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.