Yet another approach involves—you might have guessed it—extreme hypothermia. A surgeon named Hasan Alam, at Massachusetts
General Hospital, let us watch one of the surgeries. The test subjects are pigs. Alam knocks them out with an anesthetic,
opens the chest, slices open the aorta—sometimes other major organs, too—and quickly drains about 60 percent of the pig’s
blood. After a wait of thirty minutes, he inserts a catheter directly to the aorta and starts a pump that fills the animal’s
heart and blood supply with a chilled solution of organ preservation fluid: a mixture of electrolytes and antioxidants that
are typically used to extend the life of organs used in transplant operations. Forget moderation; Alam brings the temperature
down to about 10 degrees Celsius (or 50 degrees Fahrenheit). It takes almost an hour to get the pigs that cold.
At that point, he gets to the real work. “I can stop the [heart] pump. They have almost no blood in the body, no brain activity,
no heartbeat, and it gives me plenty of time to fix the underlying injuries,” said Alam. Under normal circumstances, the internal
injuries and massive blood loss would invariably be fatal to pigs, or to humans, for that matter, but in Alam’s lab, every
single test pig has survived. A few days after surgery, he puts each pig through a few paces to assess their cognitive functioning.
As best as he can tell, they suffer no brain damage at all. Even under the microscope, the brain cells show no sign of damage.
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If it works in people, this sort of procedure could have a huge impact in a hospital emergency room. Trauma is the leading
cause of death for people under fifty and kills more under thirty-five than all other causes combined.
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Alam said, “If somebody comes in tonight after getting shot in the chest, I’ll open the chest to control bleeding. If I can
control it in just a few minutes, I think they’ll live. If it’s more like five minutes, they’ll probably die. But if I can
get the brain temperature down like this, I’ll have more like two hours.”
What all these approaches have in common is that they tinker with the cellular machinery that processes oxygen. Think back
to what Lance Becker teaches: in a medical crisis like traumatic blood loss or cardiac arrest, it’s not just the loss of oxygen,
but the body’s reaction that’s dangerous. Estrogen minimizes this reaction. Hypothermia puts it into slow motion. Hydrogen
sulfide perhaps can stop the reaction altogether.
If it all sounds far-fetched, especially the approach using hydrogen sulfide, remember that nature is full of creatures that
can turn off the need to breathe. They’re everywhere. You can even find an example on the back of a comic book, next to the
ads for X-ray specs and action figures. I’m talking about the mail-order ads for creatures called Sea-Monkeys. They’re actually
a tiny kind of shrimp, marketed as “instant life” or “real live fun pets you grow yourself.” Sea-Monkeys can survive without
oxygen, in cysts, for as long as four years. Drop them into water, and as the sales pitch says, you get instant life for about
three dollars, plus shipping and handling.
It may be that creatures like this provide real clues to solving the puzzle of suspended animation. One person who believes
this is Dr. Philip Bickler, an anesthesiologist at the University of California, San Francisco, Medical Center. In the operating
room, he monitors patients during high-risk surgeries to repair brain aneurysms. An aneurysm is a blister on a blood vessel
in the brain, caused by a weakening of the blood vessel wall. Sometimes, to fix it, a neurosurgeon has to first stop blood
from flowing to the spot, usually by using a simple clip on the vessel.
Since this cuts off blood flow to the affected part of the brain, the procedure carries the risk of brain damage. The same
thing happens if the heart fails. “It’s usually said that if the heart stops beating, you’ll have severe neurological damage
if it lasts more than five minutes,” says Bickler. “We try to buy more time.” To buy time, the anesthesiologist will try to
reduce the brain’s need for oxygen with a mix of powerful drugs. Unfortunately, this safeguard doesn’t always work. During
high-risk brain surgeries, a significant number of patients emerge with brain damage due to lack of oxygen.
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During a small number of extremely complex surgeries lasting an hour or more, some patients are put into deep hypothermia,
much like Hasan Alam did in his swine experiments. For more routine aneurysm repairs, a number of doctors have tried the more
modest version of hypothermia, cooling the brain to 33 degrees Celsius, but surprisingly—to Bickler, at least—a large clinical
trial on this found no benefit.
Like many doctors, Bickler had put a lot of faith in hypothermia. He decided to try and piece together what went wrong. When
he thought about the experiment and why it failed, he reasoned that it must be because the bulk of the brain damage wasn’t
taking place
while
the oxygen was cut off, which is when the patients were being cooled. The damage was coming
afterward,
caused by the body’s reaction to oxygen deprivation. Bickler figured that the same thing must be happening in people who
suffered cardiac arrest.
Bickler’s particular interest is blood chemistry, and his focus was on how that chemistry changes after the body is deprived
of oxygen. We’ve seen that even a few minutes without oxygen will trigger a devastating cycle of inflammation and cell death,
but it’s not exactly clear
why
that is so. Some lab rats, for example, can go without oxygen much longer than humans can before suffering brain damage.
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Many reptiles are even more resistant. Bickler’s current research looks at painted turtles, the kind you find in a pet store.
Turtles breathe air, but in the wild during the winter, painted turtles will often burrow in the mud, without breathing for
as long as four months. Low temperature is part of it, says Bickler, but not all. “Even when they’re warm, their tolerance
of oxygen deprivation is about ten thousand times what it is in humans. The neurons in their brain are capable of entering
a state of suspended animation when oxygen is not available. It’s essentially a reflex,” said Bickler. “If you force him [a
turtle] to dive underwater, he’ll stay active for a number of hours, but then he’ll enter a state of quiescence, where he’s
just minimally responsive. The metabolism is reduced to what I’d call a pilot-light level. It’s about one-tenth of 1 percent
of normal.”
The turtles stay in this state all winter, about four months. After just a few hours, Bickler has found, the animal has actually
consumed every bit of oxygen in its tissues. It’s surviving on no oxygen at all. What we don’t know is just how it works.
Bickler thinks the secret lies somewhere in the chemistry of calcium and potassium, which drive the basic energy production
in each cell.
Bickler has an unusual background for a physician; he started off as a marine biologist. At the world-famous Scripps Institution
of Oceanography in San Diego, he marveled at the adaptations various animals made to survive. When we first spoke, he told
me about a creature called the Antarctic ice fish. It lives along the sandy sea bottom, underneath the ice shelves of Antarctica,
in temperatures which dip below 30 degrees Fahrenheit (the ocean’s salt content keeps it from freezing at 32 degrees Fahrenheit).
To manage this trick, the fish actually produces a type of antifreeze in its blood, which prevents ice crystals from forming.
It also manages to circulate oxygen without using red blood cells; this makes the blood more fluid and conserves energy in
the extremely harsh conditions. Asked if we might artificially produce the same effect in people, Bickler points to isoflurane,
a common anesthesia drug. It’s used in surgeries where the patient is cooled, because it seems to protect cells at low temperatures—by
affecting the balance of potassium, if you are wondering.
Bickler says, “I’ve been an anesthesiologist for twenty years, but my heart is still with those turtles and fish and hibernating
creatures.” They’re still a part of his professional life; in 2008, he won a grant for a study of diving marine mammals—whales
and dolphins—to examine how their neurons can adapt to low oxygen levels. Some marine mammals will stay underwater for more
than an hour while hunting for food.
Bickler switched to the study of medicine to see if he could find a practical application for some of this biology. If animals
could survive harsh conditions by lowering their body temperature or slowing their metabolism, perhaps there was a way for
humans to trigger the same survival mechanisms in their own bodies. Bickler is an avid mountain climber, and had already seen
the human body is more adaptable than many people know. In air as thin as it is on top of Mount Everest, an unacclimated climber
would be dead in an hour. But it’s a different story for expert climbers who train for months before an ascent and work their
way up the mountain by staying for a few days at each successive altitude. These mountaineers manage not only to survive,
but to survive without the help of supplemental oxygen, even while climbing to the summit of Mount Everest.
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What Bickler eventually hopes to find is a way to speed up those adaptations in a way that might be utilized as part of emergency
medical care. Perhaps we can develop a drug that’s akin to the chemicals naturally found in a turtle, which would give us
some of that same amazing survival ability.
In his lab in Philadelphia, Lance Becker is thinking something similar. He says that all the death pathways, all the mischief,
all the chemical chaos, seems to take place in the mitochondria—the part of the cell that produces energy. Some evolutionary
biologists say death, the way we know it, didn’t even exist until cells became complex enough to include mitochondria. These
scientists say the mitochondria in our cells actually evolved from primitive bacteria. Bacteria do not have mitochondria and
do not undergo apoptosis. They simply divide, again and again, as long as conditions are favorable. Bacteria might be eaten
or destroyed, but otherwise, they just hang around, becoming spores or entering some other form of quiescence.
Becker’s focus is on clinical practice—how to stop or reverse the death pathways when the body is deprived of oxygen due to
cardiac arrest, trauma, or some other cause. Hypothermia is one tool, so is CPR. The next step, he says, could be drugs like
the ones being tested in Mark Roth’s laboratory. Hydrogen sulfide does work on the mitochondria, binding itself to the electrons
within that organism. Says Becker, “A number of us are pursuing this very similar science.”
When we spoke, Roth contrasted his approach to what EMTs typically do when they arrive to help a cardiac arrest victim. “The
very first thing they do is to slap a mask on their face and give them 100 percent oxygen. But perhaps another idea could
be tried,” he says. “That is to take away the little bit of rope they’re using to hang themselves, to prevent them from using
the little bit of oxygen that’s killing them.”
When Roth looks around this world, he sees hints of immortality everywhere: in hibernating squirrels, in skiers who survive
a plunge through the ice, in the spores of bacteria, in the seeds of plants and in our own bodies. He sees immortality as
inextricably linked with quiescence. Quiescence, as he describes it, is a state of unchanging readiness. Again he says, “Look
at female germ cells [eggs] in an ovary, all sitting there like a fireman waiting to fight fires. Only one a month, of a bazillion,
goes out. The others sit in the fire station, doing nothing, for decades at a time.”
In smaller and simpler organisms, we find examples so stark that they fall in a different category. Some bacteria spores—including
dangerous ones, like anthrax—can last for years without any outside nourishment in a complete unchanging state. Many viruses
do the same. Eggs, seeds, spores, viruses—what these hold is the
potential
for life. Says Roth, “All these things with proliferation potential seem to have this remarkable quality, which is that they
can sit in suspended animation for this remarkable period of time.”
One thing to keep in mind—as a treatment for humans or other mammals, hydrogen sulfide as used by Ikaria does not induce suspended
animation, the way it does in roundworms. It’s still the dimmer switch. For now, Roth says he just wants to develop a drug
that can be used in a conventional medical setting, alongside other therapies like hypothermia. But I couldn’t help but wonder:
is it really impossible to think that we might someday stop time—put humans into suspended animation, the way Roth did with
his baby zebrafish?
“Of course that [research] is far more in its infancy,” says Roth. “For now I think it’s more straightforward to enable the
physician to utilize this technology by simply dimming the patient, rather than starting from an extreme situation where they
lose a lot of control that they have.” But with a mischievous grin, Roth admits he doesn’t really know how far this could
go.
“ ‘Clinical death’ might be the loss of a heartbeat, and with those fish, I turn off the heartbeat so they
are
clinically dead. But I can bring them back. So they must not have been dead,” he chuckles. To even try this in humans, to
push suspended animation to its limits, would require a wholesale change in how we view the practice of medicine. Imagine
a patient with no heartbeat, no blood pressure, no vital signs. Is she dead? Who can say? What doctor would try that experiment?
“You have to think about separating the connection between life and animation, between death and deanimation,” says Roth.
“We’ve put them together, but I think from these research studies, those are not reasonable connections to be drawing. Not
always.”
Roth’s company Ikaria takes its name from an ancient Greek island renowned for its ancient, medicinal sulfur springs. The
philosopher Herodotus was an early advocate, as was his pupil Hippocrates, the father of modern medicine. It’s not a stretch
to say that Roth enjoys tempting fate. The island Ikaria takes its name from the famed Icarus of Greek mythology. Icarus flew
on giant wings built by his father, the master craftsman Daedalus. Ignoring a warning not to soar too high, Icarus sailed
toward the sun, only for its heat to melt the wax that held together his wings, which sent him plunging to his death in the
sea below.