1. As winter sets in, many animals effectively
shut down their bodies in order to survive.
Injured humans might benefit from similar
techniques, writes Zuberoa Marcos.
O
N LONG, DARK AND cold
winter days, you probably like
to go to bed early and find it
hard to get up in the morning.
Humans survive the winter by
rugging up well, switching on the reverse-
cycle air-conditioning, and moving from
heated cars to heated offices.
Animals survive the winter by migrating
to where the weather is milder, by
remaining active but thickening their ‘coat’
or by changing their diet. But the most
extreme method is to completely shut
themselves down.
For five to seven-and-a-half months
of the year, black and brown bears turn
themselves off. They do not eat, drink,
urinate, defecate or exercise. They reduce
their metabolism by 50 to 75% of normal
rates. They breathe once every 15 to 60
seconds and their heart rate drops from
around 50 to about 10 beats per minute.
Hibernation is a strategy to combat
extreme environmental conditions. By
setting the body metabolism to a kind of
slow motion, some animals reduce their
energy costs by more than half when
food is scarce and later return
to an active state as if nothing
happened.
It’s a strategy also used by
squirrels, marmots, hedgehogs,
bats and even the fat-tailed
dwarf lemur of Madagascar.
“All land-dwelling mammals
except ungulates [mostly hoofed
mammals] and lagomorpha
[hares and rabbits] have at least
one hibernating species,” says
molecular biologist Matthew
Andrews, who has studied
hibernation for the past 12 years
at the University of Minnesota
Duluth in the U.S. Hibernators
are so widespread in nature that
getty/iSTOCK
scientists think that the genetic hardware
required to go into hibernation is common
Studying the physiology of hibernating bears offers insights that may among all mammals. So why is it that some
help treat people with such illnesses as diabetes and osteoporosis. species hibernate and some do not? >>
76 www.cosmosmagazine.com Cosmos 46 Cosmos 46 www.cosmosmagazine.com 77
2. A technique
of cooling
the brain
There is an evolutionary explanation for
>>
is helping
this, says Andrews. “Humans are largely a newborns at
istock
tropical species. We evolved in the tropics risk to avoid
permanent
where food is generally available. We have brain damage.
very thin skin because we had little need
to protect ourselves from the cold. If we GROUND SQUIRRELS can teach us School of Medicine in Wales have Nerve cell
had evolved in Siberia or Northern Canada a lot about brain regeneration. In developed a pioneering technique endings in
the brains
we might have [developed] an ability to 2006, H. Craig Heller, a biologist to save the lives of babies at risk of of ground
hibernate because we would be subjected to at Stanford University in the U.S., brain damage. Riley Joyce was born squirrels
a limited growing season.” and his colleagues reported in The in April 2010 at the Royal United change during
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Since the late 1800s, scientists have Journal of Neuroscience that during Hospital, Bath, without a pulse and hibernation.
tried unsuccessfully to unlock the inner hibernation, squirrel brains retract not breathing, and with a 50% chance
workings of hibernation. Yet molecular many of their dendrites, the tendril- of permanent brain injury. He was
biology is slowly unravelling the mysteries like nerve-cell endings that receive transferred to St Michael’s Hospital,
of this phenomenon. The spin-off is a information from other neurons. Yet Bristol, where Dingley used cooling
deeper understanding of controversial each time the squirrels wake, even and xenon gas to safeguard his brain. upon whom it was tested. First, a cold
medical technologies that can slow patients’ for only a few hours, the dendrites “Xenon is a very rare and chemically cap slowly cooled his head. Then a
respiration to almost zero – and bring them regrow… and even faster than during inert gas found in tiny quantities in xenon breathing system, working in
back from near death. embryonic development. Dendrite the air that we breathe,” explains conjunction with a mechanical lung
retraction also occurs in humans Thoresen. “In lab studies we have ventilator, administered xenon into
EVERY ANIMAL ON EARTH burns as we age, so understanding how seen it doubles the protective effect the lungs where it is absorbed into the
fuel to get the energy to walk, breathe, squirrels regenerate their dendrites of cooling on the brain because it bloodstream, via which it reaches the
sleep and keep their bodies at optimal might help develop new therapies for blocks a cell surface receptor whose brain. The xenon was administered
temperatures. Nearly everything about the Scientists from the Scandinavian Brown
damaged brains. activation can lead to the death of until Riley’s brain reached 33.5°C. He
way an animal’s body works changes when Bear Research Project take blood and fat Meanwhile, neonatologist nerve cells.” was kept cool for 72 hours and then
it hibernates, however, and preparations tissue samples from an anaesthetised Marianne Thoresen at the University The scientists have spent more than his brain was slowly re-warmed. After
ole frobert
start months in advance. hibernating bear for analysis. of Bristol in England and anaesthetist 10 years developing the technique, seven days he was doing well and able
When there is no fruit on the John Dingley at Swansea University’s and Riley became the first in the world to take milk for the first time.
ole frobert
trees and no prey to catch and eat,
“hibernators take their own fat and
break it up to produce ketone bodies,
four-carbon molecules that cross the FINDING THE ANSWER is risky. Bears “These animals eat seeds, ‘good’ fats, Cholesterol-defying arteries are not the
blood–brain barrier and fuel the brain are dangerous animals. Even when unsaturated vegetable fats and they also only evolutionary trick scientists are trying
and the rest of the organs,” Andrews hibernating, they can wake suddenly and do a good job of producing omega-3 and to understand. Colorado State University
says. “The switch-over of metabolism attack unwanted visitors. So scientists use omega-6 fats, which have beneficial effects biomedical engineer Seth Donahue studies
to use fat instead of carbohydrates as radio transmitters or GPS devices to locate on cardiovascular systems.” how hibernators preserve muscle tone and
primary fuel for the body is the main previously tagged bears in the wilds of It’s not only the hibernators’ diet that’s bone strength despite several months of
task of hibernators.” Sweden, and tranquilise the animals with desaturated. They are also pretty good at inactivity each year.
As with most biological processes, darts before approaching. Then, they take desaturating the fats in their bodies. People normally lose bone as they age.
hibernation is directed by the products blood samples and fat Studies have shown
of genes, specifically enzymes. Two
enzymes, PDK4 and PTL, are partially
tissue biopsies. Artery
samples are collected
“There is some kind of connection between that after menopause,
women lose 1 to 2%
responsible for the fuel switch that from bears killed during hibernators and human survivors, people who have of their bone mineral
is seen in hibernating animals, as the legal hunting season. density per year.
first described by Andrews and his “We have found that cheated death after being submerged in icy water, Bedridden patients
colleagues in a 1998 research article the levels of ‘good’ and may lose 3 to 4%
published in the Proceedings of the ‘bad’ cholesterol are both or buried in snow, without oxygen, for hours.” of their skeletal
National Academy of Sciences. PDK4 Breath samples are
increased in bears’ blood. mass each month.
stops carbohydrate metabolism in collected to characterise This may have some protective effect,” “If fats are saturated they will solidify, Hibernators, on the other hand, wake up
order to preserve the glucose that brown bear metabolism. Fröbert says. In his team’s experiment, turn into butter at low body temperatures” from their long-term dormancy with their
animals have stored from their last published online in Clinical and Translational so the animals could not use them, skeletons and muscles unaffected. In the
meal. PTL is responsible for starting up Science in January 2012, it’s not clear how says Andrews. “But being unsaturated case of the squirrels, they have no option
the mechanism to convert fat into usable double its body weight by adding fat during attack or a stroke,” explains Ole Fröbert, the animals keep their arteries flexible. they stay liquid even in a very cold if they want to avoid being eaten by foxes
energy at low body temperatures. summer and autumn. a cardiologist from Örebro University Researchers hope to find a molecule that environment.” How they do it is what he and panthers – they have to stay strong
Consuming 0.2–0.3% of their body mass “The cholesterol levels in their blood Hospital in Sweden. “However, brown bears could similarly affect humans’ blood vessels. and other researchers want to understand. and mobile and have developed the genetic
per day, hibernators can survive until are double that of humans and their heart do not suffer any of this.” The secret may be in the animals’ diet. “Hibernators selectively use fat all winter ability to do this.
spring. And the bigger their fat stores, the beats very, very slowly which is also a risk How bears keep their arteries safe under “The fat that hibernators use is very long and, despite the extra pounds, they Monitoring bone metabolism markers
greater their chances of getting through factor for blood clotting. These conditions these conditions is what Fröbert and his different from the fat humans consume – stay healthy. This could help us combat in the blood of five bears, Donahue found
the winter – for example, a bear is able to [would] put a person on the verge of a heart colleagues are investigating. we often eat saturated fats,” says Andrews. obesity and diabetes in humans.” that “during hibernation, bone loss and >>
78 www.cosmosmagazine.com Cosmos 46 Cosmos 46 www.cosmosmagazine.com 79
3. istoCk
bone breakdown do happen but bears have they were injected with either human
>>
developed the biological mechanism to or bear PTH and had their bone density
[keep] bone production constant”. In a 2008 measured and compared over several weeks.
getty
review published in the American Journal Bones became stronger in the rats that
wikimedia
wikimedia
of Physiology, he and his colleagues found had received the bear PTH. These results
this is due to the high levels of two chemical might lead to more effective treatments for
compounds, osteocalcin and parathyroid osteoporosis in post-menopausal women,
hormone, or PTH. who are susceptible to bone loss.
“Just as in humans, bear Another hibernating
bones release minerals animal that has caught
during periods of inactivity. “Scientists in scientists’ attention
But instead of excreting is the arctic ground
Pittsburgh revived
wikimedia
calcium, PTH induces its re- squirrel, Spermophilus
absorption by the kidneys
and puts it back in bears’
dogs after three parryii. From early
September to late April
hours of clinical
getty
skeletons,” Donahue says. this small, orange and
“Osteocalcin is a protein white squirrel cools
normally excreted in the death – no heartbeat, its body to a core
urine. Since bears do not temperature of -2.9ºC,
no breathing and no
getty
wikimedia
urinate during hibernation, which is the lowest
osteocalcin levels increase known naturally
and contribute to bone brain activity.” occurring temperature
mineralisation and in mammals. At the
building.” same time, however, it keeps its brain,
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and other parts of the body involved
HUMAN PARATHYROID hormone may in regulating and maintaining energy
not be as efficient as bears’ at recycling metabolism, above zero.
jill zamzow
minerals back into bones. Donahue and his As Andrews explains, these are
team are currently studying the hormone’s physiological feats that non-hibernating
bone-sparing power. “We have sequenced animals, including humans, could never
the gene for bear PTH, and used it to survive. “A human will go hypothermic in their muscles. Females wake long known to aestivate, the heatwave equivalent
produce a synthetic form of bear PTH [temperatures] around 32ºC. The chemical enough to birth cubs and lick of winter hibernation – holes up in tree
and reverse bone loss in rodent models of reactions in our bodies just can’t take place,” Animals around the them clean before resuming their European hedgehog trunks in groups of four to five. Surviving
osteoporosis,” says Donahue. he says. Yet the cunning arctic ground slumber, while the cubs remain Scientific name Erinaceus on fat stored in its tail, the fat-tailed dwarf
Donohue’s team used rats with surgically squirrel is not only able to cool and heat world have evolved awake, suckling their mother and europaeus lemur becomes dormant to combat drought,
removed ovaries, which simulates up its body each year – during hibernation, waiting for spring. Location Western Europe its body temperature varying with the
menopause, making their bones develop every week or so, the squirrel stirs, shivers ingenious ways to survive Hibernates for 5–7 months outside temperature – reaching up to 30°C.
osteoporosis and become spongy. Next, without waking, re-warms to 37ºC for about environmental extremes, Red-eared slider These hedgehogs build nests in which
Scientific name Trachemys scripta to hibernate when the temperature drops Black rockcod
Bears’ bodies
reports Ola Jachtorowicz. elegans below 16°C. While hibernating, they will still Scientific name Notothenia coriiceps
continue to produce Location Southern U.S. bristle (erect their spines) when touched or Location Ocean around Antarctica
bone (shown here) Common poorwill Brumates for 6–7 months exposed to noise. Hibernates for 6–8 months
during hibernation.
Scientific name Phalaenoptilus nuttali Called sliders for their ability to quickly In 2008, it became the first fish identified
Instead of excreting
minerals released Location Western North America evade predators by slipping off rocks Northern bat to change its metabolic activity as part of an
from bones as Hibernates for up to 3 months and logs and into the water, these turtles Scientific name Eptesicus nilssonii annual cycle, becoming 20 times less active.
would normally The only bird known to hibernate, the brumate (a reptilian version of hibernation) Location Northern Europe to Japan Its dormancy pattern isn’t due to water
happen during a
poorwill doesn’t build a nest but sits in piles through winter at the bottoms of ponds and Hibernates for 4–8 months temperature, but most likely to lack of light
period of non-
activity, the bears’ of rocks or clumps of grass, concealed by its shallow lakes, occasionally rising for air. Groups of two to four choose underground during Antarctica’s long winter. It waits out
bodies instead camouflage plumage. The Native American spaces such as caves, mines, cellars the darkness before resuming hunting prey.
re-absorb them Hopi people called it Hölchoko or ‘the Monito del monte and bunkers. They can hibernate in
into the kidneys
with the help of
sleeping one’. Scientific name Dromiciops gliroides conditions below 0°C, which benefits them Mountain pygmy possum
two chemical Location South America energetically and enables them to hibernate Scientific name Burramys parvus
compounds. American black bear Hibernates for up to 4 months for up to eight months in a row. Location Australia
Research into this Scientific name Ursus americanus A living fossil, the monito del monte (‘little Hibernates for 5–7 months
process could lead
Location North America mountain monkey’) is ancestral to Australian Fat-tailed dwarf lemur The critically endangered pygmy possum
SETH Donahue
to breakthroughs
in the treatment Hibernates for 5–8 months marsupials. It spends its life in trees and Scientific name Cheirogaleus medius burrows deep into snow and boulder crevices
of osteoporosis in Considered highly efficient hibernators or bamboos of Andean temperate rainforests, Location Madagascar in winter. Native to Australia’s alpine regions
humans. ‘super-hibernators’, black bears recycle their hibernating in well-hidden, spherical, water- Aestivates for 6–8 months and only 11cm long, it is the country’s only
waste into proteins, which become part of resistant nests lined with moss or grass. This primate – the only tropical mammal hibernating marsupial.
>>
80 www.cosmosmagazine.com Cosmos 46 Cosmos 46 www.cosmosmagazine.com 81
4. 12–20 hours, then goes into hibernation no heartbeat, no breathing and no brain molecules that can damage proteins and just 15 minutes this way,” adds Tisherman.
>>
again without any tissue damage. activity. While Roth’s team focusses DNA and lead to cell death, contributing to A heart–lung bypass machine will be used to
on slowing the metabolic rate and the tissue damage or organ failure. restore blood circulation and oxygenation as
SCIENTISTS HAVE identified several temperature comes down as a by-product, Later in 2012, surgeon Samuel Tisherman part of the resuscitation process.
compounds that may explain how this is Kochanek’s team cooled the body in order and his team, also at Safar Centre in Extreme cooling therapy – expanding
possible. Andrews has found that PDK4 to slow down the metabolic rate. They Pittsburgh, will start a clinical trial to see if across hospitals even before scientists
and PTL, the same enzymes that switch drained the dogs’ blood and replaced they can rescue patients who have suffered and doctors completely understand how
over metabolism, help cardiac physiology to it with a solution of low-temperature cardiac arrest due to massive bleeding, by it works – could also help treat some type
work at low temperatures. “PTL is a protein glucose, dissolved oxygen and saline. The chilling them to nearly 10°C. of poisonings, for which blood circulation
produced in the human pancreas but we dogs came back to life after a blood must be stopped. The power of
have found it in the squirrels’ heart. The transfusion and an electric shock “These are physiological feats H2S to induce hypothermia is also
reason is that it works very well in the cold. to the heart, though a few suffered being tested in patients with acute
It can burn fat in the cold and allow the minor brain damage. Using a similar that humans could never survive.” lung injury, multiple organ failure
heart to continue beating.” approach, a group of trauma surgeons and some inflammatory diseases.
In 2007, Tom Scanlan, a biologist now at Massachusetts General Hospital in “Most of the time people with severe However, failure to reproduce the effects
at Oregon Health and Science University Boston reported successful results in several trauma and blood loss don’t survive,” says seen in mice in larger animals (such as
in Portland, Oregon, published research experiments with Yorkshire pigs. Tisherman. “Rapid cooling might be able to sheep), as well as safety concerns, mean
in Stroke describing how a derivative of sustain the patient, particularly the brain, further research is needed.
ole frobert
thyroxine, a thyroid hormone, rapidly THE NEXT STEP IS to test suspended long enough to buy time for surgeons to Andrews remains optimistic. “In the
lowers body temperature and slows heart animation in humans. When a person has find the source of blood loss, repair the future maybe we will have the ability to
rate when injected into rodents. Six to eight severe trauma and massive blood loss, wound and restore heartbeat.” create transgenic hibernators, as we now
hours after injection, they resumed normal oxygen supply also falls. When deprived In the trial, body temperature will be create transgenic mice, to better understand
core body temperature and behaviour. The Some bears can double their body weight during summer in preparation for winter hibernation. of oxygen, an average person suffers brain lowered by administering up to 20 litres of how hibernation works.”
team has produced several similar synthetic damage within five minutes and dies 15 cold fluid through a large tube placed into
substances that show the same or even survival was a result of a cold-induced state humans, it enables core temperature to stay minutes later. But restoring blood flow is the aorta, the largest artery in the body. Zuberoa Marcos is a Barcelona-based science writer and
more potent induction of hypothermia. similar to hibernation, as the mountain uniform regardless of whether we are in the dangerous too. The influx of oxygen-rich “In the preclinical studies we have done in scientific director of a weekly TV magazine at the Spanish
Meanwhile, in 2006 in Nature, Cheng Chi temperature dropped as low as 10ºC. Arctic or the Caribbean. blood produces so-called reactive oxygen animals, we have cooled down the body in Broadcasting Corporation.
Lee, a molecular biologist at the University “I am convinced there is some kind At his lab at the Fred Hutchinson Cancer
of Texas in Houston, with his colleagues of connection between hibernators and Research Centre in Seattle, Washington,
showed that the 5’-AMP (five-prime human survivors, people who have cheated Roth placed mice inside tanks from which
adenosine monophosphate) molecule also death after being submerged in icy water, or nearly all of the oxygen had been removed
lowers mice’s core body temperature and buried in snow, without oxygen, for hours,” and made them breathe 80 parts per
makes animals enter hibernation. says Andrews. million of H2S. Their core body temperature
Five-prime AMP is part plunged 20°C within minutes,
of a cellular process called
oxidative phosphorylation,
The spin-off is a deeper understanding of their heart rate declined more
than 50% and their metabolic
which is the body’s power- controversial medical technologies that can rate tumbled. The animals stayed
generating apparatus. in suspended animation for up
Cells need oxygen to make slow patients’ respiration to almost zero – to six hours before the oxygen
adenosine triphosphate, supply was turned back on.
or ATP, the primary fuel and bring them back from near death. Surprisingly, they woke up with
of life. As the organism’s no brain damage.
body cools, it needs less oxygen, oxidative H2S seems to slow, or even stop, oxidative
phosphorylation slows down or stops, A lack of oxygen often kills people phosphorylation, the process by which
and the animal simply rests. This process who have had a cardiac arrest or a stroke. cells produce energy. Roth’s experiment
happens not only in mice, but also in About five years ago, doctors began to showed that mice can survive when
squirrels and other hibernating mammals. experiment with therapies to cool down, exposed to low oxygen concentrations that
Perhaps even in humans. even temporarily, such patients’ bodies and would otherwise be lethal to them. He is
In October 2006, the first known case reduce their need for oxygen. The results also one of a number of researchers who
of a human going into ‘hibernation’ was have been nothing short of extraordinary. are investigating the use of suspended
described. After slipping and breaking his In 2005, biochemist Mark Roth made animation in radical medical therapies.
pelvis, a 35-year-old hiker survived 24 headline news worldwide when Science In February 2008, anaesthetist
days in a mountain forest without food published his team’s results showing Patrick Kochanek of the Safar Centre for
or water. Mitsutaka Uchikoshi was found that exposing mice to tiny doses of Resuscitation Research at the University
unconscious on Rokko Mountain in Japan, hydrogen sulphide – H2S – induced a state of Pittsburgh at Titusville, Pennsylvania,
with a body temperature close to 22ºC. He of reversible hibernation. H2S is a foul- and his colleagues published a paper in
had a weak pulse and was suffering blood smelling, corrosive, flammable and deadly the Journal of Cerebral Blood Flow and
loss. After referral to a hospital, he made gas, produced naturally in tiny amounts in Metabolism describing how he had revived
a full recovery. His physicians believed his the bodies of humans and other animals. In dogs after three hours of clinical death –
82 www.cosmosmagazine.com Cosmos 46