However, he reports wide variability in those temperatures. The graph of patients’ temperature changes over time looks a little like the side view of a pigeonhole mailbox, with a stack of letters all jumbled together but generally leaning to the left. Reading from left to right, some lines start low and remain low. Others start high and drop. Still others float along the top. Statistically speaking, it’s a bit of a mess.
Not surprisingly, Dundee’s conclusions are correspondingly vague. “One formed the impression,” he says, “that the general condition of these cases was better than normal after operation.” Those “impressions” might be all right if you’re trying to win a beauty pageant, but what one really forms is the hope that more science will be forthcoming. Soon. Before one becomes at risk of losing a spleen or half a stomach without the comforts of anesthesia.
A LUCKY MAN
Happily, we’ve come a long way from placing bags of ice on patients’ groins. Many lives and brains have been saved by this progress. And many patients have benefited.
In order to meet one such patient, and his brain, I’m sitting in an office at a mushroom farm outside of Philadelphia. I’m waiting to talk to a man named Thomas, who works here. If anyone can convince me that we’ve come a long way since the days of the French Cocktail and bags of ice, it’s Thomas.
Today Thomas is dressed in rumpled khakis and layers of sweaters to keep warm on a cold March day. He’s short and wiry, with the deep tan, leathery skin, and prominent crow’s-feet of a man who is used to working outside in all kinds of weather. The one odd item in this picture is a pair of dainty wire-rim glasses that seem out of place on a weathered face that looks like it could have been carved out of a block of gnarled stained oak.
The oddest thing about Thomas, though, is the fact that he’s alive. He’s alive, and he’s sitting in front of me now, because he spent almost an hour in a state of medically induced hibernation. That’s an impressive trick, and one that I want to learn more about.
“It all started,” he tells me, “when I had a regular checkup with my doctor. And he was listening to my heart and heard a murmur that was new. So I had an echo, and then a CT angiogram. I went in that morning early, had the test, then waited for the results. My doctor came in and asked me how I felt.”
He pauses. “I said I was fine. Then he told me: ‘No, you’re not.’”
The angiogram showed a bulging section at the root of Thomas’s aorta, where it emerges from the heart. It was the sort of bulge you see in a balloon if you squeeze it hard enough that a bubble forms. When it comes to balloons and blood vessels, squeezing usually isn’t a good idea. What was worse, the angiogram also found a dissection of the descending aorta—a place where it was splitting apart. That’s why Thomas’s doctor arranged for a helicopter to take him to the biggest cardiovascular surgery center in the region, where he was met by a surgeon who, he hoped, would be able to fix him up.
Thomas turns to a day planner on his cluttered desk, opens it to today’s date, and pulls out a sheet of hospital stationery with an elaborate drawing of the upper part of a heart and blood vessels. “I’ll never forget; that surgeon drew out for me exactly what he did. He had to place a graft around the root of the aorta, right here, then he needed to patch up this tear farther out here.” Thomas doesn’t speak as we both look at what was a long procedure.
The problem was time. Even after the chest is open, it takes time to dissect out the heart and blood vessels, and time to excise the damaged blood vessel walls. And still more time to sew a graft into place. For some patients, surgeons can use a bypass machine connected to the aorta to maintain a circulation while they’re working on the heart. But in Thomas’s case, bypass wouldn’t be possible because of the aneurysm in his ascending aorta. So there was going to be a period of as long as an hour when his heart wasn’t working and his brain wasn’t getting any blood. When general survival and brain health are measured in minutes, an hour is a long, long time.
So what’s the solution? How do you get a patient like Thomas through a complex surgery without bypass? And how do you protect his brain so that, when he wakes up, he can go back to his life?
Patients like Thomas are why we should care about the science of hibernation. Humans don’t hibernate naturally, because we don’t need to survive long, inhospitable winters like marmots do. But we do undergo long, difficult, and complex surgical procedures like the one that Thomas endured. Indeed, if ever there were an inhospitable environment for a brain, an hour without any blood flow is it.
Actually, the hostile environment of the operating room isn’t limited to extreme surgery. All but the most minor procedures can be accompanied by wide swings in blood pressure and temperature. For instance, there may be prolonged drops in blood pressure during which the organs that need oxygen most (for example, your brain) aren’t getting enough. Add to that the specialized forms of surgery that intentionally cut off blood supply to an organ in order to fix it. Although neurosurgeons are unlikely to explain what they do in such terms, when they repair a brain aneurysm they need to shut off the brain’s blood flow in the same way—and for the same reason—that a plumber needs to shut off the water to a bathroom before fixing the toilet.
This need to reduce or eliminate blood flow has put some very strict limits on what surgeons can accomplish. It’s also forced surgeons to learn how to operate fast, and to perform increasingly complex procedures within a narrow and inflexible window of time. Surgeons start getting very worried, for instance, when blood flow to a brain is cut off for more than ten minutes. That’s not much time at all. In Richard’s case, ten minutes wouldn’t have been nearly enough time to do the complex repair work that was required.
But Thomas’s surgeon told him about another option: a procedure called deep hypothermic circulatory arrest. It’s used when a patient like Thomas has a complex surgical problem that will require a long time to correct, and when bypass isn’t an option. The heart is stopped, and the brain is cooled, allowing a surgeon to do whatever work needs to be done, hopefully without damaging too many neurons in the process.
This is essentially the same trick that Dundee and his colleagues tried back in the 1950s, but it’s much more aggressive. The degree of cooling, for instance, is more extreme. For patients like Thomas, the target temperature is 18 to 20 degrees Celsius. (A normal temperature for a non-dead human, remember, is 37 degrees Celsius.) And then there’s the long period—more than thirty minutes—that his brain would be offline.
Overall, this is one of the most complicated and dangerous medical procedures that can be performed. And the risks are correspondingly substantial. The mortality rates are 10 to 15 percent, for instance, and the risk of serious neurologic damage is another 5 to 10 percent. Add to this the risks of any major surgery like blood clots, bleeding, and infection, and you have a procedure that most sane people would avoid if they can.
So it was a big decision Thomas was facing. And he knew that. But then again, it really wasn’t much of a decision at all.
“I knew that this was bad. My mom died when she was sixty-six of an aortic aneurysm. Her sister—my aunt—died of the same thing at forty-nine. So I knew it was bad.” Bad, I’m thinking, is an understatement. So he decided to go for it.
If the theory is the same as the one that Laborit and Dundee advocated back in the ’50s, the details have come a long way. For the entire procedure, for instance, Thomas got the most intensive monitoring possible. The operating team kept a close eye on his temperature, of course. But they also monitored his brain pressure and brain activity using electroencephalography. He also received anticoagulant drugs that prevent blood clotting during cooling and especially during rewarming.
The cooling process, too, has come a long way from the days of French Cocktails and iced groins. For instance, a heart bypass machine cooled Thomas quickly by removing his blood through one catheter, chilling it, and then putting it back into
a vein with another catheter. A jacket and helmet with circulating coolant also helped to chill him to the target temperature much more quickly than a bucket of ice would have.
As this was happening, Thomas’s blood was removed and replaced—gradually—by saline. Effectively, this diluted his red blood cells to a concentration of less than 50 percent of normal. (If you skip this step and you chill normal blood, it takes on the consistency of a milkshake, with physics that are pretty much the same, except that our arteries and veins are much narrower than a straw.) Those red blood cells were stored so that they could be transfused back into Thomas on the other end of the operation. If he survived.
When his temperature got down to 20 degrees Celsius, the pump was stopped, and the real work started. Thomas’s surgeon cut away the damaged aorta and stitched in a new graft of synthetic. Once he was finished and the sutures were tight, the team restarted Thomas’s heart, warmed him up, and took him off bypass.
“You know,” he says thoughtfully, “it took me a while to bounce back.” But he did bounce back. Two months later he was up and around, and his job at the mushroom farm was waiting for him.
As we’re talking, I can’t help looking for telltale echoes of a brain that once hung up an OUT TO LUNCH sign for an hour. Slurred speech? Memory problems? Unsteadiness? But I’m not seeing anything.
Has he noticed any problems? I ask him. Has anyone noticed anything?
Thomas shakes his head. “No. Well, it took me a while to get back on my feet. But I’m back to work. Everything’s OK.”
Thomas was lucky. He’s lucky to be alive, of course. And doubly lucky to have emerged cognitively unscathed.
But whether he was truly unscathed we’ll never know. There’s just not much data about subtle cognitive changes that happen when you put a brain through what Thomas’s brain was put through. One study asked patients who had undergone a variety of procedures (either with or without hypothermia) whether they’d noticed any changes. Like Thomas, they didn’t, and as far as they were concerned, there was no apparent downside of hypothermia.
The problem, though, is you don’t know what you don’t know. Maybe some of those people were a little slower or more forgetful, but they just didn’t realize it. Still, it’s comforting to know that, at least from the perspective of people who underwent the procedure, they’re able to do whatever they could do before.
Thomas feels fine. And he’s able to do everything that he could do before all this happened. So he’s a success story.
He’s not taking it for granted, though.
“I never really thought much about my mortality until this surgery,” he says as he’s walking me out. “But I think about it every day now. Every day I keep getting older; in a few months I’ll be fifty-nine, then I’ll be sixty. And then . . .”
Still, Thomas is a living example of what the science of hibernation can accomplish. By cooling him, and by reducing his metabolism to very low levels for more than thirty minutes, Thomas is now alive and well. Even ten years ago, that wouldn’t have been possible.
And maybe what was possible for Thomas was only the tip of the iceberg, so to speak. Thomas’s brain was protected for thirty minutes. And if thirty minutes is possible, why not an hour? Or two hours?
Maybe eventually it might be possible to put a patient like Thomas into a state of suspended animation for two hours. Or even a day. That’s more time than you’d need for even the most complex surgery, of course. But for a soldier injured on a battlefield who’s twenty-four hours away or more from an operating room with the necessary equipment, stopping the clock for a day might save a life.
To see how that might work, we can’t depend on researchers and surgeons. Nor can we depend on squirrels or groundhogs. Instead, we need help from a whole different team.
TEAM LEMUR
Most of the best early hibernation research has been done on small, furry mammals. Squirrels, especially, have done more than their fair share to advance the science of suspended animation. Indeed, I think it’s safe to say that the afterlife is pretty crowded by now with the ghosts of various small critters who deeply regret humans’ seemingly insatiable interest in the whole hibernation thing.
However, there is a small but dedicated group of scientists who are convinced that this obsession with rodents amounts to scrambling up the wrong tree. If you want to develop science that will help people, they say, you need to study people. Or, since humans don’t hibernate (apart from that one Japanese office worker), you need to find a hibernating species that is as close as possible to humans. I’ve come to think of this little group of mavericks as Team Lemur.
It’s in order to hear their side of the story that I’m standing in a very small, cool room that is lit only by a red light of the sort that you’d find in a photo darkroom. Somewhere in here there are lemurs. Lots of lemurs. And I’m here because lemurs are the only primates—that we know of, at least—that hibernate.
But where are they? I wonder.
Fortunately I won’t have to find them on my own. I’m here with someone else whose gaunt form is just barely visible in the reddish glow that surrounds us. And he is someone who knows an awful lot about lemurs.
Dr. Peter Klopfer is one of the founders of the Duke Lemur Center, and he’s been semiretired since 2006. But he is still very much involved in the center’s activities, and he is a firm believer that studying lemurs—not squirrels—is the best way to glean hibernation lessons that could help people.
Tall, thin, and balding, with an overgrown hedge of a beard that curls back on itself in whorls like an ornamental shrubbery, Klopfer looks like a version of Santa Claus whose wife put him on a crash diet. He speaks intently, yet often seems to be looking off in the distance. Talking with him before we stepped into the lemurs’ darkroom was a little like finding myself in a lecture hall full of invisible students. That impression was weakened a little, though, by his decidedly nonprofessorial outfit of running shoes, tracksuit pants, and a T-shirt. In short, I suppose he looks exactly like you’d expect an emeritus professor who studies lemurs to look.
But in our dark little room surrounded by—he promises—lemurs, Klopfer magically assumes an ethologist’s mannerisms. He becomes stooped and gawky, and assumes a rapt attentiveness. In the dim light, he looks so much like a primate that I half expect to see a long ringed tail snaking up over his left shoulder. He is the Dian Fossey of the lemur world.
Before we entered the air-locked double doors, Klopfer warned me not to talk once we were inside so as not to disturb the lemurs who are hibernating. So I’m surprised when suddenly Klopfer starts emitting a loud clicking sound that is something like the noise your printer makes just before it spews out a ream of mangled paper and erupts in a puff of smoke.
As Klopfer clicks away there is no discernible activity in the cage in front of us. Then he begins making pursed-lip motions that look like something a female elephant seal might find vaguely romantic. Still, nothing happens.
“This always works,” he whispers.
But it isn’t working. I mention this.
He squints, looking very intense. Then he grins. Then he points.
A pair of googly eyes appears about six inches from my face. For a second I forget Klopfer’s earlier reassurance that the lemurs are in cages. And his admonition not to talk.
In surprise I grunt loudly enough to wake any hibernating lemur. Then I step backward onto Klopfer’s foot. He swears.
This visit, I’m thinking, is not getting off to a great start.
But things settle down, and my eyes adjust enough to see three little lemurs hopping around their cage. I’m surprised by how small they are. They’re squirrel-size, more or less. However, given the whole squirrel-lemur rivalry thing I’m guessing that Klopfer won’t want to hear this.
They’re also very agile. One is racing around the top of the cage, upside down, clinging to the wire
with tiny humanoid fingers. It moves so quickly and gracefully, it might just as well be right-side up.
And they’re very cute. That is, except for their tails, which are big and heavy, swollen with the fat they store there. In fact, the lemur who is currently staring at me through the wire mesh of his cage is equipped with a tail that’s almost as big around as he is.
As this little guy and I are watching each other, Klopfer keeps clicking away like a lemur. The lemurs aren’t talking back. But they are migrating to our side of the cage and they’re paying very close attention to this strange, bearded apparition next to me.
A few minutes later, we’ve left the lemurs to frolic in the dark by themselves. We’re outside in the laboratory and Klopfer is giving me the brief version of the history of lemur hibernation science. He tells me that until very recently, no one thought that primates hibernated. Bears, yes. Rodents, certainly. And, of course, ectotherms like reptiles brumate. But everyone assumed that when primates are faced with a tough winter we just bundle up, turn on the electric blanket, and tough it out.
In 2005, though, a German team of researchers collected the first evidence of prolonged hibernation in fat-tailed dwarf lemurs (Cheirogaleus medius). Before then, researchers had only suspected lemurs of hibernating. Although some lemur species had been described as entering a period of torpor, or reduced metabolism, when food supplies were low, no one had caught them in a prolonged period of true hibernation.
The discovery of a hibernating primate opened an entirely new universe of research. It raised the question, for instance, of whether there might be other primates who have been hibernating unnoticed all these years. And it raised the very interesting possibility that other primates—humans, for example—that don’t normally hibernate might be able to pull off the same trick.
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