(Transcribed by TurboScribe.ai. Go Unlimited to remove this message.) Did you read ahead of my notes?

No.

This is perfect.

Okay.

We're a good team.

All right.

All right.

Let's talk about pig organs.

Yeah.

So I love pig organs.

I'm Mick Ebeling, founder and CEO of Not Impossible Labs.

For the past 15 years, we've been on a mission to change the world through technology and

story by addressing societal problems to improve the lives of everyone.

With a crew of engineers, hackers, entrepreneurs, technologists, storytellers, and artists,

we've tackled and solved some of the world's most incredible challenges.

But here's the thing, we're just a small team in Venice Beach.

The world is full of people making the impossible possible.

My goal now with this podcast is to find these people, share their stories, and hopefully

together we can keep pushing the limits of what's possible.

On today's episode, we talk to Dr. Greg Fahy.

Dr. Fahy has figured out a way to freeze organs indefinitely and then use them for

life-saving transplants in the future.

They might blow out or something like that.

Or traditionally, after you've transplanted them, they would turn into large blood clots

after a while.

In this case, we undid the clamps and the organ just pinked up.

Han Solo.

Is that real?

Could he actually have survived?

Welcome.

I'm so glad you're here.

I'm looking forward to this conversation.

Thank you very much.

I want to just give you a little understanding of kind of what this podcast is all about

and also what Not Impossible is all about.

One of our kind of core tenets and our mission is to eradicate societal absurdities.

I like that.

To do that, it's based on this premise that everything that is impossible today will eventually

become possible.

I like that.

And that, as a scientist, you can appreciate, is based on the fact that the inverse of that

is already true, which everything that is possible today at one point was impossible.

Absolutely.

So with that premise, we seek to go out and we as a lab will go out and create things

that transition things from impossible to possible.

But part of our mission is also to inspire other people, one, to believe in that core

tenet, everything that's impossible today will eventually become possible.

So why can't they be the one who makes that transition or as the catalyst to that?

So this podcast is really about that.

It's to remind people that no matter how you see the world, whether you see it as as amazing,

and bountiful, or whether you see it as dismal and gray, the fact remains that things are

transitioning every single day from impossible to possible and we want to capture that.

So it makes people go, wait a second, okay.

From worse to better.

Yep.

Exactly.

It's a reason to be optimistic about the future and we could use that, I think, these days.

I think we can.

When we started this thinking about this episode, we called it, in fact, you can see from the

book and we kept it on there as a little provocative thing.

Frozen organs.

Frozen organs.

Right.

Not the case.

Frozen is a dirty word and we're going to get to that, but let's start with a little

bit about you.

Where are you from?

How did you get into this?

Like what you do is so specific and niche.

What was your pathway to get here?

Well, probably several different things coming together, but one of the elements was when

I was in high school, my mother had a subscription to Life Magazine and there was an article

about these death panels that would sit around and determine whether you could get an organ

or not because the requirements for organs are much more plentiful than the supply.

And so people would sit around and decide if Joe Doakes is going to get that kidney or

if it's going to go to Laura over here.

And I thought that's a terrible thing.

It would be really nice if we could do something about the organ shortage.

And then later on, becoming more familiar with cryobiology, I realized maybe organ cryopreservation

is really going to be necessary.

Were you always kind of a science nerd in high school?

Yeah.

I read my first book on aging when I was in high school.

Okay.

Yeah.

So I was interested in science.

And one day my stepfather went to UC Irvine library for some reason and he saw this amazing

book and he just brought it back to me.

He checked it out and it was this giant thick book called cryobiology.

Let's talk for a second because now we're getting into vitrification.

Yes.

Right.

So this is leading up to it.

This is leading up to it.

So, but now let's talk about vitrification, what it means and I'm, this is like, so I'm

going to, you tell me if I'm getting this right.

Okay.

All right.

So the whole concept of cryopreservation is in the relationship between freezing and when

you freeze something and everyone's seen this, when they freeze ice, it kind of, it freezes

at different levels.

First it freezes on the outside and the middle stays warm and then eventually freezes.

And then when you crack it open, it cracks and fractures and all kinds of things.

So it's very unstable.

It freezes.

And if you're just trying to make an ice cube for a cocktail, you're good, but probably

not so good if you're freezing organs.

The concept of vitrification is now creating a way for an organ to be completely encapsulated

or injected with a cryopreservation agent that are filled with nanoparticles and iron

oxide, which to me was a really interesting thing to learn about this.

So now you have this organ that's infused with little bits of metal in there.

You bring that down to a temperature and it's not about bringing it down.

That's about bringing it back up.

Is that right?

How am I doing so far?

Well, you're, you're telling the Bischoff line pretty well.

Oh, okay.

All right.

All right.

So tell me.

But even as Bischoff is learning that cooling down is not quite as easy as it sounds, he's

absolutely right that you need all the help you can get during the rewarming process,

which is what those little nanoparticles are for.

But it's still very tricky to get the organ in really good shape on the front end of the

procedure.

Okay.

And the reason for that without boring you to death is that...

There's nothing about this conversation that's boring.

Thanks.

The reason that it's difficult is that you're trying to accomplish something very unreasonable.

You're trying to take away that which gives cells life and not kill them.

Right.

What gives cells life is water, but water is going to freeze if you cool the system

down to too low of a temperature, so you have to replace some of that water with some alien

chemical that that cell never heard of, like dimethyl sulfoxide or whatever.

You're not going to find that in many organisms on the planet, but you have to do that if you're

going to prevent that water from freezing.

So it's a very careful dance that you have to go through to take that water out in a very

gentle way, in a very careful way, so that the cell can tolerate that dehydration.

So the way I was describing it was putting more weight on the warming, and you're saying,

no, no, no, the warming is incredibly important, but they're actually bringing it down to that

frozen state.

That's actually the harder part.

Because when you warm it back up, you're only as good as you were when you were cooled in

the first place, right?

If there's some kind of organ damage at the front end and the back end, it's going to have

that again.

It's going to be there.

That's right.

So that concept is called perfusion.

So perfusion is what your heart does to your body all the time.

It delivers fluid through your vascular system.

That fluid happens to be blood, but any fluid going to a vascular system is perfusion.

The way Dr. Fahy and his scientists use perfusion here is genius.

They identified the need to take water out of the cells and replace it with a special

liquid that stops ice from forming.

But instead of building a whole new system to do that, they use the body's own blood

vessels, the same ones that already move blood.

It's a brilliant example of leveraging an existing system to fit a new purpose.

It's frictionless innovation.

So during that perfusion process, you are taking water out and you're putting the cryoprotective

agents in.

And then on the back end of that, you have to do the reverse.

You have to put the water back in and take the cryoprotective agents out.

So fortunately-

Which we can't minimize the putting a foreign substance into something and then putting

it in and taking it out has to be done with extreme caution.

It does.

It's miraculous that it's even possible if you get right down to it.

Mammalian kidney-

But it's not impossible.

But it's not impossible.

It's not impossible.

That's right.

That's what I'm talking about right there.

Exactly.

So in cryobiology, the beauty of cryoprotective agents is that they allow you to go to lower

temperatures before ice begins to form.

It's not frozen.

It's not frozen.

It's not liquid.

It's not liquid.

It's vitrified.

It's a glass.

So you would never think that lollipops and window panes have anything to do with preserving

organs, but they do.

It's all the same physics because you are dealing with an unstructured solid material,

not a crystalline solid material.

That's a glass.

And that's the secret to banking the impossible possible with organs.

Amazing.

Let's take a moment to break this down.

Vitrification is a way to freeze organs without forming ice.

The formation of ice can be very damaging as sharp ice crystals expand and can tear

holes in cells, ruining the organ.

To stop the forming of sharp ice crystals, scientists use special chemicals called cryoprotective

agents that replace water inside the organ.

These agents lower the freezing point and make the organ turn into a smooth, glass-like

state instead of forming sharp ice crystals.

This way, the organ stays undamaged while being stored at freezing cold temperatures.

The picture behind me that we talked about earlier from the Red Cross, that was the first

rabbit kidney?

That's the first rabbit kidney.

It's actually the first organ of any kind that was loaded up with a vitrifiable concentration

of cryoprotective agent, put into a recipient...

Iron oxide or your solution?

My solution, right.

And then put back into a recipient organism and shown to function afterwards.

And what day did that happen?

I actually published it in 1997.

I probably did the work in 1987.

It sat around for a long time before I actually got it published.

Were there other people that accomplished that in between the time that you did in 87

and 97?

No, nobody was even close.

Nobody was on the trail.

So yeah, nobody was interested in this field.

Way ahead of the game, way, way ahead.

So what was that like when you witnessed it?

Describe that because that is a moment, that is a not impossible moment where something

went from impossible to not impossible.

That's true.

Describe that moment.

It was magical.

So it turns out that you can...

So the body has a big blood vessel called the aorta, which distributes most of the blood

to most of the body.

Yeah, that one I've heard of.

And it has a big vein called the vena cava, which does the reverse.

Heard of that one too.

All right.

So two for two.

Yeah.

So you take a tube and you put it in the aorta and you can hook that to the renal artery

and you take the renal vein and you hook that to the vena cava.

So now that you're using the rabbit as a perfusion machine to perfuse that kidney with blood

and you know, that's the best possible model short of transplantation because all of the

challenges of surviving in a real world environment, which you have all the different kinds of

blood cells, you have blood pressure, you have pulsations and everything.

If you have weak blood vessels, they might blow out or something like that.

Or traditionally what you saw with frozen organs is that after you transplanted them,

they would turn into large blood clots after a while, or you'd start urinating whole blood,

which we saw in some of our experiments with freezing organs in the past.

But in this case, we undid the clamps and the organ just pinked up and looked gorgeous.

What we then saw is that organs tend to turn blue for different periods of time.

And we thought, well, that may be the end of that.

But half the time the organs would then pink up again and look just beautiful like the

organ in that photograph.

And we found that they could function immediately, which is too good to be true.

And how many people were in the room when this happened?

Probably three or so.

And what did you guys start doing?

Well, we would have congratulated each other, but I think we were so fixed on the kidney

itself, just in amazement and awe.

And you saw the urine starting to come out of that ureter can and just drip, drip, drip.

And it was transparent.

There's no blood in the urine.

So we were just amazed.

And so I actually went to the next lab and got my colleague, Robert Williams, to come

in and take up the picture.

Take up the picture.

Yeah, exactly.

Amazing.

Right, exactly.

So now we have this process of having human organs.

Now we're going to move away from the kidneys and the rabbit kidneys and whatnot.

Right.

Now we're moving into a world where the potential is for human organs to go through this process.

Yes.

Now, with what we're talking about, with the vitrification of organs, now we're talking

about a situation where we're not, where it's not like an episode of 24 and we're having

to hurry and get it to that transplant O.R.

We have time to do that.

That's right.

Conceptually, got it.

Now, you know, Mick dies, Greg needs some of my organs.

It doesn't mean that we have to get it within a 24 hour clock.

Correct.

We've got time to do it.

I'm running out of time.

Let's talk about some of the ramifications of that.

So one thing that tends to happen in today's world is that if you need a kidney, you go

on the waiting list and they say, okay, well, don't go on vacation, you know, because you

never know when the kidney is going to come up.

So you wait for five years and you said, damn it, I just got to go on vacation.

You go on vacation.

Then the kidney comes up and you, yeah, you lose it.

Or you wait five years and then you go into the hospital and right before the kidney comes

up, you develop some kind of disease and they can't immunosuppress you, kidney goes out

the window.

Sure.

But nevertheless, you're kind of tied to this location, this organ procurement organization

and that location, that hospital that's capable of giving you the heart transplant you need

or whatever, not necessarily in the town in which you live.

So that heart could come up at any moment.

If the heart comes up and you have to transplant that within a few hours of the time it comes

up, you have to be there on the site all the time, which means maybe you're staying in

a hotel at tremendous cost.

Maybe you're having to rent an extra apartment.

So there are all kinds of logistic issues associated with that.

Right now, if you're waiting for an organ, your life is basically on hold.

You can't travel or make plans because the call for a transplant could come at any moment.

And after all that waiting, if you get sick right before the transplant, you might lose

your chance entirely.

It's a stressful, uncertain way to live.

But if we could safely freeze and store organs, everything changes.

The organ could wait for you, not the other way around.

So what I envision is that you'll have several centers across the United States where most

of the organs are originated and they will be vitrified right then and there.

They have to be vitrified at the point of death.

That's correct.

Essentially at the location where their organs are collected.

So every hospital ultimately will have to have a vitrification process.

Could be.

If you could plan everything in advance, if you could schedule the organ transplant as

an elective procedure, then all the organs that are originated in one place, they can

be transplanted at a series of other places.

And you could just go there one time.

So basically what you're describing is the CarMax of organs.

Yeah.

This is the AutoNation.

You go onto a website, you pick out your car, and for an extra 45 bucks, it can go from

Fort Worth, Texas to Orange County or wherever you want to pick it up.

Yeah.

You can make it into a procedure that's much more practical and affordable for all parties

concerned.

Okay.

Now talk about some of the ramifications of inequality that would take place because how

do you now have and how do you determine who gets the organ and who doesn't get the organ?

Well, those problems have been solved in the United States essentially because we have agencies

that pick recipients for organs only on the basis of their likelihood to benefit from the

organ.

Okay.

And they try to set aside most other considerations.

There's still an issue of organ supply, and we can get to that too, but within the supply

that we have now, the system bends over backwards to be as fair as possible.

Okay.

Right.

Well, let's talk about supply.

Yes.

So right now, as we get older, we have problems and that ends up causing organ failure from

time to time, especially in the case of the heart, like 70% of us die of heart failure

or whatever.

So we still need to replace the organs, and there are just so many people aging compared

to the number of people who are dying under good enough conditions so that our organs

can be used that there's a big mismatch between the demand and the supply.

So there are a variety of proposals for bridging that gap, and one of those proposals is to

manufacture organs in the laboratory.

How far away are we, in your mind, from this being something that's accessible for people?

It's going to take some time.

What does some time mean to you?

I don't know.

I wish I did.

I'm going to pin you down.

You're going to have to give me the over-under on this thing.

I see it happening as an experimental procedure, like we were just discussing, in less than

five years.

Okay.

But another possibility, which is being developed by United Therapeutics and other labs, is

to humanize animals, and in particular, humanize pigs, so that the human immune system won't

just reject the pig organ out of hand.

Did you read ahead of my notes?

No.

This is perfect.

We're a good team.

All right.

Let's talk about pig organs.

Yeah.

So I love pig organs.

They're as big as human organs, and pigs are very physiologically similar to humans.

They're not exact duplicates of humans, obviously, but close enough that if you have the opportunity

to get a pig organ and not reject it, then that's going to keep you alive indefinitely,

pretty much as though you were a human organ recipient.

And you're saying that pig organs are better because of the biology of a pig is more ... Because

I would say the biology of a primate is more similar to a human, but you're saying, au

contraire, Mick-frère, that's not the case.

Well, what primate are you going to use?

Because we're big.

Most primates are smaller than we are.

If you've got a chimpanzee kidney, it might-

And pigs are bigger.

Pigs are bigger.

That's the main advantage that the pig has.

Okay.

So it has the organ mass enough to deal with all the toxins that you have to eliminate

in your body.

And also, pigs are available in unlimited quantities, in theory.

We eat pigs, right?

So we can grow as many pigs as we want, and if we humanize them so that their organs look

like our organs, then you can transplant as many organs as you need to meet the supply,

the demand, no matter how big the demand is.

So that's why I love pig organs.

Will you?

Yes.

Of course.

Let's go.

But you're saying pig organs is the pathway.

That's the pathway that you feel is the best pathway, right?

I think that's the way that I see it right now.

Something else may come along, or maybe we'll get really good at growing organs in the lab.

But if you think about it, in order to get an adult pig, all you have to do is feed a

baby pig.

And we can make baby pigs cheaply, right?

Sure.

Whereas if you're paying 100 scientists to grow something in a laboratory, it's going

to cost more.

I know how much they're-

It's going to cost a lot more.

Yeah.

Okay.

I think it's doable.

It all depends on who decides to do what and what unknowns come up.

But there are now, contrary to my history, in which nobody really cared about this but

me, there are a lot of groups now.

We care, Greg.

Yes.

We care.

And that's wonderful.

That's heartwarming.

And not just you, but the scientists grunting it out in a laboratory in Minnesota and many

other places, there's a lot of people who are getting more and more hell bent on making

this work.

Sure.

For all the reasons we've been discussing.

And I think that's the main ingredient that you need.

You need determination.

You need to have a will to do it.

And you need to have clinicians out there who are gutsy enough to try these new things.

And there are clinicians like that.

There always have been.

And I think there will continue to be.

I think the push is on.

All right.

Let's talk about the thing that every listener who's talking to someone who works in the

space of cryobiology is going to ask.

The very first question.

I think you know where I'm going.

I know where you're going.

Yes.

Han Solo.

Correct.

Is that real?

Could he actually have survived?

Well, we don't know much about that process, but I will tell you, if you look at how that's

portrayed, it looks like it has to be vitrification to me.

Okay.

Because it happens real fast.

It happens so fast.

So if you can cool somebody fast enough that water didn't have time to rearrange into ice,

it would work.

So when you saw that, you've seen the movie.

Yes.

Okay.

Just want to make sure.

When you saw that, you're thinking like, all right, it's science fiction, but there's

some believability in there.

Vaguely.

Yeah.

Vaguely.

And they do say science fiction is the predictor of the future.

That's true.

I'm not sure we're ever going to have transporters a la Star Trek, but a lot of science fiction

does come true.

It does.

It does.

That probably covers it.

That's amazing.

I want to say thank you.

Thank you for joining us.

Thank you.

This was an incredible, incredible conversation.

Thank you.

I had a lot of fun.

As I said, what this podcast is designed to do is what you did just now, which is to talk

about things that transition from impossible to possible.

That day when you saw that kidney kind of go beautiful pink and what that could mean

for the future, I think, in terms of humans.

So thank you for your work.

Thank you for doing what you're doing.

Thank you for your interest.

And that wraps up another episode of the podcast, where we talk with people who transform the

impossible into the possible.

A big thank you to Dr. Fahy for hosting us at his laboratory and sharing his insights

on vitrification, the future of organ banking and the potential for other species to save

human lives.

It's conversations like these that remind us of the daily strides that we're making

in science and technology, health and humanity.

They remind us the world is progressing and that this world is actually a pretty amazing

place.

So don't forget to follow us on your favorite podcast platform for more discussions like

these that make you realize the world doesn't suck.

Thanks so much.

I'm Mick Ebeling.