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.

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 talked to Dr.

Greg Fahy.

Dr.

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

for lifesaving transplants in the future.

They might blow out or something like that.

Or traditionally, after you've transplanted them, they would turn

into like 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 tenants in 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 tenant, everything that's impossible today

will eventually become possible.

So why can't they be the one who makes that transition

or is 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, from worst to better.

Yep.

You know, 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 frozen organs, 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, you know, Joe Dokes 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, you know, 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, you know,

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, right?

So this is leading up to leading up to it.

So, but now let's talk about vitrification, what it means.

This is like, 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 it 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 towing the Bischoff line pretty well.

Oh, okay.

All right.

All right.

So tell me, even as Bischof 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.

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 want, you're trying to

accomplish something very unreasonable.

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

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 then 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 in the first place, right?

If there's some kind of organ damage at the front end then back end,

it's going to have that again.

It's still going to be there.

That's right.

So, 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, not impossible, but it's not impossible.

It's not impossible.

That's what I'm talking about.

Right, exactly.

So in cryobiology, the beauty of, um, cryoprotective agents is that, um,

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 making 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.

Yes.

That was the first rabbit kidney.

That's the first rabbit kidney is actually the first organ of any kind

that was loaded up with a vitrifiable concentration of cryoprotective

agent put into a recipient.

Or the, your solution.

My solution, right.

Uh, and then, uh, put back into a recipient organism and shown to function afterwards.

And what day did that happen?

I actually published 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 it 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.

Right.

So what was that like when you witnessed it, like 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.

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 into 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 started to

come out of that ureter cannula and just drip, drip, drip.

And it was, 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.

So now we have this process of having human organs, and we're going to move

away from the kidneys and the rabbit kidneys and whatnot.

Now we're moving into a world where the potential is for human organs

to go through this process.

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, that transplant O.R.

We have time to do that.

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.

We've got time to do it.

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.

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, you know?

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

at one place, they can be transplanted at a series of other places and you

could just go there one time.

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, you know, 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, 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.

Uh, and they try to set aside most other considerations.

There, there's still an issue of organ supply and we can get to that too.

But, uh, within the supply that we have now, the system bends over

backwards to be as, 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.

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

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, there's a big

mismatch between the demand and the supply.

So there are a variety of proposals for bridging that gap.

And, uh, one of those proposals is to manufacture organs in the laboratory.

How, 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 got to have to give me the over under on this thing.

I see it happening as an experimental procedures, like we're just

discussing in less than five years.

Okay.

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

other, other labs is to humanize animals and particularly 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?

This is perfect.

We're a good team.

All right.

Let's talk about pig organs.

Yeah.

So I love pig organs.

They're, uh, as big as human organs and pigs are very

physiologically similar to humans.

Not, they're not exact duplicates of humans, obviously, but close enough

that if you have the, um, 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, 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, oh, contraire McFerrer, 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, pigs are bigger, pigs are bigger.

That's the main advantage that the pig has.

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

you have to eliminate in your body.

Um, 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, uh, organs as you need to meet the supply, the

demand, no matter how big the demand is.

So that's why I love big organs.

But you're, 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 you will get really

good at growing organs in lab.

But, you know, 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 are paying a hundred scientists to grow something in a

laboratory, 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, uh, there are a lot of groups now.

Yes.

Well, and that's wonderful.

You know, that's heartwarming, and not just you, but the

scientists grunting it out in the 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 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.

Yeah.

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.

Yes.

Han Solo, 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 could cool somebody's fast enough that water didn't have time to

rearrange into ice, it would work.

So you, 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.

Oh, vaguely.

Yeah.

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

So 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.

Well, that probably covers it.

That's amazing.

Uh, I want to say thank you.

Thank you for joining us.

This was an incredible, incredible conversation.

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

to talk about things that transitioned from impossible to possible, that day when

you saw that kidney kind of go beautiful pink, and what that could mean

for the future, 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.