You Can Be a Hero: Paired Kidney Exchange | Wisconsin Public Television

You Can Be a Hero: Paired Kidney Exchange

You Can Be a Hero: Paired Kidney Exchange

Record date: Jan 24, 2018

Joshua Mezrich, Associate Professor in the Department of Surgery at UW School of Medicine, discusses the history of transplant surgeries on animals and humans. Mezrich describes how donors are chosen and the risks they face.

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Episode Transcript

- Welcome, everyone, to

Wednesday Nite @ the Lab.

I'm Tom Zinnen.

I work here at the UW-Madison Biotechnology Center.

I also work for UW-Extension

Cooperative Extension,

and on behalf of those folks

and our other co-organizers,

Wisconsin Public Television,

Wisconsin Public Radio,

the Wisconsin

Alumni Association,

and the UW-Madison

Science Alliance,

thanks again for coming to

Wednesday Nite @ the Lab.

We do this every Wednesday

night, 50 times a year.

Tonight it's my pleasure to

introduce to you Josh Mezrich.

He's with the Department of

Surgery here at UW-Madison.

He was born in

Princeton, New Jersey.

He went to Princeton Day

School for high school,

and then he went to

Princeton University

and studied Russian.

Then he went and got his MD

degree at Cornell University

Medical College

in New York City,

then went to the University

of Chicago for a residency,

back to Boston at Mass

General for a research

fellowship, back to the

University of Chicago to

finish up his residency, and

then he came here in 2005

for a transplant fellowship

and then went on the staff

at the hospital and the

faculty here at the School

of Medicine and

Public Health in 2007.

Tonight he gets to talk

with us about the kidney,

which is the second most

important part of my body,

the bladder being the first.

[laughing]

Thank you.

If you can fix

that, let me know.

- We can't transplant it but--

- Darn it.

Pretty cool thing tonight.

We get to talk about kidney

transplants and kidney

transplants from live donors.

So the topic for Josh's talk is:

Can Everybody be a Hero:

The Beauty of the

Paired Kidney Exchange.

Please join me in

welcoming Josh Mezrich

to Wednesday Nite @ the Lab.

[applauding]

- Great. Thank you so much.

Can you guys hear me? Great. It's great to be here.

And I was going to talk

about the evolution of the

chicken, but, luckily,

I decided not to.

And Tom has actually

volunteered to

donate his kidney on stage. [laughing]

So those in the front row,

you may want to--

[laughing]

No, I'm just kidding.

So I know my talk was

about paired exchange,

but I'm actually going to

use you guys to help me in a

way and talk about a

little bit more than that.

And I think it's going to be a

lot of fun and very interesting.

And we will go over

paired exchange,

but we don't necessarily

need a whole hour for that

or 50 minutes for that.

So I think transplant

surgery is really incredibly

amazing, and I think it's

amazing for a number of reasons.

But one of the reasons is

that in the '40s nobody

thought transplant

could ever happen.

In the '50s, just a

few crazy people

thought it was possible.

By the '60s, those crazy people

were actually having successes.

And by '83, with the

approval of Cyclosporine,

transplant became a field

with really good outcomes

and has only gotten better.

So when you think about it,

it's a really short

period of time.

I've been fascinated by

this for a long time,

and somewhere in

2011 I read the book

Emperor of All Maladies.

Now, perhaps some of you

read that wonderful book by

Siddhartha Mukherjee, a book

about the history of cancer,

mostly the, well, cancer.

He had recently graduated

from an oncology fellowship,

and he used his patients'

stories to then jump back

and tell the history of cancer.

And he's a beautiful writer.

He won a Pulitzer Prize

and has gone on

to write other books, The Gene.

He writes for The New Yorker.

But I was reading that book

and it was a real

epiphany for me.

I said I'm going to do this

for transplant because I

think the story of

transplant is so amazing and

a lot of the pioneers are

still alive or at least when

I started thinking about it.

Some of them have died

in the last few years.

And I started thinking

about how I would do this.

And I decided I would write

a book that described both

my coming of age as a

surgeon and the stories of

my patients, donors

and recipients,

and try and tell the

story of transplant.

And in that, I would travel

around to all the pioneers

and spend time with them

to try and make the,

understand how amazing it

was what they did and to use

me, a mere mortal, to show

how hard it was what they

did against all odds.

And I spent three or four

years working on this,

was able to get an

agent and sell it,

and actually just had it,

it's just accepted

by HarperCollins.

It's finished.

Although I don't

have a pub date yet.

So I thought I would start

talking about it now so that

you'll all buy it.

[laughing]

That's not really true, but

it's been sort of my passion,

along with my surgery

and my basic science,

and I'm very excited

to talk about it.

One of the things that

I think is amazing about

transplant is our donors.

Our donors are our heroes.

Without donors there

would be no transplant.

Donors are living and deceased,

and we're going to

talk about both today.

And I had my very first

exposure to what I like to

call taking from death,

or seeing what death can

provide to the living, in

my second year of med school

when I started working

for the skin bank.

It was called the New York

Firefighters Skin Bank.

And I was a medical student

but I had this as a side job,

and we would drive

around to hospitals all

around the tri-state area where

patients were organ donors.

And then after the

procurement of the organs,

we would then harvest the skin.

And we would take the skin

for burn victims to be used

as temporary coverage until

enough coverage from their

own body could be used.

And I was young at this point.

I didn't really understand

what it was I was getting into.

I didn't really understand

why that skin couldn't stay

on the recipient or how

this had any connection to

transplant other than

sometimes when we would go

for the procurement,

the solid organ teams,

as we call them, would

be there and I would get

to scrub in with them.

And I thought, how amazing

is it that all around the

country there are people

that are going to sleep and

are going to wake up with

this person's organs in them?

That was fascinating to me.

But I would say I was

pretty immature about it.

I was more focused on the

technical task of doing it.

My real awakening for

transplant happened during

my third year of medical school,

and it was actually my first

day on my surgery rotation

and I was pretty scared.

I remember it vividly.

They started around

four in the morning,

and that's how

surgeons, especially

young trainees, start.

And we got down by 6:30 in

the morning to present all

the patients to the residents,

and then they had me

scrub in, take cases,

and I was in cases all day.

Around the end of the day

I was told, "Oh, by the way, you're on call tonight."

So that was the beginning of

my next 20 years of my life

where I realize my time

wasn't worth that much.

But it was still amazing.

And then around 10:00 PM I scrubbed on a bowel obstruction,

and I remember I was starting

to feel kind of sick.

I was too afraid to eat.

I hadn't drank anything all day.

I was very dehydrated.

The case ended around

one in the morning,

and I thought maybe I could

go get a drink and go take a

nap and my resident said,

"Go next door and scrub on

"this kidney transplant."

And I didn't want to do that at

all, I really didn't want to.

But I went in there

and I remember it

like it was yesterday.

Dr. Stubenbord, who's a

transplant surgeon back then,

was doing the kidney

and he had the classical

music playing and he

took out the kidney and

I was cutting sutures,

either too long or too short,

which is the standard

for medical students,

and I'll never forget when

he reperfused the kidney,

and shortly after he did that this happened, this urine.

And this is one of our kidneys

squirting out on the table.

And I remember

just being amazed.

Like we just took an organ

from someone who had just died,

didn't know

this recipient at all,

and now it's making urine,

and this guy is going

to get off dialysis.

And I was hooked then.

I remember thinking

this is so amazing.

I don't understand

how this can work.

Like, this shouldn't work.

How did they figure this out?

I also was really curious,

like, can I do this?

I always was very intrigued

by the challenge of it.

The technical demands.

You know, the idea of

training for years and

trying to pick up this skill

and not knowing if you'd be

able to do it.

So I really was

intrigued by that.

And it never left me.

And still, to this day, as

much as I complain about

having to get up in the

middle of the night,

when I sew a kidney in and

it squirts urine or a liver in

and bile starts coming out,

I don't do hearts but when

you see a heart plug in and

it starts beating, you

have to look and say,

this is just too cool, I

can't believe this works.

Well, the history, let's talk

about the history a little bit.

I'll keep an eye on the time so

we get to the present as well.

The first successful kidney

transplant was December 23rd

of 1954 at Peter Bent

Brigham Hospital,

later to be known as Brigham

and Women's Hospital,

by a man named Joe Murray,

a guy who I got to spend

some time with.

He died a few years back.

He performed that surgery,

and he ultimately

won the Nobel Prize.

I believe it was 2012.

He's a very modest,

humble person, or he was.

He said, "It wasn't really me,

"it was all the

people around me."

But while that was an

important moment in 1954

because it showed the world

you could successfully

transplant an organ and have

it work, it wasn't really,

it didn't prove that much

because immunologically it

wasn't important at all.

It was a kidney between

two identical twins.

Two brothers, one of whom developed Bright's disease

is what they used to call it.

One of the

glomerulonephritis or the

autoimmune kidney diseases that

young people would develop.

And at the time there was very

little option of dialysis.

So basically it was

a death sentence.

And Joe Murray

performed that surgery.

But a lot went on before that.

And one of the cool things

about transplant is that one

of the fathers of transplant

is a basic scientist by the

name of Peter Medawar.

Peter Medawar is

like an amazing guy.

He's a Brit.

He's very proper.

He was very charismatic,

gave wonderful speeches.

I never, he died long before

I got a chance to meet him.

But I never understood why

is Peter Medawar the father

of transplant because

he wasn't a surgeon,

he didn't do transplants.

What he was famous for was

the concept of tolerance.

Now, what is tolerance?

I thought tolerance was that

you can drink a bunch and

you can handle your liquor. [laughing]

And that is true but

that's not the tolerance

he was talking about.

So, again, the first

transplants were actually

done much earlier than that.

And there's some medieval

examples of transplants,

but they didn't work at all.

Then in the early 1900s there

was a guy named Alexis Carrel.

Some of you may

have heard of him.

He actually was the

guy who figured out

how to sew two blood

vessels together.

It's hard for me to

think that surgery ever

existed without that.

But back in the early 1900s,

they didn't have a good

reason to do bypasses.

They didn't know anything

about atherosclerosis.

The only real causes of

things like aneurysms back

then was syphilis and those

patients would likely die.

You know, people, they

didn't do heart bypasses and

all these kinds of things.

But Alexis Carrel figured

out how to do that,

and he published it and he

still has a Carrel patch,

which we use all the

time, named after him.

But after he figured

out how to do that,

he started transplanting

everything.

He transplanted every organ

you can think of

between animals.

He didn't operate

on humans at all

except very early in his career.

He transplanted thyroids and

legs onto dogs and kidneys

and hearts and he

didn't do livers though.

And he was able to do them

technically because he was a

technical genius, but they

all rejected within a week.

They worked at first

and then they rejected.

And he won a Nobel

Prize in 1912.

And in his speech

he said, you know,

the details of transplant

have been worked out,

but there's some force

that will prevent it

from ever succeeding.

He had a hunch that

it involved genetics.

They didn't know the

concept of the genetics.

But they were closely related,

he had a hunch it

could last longer.

He had a hunch that you

could do some conditioning,

either to the donor

or the recipient,

and make it last longer.

But then when World

War I broke out,

he went to France,

he was French,

got involved in

the war, came back,

kind of got off

kilter after that.

He worked at Rockefeller.

He was a big eugenicist, as a

lot of leaders back then were.

Ended up in Vichy France,

was supported by the Nazis

a little bit towards

the end of his career.

Was really good

friends with Lindbergh

and ultimately got

very discredited.

So transplant was lost

until Medawar came around.

And at that point they

knew about this force.

They didn't really know

what rejection was.

Medawar got interested in

the concept of that because

he got called in when a

pilot crashed in the blitz

and had a really bad burn.

And who do they call?

They called Peter Medawar.

He's actually a zoologist,

but he was doing some

research on skin.

So he went and started,

tried to do some skin grafts

on this patient.

They didn't last.

But he analyzed them

under microscopes.

He saw the influx of cells.

He's like, what are these cells?

He tried second set grafts.

These were grafts not from

the patient, from cadavers.

And so they would reject.

He did second set, he

found they rejected faster.

He started getting interested.

Why is this happening?

He did grafts from the

same person, they lasted.

That patient ended up dying,

but then he got really into it

and he started really

writing a ton about

rejection, identifying

what the cells were,

identifying second set,

so that was very important.

He was at a cocktail

party in the late '40s,

all good science happens at

cocktail parties, I think.

[laughing]

Another investigator

came up to him and said, "Listen, I'm studying."

I'm using cows or cattle to

try and study genetic versus

environment, and the

problem is when I get a

litter of cattle or calves.

Some of you probably know

more about cows than I

do, we're in Wisconsin.

But when I get a litter I

can't tell which ones are

identical and which aren't

until they grow up a little

bit and it's screwing

up my research.

And Medawar said,

"Oh, that's easy,

"just transplant skin

grafts between them,

"and if they're accepted,

they're identical

"and if they're not identical,

they'll surely reject."

And he was like, "Okay,

can you do them for me?"

And Medawar didn't want to

do it but he's like fine.

So he goes out and does it,

and lo and behold all of

them are accepted, all of them.

And even between the

male and female calves,

so clearly they

weren't identical.

And he was like,

how can this be?

Like a real scientist,

unlike myself,

an amateur scientist where

sometimes the desire is to

make the data fit

the hypothesis,

which is never good,

Medawar made the

hypothesis fit the data;

he had some great quotes.

One of his quotes is, and he

said it much better in his

British accent, he said,

"The level or your desire

for something to be correct

"has no bearing on

whether it is correct."

[laughing]

Which is totally true.

But he realized

something was wrong.

He went back to the

literature and he came

across an article from

the '40s by Ray Owen.

Maybe some of you

guys know of him.

Ray Owen was here at the time.

He was in the Department

of Agriculture.

He ultimately made his

way out to Cal Tech.

But he's certainly one of

the very famous graduates of

University of Wisconsin

where he got his PhD.

And Ray Owen, some

years before that,

had gotten a letter.

He was running a lab that

did various things with

cattle, but he got a

letter from someone in the

northeast who had a cow

that got impregnated,

and when she had the litter,

it was clear that there were

two different fathers.

It had the markings of two

different types of cattle.

And Ray Owen was like, how can

that be, send me some blood.

When he analyzed the blood,

he found that these calves

had the blood types,

two different blood types.

They were chimeric.

They had the blood types of

the father and the mother.

And he was like,

how can that be?

Well, what they did know was

that calves, unlike humans,

they share a placenta.

So the blood, in most of them,

so the blood mixes.

And because they're

in this fetal state,

they don't reject it.

They become chimeric.

They're tolerant.

And he recognized that.

He focused more on the blood

cells and the red cells than

the white cells because

no one knew anything about

white cells really.

But he said these

animals are chimeric.

In fact, in Ray Owen's article,

he continued on and wrote:

"This could have some

"bearing in transplant."

But the editors of

Science cut that out.

They were like, that's

science fiction.

And they still

published his article.

See, that's why I won't

send my stuff to Science.

[laughing]

And they would never

read my stuff either.

But anyway, that was

what Ray Owen wrote.

So Medawar ran across

this article, he read it,

and he was like, that's it.

And, more importantly,

these animals are tolerant.

They can accept skin grafts

because they have cells,

you know, of each other

floating around in them.

So that was the first

example of where transplants

were successful from

non-identical pairs.

And Medawar ran with that.

He started studying that in

multiple different models.

And he ultimately

was able to publish

in around '53 in Nature.

Better than Science,

I don't know.

That when he injected fetal

mice with non-matched donor

cells, then after the mice

were born he could then

transplant skin into those mice

and they would be accepted.

And he called that tolerance.

And transplant

tolerance is considered

the holy grail of transplant.

We don't really try to do

transplant tolerance except

in some protocols.

We do have some successful

protocols both in large

animals and even in man in

pretty well-matched people

where we're able to

withdraw immunosuppression

and they accept the organs.

But the vast majority

of patients who get a

transplant, unless they have

an identical twin donor,

need to take immunosuppression.

So I always thought, well,

that's cool that Medawar did

that, but we don't even

do transplant tolerance,

so why is he the

father of transplant?

But what I realized is

before Medawar wrote that

and spoke beautifully about

it and inspired a generation

of people about it and

continued the science on and on,

everyone thought

there was no chance.

Transplant was a pipe dream.

It'll never work except

for some crazy fools.

And Medawar brought

this authenticity,

this love of science to

our fields and I think

rightfully deserves

to be the father.

And thankfully he

got to live through--

He was president of all our

early societies and got to

live through so many

successes in transplant and

see what he was studying

actually come to reality.

So that, I think, must

have been incredibly

satisfying for him.

He was an inspiration to Joe

Murray and to all of the others.

So after Joe Murray did

this transplant in '54,

he was like this is great

but this isn't going

to be our answer.

So he and others started

working very carefully on

different protocols to bring

it to non-identical twins.

And they moved very quickly,

and it wasn't just Murray.

There were quite a few

other people involved.

One guy worth mentioning

is Sir Roy Calne,

who was a direct

student of Medawar,

made his way over from England

and worked with Murray.

And he was the first person

who figured out that

first 6-MP, the

chemotherapeutic agent,

and then ultimately

Azathioprine could help with

prolonging transplantation.

And then, down in the '80s,

he was the one who

tried Cyclosporine.

He didn't discover

it, of course.

It was actually

discovered by someone--

The drug company had a

policy that when people did

trips they should collect

the soil and then they would

test the soil for

fungal properties,

and someone went to Norway

and ended up finding

Cyclosporine and

ultimately made its way

into the transplant clinic.

And in 1983, that

changed everything.

That's when transplant

went from this experimental

treatment to a valid

option and has just gotten better and better.

Now, one other thing I want

to add before I get into the

living donor thing, I

think we're moving along

at a good pace.

The thing about transplant

that I think is really

different than other

areas of medicine.

In other areas of

medicine we spend our time

trying to fight off death.

We're trained,

possibly not correctly,

in medical school and

through residency that we

got to keep battling,

we got to keep fighting,

we got to try and cure disease.

And obviously that's important.

I think, thankfully, over

the last few years we're

starting to think more about

death is inevitable for

everybody, and maybe part

of our job is to make that

death better, to make

people have better deaths.

And I think there's some amazing

people writing about that.

Atul Gawande and others.

But nevertheless, we still

look at death as the enemy

and we're always fighting it.

Transplant is the one

field where we, in a way,

start with death.

We need someone to

die to get our organs,

at least our deceased

donor organs.

And I truly believe that the

donors and their family are

my patients as well.

I really believe that, and

it's very important to me.

The first time I went on an

organ procurement when I was

here, I'd been on some

others but where I was

actually really

involved in the process,

we fly out in

these little planes

which is not always

that awesome. [laughing]

I'm sure some of you

have had that experience.

I think flying is fine, but

when the weather's bad you

realize how

insignificant you are.

But nevertheless, you fly out,

usually in the

middle of the night.

You go to this hospital,

wherever it may be,

and I remember being really

nervous, thinking like,

how is the family going

to think about me?

I'm this vulture coming to

take the parts from their

loved one who just

died unexpectedly.

What am I going.

They're going to always

remember me as that guy.

That was my fear.

And I thought maybe I can just

avoid the family entirely.

We went to the hospital, and

the coordinator who had been

on many, many procurements said

let's go talk to the family.

And I was like,

all right, I'll go.

And it was incredibly beautiful.

We went in and there were

like 15 people in the room.

They were all crying

and with each other.

And when we came in, the

room lit up and they wanted

to know everything about it.

This was their legacy.

Their loved one being a hero,

making some sense out of this

otherwise horrible moment.

Their loved one

was going to save

five, six, seven, eight people.

They wanted to know

about the process.

They wanted to know

about the recipients,

although we don't tell them

specific details, of course,

at first because of

protecting the recipient.

But they were fascinated by

the idea this was all going

to go on right then.

They didn't want us to leave.

And we asked them a

lot about the donor.

And it was beautiful in a way.

And then when we start

our procurements,

we always do a time out at

the beginning and will say

something about the donor,

often something the family

told us, maybe a

poem, maybe a story,

maybe something they loved

to do, their favorite song,

their favorite book.

And it gives us all this

incredible drive and passion

to do a good job.

And then the interesting

thing about surgery is once

an operation starts, it truly

becomes a puzzle or a task.

You no longer think about

the fact that this is a

person or was just a person,

that this is someone who has

someone who loves them or what

you know about the person.

And I think that about

all the surgeries I do.

Each surgery is a puzzle.

Some puzzles have

a hundred pieces,

some puzzles have

a thousand pieces,

some have a lot more than that.

But you have to solve

that puzzle and you can't--

You actually push

those emotions out,

and you rarely think about it.

Every now and then it'll

come into my mind if

something goes wrong and

we're getting into trouble,

or if I happen to turn my head

and see like their

hand undraped.

For some reason the

hands are very human.

I think everyone thinks that.

But for the most part when

you're in there working,

you're not sitting there

thinking about, "Oh my God,

"this is someone's dad

or someone's brother or

someone's wife."

Those aren't thoughts

that we typically have.

Transplant played a huge role

in defining what death was.

It seems like you should

know what death is,

but I bet a lot of you have

different opinions about that.

So there's dead dead, right?

I mean, you're dead.

That means, probably to most

of you guys that means you

have no heartbeat, you

have no blood pressure,

you have no respirations,

you're cold, you're dead.

And that is what death was.

But that definition was a

real problem for transplant.

In the '50s, it didn't

really matter because so few

transplants were being done.

A lot of them from

living donors.

Mostly people who were

getting some other operation

and the kidney was coming out.

There were some operations

back then, I won't get into,

where the kidney was removed,

was still a functioning kidney.

Some were people who died

on the table getting heart

surgery because more than

50% of those patients died

on the table.

And they didn't have

bypass back then,

and can you imagine

how difficult that was?

And those kidneys could

be pulled for transplant.

So that was dead,

but very recently dead.

But as the '60s went on

and transplant started to

improve, there was concern

about how are we going to

get enough organs.

As people started thinking

about heart transplant,

it became quite clear they

would need to have some

other definition of death

because people knew from

animal experiments and

common sense that a corpse

was likely not going to be

a good donor for a heart.

And as that got closer and

closer to reality and became

a reality in 1967 by

Christiaan Barnard,

South African, it's all

covered in the book.

Okay, the heart stuff

is fascinating, but I'm not going to get into it.

You can bring me back for that.

It became clear that they needed

better definition of death.

That sounds strange, doesn't it?

And a little conflicted,

but nevertheless it's true.

There were other problems.

There were people that were

sitting in ICUs that were

clearly feudal that were

being taken care of because

they didn't know when to stop.

And that needed to

be addressed as well.

So in the late '60s, at

Harvard of course because

everything happens at Harvard,

they had a conference

on this concept,

and Joe Murray was there.

Joe Murray, the most

famous transplant surgeon

in the world by far.

And it was run by this

anesthesiologist with the

name of Wheeler, a very

famous anesthesiologist,

an ethicist who basically

wrote the book on informed

consent, randomized trials.

He was famous and infamous

because he called out a lot

of researchers for not

doing informed consent,

for being biased.

He was brilliant, though.

And Joe Murray and Wheeler

got together and they said

we need to codify death.

There's a lot of controversy

about this because the

concept that a transplant

surgeon played a central

role has led some

ethicists to question

if that was appropriate.

It's funny, so there's a lot that got cut from my book

which I think are

the funniest stories.

I'm bummed about that.

But in one short line

Wheeler wrote a letter to

the dean of Harvard,

whose name was Ebert,

last name was

Ebert, and he said,

I want to have this conference,

I want to get this

group together and

write up what death is.

And Ebert wrote back and said,

I think that's a great idea.

And then I wrote in

parentheses, I guess you could

call that two thumbs up.

[laughing]

And my editor cut that line.

[laughing]

A lot of the humor got cut,

but we'll do a joke

night another time.

I actually love comedy but I'm

not getting into it today.

Anyway, so they got

together and they started working like crazy.

They had a few ethicists,

neurologists on the panel.

You know, all the people

you would want on there.

But mostly the article was

written by Wheeler and Murray.

They worked together every day.

Murray wrote a

good portion of it.

Murray didn't, Murray wanted not to use the term brain death.

He wanted to just call it death because he said it's confusing.

And what they came up with was,

this concept was out

there already and had

been written about.

France had a definition called

coma dépassé,

which was essentially

what we call brain death,

where the patient won't

take any respirations.

They still can have a heartbeat,

but they have no responses,

they have no cranial

nerve function.

All the things that we would say

now would be called brain death.

The thing we'd probably add

now is we typically do a

study to show no blood

flow to the brain.

But you could identify that

from clinical exam from the

cranial nerve exam, and back

then they had to do that

because they didn't

have the imaging we had.

And so they basically came

up with the exact definition

of brain death we use now,

that when you pull the

patient off the ventilator

they wouldn't take a breath.

Again, no cranial

nerves, no responses,

no overbreathing the vent.

And they called

that brain death.

Now, it's a little confusing

because is that dead?

I'd always assumed

brain death is death.

I mean, you can't

recover from it.

You don't have any

brain function.

Certainly no one would

want to live that way.

So to me I was comfortable

calling it death.

And I guess I have to feel

that way because I go out

and take organs out of

people while their hearts

are still beating.

There are a lot of

ethicists that argue,

in fact the majority

say that's not true.

I mean, you guys made that up.

They agree that you should

be able to take organs from

someone who's brain

dead, I mean everyone,

never everyone, but almost every

ethicist would agree with that.

But they say it's not death,

it's different than death.

You made that term up.

Some people don't

agree that it's death.

There are some cases out

there and some of you guys

have heard about them where

family members loss someone.

There's one case with

a young girl who

unfortunately died after a

tonsillectomy in sort of a

freak complication,

clearly became brain dead.

No one questions that diagnosis.

But to the family,

she's still alive.

To them, she still

gives them value.

They feel like she

still responds to them,

and they're like,

she's not dead.

Her heart's beating.

She feels warm when I touch her.

She still gives us value.

She's still our little girl.

You can't laugh at that.

I mean, that's their

opinion, and that's fine.

The courts backed up the

fact that they could have

disconnected this girl.

This was out in California.

But they decided not to do that.

You can imagine the PR of that.

And, in fact, she was

transferred to a long-term

care facility where

she still lives now.

I don't know.

She's still brain dead.

And there are lawsuits that

are moving their way up the

courts and likely will make

it up to the Supreme Court

to question this

definition of brain death.

That could be a real problem

for not just transplant

but also for ICU management

and end of life.

I'm very comfortable with

the idea of taking organs

from brain dead people,

but when the definition was

first made, that was not

immediately accepted.

There was a lot of controversy,

both in the American

public, or I should say

internationally, and also

in the transplant community.

And it didn't help that the

heart transplant guys

in the typical fashion of

the heart surgeons,

the second Christiaan

Barnard did one transplant,

everyone started doing

heart transplants.

No one knew anything about

immunology and all the

recipients were dying like dogs.

And people started thinking

you guys are stealing hearts

from living people and took

about 10 years for people to

accept the concept

of brain death.

It's accepted now but you'll

find a lot of articles

questioning whether

it's really death.

I don't know if

it's death or not.

I guess it doesn't

ultimately matter to me.

It's certainly not life,

that's how I look at it.

But you could say there are

other conditions that aren't

life that clearly you

wouldn't define as death.

We could have hours

of talk about this.

But the reason I bring it

up is that our donors are

either dead or alive.

Let's move on to talk

about live donors so we can

actually spend a few minutes on

what I said I would talk about.

Why do we do live donors?

Well, a couple reasons.

One, we don't have

enough deceased donors.

I mean, that's one.

But even if we did, the

outcomes for kidneys are

significantly better with a live

donor than a deceased donor.

That's inarguably.

Everybody knows that.

There are a lot of

reasons for that.

Well, they're by

definition healthy.

They didn't just die.

They've been

carefully evaluated.

They don't have diseases,

or at least minimal

level of disease.

We've deemed them

good candidates.

They didn't go through the

process of brain death or

whatever happened before

we take the organs out,

low blood pressure

and traumatic episodes

and these infections,

whatever else went on.

And we're able to take them

out and put them right in.

And that helps too.

We know the longer time

they're outside the body,

the slower they are to kick in,

and that does have

an effect on outcome.

Living donors are, for kidney, are better than brain donors.

I like to tell people the

average half-life of a

living donor kidney,

the data's not perfect,

but nevertheless is roughly

15 years and for a deceased

donor kidney it's like

eight to 10 years.

Now, the perfect deceased

donor kidney from the

20-year-old gunshot

wound to the head,

sadly that's our perfect donor,

may rival the imperfect

living donor kidney.

But just in terms of the

data, it's quite clear.

The donors, is there

risk to the donor?

Of course there is.

We had two kidneys for

some reason, I guess.

And surgery is surgery.

The risks are low.

So we evaluate donors

very, very carefully.

We try to avoid diseases.

They need to be healthy.

We try to avoid things

like high blood pressure.

Diabetes certainly

we wouldn't do.

Cancer would be out.

Heart disease would be out.

But then there are other

things that we struggle with.

What if they have

a little obesity?

What if they were a smoker?

What if they had a kidney stone?

What if they had a

kidney infection?

What if, you know, you name it. It becomes tricky.

We know a lot about

risks but not everything.

We know that the kidney

donor does have an increased

risk of renal failure, but

their risk only goes up to

one in a hundred over their

lifetime. That's pretty good.

Actually, for the longest

time we thought there was no

increased risk of renal

failure because that's

actually below the risk

of the general population.

But finally one of our good

researchers, Dory Saga,

figured out that you can't

compare the healthiest

people to the

general population.

So he was able to identify a

control group of people who

could have donated that

didn't and certainly showed

that we increase their risk

like two- to five-fold

of kidney failure,

but to a very low number,

one in a hundred.

People were freaked out

when he showed that.

To me, I was like of course,

nothing's for free in life

but in medicine for sure.

And I had always told donors,

I'm not going to tell you

there's no risk to this,

but donors get that.

They always, have always said

of course there's some risk.

Part of what makes it

so amazing, you give

this incredible gift,

you save someone's life, you

make their life so much better.

You say to them, you're sick.

One of the things I

think about illness,

serious illness, is

it's so isolating.

When you're sick, really

sick, like dying sick,

you're separated from your

family and your loved ones.

You're not enjoying kind of

the milestones and hallmarks

that make life worth living.

You're thinking about the

fact that you're not going

to see your kids get married,

or graduate, whatever it is

they're doing or

hit those things.

And even though your

family may be with you,

in the end you're

the one suffering.

You're the one sitting there

in the gown with your butt

exposed and getting

taken to tests

and not eating and worrying.

And what I think the

donors do is they say,

let me be sick with you.

Let me take a little

risk with you.

Let's be sick together, and

I'm going to make you better.

And I think it's one of the most heroic things I can imagine.

But part of that heroism

is it's not zero risk.

It's low risk, but it's

going to be painful and it's

going to be a struggle and

you're going to get through it

and you're going to say

to me, it's the best

thing I've ever done.

That's my hope, but

it's not zero risk

and it never was

and it never will be.

It's a little bit like I'm

going to be the guy who runs

into the burning building

and pulls out the kid.

If you're that guy or that

girl, you can be a donor.

And I think it's wonderful.

I have so many great

stories of donors.

Now, let's just talk

about the operation.

We do the operation

laparoscopically,

which means through small

incisions. These are little.

I hope you guys don't mind,

I have some pictures that I

think are beautiful and you

may think are gross, but

these are ports that we poke

in there and our instruments

go through those ports.

That's kind of the standard

operation. Those are the ports.

And then we remove the

kidney through a small

Pfannenstiel bikini

cut incision down low.

We actually put a bag in there, staple off the artery, the vein,

scoop the kidney in the

bag, pull the drawstring,

and hand it off like a

fish, and close him back up.

It's pretty amazing.

But even more amazing, I do

some of these through the

belly button where that's

the whole incision.

Believe it or not, you

untuck the belly button.

That looks, I hope,

incredibly tiny.

And we shove in this thing

that shoves through that

little incision, allows

three ports to work right

through this tiny

little opening.

You can picture, it's tricky

because your instruments can

cross and your

brain can go nuts. [laughing]

But you get really good

at controlling that.

And here's a couple of

examples of people that

I took kidneys out of.

That was right after surgery. And that was a little bit later.

You cannot even see it.

The only thing was he was

hairless before the surgery.

[laughing]

No, I'm just kidding.

I should have done

it the other way

and said this was the before

and this was the after.

[laughing]

But so anyway, it

just shows you.

But regardless of how

small the incision is,

it doesn't change the risk,

it doesn't change the recovery.

So I think living

donors are the best.

I think thinking about managing

risk is very interesting.

I think how paternalistic

should we be.

Whose choice should it

be, is a tricky question.

One of my favorite

stories, a guy came.

He was in his 50s.

He was overweight.

He had a little bit of

hypertension. He was a smoker.

He had those thick

hands, this thick belly.

You could tell that he had

some risk of developing

diabetes or something,

heart disease,

kidney disease down the

road, and he was like,

"Doc, I've been rejected

at two centers.

"I want to give my wife a

kidney. Let me explain this.

"Our family doesn't

work without my wife.

"She does everything."

I felt like he was

talking about me in a way.

He's like, you know, she's like the rock of our family.

She's way more

important than I am.

You know, we still got our kids, you got to let me save my wife.

He's like, I'll sign anything

you want, I won't sue you.

I'm not really

worried about that.

But what I worry about

is do you understand the

risk you're taking?

Do I understand the

risk you're taking?

Because each time

we add something on,

we don't know what

that number goes to.

We can make a prediction,

but we don't know for sure.

Does that matter? Is it my choice? I don't know.

If a father said or mother

said, I want to give my kid,

my little kid my heart,

while I might be able to

understand that as a parent,

obviously we would

never do that.

So there's clearly some

level of risk that we would

just say no way in hell.

But for this guy, I thought,

you know what, he gets it.

He has insight and I'm

going to let him do it.

I had to get him through

the committee, but we

were able to do that.

His surgery was

really difficult.

He was a really big guy.

But everything went fine.

And he saw me in clinic

about two months later,

and he gave me this big

bear hug and he was like,

I will never forget what

you let me do for my family.

And as I wrote in the book,

I said he's wrong

about one thing, he's the

one who did something

for his family, not me.

But I just remember shaking

his hand, that thick hand,

and just knowing it was a

hand that had worked so hard

to provide for his family

and he just was going to

continue doing that.

If he develops kidney

failure down the road,

was that a mistake?

I guess I don't think so.

My hope is that he'll

take care of himself.

I always tell patients, if

you donate and stop smoking,

you're probably healthier

than if you don't donate

and keep smoking.

But the likelihood is that

they donate and keep smoking.

[laughing]

Okay, now, can everybody donate?

What if you want to give me a

kidney? Can you donate to me?

Well, I don't know.

First of all, we need to be a compatible blood type.

That means if you're an O donor, you can give to anybody.

If you're an A donor, you

can give to an A or an AB.

If you're a B donor, you

can give to an B and an AB.

And if you're an AB

donor, you can only take.

I've always wondered if that

matched with personality,

but I don't think

that's been studied.

There are other scenarios

where people can't donate.

So we could be both Os and

you're going to give me a

kidney, but if I have

antibodies in my body,

it's possible I have antibodies

to proteins on your cells.

That wasn't a problem

in early transplant,

but the most common

reasons to get antibodies--

we call that

getting sensitized--

is previous transplant.

That's the number

one most common.

Previous blood transfusion

and previous pregnancy.

The most problems we have are

certainly with retransplants.

And we do a lot

of retransplants.

So we could be the

same blood type

but our cross-match

still doesn't work.

We've gotten really good

at identifying antibodies.

We use flow-based beads

that have all the different

proteins represented, and

we mix them with serum

and we're able to identify

antibodies binding.

We're quite sensitive at that,

but we're really terrible

at getting rid of them.

So we can avoid

rather than do it.

This idea, though,

of limiting donation

was a problem for a long time.

And then Alvin Roth, some of

you may have heard of him.

He's a game theory guy.

He won a Nobel Prize in 2012.

He was highly involved

in designing the

residency match system.

He didn't actually

design the first version

but he improved it.

He also came up with

a mathematical theory

of doing paired exchange.

It's not that complex, but he

did a lot of the programming.

This was around 2000.

It starts out really

simply, a two-way exchange.

So if I have a donor,

say I'm recipient two,

I have my donor who's

blood type B and I'm an A.

They can't give to me.

But if I can find someone

else that is blood type B

that has a donor that's

A, we can do a swap.

And that's quite simple.

That should be easy to do.

It doesn't just

have to be two-way.

It can be expanded to

three-way and beyond,

but you can imagine how it gets

mathematically more complicated.

The other

challenging piece is

in order to find people

that can do this,

you need a pretty big N.

You need a lot of people

and you need people

that are willing.

Likely, you need people

that can't receive from

their own donor,

at least at first,

because probably they'll

just move forward

with that donation.

If my donor is an O, should

I let someone else get that

so I can help them,

or would I rather have my

loved one give me a kidney?

I don't know.

So the early paired exchanges

were all incompatibles,

meaning everyone couldn't get

a kidney from their donor.

It seems so simple and

it should have worked.

And the first one they did

was in 2000 in New England

because that's where

Alvin Roth was.

At Harvard of course.

But then he moved to Stanford.

But it worked

and it got written up but

it just never got traction.

There were all these

groups that formed.

The Midwest Consortium,

the Northeast,

But it didn't work, it didn't work for a lot of reasons.

One, people, it was too new.

Number two, there was always

this fear that if the kidney

was outside the

body for too long,

maybe that would be a

problem for the kidney.

So if we were a few

different programs, like,

say we did it with Michigan,

we would make their donor

fly here to donate.

To transplant surgeons,

we're like yeah, why not?

They want to donate,

they should just come here,

we'll do a good job.

But it turns out most people

don't want to fly somewhere

they don't know to have

some surgeon they don't know

operate on them in some

town where they don't know

anybody, particularly while

their loved one is getting

an operation back home.

That was a nonstarter.

I mean, you're already

asking so much from donors.

Most people don't want to

have surgery where they

don't live unless

it's like a trauma.

Never got traction.

But people kept studying,

kept thinking,

and the idea came up, what

if we just fly the kidneys?

What if we take out

the kidney and fly it?

And, you know, we do

deceased donors that are out

of the body 24, 36, 48 hours.

We know that they're slower

to kick in, but, you know,

can we do that?

And people started doing it,

started showing good outcomes, and started building up.

And then something called

the National Kidney

Registry came about.

That's an organization

in New York

run by a guy named Garrett Hill.

Garrett Hill had

wanted to donate.

He was a marine and

then a businessman.

Very successful.

Very heroic character.

And he wanted to donate

his daughter a kidney

but they were not

the right blood type.

And his businesses had

involved computing

and problem-solving.

He was able to get a

family member to donate his

daughter a kidney, but he

quit his job and focused his

researchers and his programmers,

and they got help from

Alvin Roth actually,

on figuring out how to make

paired exchange work

with a real business model.

And it took them time,

but they built it up

and they built it up

and they've just done

like their 2,000th

paired exchange.

And we're a part of it.

And I just want to show you

without going all this data.

This was the one

we were a part of.

You might have seen this

in the New York Times.

This was a chain.

So if you can think about this.

I told you about the pairs.

And those ultimately have to

be an even number of people

and everyone's got to

donate and receive.

In a chain of

humanitarian donors,

someone who comes and says

I want to donate a kidney,

I want to save someone's life,

I don't even need

to know who it is,

they can donate to someone

that has an incompatible pair,

and then that donor

donates to someone

and that donor

donates to someone.

They don't, they can crisscross

the country until it breaks.

Early in paired exchange,

the thought was all the

surgeries have to go at once

because if someone backs out,

you can't force

them to go to surgery.

So if my intended recipient

gets an operation on a

Monday and then my turn to

donate is on a Tuesday

and I say, you know what,

I'm not going to do it,

they can't make me do it.

Right? I mean--

But NKR was like,

you know what,

I don't think people

are going to do that.

And if they do that, we're

so big now that we'll get

another humanitarian donor

to donate to that person.

We'll make good on it.

And it's worked.

And it's almost never happened

that someone's pulled out.

What could happen,

someone could get sick.

But then usually you can

delay and get it regoing.

The NKR has gotten so good

and so big that they have all these things they can do.

If a kidney gets injured or

something happens in flight,

they pull in another

donor and restart it.

They started a

program where,

say I have a kid who has kidney

disease but isn't going to

need a kidney for

probably 15 years,

I can donate now and get a

little token and it's as if

they had a living donor

whenever they need a kidney.

And I can actually

name up to six people

and all those people

can get tokens.

And they'll end a chain

on them in the future.

I can also say I'm a teacher,

I got to donate

during the summer,

my recipient's not ready to go.

I can do advanced

donation now, I recover.

Or maybe we're a married

couple, we have kids,

let me donate, recover,

then you can donate.

They can accommodate

all of that.

It's just incredible.

It is just incredible.

So now I do tell patients

for this long-term thing,

it's kind of like a timeshare.

If the company goes

down, there's no,

the NKR doesn't like

it when I say that. [laughing]

What it really means is

anyone can be a hero.

Anyone can donate

if you're healthy.

I think it's just

absolutely incredible.

It's, of all the surgeries I do,

it's the thing I feel

most excited about,

most nervous about,

most passionate about.

I'm not going to tell

you the story of WB,

one of the most incredible

people I've ever met with ALS,

but I think I

had included the link,

but if not, I wrote an

Atlantic article about him.

He was an ALS donor who

wanted to donate either

before he got too sick

or at the end of life.

And it's an article I'm very

proud about because of Wayne.

I can give you the link

if you don't have it.

But if you go onto

Atlantic and Google me,

you'll pull up about a

million things about my brother,

who's a famous writer.

But, eventually

you can get to me.

And then just a few

pictures I was going to end.

Here's what a kidney looks

like when you take it out.

If anyone's going

to get grossed out,

this is going to be the time.

And that's the ureter

going down there.

Here's a kidney sewn in.

You can see how

nice and pink it is.

Here's another picture.

Normally we don't enter

the abdomen to do a kidney,

but this was one of the rare

scenarios where we have to

take their kidneys out, so

you can see a little bit of

liver and some bowels.

This is a kidney I

did many years ago.

It was three arteries.

A little bit complex.

I hooked these two up

there and that one.

It's a lot of like

sewing, and it's a puzzle.

I'm telling you

it's like a puzzle.

Here's a rare

scenario where I put

two kidneys into a recipient.

Sometimes if one kidney is

not going to be quite enough

because of the

status and the donor,

we'll put both in.

This is a polycystic kidney.

You may have heard of

polycystic kidney disease.

It's an autosomal dominate

genetic disease where if you

have the gene, you have

polycystic kidneys.

They can be like this big,

and people will be walking

around with two of them and

won't even have any symptoms.

If they have bad symptoms,

we'll take them out.

I had one guy, they were so

big that we had to give him

scrubs to wear home because

his pants were falling off

of him after surgery.

So if any of you feel

like you're overweight,

maybe you have

polycystic kidneys.

[laughing]

No, it's pretty rare.

You would know if it

was in your family.

Here is cirrhotic liver.

It doesn't look good.

Here's the liver out.

Here's the fresh, beautiful

liver that I then put in.

Amazing.

I didn't talk about Tom

Starzl and liver transplant.

Another talk.

Here's a pediatric liver.

Sad that this picture

was ever taken,

but such a beautiful organ.

And here's the famous

picture of the kidney

squirting urine on the table.

Awesome.

And my kids.

[laughing]

In the Frozen Tundra

a couple years ago

but I still love it.

All right, guys, I

hope you enjoyed it,

and I'd love to come back

later when the book ever

comes out or talk

about other things.

[applauding]

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