Transcript: Jim Allison - Breakthrough | Oct 10, 2020

A caption reads "We like films. Films we like."

Jim plays the harmonica.

The caption changes to "Alice Texas."

In off, Jim says THIS IS A PART OF TEXAS
THAT ARE STILL
MAJORITY HISPANIC.
FOOTBALL REIGNED, AND YOU KNOW,
EVERYBODY, FRIDAY NIGHTS.
THAT'S WHAT IT WAS ALL ABOUT.
AND IT WAS AN OIL BOOMTOWN TOO.
ALTHOUGH THERE'S A LOT
OF AGRICULTURE AS WELL.

Jim says MY MOTHER'S FAMILY
HAS BEEN HERE
SINCE PROBABLY
THE 1840S, I THINK.
MY DAD WAS THE DOCTOR
WHO, YOU KNOW,
TOOK CARE OF PEOPLE
IN THE NEIGHBORHOOD,
DID HOUSE CALLS.

A black and white portrait of a young woman appears, followed by a picture of a man with glasses and a boy holding a fishing rod.

The caption changes to "James Allison." He is in his sixties, with a white beard and long white hair. He wears sunglasses and a black and white shirt.

Jim continues MY FATHER MOVED TO ALICE
IN THE '30S, SOMETIME,
I DON'T REMEMBER EXACTLY WHEN,
BUT I WAS BORN IN 1948.
AND WE LIVED...
I THINK HERE, ACTUALLY.
BECAUSE THERE WAS A...
WASHING MACHINE OUT IN THE YARD.
I GOT MY ARM CAUGHT
IN THE WRINGER ONE TIME.
IT PULLED ME UP, AND...
YOU KNOW, IT GOT STUCK
AND I WAS HANGING THERE
BY MY ARM.
AND SOME PEOPLE...
NEIGHBORS CAME OUT.

[light music plays]
[dog barking]

Jim says I HAVE TWO BROTHERS,
MURPHY AND MIKE.

[indistinct chatter]
A picture shows two boy wearing baseball helmets next to a baby boy.
The caption changes to "Murphy Allison, 8 years old. Mike Allison, 6 years old."

Murphy sits on a sofa. He is in his late sixties, clean-shaven with brown hair. He wears glasses and a blue shirt.

Murphy says MY MOTHER,
SHE WAS A HOUSEWIFE.
SHE WAS A GOOD INFLUENCE,
HONESTLY.
SHE'S KINDA...
GIVE US A LITTLE DISCIPLINE.
WE GET TO WASH THE DISHES
ON SUNDAY,
AND THINGS LIKE THAT.
'COURSE THAT MAY HAVE BEEN
A LITTLE BIT
BEFORE JIM'S TIME.
HE, UH, I THINK
HE GOT OUT OF THAT.

Jim says I DIDN'T REALLY KNOW
WHAT WAS GOING ON IN THOSE DAYS.
NOBODY TALKED ABOUT IT.
ONLY SHE WAS SICK.
AND, UH...
SHE HAD THESE BURNS
ON HER THROAT.
AND, UH...
YOU KNOW, SHE WAS IN BED A LOT.

[somber music plays]

Jim says I REMEMBER ONE DAY,
I MET SOME GOOD FRIENDS,
A KID MY AGE.
AND HIS MOTHER WAS GONNA TAKE US
TO THE SWIMMING POOL.
I WAS ABOUT TO GET IN THE CAR,
AND SOMEBODY CAME RUNNING OUT,
AND SAID, "HEY,
YOU GOTTA COME BACK.
YOU CAN'T GO." YOU KNOW?
SO I WENT, AND SHE WAS DYING.
AND, UM...
SO, UM, THAT MADE, UM...
SO SHE DIED THAT, THAT MORNING.
AND I FOUND OUT LATER, I DID...
I REALLY DIDN'T KNOW
WHAT IT WAS,
BUT I FOUND OUT LATER
THAT IT WAS LYMPHOMA.
SHE'D BEEN GETTING
RADIATION THERAPY.
HENCE, THE BURNS ON HER NECK.

Fast family clips flash by.

Jim says AND I SAT ON THE BED,
YOU KNOW, AND HELD HER HAND,
WELL... WELL, SHE DIED.
YOU KNOW, THERE WAS A...
SUDDENLY A BIG HOLE,
A LOT OF LONELINESS.
I WAS 11 YEARS OLD
WHEN MY MOM DIED.
MY FATHER WAS JUST HEARTBROKEN.
YOU KNOW, HE SEEMED TO KINDA
LOSE INTEREST IN THINGS.
ANYWAY, HE WAS...
HE WAS GONE A LOT.
I ENDED UP LIVING
WITH A SORT OF A FOSTER HOME.
I MEAN, NOT IN THE SENSE
THAT I WAS...
GIVEN AWAY OR EVERYTHING,
BUT A COUNSELOR FROM HIGH SCHOOL
TEED ME UP WITH A FAMILY.
THEY WERE, UH,
WORRIED ABOUT MY AGE, AND...
SO EXCEPT WHEN MY DAD WAS AWAY
I STAYED WITH THEM ALL THE TIME.

[birds chirping]

Jim says I LIKE TO WANDER
OUT IN THE WOODS.
I WAS RIGHT AT THE EDGE OF TOWN,
I USED TO WANDER IN THE WOODS
BY MY HOME.
AND I ALWAYS FELT IT WAS
COMFORTING TO HAVE A HARMONICA
AND JUST TOOT AWAY, YOU KNOW.

[dramatic music plays]
The caption changes to "Every year cancer kills more than 9 million people. For centuries scientists searched for a cure, without success. Until now."

In off, A Male Host says ON BEHALF
OF THE NOBEL ASSEMBLY
AT THE KAROLINSKA INSTITUTE,
I WISH TO CONVEY TO YOU
OUR WARMEST CONGRATULATIONS.
MAY I NOW ASK YOU
TO STEP FORWARD
TO RECEIVE THE NOBEL PRIZE
FROM THE HANDS
OF HIS MAJESTY, THE KING.

The caption changes to "In 2018, Jim Allison won the Nobel Prize in Medicine."

Jim receives the Nobel Prize in a solemn ceremony.

[fanfare music playing]
[applause]

In off, A Woman says INNOVATION
IS EXTREMELY DIFFICULT.

In off, Man 1 says WE WERE ALL VERY SKEPTICAL.

In off, Man 2 says MANY PEOPLE SAID,
"JIM ALLISON,
YOU'RE WASTING YOUR TIME."

[Light music plays]

Jim says I KNEW THAT THIS IS A WAY
TO CURE CANCER.
I KNEW THAT THAT WAS A WAY.
AND I'LL BE DAMNED
IF I'M GONNA LET
THAT JUST LAY AROUND.

As an animation shows an explosion of cells, the title of the documentary reads "Jim Allison: Breakthrough."

Jim says WELL, I GUESS MY DAD
ENCOURAGED ME TO MESS AROUND
THAT GILBERT CHEMISTRY SET
IN THE GARAGE, YOU KNOW, AND...
DISSECT FROGS AND HORNED TOADS,
AND THINGS.

[test tube clinking]

The caption changes to "Eric Benson. Reporter, Texas Monthly." Eric is in his early thirties, with a beard and brown hair. He wears a gray shirt.

Eric says HE TOLD ME ABOUT
THE BOMBS HE USED TO MAKE.
HE WOULD CONSTRUCT THESE
LITTLE BOMBS OUT IN THE WOODS.
AND HE SAID,
IN THIS VERY JIM WAY,
HE SAID...
[stutters]
"WHEN YOU TALK WITH SCIENTISTS,
YOU KNOW, LATER IN LIFE,
YOU'LL REALIZE A LOT OF US WERE
BOMB MAKERS IN THE BEGINNING."

Jim says WHEN I START LEARNING
ABOUT WHAT SCIENCE REALLY WAS
AND HOW TO DO IT,
YOU KNOW, I STARTED
DOING SOME WORK
THAT TELLS YOU THINGS
IN MAKING BOMBS.

[chalk rasping]
Old footage shows a male teacher writing on a chalkboard.

Jim says ONE OF MY TEACHERS
WHO TAUGHT ADVANCED MATHEMATICS,
PHYSICS, CHEMISTRY,
I THOUGHT HE WAS ONE OF THE
GREATEST TEACHERS I EVER HAD.
BUT I TRIED TO HAVE
A FEW CONVERSATIONS
WITH HIM ABOUT EVOLUTION,
SELECTION OF THE FITTEST,
DARWIN.
HE JUST SAID, "NO," YOU KNOW?
"THIS IS NOT...
I AM NOT ALLOWED.
WE WILL NOT TEACH THAT.
WE WILL NOT DISCUSS IT."
I REFUSED TO TAKE THE COURSE,
BECAUSE
I KNEW THAT THERE WAS
NO BIOLOGY IN IT.
THE SYLLABUS,
THERE WAS NO BIOLOGY IN IT.
SO... IT WAS A PRETTY UGLY TIME.
AND IT WAS... IT WAS BASICALLY,
ME VERSUS HIM.
I WAS STILL TAKING FAST PHYSICS
FROM HIM
WHILE I WAS HAVING THIS FIGHT
WITH THE SCHOOL.
BECAUSE HE WAS THE HEAD
OF THE SCIENCE PROGRAM.
HE WAS THE ONE THAT MADE SURE
THAT EVOLUTION WASN'T TAUGHT.
AND SO, HE REALLY DID START
TAKING IT OUT ON ME.
BACK IN THOSE DAYS, YOU KNOW,
YOU COULD USE BOARDS
TO BATTLE STUDENTS, SO...
I SEEMED TO BE GETTING
IN TROUBLE ALL THE TIME.
GETTING A COUPLE OF LICKS
JUST FOR WALKING BY, YOU KNOW.
[snickers]

[slow music plays]

Jim says EVERYBODY JUST THOUGHT
I WAS A TROUBLEMAKER.
I WASN'T. I WAS JUST TRYING
TO DO WHAT WAS RIGHT.
THAT'S THE WAY IT IS, YOU KNOW?
IF YOU, UH...
IF YOU DON'T AGREE
WITH SOMETHING,
YOU NEED TO STAND YOUR GROUND.
AND IF IT HURTS, IT HURTS,
YOU KNOW?
THAT'S THE WAY IT IS, YOU KNOW?

Murphy says WHEN HE WAS LITTLE,
WE SAID HE WAS HARDHEADED.
WE NEVER DID CALL JIM
THIS TO HIS FACE, BUT,
YOU KNOW, THEY-- THIS GUY
WOULD CALL HIM DIAMONDHEAD.
'CAUSE HIS HEAD WAS THE HARDEST
SUBSTANCE KNOWN TO MAN.

[upbeat music plays]

A Male Narrator says JIM GRADUATES
FROM HIGH SCHOOL AT AGE 16.

The caption changes to "Austin, Texas, 1965."

Fast clips show urban traffic and a lab.

He continues HE GOES TO THE UNIVERSITY
OF TEXAS IN AUSTIN
DETERMINED TO BECOME
A BIOLOGIST.

The caption changes to "G. Barbie Kitto. Professor, UT Austin." Barbie is in his seventies, with white a white beard and blond hair. He wears glasses and a pink polo-shirt.

Barbie says THERE WAS THIS KNOCK
ON THE DOOR.
DOOR OPENS, AND THIS SCRAWNY KID
POKES HIS HEAD IN,
AND SAYS, "YOU GOT A JOB?"
I SAID, "THERE'S ONE JOB LEFT,
BUT YOU MAY NOT LIKE IT.
UM, IT'S JUST A DISHWASHER."
AND HE SAID, "I'LL TAKE IT."
WE WOULD TAKE
A PIECE OF CHEESECLOTH,
AND PUT A LITTLE BIT
OF ACETONE ON IT,
AND RUB OFF THE NUMBER
OF EACH TEST TUBE.
AND LITERALLY,
THERE WERE THOUSANDS OF THEM.
AND SO HE THOUGHT THE IDEA,
"WELL, MAYBE I COULD TAKE
THOSE TEST TUBES
AND SPRAY THEM WITH
A SOLID STREAM OF ACETONE."
THIS WAS BACK IN THE '60S.
AND JUST ABOUT EVERYBODY
SMOKED THEN,
INCLUDING IN THE LAB.
JIM SPRAYED HIS TEST TUBES
WITH ACETONE,
AND THEN SAT BACK
TO HAVE A CIGARETTE.
AND... BOOM!
[explosion]
AND WE ALL RAN IN
FROM THE LAB.
AND HERE'S JIM
WITH A BLACKENED FACE.
HIS EYEBROWS WERE ALL SINGED.
I WAS ABOUT TO FIRE HIM.
BUT, IN THE SHORT TIME
HE'D BEEN THERE,
JIM, WELL, HE JUST GOT ALONG,
AND KNEW ALL THE GRADUATE
STUDENTS AND THE OTHERS.
AND THEY BESIEGED ME
ON HIS BEHALF.
"LOOK, CAN YOU FIND SOMETHING
ELSE FOR JIM TO DO?
HE'S QUITE A CHARACTER.
LET'S KEEP HIM AROUND."

Jim plays the harmonica.

He sings I AM A KING BEE
WON'T YOU BE MY QUEEN?

Malinda says IN THE SUMMER OF 1966,
THAT I WENT TO
WITH SOMEONE ELSE.

Jin sings TOGETHER
WE CAN MAKE HONEY, BABY
THAT THE WORLD
HAS NEVER SEEN

Malinda says HE WAS THE MOST
AMAZING THING
I'D EVER SEEN IN MY LIFE.

The caption changes to "Malinda Allison." Malinda is in her sixties, with short blond hair. She wears glasses, a black jacket and a gray shirt.

Malinda says I NEVER DATED ANYONE ELSE
IN COLLEGE.
WE WERE TOGETHER FROM THEN ON.
IT WAS A REALLY KINDA
MAGICAL TIME TO BE IN COLLEGE.
IT WAS SO MUCH FUN,
SO MUCH GOING ON.

Pictures of the couple flash by.

Jim says WE WERE LUCKY ENOUGH
TO BE IN COLLEGE IN AUSTIN.
JUST AS EVERYTHING WAS BEGINNING
TO HAPPEN THERE.
IT REALLY MADE IT WHEN
WILLIE NELSON MOVED THERE.
I THINK THE FIRST TIME
I SAW HIM LIVE,
HE WAS PLAYING
ON A FLATBED TRUCK.
IN A FORD DEALERSHIP
OF SOUTH LAMAR IN AUSTIN.

Giving a concert, Willie sings FOR A LOVE THAT USED TO BE
IT'S A LONELY SONG
ABOUT A LONELY MAN
LIKE ME

Man 1 says YEAH!

Willie sings THERE WAS SOMETHING
ABOUT A LOVE

Malinda says BUT EVERYONE WAS ALSO REAL
SERIOUS ABOUT THEIR STUDIES.
JIM WAS PASSIONATE
ABOUT SCIENCE.

[glasses clinking]

Jim says WHEN I WAS
AT THE UNIVERSITY OF TEXAS,
THE NUMBER ONE THING I LEARNED
IN THE LAB,
WHICH IS HOW IMPORTANT IT IS
JUST TO PERSEVERE.
NOT BEING SO DISAPPOINTED,
YOU WANNA... YOU GIVE UP,
JUST KEEP WORKING.

Malinda says WE COULD NEVER GO ANYWHERE
WITHOUT GOING TO THE LAB,
CHECKING ON THIS OR THAT,
EXPERIMENT IN PROCESS.

Close-up shots show chemical experiments.

Jim says T CELLS WERE DISCOVERED
WHEN I WAS IN COLLEGE.
AND I TOOK
AN UNDERGRADUATE CLASS,
AND MY PROFESSOR BILL MANDY,
YOU KNOW, TAUGHT, UH,
ONE LECTURE...
ABOUT T CELLS, BECAUSE ALMOST
NOTHING WAS KNOWN ABOUT THEM.

The Narrator says THE HUMAN IMMUNE
SYSTEM CIRCULATES IN OUR BLOOD
AND PROTECTS US FROM DISEASE.
WE NOW KNOW THAT AT THE CENTER
OF THE IMMUNE SYSTEM
IS THE T CELL.

The caption changes to "Lewis Lanier. Professor, UC San Francisco." Lewis is in his fifties, with a goatee and curly brown hair. He wears glasses and a gray shirt.

Lewis says T CELLS ARE A TYPE
OF WHITE BLOOD CELL.
AND THESE ARE THE CELLS
THAT ACTUALLY RESPOND
AGAINST VIRAL INFECTIONS,
BACTERIAL INFECTIONS,
AND THEY START TO FIGHT
TO KEEP YOU HEALTHY.

Jim says THESE CELLS
THAT ARE ALL OVER YOUR BODY,
AND MANAGE TO PROTECT YOU
AND NOT KILL YOU.
[scoffs]
AND STILL...
TO ME, JUST... JUT WONDROUS.
I WANTED TO TRY
TO DO SOMETHING,
SOMETHING VERY KITTO.
I ALWAYS THOUGHT WAS...
YOU KNOW, YOU SHOULD TRY
TO DO THINGS.
IF YOU'RE GONNA DO THIS STUFF,
YOU OUGHTA,
AT LEAST DO THINGS
THAT HELP PEOPLE.
MY MOTHER
HAD THREE BROTHERS.
ONE DIED FROM MELANOMA.
AND THOSE DAYS, MELANOMA
WAS A DEATH SENTENCE, SO...
HE DIDN'T EVEN GET THERAPY
WHEN HE WAS DIAGNOSED.
HE JUST SAID, "THAT'S IT,"
YOU KNOW?
HAD A REALLY GOOD TIME
FOR THE MONTHS THAT HE HAD.
THE OTHER BROTHER
WAS A FORMER RANCHER.
HE COULD ROLL
A BULL DURHAM CIGARETTE
WITH ONE HAND
WHILE HE WAS ON A HORSE.
YOU KNOW, BUT HE PAID FOR THAT.
HE HAD LUNG CANCER
AND DIED FROM THAT.
I SAW HIM IN AN OXYGEN TENT.
HE GOT TO THE POINT THAT HIS,
YOU KNOW, HIS EMPHYSEMA
OR WHATEVER, WAS SO BAD,
HE NEEDED HELP TO BREATHE.
UM, THOSE MADE KIND OF
AN IMPRESSION.

[tense music plays]

Barbie says MY OWN LAB WAS NOT INVOLVED
WITH CANCER
WHEN JIM, UH,
CAME TO WORK WITH US.
BUT HE HAD HAD
A TREMENDOUSLY DIFFICULT
RELATIONSHIP WITH CANCER.
SO, AT GRADUATE SCHOOL,
HE CONVINCED ME TO... PERHAPS
WE COULD LOOK AT SOMETHING
IN THE CANCER FIELD.

Jim says THERE WAS AN ENZYME
CALLED ASPARAGINASE
THAT WHEN INJECTED
INTO KIDS WITH LEUKEMIA
COULD INDUCE REMISSIONS.
IT WAS FIRST THOUGHT
THEY WERE CURED,
BUT IT TURNED OUT
THEY WEREN'T...
I MEAN, THEY WERE FOR A TIME,
BUT THEN THEY ALWAYS CAME BACK.
MY THESIS PROJECT WAS TO FIND
OTHER ASPARAGINASES
FROM OTHER BACTERIA
THAT WOULD BE SO DIFFERENT
THAT THEY COULD BE USED
IN SUCCESSION.
[water churning]

Barbie says WE PULLED WATER
OUT OF THE LOCAL STREAM.
AND SURVEYED THAT
FOR ASPARAGINASE ACTIVITY.
JIM PURIFIED THAT.
AND IN MY... IT'S THAT WORKED
VERY WELL INDEED.

[squeaking]
Mice sit in a cage.

The Narrator says JIM'S WORK
ON ASPARAGINASE
CONVINCES HIM THE IMMUNE SYSTEM
PLAYS AN IMPORTANT ROLE
IN RESPONDING TO CANCER.

[exhales sharply]
Sharon trains in a yard. She is in her thirties, with long straight blond hair. She wears a purple sleeveless shirt.

The caption changes to "Sharon Belvin."

Sharon says I WAS A BIGGER KID GROWING UP.
I'VE REALLY ATE
WAY TOO MUCH SUGAR.
[laughs]
I KNOW THAT NOW.
I PLAYED
A LOT OF SPORTS.
BASKETBALL WAS MY THING.
I PLAYED MY FIRST YEAR
OF HIGH SCHOOL
AND THEN INJURED MY KNEE
PRETTY DARN BAD.
KIND OF LUCKY THAT I DID,
BECAUSE I COULDN'T PLAY
BASKETBALL ANYMORE.
BUT I JOINED
THE MARCHING BAND...
[fanfare music playing]...
WHERE I ENDED UP MEETING
MY SOON-TO-BE HUSBAND.
I WAS FINISHING UP
MY GRADUATE YEAR.
I HAD WHAT, YOU KNOW,
FEELS LIKE BRONCHITIS.
YOU WERE COUGHING,
BREATHING WITH A LITTLE BIT
OF AN ISSUE.
PROGRESSIVELY,
OVER THE NEXT COUPLE OF MONTHS,
I DIDN'T GET BETTER.
I WAS WALKING UP A HILL ONE DAY,
AND I COULD NOT TAKE
A DEEP BREATH.
MY MOTHER WORKED
FOR A PRIMARY CARE DOCTOR.

Pictures of Sharon and her husband appear.

She continues AND SHE SAID, "GO, SWEETIE,
WHEN YOU GET HOME,
COME ON SEE HIM
AND WE'LL GET THIS SORTED OUT."
LITTLE DID I KNOW THAT JUST
A FEW WEEKS BEFORE THAT,
I WAS GONNA DEVELOP
A MASS GROWING OUT OF MY CHEST.
AND I THOUGHT
IT WAS BREAST CANCER
BECAUSE OF WHERE IT'S LOCATED.
UM...
SO, GOING TO SEE HER DOCTOR,
THEY NOTICED THE TUMOR
AND THEY DID A BIOPSY.
AND MY WORLD CHANGED.

[slow country music plays]
The caption changes to "San Diego, California, 1974."

Jim says I WENT TO SCRIPPS
BECAUSE I WANTED TO LEARN
ABOUT THE IMMUNE SYSTEM.
I WANTED TO ASK QUESTIONS ABOUT
HOW THE IMMUNE SYSTEM WORKED.

Malinda says STRANGELY ENOUGH,
THERE WAS A GROUP
OF EXPATRIATE TEXANS THERE.
AND, UH, WE WOULD ALL GO
TO A LITTLE BAR
CALLED THE STINGAREE.
AND THERE WAS A BAND THERE
THAT HE WOULD SOMETIMES
PLAY HARMONICA WITH.

Jim says COLUMBIA RECORDS
WAS HAVING THEIR
ANNUAL CONVENTION IN SAN DIEGO.
AND WILLIE NELSON'S RECORD,
THE
RED HEADED STRANGER,
HAD JUST GONE PLATINUM,
SO THEY DECIDED
TO HAVE A BIG PARTY FOR HIM.
THE GUY THAT WAS
IN THE SHERIFF'S DEPARTMENT
WAS A REAL DEVOTEE OF OUR BAND.
HE CAME AND TOLD ME
ABOUT THIS, YOU KNOW?
AND SAID,
"WE'RE DOING SECURITY FOR IT."
HE LET ME GO IN, YOU KNOW?
LET ME THROUGH SECURITY
TO GO TO THIS PRIVATE PARTY.
WILLIE NELSON CAME OVER,
AND HE SAID,
"WELL, YOU KNOW SOME PLACE WE
COULD GO PICKING TOMORROW NIGHT?
'CAUSE I GOT TOMORROW NIGHT OFF.
AND I'D SURE LIKE
TO PLAY SOME MUSIC."
AND SO...
I SAID, "WELL, THERE'S
TALENT NIGHT AT THE STINGAREE."

[engine idling]

Malinda says SO, WE, UH, LOADED UP
IN OUR LITTLE VW CAMPER.
WE WALKED IN, AND PEOPLE JUST
FELL ON THE FLOOR.
[chuckles]

Jim says WILLIE BASICALLY ASKED,
"YOU GUYS MIND IF I PLAY?"
HE AND HIS DRUMMER
AND HIS BASS PLAYER
STARTED PLAYING.
THEY PLAYED FOR THREE HOURS
AT LEAST.
AND, YOU KNOW,
IT WAS A LITTLE DIVE BAR.
AND THERE'S ABOUT EIGHT PEOPLE
AT THIS PLACE, YOU KNOW?
THERE WAS ONE PAY PHONE
ON THE WALL.

At a lab, he continues AND SO, THOSE EIGHT OR SO,
WENT UP, CALLED PEOPLE,
AND PRETTY SOON
THE PLACE FILLED UP,
AND PEOPLE CALLED OTHER PEOPLE.
IT WAS FULL, THE PEOPLE WERE OUT
ON THE STREET.
IT WAS AMAZING.
I DIDN'T HAVE TO BUY BEER
AT THAT PLACE
FOR ABOUT TWO YEARS AFTER THAT.

[people applauding, cheering]
The caption changes to "Smithville, Texas, 1977."

An aerial view of a center up in a hill appears.

Jim says THAT OLD COLLEGE ROOMMATE
OF MINE.
HE HEARD THAT MD ANDERSON
WAS OPENING
A NEW LABORATORY NEAR AUSTIN.
TO TELL YOU THE TRUTH,
THE MAIN REASON I WENT THERE
WAS 'CAUSE I THOUGHT
I WOULD HAVE FREEDOM.
THE FIRST TIME I CONNECTED
WITH JIM,
WAS, I THINK, IN ABOUT 1980.
I WAS A POSTDOC IN NEW MEXICO.

Lewis says I WENT TO MD ANDERSON,
AND THEY ASKED ME
TO GIVE A SEMINAR.
AND THEY SAID,
"WELL, YOU'RE BEING LIVESTREAMED
TO SMITHVILLE, TEXAS."
AND, UH, SO I GAVE MY SEMINAR,
AND THEY SAID,
"DO WE HAVE ANY QUESTIONS
FROM SMITHVILLE?"
AND I'M THINKING,
"WHERE IN THE HELL
IS SMITHVILLE?"
AND THEN, THIS VOICE COMES OVER
WITH THIS, YOU KNOW,
NICE TEXAS ACCENT.
AND ASKED ME
THIS INCREDIBLE QUESTION.

Jim says WITH A GIVEN MOLECULE
ON A PATH WAVE, FOR EXAMPLE,
WITH A MAP KIND OF
THIS PATH WAVE, WHICH...

Lewis says HE GOT RIGHT
TO THE HEART OF, YOU KNOW,
THE HARDEST QUESTION
HE COULD ASK
ABOUT THE SCIENCE
I WAS DOING AT THE TIME.
I CONSIDER JIM MY BROTHER.
SCIENTIFICALLY,
AS WELL AS PERSONALLY.
I WOULD CONSIDER HIM
MY BEST FRIEND
FOR THE LAST 30 ODD YEARS.

Jim says I REALLY WANTED
TO UNDERSTAND
THE IMMUNE SYSTEM
AND EVERYTHING.
'CAUSE I REALLY WANTED TO KNOW
HOW THE T CELLS WORKED.
AND AT THE TIME, ALL WE
REALLY KNEW IS THAT T CELLS
RAN AROUND THE BODY
AND TOOK CARE OF STUFF
AND DIDN'T HURT YOU.

An animation shows healthy cells near a T Cell. Then, the T Cell turns red transmitting red dots to a diseased cell.

The Narrator says SCIENTISTS KNOW
THAT T CELLS DISTINGUISHED
BETWEEN HEALTHY CELLS
AND THE THREATENING ONES,
BY USING A MOLECULE
ON THEIR SURFACE
CALLED THE T-CELL RECEPTOR.
BUT THEY DON'T KNOW HOW
THE RECEPTOR WORKS.

Lewis says WE DIDN'T KNOW HOW
THOSE WHITE BLOOD CELLS,
THESE T CELLS
WOULD ACTUALLY RECOGNIZE
THE VIRUS AS BEING DIFFERENT
AND NEEDING TO BE ELIMINATED.
AND THAT WAS THE HOLY GRAIL
IN THE LATE '70S AND EARLY '80S.
YOU KNOW, ALL THE TOP LABS
IN IMMUNOLOGY,
THAT WAS THE QUEST.

Jim says I READ THE LITERATURE
AND THERE WAS...
A LOT OF STUFF
JUST CONTRADICTORY,
A LOT OF STUFF
THAT SEEMED LIKE FANTASY.
I COULD NOT POSSIBLY IMAGINE
HOW SOME OF THE MECHANISMS
THAT WERE PROPOSED
ACTUALLY WORKED.
I SAID,
"WELL, EITHER I'M A TOTAL MORON
AND CAN'T FOLLOW
THIS COMPLICATED STUFF,
OR PEOPLE ARE JUST, YOU KNOW,
IT'S ALL... IT'S ALL NONSENSE."
YOU KNOW, IT'S SO FUNNY,
I SAID THAT, "FORGET IT.
I'M NOT GONNA PAY ANY INTEREST
IN THE LITERATURE."

The caption changes to "Tyler Jacks. Director Koch Institute for Cancer Research, MIT." Tyler is in his mid-fifties, clean-shaven with thin blond hair. He wears a deep blue jacket over a pale shirt.

Tyler says PART OF JIM'S SUCCESS
IS THE FACT THAT
HE'S AN ICONOCLAST.
YOU KNOW, HE DOESN'T CARE.
HE DOESN'T CARE THAT
HE'S NOT FOLLOWING CONVENTION.
HE'S FOLLOWING HIS OWN THOUGHTS,
HIS OWN MOTIVATIONS.
HE'S WILLING TO DO IT
IN THE FACE OF, UH...
HIS COLLEAGUES
NOT NECESSARILY BELIEVING HIM.

Jim says I GOT A NOTICE
THAT IRV WEISSMAN FROM STANFORD
WHO IS A VERY NOTED IMMUNOLOGIST
WAS GIVING A LECTURE.
SO I DROVE THREE HOURS
FROM SMITHVILLE INTO HOUSTON.
I WAS DRIVING BACK,
REPLAYING HIS TALK IN MY HEAD.
WHERE IT JUST FIXED
AND IT CLICKED.
I SAID, "I KNOW HOW TO FIND
THE T-CELL RECEPTOR."

Tyler says GREAT SCIENTISTS
ARE CREATIVE PEOPLE.
THEY'RE NOT JUST FOCUSED
ON THEIR DETAILED WORK.
THEY'RE THINKING BEYOND.
THERE'S A CREATIVITY
TO THIS WORK.
AND FRANKLY, IF NOT
FOR THE CREATIVE SCIENTISTS,
WE WOULD MAKE LITTLE PROGRESS.

A song plays I SAW MILES AND MILES
OF TEXAS
ALL THE STARS UP IN THE SKY
I SAW MILES AND MILES
OF TEXAS

Jim says I DROVE BACK THAT NIGHT
WITH THIS GOING IN MY HEAD
AND EVERYTHING, AND...
YOU KNOW, THE NEXT FEW DAYS,
I FIND THE T-CELL RECEPTOR.

The Narrator says OVER THE NEXT FEW MONTHS,
JIM USES THE LATEST
GENETIC ENGINEERING TECHNIQUES
TO TEST HIS HYPOTHESIS.

Jim says WORK HARD ALL DAY,
GET AN INCUBATION PERIOD
OR SOMETHING,
GO TO THE BEER HALL,
YOU KNOW, KNOCK DOWN SOME BEERS,
GO BACK AND FINISH
THE EXPERIMENT.
YOU KNOW, GO TO SLEEP, GET UP.
START IT ALL OVER AGAIN.

Eric says I THINK THE GUY
IS JUST INCREDIBLY PASSIONATE.
SO, HE'LL SPEND A NIGHT
GOING OUT
TO A HONKY-TONK,
AND HE'LL BE OUT ALL NIGHT,
AND HE'LL DRINK,
AND HE'LL HAVE A GREAT TIME.
AND THEN,
THERE'S THAT SAME ENERGY
THAT WOULD PUT HIM
IN THE LAB AT SMITHVILLE.
THEY'RE DOING
A 36-HOUR EXPERIMENT.
AND HE'S STAYING UP FOR THAT.
AND HE'S JUST AS DRIVEN
AND TURNED ON
BY THAT WHOLE EXPERIENCE
OF BEING IN THE LAB.

The song continues I'M GONNA LIVE UNTIL I DIE

Lewis says WE WENT TO A CONFERENCE
IN CALIFORNIA.
THIS IS WHERE
YOU PRESENT YOUR DATA.
YOU'RE... YOU'RE NOT WELL-KNOWN
ENOUGH TO BE INVITED
TO GET UP ON THE PODIUM
AND GIVE A TALK AT THAT POINT.
YOU KNOW, YOU'RE RELEGATED
TO PUT YOUR WORK
ON A POSTER BOARD.
SO, JIM HAD A POSTER THERE,
AND I REMEMBER WALKING,
LOOKING AT HIS POSTER,
AND WE JUST KINDA MET
RECENTLY THEN,
AND HE POINTED TO THE SPOT
ON THE POSTER
AND SAYS,
"THAT'S THE T-CELL RECEPTOR."
AND HE WAS RIGHT.
[chuckles]

Tyler says HIS CONTRIBUTIONS
TO OUR UNDERSTANDING
OF THE T-CELL RECEPTOR.
THE MOLECULE
MOST CENTRALLY IDENTIFIED
AS THE THING THAT RECOGNIZES
THE TARGET,
AND ALLOWS FOR IT
TO BE ELIMINATED.
EXTREMELY IMPORTANT.

The caption changes to "Michael Curran. Assistant Professor University of Texas, MD Anderson Cancer Center." Michael is in his forties, clean-shaven with brown hair. He wears a white doctor apron over a gray shirt.

In a lab, Michael says HE WAS THE FIRST ONE
TO ACTUALLY PURIFY THE MOLECULE
BY WHICH T CELLS
RECOGNIZE EVERYTHING.

Michael says THIS IS HOW T CELLS
RECOGNIZE INFECTIOUS DISEASE.
THIS IS HOW T CELLS
ARE RECOGNIZING THINGS
THEY SHOULDN'T RECOGNIZE
WHEN YOU GET
AUTOIMMUNE DISEASES.
SO THIS WAS
THE SEMINAL DISCOVERY.

Barbie says JIM WAS INVITED TO
MAJOR IMMUNOLOGY CONFERENCES,
AND IT WAS RECOGNIZED
THAT THIS WOULD CONSTITUTE
A REAL BREAKTHROUGH.

[ball thumps]
[panting]
Sharon watches Rob and her daughter play with a ball in her front yard.

Sharon says HE'LL CATCH YOU, GUYS.

[chuckling]
[somber music plays]

Sharon says WHEN THEY CAME BACK
AND SAID,
"SHARON, YOU HAVE MELANOMA,"
I WAS COMPLETELY SHAKEN.
UNBELIEVABLE.
I COULDN'T BELIEVE THAT
THAT WAS MY LIFE.
I THOUGHT I WAS GONNA DIE.

Rob says GOOD JOB.

Sharon says THE DOCTOR CANCELED
ALL HIS PATIENTS
AND SHUT HIS OFFICE DOOR,
AND GOT ON THE PHONE, AND SAID,
"I HAVE A 22-YEAR-OLD PATIENT
HERE WHO NEEDS TO SEE YOU NOW."
AND HE WAS ON THE PHONE ALL DAY.
BUT I HAD AN APPOINTMENT
WITH SLOAN BY THE END OF IT.
SO THEN I SAW DR. WOLCHOK
JUST A COUPLE OF DAYS LATER.

The caption changes to "Doctor Jedd Wolchok. Chief, Melanoma and Immunotherapeutics Memorial Sloan Kettering Hospital." Jedd is in his late forties, clean-shaven with wavy graying hair. He wears a dark blue suit, light blue shirt and dark blue tie.

In an office, Jedd says SHARON BELVIN,
WHEN I FIRST MET HER
WAS 23 YEARS OLD.
SHE WAS SEEN BY AN ONCOLOGIST
NEAR HER HOME
IN THE NEW JERSEY SHORE,
UM, WHO CALLED ME AND SAID,
"YOU NEED TO SEE
THIS YOUNG WOMAN."
SO I SEE HER,
AND IT'S A ROOM FULL OF...
VERY SAD, YOU KNOW, UM,
FAMILY MEMBERS.
UM, TRYING TO GET
THEIR HEAD AROUND
THIS SEEMINGLY
UNBELIEVABLE SITUATION.
WE STARTED HER ON CHEMOTHERAPY,
VERY QUICKLY THEREAFTER.

Sharon says SO, I HAD CHEMOTHERAPY
MONDAY, TUESDAY, WEDNESDAY,
AND GOT MARRIED THAT SATURDAY.
WE DECIDED
TO GO THROUGH THE WEDDING
BECAUSE IT'S FOR BETTER
OR WORSE.
[chuckles]
I MEAN, WE WERE JOKING AROUND
A COUPLE OF DAYS BEFORE,
AND WE WERE JUST LIKE, "OKAY.
WE ARE GONNA GET THE WORST OVER
WITH RIGHT IN THE BEGINNING,
AND THEN THE REST OF LIFE
WILL BE GREAT.
UH, AND ROB IS REALLY A...
PROBABLY A SAINT,
AND DON'T TELL HIM I SAID THAT.
WHO CAN LOOK
AT SOMEBODY AND SAY,
"HERE'S A TERMINAL DIAGNOSIS,
AND I'M GONNA MARRY YOU ANYWAY."

A newspaper headline reads "Legislators trying to put religion into lawbooks."

Tyler says IN 1981, THERE WAS
A BILL THAT WAS INTRODUCED
BY A VERY CONSERVATIVE STATE
SENATOR FROM EAST TEXAS,
SAYING THAT CREATIONISM
NEEDED TO BE TAUGHT IN SCHOOLS.

Malinda says ONE OF HIS TEACHERS
FROM ALICE HAD ACTUALLY BEEN
ELECTED AS THE STATE
REPRESENTATIVE FROM ALICE.
NOT THE SCIENCE TEACHER,
OF COURSE.
AND SHE CALLED HIM UP AND SAID,
"SOMEONE HAS INTRODUCED A BILL
TO OUTLAW THE TEACHING
OF EVOLUTION
IN THE PUBLIC SCHOOLS,
AND WE'VE GOT
A HEARING COMING UP,
AND WE NEED SOMEONE
TO COME AND TALK."

Jim says SHE SAID HE'S GONNA HAVE
300 PEOPLE, YOU KNOW,
SUPPORTING THE BILL,
OPPOSING EVOLUTION.
AND SO,
IF WE DON'T HAVE SOMEBODY,
YOU KNOW,
SPEAKING TO THE OTHER SIDE,
IT'S LIKELY TO PASS COMMITTEE
OUT TO THE HOUSE FLOOR.
YOU KNOW, GOD KNOWS
WHAT'S GONNA HAPPEN.
I TRIED TO FIND OTHER PEOPLE
WHO WOULD DO IT.
I ONLY FOUND ONE OTHER SCIENTIST
THAT WAS WILLING TO DO THAT.

The caption changes to "Voice of Jim Allison."

A black and white picture of a Congress session appears.

Jim says I'M HERE TONIGHT
SPEAKING BEFORE THIS COMMITTEE,
BECAUSE I FEEL, THAT IN THIS
HIGHLY TECHNOLOGICAL AGE,
AN EDUCATION IN SCIENCE
IS ESSENTIAL THAT MEMBERS
OF OUR SOCIETY
TO BE ABLE TO UNDERSTAND
AND DEAL WITH COMPLEX
AND DIVERSE PROBLEMS
FACING THEM. AND I KNOW...

The audio fragment ends.

Jim says YOU KNOW, I SAID, "SCIENCE
IS SOMETHING YOU CAN USE."
YOU KNOW, IT'S NOT JUST A COUCH
FROM THE PAST.
IT DOES THAT...
IT ALSO ALLOWS YOU TO KNOW,
UNDERSTAND WHAT'S GONNA HAPPEN
IN THE FUTURE,
THE SITUATIONS
THAT YOU'VE NEVER SEEN BEFORE,
THAT HAVE NEVER ARISEN.
THAT'S WHAT SCIENCE IT.

Back in the audio fragment, Jim says THAT IS THE CHIEF PROBLEM
WITH CREATIONISM,
PURPORTING TO BE A SCIENCE.
IT CANNOT BE USED
TO CONSTRUCT EXPLANATIONS
AND MERELY OBSERVE FACT.
IT DOES NOT GIVE US
ANY HELP WHATSOEVER
IN UNDERSTANDING
HOW TUMOR CELLS ARISE,
AND HOW THEY ARE ELIMINATED
BY THE IMMUNE SYSTEM.

Eric says HE TALKS ABOUT USING
THE IMMUNE SYSTEM
TO CURE CANCER, AT THAT POINT,
EVEN IN 1981.

Jim says I SAID, "I'D CHALLENGE THIS MAN
TO USE HIS 'CREATION-SCIENCE',
SUCH AS IT IS,
TO UNDERSTAND HOW A TUMOR
ESCAPES THE IMMUNE SYSTEM."

[calm music plays]

A newspaper article reads "House defeats 'creation-science' curriculum."

Jim says IT'S HILARIOUS,
THE LIMITS OF THEIR ARGUMENTS.
PROBABLY THE BEST ONE WAS,
"IF YOU PUT A FORD IN A FIELD,
IT RUSTS, IT DON'T TURN
INTO NO CADILLAC."
YOU KNOW, I SAID,
"OH. YEAH. OKAY, I GOT IT."
OBVIOUSLY, THAT CAN'T BE,
THAT'S NOT LIKE EVOLUTION.

[chuckles]

A clip shows Jim playing the harmonica in a concert.

Eric says PRETTY SOON AFTER THAT,
HE GOT AN OFFER FROM
THE UNIVERSITY OF CALIFORNIA
AT BERKELEY, TO GO OUT THERE.

Jim says AFTER THE T-CELL RECEPTOR,
I WAS OFFERED A
FULL PROFESSORSHIP AT BERKELEY.
AND I WAS REALLY HAPPY.
OUT OF SMITHVILLE,
LIVIN' IN AUSTIN,
WORKING IN SMITHVILLE.
I'M JUST DOING SCIENCE,
IT WAS JUST AS CLEAN
AS IT COULD GET.
I WAS DOING
EXACTLY WHAT I WANTED TO.
I DIDN'T ANSWER
TO ANYBODY.
I DIDN'T HAVE TO DO
ANY ADMINISTRATION OR ANYTHING.
SO THE IDEA OF GOING
INTO SOME BIG-TIME PLACE,
AND HAVING TO, YOU KNOW, COMPETE
WAS A LITTLE SCARY, BUT...
OLD FRIEND OF MINE
CAUGHT ME UP AND SAID,
"WHAT ARE YOU DOIN'?"
AND I TOLD HIM THAT
I'M COMFORTABLE HERE,
I'M HAPPY HERE.
HE SAYS, "YEAH, IN 20 YEARS
YOU'RE GONNA BE SITTIN' THERE
WITH YOUR FEET UP
ON THE PORCH SAYING,
'I COULD HAVE BEEN
A CONTENDER.'"
AND I KINDA WENT, "YEAH.
[laughs]
I UNDERSTAND WHAT YOU MEAN."

A man plays the saxophone on the street.

The caption changes to "Berkeley, California, 1985."

Jim says WHEN I DECIDE
WHO TO HIRE IN MY LAB,
I ALWAYS AM LOOKING FOR
ONE THING, REALLY,
AND THAT'S CURIOSITY.

The caption changes to "Max Krummel. Former PhD student, UC Berkeley." Max is in his thirties, clean-shaven and bald. He wears a blue cap and a striped blue polo-shirt.

Max says BERKELEY DREW ME IN
IN A LOT OF DIFFERENT WAYS.
IT'S FILLED WITH
VERY SMART PEOPLE,
BUT VERY FREAKY PEOPLE.
AND THEY ALL SORT OF
INTERMINGLE.
AND YOU DON'T EVER KNOW
WHAT'S A CRAZY IDEA
AND WHAT'S A GREAT IDEA.
EVEN AT BERKELEY,
JIM WAS A STANDOUT.
HE DIDN'T LOOK LIKE
THE OTHER PEOPLE.
BERKELEY HAS ITS OWN
CONSERVATIVE/LIBERAL SIDE OF IT,
WHICH IS THAT, YOU KNOW,
YOU CAN BE
LIBERAL UP TO A POINT,
BUT TEXAN IS ACTUALLY,
IT'S TOO FAR.
YOU KNOW, IT'S...
[chuckles]
IT'S LIKE YOU'RE CARRYING A GUN,
AND, I DON'T KNOW, ALL KINDS
OF THINGS THAT COULD BE BAD.
AND SO, JIM WAS LIKE
JUST OVER THAT LINE,
AND REPRESENTED
JUST THE, YOU KNOW,
ADDITIONAL FRONTIER,
EVEN AT BERKELEY.

Scientists work in a lab.

Max says BUT ALSO, IMMUNOLOGY
WAS NOT CONSIDERED A SCIENCE.
THE CLASSIC PEOPLE SAID,
"OH, IMMUNOLOGY,
THAT'S SORT OF
A PSEUDO DISCIPLINE.
THAT'S REALLY, LIKE,
ALMOST, LIKE, GIVING, UH,
HOLISTIC MEDICINE
OR SOMETHING, RIGHT?"
IT'S LIKE, "WHAT IS THAT?"
YOU DON'T EVEN KNOW
WHAT THAT IS.
SO, JIM'S LAB HAS A FEEL
OF BEING LIKE A PIRATE SHIP.
THERE WERE PERSONALITIES DOING
THEIR OWN CRAZY STUFF.
AND YET, THERE IS A, YOU KNOW,
DEDICATION TO PURPOSE
OF DRIVING THE BOAT FORWARD.

Jim says I WAS WORKING A LOT.
NOT AS HARD AS THE PEOPLE
IN THE LAB, OF COURSE,
I MEAN, THEY WERE WORKING
ALL THE TIME.
BUT WE ALSO
ALL PARTIED TOGETHER.
YOU KNOW, I JUST HAD
SOME INCREDIBLE PARTIES.

Max says THERE IS THE RIGID
THOUGHT PROCESS
THAT IS LIKE, CONNECT THE DOTS
A TO B TO C, TO...
YOU KNOW LIKE THAT.
AND THAT,
YOU DO DURING THE DAYTIME.
BUT I THINK
THERE'S A WHOLE ELEMENT
OF THE IDEA OF UNWINDING
AND NOT LETTING THE MIND
GO LINEAR.
AND JUST SAYIN', WHAT IS...
YOU KNOW, WHAT IF IT WEREN'T...
WHAT IF NOTHING WE THOUGHT
WAS RIGHT?

The Narrator says JIM'S WORK
ON THE T-CELL RECEPTOR
HAS SPARKED A RACE
TO DISCOVER MORE SECRETS
OF THE T CELL.
SOON, A FRENCH SCIENTIST
FINDS A NEW PROTEIN
ON THE SURFACE OF T CELLS,
CALLED CTLA-4.
MOST RESEARCHERS ASSUME
THAT IT ACTIVATES
THE IMMUNE SYSTEM
LIKE THE T-CELL RECEPTOR.

Jim says THE ONLY RIGHT WAY TO DO SCIENCE
IS NOT TO DO EXPERIMENTS
TO GIVE YOU AN ANSWER
THAT'S CONSISTENT WITH WHAT
YOU THINK YOU OUGHT TO GET.
BUT DO THE KILLER EXPERIMENT
THAT CAN ONLY BE RIGHT
IF YOU'RE RIGHT.

Lewis says JIM STARTED LOOKING AT
THE DATA ON CTLA-4, CRITICALLY.
AND HE AND MAX KRUMMEL,
HIS GRADUATE STUDENT,
STARTED SAYING, "WELL, LET'S SEE
WHAT THE REAL DATA IS,
IF WE DO EXPERIMENTS,
IS THAT TRUE OR NOT?"

Max says SO WE JUST HAD
THIS STUPID QUESTION, LIKE,
"WHAT DOES IT DO?"
AND IT WASN'T LIKE
JUST TO CURE CANCER,
IT WAS LIKE,
"WHAT DOES THAT DO?"

A family clip plays.

Malinda says ARE YOU SHOOTING HIM?

Jim says YES.

Malinda says WELL, IT'S CHRISTMAS, IT'S 1991.
AND WE'RE LOADING A PIÑATA HERE,
AS YOU CAN SEE.

[Robert shrieking]

Malinda says THERE'S ROBERT.

Jim says ROBERT.

Two-year old Robert looks up to the piñata.

The caption changes to "Robert Allison."

The clip ends.

The Narrator says TO STUDY CTLA-4
IN A MOUSE,
KRUMMEL MUST BUILD
A MOUSE ANTIBODY.
A Y-SHAPED PROTEIN
THAT WILL TRIGGER A REACTION
FROM CTLA-4.

In another family clip, Robert plays with a car next to presents on the floor.

The caption changes to "December 25 1992."

Jim says OH.

Robert says POLICE CAR.

Malinda says SANTA BROUGHT ROBERT
A POLICE CAR.

The caption changes to "December 31 1993."

Robert skates in the snow.

Jim says OKAY, LET'S GO!

Max says WHAT MADE THAT
WHOLE THREE-YEAR STRETCH FOR ME
VERY DIFFICULT,
WAS THAT I DIDN'T GET
ANY PROGRESS, SCIENTIFICALLY.

The caption changes to "June 11 1994."

Robert wears a Batman costume.

In off, a man says ALL RIGHT, JUST A LITTLE BIT...

Jim says ROBERT'S FIRST...
FOURTH BIRTHDAY.
ROBERT, LOOK OVER HERE.
LOOKS... ARE YOU BATMAN?

Max says AND THIS IS,
THIS IS REALLY COMMON FOR US.
THREE YEARS. NADA.
YOU KNOW, LIKE,
EVERYTHING I DID,
REALLY DIDN'T AMOUNT
TO ANYTHING.

The caption changes to "Dan Littman. Professor, New York University." Dan is in his late fifties, clean-shaven with white hair. He wears a dark sweater and blue frame glasses.

Dan says RUNNING LABORATORIES,
IT'S NOT EASY TO HAVE PEOPLE
DO THE EXPERIMENTS
YOU WANT THEM TO DO.
I REGRET, AT TIMES,
NOT BEING ABLE
TO MOTIVATE PEOPLE
TO DO THE KINDS OF EXPERIMENTS
THAT I WAS SURE,
NEEDED TO BE DONE.
UH, BUT JIM HAS THAT ABILITY
TO DO THAT.
SO, BECAUSE OF THAT,
PEOPLE IN THIS LAB
HAVE DONE THINGS
THAT WERE CRAZY AT SOME TIMES,
BUT HE ALSO WAS ABLE
TO GET PEOPLE
TO DO THE THINGS THAT
HE WAS REALLY PASSIONATE ABOUT.

The Narrator says WHILE MAX STRUGGLES
TO MAKE HIS ANTIBODY,
ANOTHER LAB BEATS HIM TO IT.
PETER LINSLEY,
A SCIENTIST WORKING
WITH THE DRUG COMPANY,
BRISTOL-MYER SQUIBB,
PUBLISHES RESULTS SAYING THAT
CTLA-4 IS
AN ACTIVATING RECEPTOR.
WHEN IT'S ENGAGED,
IT REVS UP THE IMMUNE RESPONSE
AGAINST TARGETS.

Jim says THEN THESE PAPERS CAME OUT
SAYING IT'S A POSITIVE REGULATOR
AND...
SO, YOU KNOW, THE ATTITUDE WAS,
WELL, WE'VE BEEN SCOOPED.
YOU KNOW, IT'S DONE.
EXCEPT, I SAID,
"I DON'T THINK SO."
THERE'S SOMETHING ABOUT,
YOU KNOW, SOME...
I SAW SOME HOLES
IN THAT PAPER, AND SO...
WE'RE GONNA TEST THIS FUCKER
AND SEE IF IT'S REALLY RIGHT.

The caption changes to "Matt Richtel. Reporter, The New York Times." Matt is in his late forties, clean-shaven with receding hair. He wears a checked blue shirt.

Matt says YOU HAVE THIS PICTURE
OF EINSTEIN
SITTING AT THE WHITE BOARD,
HAIR FRAYED,
YOU KNOW, WRITING EQUATIONS
THAT NO ONE CAN SEE.
REALLY, WHAT HE'S DOING
IS SAYING,
"THERE'S A FUNDAMENTAL QUESTION,
AN ASSUMPTION PEOPLE HAVE MADE,
THAT DOESN'T MAKE SENSE
IF YOU LOOK AT THIS
IN A CLEAR-EYED WAY."
"WHAT IF I STEP BACK HERE,
AND JUST OBSERVE, AND SAY,
THESE PIECES OF INFORMATION
NEED TO BE PUT TOGETHER
IN A DIFFERENT WAY."
I THINK THAT IS
WHAT PIONEERS DO.
AND WEIRDLY, IT'S CHILDLIKE.

Max says THIS IS, UH,
THIS IS A HARD THING.
IT TOOK ME A WHILE TO BE ABLE
TO SAY THIS TO PEOPLE, RIGHT,
BUT I THINK THERE WAS
A FORMATIVE MOTIVE.
WHEN I WAS IN JIM'S OFFICE
AND I ACTUALLY STARTED TO CRY.
'CAUSE I'VE BEEN WORKING
ON SOMETHING FOR SO LONG,
AND THEN HE TOLD ME SOMETHING,
AGAIN, A MISTAKE THAT I'D MADE.
AND, UH, YOU KNOW,
I JUST STARTED TO CRY.
AND, UH,
AND THEN, I GOT OVER THAT.
I MEAN, THERE'S A PERIOD OF THAT
THAT YOU JUST HAVE
TO GET THROUGH AND JUST SAY,
"OKAY, GO BACK AT IT."

The Narrator says KRUMMEL FINALLY MAKES
HIS CTLA-4 ANTIBODY.
AND LAUNCHES JIM'S EXPERIMENTS.
HE QUICKLY DEMONSTRATES
THAT LINSLEY'S IDEA
OF HOW CTLA-4 WORKS IS WRONG.
THE EXPERIMENT PROVES
THAT ENGAGING CTLA-4
DOESN'T ACTIVATE
THE IMMUNE RESPONSE,
IT STOPS IT.

An animation shows the process explained.

Lewis says JIM AND MAX KRUMMEL,
AS WELL AS JEFF BLUESTONE
AND HIS GRAD STUDENTS,
TURNED THE THING
COMPLETELY AROUND
AND SAID, "NOPE."
ALL THESE PRIOR PAPERS
ARE SAYING
THAT CTLA-4
IS ANOTHER GAS PEDAL,
THAT'S NOT CORRECT.
IT'S ACTUALLY A BRAKE.

The caption changes to "Jeffrey Bluestone. Former Professor, University of Chicago." Jeffrey is in his late fifties, with a short white beard and white hair. He wears a white shirt.

Jeffrey says LIKE JIM, I WAS ABLE
TO FIGURE OUT CTLA-4.
AND I, I WAS SHOCKED.
CTLA-4 WAS THE WACKIEST THING
IN THE WORLD, RIGHT?
NOBODY BELIEVED
THAT YOU WOULD ACTUALLY HAVE
A WHOLE SYSTEM IN PLACE
TO SHUT DOWN
THE MOST IMPORTANT THING
GOING ON IN YOUR BODY,
WHICH IS AN IMMUNE RESPONSE,
AND YOU'RE GONNA
SHUT THIS THING DOWN
AND MAKE SURE IT DOESN'T WORK?

Tyler says THE BODY DOES NOT WANT
AN OVER-EXUBERANT IMMUNE SYSTEM.
BECAUSE IF WE DID HAVE ONE,
WE WOULD ALL BE SUFFERING
FROM AUTOIMMUNE DISEASE.

A close-up shot shows a young woman using a wheelchair.

The Narrator says AUTOIMMUNE DISEASES,
LIKE MULTIPLE SCLEROSIS,
ARE CAUSED
WHEN THE IMMUNE SYSTEM
ATTACKS HEALTHY CELLS.
JIM'S DISCOVERY
PROMPTS MANY IMMUNOLOGISTS
TO THINK ABOUT
CURING THESE DISEASES.
THEY WILL ENGAGE CTLA-4
AND STOP T CELLS
FROM GOING ON THE ATTACK.
JIM HEADS
IN A DIFFERENT DIRECTION.

Matt says THERE'S THIS BIG PART
OF THE IMMUNE SYSTEM
THAT IS BUILT
ON STOPPING ITSELF.
NOW, WHAT THE HECK DOES THAT
HAVE TO DO WITH CANCER?

Michael says CANCERS,
WE KNOW THEY HAVE MUTATIONS,
WE KNOW THEY'RE DIFFERENT
FROM NORMAL.
THEY SHOULD BE VISIBLE
TO THE IMMUNE SYSTEM
AND FOR A LONG TIME,
WE STRUGGLED.
WHY CAN'T THE IMMUNE SYSTEM
SEE CANCER?
IT CAN SEE FLU.

The Narrator says JIM THEORIZES
THAT TUMORS HAVE EVOLVED
TO TRICK THE IMMUNE SYSTEM.
THEY ENGAGE CTLA-4,
TURNING ON THE T CELL'S BRAKE.
THIS STOPS T CELLS
FROM ATTACKING THE TUMORS.
IF YOU WERE A CANCER,
IT WOULD CERTAINLY BE
ADVANTAGEOUS
IF YOU CONTACTED THAT RECEPTOR
AND TURNED OFF ALL THOSE T CELLS
THAT MIGHT, OTHERWISE,
COME TO KILL YOU.
THIS WOULD MAKE SENSE.

Michael says AT THE TIME,
IT WAS A CRAZY IDEA.
NOBODY THOUGHT
TUMORS WERE TRYING
TO TURN OFF THE IMMUNE SYSTEM.
BUT, HE SAID,
"WELL, WHAT IF I BLOCK THIS?"
"WHY DON'T WE SEE
WHAT THAT DOES
TO CERTAIN CANCERS."

The Narrator says JIM HYPOTHESIZES
THAT IF HE INSERTS AN ANTIBODY
TO BLOCK THE CONNECTION BETWEEN
THE TUMOR AND CTLA-4,
THE T CELL WILL BE FREE
TO ATTACK THE TUMOR.

Max says JIM HAD ALL THESE TUMORS
IN THE FREEZER.
SO I WAS MAKING THE ANTIBODIES
AS FAST AS I COULD,
AND A GUY NAMED
DANIEL LEITCH CAME.
HE WAS A POST-DOC IN THE LAB.
A NEW POST-DOC.
AND JIM GAVE HIM
THE TUMOR MODELS,
AND YOU KNOW,
I GAVE HIM THE ANTIBODY.

Michael says THE STUDENT WHO WAS
DOING THE EXPERIMENT
HAD PUT THE TUMORS IN THE MICE
AND GONE AWAY FOR THE HOLIDAYS.
AND SO,
IT WAS ACTUALLY LEFT TO JIM
TO CHECK ON THESE MICE,
AND THEN YOU KNOW,
SHORTLY BEFORE CHRISTMAS,
I THINK,
HE SAW THE TUMORS ARE GROWING,
MAYBE NOTHING'S GOING ON.
KINDA SAD ABOUT THAT.
IT'S NOT A HAPPY THING TO SEE,
BUT YOU KNOW,
THAT'S WHAT THE DATA WAS.

Lewis says WE HAD THANKSGIVING
AND CHRISTMAS TOGETHER
FOR PROBABLY,
YOU KNOW, ALMOST 20 YEARS.
I REMEMBER THAT CHRISTMAS.
HE WAS MUMBLING ABOUT,
YOU KNOW, THE STUDENT
TAKING OFF AND GOING ON HOLIDAY.

Jim says I HAD FAMILY VISITING
AND EVERYTHING, AND...
SO I DID SOMETHING THAT WAS...
UNFORGIVABLE, REALLY.
IF HE HAD DONE IT,
I'D HAVE FIRED HIM PROBABLY BUT,
I SKIPPED A COUPLE OF READINGS.
[laughs]
FOR THE CHRISTMAS HOLIDAYS.

Michael says A FEW DAYS LATER, THOUGH.
JIM REMEMBERED,
"OH, YEAH, I'M SUPPOSED TO BE
CHECKING ON THIS GUY'S MICE.
'CAUSE HE'S STILL OFF
CELEBRATING CHRISTMAS
WITH HIS FAMILY,
AND CAME BACK TO FIND THAT,
YOU KNOW,
IN THE MICE THAT HAD RECEIVED
THE ANTIBODY,
THE TUMORS WERE GONE.

[uplifting music plays]

Jim says IT WAS ONE OF THESE,
YOU KNOW,
TRULY ONE OF THESE AHA-MOMENTS
WHEN I WAS GOING,
"OH, JESUS, YOU KNOW,
THIS IS, THIS IS SOMETHING BIG."
'CAUSE I'VE BEEN DOING
TUMOR IMMUNOLOGY ENOUGH,
BUT I DIDN'T KNOW ALL OF IT.
THIS EXPERIMENT WAS SO COOL,
YOU DIDN'T NEED A STATISTICIAN.
THEY WERE ALL ALIVE,
OR ALL DEAD.
YOU KNOW?

Matt says THESE TUMORS HAVE DISAPPEARED.
I MEAN, THIS IS IMPOSSIBLE.
THIS IS NOT POSSIBLE.
THAT, THAT'S HOW MIND-BOGGLING
YOU HAVE TO THINK OF THIS AS.
BECAUSE THE HUMAN BODY,
WITH 480 MILLION YEARS
OF EVOLUTION BEHIND IT
CAN'T GET RID OF THIS STUFF.
AND NOW THE TUMORS
HAVE DISAPPEARED.

Lewis says FROM THEN ON,
FOR THE NEXT DECADE,
ESSENTIALLY, HE HAD ONE GOAL.
TO GET THAT MADE INTO A DRUG
FOR CANCER PATIENTS.

Jim says I DIDN'T COME OUT OF CANCER,
BUT ONCE IT WAS THERE,
IT WAS THERE.
AND I'LL BE DAMNED IF I'M GONNA
LET THAT JUST LAY AROUND.
THIS IS A WAY TO CURE CANCER,
I KNEW THAT THAT WAS THE WAY.

Sharon cycles down a road.

A song plays WELL, I'M A KING BEE
BUZZIN' AROUND YO' HIVE
WELL, I'M A KING BEE

Sharon says IN MY TEEN YEARS
AND IN MY COLLEGE DAYS,
I WAS THE DORK.
THE ONE THAT
STUDIED REALLY HARD,
GOT GOOD GRADES.
BECAUSE I WAS THE FIRST
IN MY FAMILY TO GO TO COLLEGE.
I HAD A LOT TO LIVE UP TO
WITH THAT.
SO I HAD TO MAKE SURE
THAT WHILE FRIENDS
WERE OUT PARTYING,
AND THEIR GRADES WERE C'S,
I NEEDED TO GET A'S.
AND I KNEW IT.
KNOWING WHAT I KNOW NOW, HOW...
WHAT LIFE HAD IN STORE FOR ME,
MAYBE I WOULDA HAD
A LITTLE BIT MORE FUN.
I PROBABLY WOULD HAVE.

Jedd says WE STARTED HER
ON CHEMOTHERAPY.
AND THAT CHEMOTHERAPY
REALLY DIDN'T WORK FOR HER.
SO WE TRIED ANOTHER KIND
OF CHEMOTHERAPY.

Sharon says I KNOW
THAT CHEMOTHERAPY
IS SUPPOSED TO KILL CANCER,
IT CAN GIVE YOU BACK YOUR LIFE.
CHEMOTHERAPY MADE ME FEEL
LIKE I HAD CANCER.
I FELT LIKE DEATH WARMED OVER.
I GOT SEVERE
PERIPHERAL NEUROPATHY
FROM THE CHEMOTHERAPY.
UM, THAT'S NUMBNESS AND TINGLING
IN YOUR HANDS AND FEET.
IT WASN'T JUST HANDS
AND FEET THOUGH,
IT WENT UP MY LEG,
AND I COULDN'T HOLD
A PENCIL TO WRITE.
YOUR SKIN PEELS OFF. ALL OF IT.
PEELS OFF.
SO IT LOOKS LIKE YOU HAVE
A MASSIVE SUNBURN EVERYWHERE.
I WAS ITCHY EVERYWHERE.
IT WAS LIKE AN ITCH
THAT YOU COULD NEVER STOP.

[machine beeping]

Jedd says AND THAT CHEMOTHERAPY
DIDN'T WORK FOR HER.
AND THEN I SENT HER TO GET
HIGH-DOSE INTERLEUKIN-2.

Sharon says MY CHEST
STARTED TO FILL UP WITH FLUID.
I REMEMBER SITTING ACROSS,
JUST LIKE THIS, FROM MY MOM
IN THE FAMILY ROOM OF HER HOUSE,
AND I WOULD HAVE TO GO, "MOM...
[breathes deeply]
WHAT ARE WE GOING TO..."
[breathes deeply]
THAT WAS MY BREATHING.

Jedd says AND THE HIGH-DOSE INTERLEUKIN-2
DIDN'T WORK.

Sharon says SAME TIME, THOUGH,
I HAD AN MRI DONE, WHICH I HAD
NOT HAD DONE PREVIOUSLY.
AND THEY FOUND A BRAIN TUMOR.

Jedd says SO SHE NEEDED RADIATION
TO HER BRAIN.

Sharon says YOU KNOW
WHEN YOU BREAK YOUR NECK,
AND THAT THING SITS
ON YOUR SHOULDERS
AND THEY SCREW IT
INTO YOUR HEAD.
UM, THAT'S WHAT THEY PUT ON YOU
WHEN YOU HAVE TO BE
BOLTED TO A TABLE.
WHEN THEY GIVE YOU
BRAIN RADIATION.
SO I HAD SOMEBODY COME AT ME
WITH A DRILL,
AND SCREW THINGS INTO MY HEAD
WHILE FULLY AWAKE AND CONSCIOUS.

Jedd says THE LIFE EXPECTANCY OF SOMEONE
WITH METASTATIC MELANOMA
AT THE TIME,
WAS ABOUT SEVEN MONTHS.
SO WE ARE WAY INTO THAT
AT THIS POINT.

A picture shows a smiling Sharon wearing a metallic structure attached to her head.

Jim says WE PUBLISHED THE PAPER
IN 1996.
EVERYBODY KINDA WENT, "WOW."
AND, UM...
THAT WAS KINDA IT.
[chuckles]

[suspenseful music plays]

Dan says WE WERE ALL VERY SKEPTICAL
OF THE SCIENCE
OF CANCER IMMUNOLOGY.

Tyler says I WASN'T SURE
THAT WHAT HE HAD DONE
SUCCESSFULLY IN A MOUSE,
IN A VERY CONTROLLED SETTING,
WOULD ULTIMATELY TRANSLATE
TO A METHOD THAT WOULD WORK
IN A HUMAN BEING.

In a clip, a Male TV Host says YOU'RE GONNA BE HEARING
A GOOD DEAL MORE
ABOUT SOMETHING CALLED
INTERFERON THESE DAYS.

The Narrator says SKEPTICISM ABOUT
STEMS FROM THE 1980S...

Male Host 1 says RESEARCHERS ARE NOW CALLING
A NEW CANCER TREATMENT
THE MOST PROMISING IN 30 YEARS.

The Narrator says WHEN ATTEMPTS
AT USING THE IMMUNE SYSTEM
TO FIGHT CANCER
OFFERED ENORMOUS PROMISE.

In off, Reporter 1 says A DRUG
CALLED INTERLEUKIN-2...

The Narrator says AND THEN,
DEVASTATING DISAPPOINTMENT.

In off, Reporter 2 says AS
FEWER PATIENTS THAN EXPECTED
SEEM TO BENEFIT.

Michael says FOR YEARS,
THERE WERE CLINICAL TRIALS,
AND NONE OF THESE WORKED.

In off, Reporter 1 says AS WE STARTED
TO SEE SOME BAD SIDE EFFECTS.

Michael says AND I CAN TELL YOU
THESE WERE NOT HAPPY MEETINGS
TO ATTEND.
THEY ALL STARTED WITH,
"WE DID THIS EXPERIMENT
IN ANIMALS, IN OUR LAB,
AND IT LOOKED GREAT.
AND THEN WE DID A CLINIC TRIAL,
AND NOBODY GOT BETTER.
YEARS OF THAT
HAD LED TO A VIEW
THAT IMMUNOTHERAPY
WOULD JUST NEVER WORK.

The caption changes to "Andrew Pollack. Reporter, The New York Times." Andrew is in his early fifties, with a graying beard and receding brown hair. He wears a black polo-shirt.

Andrew says TWENTY OR THIRTY YEARS AGO,
CANCER WAS NOT A VERY BIG THING
FOR DRUG COMPANIES.
THE DRUGS
DIDN'T WORK THAT WELL,
THE PATIENTS DIDN'T
LIVE THAT LONG.
THE MUCH MORE LUCRATIVE DRUGS
WERE FOR HEART DISEASE,
OR DIABETES.
CHRONIC DISEASES THAT PEOPLE
WOULD TAKE DRUGS FOR,
FOR THE REST OF THEIR LIVES.

Lewis says JIM FIRST GOES TO BMS,
WHO HAD HELD THE PATENTS,
AND PETER LINSLEY
WORKED FOR THEM AT THE TIME.
THE GUYS AT BMS
HAD TOLD HIM, "WE LIKE CTLA-4,
BUT WE THINK
IT HAS OTHER APPLICATIONS.
BUT IN FACT, THEY WEREN'T DOING
ANYTHING CLINICALLY
WITH IT AT ALL.

Pictures of different pharmaceutical companies appear.

Jim says I WAS VERY DISAPPOINTED
IN THE INITIAL RESPONSE,
BUT IT GOT MORE
AND MORE FRUSTRATING WITH TIME.
IT WAS JUST, "NO."
PLACE AFTER PLACE AFTER PLACE.
THE SCIENTISTS WOULD GET HAPPY,
YOU KNOW, AND EXCITED,
AND ATTORNEYS WOULD SAY,
"NO, NO, NO. YOU CAN'T DO THIS,
BECAUSE
BRISTOL-MYER SQUIBB PARTIES
FILED FOR PATENT
ON THEIR ANTIBODY."
THEN I SAID,
"HAVE YOU READ THEIR PATENT?
THEIR PATENT IS BACKWARDS."
BUT STILL, YOU KNOW,
THEY COME HERE AND SAY,
"WELL BMS
HAS GOT MORE LAWYERS TO...
[sighs deeply]
WE'D HAD A BIG COMPANY,
AND SO...
TOO BAD."

Max says SO THERE WERE ALL KINDS
OF THINGS THAT, LIKE,
STOOD IN THE WAY
OF THIS HAPPENING.
AND I WOULD SAY, YOU KNOW,
HIS EXPERIMENT IN THIS
WAS TO JUST KEEP FIGHTING
TO SAY,
"THERE'S SOMETHING HERE,
THERE'S SOMETHING HERE,
THERE'S SOMETHING HERE."

Lewis says AND THAT'S WHERE
I REALLY GIVE HIM CREDIT.
HE'S LIKE A BLOODHOUND
ON THE SCENT.
HE'S NOT GONNA
GET TAKEN OFF THE SCENT
UNTIL HE'S FOUND THE...
FOUND THE FOX.

Jim and his team have a meeting.

A young man says BUT I SAY THIS MODEL
IS OUT OF OUR CONTROL
BECAUSE I'M JUDGING
MYSELF INITIALLY,
IT COMES FROM...

Malinda says I WOULD ALWAYS
PLAN VACATIONS,
PLACES WHERE HE COULD NOT
GET A PHONE CALL.
AND HE COULD NOT BE CONNECTED
TO THE INTERNET.

A clip plays. Jim cuts wood in the forest.

Robert says DAD IS DOING A GREAT JOB
OF CHOPPING WOOD!

Malinda says ROBERT, GO OVER THERE
AND STAND BY DAD.

Robert says OKAY.

[indistinct dialogue]

The clip ends.

Jim says THERE WAS ABOUT TWO YEARS
THAT NOBODY WOULD LISTEN,
AND, AND, UH,
SO IT WAS GETTING DEPRESSING.
MY BROTHER MIKE
HAD METASTATIC PROSTATE CANCER.
HE PRESENTED
WITH A LOT OF JOINT PAIN
WHICH IS HOW THEY FOUND IT.

Lewis says WE OFTEN HAD
THANKSGIVING WITH MIKE.
FOR MANY YEARS IN BERKELEY,
HE'D COME OUT,
AND SO I GOT TO L KNOW HIM
QUITE WELL.
MIKE GOT DIAGNOSED IN HIS 50S,
WITH METASTATIC PROSTATE CANCER
TO THE BONE.
THAT'S HOW
HE WAS FIRST DIAGNOSED.
AND THAT PRETTY MUCH
IS A DEATH SENTENCE.
AND THAT ALSO, DURING THIS TIME,
WHILE JIM WAS TRYING TO
MARCH FORWARD THIS NEW THERAPY.
HE REALLY WANTED TO BE ABLE
TO GIVE THIS TO HIS BROTHER.

Jim says I NEED TO GET IT INTO PEOPLE.
I NEED TO GET IT INTO PATIENTS.

The Narrator says JIM TURNS HIS SEARCH TOWARDS
SMALLER AND SMALLER
BIOTECH COMPANIES.
LOOKING FOR ANYONE WILLING
TO TAKE A GAMBLE ON HIS IDEA.
IN BOULDER, COLORADO,
HE FINDS ALAN KORMAN,
WHO WAS CREATING DRUGS
FOR AUTOIMMUNE DISEASE.

The caption changes to "Alan Korman. Former Director of Immunology NeXstar." Alan is in his late fifties, clean-shaven with white hair. He wears a black sweater.

Alan says MY INTEREST WAS
IN IMMUNOLOGY.
I DIDN'T REALLY KNOW MUCH
ABOUT CANCER BIOLOGY
OR CANCER THERAPY.
I THINK IT WAS USEFUL
NOT TO BE BIASED
BY THE CURRENT THINKING
OF HOW TO GO AFTER CANCER.

A goat climbs a mountain.

Max says THE CONCEPT
OF JUMPING INTO A PROBLEM
AND BEING THE NAIVE ONE,
IS REALLY USEFUL.
THE PEOPLE THAT HAVE BEEN
IN THAT FIELD VERY LONG,
THEY JUST KEEP DOING
THE EXACT SAME THING,
I THINK YOU GET TUNNEL VISION.

The Narrator says KORMAN'S JOB WILL BE
TO TAKE THE CTLA-4 ANTIBODY
THAT JIM AND MAX
DEVELOPED FOR MICE,
AND MAKE IT INTO A DRUG
THAT CAN WORK SAFELY IN HUMANS.
THE DRUG
WILL BE CALLED IPILIMUMAB.

Alan says I ENDED UP COLLABORATING
WITH SOMEONE THAT I KNEW
FROM GRADUATE SCHOOL,
A GUY NAMED NILS LONBERG.

The Narrator says NILS LONBERG
WORKS FOR MEDAREX.
A SMALL BIOTECH COMPANY
BASED IN SAN FRANCISCO.

The caption changes to "Nils Lonberg. Former Scientific Director, Medarex." Nils is in his late fifties, clean-shaven with receding short hair. He wears a blue shirt.

Nils says I GOT A CALL FROM ALAN.
WE STARTED TALKING ABOUT
THE IDEA OF IPILIMUMAB.
IPILIMUMAB HADN'T BEEN
CREATED YET.
AND I CONVINCED HIM
TO LET ME IN ON THIS.
UM, I WAS FASCINATED.

Eric says JIM AND ALAN KORMAN,
AND NILS LONBERG,
ALL GET TOGETHER AT THE BAR
IN THE BASEMENT
OF THE HOTEL BOULDERADO
RIGHT IN DOWNTOWN BOULDER.

Nils says JIM'S PRIMARY CONCERN
WAS THAT WE MOVE QUICKLY.
I THINK HE WAS VERY SKEPTICAL
OF THE WHOLE
BIOTECH PHARMACEUTICAL INDUSTRY.
HE DIDN'T THINK
WE HAD THE URGENCY.
I ENDED UP SITTING UP
WITH HIM MOST OF THE NIGHT,
WITH A BOTTLE OF WHISKEY.
OUT OF THAT CONVERSATION,
WE HAD A HANDSHAKE AGREEMENT.
AND WITH THAT HANDSHAKE,
WE STARTED WORK
BACK IN CALIFORNIA,
BACK IN THE LAB.
FOUR HUNDRED
SIXTY-SIX DAYS LATER,
WE HAD IPILIMUMAB IN A PATIENT.
AND I THINK
THAT'S THE WORLD'S RECORD.

Andrew says PHASE ONE
TESTS RELATIVELY SMALL NUMBER
OF PEOPLE, GENERALLY,
FOR SAFETY.
SOMETIMES THEY GET A LITTLE HINT
OF WHETHER THE DRUG'S WORKING,
BUT GENERALLY,
IT'S JUST TO MAKE SURE
THAT THE DRUG
IS NOT GONNA HARM SOMEBODY.

Alan says WE PICKED A DOSE
THAT WAS...
YOU KNOW, A COIN TOSS,
THAT WAS BASED, YOU KNOW,
SOMEWHAT LOOSELY
ON WHAT WE HAD DONE
IN THE MOUSE.
BUT CLEARLY, YOU KNOW,
WE DIDN'T KNOW ENOUGH OF THAT,
HOW TO FIGURE OUT ITS POTENCY.

The caption changes to "Doctor Padmanee Sharma. Former Clinical Fellow Memorial Sloan-Kettering Cancer Center." Padmanee is in her early forties, with shoulder-length black hair. She wears a white doctor apron and long earrings.

In a lab, Padmanee says WHEN WE WERE DEVELOPING
THE PHASE ONE CLINICAL TRIALS,
THERE WERE MANY STOPS
AND STARTS.
THERE WERE MANY TIMES
WHEN IT WAS WONDERED
WHETHER OR NOT
THE CLINICAL TRIAL
COULD EVEN START.
"WHICH TUMOR TYPE
SHOULD WE DO IT IN?"
"SHOULD IT BE ALL COMERS?"
"SHOULD WE FOCUS
ON MELANOMA PATIENTS?"
"HOW MANY PATIENTS
SHOULD WE ENROLL
IN THE PHASE ONE
CLINICAL TRIAL?"
"HOW MUCH OF A BUDGET
DID WE HAVE
TO ENROLL THESE PATIENTS?"
UH, "WHAT WAS THE STARTING DOSE
OF THE DRUG
THAT WE WERE GOING TO GIVE?
WERE WE TAKING THE STARTING DOSE
JUST BASED ON MOUSE DATA?"
WHICH, BY THE WAY,
IS WHAT WE DID.

[car whooshes]

Lewis says WHEN DRUGS GO INTO
PHASE ONE TRIALS,
THEIR FIRST TRIALS IN PEOPLE,
NINE OUT OF TEN OR MORE, FAIL.
AND THAT'S IT, YOU PULL THE PLUG
AT THAT FIRST STAGE.

[patient groans]

Padmanee says I'D RAN
THAT CLINIC TRIAL AT THAT TIME.
IT WAS AMAZING, BECAUSE
THREE OUT OF THE 12 PATIENTS,
THIS WAS
A VERY SMALL CLINICAL TRIAL,
THREE OUT OF THE 12 PATIENTS
SHOWED THAT ALL OF THE TUMOR
WENT AWAY.
WE NEVER SEE THIS
IN A PHASE ONE TRIAL,
IT'S SO RARE THAT
IT'S SORT OF LIKE, YOU KNOW,
UM, FINDING THE POT AT THE END
OF THE RAINBOW, YOU KNOW?
YOU, YOU FEEL LIKE,
"AM I REALLY SEEING THIS
OR AM I IMAGINING IT?" RIGHT?
IT'S JUST UNBELIEVABLE.

Jedd says I BECAME AWARE
THAT CTLA-4
WAS THE FOCUS OF AN EARLY SET
OF CLINICAL TRIALS
THAT WAS...
THROUGH
THE CLINICAL TRIAL GRAPEVINE,
PRODUCING
A LITTLE BIT OF ACTIVITY
IN PATIENTS
WITH ADVANCED MELANOMA.
AND OBVIOUSLY, I WANTED
TO BE PART OF THAT.

[festive music playing]
[bells clinking]
People walk in a shopping mall during the Christmas season.

Sharon says I REMEMBER GOING
CHRISTMAS SHOPPING
IN A WHEELCHAIR,
IN A MALL WHERE WE GREW UP.
THAT WAS PROBABLY
THE WORST CHRISTMAS EVER.
I REMEMBER SITTING UNDERNEATH
THE CHRISTMAS TREE WITH ROB,
AND I WAS A HUDDLING MESS
ON THE FLOOR.
AND HE JUST HELD ME
AND TOLD ME "WE'LL WORK IT OUT."
With tears in her eyes, she continues THAT CHRISTMAS WAS HARD,
'CAUSE I DIDN'T THINK
I WAS GONNA SEE THE NEXT ONE.
[sighs deeply]

Jedd says SHE COMES TO CLINIC
AND, UH, I SAID,
"I THINK THAT
WE'RE REALLY AT THE POINT
WHERE THE READILY AVAILABLE
STANDARD OPTIONS
ARE NOT WORKING FOR YOU.
THERE IS A CLINICAL TRIAL
THAT YOU COULD CONSIDER
PARTICIPATING IN."

Sharon says I REMEMBER DR. WOLCHOK
EXPLAINING IT TO ME.
UM, IN VERY, VERY SIMPLE TERMS,
THAT INSTEAD OF AN OUTSIDE AGENT
LIKE CHEMOTHERAPY,
YOUR BODY THEN USES
ITS OWN IMMUNE SYSTEM
TO FIGHT OFF CANCER.
IT ALLOWS IT TO TURN ON
THE IMMUNE SYSTEM
AND RECOGNIZE CANCER IN A WAY
THAT IT PREVIOUSLY COULDN'T.

Jedd says SHARON GOT FOUR DOSES
OF IPILIMUMAB.

Sharon says THE TREATMENTS
WERE NOT LIKE CHEMOTHERAPY.
CHEMOTHERAPY, YOU'D GO BACK,
THREE OR FOUR DAYS IN THAT WEEK,
YOU BAS...
YOU LIVE AT
AN ONCOLOGIST'S OFFICE.
IT'S YOUR HOME.
THIS WAS DIFFERENT.
I HAD A SHOT IN MY LEG.
AND THEN I HAD
A 90-MINUTE IV INFUSION.
THAT WAS IT.
BECAUSE I WASN'T
IN CHEMOTHERAPY EITHER,
I DIDN'T FEEL NAUSEOUS.
I DIDN'T FEEL
THE INCREDIBLE FATIGUE
THAT CAME ALONG WITH IT.
I NOTICED A DIFFERENCE
IN MYSELF,
JUST FROM CHANGING TREATMENTS.

The Narrator says ONCE A DRUG IS PROVEN SAFE
IN PHASE ONE TRIALS,
IT MOVES INTO PHASE TWO
AND PHASE THREE.
THESE TRIALS INCLUDE
FAR MORE PATIENTS
STUDIED OVER
MUCH LONGER TIME PERIODS.
THEY CAN COST HUNDREDS
OF MILLIONS OF DOLLARS.

Nils says WE NEVER
COULD HAVE DEVELOPED IPILIMUMAB
AS A SMALL COMPANY.
EVEN A PUBLICLY TRADED COMPANY,
WE NEVER COULD HAVE RAISED
THAT MUCH MONEY.

The Narrator says MEDAREX HAS TO FIND
A PARTNER WITH DEEP POCKETS.
BUT THE BIG PHARMA COMPANIES
ARE WEARY OF THE RISK.
FOR ANY HOPE OF SUCCESS,
IPILIMUMAB NEEDS A CHAMPION
INSIDE
THE PHARMACEUTICAL INDUSTRY.

The caption changes to "Doctor Rachel Humphrey. Former VP, Head of Ipilimunab Program, Bristol-Myres Squibb." Rachel is in her late fifties, with short wavy light brown hair. She wears black frame glasses and a dark blue blazer.

In an office, Rachel says WHEN I LEFT THE NIH
TO GO TO INDUSTRY,
I WENT TO BEAR THAT WAS BUILDING
A ONCOLOGY PROGRAM.
I REALLY WANTED TO SUPERVISE
THE DEVELOPMENT OF IPI.
WHEN BEAR DECLINED,
I LEFT BEAR AFTER SEVEN YEARS.
SPECIFICALLY TO BRING
IPILIMUMAB FORWARD.
BMS WAS NOT SURE
THEY WERE GONNA TAKE IT AT ALL.
SO I CAME
AT JUST THE RIGHT TIME.
AND I WAS READY
TO ADVOCATE FOR IT.
I WENT TO BMS,
I SAID "LET ME WALK YOU THROUGH
WHY THIS IS IMPORTANT."

Jim says I MUST ADMIT
I WAS APPREHENSIVE.
AND IN FACT,
IF BMS HAD ANOTHER ANTIBODY
IT WOULD'VE BEEN ONE
OF THE REASONS THAT
A LOT OF COMPANIES
WOULD'VE GIVEN
FOR NOT WORKING WITH US.
YOU KNOW, BMS CAN KILL YOU.

In a clip, a female news anchor says STOCKS TO WATCH TODAY?

A middle-aged man in a suit says A BIG ONE WILL BE
BRISTOL-MYERS SQUIBB.

The clip ends.

The Narrator says THERE WERE OTHER REASONS
TO BE APPREHENSIVE
OF BRISTOL-MYERS SQUIBB.

Andrew says BRISTOL-MYERS HAD
A PRETTY GOOD REPUTATION.
THEN THAT STARTED TO FADE.

[bottles clinking]

Reporter 3 says ERBITUX...

Andrew says THEY DID A DEAL
FOR A DRUG
FROM A SMALL COMPANY
CALLED IMCLONE.

Reporter 3 says THE DRUGS SPARKED
AN INSIDER TRADING SCANDAL
THAT LED TO A SEVEN-YEAR
PRISON SENTENCE.

Reporter 4 says PESSIMISM PROPELLED
BY NEWS
MAY HAVE ACCOUNTING PROBLEMS.
TODAY IT'S BRISTOL-MYERS SQUIBB
IN THE GOVERNMENT'S CROSSHAIRS.

Andrew says SO THEY WENT THROUGH
IN THE EARLY TO MID-2000S.
A VERY HARD PERIOD.

The caption changes to "Hillary Johnson. CNBC."

In a TV news clip, Hillary says BRISTOL-MYERS SQUIBB,
ONE OF THE LEADERS
IN THE INDUSTRY
FORECAST DISAPPOINTING EARNING
SQUARES FOR ITS SECOND QUARTER.

Rachel says SO WHAT WE WERE
ASKING BMS TO DO
IS INVEST A HEALTHY AMOUNT
OF MONEY
INTO THE BELIEF
THAT THESE DRUGS
WERE GONNA WORK.

The caption changes to "Doctor Elliott Sigal. Former Chief Scientific Officer, Bristol-Myers Squibb." Elliott is in his fifties, clean-shaven with blond hair. He wears glasses, a dark blue jacket and an open-necked gray shirt.

Elliott says IT WAS AGAINST THE GRAIN.
A LOT OF OUR EXTERNALS
ADVISERS SAID
WE WERE PROBABLY INVESTING
TOO MUCH
IN IMMUNOTHERAPY.
'CAUSE NOTHING
HAD WORKED BEFORE.

Rachel says MY PRESENTATION FOCUSED
NOT ON THE RESPONSE RATE,
WHICH WAS VERY LOW AT THE TIME.
BUT ONE PATIENT
WHO HAD RECEIVED,
UM, I THINK IT WAS A SINGLE DOSE
AT THE TIME,
THAT NOW TWO
AND THREE YEARS OUT,
WAS STILL IN REMISSION.

Jim says THE VERY FIRST
PUBLIC MEETING,
RACHEL MADE IT A POINT FOR ME
TO COME AND SIT NEXT TO HER.
AND I COULDN'T FORGET,
BECAUSE I WAS SITTING THERE
AND THERE WERE SOME PEOPLE
WHO HAD VERY LITTLE
UNDERSTANDING IN IMMUNOLOGY,
THEY WERE MAKING COMMENTS.
AND YOU KNOW,
ABOUT WHAT THEY THOUGHT
THIS MEANT AND EVERYTHING.
AND I WAS JUST GOING,
"OH, BULLSHIT."
YOU KNOW, JUST SORT OF
UNDER MY BREATH, YOU KNOW.
GOING, "OH, MY GOSH."
AND OBVIOUSLY GETTING AGITATED.
AND RACHEL, YOU KNOW,
KEPT LOOKING AT ME, AND SHE...
AND AFTERWARDS,
SHE SAYS,
"OKAY, WELL, I WROTE DOWN
EVERY TIME YOU STARTED
SNORTING AND STUFF.
AND SO WHAT ABOUT THIS,
WHAT'S WRONG WITH THAT?
WHAT'S WRONG WITH THIS?"
FROM HER NOTES.
AND SO WE WENT OVER THE NOTES
FOR HOURS.
IT WASN'T A LOT OF FUN.
[chuckles]

Tyler says I WAS PART
OF THE GROUP OF PEOPLE
WHO WAS FOLLOWING, LET'S CALL IT
THE CONVENTIONAL PATH
OF CANCER RESEARCH.
JIM ALLISON
AND THE IMMUNOLOGY CROWD
WAS THINKING
ABOUT IT DIFFERENTLY.
AND THE MAINSTREAM
WAS MORE OR LESS IGNORING THAT.

Rachel says INNOVATION
IS EXTREMELY DIFFICULT.
THERE WAS SOMEBODY,
A REGULATORY PERSON ON MY TEAM
WHO YELLED AT ME,
SCREAMED AT ME.
"WE DON'T GET IT.
WE'RE WASTING OUR TIME."
AND IT WAS NOT JUST
THE MEMBERS OF THE TEAM.
BECAUSE BACK IN THE DAY,
MOST OF THE DOCTORS WERE NOT
IMMUNO-ONCOLOGY BELIEVERS.
THAT'S WHY IT WAS HARD TO GET
PATIENTS ON THE STUDY INITIALLY.
THAT'S WHY IT TOOK SO LONG.
THERE WAS LIKE A YEAR
WHERE THAT CLINICAL STUDY
COULD NOT BE ENROLLED.
IT WAS VERY, VERY SLOW.
NO ONE WANTED TO HEAR ABOUT
ANOTHER CANCER
IMMUNOTHERAPY AGENT.
IT WAS, YOU KNOW, "FORGET IT.
WE DON'T WANNA TALK TO YOU."

Padmanee says AND YOU CAN IMAGINE
A LOT OF DOORS
SLAMMED IN HIS FACE.
YOU MIGHT ARGUE
THAT THERE IS
A DEFENSE MECHANISM
AGAINST NEW IDEAS.
THEY ARE SEEN AS MUTATIONS,
AS CANCEROUS
TO A BODY OF THOUGHT.

Matt says YOU DON'T KNOW
WHETHER THE NEW IDEA
IS SOMETHING POTENT OR DEADLY.
AND THAT'S WHY THEY'RE OFTEN
VIEWED WITH SKEPTICISM.
AND THAT'S WHY IT TAKES
A REALLY POWERFUL IDEA
COMBINED WITH SOMEONE
WILLING TO PUSH IT FORWARD
TO MAKE IT HAPPEN.

Rachel says I INHERITED PREDISPOSITION
FOR CANCER.
UH, MY MOTHER HAD MELANOMA.
MY GRANDFATHER
HAD PANCREATIC CANCER.
AND MY BELOVED UNCLE GOT GLIOMA
WHEN HE WAS 58.
SO, I KNOW THAT CANCER
IS COMING FOR ME.
I KNOW IT'S COMING
FOR MY FAMILY.
UM, I'M JUST
ABOUT THE AGE MY UNCLE WAS
WHEN HE GOT HIS BRAIN TUMOR.
THE STAKES ARE SO HIGH.
THE OPPORTUNITIES SO GREAT,
THAT...
She gets emotional and continues SOMEHOW, IT JUST DIDN'T MATTER,
WHEN PEOPLE YELLED AT ME
OR CREATED BARRIERS.
[whimpering]
'CAUSE WE'RE GONNA MAKE IT WORK.
WE'RE GONNA MAKE IT HAPPEN.

Jim says I'M STILL AT BERKELEY.
BUT THE ACTION HAD MOVED
TO NEW YORK,
WHERE THE COMPANIES ARE,
AND A LOT OF THE STUDIES WERE
GOING ON AT SLOAN KETTERING.
I THOUGHT, "WELL...
THERE'S SOME NOT-SO-GOOD STUFF
HAPPENING TO MY BABY OVER THERE.
I BETTER MOVE AGAIN," YOU KNOW.

The caption changes to "New York City, 2004."

Eric says JIM DECIDES HE NEEDS
TO BE IN NEW YORK
WHERE THE MAJOR TRIALS
ARE GOING ON.
WHEN I ASKED JIM
WHY HE NEEDED TO BE THERE,
HE SAID, "I WENT THERE
TO BE A NUISANCE."
HE WANTED TO STAY
ON THE SCIENTIST.
HE WANTED TO STAY ON THE FDA.
HE WANTED TO STAY
ON BRISTOL-MYERS SQUIBB.

Michael says ANY TIME
THE LAB MOVES,
IT'S ALWAYS A TOUGH DECISION.
ESPECIALLY IF YOU'RE MOVING,
YOU KNOW, ACROSS THE COUNTRY.
PEOPLE HAVE ROOTS
IN A GIVEN AREA.
I HAD BEEN IN THE BAY AREA FOR,
YOU KNOW, ALMOST A DOZEN YEARS
AT THAT POINT.
SO, WHEN JIM DECIDED TO MOVE
FROM BERKELEY
TO SLOAN KETTERING,
I THINK IT'S A TESTAMENT
TO HOW DEDICATED ALL OF US WERE
TO THIS WORK
AND THE PROMISE
WE SAW IN IT, THAT...
I WOULD SAY AT LEAST 90 PERCENT
OF THE PEOPLE AT JIM'S LAB
PICKED UP
AND MOVED CROSS COUNTRY.
IT WAS A TOUGH MOVE
IN THAT,
YOU KNOW, YOU'RE MOVING ALL
YOUR STUFF, YOU'RE MOVING A LAB.
THINGS IN LABS ARE DELICATE.
WE ACTUALLY LOST
AN ENTIRE FREEZER
FULL OF, OF SORT OF CRITICAL,
UN-REPLACEABLE REGIONS.
SOMEWHERE IN THE DESERT,
HALFWAY ACROSS,
THE REFRIGERATED TRUCK
THAT IT WAS PLUGGED INTO
BLEW A FUSE.
SO, THERE WAS SOME PAIN
TO GO WITH THAT MOVE.

[siren blaring]
Jim stands on a corner looking at the traffic.

Dan says JIM BEING IN NEW YORK,
WAS TRULY A FISH OUT OF WATER.
I'M NOT SURE JIM WALKED MORE
THAN THREE BLOCKS
FROM HIS APARTMENT
ON THE UPPER EAST SIDE.
BUT, YOU KNOW,
HE DIDN'T MOVE TO NEW YORK
TO TAKE ADVANTAGE
OF WHAT NEW YORK HAS TO OFFER.
HE MOVED, TO TAKE ADVANTAGE
OF WHAT SLOAN KETTERING
HAD TO OFFER.

The Narrator says PUTTING PRESSURE
ON JIM IS PFIZER,
THE WORLD'S LARGEST
DRUG COMPANY.
SEEING THE PROGRESS OF IPI,
PFIZER HAS LAUNCHED
A COMPETITIVE CANCER DRUG.
DRAWING FROM
JEFFREY BLUESTONE'S WORK.

Jeffrey says I WENT TO PFIZER,
AND THEY GOT EXCITED ABOUT IT.
WE WERE ON TRACK.
I WAS WORKING ON THEN
TO MAKE THE DRUG.
AND THINGS LOOKED REALLY GOOD.

Jedd says TREMELIMUMAB WAS BEING
DEVELOPED BY PFIZER.
AND THE EARLY SIGNALS
FOR BOTH OF THE MEDICINES
WERE REMARKABLY SIMILAR.

Rachel says PFIZER CAME IN LATE
WHEN THEY SAW REASONS
TO BELIEVE.
VERY CLASSIC.
"WE THINK MAYBE
YOU HAVE SOMETHING HERE.
WE HAVE ONE JUST LIKE IT.
WE'RE GOING TO BEAT YOU."

The Narrator says THE RACE IS ON.
AND WATCHING IT CLOSELY
IS THE FDA,
THE US GOVERNMENT AGENCY
THAT DETERMINES
WHETHER A DRUG IS SAFE AND
EFFECTIVE ENOUGH FOR PATIENTS.
THE FDA IS JUDGING
THE CLINICAL TRIALS
BY STANDARDS DEVELOPED
FOR EVALUATING CHEMOTHERAPY.

Michael says THE RULES SAID IF A PATIENT
HADN'T HAD THEIR TUMORS SHRINK
BY 30 PERCENT WITHIN 12 WEEKS,
THEY FAILED.

The Narrator says IN PFIZER'S TRIAL,
THE TUMORS DON'T SHRINK
AFTER 12 WEEKS.
THEY GROW.
FAILING TO MEET FDA STANDARDS,
PFIZER DECIDES
TO CUT ITS LOSSES.

An article reads "Pfizer announcer discontinuation of phase III clinical trial for patients with advanced melanoma."

Jim says PFIZER DID THIS
GIANT TRIAL.
AND JUST,
EVERYBODY WAS WATCHING.
IT FAILED.
YOU KNOW, BIG BLOW.
YOU KNOW, THE BIGGEST
DRUG COMPANY IN THE WORLD
JUST ABANDONS THE WHOLE FIELD.
I MEAN EVERYBODY,
WHEN WE STARTED OUT,
ONE OF THE MAIN CRITICISMS
WE HAD WAS,
"IMMUNOTHERAPIES NEVER WORK,
IT'LL NEVER WORK.
IT'S A BUNCH OF VOODOO.
AND, UH,
YOU SHOULDN'T EVEN TRY IT."
NOW HERE'S
THIS BIG FAILURE.

Rachel says BMS THOUGHT,
THERE'S ONLY ONE OTHER
IN THE CLASS, IT JUST FAILED.
WE DON'T WANNA PUT
MORE MONEY IN.
IN FACT, SURELY WE'LL BE CLOSING
THE STUDIES YOU'RE DOING NOW.

Tyler says MANY OF MY COLLEAGUES SAID,
THIS WILL NEVER WORK.
THIS IS A DRY WELL.

The Narrator says JIM STRUGGLES
TO MAKE IT CLEAR
THAT IPILIMUMAB
IS NOT A CHEMOTHERAPY DRUG
AND DOESN'T BEHAVE LIKE ONE...

Jim says PEOPLE GO BACK
TO THEIR COMMUNITY.
AS SOON AS THEY GOT BACK,
THEY PUT THEM ON
SOME CHEMOTHERAPY DRUGS
THAT HAD BEEN SHOWN
NEVER TO WORK.
BUT NOW THEY'RE RESPONDING
TO SUCH, SUCH...
I SAID "YEAH, RIGHT."
YOU KNOW, THERE'S ANOTHER
GOOD EXPLANATION.
THAT STAGE WAS RESPONDING LATE,
WHICH IS WHY, THAT SHOWED YOU
IN THE MICE.

Eric says YOU GO BACK TO JIM'S
EARLIER EXPERIMENTS IN MICE
WITH CTLA-4.
JIM OBSERVED
THAT THE T CELLS WERE ENTERING
INTO THE TUMORS
AND THEY WERE EXPANDING IN SIZE
BEFORE THE T CELLS THEN
WERE ABLE TO DESTROY THE TUMORS
AND THEN THEY WOULD SHRINK
IN SIZE.

Jim plays the harmonica in a bar.

Eric says SO JIM HAD TO CONVINCE
BRISTOL-MYERS SQUIBB
TO DO A MUCH MORE EXPENSIVE,
MUCH MORE LENGTHY TRIAL.

Jeffrey says UNLIKE JIM,
WHO, TO HIS CREDIT,
PERSEVERED
AND DID WHATEVER IT TOOK,
I FELT THAT I HAD DONE EXACTLY
WHAT I NORMALLY WOULD DO,
WHICH IS TO JUST LET
THE OTHER FOLKS MAKE THE DRUG.
LITTLE DID I KNOW, AT THAT TIME,
THAT THEY WOULD...
GIVE UP ON IT SO QUICKLY.

Lewis says JIM WAS VISIBLY ANGRY.
HE JUST GO INTO A TIRADE,
"I'VE GOTTA MAKE THIS HAPPEN."
BECAUSE THE EASIEST...
YOU'LL NEVER GET FIRED
FOR SAYING NO.
[chuckles]
IF YOU'RE RESPONSIBLE
FOR SPENDING A LOT OF MONEY.

Tyler says THE SKEPTICISM WAS WIDESPREAD.
AND FRANKLY, JIM EXPERIENCED IT
PROBABLY, EVERY DAY.

Lewis says EVERY TIME I SEE HIM,
YOU COULD SEE
HIS BLOOD PRESSURE GOING UP.
THAT WAS HARD ON HIM
DURING THOSE YEARS,
AND HARD ON PEOPLE AROUND HIM.

Malinda says THAT WAS A TRYING TIME.
JIM BECAME RATHER OBSESSED.
THE SCIENCE AND THE PROJECT
JUST CONSUMED HIM,
AND I REALLY COULDN'T BE
A PART OF THAT.
WITH NO SCIENCE
BACKGROUND OF MY OWN,
OUR SON OFF IN COLLEGE,
WE, WE HAD LESS
AND LESS IN COMMON.
THAT DIDN'T MEAN THAT
WE DIDN'T ADMIRE EACH OTHER
AND CARE GREATLY FOR EACH OTHER,
BUT WE JUST DECIDED
TO GO OUR SEPARATE WAYS.

(soft music plays)

Jim says I WAS AFRAID THAT
THIS DRUG WAS GONNA GO DOWN.
AND UH, I'VE INVESTED
NOT JUST...
MYSELF, BUT MY FAMILY, YOU KNOW.
AND IT WAS, IT WAS A TOUGH TIME.
I THINK ANY GREAT, BIG,
DISRUPTIVE CHANGE
THAT YOU'RE PUSHING FOR
IS GONNA TAKE
SOME SINGLE-MINDEDNESS.
WHETHER THERE HAS
TO BE SACRIFICE,
I DON'T KNOW, I SUPPOSE,
MAYBE IT DOES.

The Narrator says AT MEMORIAL SLOAN
KETTERING CANCER CENTER,
DOCTORS ARE SEEING IN PATIENTS
EXACTLY WHAT JIM HAS PREDICTED.

Padmanee says PATIENTS WERE
COMING IN AND TELLING US
THAT THEY FELT WELL.
EVEN THOUGH THE CAT SCANS
WERE SHOWING
THAT THE TUMORS ARE GROWING,
THESE PATIENTS SAID
"I'M FEELING REALLY GREAT
ON THIS TREATMENT."

Jedd says SOME PEOPLE, AFTER THEY CAME OFF
OF THE CLINICAL TRIALS
OF IPILIMUMAB,
BEGAN TO GET BETTER,
WITH NO FURTHER THERAPY.
AND THIS WAS QUITE STRIKING.

Eric says AND SO AT THAT POINT,
CLINICIANS LIKE JEDD WOLCHOK
ASKED THESE KIND OF IMMOVABLE,
IMPLACABLE FORCES,
BIG PHARMA AND THE UNITED STATES
GOVERNMENT, THE FDA,
TO CHANGE THE TRIAL.

Rachel says THE RISK BMS
WAS TAKING AT THE TIME
WAS WE WERE COMMITTING
TO YEARS MORE OF CLINICAL STUDY
BEFORE WE'D EVER GET APPROVAL.
IN AN ENVIRONMENT WHERE
THERE WAS TREMENDOUS UNCERTAINTY
ABOUT WHETHER THIS THING
WAS GONNA WORK OR NOT.

Elliott says WE WERE ASKED TO DO
ANOTHER FIVE YEARS
OF EXPENSIVE, LONG, TEDIOUS...
TRIALS.
THERE WERE INVESTORS THAT DIDN'T
THINK THIS WAS GONNA WORK.
WE HADN'T HAD A LONG TRACK
RECORD OF RECENT SUCCESS.
THIS TAKES A TOLL.
THIS TAKES A TOLL.

Jim says MY BROTHER WAS IN A...
FINAL THROES OF METASTATIC
PROSTATE CANCER,
AND THE DRUG WAS IN TRIALS
BY THEN.
AND THERE WERE REALLY
GOOD RESULTS COMING BACK.
BUT IT WAS,
IT WAS JUST NOT POSSIBLE.
THAT WAS, YOU KNOW,
IT WAS FRUSTRATING.
BUT, YOU KNOW, AT THE TIME,
I JUST WASN'T SO SURE
ABOUT WHETHER IT WOULD REALLY,
AT THE END OF THE DAY
DO MY BROTHER ANY GOOD,
BECAUSE HE WAS SO SICK, MAN.

Lewis says I REMEMBER HIM CALLING ME
FROM DALLAS
WHEN, YOU KNOW, MIKE WAS DYING.
AND HE, HE WAS IN HIS ARMS
AT THE TIME.
AND YOU COULD IMAGINE, YOU KNOW,
WHAT THAT WOULD DO TO YOU.

An old clip shows the three brothers playing in the sea.

Jim says WHEN I WAS FIRST TOLD
I HAD, UH, PROSTATE CANCER,
I WAS TERRIFIED,
BECAUSE IT WAS A WEEK
AFTER MY BROTHER HAD DIED.
I'D BEEN WORKING
WITH THE PROSTATE GROUP
AT SLOAN KETTERING.
SO I WENT OVER
TO THE ONCOLOGIST OFFICE,
THE SECRETARY SAID,
"HE'S WITH SOMEBODY."
I SAID, "I DON'T CARE."
I BEAT ON HIS DOOR.
[chuckling]
AND, UH, SAID,
"CAN I TALK WITH YOU?"
AND HE SAID I'LL BE NEXT.
I SAID, "NO, NOW." YOU KNOW.
"I NEED TO TALK TO YOU
RIGHT NOW."
MY ONCOLOGIST SAID THAT,
"YOUR CASE IS A FAMILY HISTORY.
I THINK WE BETTER TAKE IT OUT."
ANYWAY, THEY CAUGHT IT
VERY EARLY.

Jedd says SHARON CAME BACK
FROM HER FIRST SET OF IMAGING.
I GOT A PHONE CALL
FROM THE RADIOLOGIST.
NOW, USUALLY, YOU SHOULD KNOW
RADIOLOGISTS DON'T CALL
WITH GOOD NEWS.
THEY CALL TO MAKE YOU AWARE
OF SOME AWFULNESS
THAT THEY HAVE SEEN ON A SCAN.
AND THIS WAS
A VERY SERIOUS RADIOLOGIST,
VERY WELL-RESPECTED.
AND HE CALLED AND HE SAID, "JED,
I'M READING YOUR PATIENT
SHARON'S CAT SCANS, IS...
I HAVE TO ASK YOU SOMETHING."
THEN HE GOES,
"WHAT HAPPENED TO HER?"
I'M LIKE, "WHAT DO YOU MEAN?
WHAT HAPPENED?" HE GOES,
"WHAT DID SHE GET?
ALL THE CANCER WENT AWAY."
AND SO, THAT WAS AN IMPORTANT
MOMENT FOR MANY OF US.

The Narrator says WITH ENOUGH PATIENTS
SHOWING IMPROVED HEALTH,
BMS DECIDES TO COMMIT
TO THE FULL FIVE-YEAR STUDY
AND ACCEPT THE ENORMOUS
FINANCIAL RISK.

Padmanee says BRISTOL-MYERS SQUIBB
MADE THE DECISION
WITH EVERYBODY IN THE ROOM THEN.
TO USE OVERALL SURVIVAL
AS THE END POINT.
AND NOT TO USE
THE TYPICAL SORT OF,
TUMOR SHRINKAGE/IMMEDIATELY
END POINT.
BUT LOOK TO SEE HOW PATIENTS DID
OVER A LONG PERIOD OF TIME.

Jedd says I GIVE THE TEAM
AT BRISTOL-MYERS,
AND RACHEL WAS THE LEAD
OF THAT TEAM,
CREDIT FOR LISTENING TO US.
AND FOR BEING OPEN
TO THE OBSERVATIONS
THAT WE WERE REALLY MAKING
ON THE FRONT LINES,
AND TO WORKING WITH US
TO FIND A WAY
TO CAPTURE THIS NEW BIOLOGY.

Tyler says MOST COMPANIES,
AND MOST PEOPLE
IN THOSE COMPANIES AT THAT TIME
WOULD WASH THEIR HANDS
AND WALK AWAY.
AND SO, I GIVE GREAT CREDIT
TO BMS.
THEY WENT WITH THE SCIENCE.
THEY BELIEVED THE SCIENTIST.
AND THEY BELIEVED THE DATA.

Sharon says DOCTOR WOLCHOK
IN HIS EVER SO CALM VOICE SAID,
"SO, SHARON, THE MAN THAT
INVENTED THIS, IS HERE TODAY.
WOULD YOU LIKE TO MEET HIM?"
YES!

Jim says YOU KNOW, HE CALLS ME, HE SAYS,
"COME IN."
HE DIDN'T TELL ME THAT,
YOU KNOW, I FOUND OUT
WHY I WAS THERE
ONLY WHEN I WALKED IN THE ROOM.

Sharon says DOCTOR ALLISON WALKED IN,
AND I PRETTY MUCH ALMOST
LIFT HIM UP OFF THE FLOOR,
GAVE HIM A GIANT BEAR HUG.
I JUST COULDN'T TALK.
I COULDN'T TALK.
HOW IN THE WORLD ARE YOU
SUPPOSED TO ADEQUATELY THANK
SOMEBODY STANDING ACROSS
FROM YOU
THAT YOU WERE A HUNDRED PERCENT
POSITIVE THAT WITHOUT THEM,
YOU WOULDN'T BE HERE?
THERE IS NO "THANK YOU."
FOR THAT.

Jim says OH, MEETING HER
WAS AMAZING, BECAUSE...
UNTIL THEN, YOU KNOW,
IT WAS JUST NUMBERS.
YOU KNOW, IT WAS,
IT WAS A CONCEPT.
I'D EVER MET.

A picture shows a smiling Sharon hugging Jim and Jedd.

The caption changes to "September 26, 2006."

Sharon says AND ALL WE COULD THINK
ABOUT AT THE END OF THAT,
WAS "WE GOTTA GET A PICTURE."
WE LOOKED AROUND THE ROOM
AND NOBODY HAS A CAMERA.
THE ONLY CAMERA
THAT WE COULD FIND
WAS ONE THAT THEY TOOK PICTURES
OF THE MELANOMA WITH,
TO SEND OUT AND GET STUDIED.
IT'S NOT THE BEST QUALITY
IN THE WORLD,
BUT IT DEFINITELY MEMORIALIZES
ONE OF THE BEST DAYS EVER.
EVERY SINGLE SCAN SINCE,
She crosses her fingers and continues I HAVE ANOTHER MRI COMING UP
HERE IN ABOUT TWO WEEKS,
SO SAY A LITTLE PRAYER.
[chuckles]
UM...
NO EVIDENCE OF DISEASE.
IN EVERY ONE SINCE.

Jim says NOW SHE HAS HER FAMILY.
TWO KIDS, TWO BEAUTIFUL KIDS.
I STILL CHOKE UP
WHEN I THINK ABOUT THAT.

[light music plays]
Pictures of Sharon next to her husband and kids flash by.

The Narrator says IN 2011,
FIFTEEN YEARS AFTER JIM ALLISON
MADE HIS INITIAL DISCOVERY,
THE CLINICAL TRIALS
ARE FINALLY COMPLETE.

Rachel says I REMEMBER THE MOMENT
WHEN WE SAW THE DATA.
I CAN SEE THE PEOPLE AROUND ME.
IT IS IMPRINTED LIKE A PICTURE.
UM, BECAUSE WE KNEW
WE WERE CHANGING THE WORLD.

Elliott says RACHEL HUMPHREY
CAME RUNNING UP THE STAIRS,
BREATHLESS, TO SHOW ME
THE SURVIVAL CURVES.
ONE FOR THE CONTROL,
AND ONE FOR THE PATIENTS
THAT RECEIVED IPI.

An animated line graph shows the data mentioned.

He continues ONE CURVE STAYED DIFFERENT
FOR AS LONG AS WE STUDIED.
AFTER YEARS,
YOU START TO THINK THAT MAYBE
YOU'VE CURED THESE PATIENTS.

The caption changes to "March 25, 2011."

Jim says I HAPPENED TO BE
IN A MELANOMA MEETING
IN COLD SPRING HARBOR.
SITTING NEXT TO HAROLD VARMUS,
I HAD MY IPAD ON.
I KEPT CHECKING IT, AND HE SAID,
YOU KNOW, "WHAT ARE YOU DOING?"
AND I SAID, "WELL, THE FDA'S
SUPPOSED TO ANNOUNCE
ITS DECISION ON IPI TODAY."
ALL OF A SUDDEN
I GOT THIS E-MAIL,
IT WAS ABOUT 11:00
ON THE EAST COAST
WHICH MEANS IT WAS 8:00...
IN CALIFORNIA.
AND THERE'S ALAN
AND THE MEDAREX CROWD
HOLDING GLASSES OF WHISKEY.
AND I LOOKED AT HAROLD, I SAID,
"I GUESS..."
HE SAID,
"I GUESS THAT'S GOOD NEWS."
I SAID, "I THINK
THAT'S GOOD NEWS. YES."
AND HE SAID, "EITHER THAT,
OR THEY JUST LIKE TO DRINK
IN THE MORNING."
[chuckles]

The caption changes to "Ipi and successor Immuno-Oncology drugs have treated nearly a million patients worldwide. Jim Allison, now facing cancer for the third time, is one of them. Although Immuno-Oncology drugs don't' work for everyone they've already been a miracle for hundreds of thousands of people."

Matt says ALLISON AND OTHERS LIKE
HIM HAVE ONLY BEGUN THE THING.
EACH GENERATION WILL BUILD
ON THE NEXT.
WE'RE NOT NEARLY AT THE END
OF THIS STORY.
I MEAN, WE'RE SOMEWHERE
IN THE VERY FIRST FEW CHAPTERS.

Jim says THIS HAPPENS
FAIRLY REGULARLY.
I GET E-MAILS, BUT MANY TIMES,
A HANDWRITTEN NOTE.
THIS IS FROM SOMEBODY
I'VE NEVER MET.
He reads "DEAR DOCTOR ALLISON,
TWO YEARS AGO TODAY,
MY 63-YEAR YOUNG HUSBAND,
RICHARD, WAS DIAGNOSED WITH
METASTATIC MELANOMA TO THE BRAIN
AND EVERYWHERE ELSE.
THANKS TO YOU,
YOUR, UM...
[sobs]...
UH, FORTITUDE
AND DETERMINATION TO PROVE
THAT IMMUNOTHERAPY HAD PROMISE,
RICHARD IS ALIVE AND WELL,
HEALTHY AND HAPPY,
AND HAS BEEN TREATMENT-FREE
FOR OVER A YEAR."
[clears throat]
ANYWAY, IT SAYS THE WORDS
"THANK YOU."
[sighs heavily]
UM, "COULD NOT BEGIN TO COMPLETE
GRATITUDE WE HAVE FOR YOU.
AND YOUR PERSISTENCE
THROUGH ALL THIS
TO SEE THAT IMMUNOTHERAPY
BE BROUGHT TO PEOPLE WORLDWIDE.
OUR FAMILY IS ETERNALLY GRATEFUL
FOR THE EXTRA YEARS YOU HAVE
GIVEN US WITH RICHARD,
A WONDERFUL FATHER, HUSBAND.
SINCERELY..."
AND IT'S FROM HIS WIFE.
[sniffles]
FOR SURE, THIS, KNOWING THAT
GETTING SOME MAIL LIKE THIS
THAT MAKES IT ALL WORTHWHILE.
SO...
I NEED A DRINK.

[crowd applauding, cheering]

Willie Nelson gives a concert. Jim stands next to him holding a harmonica.

Willie plays the guitar and sings ROLL ME UP
AND SMOKE ME WHEN I DIE
AND IF ANYONE DON'T LIKE IT
JUST LOOK 'EM IN THE EYE
I DIDN'T COME HERE,
AND I AIN'T LEAVING
SO DON'T SIT AROUND AND CRY
JUST ROLL ME UP
AND SMOKE ME WHEN I DIE
NOW, YOU WON'T SEE
NO SAD AND TEARY EYES
WHEN I GET MY WINGS
AND IT'S MY TIME TO FLY
CALL MY FRIENDS AND TELL 'EM
THERE'S A PARTY, COME ON BY
NOW JUST ROLL ME UP
AND SMOKE ME WHEN I DIE

The end credits roll.

Written, Produced and Directed by Bill Haney.

Jim says WHEN I PLAYED
WITH WILLIE NELSON
AT THE AUSTIN CITY LIMITS
FESTIVAL...
I WAS SCARED.
[chuckles]

Willie sings LOOK 'EM IN THE EYE

Jim says IT WAS HARD TO RELAX.
YOU KNOW, WHEN I'M PLAYING
WITH MY BUDDIES, YOU KNOW,
IT'S LIKE FUN.
BUT YOU'RE PLAYING WITH WILLIE,
YOU KNOW, "I GOTTA GET THIS,
I GOTTA GET THIS."

[harmonica playing]
[crowd cheers]

Jim listens to a man on his cell phone.

The man says MY WARM CONGRATULATIONS
ON BEHLAF
OF THE NOBEL ASSEMBLY.

The caption changes to "Filmed by Jim's son, Robert Allison."

Jim says THANK YOU, THANK YOU SO MUCH.
I'M, I'M...
I'M SO HONORED, YOU KNOW.
OF COURSE, IT'S A...
IT'S A SCIENTIST'S DREAM.

The man says WE THINK
THAT THE DISCOVERIES THAT
YOU HAVE MADE
HAVE ENABLED AN ENTIRELY
NEW PRINCICPLE FOR
CANCER THERAPY
AND WE THINK
IT'S ABSOLUTELY FANTASTIC.

Willie sings TAKE ME OUT AND BUILD
A ROARING FIRE
ROLL ME IN THE FLAMES
FOR ABOUT AN HOUR
TAKE ME OUT AND TWIST ME UP
AND POINT ME TOWARDS THE SKY
AND JUST ROLL ME UP
AND SMOKE ME WHEN I DIE
ROLL ME UP
AND SMOKE ME WHEN I DIE
AND IF ANYONE DON'T LIKE IT
JUST LOOK 'EM IN THE EYE
I DIDN'T COME HERE
AND I AIN'T LEAVING
SO DON'T SIT AROUND AND CRY
JUST ROLL ME UP
AND SMOKE ME WHEN I DIE
I DIDN'T COME HERE,
AND I AIN'T LEAVING
SO DON'T SIT AROUND AND CRY
JUST...
[crowd sings]
ROLL ME UP AND SMOKE ME
WHEN I DIE

The caption changes to "Jim has returned to Texas. He is now Chairman of the Department of Immunology at MD Anderson Cancer Center in Houston. 3 years after the approval of Ipi..."

Eric says PAM SHARMA WAS TENURED
AT MD ANDERSON.
SHE WAS A BIG NAME IN THE
CANCER WORLD IN HER OWN RIGHT.
IT WAS TALKING PROFESSIONALLY
FOR QUITE A FEW YEARS.
AND THEN EVENTUALLY,
THERE WAS A ROMANCE.
JIM SAID TO HER ONE DAY,
"THERE'S NO ONE
WHO CAN STAND EITHER OF US.
ABOUT T CELLS ALL DAY?
YOU KNOW,
WE SHOULD GET MARRIED."

Copyright 2019, What We Can Win LLC, All Rights Reserved.

Watch: Jim Allison - Breakthrough