Fortunately for science, it seems no one paid much heed to Aristotle’s opinions about hibernation. And fortunately for swallows, no one else seemed to think that poking their eyes out was a particularly good idea. Unfortunately, though, no one really thought much at all about hibernation for the next two thousand years. In fact, it’s not until the 1940s that people seemed once again to notice that some members of the animal kingdom disappear during winter.
Even then, some of the first “scientific” studies weren’t much more helpful than Aristotle’s experiments with swallows had been. Consider this gem from an early study of hibernation in hamsters: “That the golden hamster while hibernating is functionally deaf is borne out by the fact that we have never been able to arouse a hibernating hamster by the stimulus of sound.” There you have it—the state of much of the science at the time: if you yell at a hamster and the hamster doesn’t react, that hamster is deaf.
Soon, though, the science of hibernation itself would wake up. In the 1950s and 1960s, the world began to see a barrage of new research resulting in journal articles with hot titles like “Concentration of urine in the hibernating marmot” and “The unique maturation response of the graafian follicles of hibernating vespertilionid bats and the question of its significance.” Its significance is indeed an excellent question, and one that I regret to report no one has yet succeeded in figuring out.
This area of research got a boost in the 1950s, when interest was heightened by a growing realization that hibernation might be protective in the event of nuclear holocaust. In one typical experiment, researchers gave groundhogs a massive dose of radiation and found that hibernating groundhogs lived twice as long as their awake counterparts did. History, alas, is silent about how much this information allayed the pervasive Cold War terror.
Soon an entire generation of researchers would embark on a relentless search for an animal that could help us understand how hibernation works. The list of potential candidates was a long one, though not as long as Aristotle would have us believe. It included bats, woodchucks, marmots, bears, and all sorts of rodents.
Eventually, the scientific community seemed to settle on the humble thirteen-lined ground squirrel (Spermophilus tridecemlineatus) as its preferred research subject. This decision was to prove a fateful one for hibernation research. It would also be a turning point for generations of thirteen-lined ground squirrels, for whom life would never again be quite the same.
Thirteen-lined ground squirrels are reliable hibernators. They are also plentiful. No one, it seems, would miss a few who were used for medical experiments. (Note: In the world of research, you really don’t want to be a plentiful species.)
Before we get to those experiments, I’d like to meet a thirteen-lined ground squirrel in person. They seem to prefer open grassy areas, like golf courses and cemeteries. But I don’t think I’ve ever seen one. Fortunately, though, I hear about a man in central Ohio who keeps them as pets. So I set off in search of a man and his “thirteen-liners,” as they’re known in squirrel circles.
CHUCKY THE TRIBBLE
“My wife thinks they’re like Tribbles,” Joseph admits sheepishly. “You know, those furry little critters on old Star Trek reruns?”
He shrugs and chuckles, as if to say, Women are so silly. But I see what his wife means. The creature I’m holding in my cupped hands is indeed a bit like the fuzzy little creatures of Star Trek fame. But Tribbles were cute, I recall, only until they started multiplying in a way that would position them to take over the universe. That’s unlikely with a squirrel, but still, I resolve to maintain a firm grip.
I’m standing in the disused stable of a barn on Joseph’s farm. Joseph (most emphatically not “Joe”), is a tanned, clean-cut guy in his sixties who has become fascinated by thirteen-lined ground squirrels and their ability to hibernate. But Joseph isn’t a researcher; he’s a soybean farmer. Or he used to be. Now he’s semiretired and he leases most of his land to a consortium. He’s also a squirrel caretaker.
Joseph’s fascination with thirteen-lined ground squirrels began one cool September day almost a decade ago when he trapped one for a grandson’s science experiment. His grandson lost interest by Christmas, but Joseph was hooked. He kept taking care of the squirrel, and would go out to see it a couple of times every day. He built a bigger cage for it, and then an even bigger one, until finally he had a cage that was larger than many studio apartments.
Joseph explains that he traps all the squirrels he takes care of. “You have to trap them,” he explains. “You can’t really breed them. Or you can, but it’s very, very difficult.” They’re also asocial and tend to be loners, so he never has more than one in a cage at a time.
If they wander into one of his traps, he says, they must be old and frail. They wouldn’t live much longer in the wild. “I think of this as an old-folks home for squirrels,” he says. The cage that Joseph proudly shows me is about ten by ten in all dimensions, and it’s full of wood shavings, branches, and a pile of hollow logs in a jumble in the corner.
A small metal bowl in one corner is half filled with Purina Cat Chow. According to Joseph, the squirrels love it. He also feeds them insects and berries as a special treat.
OK, so this is really a pretty good life. It’s like a squirrel spa.
Joseph has also suspended a couple of large branches from the roof of the cage, presumably as a sort of rodent StairMaster. But none of these is being used right now, because the cage’s sole inhabitant, whom Joseph has named Chucky, is in my cupped hands. And Chucky is not in the mood for a workout.
Chucky is curled up tightly in a ball, nose to butt, with his tail wrapped over his head. It’s hard to tell, but he looks like he’d be about six inches long, if he were unfolded, not counting his thin, lightly furred tail. In his furled hibernation position, he is approximately the size, shape, and weight of a baseball. Squirrels lose up to one-third of their weight over the winter, and it’s December now, so Chucky is probably about halfway down to his dry weight.
Joseph is telling me that Chucky began to hibernate back in mid-October. He’ll probably stay asleep, more or less, until April. Males seem to emerge from hibernation first, he says thoughtfully, as if he’s not sure what to make of this. Neither am I. But one theory is that since breeding is polygenous, with several males mating with each female, early waking males have the advantage. Alas, Chucky is unlikely to benefit from being an early riser, since he’s alone in his cage. He might as well sleep in.
And Chucky seems to be following this plan. Despite the gentle handling that has brought him out of his cage and into my hands, he’s not showing any sign of alarm or interest. He is truly out of it.
What’s really strange about holding this sleeping squirrel, though, is that he feels . . . cold. It’s a little unnerving to hold something that is supposedly alive and to feel no body heat whatsoever. The ambient temperature in the barn is 2 degrees Celsius according to the thermometer on the wall, and I’d believe that Chucky is in that neighborhood. He feels . . . dead.
Yet Chucky is definitely alive. His paws are a bright pink, for instance. And he’s breathing, although it takes twenty seconds before I see a breath. He also has a heartbeat, albeit a barely detectable one, which I can feel every five seconds or so. That would be about 12 beats per minute, compared to a normal rate of 200 to 300 beats per minute for a thirteen-lined ground squirrel. I run these numbers by Joseph and he nods.
“Their metabolism winds way, way down. You or I would be dead if our heart rate and breathing got that slow. But these guys . . .” He shakes his head in wonder. “They can stay like this for months.”
“Actually,” he corrects himself, “they don’t stay exactly like this.”
And he’s right. You’d never guess it from looking at Chucky today, but hibernating ground squirrels do get restless. They don’t wake up entirely, but they move around a bit. Joseph discovered this because squirre
ls like to burrow, and they’re happiest if they’re covered by a layer of leaves or other debris. Joseph sprinkles their backs with wood shavings from his workshop, so when one is uncovered, he knows that it’s been awake.
As my visit wraps up and Joseph walks me back to my car, we talk about how a slowed metabolism might lead to longer life. Sleep for a year and live an extra year? Would that be a good trade-off, he wonders?
Joseph and I are not the only ones pondering this question. In fact, there are a lot of researchers who have been thinking about this trade-off very, very carefully. But they’re thinking about a version in which the time asleep is measured in hours and the additional life is measured in years. Specifically, they’re wondering whether the trick of hibernation that the thirteen-lined ground squirrel has mastered might someday help people to live for a long time. That story is as strange as any science fiction, and thirteen-lined ground squirrels have a starring role. It starts more than fifty years before Joseph trapped his first squirrel.
SLEEP, SEX, AND SQUIRRELS
Have you ever had one of those restless nights when you just can’t seem to fall asleep? When you’ve tried everything—counting sheep, reading the phone book, doing a crossword puzzle—but nothing seems to work? Well, hope may be on the way. All you need is a glass of warm milk and . . . a tablespoon of squirrel blood. That’s the message from a series of experiments way back in the ’50s that were designed to find out how squirrels hibernate.
Those studies got off to a rough start. When scientists first began to examine what actually happens to these little guys when they’re hibernating, they were nonplussed by what seemed to be a tumultuous physiology. They noted with growing alarm that heart arrhythmias were very common, as were drops in respiration down to a dangerous one to two breaths per minute. These peacefully resting rodents, it seemed, were teetering on the brink of being dead rodents.
Reading this, one begins to worry for the squirrels. Is this normal? Are these little guys OK?
The researchers, too, are obviously concerned about the well-being of their furry friends. To alleviate the anxiety of anyone reading the report, they offer this hearty reassurance: “When an animal in the hibernating state was decapitated, the stump of the corpus showed bright cherry-red blood.” So squirrels seemed to be able to survive changes in heart rate and blood pressure that would kill them when they were awake. (They were significantly less well prepared to survive the vicissitudes of being subjects in hibernation research.)
Once researchers figured out that wide swings in heart rate and breathing and blood pressure were normal—and survivable—they wanted to know how hibernation worked. What was it that nudged squirrels into a state that would let them endure these wild physiological changes? And what was it that kept them in this state for an entire winter?
One early theory was that the brain was responsible. Specifically, researchers focused on an area of the brain—the anterior hypothalamus—that they thought might control temperature and metabolism. To test this hypothesis, one researcher by the name of Dr. Evelyn Satinoff placed lucky squirrels in airtight cages. Then she reduced the ambient temperature to 0 degrees Celsius.
“As the oxygen in the container is used up and the concentration of carbon dioxide increases,” she reports, “the animal loses its ability to maintain normal body temperature and its temperature falls rapidly.” It probably also wonders what the hell is going on.
But once temperature and oxygen are restored, she says, the squirrels recover. Good news, right? Well, it turns out that recovery didn’t go so well after Satinoff and her colleagues used electricity to create lesions of the anterior hypothalamus. (If the hypothalamus was responsible for the regulation of metabolism, they reasoned, then damaging that part of the brain would disrupt the body’s ability to regulate its temperature.) Indeed, after undergoing this procedure, one poor squirrel (code named CT6) took eleven hours to climb back to his normal temperature (rather than an hour for a normal squirrel), at which point he no doubt heaved a room temperature sigh of relief.
That laborious return to normal earned him a special mention, and even a picture in the resulting journal article. There he is, CT6, in a caption under a photograph. (Unfortunately for CT6, the photograph displays a slice of his brain—a brain that CT6’s body was probably not very happy to part with.)
So the brain has something to do with temperature regulation, and maybe it has a role to play in hibernation. Perhaps the brain secretes something that initiates cooling and warming. But what?
The most intriguing answer to that question came a few years later, when a physiologist named Dr. Albert Dawe led a team of researchers to study the hibernation habits of a colony of ground squirrels. During the winter of 1967–68, all the members of that colony of twenty squirrels went into hibernation. The following spring—by March 6, 1968, to be precise—they were awake. All except one.
Already, you may get the feeling that things are not going to end well for this sleeping squirrel. And indeed they do not. If you’re a ground squirrel living in a colony of ground squirrels under the supervision of scientists interested in what makes you hibernate, you really don’t want to sleep in. You really just don’t.
How do I know this? Because in the same paragraph that introduces the lone hypersomnolent rodent, Dawe and his team begin referring to it as “the donor.” Even I know enough about scientific experiments to know that if there’s one thing you don’t want to be, it’s a donor.
This particular donor did not fare well. Once all the other squirrels had woken up, bright-eyed and refreshed, Dawe and his colleagues opened the donor’s abdominal cavity and extracted three milliliters of blood from its aorta. It was at that point that the poor squirrel decided that it would be an excellent time to check out. So he died.
Undeterred, the researchers took the donated blood and injected it intravenously into two of the donor’s buddies, who were placed in a cold room at 23 degrees Celsius along with three other ground squirrels who hadn’t been subjected to this surprise transfusion. Then, in a move that would certainly have further unnerved five already confused ground squirrels, the researchers began to watch them very, very carefully. Now at least some of these squirrels might have begun to entertain the notion that they, too, were at risk of becoming donors.
They didn’t have to wait long. Within forty-eight hours, the two transfusion recipients fell asleep. And they stayed asleep, more or less constantly, for the next three months. Even more interesting, those squirrels weren’t just asleep. Dawe reports proudly that they also demonstrated signs of “true” hibernation, including a balled-up posture, reduced temperature, slowed respiration, and, presumably, growing sexual frustration. (Did I mention that ground squirrels breed in the spring?)
Not content to let sleeping squirrels lie, the researchers began a series of Frankensteinian experiments in which they took blood from the hibernating subjects and transfused it into other squirrels “in a similar way.” The report is a little vague about what that means, but one is left to conclude that these transfusions were only made possible by additional untimely deaths for more “donors.”
To a discerning reader, this chain of events might bring to mind the sudden deaths of the three unfortunate astronauts in 2001: A Space Odyssey, which had been released just that year. Early in that film, HAL ends their suspended animation abruptly, irreversibly, and fatally.
Nevertheless, those squirrels gave their lives for what would prove to be the most significant advance in hibernation research thus far. In that daisy chain of transfusions, Dawe discovered something that became known by the acronym HIT: hibernation induction trigger. That is, they’d discovered a massively souped-up version of squirrel Ambien. There was obviously something in the blood of hibernating squirrels that, in the setting of cold, induced hibernation.
Before Dawe could figure out what that substance might be, his experiment came to an end. It was fall,
and all of the squirrels started falling asleep naturally, bringing that particular chapter of rodent science to an abrupt end. And none too soon, if you happen to be a thirteen-lined ground squirrel.
So Dawe and his colleagues knew HIT existed. They deduced that it had to exist, given what they’d observed. But they still had no idea what it was. The scientific instruments hadn’t yet been invented that would have let them define its chemical composition. That would come later.
PROTECTING HEARTS AND MINDS
Alas, subsequent attempts to replicate some of those early studies have not been terribly successful. Nevertheless, the search for HIT went on. And eventually science began to make some progress.
One of the frontrunners in the scientific search for HIT’s identity (a search that, as you may have guessed, has not been kind to the ground squirrel population) is D-alanine-D-leucine-enkephalin. In this nomenclature, alanine and leucine are amino acids, building blocks of proteins. The D refers to amino acids’ shape, and whether their structure is right- or left-handed (D or L, respectively). Enkephalins are peptides (small proteins) that play a prominent role in the regulation of pain sensation and other functions. They act as a class of opioid receptors (or delta receptors), which are also sensitive to centrally produced endorphins and exogenous compounds like morphine.
I regret to report that this peptide was described, unfortunately and irrevocably, with the melodic but scientifically unprepossessing acronym “DADLE.” That medicine has a reliable tendency to turn nouns into active verbs apparently didn’t occur to the folks responsible for this particular acronym. While it is routine to “intubate” a patient, to “defibrillate” him, and to “dialyze” him, apparently no one thought ahead to the implications of a medical world in which patients are routinely “DADLEd.”
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