WEBVTT - Ep32 "Is death reversible?"

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<v Speaker 1>From the point of view of biology, what is life

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<v Speaker 1>and what is death and what is the line between them?

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<v Speaker 1>Could you freeze your body to come back sometime in

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<v Speaker 1>the future, and what does this have to do with

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<v Speaker 1>Mary Shelley's Frankenstein or housefly or the poet John Dunn.

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<v Speaker 1>Welcome to Inner Cosmos with me David Eagleman. I'm a

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<v Speaker 1>neuroscientist and an author at Stanford and in these episodes

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<v Speaker 1>we sail deeply into our three pound universe to understand

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<v Speaker 1>why and how our lives look the way they do,

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<v Speaker 1>and in this case, whether life is something that comes

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<v Speaker 1>to an end inevitably or only because we don't understand

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<v Speaker 1>the biology well enough yet. So today day's episode is

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<v Speaker 1>about understanding what happens when your molecular cycles grind to

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<v Speaker 1>a halt, and whether there's anything we can do to

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<v Speaker 1>hit control z on that can death be reversed. A

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<v Speaker 1>few months ago, my dog was lying on the floor

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<v Speaker 1>and we were all gathered around her, and my kids

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<v Speaker 1>were coming in and out, and everyone was crying because

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<v Speaker 1>my dog was dying. She was fifteen and a half

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<v Speaker 1>years old, which for a dog her size was quite old,

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<v Speaker 1>and her body was shutting down and as I sat

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<v Speaker 1>on the floor stroking her back, I was thinking about

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<v Speaker 1>a poem by John Dunn that I had first read

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<v Speaker 1>when I was a child, probably about ten years old.

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<v Speaker 1>The poem is called Death Be Not Proud, and it

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<v Speaker 1>really blew my young mind when I read it. It

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<v Speaker 1>begins with these lines, death be not proud, though some

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<v Speaker 1>have called thee mighty and dreadful, for thou art not

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<v Speaker 1>so now. In this poem, one of his nineteen holy sonnets,

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<v Speaker 1>Done gets right up in Death's face and he challenges

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<v Speaker 1>Death's power and importance, and he tells death not to

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<v Speaker 1>be proud because it is not as fearsome as it

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<v Speaker 1>might seem. And the sonnet ends with the lines one

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<v Speaker 1>short sleep past, we wake eternally, and death shall be

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<v Speaker 1>no more death, thou shalt die so. Done ends the

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<v Speaker 1>poem by spitting right in death's champagne glass, and he

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<v Speaker 1>tells Death that he is going to die now. John

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<v Speaker 1>Dunn wrote this poem through a religious lens. He was

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<v Speaker 1>giving the interpretation of the victory of the soul over death.

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<v Speaker 1>But I had a different interpretation. I was struck by

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<v Speaker 1>this idea of defeating death. After all, biologists, we study

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<v Speaker 1>life and each decade we know more and more about

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<v Speaker 1>how it works, and the more we know about life,

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<v Speaker 1>the more we can know about how to keep it

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<v Speaker 1>going and possibly how to even reboot it. Now that

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<v Speaker 1>sounds crazy, but we're going to unpack that carefully in

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<v Speaker 1>this episode. There are many ways to look at what

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<v Speaker 1>life is. I did an on stage conversation some years

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<v Speaker 1>ago with a mystic named Saguru, and we discussed and

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<v Speaker 1>debated a number of issues, but he said one thing

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<v Speaker 1>that was phrased very simply, and it proved hard for

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<v Speaker 1>me to forget. He said, the physical body is like

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<v Speaker 1>a fruit, and when the person is gone, the person

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<v Speaker 1>that you loved, all you have left now is the rind.

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<v Speaker 1>There's nothing special about the body, the physical body, and

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<v Speaker 1>I loved that description, but as a biologist, I wanted

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<v Speaker 1>to dig deeper. And this is a problem I had

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<v Speaker 1>actually started thinking about years earlier, because I once went

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<v Speaker 1>to wash a dish in the sink and there was

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<v Speaker 1>a tupperware in there with some water in it, and

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<v Speaker 1>there was a house fly that had died in the tupperware.

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<v Speaker 1>And I looked at the poor little lifeless fly, and

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<v Speaker 1>a question struck me, What is the difference between the

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<v Speaker 1>live fly and the dead fly. If you do a

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<v Speaker 1>chemical analysis, it's exactly the same stuff. You have x

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<v Speaker 1>number of carbon atoms in the quadrillions or ten to

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<v Speaker 1>the eighteenth, and you have Y number of nitrogen atoms,

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<v Speaker 1>and you have Z number of oxygen atoms, and so on.

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<v Speaker 1>The weight of this little dead fly is exactly the

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<v Speaker 1>same as a living fly. The chemical composition is the same,

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<v Speaker 1>All the trillions of proteins are the same. Everything is

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<v Speaker 1>the same between the living fly and the dead fly.

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<v Speaker 1>The only different is the molecular momentum. All the cascades

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<v Speaker 1>have come to a stop. All the crebs cycles and

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<v Speaker 1>the action of the proteins around the DNA and the

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<v Speaker 1>endoplasmic particulum, and all the step by step chemical reactions

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<v Speaker 1>in the cell, they've all just come to a standstill.

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<v Speaker 1>So what Saguru referred to as the fruit to the

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<v Speaker 1>part we love and lament I interpret this as the

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<v Speaker 1>ongoing cascades of the cellular processes. This leads to this

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<v Speaker 1>leads to this, and as long as everything keeps going,

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<v Speaker 1>then the fly is alive and it moves around. As

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<v Speaker 1>soon as something breaks about these cycles, then everything just

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<v Speaker 1>grinds to a halt. So this leads to the question

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<v Speaker 1>what does it require to keep everything going for cells

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<v Speaker 1>to stay alive? And the related question is if they stopped,

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<v Speaker 1>would there be any way to you reboot the system

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<v Speaker 1>to get the cycles going again. So when I read

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<v Speaker 1>Dunn's poem as a kid, where he says that death

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<v Speaker 1>shall die, I imagined that someday, in the very distant

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<v Speaker 1>sci fi future, we might actually be able to make

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<v Speaker 1>this true, to get cells going again that had come

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<v Speaker 1>to a stop. But of course, when imagining this future

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<v Speaker 1>as a kid, you imagine it as people in silver

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<v Speaker 1>suits zipping around in the skies. So as I got

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<v Speaker 1>older and studied biology and became more realistic about this,

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<v Speaker 1>I realized, of course that we were all going to

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<v Speaker 1>die after all. So given that perspective about how distantly

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<v Speaker 1>in the future this would happen, you can imagine how

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<v Speaker 1>surprised I was to see the speed at which this

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<v Speaker 1>field is moving along. I suspect that I will die

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<v Speaker 1>and perhaps the next few or several generations. But the

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<v Speaker 1>idea of reversing deaths, at least in some cases, is

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<v Speaker 1>not a subject constrained to the pens of poets. Anymore.

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<v Speaker 1>Over the past several years, you can find the beginnings

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<v Speaker 1>of this endeavor published in the top scientific journals. And

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<v Speaker 1>we're not talking about longevity in this episode. I'm going

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<v Speaker 1>to talk about that in the future episode. Instead, we're

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<v Speaker 1>talking about this completely wacky idea of reversing death, taking

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<v Speaker 1>an organism that has already died, and reversing back out

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<v Speaker 1>of that. Now, this sounds like something straight out of

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<v Speaker 1>Mary Shelley's novel Frankenstein, which, as you remember, tells the

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<v Speaker 1>story of a scientist named Victor Frankenstein who figures out

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<v Speaker 1>how to reanimate the dead. But the whole thing doesn't

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<v Speaker 1>turn out so well, and Frankenstein's monster ends up getting

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<v Speaker 1>rejected by mankind in general, and he regretfully murders people

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<v Speaker 1>to get revenge on his maker. But anyway, put that

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<v Speaker 1>interpretation aside for a moment while we talk about this,

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<v Speaker 1>because in the early twenty first century, we're now in

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<v Speaker 1>a more realistic position to assess what is possible and

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<v Speaker 1>to think deeply about the ethics. Now, it may sound

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<v Speaker 1>surprising that there's enough science now to even talk about

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<v Speaker 1>this topic, but hangtight, because we're about to see some

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<v Speaker 1>very strange stuff. First, this question of whether death could

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<v Speaker 1>be reversible has long been entertained, because sometimes people can

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<v Speaker 1>fall to the bottom of a lake and freeze to

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<v Speaker 1>death and lose all their function, and they are really

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<v Speaker 1>truly at a stop, and then sometimes they can be

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<v Speaker 1>brought to a hospital and revivified. For example, I remember

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<v Speaker 1>reading a story in two thousand about a young doctor

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<v Speaker 1>in Norway named Anna. She was a trainee surgeon who

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<v Speaker 1>was exactly my age, and she was skiing when she

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<v Speaker 1>fell through a rosen river and got trapped under the ice. Now,

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<v Speaker 1>her colleagues were there and they saw her, but they

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<v Speaker 1>couldn't get her out, and they struggled and struggled to

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<v Speaker 1>rescue her. But she ended up being under the ice

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<v Speaker 1>for forty minutes, and not surprisingly, her organs shut down

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<v Speaker 1>and she died. Her body temperature had fallen more than

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<v Speaker 1>twenty three degrees below normal. But Anna was eventually pulled

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<v Speaker 1>out from the ice and put on an air ambulance,

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<v Speaker 1>and she wasn't breathing when she got to the hospital.

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<v Speaker 1>Her blood circulation had stopped, her pupils were not responding

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<v Speaker 1>to light, but the doctors put her on a heart

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<v Speaker 1>and lung machine and re warmed her while the circulation

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<v Speaker 1>was kept going. They used a machine that warmed her

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<v Speaker 1>blood and oxygenated it and then put it back in

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<v Speaker 1>her body, and things weren't easy. She spent sixty days

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<v Speaker 1>in intensive care in the hospital, but five months after

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<v Speaker 1>she was frozen to death, she was back to work

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<v Speaker 1>as a doctor and she still skis now. You can

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<v Speaker 1>find this case in the Lancet, which is a top

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<v Speaker 1>medical journal in the field. So this stuff happens, and

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<v Speaker 1>it happens more than you might think. I read another

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<v Speaker 1>article in twenty sixteen about a guy walking home from

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<v Speaker 1>a party and he slipped and hit his head and

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<v Speaker 1>went unconscious and wasn't found until the next morning when

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<v Speaker 1>his father was driving around looking for him and found

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<v Speaker 1>him buried in the snow, frozen, no vital signs. They

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<v Speaker 1>rushed him to the hospital. They pumped him full of warm,

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<v Speaker 1>oxygenated blood, and it wasn't an easy recovery. But a

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<v Speaker 1>year later, even though he's missing all his toes and

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<v Speaker 1>pinkies from frostbite, he is indistinguishable from anyone else you

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<v Speaker 1>might meet. Essentially, he was frozen in the same way

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<v Speaker 1>that we might put meat in the freezer, so it

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<v Speaker 1>doesn't go bad. But it's the same principle. Despite our

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<v Speaker 1>sense of our beautiful essences, it's also the case that

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<v Speaker 1>we are meat and we can be frozen and we

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<v Speaker 1>can be thawed. Now, why can't you revivify any person

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<v Speaker 1>who has died. Well, if things aren't frozen, then the

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<v Speaker 1>biology decomposes, the cells break down. This is of course

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<v Speaker 1>the same thing that happens if you leave a piece

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<v Speaker 1>of meat on your counter instead of putting it in

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<v Speaker 1>the freezer, and in the case of a person, that

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<v Speaker 1>causes irreversible damage to the brain. But a frozen body

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<v Speaker 1>doesn't decay, at least not rapidly. It stays intact because

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<v Speaker 1>the molecules can't move around as much. Everything is held

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<v Speaker 1>into place. So the observation that people could be frozen

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<v Speaker 1>and unfrozen got scientists interested in the speculation of whether

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<v Speaker 1>you could take a person who has just died and

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<v Speaker 1>freeze them on purpose, with the idea of unfreezing them later.

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<v Speaker 1>And this successfully started in the nineteen in seventies with

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<v Speaker 1>freezing mouse embryos, and then that became a successful way

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<v Speaker 1>to freeze human embryos. But keep in mind a human

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<v Speaker 1>embryo is the size of a grain of salt, and

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<v Speaker 1>so the challenges are a little less in successfully freezing

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<v Speaker 1>and unfreezing those. But the question people have been asking is,

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<v Speaker 1>could you actually freeze an entire adult body and unfreeze

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<v Speaker 1>it later, Let's say, because they have cancer that we

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<v Speaker 1>don't know how to cure. But maybe in seventy years

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<v Speaker 1>the medical community will have no problem curing this. It'll

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<v Speaker 1>be easy. Could you reanimate somebody in the same way

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<v Speaker 1>that has been done on a much shorter timescale with

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<v Speaker 1>the woman in the icy river or the man who

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<v Speaker 1>fell into the snow bank. Well, in a previous episode,

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<v Speaker 1>I mentioned a company in Arizona called Alcore, which strives

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<v Speaker 1>to do exactly this. They are a cryogenics company, and

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<v Speaker 1>upon your death, they will swoop in to perfuse your

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<v Speaker 1>body with the right chemicals and get you to the

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<v Speaker 1>facility in Arizona, and there they will lower you into

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<v Speaker 1>a vat of liquid nitrogen. Now, do they know how

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<v Speaker 1>to cure whatever your disease was, or, for that matter,

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<v Speaker 1>do they even know how to unfreeze you successfully? No,

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<v Speaker 1>But that's not the point. The point is that sometime

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<v Speaker 1>in the distant future, our great grand descendants may know

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<v Speaker 1>how to do this, and at that point they can

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<v Speaker 1>unfreeze you and cure you of whatever ailment you have,

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<v Speaker 1>presumably something that was totally opaque or confusing for twenty

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<v Speaker 1>first century minds, but easily curable with a twenty second

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<v Speaker 1>century toolbox. Now here's something of interest. It turns out

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<v Speaker 1>the first person to ever get frozen on purpose in

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<v Speaker 1>this new field called cryogenics was born in what year,

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<v Speaker 1>take a guess, eighteen ninety three, a guy named James

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<v Speaker 1>Bedford who died in January of nineteen sixty seven from

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<v Speaker 1>terminal cancer. He was the first person to do this.

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<v Speaker 1>But did he die? Interesting question? I would say unresolved

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<v Speaker 1>so far, because it's yet to be seen whether he

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<v Speaker 1>can be rebooted nineteen sixty seven. So although this is

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<v Speaker 1>science fiction y, it's not even that new. Now. Since

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<v Speaker 1>that time, people have worked on the cryogenic technology to

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<v Speaker 1>figure out how to make the freezing process better and

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<v Speaker 1>better to prevent cell damage, because the problem is if

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<v Speaker 1>you get an ice crystal during the freezing process, that

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<v Speaker 1>will rupture the cell membrane and then the body that

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<v Speaker 1>you hoped to revive is too damaged. Like when you

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<v Speaker 1>stick a strawberry in the freezer to try to make

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<v Speaker 1>it last longer. But once you unthought, it gets all mushy.

0:14:51.040 --> 0:14:53.760
<v Speaker 1>That's the same thing that happens with any cells if

0:14:53.800 --> 0:14:57.640
<v Speaker 1>they get ice crystals in it. So will Bedford's body

0:14:57.720 --> 0:15:01.400
<v Speaker 1>be able to be reanimated? Who knows? And experts have

0:15:01.440 --> 0:15:04.880
<v Speaker 1>different opinions about whether the bodies at the alcore facility

0:15:04.960 --> 0:15:09.120
<v Speaker 1>will be reeve vivifiable. But the idea of cryogenics is

0:15:09.200 --> 0:15:13.360
<v Speaker 1>straightforward in the sense that even if these first few

0:15:13.480 --> 0:15:17.240
<v Speaker 1>hundred experiments fail, will surely get better and better at

0:15:17.240 --> 0:15:21.120
<v Speaker 1>cryogenics in the future, and the hope is that someone

0:15:21.640 --> 0:15:25.880
<v Speaker 1>fifty generations from now will know how to reverse the process.

0:15:26.920 --> 0:15:28.480
<v Speaker 1>And before I go to the next step, I just

0:15:28.520 --> 0:15:32.840
<v Speaker 1>want to say this idea about confronting death is not

0:15:32.880 --> 0:15:36.960
<v Speaker 1>just about freezing and unfreezing. The deeper issues in biology

0:15:37.440 --> 0:15:41.560
<v Speaker 1>have to do with how individual cells die. It turns

0:15:41.560 --> 0:15:44.720
<v Speaker 1>out that cells can get injured by various things, let's say,

0:15:44.760 --> 0:15:48.480
<v Speaker 1>a lack of blood flow or a chemical insult, and

0:15:48.520 --> 0:15:51.520
<v Speaker 1>then they essentially blow up and die and cause a

0:15:51.520 --> 0:15:55.360
<v Speaker 1>lot of inflammation. This is called necrosis. But in nineteen

0:15:55.400 --> 0:15:58.560
<v Speaker 1>seventy two it was discovered that this isn't the way

0:15:58.840 --> 0:16:03.440
<v Speaker 1>cells have to die. Cells can actually die on purpose,

0:16:03.880 --> 0:16:07.720
<v Speaker 1>and this is known as a potosis. A potosis means

0:16:07.720 --> 0:16:11.040
<v Speaker 1>that instead of a cell simply just falling apart, instead

0:16:11.080 --> 0:16:15.640
<v Speaker 1>it implements a controlled process by which it folds up

0:16:15.720 --> 0:16:20.280
<v Speaker 1>shop and cleanly commits suicide. Scientists came to understand that

0:16:20.360 --> 0:16:23.680
<v Speaker 1>this is a very purposeful process, and over many years

0:16:23.760 --> 0:16:28.120
<v Speaker 1>they showed how apotosis is actually the way that biological

0:16:28.280 --> 0:16:34.960
<v Speaker 1>organisms structure themselves. For example, a human embryo has webbed fingers,

0:16:35.000 --> 0:16:38.240
<v Speaker 1>in other words, little sheets of skin between the fingers

0:16:38.680 --> 0:16:41.280
<v Speaker 1>of exactly the type that you would need for swimming.

0:16:41.520 --> 0:16:45.000
<v Speaker 1>But in the case of our particular species, the cells

0:16:45.080 --> 0:16:48.800
<v Speaker 1>making up that webbing. Those cells die off before the

0:16:48.840 --> 0:16:52.400
<v Speaker 1>baby is born, such that we have independently moving fingers.

0:16:52.880 --> 0:16:56.040
<v Speaker 1>But those cells between our fingers wouldn't die off if

0:16:56.080 --> 0:16:59.640
<v Speaker 1>we were another mammal, say a bat, or a kangaroo,

0:17:00.120 --> 0:17:03.480
<v Speaker 1>or a whale or a manatee. I'm actually going to

0:17:03.480 --> 0:17:05.800
<v Speaker 1>put an X ray picture of a manatee fin on

0:17:05.800 --> 0:17:10.200
<v Speaker 1>my website because it's so stunning how the bones inside

0:17:10.240 --> 0:17:13.679
<v Speaker 1>their fin look just like a human hand. The bones

0:17:13.720 --> 0:17:16.600
<v Speaker 1>look that way, but the difference is that the cells

0:17:16.640 --> 0:17:20.159
<v Speaker 1>between their fingers, that webbing that doesn't die off, so

0:17:20.240 --> 0:17:25.760
<v Speaker 1>what you get is a fin Anyway, apotosis is everywhere.

0:17:25.800 --> 0:17:29.760
<v Speaker 1>Your body has about a trillion new cells developing every day,

0:17:30.200 --> 0:17:33.439
<v Speaker 1>and so you need to kill off a similar number

0:17:33.680 --> 0:17:36.480
<v Speaker 1>to keep the system from getting overrun. And this is

0:17:36.600 --> 0:17:40.639
<v Speaker 1>all done with this very controlled process of cell death.

0:17:41.440 --> 0:17:45.960
<v Speaker 1>And the scientists behind these discoveries Horbitz and Brenner and Sulstan.

0:17:46.320 --> 0:17:49.040
<v Speaker 1>They won the Nobel Prize for this in two thousand

0:17:49.040 --> 0:17:52.239
<v Speaker 1>and two. But it turns out since then biologists have

0:17:52.280 --> 0:17:56.200
<v Speaker 1>discovered that necrosis and apotosis are not even the only

0:17:56.280 --> 0:17:59.760
<v Speaker 1>game in town. We now know there are many flavors

0:17:59.840 --> 0:18:04.880
<v Speaker 1>of program cell death, like what's called pyrotosis or ferrotosis

0:18:05.000 --> 0:18:09.639
<v Speaker 1>or necrotosis. These are all different mechanisms that tip the

0:18:09.760 --> 0:18:14.439
<v Speaker 1>balance between different cell fates, and people are working on

0:18:14.560 --> 0:18:18.639
<v Speaker 1>drugs to block all these very specific flavors of cell death.

0:18:19.320 --> 0:18:22.679
<v Speaker 1>It's no longer just the cell gets sick and falls apart,

0:18:22.920 --> 0:18:26.240
<v Speaker 1>but it's much more sophisticated now and that gives the

0:18:26.359 --> 0:18:32.320
<v Speaker 1>possibility to molecularly block the process. So now let zoom

0:18:32.359 --> 0:18:35.920
<v Speaker 1>out to the big picture. There's an increasing amount known

0:18:35.960 --> 0:18:39.600
<v Speaker 1>about how cells actually shut down, and we have proof

0:18:39.600 --> 0:18:43.600
<v Speaker 1>of principle that systems can get going again even after

0:18:43.600 --> 0:18:48.080
<v Speaker 1>they've stopped. And all this has led to the possibility

0:18:48.560 --> 0:18:50.600
<v Speaker 1>that we might be able to take something like a

0:18:50.800 --> 0:18:55.920
<v Speaker 1>dead brain or dead body and reboot it. Now this

0:18:56.040 --> 0:18:58.560
<v Speaker 1>sounds so crazy, but the question I want to ask

0:18:58.680 --> 0:19:01.600
<v Speaker 1>is are we actually going to have to wait fifty

0:19:01.680 --> 0:19:05.000
<v Speaker 1>generations to see this happen? Or is it possible that

0:19:05.080 --> 0:19:08.479
<v Speaker 1>things are moving so rapidly that there's some reason to

0:19:08.520 --> 0:19:11.040
<v Speaker 1>think that we could take, say, a dead brain, a

0:19:11.119 --> 0:19:13.960
<v Speaker 1>totally dead brain that's been dead for four hours, and

0:19:14.000 --> 0:19:17.480
<v Speaker 1>get the whole factory running again. Well you'd agree that

0:19:17.600 --> 0:19:21.679
<v Speaker 1>seems like a science fiction fantasy. But a colleague of

0:19:21.720 --> 0:19:25.199
<v Speaker 1>mine recently published two papers in the journal Nature, and

0:19:25.320 --> 0:19:28.720
<v Speaker 1>it seems we're already at the point, give or take,

0:19:29.160 --> 0:19:32.119
<v Speaker 1>where we may be able to do something just about

0:19:32.200 --> 0:19:35.639
<v Speaker 1>like that, at least in pigs. In the journals, this

0:19:35.720 --> 0:19:39.600
<v Speaker 1>is cast in the paper as quote Cellular and molecular

0:19:39.680 --> 0:19:43.280
<v Speaker 1>recovery in pigs, which I suspect doesn't sound that interesting

0:19:43.320 --> 0:19:45.080
<v Speaker 1>to most people on the planet, and so it didn't

0:19:45.080 --> 0:19:48.680
<v Speaker 1>get that much attention. But this is seriously big stuff.

0:19:49.359 --> 0:19:52.160
<v Speaker 1>So I called up my colleague who wrote these recent papers,

0:19:52.600 --> 0:19:56.880
<v Speaker 1>and I asked him, is cell death inevitable? Let's say

0:19:56.920 --> 0:19:59.320
<v Speaker 1>when a person has a stroke and there's no blood

0:19:59.320 --> 0:20:02.040
<v Speaker 1>going to the set. Well, we've always thought of that

0:20:02.119 --> 0:20:05.879
<v Speaker 1>as being a really terrible scenario that inevitably leads to

0:20:05.960 --> 0:20:08.919
<v Speaker 1>sell death. But is that the case?

0:20:25.160 --> 0:20:27.080
<v Speaker 2>So we used to think that, and we had a

0:20:27.280 --> 0:20:31.919
<v Speaker 2>publication four years ago where we actually christened if sales

0:20:31.960 --> 0:20:35.359
<v Speaker 2>actually die after death after blood flow stops, and we

0:20:35.440 --> 0:20:40.000
<v Speaker 2>realized that actually death is a portracted process. It takes

0:20:40.000 --> 0:20:42.440
<v Speaker 2>a bit actually for sales to die, and if you

0:20:42.560 --> 0:20:46.440
<v Speaker 2>intervene properly, you can maybe reverse those processes.

0:20:47.320 --> 0:20:53.000
<v Speaker 1>That's Vanimir Russella. He's an mdphd originally from Croatia. He

0:20:53.040 --> 0:20:56.080
<v Speaker 1>did his postalk and became a research scientist at Yale

0:20:56.160 --> 0:20:58.719
<v Speaker 1>School of Medicine, and now he's spun off a company

0:20:58.720 --> 0:21:06.080
<v Speaker 1>around this called Becksore. So you mean the death of

0:21:06.320 --> 0:21:09.399
<v Speaker 1>an organism, let's say, of a person. You're saying it

0:21:09.440 --> 0:21:14.200
<v Speaker 1>doesn't happen all at once, but it takes time to die.

0:21:14.600 --> 0:21:16.320
<v Speaker 2>So yeah, yeah, So I think I just want to

0:21:16.320 --> 0:21:19.720
<v Speaker 2>be like a nuance here. There were instances that so

0:21:19.880 --> 0:21:23.280
<v Speaker 2>it is well known that For example, you can find

0:21:23.400 --> 0:21:27.800
<v Speaker 2>living cells in human specimens after hours of death, and

0:21:28.119 --> 0:21:31.000
<v Speaker 2>scientists have used like chunks of tissue to find like

0:21:31.040 --> 0:21:32.840
<v Speaker 2>living sales and record from them.

0:21:33.200 --> 0:21:35.200
<v Speaker 3>It was also observed.

0:21:34.800 --> 0:21:39.040
<v Speaker 2>That people who have died and were undercolt conditions that

0:21:39.480 --> 0:21:42.840
<v Speaker 2>they could be actually brought sort of The implication there

0:21:42.920 --> 0:21:46.320
<v Speaker 2>is that there are cells o functional. So there were

0:21:46.320 --> 0:21:50.200
<v Speaker 2>instances where this was a scene and recorded in the literature.

0:21:50.600 --> 0:21:53.119
<v Speaker 1>So let's just double click on that. So tell us

0:21:53.119 --> 0:21:57.119
<v Speaker 1>what you mean about people who were frozen and were recovered.

0:21:57.440 --> 0:22:00.800
<v Speaker 2>Give us an example, So on the macros kale, like right,

0:22:00.960 --> 0:22:03.840
<v Speaker 2>talking about the whole human, not about.

0:22:03.600 --> 0:22:06.159
<v Speaker 3>A single cell. It was observed that people.

0:22:05.880 --> 0:22:08.760
<v Speaker 2>Who have drowned their bodies would cool down as they

0:22:08.800 --> 0:22:12.200
<v Speaker 2>were drowning, that after a prolonged period of time, these

0:22:12.240 --> 0:22:16.080
<v Speaker 2>people could be resuscitated. So the time it was, you know,

0:22:16.240 --> 0:22:19.800
<v Speaker 2>we are not used as seeing like someone resuscitated after

0:22:19.880 --> 0:22:24.879
<v Speaker 2>that how long, Well, I don't know specifics, but just

0:22:24.920 --> 0:22:28.159
<v Speaker 2>to give you like a benchmark data point. Usually it

0:22:28.240 --> 0:22:32.240
<v Speaker 2>is assumed from the classical literature that four minutes after

0:22:32.520 --> 0:22:35.680
<v Speaker 2>blood flow stops, bodies cells just die.

0:22:35.760 --> 0:22:36.360
<v Speaker 3>So that was.

0:22:36.359 --> 0:22:41.040
<v Speaker 2>Always like a clinical data point, after which was really

0:22:41.080 --> 0:22:45.000
<v Speaker 2>difficult to bring people back with resuscitation.

0:22:45.920 --> 0:22:50.200
<v Speaker 1>Okay, so you started suspecting that maybe cells aren't as

0:22:50.240 --> 0:22:52.600
<v Speaker 1>fragile as we thought. So what did you do?

0:22:53.840 --> 0:22:58.760
<v Speaker 2>So yeah, so we have it's interesting storied up my

0:22:58.920 --> 0:23:04.480
<v Speaker 2>pi at the time. And then a Sistan received a

0:23:04.520 --> 0:23:09.119
<v Speaker 2>tissue specimens from abroad and they got stuck at customs

0:23:09.160 --> 0:23:12.000
<v Speaker 2>for a really long period of time. And so by

0:23:12.080 --> 0:23:14.520
<v Speaker 2>the time they came in the lab, you know, the

0:23:14.640 --> 0:23:16.639
<v Speaker 2>researchers were like thinking, oh.

0:23:16.280 --> 0:23:19.360
<v Speaker 3>You know, it's done, like the specimen is useless.

0:23:19.400 --> 0:23:22.400
<v Speaker 2>But they still made slice sculptures and after a week

0:23:22.440 --> 0:23:24.600
<v Speaker 2>they realized that they were living cells.

0:23:24.960 --> 0:23:28.199
<v Speaker 3>So that was the first observation that got the group like.

0:23:28.240 --> 0:23:31.840
<v Speaker 2>Thinking, and in our case in particular, we just wanted

0:23:31.880 --> 0:23:36.240
<v Speaker 2>to scale the whole approach, initially going from a small.

0:23:35.920 --> 0:23:38.040
<v Speaker 3>Slice to a whole inteked brain.

0:23:38.240 --> 0:23:42.000
<v Speaker 1>Right, So you said, hey, what if you could get

0:23:42.119 --> 0:23:46.680
<v Speaker 1>a brain of an organism that has died, could you

0:23:46.880 --> 0:23:50.040
<v Speaker 1>restore the function somehow? So what did you do to

0:23:50.080 --> 0:23:52.080
<v Speaker 1>try to tackle that problem?

0:23:52.119 --> 0:23:55.879
<v Speaker 3>So, you know, as one does, we started going to

0:23:55.920 --> 0:24:00.000
<v Speaker 3>a local slaughterhouse and we were procuring a tissue.

0:24:00.320 --> 0:24:02.680
<v Speaker 1>You were getting pig brains, right, pig reins.

0:24:02.760 --> 0:24:05.919
<v Speaker 2>Yes, so people don't. Luckily there we are like, people

0:24:05.920 --> 0:24:07.760
<v Speaker 2>don't eat the pig brains.

0:24:07.640 --> 0:24:10.280
<v Speaker 1>And this was the el right, yes, yes, yes, yes.

0:24:10.200 --> 0:24:13.879
<v Speaker 3>Yes, So we will go to the local slaughterhouse. You know,

0:24:14.000 --> 0:24:15.120
<v Speaker 3>they would do their job.

0:24:15.200 --> 0:24:17.720
<v Speaker 2>By the time when they are done, we would get

0:24:17.920 --> 0:24:20.560
<v Speaker 2>pig hits and so we'll bring them to the lab.

0:24:20.760 --> 0:24:23.439
<v Speaker 3>We would take the brain out, and.

0:24:23.320 --> 0:24:26.679
<v Speaker 2>Then we started developing this technology that could connect with

0:24:26.720 --> 0:24:30.320
<v Speaker 2>the vascular system of the brain and profuse a fluid

0:24:30.760 --> 0:24:34.240
<v Speaker 2>to sort of reboot the self functionality.

0:24:34.480 --> 0:24:36.680
<v Speaker 1>And how long had these pigs been dead?

0:24:37.720 --> 0:24:40.679
<v Speaker 3>On every g it was four hours, So from the

0:24:40.760 --> 0:24:45.240
<v Speaker 3>time of pig being killed in the slaughterhouse to the

0:24:45.280 --> 0:24:48.879
<v Speaker 3>time point where we started our profusion intervention, it was

0:24:49.000 --> 0:24:50.360
<v Speaker 3>usually four hours.

0:24:50.720 --> 0:24:53.360
<v Speaker 1>So then what you did is you profused and tell

0:24:53.440 --> 0:24:56.359
<v Speaker 1>us about profusion and what that means and what that

0:24:56.440 --> 0:24:56.879
<v Speaker 1>looks like.

0:24:57.640 --> 0:25:01.440
<v Speaker 2>So there's a device, so you take the isolated brain,

0:25:01.560 --> 0:25:04.159
<v Speaker 2>which is sort of front of you. You load the

0:25:04.160 --> 0:25:08.800
<v Speaker 2>brain into this device and then the device pushes artificial

0:25:08.840 --> 0:25:12.840
<v Speaker 2>blood or blood like fluid through the brain and it

0:25:12.880 --> 0:25:16.000
<v Speaker 2>does it under controlled conditions. It has a bunch of

0:25:16.320 --> 0:25:21.720
<v Speaker 2>drugs inside that counter certain cell processes. So the whole

0:25:21.760 --> 0:25:27.040
<v Speaker 2>point is to try to reinstate homeosthetic environment or this

0:25:27.200 --> 0:25:32.560
<v Speaker 2>like like normal environment in which cells are usually accustomed.

0:25:31.960 --> 0:25:34.320
<v Speaker 1>To be and so what did you find?

0:25:34.600 --> 0:25:38.479
<v Speaker 2>So we found that So this is an interesting equation.

0:25:38.560 --> 0:25:40.679
<v Speaker 2>So first of all, we found that we could revert

0:25:41.160 --> 0:25:44.080
<v Speaker 2>cell death. It was an interesting thing because at the

0:25:44.160 --> 0:25:46.560
<v Speaker 2>time we were trying to define like what does it

0:25:46.600 --> 0:25:48.879
<v Speaker 2>mean for a cell to be dead, like right, and

0:25:48.920 --> 0:25:51.800
<v Speaker 2>how do you define cell death? So we found it

0:25:51.880 --> 0:25:56.800
<v Speaker 2>cells that were considered dead they were actually still some adjective.

0:25:57.280 --> 0:26:01.080
<v Speaker 2>And with our interventions we could restore or functionality and

0:26:01.160 --> 0:26:05.159
<v Speaker 2>observed functions in those cells that we usually observe in

0:26:05.280 --> 0:26:08.080
<v Speaker 2>cells that we sort of think or consider alive.

0:26:08.920 --> 0:26:14.720
<v Speaker 1>So were the cells completely restored or are there still

0:26:15.160 --> 0:26:17.960
<v Speaker 1>things you need to do to get to the next level.

0:26:18.320 --> 0:26:20.119
<v Speaker 3>There is a lot more to do there.

0:26:20.680 --> 0:26:24.639
<v Speaker 2>What we have done we took a particular number of

0:26:24.720 --> 0:26:27.840
<v Speaker 2>tests and we conducted those tests and so I can

0:26:27.920 --> 0:26:29.119
<v Speaker 2>only speak about those.

0:26:29.760 --> 0:26:32.359
<v Speaker 3>They were pretty good broad tests that sort of speak

0:26:32.480 --> 0:26:36.280
<v Speaker 3>on the state of these cells. So these same tests

0:26:36.359 --> 0:26:39.359
<v Speaker 3>show that these cells performed in a similar way as

0:26:39.600 --> 0:26:40.359
<v Speaker 3>normal cells.

0:26:40.840 --> 0:26:43.480
<v Speaker 2>And on top of it, with subsequent research data was done,

0:26:43.480 --> 0:26:45.760
<v Speaker 2>we actually showed that it's clear that these cells go

0:26:45.880 --> 0:26:48.800
<v Speaker 2>through stress of dying. So we've shown that we can

0:26:49.160 --> 0:26:54.160
<v Speaker 2>stop it, and we even showed on the molecular scale

0:26:54.359 --> 0:26:57.000
<v Speaker 2>that we can basically persuade sales like not to die

0:26:57.040 --> 0:27:00.800
<v Speaker 2>and they can start to repair themselves and basically just

0:27:01.680 --> 0:27:04.480
<v Speaker 2>say to them like, don't die, like they just want

0:27:04.480 --> 0:27:05.080
<v Speaker 2>to live, you know.

0:27:05.240 --> 0:27:07.959
<v Speaker 1>So you take a pig brain that's been dead for

0:27:08.000 --> 0:27:12.920
<v Speaker 1>four hours and you perfuse this this solution through it.

0:27:12.920 --> 0:27:15.040
<v Speaker 1>It's like blood, but it doesn't have cells in it.

0:27:15.040 --> 0:27:17.520
<v Speaker 1>It has lots of meds and the proper kind of

0:27:17.600 --> 0:27:20.600
<v Speaker 1>molecules in it. You push that through and then you

0:27:20.640 --> 0:27:23.560
<v Speaker 1>can measure things about the cells and see that it's

0:27:23.680 --> 0:27:26.800
<v Speaker 1>like they're cooking along. They're doing their thing that cells

0:27:26.800 --> 0:27:27.280
<v Speaker 1>normally do.

0:27:28.119 --> 0:27:28.639
<v Speaker 3>Absolutely.

0:27:28.720 --> 0:27:30.919
<v Speaker 2>So the point is like, you know, you just go

0:27:31.040 --> 0:27:34.639
<v Speaker 2>to like meet school biology and it's you know, you

0:27:34.760 --> 0:27:37.080
<v Speaker 2>see if oxygen is going in, you see if glucose

0:27:37.200 --> 0:27:40.640
<v Speaker 2>is going in, so you're expecting CO two to come out,

0:27:40.760 --> 0:27:44.280
<v Speaker 2>so you know that's happening, and then you compare those results.

0:27:44.359 --> 0:27:48.119
<v Speaker 3>I'm simplifying this, but you know, conceptually it works.

0:27:48.520 --> 0:27:51.840
<v Speaker 2>You can provide stimuli or for example, drugs because you know,

0:27:52.040 --> 0:27:54.320
<v Speaker 2>like you can take a drug, which we have done actually,

0:27:54.320 --> 0:27:56.360
<v Speaker 2>so we would take a drug that works in humans,

0:27:56.720 --> 0:27:59.040
<v Speaker 2>it's well known, and we would see if it's exerting

0:27:59.080 --> 0:28:01.760
<v Speaker 2>the same effect in these restored cells.

0:28:02.119 --> 0:28:02.800
<v Speaker 3>And it worked.

0:28:02.840 --> 0:28:05.240
<v Speaker 2>So these cells can also be like stimulated and you

0:28:05.240 --> 0:28:08.679
<v Speaker 2>can observe how they respond. You can compare those responses

0:28:08.680 --> 0:28:10.359
<v Speaker 2>and learn about the brain, you know.

0:28:11.240 --> 0:28:14.640
<v Speaker 1>And so you have been doing this in pig brains

0:28:14.680 --> 0:28:18.160
<v Speaker 1>since the first paper you did was in twenty nineteen

0:28:18.440 --> 0:28:20.960
<v Speaker 1>or yes, okay, so you've been doing it in pig

0:28:21.000 --> 0:28:25.000
<v Speaker 1>brains since then. What is the road that you see

0:28:25.119 --> 0:28:26.920
<v Speaker 1>two human brains?

0:28:27.600 --> 0:28:32.080
<v Speaker 2>So this is a new type of research, and we

0:28:32.080 --> 0:28:35.359
<v Speaker 2>were pretty lucky from day one to have ANIH and

0:28:35.440 --> 0:28:39.920
<v Speaker 2>other institutions Yale including involved in helping us put the

0:28:39.960 --> 0:28:42.800
<v Speaker 2>guidelines and think about like where this research should go

0:28:42.880 --> 0:28:45.760
<v Speaker 2>and how it should be conducted. So what we have

0:28:45.840 --> 0:28:48.640
<v Speaker 2>done we really wanted to build like a ground up approach,

0:28:49.120 --> 0:28:52.240
<v Speaker 2>and so we wanted to show that these interventions are

0:28:52.440 --> 0:28:55.240
<v Speaker 2>opening new spaces, and so we went to do it

0:28:55.280 --> 0:28:58.360
<v Speaker 2>in the smart way. So that said going to humans

0:28:58.360 --> 0:29:00.680
<v Speaker 2>and what it really means, you know, think about like

0:29:00.920 --> 0:29:04.040
<v Speaker 2>restoring cells and their function, like you can think about

0:29:04.040 --> 0:29:07.440
<v Speaker 2>clinical applications of the technology like SOAK is the first

0:29:07.440 --> 0:29:08.640
<v Speaker 2>thing that comes to one mind.

0:29:09.480 --> 0:29:11.920
<v Speaker 3>So it will take a bit more time to get there.

0:29:12.040 --> 0:29:14.600
<v Speaker 2>Because we need to really understand, like deeply what's going

0:29:14.640 --> 0:29:16.280
<v Speaker 2>on on the cellular level.

0:29:16.320 --> 0:29:17.680
<v Speaker 3>But this is one approach.

0:29:17.760 --> 0:29:21.080
<v Speaker 2>Another approach that we have taken was in collaboration with

0:29:21.200 --> 0:29:25.400
<v Speaker 2>a transplant team here at Yale. So we actually wanted

0:29:25.440 --> 0:29:28.680
<v Speaker 2>to see if we could deploy our technology in dead pigs.

0:29:28.800 --> 0:29:32.320
<v Speaker 3>Essentially and see if we could restore like kidneys or

0:29:32.400 --> 0:29:34.040
<v Speaker 3>liver for transplant.

0:29:34.120 --> 0:29:38.560
<v Speaker 2>Because if this works in the clinical sense, then there

0:29:38.600 --> 0:29:42.840
<v Speaker 2>is a chance to readically expand organ pool or organ donations.

0:29:43.320 --> 0:29:47.200
<v Speaker 1>Oh incredible. And when it comes to restoring the brain,

0:29:47.680 --> 0:29:50.640
<v Speaker 1>when you think down the road, you think ten twenty

0:29:50.680 --> 0:29:53.160
<v Speaker 1>years in the future, what are the ethical questions here?

0:29:53.880 --> 0:29:58.920
<v Speaker 3>Well they are big. So the first thing is clearly,

0:29:59.360 --> 0:30:03.080
<v Speaker 3>are we sort of rebooting this brain like big where

0:30:03.080 --> 0:30:06.760
<v Speaker 3>it was. I'm really particular how I speak about these things,

0:30:06.760 --> 0:30:09.360
<v Speaker 3>So I talk about sales, I don't actually talk about

0:30:09.400 --> 0:30:13.560
<v Speaker 3>brain function. The reason is because we are making sure

0:30:13.600 --> 0:30:18.120
<v Speaker 3>that we are not rebooting global network or EG. But

0:30:18.280 --> 0:30:21.720
<v Speaker 3>one could go in that phase. So that is definitely

0:30:21.920 --> 0:30:23.320
<v Speaker 3>something that can be explored.

0:30:23.360 --> 0:30:26.240
<v Speaker 2>So now you can think about all the ethical implications

0:30:26.280 --> 0:30:29.400
<v Speaker 2>that our eyes with this technology.

0:30:29.800 --> 0:30:33.240
<v Speaker 1>So you said you're being careful not to reboot the

0:30:33.440 --> 0:30:35.960
<v Speaker 1>function of the brain. Correct me if I'm wrong, But

0:30:36.000 --> 0:30:39.000
<v Speaker 1>you're not actually sure when or why that would happen.

0:30:39.120 --> 0:30:41.000
<v Speaker 1>It's just that in the experience you've done so far,

0:30:41.480 --> 0:30:45.120
<v Speaker 1>the electrical signaling, the global functioning the brain wasn't restored

0:30:45.200 --> 0:30:47.880
<v Speaker 1>in the pigs, but we don't know why that's the case,

0:30:47.920 --> 0:30:51.520
<v Speaker 1>and it could happen with another few molecules or whatever

0:30:51.560 --> 0:30:52.440
<v Speaker 1>of the right flavor.

0:30:53.280 --> 0:30:57.880
<v Speaker 2>Absolutely, so there is research already showing thatta done in

0:30:57.920 --> 0:31:01.280
<v Speaker 2>the pace that this could be done. And also in

0:31:01.320 --> 0:31:05.120
<v Speaker 2>our case, it is basically the design of the experiments.

0:31:05.240 --> 0:31:09.480
<v Speaker 2>Our experiments we were actively suppressing or we were avoiding

0:31:09.840 --> 0:31:15.920
<v Speaker 2>that situation because even without the network being rewooted, we

0:31:16.080 --> 0:31:19.479
<v Speaker 2>still have an extremely valuable tool to understand how the

0:31:19.480 --> 0:31:23.200
<v Speaker 2>brain works and functions. So in the future, the question

0:31:23.400 --> 0:31:25.440
<v Speaker 2>has definitely been the technology, as you said, been the

0:31:25.480 --> 0:31:29.880
<v Speaker 2>technology is matured and we actually know exactly every single

0:31:29.880 --> 0:31:32.240
<v Speaker 2>thing that goes into it and what happens, then the

0:31:32.320 --> 0:31:34.000
<v Speaker 2>question is like what should be done next?

0:31:34.520 --> 0:31:35.960
<v Speaker 1>And so what do you think about that, what are

0:31:36.000 --> 0:31:39.440
<v Speaker 1>your thoughts on the ethics of you know, somebody has

0:31:39.480 --> 0:31:42.720
<v Speaker 1>found drowned at the bottom of a lake and it's

0:31:43.080 --> 0:31:46.000
<v Speaker 1>four hours later and you say, hey, I've got a

0:31:46.000 --> 0:31:47.960
<v Speaker 1>solution here to bring this person back.

0:31:48.520 --> 0:31:54.360
<v Speaker 4>Oh yeah, so definitely not now, and technologically and our understanding,

0:31:54.840 --> 0:31:56.880
<v Speaker 4>we're just not there yet, and there's a lot of

0:31:56.920 --> 0:31:59.760
<v Speaker 4>research that has to be done. I think it also

0:31:59.840 --> 0:32:01.600
<v Speaker 4>been comes an interesting.

0:32:01.240 --> 0:32:05.520
<v Speaker 2>Question like assuming that the technology is capable of doing

0:32:05.680 --> 0:32:08.960
<v Speaker 2>such a feit, you know, you have a question from

0:32:09.080 --> 0:32:10.600
<v Speaker 2>you like should you do this?

0:32:11.080 --> 0:32:13.720
<v Speaker 3>Like should you go and save this person? I'm a

0:32:13.760 --> 0:32:16.760
<v Speaker 3>trained physician, so that's the goal. You know, you want

0:32:16.800 --> 0:32:19.080
<v Speaker 3>to go and save someone. So this should become just

0:32:19.160 --> 0:32:22.640
<v Speaker 3>another tool that allows us to do our job. So,

0:32:22.840 --> 0:32:25.720
<v Speaker 3>but it needs to be it really needs to be

0:32:26.040 --> 0:32:29.160
<v Speaker 3>researched over time and show that there is value and

0:32:29.280 --> 0:32:31.040
<v Speaker 3>potential for this outcome.

0:32:31.200 --> 0:32:35.320
<v Speaker 1>So let's imagine forty seven years from now where it's

0:32:35.360 --> 0:32:37.840
<v Speaker 1>really been researched and it really works well and you

0:32:37.880 --> 0:32:40.800
<v Speaker 1>know exactly the solution to profuse into the brain to

0:32:40.920 --> 0:32:45.120
<v Speaker 1>restore the function. So, first of all, what's your guest

0:32:45.160 --> 0:32:49.360
<v Speaker 1>about how many hours let's say you find somebody who

0:32:49.360 --> 0:32:52.840
<v Speaker 1>has passed away ten hours ago. Is that too late?

0:32:53.440 --> 0:32:56.480
<v Speaker 3>That's a difficult question to answer.

0:32:56.800 --> 0:32:59.760
<v Speaker 2>We do know that their process is still ongoing then

0:33:00.400 --> 0:33:03.600
<v Speaker 2>after death, but I don't believe that you can sum

0:33:03.960 --> 0:33:07.640
<v Speaker 2>certain processes that hip on it those time points to

0:33:07.680 --> 0:33:11.520
<v Speaker 2>the whole human being. So I don't see that happening.

0:33:11.560 --> 0:33:15.520
<v Speaker 2>I think there is definitely like a time limit, you know,

0:33:15.560 --> 0:33:18.480
<v Speaker 2>if you think about the current practice now, which is

0:33:18.520 --> 0:33:21.680
<v Speaker 2>in minutes. So basically, whatever V do, we would be

0:33:21.680 --> 0:33:24.760
<v Speaker 2>a huge feit really difficult.

0:33:25.000 --> 0:33:27.000
<v Speaker 1>Absolutely, So I just want to press one more time

0:33:27.040 --> 0:33:30.000
<v Speaker 1>on this issue about what are the ethical questions that

0:33:30.160 --> 0:33:32.720
<v Speaker 1>come up for you. So let's imagine forty seven years

0:33:32.720 --> 0:33:37.400
<v Speaker 1>from now, the technology works great, and the question is, Okay,

0:33:37.680 --> 0:33:42.160
<v Speaker 1>somebody has passed away, how do we decide about restoring them,

0:33:42.640 --> 0:33:44.920
<v Speaker 1>whether it's the right thing to do when when it's not.

0:33:45.640 --> 0:33:49.560
<v Speaker 3>Yeah, so this is a really complex question.

0:33:50.360 --> 0:33:53.480
<v Speaker 2>There are bodies that deal with the definition of death,

0:33:53.520 --> 0:33:56.920
<v Speaker 2>and one thing in particular there which is interesting is

0:33:57.480 --> 0:34:02.400
<v Speaker 2>a distinction between something that's reversible and something that's permanent.

0:34:02.520 --> 0:34:04.440
<v Speaker 2>And I think it is going to be really interesting

0:34:04.480 --> 0:34:08.120
<v Speaker 2>to understand like which one is which, because there are

0:34:08.160 --> 0:34:12.200
<v Speaker 2>instances where you know, brain can get completely destroyed and

0:34:12.239 --> 0:34:15.200
<v Speaker 2>then you can die because your brain was destroyed, like right,

0:34:15.560 --> 0:34:19.480
<v Speaker 2>So there's no point in doing that is a permanent

0:34:19.520 --> 0:34:24.200
<v Speaker 2>death by itself. So if you go to a cardiac arrest,

0:34:24.320 --> 0:34:27.600
<v Speaker 2>if your heart stops, so then actually your brain is

0:34:28.239 --> 0:34:30.839
<v Speaker 2>going to die because your heart has stopped, like right.

0:34:31.320 --> 0:34:34.000
<v Speaker 2>So there are instances where it makes sense from the

0:34:34.000 --> 0:34:36.920
<v Speaker 2>clinical point of view to intervene in the future, like

0:34:37.080 --> 0:34:40.600
<v Speaker 2>assuming that this technology is effective.

0:34:40.400 --> 0:34:43.719
<v Speaker 1>Okay, great, and I assume that there will be bodies

0:34:43.760 --> 0:34:46.560
<v Speaker 1>of philosophers and so on who get involved with this

0:34:46.719 --> 0:34:48.759
<v Speaker 1>question about when is it the right thing to do?

0:34:49.200 --> 0:34:50.080
<v Speaker 1>When does it make sense?

0:34:50.440 --> 0:34:54.640
<v Speaker 2>Absolutely so yeah, So we hit with both publications, we

0:34:54.760 --> 0:34:59.040
<v Speaker 2>hit commentary work actually on this particular topic.

0:34:59.160 --> 0:35:01.319
<v Speaker 3>And I think it's really interesting to see how the

0:35:01.360 --> 0:35:05.239
<v Speaker 3>field is developing now and how people are thinking now

0:35:05.280 --> 0:35:07.680
<v Speaker 3>with these new technologies that are coming to a right,

0:35:07.840 --> 0:35:11.279
<v Speaker 3>including ours and others. If you just think about now,

0:35:11.320 --> 0:35:14.160
<v Speaker 3>like I think last week or this week actually what

0:35:14.320 --> 0:35:30.520
<v Speaker 3>was done with transplants and other things.

0:35:33.320 --> 0:35:36.719
<v Speaker 1>Here's a question for you. So you, as a scientist

0:35:36.760 --> 0:35:39.920
<v Speaker 1>and a physician, you're very careful about saying, you know,

0:35:40.000 --> 0:35:42.799
<v Speaker 1>if this works and this doesn't work yet, and so on.

0:35:43.120 --> 0:35:46.879
<v Speaker 1>But what is your guests in a century from now.

0:35:47.000 --> 0:35:50.479
<v Speaker 1>Let's say, do you feel like this is a dead

0:35:50.560 --> 0:35:53.080
<v Speaker 1>on winner, this is definitely going to work, or do

0:35:53.080 --> 0:35:55.680
<v Speaker 1>you feel there are some problems that are insurmountable.

0:35:56.440 --> 0:35:59.319
<v Speaker 3>I'm positive that this is going to work. I think

0:35:59.400 --> 0:36:02.640
<v Speaker 3>we are going to it. I think we're developing new

0:36:02.680 --> 0:36:06.280
<v Speaker 3>tools now. I think our ideas about what death is

0:36:06.280 --> 0:36:10.080
<v Speaker 3>is changing. In particular, I'm referring to cells here, but

0:36:10.200 --> 0:36:11.799
<v Speaker 3>we can build a death like we can do like

0:36:11.800 --> 0:36:12.840
<v Speaker 3>a ground up approach.

0:36:12.880 --> 0:36:17.480
<v Speaker 2>We can really develop new approaches and therapist I'm confident

0:36:17.520 --> 0:36:20.280
<v Speaker 2>that this is a field that is going to advance

0:36:20.400 --> 0:36:21.120
<v Speaker 2>in the future.

0:36:22.000 --> 0:36:23.440
<v Speaker 1>Let me just double click on that. What do you

0:36:23.480 --> 0:36:26.360
<v Speaker 1>mean by we're having a new understanding of what death is?

0:36:27.320 --> 0:36:27.520
<v Speaker 3>Well?

0:36:28.800 --> 0:36:31.520
<v Speaker 2>As I said, you know, I went to med school

0:36:31.520 --> 0:36:34.520
<v Speaker 2>like recently, I still would like to think that I'm young,

0:36:35.160 --> 0:36:36.560
<v Speaker 2>although it's starting to show.

0:36:37.160 --> 0:36:40.880
<v Speaker 3>I was thought that once there's blood laws, that sales

0:36:41.000 --> 0:36:44.200
<v Speaker 3>just die like after a couple of minutes.

0:36:44.320 --> 0:36:47.000
<v Speaker 2>And you know, there have been like instances where people

0:36:47.000 --> 0:36:50.000
<v Speaker 2>have observed it in their work. But it's not this

0:36:50.520 --> 0:36:54.520
<v Speaker 2>reasoning or under tending that the death is a process

0:36:54.640 --> 0:36:59.040
<v Speaker 2>it's not ubiquitous, it's not widespread, and so you know,

0:36:59.400 --> 0:37:03.280
<v Speaker 2>taking data into account first and then start to do research.

0:37:02.960 --> 0:37:05.600
<v Speaker 3>On these things. I think that's going to lead to

0:37:05.680 --> 0:37:07.480
<v Speaker 3>new tools and new developments.

0:37:07.520 --> 0:37:10.799
<v Speaker 2>Just to give you like a simple example, we had

0:37:10.840 --> 0:37:14.080
<v Speaker 2>a so in in the team, we would always have

0:37:14.160 --> 0:37:18.520
<v Speaker 2>our electrophysiologists. So these are people who take slices of

0:37:18.560 --> 0:37:22.880
<v Speaker 2>tissue like right, and they record electrical properties from cells

0:37:22.920 --> 0:37:27.400
<v Speaker 2>from neurons. I remember one instance, we had a slide,

0:37:27.840 --> 0:37:30.160
<v Speaker 2>a really bad run, and sales were, like, you know,

0:37:30.280 --> 0:37:31.560
<v Speaker 2>they were not doing well.

0:37:31.960 --> 0:37:35.640
<v Speaker 3>This was early on, and this new person came and

0:37:35.680 --> 0:37:38.120
<v Speaker 3>so he's looking at the cells in there around which

0:37:38.160 --> 0:37:39.960
<v Speaker 3>is usually a bad thing because they go from like

0:37:40.000 --> 0:37:43.319
<v Speaker 3>a triangle to like a rounding and so because so

0:37:43.360 --> 0:37:46.200
<v Speaker 3>he just goes like, oh, these cells are dead, because

0:37:46.239 --> 0:37:49.279
<v Speaker 3>he's accustomed to thinking that these cells are dead and

0:37:49.320 --> 0:37:50.239
<v Speaker 3>they're useless, like.

0:37:50.239 --> 0:37:53.239
<v Speaker 2>Right, and so you know, so after a whole day

0:37:53.239 --> 0:37:55.520
<v Speaker 2>of work, we go like, maybe you should think about

0:37:55.520 --> 0:37:58.680
<v Speaker 2>these cells and maybe they're not dead yet, maybe they

0:37:58.680 --> 0:37:59.400
<v Speaker 2>can be saved.

0:37:59.400 --> 0:38:01.960
<v Speaker 3>And so it's interesting, you know, from our point of view.

0:38:03.239 --> 0:38:05.480
<v Speaker 2>He was new to the whole team, and so it's

0:38:05.520 --> 0:38:09.680
<v Speaker 2>really interesting like his perception of like one thing and ours.

0:38:09.760 --> 0:38:12.239
<v Speaker 2>It's basically like it's the glass like half full or

0:38:12.280 --> 0:38:14.160
<v Speaker 2>half empty situation.

0:38:14.960 --> 0:38:16.920
<v Speaker 1>And have you been able to show that you can

0:38:16.960 --> 0:38:20.600
<v Speaker 1>take those bloated cells and reverse the processes?

0:38:21.560 --> 0:38:25.040
<v Speaker 2>So absolutely, so this was the first So going back

0:38:25.080 --> 0:38:27.200
<v Speaker 2>to who were doing like initial research, that was the

0:38:27.239 --> 0:38:30.520
<v Speaker 2>first observation that we made. So because I trained in

0:38:30.640 --> 0:38:34.120
<v Speaker 2>radiology and so you know, you do an MRI in

0:38:34.200 --> 0:38:36.319
<v Speaker 2>the brain, like you know sort of like how the

0:38:36.360 --> 0:38:39.480
<v Speaker 2>signal is going to change based on the fake that

0:38:39.600 --> 0:38:42.960
<v Speaker 2>sales are becoming round or bloated. And so you know,

0:38:42.960 --> 0:38:46.040
<v Speaker 2>if we're looking these slices, like these cells and we're

0:38:46.080 --> 0:38:48.520
<v Speaker 2>seeing that they're not round, they're starting to regain their

0:38:49.080 --> 0:38:51.120
<v Speaker 2>their shape like right, And that was the first thing

0:38:51.160 --> 0:38:52.360
<v Speaker 2>we observed with the technology.

0:38:52.360 --> 0:38:56.319
<v Speaker 1>So that's why, oh incredible, wow, what was that like

0:38:56.360 --> 0:38:58.640
<v Speaker 1>for you the first time you saw that reversal?

0:38:59.560 --> 0:39:02.239
<v Speaker 2>The whole was really you know now with like a

0:39:02.320 --> 0:39:05.640
<v Speaker 2>benefit of the hindside, Like just for us, we started

0:39:05.680 --> 0:39:08.960
<v Speaker 2>in a closet like Atale University, we cleared out the

0:39:09.040 --> 0:39:12.520
<v Speaker 2>closet and we just started doing stuff there and it

0:39:12.640 --> 0:39:16.640
<v Speaker 2>went from like basic stuff because because people think that

0:39:17.200 --> 0:39:20.160
<v Speaker 2>when they think about research. They have these like grand

0:39:20.200 --> 0:39:23.000
<v Speaker 2>ideas of like you know, scientists and like fight codes

0:39:23.040 --> 0:39:24.239
<v Speaker 2>like doing some capitalists.

0:39:24.680 --> 0:39:29.840
<v Speaker 3>This was such a completely opposite thing. And so you know,

0:39:30.160 --> 0:39:33.640
<v Speaker 3>you go through these motions daily twenty four to seven.

0:39:33.719 --> 0:39:36.160
<v Speaker 3>You're grinding, and you finally you start to see stuff.

0:39:36.880 --> 0:39:39.359
<v Speaker 2>And then the first thing, like like the genuine first

0:39:39.400 --> 0:39:41.880
<v Speaker 2>thing is confusion because you see something.

0:39:41.520 --> 0:39:44.840
<v Speaker 3>And you're like, well, this doesn't like go you know, it's.

0:39:44.840 --> 0:39:47.480
<v Speaker 2>It's sort of go against the grain, right, So it's

0:39:47.560 --> 0:39:50.200
<v Speaker 2>like like what do I do now? And so it's

0:39:50.239 --> 0:39:52.719
<v Speaker 2>like a confusion and excitement because you want to be

0:39:52.760 --> 0:39:54.880
<v Speaker 2>sure that that you don't fool yourself, like that's the

0:39:54.880 --> 0:39:56.200
<v Speaker 2>biggest mistaked.

0:39:55.840 --> 0:39:57.960
<v Speaker 3>You know, you can make. But you know, it was

0:39:58.000 --> 0:40:00.440
<v Speaker 3>really funny, you know, the whole thing. Yeah, it was

0:40:00.480 --> 0:40:01.080
<v Speaker 3>really fun.

0:40:01.320 --> 0:40:04.160
<v Speaker 1>Wow, did you realize at that moment what you were

0:40:04.160 --> 0:40:06.960
<v Speaker 1>on the verge of because then you published paper. You know,

0:40:07.000 --> 0:40:10.960
<v Speaker 1>you've had really terrific publications that you've put out about

0:40:11.080 --> 0:40:14.239
<v Speaker 1>you know, the pig brain and the cellular functions. Did

0:40:14.280 --> 0:40:16.160
<v Speaker 1>you did you realize when you were first seeing that

0:40:16.200 --> 0:40:17.160
<v Speaker 1>what this was going to lead to?

0:40:17.480 --> 0:40:21.480
<v Speaker 2>I you know, like if you still understand like where

0:40:21.480 --> 0:40:24.200
<v Speaker 2>these can go and there's always like something, you know,

0:40:24.520 --> 0:40:26.000
<v Speaker 2>like if you look at something and you like, oh,

0:40:26.080 --> 0:40:28.560
<v Speaker 2>like these capabilities are like new, you know, like these

0:40:28.600 --> 0:40:31.960
<v Speaker 2>implications are huge and it's still ongoing and potential.

0:40:35.880 --> 0:40:39.839
<v Speaker 1>So that was Vonimir Russella. And it's clear that as

0:40:39.840 --> 0:40:44.000
<v Speaker 1>a community, our biological insights are opening up big new

0:40:44.080 --> 0:40:47.719
<v Speaker 1>questions for us. Now this really complicates things from a

0:40:47.800 --> 0:40:52.799
<v Speaker 1>clinical and legal perspective. Death is usually defined as the

0:40:52.880 --> 0:40:56.719
<v Speaker 1>cessation of biological functions. Traditionally this had to do with

0:40:56.840 --> 0:40:59.840
<v Speaker 1>the stopping of the breath and the stopping of the pulse,

0:41:00.400 --> 0:41:03.360
<v Speaker 1>but even that started to get complicated by the nineteen

0:41:03.440 --> 0:41:08.680
<v Speaker 1>fifties because people had invented ventilators so it didn't necessarily

0:41:08.719 --> 0:41:13.200
<v Speaker 1>matter if you stopped breathing, and people invented defibrillators so

0:41:13.239 --> 0:41:16.120
<v Speaker 1>they could get your heart going again, so that no

0:41:16.239 --> 0:41:19.239
<v Speaker 1>longer made sense to define death that way. And in

0:41:19.320 --> 0:41:22.200
<v Speaker 1>nineteen sixty eight Harvard Medical School got together to put

0:41:22.200 --> 0:41:25.080
<v Speaker 1>together a definition of brain death and they said, look,

0:41:25.400 --> 0:41:28.359
<v Speaker 1>if you are in a coma that's irreversible, then we'll

0:41:28.360 --> 0:41:32.640
<v Speaker 1>say you're dead. And different places took on different versions

0:41:32.680 --> 0:41:35.719
<v Speaker 1>of this until nineteen eighty when the United States came

0:41:35.760 --> 0:41:39.719
<v Speaker 1>up with a Uniform Determination of Death Act and they said, look,

0:41:40.400 --> 0:41:44.800
<v Speaker 1>you're dead if you've had an irreversible cessation of blood

0:41:44.800 --> 0:41:49.600
<v Speaker 1>flow and breathing, or an irreversible cessation of the function

0:41:49.760 --> 0:41:54.120
<v Speaker 1>of your brain. But the interesting thing is how interventions

0:41:54.160 --> 0:41:57.080
<v Speaker 1>could play a role here, because the key word that

0:41:57.160 --> 0:42:02.399
<v Speaker 1>needs to come under scrutiny is reversible. What do we do,

0:42:02.440 --> 0:42:07.040
<v Speaker 1>How do we redefine death when many problems are no

0:42:07.120 --> 0:42:11.600
<v Speaker 1>longer going to be irreversible. Now, I want to be clear,

0:42:11.640 --> 0:42:13.680
<v Speaker 1>there's still a long way to go with the science.

0:42:13.719 --> 0:42:16.759
<v Speaker 1>The work is underway in pigs, but no one's even

0:42:16.800 --> 0:42:19.920
<v Speaker 1>talking about humans at this point, in part because the

0:42:20.040 --> 0:42:24.120
<v Speaker 1>ethical questions are something we can't even wrap our heads around.

0:42:25.160 --> 0:42:27.560
<v Speaker 1>But the thing I want to point out is that

0:42:27.680 --> 0:42:31.600
<v Speaker 1>this is now a question. It is a scientific problem

0:42:31.640 --> 0:42:35.000
<v Speaker 1>being studied in the labs and published in the top journals.

0:42:35.600 --> 0:42:38.440
<v Speaker 1>It'll be a long while before you hear about this

0:42:38.600 --> 0:42:42.440
<v Speaker 1>past the walls of the lab, but it's coming. So

0:42:42.520 --> 0:42:46.920
<v Speaker 1>consider this in the context of recent history. When Mary

0:42:47.000 --> 0:42:50.200
<v Speaker 1>Shelley wrote her novel Frankenstein that was just over two

0:42:50.280 --> 0:42:53.600
<v Speaker 1>hundred years ago, it was cast as a warning against

0:42:53.680 --> 0:42:57.720
<v Speaker 1>the dangers of playing God. But it's fascinating to see

0:42:58.040 --> 0:43:01.960
<v Speaker 1>how the concept of playing god evolved. After all, you

0:43:01.960 --> 0:43:05.239
<v Speaker 1>can imagine a time when someone might have said, Hey,

0:43:05.320 --> 0:43:08.399
<v Speaker 1>if you crack open someone's chest and operate on their heart,

0:43:08.600 --> 0:43:11.799
<v Speaker 1>you're playing God. Or if you take out someone's heart

0:43:11.920 --> 0:43:15.840
<v Speaker 1>entirely and replace it with an artificial, pulseless blood pump,

0:43:16.080 --> 0:43:18.719
<v Speaker 1>you are playing God. Or what about doing an open

0:43:18.800 --> 0:43:21.760
<v Speaker 1>head surgery to cut out a brain tumor playing god?

0:43:22.160 --> 0:43:26.920
<v Speaker 1>Or injecting someone with a medication that reverses at the

0:43:27.000 --> 0:43:31.520
<v Speaker 1>level of invisibly small molecules whatever process in their body

0:43:31.640 --> 0:43:35.480
<v Speaker 1>is making them sick. You can imagine any moment in

0:43:35.640 --> 0:43:37.880
<v Speaker 1>history where someone would have looked at this and said,

0:43:38.360 --> 0:43:41.160
<v Speaker 1>you're messing with the body and playing the role of

0:43:41.200 --> 0:43:44.759
<v Speaker 1>a deity. But when we look at the long arc

0:43:44.880 --> 0:43:48.759
<v Speaker 1>of human understanding of science, we see this is the

0:43:48.880 --> 0:43:52.200
<v Speaker 1>natural direction of things. As we come to understand that

0:43:52.239 --> 0:43:54.840
<v Speaker 1>the heart is just a pump, we can fix it

0:43:54.920 --> 0:43:58.839
<v Speaker 1>or replace it. Once we understand what a tumor is

0:43:59.160 --> 0:44:02.040
<v Speaker 1>a cell that keep dividing out of control, we can

0:44:02.120 --> 0:44:05.000
<v Speaker 1>learn how to open the skull and control the bleeding

0:44:05.040 --> 0:44:07.920
<v Speaker 1>of the brain tissue, and the whole issue of tumor

0:44:07.960 --> 0:44:13.479
<v Speaker 1>removal becomes routine. Once we know how molecular cascades work,

0:44:13.560 --> 0:44:16.640
<v Speaker 1>then we put them in the textbooks of high school students,

0:44:16.880 --> 0:44:20.600
<v Speaker 1>and we find drugs that interact with those cascades, and

0:44:20.640 --> 0:44:22.799
<v Speaker 1>we don't think twice about this stuff. We don't think

0:44:22.840 --> 0:44:27.040
<v Speaker 1>about it as deity playing, just that someone is hurt

0:44:27.120 --> 0:44:29.960
<v Speaker 1>or sick and needs our help, and that this is

0:44:30.200 --> 0:44:34.600
<v Speaker 1>some operation or medication that we now understand that we

0:44:34.680 --> 0:44:38.840
<v Speaker 1>didn't used to. So John Dunn, who died in sixteen

0:44:38.880 --> 0:44:42.439
<v Speaker 1>thirty one, coming up on four hundred years ago, could

0:44:42.480 --> 0:44:46.399
<v Speaker 1>have never imagined that when he penned the poem death

0:44:46.480 --> 0:44:49.839
<v Speaker 1>Be not Proud, that we'd actually be talking about the

0:44:50.080 --> 0:44:54.600
<v Speaker 1>end of death as just a molecular puzzle about which

0:44:54.640 --> 0:44:57.520
<v Speaker 1>we say not now, but at some point, okay, we

0:44:57.560 --> 0:45:00.600
<v Speaker 1>got it. Just block these pathways by which die or

0:45:00.600 --> 0:45:04.600
<v Speaker 1>commit suicide, and then these cells stay alive and the

0:45:04.680 --> 0:45:08.560
<v Speaker 1>whole system just keeps on trucking. And he could never

0:45:08.760 --> 0:45:12.640
<v Speaker 1>imagined that we'd even be talking about rebooting a system

0:45:13.000 --> 0:45:17.640
<v Speaker 1>that has already ground to a halt. Now. Mary Shelley

0:45:17.760 --> 0:45:21.000
<v Speaker 1>died in the mid nineteenth century, two centuries after done,

0:45:21.600 --> 0:45:24.520
<v Speaker 1>and most of us will see the mid twenty first century,

0:45:24.640 --> 0:45:28.960
<v Speaker 1>two centuries after Mary Shelley, and it looks likely that we,

0:45:29.360 --> 0:45:32.239
<v Speaker 1>or our children or our near term descendants will be

0:45:32.320 --> 0:45:37.800
<v Speaker 1>the first to see Shelley's ethical questions get tackled. Should

0:45:37.880 --> 0:45:42.000
<v Speaker 1>we revivify a system that's come to a halt under

0:45:42.000 --> 0:45:47.160
<v Speaker 1>what circumstances? What will be the consequences for society as

0:45:47.160 --> 0:45:50.440
<v Speaker 1>a community will come to address Shelley's questions not as

0:45:50.480 --> 0:45:54.239
<v Speaker 1>a science fiction fantasy, but as a basic challenge of

0:45:54.280 --> 0:45:58.719
<v Speaker 1>passing the right legislation and determining how hospital ethics committees

0:45:59.040 --> 0:46:02.640
<v Speaker 1>should make their decay decisions about reversing death. And there

0:46:02.719 --> 0:46:05.280
<v Speaker 1>might be whole groups of people that are your friends

0:46:05.280 --> 0:46:08.680
<v Speaker 1>and neighbors and work colleagues, and some of them will

0:46:08.719 --> 0:46:11.720
<v Speaker 1>have ground to a halt. At some point they're revivified,

0:46:12.080 --> 0:46:14.960
<v Speaker 1>just as you currently have friends and neighbors and colleagues

0:46:15.000 --> 0:46:17.839
<v Speaker 1>who were under anesthesia and woke up, or they had

0:46:17.840 --> 0:46:20.600
<v Speaker 1>a heart attack and had their heart defibrillated, or they

0:46:20.600 --> 0:46:24.319
<v Speaker 1>were in a coma for weeks and regained consciousness. And

0:46:24.400 --> 0:46:27.640
<v Speaker 1>at some point we'll all live in this new world

0:46:27.920 --> 0:46:32.200
<v Speaker 1>where we have to address whole new fields of question marks.

0:46:32.960 --> 0:46:41.600
<v Speaker 1>Because as John Dunn predicted death will have died. Go

0:46:41.640 --> 0:46:44.719
<v Speaker 1>to eagleman dot com slash podcast for more information and

0:46:44.760 --> 0:46:48.960
<v Speaker 1>to find further reading. Send me an email at podcasts

0:46:48.960 --> 0:46:52.040
<v Speaker 1>at eagleman dot com with questions or discussions, and I'll

0:46:52.040 --> 0:46:58.840
<v Speaker 1>be making sporadic episodes in which I address those until

0:46:58.840 --> 0:47:02.880
<v Speaker 1>next time. I'm David Eagleman, and this is Inner Cosmos