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