Hibernation is a concept we're very familiar with. Many sci-fi stories require
hibernation to work. While imaginations have been running wild in pop culture, the science of hibernation and a shorter state called
torpor have been lagging behind. Now this is changing. An array of potential medical
benefits is driving scientists from labs around the world to search for the underlying mechanisms
of this near-magical state. To travel for centuries or for millennia, that's way out of our reach at the moment but hibernation could
bridge you from a condition in which you could not live any longer to one in which you may still live. As well as helping to buy time for people on the waiting list for an organ, a synthetic form of hibernation could also possibly offer
protection against radiation to cancer patients and space travelers. There are serious experiments
that have been done. There are significant and serious results that have been produced, so I would say it's not
science fiction anymore. Now is the moment, yes. Now we at least have
a path in front of us, a research path that we
know could lead there. Torpor is the actual state
in which our metabolism - the energy we use - drops to a minimum, so it is a suspended animation state. Many episodes of torpor,
one after the other, interrupted by a brief,
very brief arousal, that's what makes hibernation. We have bats that go into hibernation, bears, rodents, primates. Some animals can enter
brief episodes of torpor. You'd be surprised how many
hamsters get thrown away because their owner think they're dead, but actually they're just in torpor. While it might not be
something that humans do, hibernation or torpor is common in species across the many orders of mammals. This might mean that the
genes involved in triggering and controlling these states were present in our common ancestor who
needed a survival strategy. When we first, as mammals,
appeared on this planet, we were hunted by
something about this size, even a bit smaller. So this is actually an
herbivore, to be honest, but just imagine like a giant
ostrich or even a turkey that were velociraptors and mini-raptors. Our ancestors developed a new ability: generating heat within our
own cells, instead of relying on an outside source, like the sun. That helped them hunt at night when dinosaurs were less active. But generating energy to
maintain the body's temperature requires resources which might have been often hard to come by. The idea to turn off the heater, turn off the unnecessary energy
use that your body requires even when we're resting,
is an energy-saving and a life-saving strategy. There is nothing you're
doing in this state, besides surviving. You're bridging a time in which you couldn't be alive -
because there was no food or water or whatever resources you needed, get very, very near death without touching that impenetrable wall. Unlike sleep, in a state of torpor the physiology of an
animal changes completely. The majority of cells that produce or use energy simply stop, and as a result, the body's
temperature goes down and its oxygen consumption decreases. The kidneys shut down as they
don't need to expel nitrogen, and with no food to process, the gastrointestinal tract changes. Muscle and bones enter a resting stage but don't lose their strength. With a breath drawn every minute or so, the heart is barely beating, pumping just enough blood
to keep vital organs alive. And the most energy-consuming
organ - the brain - also changes its rhythm. We don't need the brain
during torpor pretty much. The synapses get reabsorbed, meaning neurons will
withdraw their handshake, and then talk way less to each other. So they speak with different rhythms, and those rhythms during
torpor are the same rhythm we use when we are awake or at
least they very much resemble the intense activity that
we use when we are awake, but much, much slower. It's a slow wakefulness, if
we allow me to pass this term. Let's say it's like watching a movie, and we see the frame of
this movie going slower and slower progressively, and at the end, we just stick with one single picture. Torpor is very, very different from sleep, from coma, from general anesthesia, from any behavior we think about like resting or inactivity. We're not even sure
that torpor is resting. The body needs to recover
from torpor after torpor. After the dinosaurs disappeared, mammals took over the world and many species lost this
once life-saving ability. But restoring it presents
an exciting possibility. Hibernation and torpor is something hidden within our genetic code and within our brain regulation, probably. And we think that today we have lost maybe the ability to initiate this behavior because we didn't need it for a long time. But we are trying to discover
what is the ignition key. Here, at one of the oldest universities in the world, Matteo Cerri
is a professor of physiology. In 2013, he and his team were the first to induce what he calls
synthetic torpor in an animal that doesn't naturally
enter this state - a rat. It was just by accident. I worked before on
metabolism and the idea was to increase metabolism to lose weight. One day we just tried
to see what could happen if we were actually
shutting down metabolism. We block, we inhibit a
small group of neurons in a very old region of the
brain called raphe pallidus. The raphe pallidus is
a very interesting area of the brain stem. It controls a lot of our body function; the heart rate, body temperature,
respiration, breathing. So it's the area we use to
defend ourself from the cold. It makes you breathe faster
because you need more oxygen to sustain heat production. We were sure if we were stopping
that flow of information, we could see torpor, and yes, we did. The first experiment worked
and it was very lucky, it never happens the first time. Still one of the happiest
moments in my professional life. With this thermal camera, we can record the
temperature of the surface. Coolest is blue and black,
the red and white is warmer. Using drugs to switch off this part of the brain,
the team bring the animal in and out of a torpor-like state. Just like natural torpor, the
animal's temperature drops and a period of inactivity follows. Once the animal is brought out of it, it's as though nothing happened. Scientists have now found even more ways of inducing this state artificially, and many teams are investigating the body's adaptations during torpor. In Germany, a team led
by Walter Tinganelli is using a particle accelerator
to further this research. We try to understand
the molecular mechanism behind the hibernation itself. So we try to simulate in-vitro,
so on cells, cell culture, the physiological change
at which the cells are during hibernation. A complex process like torpor can't be simply induced in a petri dish, but the team can simulate its conditions on a cellular level. We perform experiments changing
the oxygen concentration of the cells, changing
the metabolism of cells. For example, producing starvation on cells or changing the temperature, of course. Although this research into hibernation relies on cutting-edge science, its foundations can be
traced back decades. The most important
experiment with hibernators, they happen around the '60s when the first human space missions start. With Apollo 11, of course,
they take the astronauts on the moon in 1969. Because the physiological changes that happen in natural hibernators are very interesting for space. And then what the researchers found out was that the radioresistance of an animal during hibernation increases. But then the idea was okay,
but if humans cannot hibernate, why we should continue
this kind of experiment, such an experiment. And then the interest,
let's say, on hibernation was fading a little bit. Developments in the past decade have revived interest in the resistance to radiation while in torpor. The team at GSI is particularly interested in how this could one day be harnessed in radiotherapy for cancer patients. You want to kill the tumor
and spare the healthy tissue. If you can bring the patients
into synthetic hibernation, then first of all, most
probably you will stop the tumor growth. But then if you are also able to reduce the healthy tissue damage
and to treat with, let's say, a higher than today dose, this could be in future,
perhaps a very nice tool. And we try to understand if this process increases the radio-resistance just in the healthy tissue and
not in the tumor tissue. And so a few times a year, cancer cells in a state of
simulated synthetic torpor, like these taken from a mouse, are put into one of GSI's caves. These are rooms where outlets from the particle accelerator lead, and so the cells are
irradiated with heavy ions. Here is where we put our flask with cells. You do not shoot a radioactive particle. You just shoot the ion, so it's an atom without some electrons, and
then this does a certain damage, especially at the end of its track. Along the lines where the ions have pierced the cell, the
molecules, highlighted in green, are trying to mend the damaged DNA. Torpor doesn't stop cell
damage but one theory is that the repair might be
carried out more smoothly. That cell is not really
working because it's in torpor. It's like if you had to
fix a car that broke, it would be much harder to fix a car while the engine was running,
while the car was running. And that's why we think
cells in torpor are better at dealing with radiation damage. After irradiation, the team analyzes how many cells survive and
which genes were involved. Then you can play with
these cells, changing for example, silencing a specific gene. And then to understand
which of these genes are very important for the
synthetic hibernation process, for increasing the radioresistance. So playing with all these different tools, we will be able to understand
as much as possible about this very complex process. GSI's ability to bombard cells with heavy ions also has
applications for space radiation, one of the main problems agencies like ESA and NASA need to overcome
for human exploration of the solar system. In space, the most dangerous radiation are essentially particles,
so 70% are protons, very energetic protons. But then you have a lot
of ions up to the iron, so that really hits the astronaut
like a small projectile. During a long voyage to Mars, synthetic torpor could
offer added protection, not only from radiation,
but also from loss of bone and muscle strength. And there would be other
practical benefits. No need for extra food,
or to mitigate the stress of prolonged isolation. And as the team continues to
observe the impact of torpor on the body and mind,
there could also be clues as to how we tackle and
perhaps even reverse other forms of degeneration here on Earth. In the brain during torpor,
some markers start to appear. What am I'm saying with markers? Markers are an indication that
something usually is wrong. We use markers to identify diseases. One of those markers is a hallmark of Alzheimer's disease. The brain of a squirrel in torpor will drastically resemble the
brain of an Alzheimer patient. We could say hibernation
is a dive in dementia. What is interesting is
that when animals arouse from torpor and hibernation,
their brain very quickly returns to normal. Synapses again reform in
stronger numbers eventually. Some evidence suggests that the brain works even better after torpor. The arousal from torpor
is a neurotrophic storm. To be honest, it's the most
intense neural plasticity I've ever seen. The brain is really rewiring. Could we exploit and understand
what is the mechanism behind this extremely intense plasticity and apply it to a
neurodegenerative disorder? Or could we manipulate
memories or neural trace or behavior that we have
learned, like addiction and kind of prevent
themselves to be rewired? This is all unknown,
but it's quite possible. With trials so far only done in rodents, there are still questions to be answered before moving forward. During natural hibernation, animals have to come out
of torpor occasionally and we don't know why. We also still don't know how long a synthetic torpor could last safely, and if humans would need to be brought out of this state periodically as well. All of this means that
getting to the stage of human clinical trials won't be easy. My feeling is that if we're
ever gonna reach the phase of testing it in humans,
it will be on some patient that is really in a
very critical condition, something that has no treatment at all and death is looming and
there's no way out of that. Someone on the waiting
list for a transplant could be the case, a
very aggressive cancer could be another case. But even if synthetic torpor and hibernation can one day save lives, and perhaps even smooth
out our road to the stars, there are still many ethical questions that will need answers. What's the status of a
human in synthetic torpor for a long time? Let's say you stay for a year or two. What if you get divorced by
your partner during torpor? You have to be woken up? Who has the right to wake you up? What if the stock market collapses? What if you were charged with crimes? What if you were convicted and then you wanna spend your time in prison in synthetic torpor? So there are plenty of
ethical implications. This research is still
the domain of academia, but private investment
might not be too far away. Some private company,
space-related companies, I'm sure they are interested in that because even in conferences sometimes they come to my colleagues, they would like to know more
which stage we are and so on. Something like, okay, it's interesting but let's leave them to do,
let's say, the dirty job now and then if we recognize that in the end something good can come out from that, perhaps we will jump on it. The way research is structured today, you have to compete with your
colleagues to get funding. This is slowing science down
and is slowing innovation down. And I'm afraid of this switch
in the focus of research from public university, or
from university in general, to the private sector. But maybe that's the way it's gonna go. I'm just worried that some
critical technology could be owned and therefore used as
a mean to power eventually.
