sleep-deprived hydra. Several of these
genes are involved with sleep in fruit flies,
they noted.
“We are moving from a behavioral
or physiological definition to a cellular
and molecular definition,” says Philippe
Mourrain, a neurobiologist at Stanford Uni-
versity. “As we define more and more what
sleep is [on those levels], we will have an
idea of its function.”SCIENCE science.org 29 OCTOBER 2021 • VOL 374 ISSUE 6567 527
One of the first brainless creatures shown to
sleep, the upside-down jellyfish, pulses
its bell more slowly at night than in the day.NEWS