Out of the closet: Intriguing research suggests that sleep has a long evolutionary history
P. Rajendran
Photo: John A De Modena
Sometimes great ideas come to life in garages, at others in closets, as in the case of Salman Khan’s Khan Academy. Or the discovery that Ravi Nath and his colleagues at Caltech made – that sleep stretches back longer in time than most scientists imagine, all the way to jellyfish.
But before they got there, there were a few caffeine-driven circular arguments about the ubiquitousness of sleep with fellow graduate students Claire Bedbrook and Michael Abrams.
“Mike and I were getting coffee and we were talking about testing this – sleep in jellyfish,” Nath told Truly Curious. “Then Claire walks in and began challenging our experiments [saying] it’s very unlikely that they sleep.”
The trio had different research viewpoints, coming as they did from different labs.
Nath was part of the Paul Sternberg group where he studied, among other things, stress-induced sleep in Caenorhabditis elegans, a harmless soil nematode that researchers love dearly for its simple structure and a body so transparent that they can look right through it. His team’s lab work extended the work of David Raizen of the University of Pennsylvania, who discovered that C. elegans has a sleep-like stage called lethargus. Nath presented that research at the 2017 Society for Neuroscience convention in Washington, DC.
The Viviana Gradinaru lab that Claire Bedbrook works in focused on optogenetics, wherein light is used to either stop or start the activity of certain proteins. Bedbrook, too, was at the SfN, presenting her work on machine learning models involving light-operated proteins.
And Mike Abrams? He has worked on the moon jellyfish – Aurelia aurita – in the lab of Lea Goentoro. In earlier work, he had found that when Aurelia loses an arm, it makes the best of a bad job and reorganizes the remaining appendages to regain symmetry.
The problem of sleep
Most people are quite sure that all animals sleep. But that is a deceptive assumption to make. There was insufficient evidence to believe that what applies to animals like us may apply to them all.
There are certain regular rhythms in all creatures, even in bacteria, but the kind of programmed, cascading changes that we see in what we call sleep requires a nervous system to coordinate cellular behavior, Nath said.
He said they worked with a behavioral definition of sleep, which calls for reduced activity and to responses to stimulation at night, which is reversed rapidly when required. Finally, if these behaviors are blocked for a while, the standard signs of sleep deprivation show up: lethargy, mood shifts, reduced coordination and the rest of the symptoms you experience after staying up through the night.
A diabolical experiment
Photo: L Goentoro lab/Caltech
The three researchers decided to test their assumptions against reality by conducting an unapproved experiment. Paul Sternberg, Nath’s mentor, suggested they do the experiment in an available closet that, despite the presence of junk, still had some space.
They worked with the Cassiopea species, jellyfish that move about upside down and which is usually found in shallow waters. Jellyfish are Cnidarians, a group of animals that broke off early from the evolutionary lineage that led to mollusks, then roundworms like C. elegans that Nath studied, all the way to mammals, including humans. If the animals exhibited sleep-like behavior, it likely came down from their common ancestor with the rest of the animal kingdom, thus making sleep a really old set of behaviors.
The researchers observed the behavior of 16 jellyfish in a 10-gallon tank for three days and nights. The animals pulsed rhythmically at the rate of once every second usually, but when the lights were turned off reduced their activity to nearly half three to six hours later, the lowest amount of pulsing occurring 6-12 hours after the onset of darkness.
To see if this restful phase could be reversed, they provided the jellyfish with food during the dark phase. Sure enough, the jellyfish woke up for the midnight snack and were about as active as they were when the lights were on.
That is when the experiment became almost evil.
Within the tank, the researchers kept the creatures in a PVC tube with a mesh bottom that would allow water out. They raised the tube slowly, gave the jellyfish 5 minutes to settle, then quickly lowered it, leaving the resting Cassiopea suspended well above the floor.
Consider this: You carry a bed bearing a sleeping friend to the porch, pull him off the bed, and while he is still recovering, take the bed back to the bedroom. The idea is to see how long it takes for your now former friend to recover and grumble his way back to bed.
In this experiment, like our cruelly pranked sleeper, it took the jellyfish some time to find their way back to their preferred bed on the tank floor.
They tried a variety of different manipulations, including jogging the resting creatures with 10-second pulses of water. This was to see if lack of the sleep-like behavior could reduce activity the next ‘day.’ In the light phase it made little difference; during the dark one, it resulted in a significant reduction in activity.
Additionally, they found that melatonin, which is linked to sleep-like behavior in many creatures, including humans, also reduced activity in the jellyfish during the day.
The same went for pyrilamine, a drug that blocks a receptor that usually binds with histamine. Histamine is a body chemical that promotes wakefulness. Pyrilamine makes humans and other vertebrates sleepy; in Cassiopea it reduced activity in a fashion reminiscent of sleep. This suggests that some of the same mechanisms that work in vertebrate sleep may have been present in the ancestor that we have in common with jellyfish.
The way ahead
One possible consolation for indignant jellyfish right activists might be that the three researchers had to be up all hours. They were up during the day working on their other lab research, working on the sleep experiment at 11 pm, and then 3 pm, before being up again at 7 am.
Still, some of those sleepless nights might have been worth it, since they could happily conclude in their paper, “Our discovery of a sleep-like state in an ancient metazoan phylum [Cnidaria] suggests that the ancestral role of sleep is rooted in basic requirements that are conserved across the animal kingdom.”
As Nath put it, “This has implications on how fundamental sleep is and what we have in common with jellyfish. Sleep is basic to the animal lineage.”
Not all agree that jellyfish actually do sleep.
As Anders Garm of the University of Copenhagen told Science, “I would hesitate to call it sleep until you actually look at what happens in the nervous system. There could be other mechanisms explaining this behavior.”
While Nath is ready to move on to other research – aging and neurodegeneration in a fish model – he believes that modified jellyfish that have key genes knocked out could help tease out the details in the mechanism of sleep.
For now, though, Nath and his friends have roused a whole community of sleep researchers.
The research was published in Current Biology.
A Caltech video about the research:
