Mark Roth: Suspended animation is within our grasp

94,211 views ・ 2010-03-15

TED


Please double-click on the English subtitles below to play the video.

00:16
I'm going to talk to you today about my work on suspended animation.
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Now, usually when I mention suspended animation,
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people will flash me the Vulcan sign and laugh.
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But now, I'm not talking about gorking people out
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to fly to Mars or even Pandora,
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as much fun as that may be.
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I'm talking about
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the concept of using suspended animation
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to help people out in trauma.
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So what do I mean
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when I say "suspended animation"?
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It is the process by which
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animals de-animate,
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appear dead
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and then can wake up again without being harmed.
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OK, so here is the sort of big idea:
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If you look out at nature,
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you find that
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as you tend to see suspended animation,
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you tend to see immortality.
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And so, what I'm going to tell you about
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is a way to tell a person who's in trauma --
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find a way to de-animate them a bit
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so they're a little more immortal
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when they have that heart attack.
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An example of an organism or two
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that happens to be quite immortal
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would be plant seeds
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or bacterial spores.
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These creatures are
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some of the most immortal life forms on our planet,
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and they tend to spend most of their time
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in suspended animation.
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Bacterial spores are thought now by scientists
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to exist as individual cells
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that are alive, but in suspended animation
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for as long as 250 million years.
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To suggest that this all, sort of, about little, tiny creatures,
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I want to bring it close to home.
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In the immortal germ line
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of human beings --
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that is, the eggs that sit in the ovaries --
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they actually sit there in a state of suspended animation
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for up to 50 years in the life of each woman.
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So then there's also my favorite example
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of suspended animation.
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This is Sea-Monkeys.
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Those of you with children,
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you know about them.
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You go to the pet store or the toy store,
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and you can buy these things.
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You just open the bag, and you just dump them
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into the plastic aquarium,
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and in about a week or so, you'll have little shrimps swimming around.
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Well, I wasn't so interested in the swimming.
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I was interested in what was going on in the bag,
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the bag on the toy store shelf
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where those shrimp sat
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in suspended animation indefinitely.
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So these ideas of suspended animation
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are not just about cells and weird, little organisms.
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Occasionally, human beings
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are briefly de-animated,
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and the stories of people who are briefly de-animated
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that interest me the most
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are those having to do with the cold.
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Ten years ago, there was a skier in Norway
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that was trapped in an icy waterfall,
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and she was there for two hours before they extracted her.
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She was extremely cold,
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and she had no heartbeat --
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for all intents and purposes she was dead, frozen.
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Seven hours later,
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still without a heartbeat,
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they brought her back to life, and she went on to be
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the head radiologist
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in the hospital that treated her.
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A couple of years later --
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so I get really excited about these things --
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about a couple of years later,
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there was a 13-month-old, she was from Canada.
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Her father had gone out in the wintertime; he was working night shift,
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and she followed him outside in nothing but a diaper.
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And they found her hours later,
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frozen, lifeless,
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and they brought her back to life.
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There was a 65-year-old woman
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in Duluth, Minnesota last year
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that was found frozen and without a pulse
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in her front yard one morning in the winter,
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and they brought her back to life.
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The next day, she was doing so well, they wanted to run tests on her.
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She got cranky and just went home.
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(Laughter)
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So, these are miracles, right?
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These are truly miraculous things that happen.
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Doctors have a saying
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that, in fact, "You're not dead until you're warm and dead."
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And it's true. It's true.
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In the New England Journal of Medicine,
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there was a study published that showed
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that with appropriate rewarming,
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people who had suffered without a heartbeat for three hours
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could be brought back to life without any neurologic problems.
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That's over 50 percent.
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So what I was trying to do is think of a way
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that we could study
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suspended animation
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to think about a way
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to reproduce, maybe,
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what happened to the skier.
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Well, I have to tell you something very odd,
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and that is that being exposed to low oxygen
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does not always kill.
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So, in this room, there's 20 percent oxygen or so,
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and if we reduce the oxygen concentration,
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we will all be dead.
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And, in fact, the animals we were working with in the lab --
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these little garden worms, nematodes --
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they were also dead when we exposed them to low oxygen.
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And here's the thing that should freak you out.
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And that is that, when we lower the oxygen concentration further
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by 100 times, to 10 parts per million,
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they were not dead,
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they were in suspended animation,
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and we could bring them back to life without any harm.
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And this precise oxygen concentration,
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10 parts per million,
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that caused suspended animation,
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is conserved.
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We can see it in a variety of different organisms.
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One of the creatures we see it in
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is a fish.
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And we can turn its heartbeat on and off by going in and out
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of suspended animation like you would a light switch.
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So this was pretty shocking to me,
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that we could do this.
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And so I was wondering, when we were trying
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to reproduce the work with the skier,
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that we noticed that, of course,
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she had no oxygen consumption,
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and so maybe she was in a similar state of suspended animation.
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But, of course, she was also extremely cold.
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So we wondered what would happen
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if we took our suspended animals and exposed them to the cold.
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And so, what we found out
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was that, if you take animals
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that are animated like you and I,
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and you make them cold -- that is, these were the garden worms --
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now they're dead.
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But if you have them in suspended animation,
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and move them into the cold, they're all alive.
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And there's the very important thing there:
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If you want to survive the cold,
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you ought to be suspended. Right?
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It's a really good thing.
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And so, we were thinking about that,
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about this relationship between these things,
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and thinking about whether or not that's what happened to the skier.
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And so we wondered: Might there be some agent
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that is in us, something that we make ourselves,
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that we might be able to regulate our own metabolic flexibility
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in such a way as to be able to survive
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when we got extremely cold, and might otherwise pass away?
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I thought it might be interesting to sort of hunt for such things.
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You know?
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I should mention briefly here
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that physiology textbooks that you can read about
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will tell you that this is a kind of heretical thing to suggest.
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We have, from the time we are slapped on the butt
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until we take our last dying breath --
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that's when we're newborn to when we're dead --
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we cannot reduce our metabolic rate
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below what's called a standard,
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or basal metabolic rate.
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But I knew that there were examples
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of creatures, also mammals,
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that do reduce their metabolic rate
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such as ground squirrels and bears,
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they reduce their metabolic rate
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in the wintertime when they hibernate.
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So I wondered: Might we be able to find some agent or trigger
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that might induce such a state in us?
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And so, we went looking for such things.
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And this was a period of time when we failed tremendously.
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Ken Robinson is here. He talked about the glories of failure.
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Well, we had a lot of them.
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We tried many different chemicals and agents,
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and we failed over and over again.
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So, one time, I was at home
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watching television on the couch
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while my wife was putting our child to bed,
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and I was watching a television show.
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It was a television show --
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it was a NOVA show on PBS --
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about caves in New Mexico.
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And this particular cave was Lechuguilla,
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and this cave is incredibly toxic to humans.
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The researchers had to suit up just to enter it.
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It's filled with this toxic gas,
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hydrogen sulfide.
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Now, hydrogen sulfide is curiously present in us.
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We make it ourselves.
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The highest concentration is in our brains.
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Yet, it was used
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as a chemical warfare agent in World War I.
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It's an extraordinarily toxic thing.
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In fact, in chemical accidents,
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hydrogen sulfide is known to --
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if you breathe too much of it, you collapse to the ground,
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you appear dead,
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but if you were brought out into room air, you can be reanimated without harm,
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if they do that quickly.
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So, I thought, "Wow, I have to get some of this."
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(Laughter)
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Now, it's post-9/11 America,
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and when you go into the research institute,
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and you say, "Hi.
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I'd like to buy some concentrated,
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compressed gas cylinders
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of a lethal gas
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because I have these ideas, see,
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about wanting to suspend people.
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It's really going to be OK."
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So that's kind of a tough day,
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but I said, "There really is
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some basis for thinking why you might want to do this."
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As I said, this agent is in us,
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and, in fact, here's a curious thing,
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it binds to the very place inside of your cells
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where oxygen binds, and where you burn it,
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and that you do this burning to live.
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And so we thought, like in a game of musical chairs,
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might we be able to give a person
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some hydrogen sulfide,
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and might it be able to occupy that place
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like in a game of musical chairs where oxygen might bind?
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And because you can't bind the oxygen,
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maybe you wouldn't consume it,
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and then maybe it would reduce your demand for oxygen.
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I mean, who knows?
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So -- (Laughter)
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So, there's the bit about the dopamine
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and being a little bit, what do you call it, delusional,
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and you might suggest that was it.
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And so, we wanted to find out
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might we be able to use
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hydrogen sulfide in the presence of cold,
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and we wanted to see whether we could
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reproduce this skier in a mammal.
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Now, mammals are warm-blooded creatures,
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and when we get cold, we shake and we shiver, right?
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We try to keep our core temperature at 37 degrees
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by actually burning more oxygen.
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So, it was interesting for us
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when we applied hydrogen sulfide
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to a mouse when it was also cold
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because what happened is the core temperature
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of the mouse got cold.
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It stopped moving.
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It appeared dead.
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Its oxygen consumption rate
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fell by tenfold.
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And here's the really important point.
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I told you hydrogen sulfide is in us.
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It's rapidly metabolized,
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and all you have to do after six hours of being
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in this state of de-animation
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is simply put the thing out in room air,
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and it warms up, and it's none the worse for wear.
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Now, this was cosmic.
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Really. Because we had found a way
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to de-animate a mammal,
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and it didn't hurt it.
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Now, we'd found a way to reduce
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its oxygen consumption
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to rock-bottom levels, and it was fine.
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Now, in this state of de-animation,
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it could not go out dancing,
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but it was not dead,
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and it was not harmed.
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So we started to think: Is this the agent
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that might have been present in the skier,
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and might have she had more of it than someone else,
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and might that have been able to reduce
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her demand for oxygen
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before she got so cold that
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she otherwise would have died,
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as we found out with our worm experiments?
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So, we wondered:
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Can we do anything useful
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with this capacity to
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control metabolic flexibility?
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And one of the things we wondered --
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I'm sure some of you out there are economists,
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and you know all about supply and demand.
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And when supply is equal to demand,
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everything's fine,
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but when supply falls,
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in this case of oxygen,
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and demand stays high, you're dead.
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So, what I just told you
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is we can now reduce demand.
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We ought to be able to lower supply
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to unprecedented low levels without killing the animal.
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And with money we got from DARPA,
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we could show just that.
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If you give mice hydrogen sulfide,
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you can lower their demand for oxygen,
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and you can put them into oxygen concentrations
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that are as low as 5,000 feet above the top of Mt. Everest,
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and they can sit there for hours, and there's no problem.
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Well this was really cool.
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We also found out that we could subject animals
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to otherwise lethal blood loss, and we could save them
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if we gave them hydrogen sulfide.
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So these proof of concept experiments
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led me to say "I should found a company,
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and we should take this out to a wider playing field."
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I founded a company called Ikaria
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with others' help.
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And this company, the first thing it did
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was make a liquid formulation of hydrogen sulfide
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an injectable form that we could put in
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and send it out to physician scientists all over the world
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who work on models of critical care medicine,
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and the results are incredibly positive.
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In one model of heart attack,
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animals given hydrogen sulfide
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showed a 70 percent reduction in heart damage
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compared to those who got the standard of care that
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you and I would receive if we were to have a heart attack here today.
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Same is true for organ failure,
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when you have loss of function owing to poor perfusion of kidney, of liver,
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acute respiratory distress syndrome
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and damage suffered in cardiac-bypass surgery.
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So, these are the thought leaders in trauma medicine
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all over the world saying this is true,
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so it seems that exposure to hydrogen sulfide
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decreases damage that you receive
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from being exposed to otherwise lethal-low oxygen.
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And I should say that the concentrations of hydrogen sulfide
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required to get this benefit
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are low, incredibly low.
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In fact, so low that physicians will not have to lower or dim
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the metabolism of people much at all
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to see the benefit I just mentioned,
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which is a wonderful thing, if you're thinking about adopting this.
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You don't want to be gorking people out
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just to save them, it's really confusing.
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(Laughter)
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So, I want to say that we're in human trials.
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Now, and so --
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(Applause)
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Thank you. The Phase 1 safety studies are over,
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and we're doing fine, we're now moved on.
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We have to get to Phase 2 and Phase 3. It's going to take us a few years.
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This has all moved very quickly,
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and the mouse experiments
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of hibernating mice happened in 2005;
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the first human studies were done in 2008,
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and we should know in a couple of years
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whether it works or not.
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And this all happened really quickly
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because of a lot of help from a lot of people.
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I want to mention that, first of all,
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my wife, without whom this talk and my work would not be possible,
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so thank you very much.
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Also, the brilliant scientists who work at my lab
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and also others on staff,
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the Fred Hutchinson Cancer Research Center in Seattle, Washington --
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wonderful place to work.
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And also the wonderful scientists
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and businesspeople at Ikaria.
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One thing those people did out there
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was take this technology of hydrogen sulfide,
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which is this start-up company that's burning venture capital very quickly,
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and they fused it with another company
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that sells another toxic gas
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that's more toxic than hydrogen sulfide,
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and they give it to newborn babies who would otherwise die
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from a failure to be able to oxygenate their tissues properly.
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And this gas that is delivered in over
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a thousand critical care hospitals worldwide,
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now is approved, on label,
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and saves thousands of babies a year
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from certain death.
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(Applause)
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So it's really incredible
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for me to be a part of this.
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And I want to say that I think we're on the path
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of understanding metabolic flexibility
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in a fundamental way,
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and that in the not too distant future,
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an EMT might give an injection of hydrogen sulfide,
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or some related compound,
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to a person suffering severe injuries,
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and that person might de-animate a bit,
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they might become a little more immortal.
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Their metabolism will fall
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as though you were dimming a switch on a lamp at home.
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And then, they will have the time, that will buy them the time,
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to be transported to the hospital
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to get the care they need.
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And then, after they get that care --
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like the mouse, like the skier,
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like the 65-year-old woman --
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they'll wake up.
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A miracle?
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We hope not, or maybe we just hope
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to make miracles a little more common.
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Thank you very much.
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(Applause)
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About this website

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