October 30, 2023 • 47 mins
Does life end inevitably or instead only because we don’t understand biology well enough yet? Today’s episode is about understanding what happens when your molecular cycles grind to a halt... and whether there's anything we can do to hit control-Z. Join Eagleman and his guest Dr. Zvonimir Vrselja to dive into the weird possibility of understanding cells well enough to reverse death.
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Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Speaker 1 (00:04):
From the point of view of biology, what is life
and what is death and what is the line between them?
Could you freeze your body to come back sometime in
the future, and what does this have to do with
Mary Shelley's Frankenstein or housefly or the poet John Dunn.
(00:28):
Welcome to Inner Cosmos with me David Eagleman. I'm a
neuroscientist and an author at Stanford and in these episodes
we sail deeply into our three pound universe to understand
why and how our lives look the way they do,
and in this case, whether life is something that comes
to an end inevitably or only because we don't understand
(00:52):
the biology well enough yet. So today day's episode is
about understanding what happens when your molecular cycles grind to
a halt, and whether there's anything we can do to
hit control z on that can death be reversed. A
(01:18):
few months ago, my dog was lying on the floor
and we were all gathered around her, and my kids
were coming in and out, and everyone was crying because
my dog was dying. She was fifteen and a half
years old, which for a dog her size was quite old,
and her body was shutting down and as I sat
(01:38):
on the floor stroking her back, I was thinking about
a poem by John Dunn that I had first read
when I was a child, probably about ten years old.
The poem is called Death Be Not Proud, and it
really blew my young mind when I read it. It
begins with these lines, death be not proud, though some
(01:59):
have called thee mighty and dreadful, for thou art not
so now. In this poem, one of his nineteen holy sonnets,
Done gets right up in Death's face and he challenges
Death's power and importance, and he tells death not to
be proud because it is not as fearsome as it
(02:20):
might seem. And the sonnet ends with the lines one
short sleep past, we wake eternally, and death shall be
no more death, thou shalt die so. Done ends the
poem by spitting right in death's champagne glass, and he
tells Death that he is going to die now. John
(02:44):
Dunn wrote this poem through a religious lens. He was
giving the interpretation of the victory of the soul over death.
But I had a different interpretation. I was struck by
this idea of defeating death. After all, biologists, we study
life and each decade we know more and more about
(03:06):
how it works, and the more we know about life,
the more we can know about how to keep it
going and possibly how to even reboot it. Now that
sounds crazy, but we're going to unpack that carefully in
this episode. There are many ways to look at what
life is. I did an on stage conversation some years
(03:28):
ago with a mystic named Saguru, and we discussed and
debated a number of issues, but he said one thing
that was phrased very simply, and it proved hard for
me to forget. He said, the physical body is like
a fruit, and when the person is gone, the person
that you loved, all you have left now is the rind.
(03:51):
There's nothing special about the body, the physical body, and
I loved that description, but as a biologist, I wanted
to dig deeper. And this is a problem I had
actually started thinking about years earlier, because I once went
to wash a dish in the sink and there was
a tupperware in there with some water in it, and
(04:11):
there was a house fly that had died in the tupperware.
And I looked at the poor little lifeless fly, and
a question struck me, What is the difference between the
live fly and the dead fly. If you do a
chemical analysis, it's exactly the same stuff. You have x
number of carbon atoms in the quadrillions or ten to
(04:35):
the eighteenth, and you have Y number of nitrogen atoms,
and you have Z number of oxygen atoms, and so on.
The weight of this little dead fly is exactly the
same as a living fly. The chemical composition is the same,
All the trillions of proteins are the same. Everything is
the same between the living fly and the dead fly.
(04:58):
The only different is the molecular momentum. All the cascades
have come to a stop. All the crebs cycles and
the action of the proteins around the DNA and the
endoplasmic particulum, and all the step by step chemical reactions
in the cell, they've all just come to a standstill.
(05:22):
So what Saguru referred to as the fruit to the
part we love and lament I interpret this as the
ongoing cascades of the cellular processes. This leads to this
leads to this, and as long as everything keeps going,
then the fly is alive and it moves around. As
soon as something breaks about these cycles, then everything just
(05:45):
grinds to a halt. So this leads to the question
what does it require to keep everything going for cells
to stay alive? And the related question is if they stopped,
would there be any way to you reboot the system
to get the cycles going again. So when I read
(06:06):
Dunn's poem as a kid, where he says that death
shall die, I imagined that someday, in the very distant
sci fi future, we might actually be able to make
this true, to get cells going again that had come
to a stop. But of course, when imagining this future
as a kid, you imagine it as people in silver
(06:27):
suits zipping around in the skies. So as I got
older and studied biology and became more realistic about this,
I realized, of course that we were all going to
die after all. So given that perspective about how distantly
in the future this would happen, you can imagine how
(06:48):
surprised I was to see the speed at which this
field is moving along. I suspect that I will die
and perhaps the next few or several generations. But the
idea of reversing deaths, at least in some cases, is
not a subject constrained to the pens of poets. Anymore.
(07:09):
Over the past several years, you can find the beginnings
of this endeavor published in the top scientific journals. And
we're not talking about longevity in this episode. I'm going
to talk about that in the future episode. Instead, we're
talking about this completely wacky idea of reversing death, taking
(07:29):
an organism that has already died, and reversing back out
of that. Now, this sounds like something straight out of
Mary Shelley's novel Frankenstein, which, as you remember, tells the
story of a scientist named Victor Frankenstein who figures out
how to reanimate the dead. But the whole thing doesn't
(07:49):
turn out so well, and Frankenstein's monster ends up getting
rejected by mankind in general, and he regretfully murders people
to get revenge on his maker. But anyway, put that
interpretation aside for a moment while we talk about this,
because in the early twenty first century, we're now in
a more realistic position to assess what is possible and
(08:13):
to think deeply about the ethics. Now, it may sound
surprising that there's enough science now to even talk about
this topic, but hangtight, because we're about to see some
very strange stuff. First, this question of whether death could
be reversible has long been entertained, because sometimes people can
(08:34):
fall to the bottom of a lake and freeze to
death and lose all their function, and they are really
truly at a stop, and then sometimes they can be
brought to a hospital and revivified. For example, I remember
reading a story in two thousand about a young doctor
in Norway named Anna. She was a trainee surgeon who
(08:55):
was exactly my age, and she was skiing when she
fell through a rosen river and got trapped under the ice. Now,
her colleagues were there and they saw her, but they
couldn't get her out, and they struggled and struggled to
rescue her. But she ended up being under the ice
for forty minutes, and not surprisingly, her organs shut down
(09:18):
and she died. Her body temperature had fallen more than
twenty three degrees below normal. But Anna was eventually pulled
out from the ice and put on an air ambulance,
and she wasn't breathing when she got to the hospital.
Her blood circulation had stopped, her pupils were not responding
to light, but the doctors put her on a heart
(09:41):
and lung machine and re warmed her while the circulation
was kept going. They used a machine that warmed her
blood and oxygenated it and then put it back in
her body, and things weren't easy. She spent sixty days
in intensive care in the hospital, but five months after
she was frozen to death, she was back to work
(10:02):
as a doctor and she still skis now. You can
find this case in the Lancet, which is a top
medical journal in the field. So this stuff happens, and
it happens more than you might think. I read another
article in twenty sixteen about a guy walking home from
a party and he slipped and hit his head and
went unconscious and wasn't found until the next morning when
(10:24):
his father was driving around looking for him and found
him buried in the snow, frozen, no vital signs. They
rushed him to the hospital. They pumped him full of warm,
oxygenated blood, and it wasn't an easy recovery. But a
year later, even though he's missing all his toes and
pinkies from frostbite, he is indistinguishable from anyone else you
(10:49):
might meet. Essentially, he was frozen in the same way
that we might put meat in the freezer, so it
doesn't go bad. But it's the same principle. Despite our
sense of our beautiful essences, it's also the case that
we are meat and we can be frozen and we
can be thawed. Now, why can't you revivify any person
(11:11):
who has died. Well, if things aren't frozen, then the
biology decomposes, the cells break down. This is of course
the same thing that happens if you leave a piece
of meat on your counter instead of putting it in
the freezer, and in the case of a person, that
causes irreversible damage to the brain. But a frozen body
(11:32):
doesn't decay, at least not rapidly. It stays intact because
the molecules can't move around as much. Everything is held
into place. So the observation that people could be frozen
and unfrozen got scientists interested in the speculation of whether
you could take a person who has just died and
(11:52):
freeze them on purpose, with the idea of unfreezing them later.
And this successfully started in the nineteen in seventies with
freezing mouse embryos, and then that became a successful way
to freeze human embryos. But keep in mind a human
embryo is the size of a grain of salt, and
so the challenges are a little less in successfully freezing
(12:16):
and unfreezing those. But the question people have been asking is,
could you actually freeze an entire adult body and unfreeze
it later, Let's say, because they have cancer that we
don't know how to cure. But maybe in seventy years
the medical community will have no problem curing this. It'll
be easy. Could you reanimate somebody in the same way
(12:38):
that has been done on a much shorter timescale with
the woman in the icy river or the man who
fell into the snow bank. Well, in a previous episode,
I mentioned a company in Arizona called Alcore, which strives
to do exactly this. They are a cryogenics company, and
upon your death, they will swoop in to perfuse your
(13:01):
body with the right chemicals and get you to the
facility in Arizona, and there they will lower you into
a vat of liquid nitrogen. Now, do they know how
to cure whatever your disease was, or, for that matter,
do they even know how to unfreeze you successfully? No,
But that's not the point. The point is that sometime
(13:21):
in the distant future, our great grand descendants may know
how to do this, and at that point they can
unfreeze you and cure you of whatever ailment you have,
presumably something that was totally opaque or confusing for twenty
first century minds, but easily curable with a twenty second
(13:41):
century toolbox. Now here's something of interest. It turns out
the first person to ever get frozen on purpose in
this new field called cryogenics was born in what year,
take a guess, eighteen ninety three, a guy named James
Bedford who died in January of nineteen sixty seven from
(14:02):
terminal cancer. He was the first person to do this.
But did he die? Interesting question? I would say unresolved
so far, because it's yet to be seen whether he
can be rebooted nineteen sixty seven. So although this is
science fiction y, it's not even that new. Now. Since
that time, people have worked on the cryogenic technology to
(14:26):
figure out how to make the freezing process better and
better to prevent cell damage, because the problem is if
you get an ice crystal during the freezing process, that
will rupture the cell membrane and then the body that
you hoped to revive is too damaged. Like when you
stick a strawberry in the freezer to try to make
(14:47):
it last longer. But once you unthought, it gets all mushy.
That's the same thing that happens with any cells if
they get ice crystals in it. So will Bedford's body
be able to be reanimated? Who knows? And experts have
different opinions about whether the bodies at the alcore facility
will be reeve vivifiable. But the idea of cryogenics is
(15:09):
straightforward in the sense that even if these first few
hundred experiments fail, will surely get better and better at
cryogenics in the future, and the hope is that someone
fifty generations from now will know how to reverse the process.
And before I go to the next step, I just
want to say this idea about confronting death is not
(15:32):
just about freezing and unfreezing. The deeper issues in biology
have to do with how individual cells die. It turns
out that cells can get injured by various things, let's say,
a lack of blood flow or a chemical insult, and
then they essentially blow up and die and cause a
lot of inflammation. This is called necrosis. But in nineteen
(15:55):
seventy two it was discovered that this isn't the way
cells have to die. Cells can actually die on purpose,
and this is known as a potosis. A potosis means
that instead of a cell simply just falling apart, instead
it implements a controlled process by which it folds up
(16:15):
shop and cleanly commits suicide. Scientists came to understand that
this is a very purposeful process, and over many years
they showed how apotosis is actually the way that biological
organisms structure themselves. For example, a human embryo has webbed fingers,
in other words, little sheets of skin between the fingers
(16:38):
of exactly the type that you would need for swimming.
But in the case of our particular species, the cells
making up that webbing. Those cells die off before the
baby is born, such that we have independently moving fingers.
But those cells between our fingers wouldn't die off if
we were another mammal, say a bat, or a kangaroo,
(17:00):
or a whale or a manatee. I'm actually going to
put an X ray picture of a manatee fin on
my website because it's so stunning how the bones inside
their fin look just like a human hand. The bones
look that way, but the difference is that the cells
between their fingers, that webbing that doesn't die off, so
(17:20):
what you get is a fin Anyway, apotosis is everywhere.
Your body has about a trillion new cells developing every day,
and so you need to kill off a similar number
to keep the system from getting overrun. And this is
all done with this very controlled process of cell death.
(17:41):
And the scientists behind these discoveries Horbitz and Brenner and Sulstan.
They won the Nobel Prize for this in two thousand
and two. But it turns out since then biologists have
discovered that necrosis and apotosis are not even the only
game in town. We now know there are many flavors
of program cell death, like what's called pyrotosis or ferrotosis
(18:05):
or necrotosis. These are all different mechanisms that tip the
balance between different cell fates, and people are working on
drugs to block all these very specific flavors of cell death.
It's no longer just the cell gets sick and falls apart,
but it's much more sophisticated now and that gives the
(18:26):
possibility to molecularly block the process. So now let zoom
out to the big picture. There's an increasing amount known
about how cells actually shut down, and we have proof
of principle that systems can get going again even after
they've stopped. And all this has led to the possibility
(18:48):
that we might be able to take something like a
dead brain or dead body and reboot it. Now this
sounds so crazy, but the question I want to ask
is are we actually going to have to wait fifty
generations to see this happen? Or is it possible that
things are moving so rapidly that there's some reason to
think that we could take, say, a dead brain, a
(19:11):
totally dead brain that's been dead for four hours, and
get the whole factory running again. Well you'd agree that
seems like a science fiction fantasy. But a colleague of
mine recently published two papers in the journal Nature, and
it seems we're already at the point, give or take,
where we may be able to do something just about
(19:32):
like that, at least in pigs. In the journals, this
is cast in the paper as quote Cellular and molecular
recovery in pigs, which I suspect doesn't sound that interesting
to most people on the planet, and so it didn't
get that much attention. But this is seriously big stuff.
So I called up my colleague who wrote these recent papers,
(19:52):
and I asked him, is cell death inevitable? Let's say
when a person has a stroke and there's no blood
going to the set. Well, we've always thought of that
as being a really terrible scenario that inevitably leads to
sell death. But is that the case?
Speaker 2 (20:25):
So we used to think that, and we had a
publication four years ago where we actually christened if sales
actually die after death after blood flow stops, and we
realized that actually death is a portracted process. It takes
a bit actually for sales to die, and if you
intervene properly, you can maybe reverse those processes.
Speaker 1 (20:47):
That's Vanimir Russella. He's an mdphd originally from Croatia. He
did his postalk and became a research scientist at Yale
School of Medicine, and now he's spun off a company
around this called Becksore. So you mean the death of
an organism, let's say, of a person. You're saying it
(21:09):
doesn't happen all at once, but it takes time to die.
Speaker 2 (21:14):
So yeah, yeah, So I think I just want to
be like a nuance here. There were instances that so
it is well known that For example, you can find
living cells in human specimens after hours of death, and
scientists have used like chunks of tissue to find like
living sales and record from them.
Speaker 3 (21:33):
It was also observed.
Speaker 2 (21:34):
That people who have died and were undercolt conditions that
they could be actually brought sort of The implication there
is that there are cells o functional. So there were
instances where this was a scene and recorded in the literature.
Speaker 1 (21:50):
So let's just double click on that. So tell us
what you mean about people who were frozen and were recovered.
Speaker 2 (21:57):
Give us an example, So on the macros kale, like right,
talking about the whole human, not about.
Speaker 3 (22:03):
A single cell. It was observed that people.
Speaker 2 (22:05):
Who have drowned their bodies would cool down as they
were drowning, that after a prolonged period of time, these
people could be resuscitated. So the time it was, you know,
we are not used as seeing like someone resuscitated after
that how long, Well, I don't know specifics, but just
to give you like a benchmark data point. Usually it
(22:28):
is assumed from the classical literature that four minutes after
blood flow stops, bodies cells just die.
Speaker 3 (22:35):
So that was.
Speaker 2 (22:36):
Always like a clinical data point, after which was really
difficult to bring people back with resuscitation.
Speaker 1 (22:45):
Okay, so you started suspecting that maybe cells aren't as
fragile as we thought. So what did you do?
Speaker 2 (22:53):
So yeah, so we have it's interesting storied up my
pi at the time. And then a Sistan received a
tissue specimens from abroad and they got stuck at customs
for a really long period of time. And so by
the time they came in the lab, you know, the
(23:14):
researchers were like thinking, oh.
Speaker 3 (23:16):
You know, it's done, like the specimen is useless.
Speaker 2 (23:19):
But they still made slice sculptures and after a week
they realized that they were living cells.
Speaker 3 (23:24):
So that was the first observation that got the group like.
Speaker 2 (23:28):
Thinking, and in our case in particular, we just wanted
to scale the whole approach, initially going from a small.
Speaker 3 (23:35):
Slice to a whole inteked brain.
Speaker 1 (23:38):
Right, So you said, hey, what if you could get
a brain of an organism that has died, could you
restore the function somehow? So what did you do to
try to tackle that problem?
Speaker 3 (23:52):
So, you know, as one does, we started going to
a local slaughterhouse and we were procuring a tissue.
Speaker 1 (24:00):
You were getting pig brains, right, pig reins.
Speaker 2 (24:02):
Yes, so people don't. Luckily there we are like, people
don't eat the pig brains.
Speaker 1 (24:07):
And this was the el right, yes, yes, yes, yes.
Speaker 3 (24:10):
Yes, So we will go to the local slaughterhouse. You know,
they would do their job.
Speaker 2 (24:15):
By the time when they are done, we would get
pig hits and so we'll bring them to the lab.
Speaker 3 (24:20):
We would take the brain out, and.
Speaker 2 (24:23):
Then we started developing this technology that could connect with
the vascular system of the brain and profuse a fluid
to sort of reboot the self functionality.
Speaker 1 (24:34):
And how long had these pigs been dead?
Speaker 3 (24:37):
On every g it was four hours, So from the
time of pig being killed in the slaughterhouse to the
time point where we started our profusion intervention, it was
usually four hours.
Speaker 1 (24:50):
So then what you did is you profused and tell
us about profusion and what that means and what that
looks like.
Speaker 2 (24:57):
So there's a device, so you take the isolated brain,
which is sort of front of you. You load the
brain into this device and then the device pushes artificial
blood or blood like fluid through the brain and it
does it under controlled conditions. It has a bunch of
drugs inside that counter certain cell processes. So the whole
(25:21):
point is to try to reinstate homeosthetic environment or this
like like normal environment in which cells are usually accustomed.
Speaker 1 (25:31):
To be and so what did you find?
Speaker 2 (25:34):
So we found that So this is an interesting equation.
So first of all, we found that we could revert
cell death. It was an interesting thing because at the
time we were trying to define like what does it
mean for a cell to be dead, like right, and
how do you define cell death? So we found it
cells that were considered dead they were actually still some adjective.
(25:57):
And with our interventions we could restore or functionality and
observed functions in those cells that we usually observe in
cells that we sort of think or consider alive.
Speaker 1 (26:08):
So were the cells completely restored or are there still
things you need to do to get to the next level.
Speaker 3 (26:18):
There is a lot more to do there.
Speaker 2 (26:20):
What we have done we took a particular number of
tests and we conducted those tests and so I can
only speak about those.
Speaker 3 (26:29):
They were pretty good broad tests that sort of speak
on the state of these cells. So these same tests
show that these cells performed in a similar way as
normal cells.
Speaker 2 (26:40):
And on top of it, with subsequent research data was done,
we actually showed that it's clear that these cells go
through stress of dying. So we've shown that we can
stop it, and we even showed on the molecular scale
that we can basically persuade sales like not to die
and they can start to repair themselves and basically just
(27:01):
say to them like, don't die, like they just want
to live, you know.
Speaker 1 (27:05):
So you take a pig brain that's been dead for
four hours and you perfuse this this solution through it.
It's like blood, but it doesn't have cells in it.
It has lots of meds and the proper kind of
molecules in it. You push that through and then you
can measure things about the cells and see that it's
like they're cooking along. They're doing their thing that cells
(27:26):
normally do.
Speaker 3 (27:28):
Absolutely.
Speaker 2 (27:28):
So the point is like, you know, you just go
to like meet school biology and it's you know, you
see if oxygen is going in, you see if glucose
is going in, so you're expecting CO two to come out,
so you know that's happening, and then you compare those results.
Speaker 3 (27:44):
I'm simplifying this, but you know, conceptually it works.
Speaker 2 (27:48):
You can provide stimuli or for example, drugs because you know,
like you can take a drug, which we have done actually,
so we would take a drug that works in humans,
it's well known, and we would see if it's exerting
the same effect in these restored cells.
Speaker 3 (28:02):
And it worked.
Speaker 2 (28:02):
So these cells can also be like stimulated and you
can observe how they respond. You can compare those responses
and learn about the brain, you know.
Speaker 1 (28:11):
And so you have been doing this in pig brains
since the first paper you did was in twenty nineteen
or yes, okay, so you've been doing it in pig
brains since then. What is the road that you see
two human brains?
Speaker 2 (28:27):
So this is a new type of research, and we
were pretty lucky from day one to have ANIH and
other institutions Yale including involved in helping us put the
guidelines and think about like where this research should go
and how it should be conducted. So what we have
done we really wanted to build like a ground up approach,
(28:49):
and so we wanted to show that these interventions are
opening new spaces, and so we went to do it
in the smart way. So that said going to humans
and what it really means, you know, think about like
restoring cells and their function, like you can think about
clinical applications of the technology like SOAK is the first
thing that comes to one mind.
Speaker 3 (29:09):
So it will take a bit more time to get there.
Speaker 2 (29:12):
Because we need to really understand, like deeply what's going
on on the cellular level.
Speaker 3 (29:16):
But this is one approach.
Speaker 2 (29:17):
Another approach that we have taken was in collaboration with
a transplant team here at Yale. So we actually wanted
to see if we could deploy our technology in dead pigs.
Speaker 3 (29:28):
Essentially and see if we could restore like kidneys or
liver for transplant.
Speaker 2 (29:34):
Because if this works in the clinical sense, then there
is a chance to readically expand organ pool or organ donations.
Speaker 1 (29:43):
Oh incredible. And when it comes to restoring the brain,
when you think down the road, you think ten twenty
years in the future, what are the ethical questions here?
Speaker 3 (29:53):
Well they are big. So the first thing is clearly,
are we sort of rebooting this brain like big where
it was. I'm really particular how I speak about these things,
So I talk about sales, I don't actually talk about
brain function. The reason is because we are making sure
that we are not rebooting global network or EG. But
(30:18):
one could go in that phase. So that is definitely
something that can be explored.
Speaker 2 (30:23):
So now you can think about all the ethical implications
that our eyes with this technology.
Speaker 1 (30:29):
So you said you're being careful not to reboot the
function of the brain. Correct me if I'm wrong, But
you're not actually sure when or why that would happen.
It's just that in the experience you've done so far,
the electrical signaling, the global functioning the brain wasn't restored
in the pigs, but we don't know why that's the case,
and it could happen with another few molecules or whatever
(30:51):
of the right flavor.
Speaker 2 (30:53):
Absolutely, so there is research already showing thatta done in
the pace that this could be done. And also in
our case, it is basically the design of the experiments.
Our experiments we were actively suppressing or we were avoiding
that situation because even without the network being rewooted, we
(31:16):
still have an extremely valuable tool to understand how the
brain works and functions. So in the future, the question
has definitely been the technology, as you said, been the
technology is matured and we actually know exactly every single
thing that goes into it and what happens, then the
question is like what should be done next?
Speaker 1 (31:34):
And so what do you think about that, what are
your thoughts on the ethics of you know, somebody has
found drowned at the bottom of a lake and it's
four hours later and you say, hey, I've got a
solution here to bring this person back.
Speaker 4 (31:48):
Oh yeah, so definitely not now, and technologically and our understanding,
we're just not there yet, and there's a lot of
research that has to be done. I think it also
been comes an interesting.
Speaker 2 (32:01):
Question like assuming that the technology is capable of doing
such a feit, you know, you have a question from
you like should you do this?
Speaker 3 (32:11):
Like should you go and save this person? I'm a
trained physician, so that's the goal. You know, you want
to go and save someone. So this should become just
another tool that allows us to do our job. So,
but it needs to be it really needs to be
researched over time and show that there is value and
potential for this outcome.
Speaker 1 (32:31):
So let's imagine forty seven years from now where it's
really been researched and it really works well and you
know exactly the solution to profuse into the brain to
restore the function. So, first of all, what's your guest
about how many hours let's say you find somebody who
has passed away ten hours ago. Is that too late?
Speaker 3 (32:53):
That's a difficult question to answer.
Speaker 2 (32:56):
We do know that their process is still ongoing then
after death, but I don't believe that you can sum
certain processes that hip on it those time points to
the whole human being. So I don't see that happening.
I think there is definitely like a time limit, you know,
if you think about the current practice now, which is
(33:18):
in minutes. So basically, whatever V do, we would be
a huge feit really difficult.
Speaker 1 (33:25):
Absolutely, So I just want to press one more time
on this issue about what are the ethical questions that
come up for you. So let's imagine forty seven years
from now, the technology works great, and the question is, Okay,
somebody has passed away, how do we decide about restoring them,
whether it's the right thing to do when when it's not.
Speaker 3 (33:45):
Yeah, so this is a really complex question.
Speaker 2 (33:50):
There are bodies that deal with the definition of death,
and one thing in particular there which is interesting is
a distinction between something that's reversible and something that's permanent.
And I think it is going to be really interesting
to understand like which one is which, because there are
instances where you know, brain can get completely destroyed and
(34:12):
then you can die because your brain was destroyed, like right,
So there's no point in doing that is a permanent
death by itself. So if you go to a cardiac arrest,
if your heart stops, so then actually your brain is
going to die because your heart has stopped, like right.
So there are instances where it makes sense from the
(34:34):
clinical point of view to intervene in the future, like
assuming that this technology is effective.
Speaker 1 (34:40):
Okay, great, and I assume that there will be bodies
of philosophers and so on who get involved with this
question about when is it the right thing to do?
When does it make sense?
Speaker 2 (34:50):
Absolutely so yeah, So we hit with both publications, we
hit commentary work actually on this particular topic.
Speaker 3 (34:59):
And I think it's really interesting to see how the
field is developing now and how people are thinking now
with these new technologies that are coming to a right,
including ours and others. If you just think about now,
like I think last week or this week actually what
was done with transplants and other things.
Speaker 1 (35:33):
Here's a question for you. So you, as a scientist
and a physician, you're very careful about saying, you know,
if this works and this doesn't work yet, and so on.
But what is your guests in a century from now.
Let's say, do you feel like this is a dead
on winner, this is definitely going to work, or do
you feel there are some problems that are insurmountable.
Speaker 3 (35:56):
I'm positive that this is going to work. I think
we are going to it. I think we're developing new
tools now. I think our ideas about what death is
is changing. In particular, I'm referring to cells here, but
we can build a death like we can do like
a ground up approach.
Speaker 2 (36:12):
We can really develop new approaches and therapist I'm confident
that this is a field that is going to advance
in the future.
Speaker 1 (36:22):
Let me just double click on that. What do you
mean by we're having a new understanding of what death is?
Speaker 3 (36:27):
Well?
Speaker 2 (36:28):
As I said, you know, I went to med school
like recently, I still would like to think that I'm young,
although it's starting to show.
Speaker 3 (36:37):
I was thought that once there's blood laws, that sales
just die like after a couple of minutes.
Speaker 2 (36:44):
And you know, there have been like instances where people
have observed it in their work. But it's not this
reasoning or under tending that the death is a process
it's not ubiquitous, it's not widespread, and so you know,
taking data into account first and then start to do research.
Speaker 3 (37:02):
On these things. I think that's going to lead to
new tools and new developments.
Speaker 2 (37:07):
Just to give you like a simple example, we had
a so in in the team, we would always have
our electrophysiologists. So these are people who take slices of
tissue like right, and they record electrical properties from cells
from neurons. I remember one instance, we had a slide,
(37:27):
a really bad run, and sales were, like, you know,
they were not doing well.
Speaker 3 (37:31):
This was early on, and this new person came and
so he's looking at the cells in there around which
is usually a bad thing because they go from like
a triangle to like a rounding and so because so
he just goes like, oh, these cells are dead, because
he's accustomed to thinking that these cells are dead and
they're useless, like.
Speaker 2 (37:50):
Right, and so you know, so after a whole day
of work, we go like, maybe you should think about
these cells and maybe they're not dead yet, maybe they
can be saved.
Speaker 3 (37:59):
And so it's interesting, you know, from our point of view.
Speaker 2 (38:03):
He was new to the whole team, and so it's
really interesting like his perception of like one thing and ours.
It's basically like it's the glass like half full or
half empty situation.
Speaker 1 (38:14):
And have you been able to show that you can
take those bloated cells and reverse the processes?
Speaker 2 (38:21):
So absolutely, so this was the first So going back
to who were doing like initial research, that was the
first observation that we made. So because I trained in
radiology and so you know, you do an MRI in
the brain, like you know sort of like how the
signal is going to change based on the fake that
sales are becoming round or bloated. And so you know,
(38:42):
if we're looking these slices, like these cells and we're
seeing that they're not round, they're starting to regain their
their shape like right, And that was the first thing
we observed with the technology.
Speaker 1 (38:52):
So that's why, oh incredible, wow, what was that like
for you the first time you saw that reversal?
Speaker 2 (38:59):
The whole was really you know now with like a
benefit of the hindside, Like just for us, we started
in a closet like Atale University, we cleared out the
closet and we just started doing stuff there and it
went from like basic stuff because because people think that
when they think about research. They have these like grand
(39:20):
ideas of like you know, scientists and like fight codes
like doing some capitalists.
Speaker 3 (39:24):
This was such a completely opposite thing. And so you know,
you go through these motions daily twenty four to seven.
You're grinding, and you finally you start to see stuff.
Speaker 2 (39:36):
And then the first thing, like like the genuine first
thing is confusion because you see something.
Speaker 3 (39:41):
And you're like, well, this doesn't like go you know, it's.
Speaker 2 (39:44):
It's sort of go against the grain, right, So it's
like like what do I do now? And so it's
like a confusion and excitement because you want to be
sure that that you don't fool yourself, like that's the
biggest mistaked.
Speaker 3 (39:55):
You know, you can make. But you know, it was
really funny, you know, the whole thing. Yeah, it was
really fun.
Speaker 1 (40:01):
Wow, did you realize at that moment what you were
on the verge of because then you published paper. You know,
you've had really terrific publications that you've put out about
you know, the pig brain and the cellular functions. Did
you did you realize when you were first seeing that
what this was going to lead to?
Speaker 2 (40:17):
I you know, like if you still understand like where
these can go and there's always like something, you know,
like if you look at something and you like, oh,
like these capabilities are like new, you know, like these
implications are huge and it's still ongoing and potential.
Speaker 1 (40:35):
So that was Vonimir Russella. And it's clear that as
a community, our biological insights are opening up big new
questions for us. Now this really complicates things from a
clinical and legal perspective. Death is usually defined as the
cessation of biological functions. Traditionally this had to do with
(40:56):
the stopping of the breath and the stopping of the pulse,
but even that started to get complicated by the nineteen
fifties because people had invented ventilators so it didn't necessarily
matter if you stopped breathing, and people invented defibrillators so
they could get your heart going again, so that no
longer made sense to define death that way. And in
(41:19):
nineteen sixty eight Harvard Medical School got together to put
together a definition of brain death and they said, look,
if you are in a coma that's irreversible, then we'll
say you're dead. And different places took on different versions
of this until nineteen eighty when the United States came
up with a Uniform Determination of Death Act and they said, look,
(41:40):
you're dead if you've had an irreversible cessation of blood
flow and breathing, or an irreversible cessation of the function
of your brain. But the interesting thing is how interventions
could play a role here, because the key word that
needs to come under scrutiny is reversible. What do we do,
(42:02):
How do we redefine death when many problems are no
longer going to be irreversible. Now, I want to be clear,
there's still a long way to go with the science.
The work is underway in pigs, but no one's even
talking about humans at this point, in part because the
ethical questions are something we can't even wrap our heads around.
(42:25):
But the thing I want to point out is that
this is now a question. It is a scientific problem
being studied in the labs and published in the top journals.
It'll be a long while before you hear about this
past the walls of the lab, but it's coming. So
consider this in the context of recent history. When Mary
(42:47):
Shelley wrote her novel Frankenstein that was just over two
hundred years ago, it was cast as a warning against
the dangers of playing God. But it's fascinating to see
how the concept of playing god evolved. After all, you
can imagine a time when someone might have said, Hey,
if you crack open someone's chest and operate on their heart,
(43:08):
you're playing God. Or if you take out someone's heart
entirely and replace it with an artificial, pulseless blood pump,
you are playing God. Or what about doing an open
head surgery to cut out a brain tumor playing god?
Or injecting someone with a medication that reverses at the
level of invisibly small molecules whatever process in their body
(43:31):
is making them sick. You can imagine any moment in
history where someone would have looked at this and said,
you're messing with the body and playing the role of
a deity. But when we look at the long arc
of human understanding of science, we see this is the
natural direction of things. As we come to understand that
(43:52):
the heart is just a pump, we can fix it
or replace it. Once we understand what a tumor is
a cell that keep dividing out of control, we can
learn how to open the skull and control the bleeding
of the brain tissue, and the whole issue of tumor
removal becomes routine. Once we know how molecular cascades work,
(44:13):
then we put them in the textbooks of high school students,
and we find drugs that interact with those cascades, and
we don't think twice about this stuff. We don't think
about it as deity playing, just that someone is hurt
or sick and needs our help, and that this is
some operation or medication that we now understand that we
(44:34):
didn't used to. So John Dunn, who died in sixteen
thirty one, coming up on four hundred years ago, could
have never imagined that when he penned the poem death
Be not Proud, that we'd actually be talking about the
end of death as just a molecular puzzle about which
we say not now, but at some point, okay, we
(44:57):
got it. Just block these pathways by which die or
commit suicide, and then these cells stay alive and the
whole system just keeps on trucking. And he could never
imagined that we'd even be talking about rebooting a system
that has already ground to a halt. Now. Mary Shelley
(45:17):
died in the mid nineteenth century, two centuries after done,
and most of us will see the mid twenty first century,
two centuries after Mary Shelley, and it looks likely that we,
or our children or our near term descendants will be
the first to see Shelley's ethical questions get tackled. Should
(45:37):
we revivify a system that's come to a halt under
what circumstances? What will be the consequences for society as
a community will come to address Shelley's questions not as
a science fiction fantasy, but as a basic challenge of
passing the right legislation and determining how hospital ethics committees
(45:59):
should make their decay decisions about reversing death. And there
might be whole groups of people that are your friends
and neighbors and work colleagues, and some of them will
have ground to a halt. At some point they're revivified,
just as you currently have friends and neighbors and colleagues
who were under anesthesia and woke up, or they had
a heart attack and had their heart defibrillated, or they
(46:20):
were in a coma for weeks and regained consciousness. And
at some point we'll all live in this new world
where we have to address whole new fields of question marks.
Because as John Dunn predicted death will have died. Go
(46:41):
to eagleman dot com slash podcast for more information and
to find further reading. Send me an email at podcasts
at eagleman dot com with questions or discussions, and I'll
be making sporadic episodes in which I address those until
next time. I'm David Eagleman, and this is Inner Cosmos
From the point of view of biology, what is life
and what is death and what is the line between them?
Could you freeze your body to come back sometime in
the future, and what does this have to do with
Mary Shelley's Frankenstein or housefly or the poet John Dunn.
(00:28):
Welcome to Inner Cosmos with me David Eagleman. I'm a
neuroscientist and an author at Stanford and in these episodes
we sail deeply into our three pound universe to understand
why and how our lives look the way they do,
and in this case, whether life is something that comes
to an end inevitably or only because we don't understand
(00:52):
the biology well enough yet. So today day's episode is
about understanding what happens when your molecular cycles grind to
a halt, and whether there's anything we can do to
hit control z on that can death be reversed. A
(01:18):
few months ago, my dog was lying on the floor
and we were all gathered around her, and my kids
were coming in and out, and everyone was crying because
my dog was dying. She was fifteen and a half
years old, which for a dog her size was quite old,
and her body was shutting down and as I sat
(01:38):
on the floor stroking her back, I was thinking about
a poem by John Dunn that I had first read
when I was a child, probably about ten years old.
The poem is called Death Be Not Proud, and it
really blew my young mind when I read it. It
begins with these lines, death be not proud, though some
(01:59):
have called thee mighty and dreadful, for thou art not
so now. In this poem, one of his nineteen holy sonnets,
Done gets right up in Death's face and he challenges
Death's power and importance, and he tells death not to
be proud because it is not as fearsome as it
(02:20):
might seem. And the sonnet ends with the lines one
short sleep past, we wake eternally, and death shall be
no more death, thou shalt die so. Done ends the
poem by spitting right in death's champagne glass, and he
tells Death that he is going to die now. John
(02:44):
Dunn wrote this poem through a religious lens. He was
giving the interpretation of the victory of the soul over death.
But I had a different interpretation. I was struck by
this idea of defeating death. After all, biologists, we study
life and each decade we know more and more about
(03:06):
how it works, and the more we know about life,
the more we can know about how to keep it
going and possibly how to even reboot it. Now that
sounds crazy, but we're going to unpack that carefully in
this episode. There are many ways to look at what
life is. I did an on stage conversation some years
(03:28):
ago with a mystic named Saguru, and we discussed and
debated a number of issues, but he said one thing
that was phrased very simply, and it proved hard for
me to forget. He said, the physical body is like
a fruit, and when the person is gone, the person
that you loved, all you have left now is the rind.
(03:51):
There's nothing special about the body, the physical body, and
I loved that description, but as a biologist, I wanted
to dig deeper. And this is a problem I had
actually started thinking about years earlier, because I once went
to wash a dish in the sink and there was
a tupperware in there with some water in it, and
(04:11):
there was a house fly that had died in the tupperware.
And I looked at the poor little lifeless fly, and
a question struck me, What is the difference between the
live fly and the dead fly. If you do a
chemical analysis, it's exactly the same stuff. You have x
number of carbon atoms in the quadrillions or ten to
(04:35):
the eighteenth, and you have Y number of nitrogen atoms,
and you have Z number of oxygen atoms, and so on.
The weight of this little dead fly is exactly the
same as a living fly. The chemical composition is the same,
All the trillions of proteins are the same. Everything is
the same between the living fly and the dead fly.
(04:58):
The only different is the molecular momentum. All the cascades
have come to a stop. All the crebs cycles and
the action of the proteins around the DNA and the
endoplasmic particulum, and all the step by step chemical reactions
in the cell, they've all just come to a standstill.
(05:22):
So what Saguru referred to as the fruit to the
part we love and lament I interpret this as the
ongoing cascades of the cellular processes. This leads to this
leads to this, and as long as everything keeps going,
then the fly is alive and it moves around. As
soon as something breaks about these cycles, then everything just
(05:45):
grinds to a halt. So this leads to the question
what does it require to keep everything going for cells
to stay alive? And the related question is if they stopped,
would there be any way to you reboot the system
to get the cycles going again. So when I read
(06:06):
Dunn's poem as a kid, where he says that death
shall die, I imagined that someday, in the very distant
sci fi future, we might actually be able to make
this true, to get cells going again that had come
to a stop. But of course, when imagining this future
as a kid, you imagine it as people in silver
(06:27):
suits zipping around in the skies. So as I got
older and studied biology and became more realistic about this,
I realized, of course that we were all going to
die after all. So given that perspective about how distantly
in the future this would happen, you can imagine how
(06:48):
surprised I was to see the speed at which this
field is moving along. I suspect that I will die
and perhaps the next few or several generations. But the
idea of reversing deaths, at least in some cases, is
not a subject constrained to the pens of poets. Anymore.
(07:09):
Over the past several years, you can find the beginnings
of this endeavor published in the top scientific journals. And
we're not talking about longevity in this episode. I'm going
to talk about that in the future episode. Instead, we're
talking about this completely wacky idea of reversing death, taking
(07:29):
an organism that has already died, and reversing back out
of that. Now, this sounds like something straight out of
Mary Shelley's novel Frankenstein, which, as you remember, tells the
story of a scientist named Victor Frankenstein who figures out
how to reanimate the dead. But the whole thing doesn't
(07:49):
turn out so well, and Frankenstein's monster ends up getting
rejected by mankind in general, and he regretfully murders people
to get revenge on his maker. But anyway, put that
interpretation aside for a moment while we talk about this,
because in the early twenty first century, we're now in
a more realistic position to assess what is possible and
(08:13):
to think deeply about the ethics. Now, it may sound
surprising that there's enough science now to even talk about
this topic, but hangtight, because we're about to see some
very strange stuff. First, this question of whether death could
be reversible has long been entertained, because sometimes people can
(08:34):
fall to the bottom of a lake and freeze to
death and lose all their function, and they are really
truly at a stop, and then sometimes they can be
brought to a hospital and revivified. For example, I remember
reading a story in two thousand about a young doctor
in Norway named Anna. She was a trainee surgeon who
(08:55):
was exactly my age, and she was skiing when she
fell through a rosen river and got trapped under the ice. Now,
her colleagues were there and they saw her, but they
couldn't get her out, and they struggled and struggled to
rescue her. But she ended up being under the ice
for forty minutes, and not surprisingly, her organs shut down
(09:18):
and she died. Her body temperature had fallen more than
twenty three degrees below normal. But Anna was eventually pulled
out from the ice and put on an air ambulance,
and she wasn't breathing when she got to the hospital.
Her blood circulation had stopped, her pupils were not responding
to light, but the doctors put her on a heart
(09:41):
and lung machine and re warmed her while the circulation
was kept going. They used a machine that warmed her
blood and oxygenated it and then put it back in
her body, and things weren't easy. She spent sixty days
in intensive care in the hospital, but five months after
she was frozen to death, she was back to work
(10:02):
as a doctor and she still skis now. You can
find this case in the Lancet, which is a top
medical journal in the field. So this stuff happens, and
it happens more than you might think. I read another
article in twenty sixteen about a guy walking home from
a party and he slipped and hit his head and
went unconscious and wasn't found until the next morning when
(10:24):
his father was driving around looking for him and found
him buried in the snow, frozen, no vital signs. They
rushed him to the hospital. They pumped him full of warm,
oxygenated blood, and it wasn't an easy recovery. But a
year later, even though he's missing all his toes and
pinkies from frostbite, he is indistinguishable from anyone else you
(10:49):
might meet. Essentially, he was frozen in the same way
that we might put meat in the freezer, so it
doesn't go bad. But it's the same principle. Despite our
sense of our beautiful essences, it's also the case that
we are meat and we can be frozen and we
can be thawed. Now, why can't you revivify any person
(11:11):
who has died. Well, if things aren't frozen, then the
biology decomposes, the cells break down. This is of course
the same thing that happens if you leave a piece
of meat on your counter instead of putting it in
the freezer, and in the case of a person, that
causes irreversible damage to the brain. But a frozen body
(11:32):
doesn't decay, at least not rapidly. It stays intact because
the molecules can't move around as much. Everything is held
into place. So the observation that people could be frozen
and unfrozen got scientists interested in the speculation of whether
you could take a person who has just died and
(11:52):
freeze them on purpose, with the idea of unfreezing them later.
And this successfully started in the nineteen in seventies with
freezing mouse embryos, and then that became a successful way
to freeze human embryos. But keep in mind a human
embryo is the size of a grain of salt, and
so the challenges are a little less in successfully freezing
(12:16):
and unfreezing those. But the question people have been asking is,
could you actually freeze an entire adult body and unfreeze
it later, Let's say, because they have cancer that we
don't know how to cure. But maybe in seventy years
the medical community will have no problem curing this. It'll
be easy. Could you reanimate somebody in the same way
(12:38):
that has been done on a much shorter timescale with
the woman in the icy river or the man who
fell into the snow bank. Well, in a previous episode,
I mentioned a company in Arizona called Alcore, which strives
to do exactly this. They are a cryogenics company, and
upon your death, they will swoop in to perfuse your
(13:01):
body with the right chemicals and get you to the
facility in Arizona, and there they will lower you into
a vat of liquid nitrogen. Now, do they know how
to cure whatever your disease was, or, for that matter,
do they even know how to unfreeze you successfully? No,
But that's not the point. The point is that sometime
(13:21):
in the distant future, our great grand descendants may know
how to do this, and at that point they can
unfreeze you and cure you of whatever ailment you have,
presumably something that was totally opaque or confusing for twenty
first century minds, but easily curable with a twenty second
(13:41):
century toolbox. Now here's something of interest. It turns out
the first person to ever get frozen on purpose in
this new field called cryogenics was born in what year,
take a guess, eighteen ninety three, a guy named James
Bedford who died in January of nineteen sixty seven from
(14:02):
terminal cancer. He was the first person to do this.
But did he die? Interesting question? I would say unresolved
so far, because it's yet to be seen whether he
can be rebooted nineteen sixty seven. So although this is
science fiction y, it's not even that new. Now. Since
that time, people have worked on the cryogenic technology to
(14:26):
figure out how to make the freezing process better and
better to prevent cell damage, because the problem is if
you get an ice crystal during the freezing process, that
will rupture the cell membrane and then the body that
you hoped to revive is too damaged. Like when you
stick a strawberry in the freezer to try to make
(14:47):
it last longer. But once you unthought, it gets all mushy.
That's the same thing that happens with any cells if
they get ice crystals in it. So will Bedford's body
be able to be reanimated? Who knows? And experts have
different opinions about whether the bodies at the alcore facility
will be reeve vivifiable. But the idea of cryogenics is
(15:09):
straightforward in the sense that even if these first few
hundred experiments fail, will surely get better and better at
cryogenics in the future, and the hope is that someone
fifty generations from now will know how to reverse the process.
And before I go to the next step, I just
want to say this idea about confronting death is not
(15:32):
just about freezing and unfreezing. The deeper issues in biology
have to do with how individual cells die. It turns
out that cells can get injured by various things, let's say,
a lack of blood flow or a chemical insult, and
then they essentially blow up and die and cause a
lot of inflammation. This is called necrosis. But in nineteen
(15:55):
seventy two it was discovered that this isn't the way
cells have to die. Cells can actually die on purpose,
and this is known as a potosis. A potosis means
that instead of a cell simply just falling apart, instead
it implements a controlled process by which it folds up
(16:15):
shop and cleanly commits suicide. Scientists came to understand that
this is a very purposeful process, and over many years
they showed how apotosis is actually the way that biological
organisms structure themselves. For example, a human embryo has webbed fingers,
in other words, little sheets of skin between the fingers
(16:38):
of exactly the type that you would need for swimming.
But in the case of our particular species, the cells
making up that webbing. Those cells die off before the
baby is born, such that we have independently moving fingers.
But those cells between our fingers wouldn't die off if
we were another mammal, say a bat, or a kangaroo,
(17:00):
or a whale or a manatee. I'm actually going to
put an X ray picture of a manatee fin on
my website because it's so stunning how the bones inside
their fin look just like a human hand. The bones
look that way, but the difference is that the cells
between their fingers, that webbing that doesn't die off, so
(17:20):
what you get is a fin Anyway, apotosis is everywhere.
Your body has about a trillion new cells developing every day,
and so you need to kill off a similar number
to keep the system from getting overrun. And this is
all done with this very controlled process of cell death.
(17:41):
And the scientists behind these discoveries Horbitz and Brenner and Sulstan.
They won the Nobel Prize for this in two thousand
and two. But it turns out since then biologists have
discovered that necrosis and apotosis are not even the only
game in town. We now know there are many flavors
of program cell death, like what's called pyrotosis or ferrotosis
(18:05):
or necrotosis. These are all different mechanisms that tip the
balance between different cell fates, and people are working on
drugs to block all these very specific flavors of cell death.
It's no longer just the cell gets sick and falls apart,
but it's much more sophisticated now and that gives the
(18:26):
possibility to molecularly block the process. So now let zoom
out to the big picture. There's an increasing amount known
about how cells actually shut down, and we have proof
of principle that systems can get going again even after
they've stopped. And all this has led to the possibility
(18:48):
that we might be able to take something like a
dead brain or dead body and reboot it. Now this
sounds so crazy, but the question I want to ask
is are we actually going to have to wait fifty
generations to see this happen? Or is it possible that
things are moving so rapidly that there's some reason to
think that we could take, say, a dead brain, a
(19:11):
totally dead brain that's been dead for four hours, and
get the whole factory running again. Well you'd agree that
seems like a science fiction fantasy. But a colleague of
mine recently published two papers in the journal Nature, and
it seems we're already at the point, give or take,
where we may be able to do something just about
(19:32):
like that, at least in pigs. In the journals, this
is cast in the paper as quote Cellular and molecular
recovery in pigs, which I suspect doesn't sound that interesting
to most people on the planet, and so it didn't
get that much attention. But this is seriously big stuff.
So I called up my colleague who wrote these recent papers,
(19:52):
and I asked him, is cell death inevitable? Let's say
when a person has a stroke and there's no blood
going to the set. Well, we've always thought of that
as being a really terrible scenario that inevitably leads to
sell death. But is that the case?
Speaker 2 (20:25):
So we used to think that, and we had a
publication four years ago where we actually christened if sales
actually die after death after blood flow stops, and we
realized that actually death is a portracted process. It takes
a bit actually for sales to die, and if you
intervene properly, you can maybe reverse those processes.
Speaker 1 (20:47):
That's Vanimir Russella. He's an mdphd originally from Croatia. He
did his postalk and became a research scientist at Yale
School of Medicine, and now he's spun off a company
around this called Becksore. So you mean the death of
an organism, let's say, of a person. You're saying it
(21:09):
doesn't happen all at once, but it takes time to die.
Speaker 2 (21:14):
So yeah, yeah, So I think I just want to
be like a nuance here. There were instances that so
it is well known that For example, you can find
living cells in human specimens after hours of death, and
scientists have used like chunks of tissue to find like
living sales and record from them.
Speaker 3 (21:33):
It was also observed.
Speaker 2 (21:34):
That people who have died and were undercolt conditions that
they could be actually brought sort of The implication there
is that there are cells o functional. So there were
instances where this was a scene and recorded in the literature.
Speaker 1 (21:50):
So let's just double click on that. So tell us
what you mean about people who were frozen and were recovered.
Speaker 2 (21:57):
Give us an example, So on the macros kale, like right,
talking about the whole human, not about.
Speaker 3 (22:03):
A single cell. It was observed that people.
Speaker 2 (22:05):
Who have drowned their bodies would cool down as they
were drowning, that after a prolonged period of time, these
people could be resuscitated. So the time it was, you know,
we are not used as seeing like someone resuscitated after
that how long, Well, I don't know specifics, but just
to give you like a benchmark data point. Usually it
(22:28):
is assumed from the classical literature that four minutes after
blood flow stops, bodies cells just die.
Speaker 3 (22:35):
So that was.
Speaker 2 (22:36):
Always like a clinical data point, after which was really
difficult to bring people back with resuscitation.
Speaker 1 (22:45):
Okay, so you started suspecting that maybe cells aren't as
fragile as we thought. So what did you do?
Speaker 2 (22:53):
So yeah, so we have it's interesting storied up my
pi at the time. And then a Sistan received a
tissue specimens from abroad and they got stuck at customs
for a really long period of time. And so by
the time they came in the lab, you know, the
(23:14):
researchers were like thinking, oh.
Speaker 3 (23:16):
You know, it's done, like the specimen is useless.
Speaker 2 (23:19):
But they still made slice sculptures and after a week
they realized that they were living cells.
Speaker 3 (23:24):
So that was the first observation that got the group like.
Speaker 2 (23:28):
Thinking, and in our case in particular, we just wanted
to scale the whole approach, initially going from a small.
Speaker 3 (23:35):
Slice to a whole inteked brain.
Speaker 1 (23:38):
Right, So you said, hey, what if you could get
a brain of an organism that has died, could you
restore the function somehow? So what did you do to
try to tackle that problem?
Speaker 3 (23:52):
So, you know, as one does, we started going to
a local slaughterhouse and we were procuring a tissue.
Speaker 1 (24:00):
You were getting pig brains, right, pig reins.
Speaker 2 (24:02):
Yes, so people don't. Luckily there we are like, people
don't eat the pig brains.
Speaker 1 (24:07):
And this was the el right, yes, yes, yes, yes.
Speaker 3 (24:10):
Yes, So we will go to the local slaughterhouse. You know,
they would do their job.
Speaker 2 (24:15):
By the time when they are done, we would get
pig hits and so we'll bring them to the lab.
Speaker 3 (24:20):
We would take the brain out, and.
Speaker 2 (24:23):
Then we started developing this technology that could connect with
the vascular system of the brain and profuse a fluid
to sort of reboot the self functionality.
Speaker 1 (24:34):
And how long had these pigs been dead?
Speaker 3 (24:37):
On every g it was four hours, So from the
time of pig being killed in the slaughterhouse to the
time point where we started our profusion intervention, it was
usually four hours.
Speaker 1 (24:50):
So then what you did is you profused and tell
us about profusion and what that means and what that
looks like.
Speaker 2 (24:57):
So there's a device, so you take the isolated brain,
which is sort of front of you. You load the
brain into this device and then the device pushes artificial
blood or blood like fluid through the brain and it
does it under controlled conditions. It has a bunch of
drugs inside that counter certain cell processes. So the whole
(25:21):
point is to try to reinstate homeosthetic environment or this
like like normal environment in which cells are usually accustomed.
Speaker 1 (25:31):
To be and so what did you find?
Speaker 2 (25:34):
So we found that So this is an interesting equation.
So first of all, we found that we could revert
cell death. It was an interesting thing because at the
time we were trying to define like what does it
mean for a cell to be dead, like right, and
how do you define cell death? So we found it
cells that were considered dead they were actually still some adjective.
(25:57):
And with our interventions we could restore or functionality and
observed functions in those cells that we usually observe in
cells that we sort of think or consider alive.
Speaker 1 (26:08):
So were the cells completely restored or are there still
things you need to do to get to the next level.
Speaker 3 (26:18):
There is a lot more to do there.
Speaker 2 (26:20):
What we have done we took a particular number of
tests and we conducted those tests and so I can
only speak about those.
Speaker 3 (26:29):
They were pretty good broad tests that sort of speak
on the state of these cells. So these same tests
show that these cells performed in a similar way as
normal cells.
Speaker 2 (26:40):
And on top of it, with subsequent research data was done,
we actually showed that it's clear that these cells go
through stress of dying. So we've shown that we can
stop it, and we even showed on the molecular scale
that we can basically persuade sales like not to die
and they can start to repair themselves and basically just
(27:01):
say to them like, don't die, like they just want
to live, you know.
Speaker 1 (27:05):
So you take a pig brain that's been dead for
four hours and you perfuse this this solution through it.
It's like blood, but it doesn't have cells in it.
It has lots of meds and the proper kind of
molecules in it. You push that through and then you
can measure things about the cells and see that it's
like they're cooking along. They're doing their thing that cells
(27:26):
normally do.
Speaker 3 (27:28):
Absolutely.
Speaker 2 (27:28):
So the point is like, you know, you just go
to like meet school biology and it's you know, you
see if oxygen is going in, you see if glucose
is going in, so you're expecting CO two to come out,
so you know that's happening, and then you compare those results.
Speaker 3 (27:44):
I'm simplifying this, but you know, conceptually it works.
Speaker 2 (27:48):
You can provide stimuli or for example, drugs because you know,
like you can take a drug, which we have done actually,
so we would take a drug that works in humans,
it's well known, and we would see if it's exerting
the same effect in these restored cells.
Speaker 3 (28:02):
And it worked.
Speaker 2 (28:02):
So these cells can also be like stimulated and you
can observe how they respond. You can compare those responses
and learn about the brain, you know.
Speaker 1 (28:11):
And so you have been doing this in pig brains
since the first paper you did was in twenty nineteen
or yes, okay, so you've been doing it in pig
brains since then. What is the road that you see
two human brains?
Speaker 2 (28:27):
So this is a new type of research, and we
were pretty lucky from day one to have ANIH and
other institutions Yale including involved in helping us put the
guidelines and think about like where this research should go
and how it should be conducted. So what we have
done we really wanted to build like a ground up approach,
(28:49):
and so we wanted to show that these interventions are
opening new spaces, and so we went to do it
in the smart way. So that said going to humans
and what it really means, you know, think about like
restoring cells and their function, like you can think about
clinical applications of the technology like SOAK is the first
thing that comes to one mind.
Speaker 3 (29:09):
So it will take a bit more time to get there.
Speaker 2 (29:12):
Because we need to really understand, like deeply what's going
on on the cellular level.
Speaker 3 (29:16):
But this is one approach.
Speaker 2 (29:17):
Another approach that we have taken was in collaboration with
a transplant team here at Yale. So we actually wanted
to see if we could deploy our technology in dead pigs.
Speaker 3 (29:28):
Essentially and see if we could restore like kidneys or
liver for transplant.
Speaker 2 (29:34):
Because if this works in the clinical sense, then there
is a chance to readically expand organ pool or organ donations.
Speaker 1 (29:43):
Oh incredible. And when it comes to restoring the brain,
when you think down the road, you think ten twenty
years in the future, what are the ethical questions here?
Speaker 3 (29:53):
Well they are big. So the first thing is clearly,
are we sort of rebooting this brain like big where
it was. I'm really particular how I speak about these things,
So I talk about sales, I don't actually talk about
brain function. The reason is because we are making sure
that we are not rebooting global network or EG. But
(30:18):
one could go in that phase. So that is definitely
something that can be explored.
Speaker 2 (30:23):
So now you can think about all the ethical implications
that our eyes with this technology.
Speaker 1 (30:29):
So you said you're being careful not to reboot the
function of the brain. Correct me if I'm wrong, But
you're not actually sure when or why that would happen.
It's just that in the experience you've done so far,
the electrical signaling, the global functioning the brain wasn't restored
in the pigs, but we don't know why that's the case,
and it could happen with another few molecules or whatever
(30:51):
of the right flavor.
Speaker 2 (30:53):
Absolutely, so there is research already showing thatta done in
the pace that this could be done. And also in
our case, it is basically the design of the experiments.
Our experiments we were actively suppressing or we were avoiding
that situation because even without the network being rewooted, we
(31:16):
still have an extremely valuable tool to understand how the
brain works and functions. So in the future, the question
has definitely been the technology, as you said, been the
technology is matured and we actually know exactly every single
thing that goes into it and what happens, then the
question is like what should be done next?
Speaker 1 (31:34):
And so what do you think about that, what are
your thoughts on the ethics of you know, somebody has
found drowned at the bottom of a lake and it's
four hours later and you say, hey, I've got a
solution here to bring this person back.
Speaker 4 (31:48):
Oh yeah, so definitely not now, and technologically and our understanding,
we're just not there yet, and there's a lot of
research that has to be done. I think it also
been comes an interesting.
Speaker 2 (32:01):
Question like assuming that the technology is capable of doing
such a feit, you know, you have a question from
you like should you do this?
Speaker 3 (32:11):
Like should you go and save this person? I'm a
trained physician, so that's the goal. You know, you want
to go and save someone. So this should become just
another tool that allows us to do our job. So,
but it needs to be it really needs to be
researched over time and show that there is value and
potential for this outcome.
Speaker 1 (32:31):
So let's imagine forty seven years from now where it's
really been researched and it really works well and you
know exactly the solution to profuse into the brain to
restore the function. So, first of all, what's your guest
about how many hours let's say you find somebody who
has passed away ten hours ago. Is that too late?
Speaker 3 (32:53):
That's a difficult question to answer.
Speaker 2 (32:56):
We do know that their process is still ongoing then
after death, but I don't believe that you can sum
certain processes that hip on it those time points to
the whole human being. So I don't see that happening.
I think there is definitely like a time limit, you know,
if you think about the current practice now, which is
(33:18):
in minutes. So basically, whatever V do, we would be
a huge feit really difficult.
Speaker 1 (33:25):
Absolutely, So I just want to press one more time
on this issue about what are the ethical questions that
come up for you. So let's imagine forty seven years
from now, the technology works great, and the question is, Okay,
somebody has passed away, how do we decide about restoring them,
whether it's the right thing to do when when it's not.
Speaker 3 (33:45):
Yeah, so this is a really complex question.
Speaker 2 (33:50):
There are bodies that deal with the definition of death,
and one thing in particular there which is interesting is
a distinction between something that's reversible and something that's permanent.
And I think it is going to be really interesting
to understand like which one is which, because there are
instances where you know, brain can get completely destroyed and
(34:12):
then you can die because your brain was destroyed, like right,
So there's no point in doing that is a permanent
death by itself. So if you go to a cardiac arrest,
if your heart stops, so then actually your brain is
going to die because your heart has stopped, like right.
So there are instances where it makes sense from the
(34:34):
clinical point of view to intervene in the future, like
assuming that this technology is effective.
Speaker 1 (34:40):
Okay, great, and I assume that there will be bodies
of philosophers and so on who get involved with this
question about when is it the right thing to do?
When does it make sense?
Speaker 2 (34:50):
Absolutely so yeah, So we hit with both publications, we
hit commentary work actually on this particular topic.
Speaker 3 (34:59):
And I think it's really interesting to see how the
field is developing now and how people are thinking now
with these new technologies that are coming to a right,
including ours and others. If you just think about now,
like I think last week or this week actually what
was done with transplants and other things.
Speaker 1 (35:33):
Here's a question for you. So you, as a scientist
and a physician, you're very careful about saying, you know,
if this works and this doesn't work yet, and so on.
But what is your guests in a century from now.
Let's say, do you feel like this is a dead
on winner, this is definitely going to work, or do
you feel there are some problems that are insurmountable.
Speaker 3 (35:56):
I'm positive that this is going to work. I think
we are going to it. I think we're developing new
tools now. I think our ideas about what death is
is changing. In particular, I'm referring to cells here, but
we can build a death like we can do like
a ground up approach.
Speaker 2 (36:12):
We can really develop new approaches and therapist I'm confident
that this is a field that is going to advance
in the future.
Speaker 1 (36:22):
Let me just double click on that. What do you
mean by we're having a new understanding of what death is?
Speaker 3 (36:27):
Well?
Speaker 2 (36:28):
As I said, you know, I went to med school
like recently, I still would like to think that I'm young,
although it's starting to show.
Speaker 3 (36:37):
I was thought that once there's blood laws, that sales
just die like after a couple of minutes.
Speaker 2 (36:44):
And you know, there have been like instances where people
have observed it in their work. But it's not this
reasoning or under tending that the death is a process
it's not ubiquitous, it's not widespread, and so you know,
taking data into account first and then start to do research.
Speaker 3 (37:02):
On these things. I think that's going to lead to
new tools and new developments.
Speaker 2 (37:07):
Just to give you like a simple example, we had
a so in in the team, we would always have
our electrophysiologists. So these are people who take slices of
tissue like right, and they record electrical properties from cells
from neurons. I remember one instance, we had a slide,
(37:27):
a really bad run, and sales were, like, you know,
they were not doing well.
Speaker 3 (37:31):
This was early on, and this new person came and
so he's looking at the cells in there around which
is usually a bad thing because they go from like
a triangle to like a rounding and so because so
he just goes like, oh, these cells are dead, because
he's accustomed to thinking that these cells are dead and
they're useless, like.
Speaker 2 (37:50):
Right, and so you know, so after a whole day
of work, we go like, maybe you should think about
these cells and maybe they're not dead yet, maybe they
can be saved.
Speaker 3 (37:59):
And so it's interesting, you know, from our point of view.
Speaker 2 (38:03):
He was new to the whole team, and so it's
really interesting like his perception of like one thing and ours.
It's basically like it's the glass like half full or
half empty situation.
Speaker 1 (38:14):
And have you been able to show that you can
take those bloated cells and reverse the processes?
Speaker 2 (38:21):
So absolutely, so this was the first So going back
to who were doing like initial research, that was the
first observation that we made. So because I trained in
radiology and so you know, you do an MRI in
the brain, like you know sort of like how the
signal is going to change based on the fake that
sales are becoming round or bloated. And so you know,
(38:42):
if we're looking these slices, like these cells and we're
seeing that they're not round, they're starting to regain their
their shape like right, And that was the first thing
we observed with the technology.
Speaker 1 (38:52):
So that's why, oh incredible, wow, what was that like
for you the first time you saw that reversal?
Speaker 2 (38:59):
The whole was really you know now with like a
benefit of the hindside, Like just for us, we started
in a closet like Atale University, we cleared out the
closet and we just started doing stuff there and it
went from like basic stuff because because people think that
when they think about research. They have these like grand
(39:20):
ideas of like you know, scientists and like fight codes
like doing some capitalists.
Speaker 3 (39:24):
This was such a completely opposite thing. And so you know,
you go through these motions daily twenty four to seven.
You're grinding, and you finally you start to see stuff.
Speaker 2 (39:36):
And then the first thing, like like the genuine first
thing is confusion because you see something.
Speaker 3 (39:41):
And you're like, well, this doesn't like go you know, it's.
Speaker 2 (39:44):
It's sort of go against the grain, right, So it's
like like what do I do now? And so it's
like a confusion and excitement because you want to be
sure that that you don't fool yourself, like that's the
biggest mistaked.
Speaker 3 (39:55):
You know, you can make. But you know, it was
really funny, you know, the whole thing. Yeah, it was
really fun.
Speaker 1 (40:01):
Wow, did you realize at that moment what you were
on the verge of because then you published paper. You know,
you've had really terrific publications that you've put out about
you know, the pig brain and the cellular functions. Did
you did you realize when you were first seeing that
what this was going to lead to?
Speaker 2 (40:17):
I you know, like if you still understand like where
these can go and there's always like something, you know,
like if you look at something and you like, oh,
like these capabilities are like new, you know, like these
implications are huge and it's still ongoing and potential.
Speaker 1 (40:35):
So that was Vonimir Russella. And it's clear that as
a community, our biological insights are opening up big new
questions for us. Now this really complicates things from a
clinical and legal perspective. Death is usually defined as the
cessation of biological functions. Traditionally this had to do with
(40:56):
the stopping of the breath and the stopping of the pulse,
but even that started to get complicated by the nineteen
fifties because people had invented ventilators so it didn't necessarily
matter if you stopped breathing, and people invented defibrillators so
they could get your heart going again, so that no
longer made sense to define death that way. And in
(41:19):
nineteen sixty eight Harvard Medical School got together to put
together a definition of brain death and they said, look,
if you are in a coma that's irreversible, then we'll
say you're dead. And different places took on different versions
of this until nineteen eighty when the United States came
up with a Uniform Determination of Death Act and they said, look,
(41:40):
you're dead if you've had an irreversible cessation of blood
flow and breathing, or an irreversible cessation of the function
of your brain. But the interesting thing is how interventions
could play a role here, because the key word that
needs to come under scrutiny is reversible. What do we do,
(42:02):
How do we redefine death when many problems are no
longer going to be irreversible. Now, I want to be clear,
there's still a long way to go with the science.
The work is underway in pigs, but no one's even
talking about humans at this point, in part because the
ethical questions are something we can't even wrap our heads around.
(42:25):
But the thing I want to point out is that
this is now a question. It is a scientific problem
being studied in the labs and published in the top journals.
It'll be a long while before you hear about this
past the walls of the lab, but it's coming. So
consider this in the context of recent history. When Mary
(42:47):
Shelley wrote her novel Frankenstein that was just over two
hundred years ago, it was cast as a warning against
the dangers of playing God. But it's fascinating to see
how the concept of playing god evolved. After all, you
can imagine a time when someone might have said, Hey,
if you crack open someone's chest and operate on their heart,
(43:08):
you're playing God. Or if you take out someone's heart
entirely and replace it with an artificial, pulseless blood pump,
you are playing God. Or what about doing an open
head surgery to cut out a brain tumor playing god?
Or injecting someone with a medication that reverses at the
level of invisibly small molecules whatever process in their body
(43:31):
is making them sick. You can imagine any moment in
history where someone would have looked at this and said,
you're messing with the body and playing the role of
a deity. But when we look at the long arc
of human understanding of science, we see this is the
natural direction of things. As we come to understand that
(43:52):
the heart is just a pump, we can fix it
or replace it. Once we understand what a tumor is
a cell that keep dividing out of control, we can
learn how to open the skull and control the bleeding
of the brain tissue, and the whole issue of tumor
removal becomes routine. Once we know how molecular cascades work,
(44:13):
then we put them in the textbooks of high school students,
and we find drugs that interact with those cascades, and
we don't think twice about this stuff. We don't think
about it as deity playing, just that someone is hurt
or sick and needs our help, and that this is
some operation or medication that we now understand that we
(44:34):
didn't used to. So John Dunn, who died in sixteen
thirty one, coming up on four hundred years ago, could
have never imagined that when he penned the poem death
Be not Proud, that we'd actually be talking about the
end of death as just a molecular puzzle about which
we say not now, but at some point, okay, we
(44:57):
got it. Just block these pathways by which die or
commit suicide, and then these cells stay alive and the
whole system just keeps on trucking. And he could never
imagined that we'd even be talking about rebooting a system
that has already ground to a halt. Now. Mary Shelley
(45:17):
died in the mid nineteenth century, two centuries after done,
and most of us will see the mid twenty first century,
two centuries after Mary Shelley, and it looks likely that we,
or our children or our near term descendants will be
the first to see Shelley's ethical questions get tackled. Should
(45:37):
we revivify a system that's come to a halt under
what circumstances? What will be the consequences for society as
a community will come to address Shelley's questions not as
a science fiction fantasy, but as a basic challenge of
passing the right legislation and determining how hospital ethics committees
(45:59):
should make their decay decisions about reversing death. And there
might be whole groups of people that are your friends
and neighbors and work colleagues, and some of them will
have ground to a halt. At some point they're revivified,
just as you currently have friends and neighbors and colleagues
who were under anesthesia and woke up, or they had
a heart attack and had their heart defibrillated, or they
(46:20):
were in a coma for weeks and regained consciousness. And
at some point we'll all live in this new world
where we have to address whole new fields of question marks.
Because as John Dunn predicted death will have died. Go
(46:41):
to eagleman dot com slash podcast for more information and
to find further reading. Send me an email at podcasts
at eagleman dot com with questions or discussions, and I'll
be making sporadic episodes in which I address those until
next time. I'm David Eagleman, and this is Inner Cosmos
Host
David Eagleman
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