WEBVTT
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¶ ¶
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NARRATOR: HOW MANY
PEOPLE ARE ALIVE ON
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PLANET EARTH RIGHT NOW?
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7,400,000,000 GIVE OR TAKE.
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WHATEVER YOU DO OR DON'T
BELIEVE ABOUT HOW WE GOT HERE,
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THE FACT IS, WE ARE
ALIVE, HERE AND NOW.
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THERE ARE THREATS TO OUR VERY
EXISTENCE ON A DAILY BASIS;
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INTERNAL AND EXTERNAL CHAOS,
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NATURAL DISASTERS,
WAR, DISEASES.
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AND RIGHT NOW, THERE IS
A MONSTER ON THE LOOSE.
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DR. ANDRE CHOULIKA: THE BEST
IMAGE THAT YOU CAN TAKE IS
00:01:01.662 --> 00:01:03.996
LIKE THESE ZOMBIES MOVIES.
00:01:06.867 --> 00:01:12.404
SOME PEOPLE TURN TOTALLY WILD,
AND GO AND START BITING EACH
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OTHER AND CONVERT THE OTHERS.
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DR. DAVID PORTER:
DARK, SCARY MONSTER.
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DR. PAUL VEYS: CAN'T SEE IT TILL
IT'S SORT OF RIGHT UPON YOU.
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DR. BRUCE LEVINE: IT COMES
IN AND POSSESSES YOU.
00:01:32.693 --> 00:01:34.693
DR. CARL JUNE: YOU DON'T KNOW
WHERE THE ENEMY REALLY IS.
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IT'S AMONG US.
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¶ [THEME MUSIC PLAYS] ¶
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DR. DAVID PORTER: CANCER
IS WHEN CELLS GO BAD.
00:02:03.674 --> 00:02:05.474
THEY GROW INAPPROPRIATELY.
00:02:05.593 --> 00:02:08.960
THEY GROW FASTER THAN THEY
SHOULD OR THEY GROW IN PLACES
00:02:09.063 --> 00:02:11.897
THAT THEY SHOULDN'T GROW.
00:02:11.982 --> 00:02:14.983
I DON'T THINK THE IDEA OF
CURING CANCER IS NAIVE.
00:02:15.102 --> 00:02:17.019
I THINK IT'S MANDATORY.
00:02:17.104 --> 00:02:19.905
I MIGHT, I MIGHT JUST CHANGE
IT A LITTLE BIT AND I WOULD
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SAY CURING CANCERS.
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NARRATOR: AT
THIS VERY MOMENT,
00:02:29.450 --> 00:02:32.817
POTENTIAL CANCER CELLS
EXIST INSIDE OUR BODIES.
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CELLS THAT NEED JUST A
FEW GENETIC MUTATIONS
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TO BECOME CANCER.
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OF THE TENS OF TRILLIONS
OF CELLS IN YOUR BODY,
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IT ONLY TAKES ONE SINGLE
CELL TO START THE
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CHAIN REACTION
TOWARDS CANCER.
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IF IT IS CAUGHT EARLY
ENOUGH, THERE ARE OPTIONS.
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BUT CANCER IS CUNNING
AND RELENTLESS.
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IT KNOWS HOW TO HIDE
AND PROTECT ITSELF.
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DOUG OLSON: I THINK WHAT'S
SO TERRIFYING ABOUT CANCER
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IS THAT IT'S YOUR OWN
BODY TRYING TO KILL YOU.
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IT'S NOT BACTERIA.
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IT'S NOT A VIRUS.
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IT'S YOUR OWN BODY.
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IT'S PART OF YOU
THAT'S BETRAYING YOU.
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IT DEVELOPS WAYS IN WHICH
TO FOOL THE SYSTEM THAT'S
00:03:43.274 --> 00:03:45.691
SUPPOSED TO KEEP YOU SAFE.
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AS IF THESE CELLS
ACTUALLY THOUGHT ABOUT IT.
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WHAT DO I DO TO ESCAPE THE
IMMUNE SYSTEM SO I CAN TAKE
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THIS PERSON DOWN?
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YOU GOT ANY HOT COFFEE THERE?
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SO MY NAME IS DOUG OLSON.
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I'M 69 YEARS OLD.
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WHEN I WAS 49 YEARS OLD,
I WAS DIAGNOSED WITH
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CHRONIC LYMPHOCYTIC LEUKEMIA.
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IT WAS JULY OF 1996, AND I
WAS FEELING KIND OF PUNK,
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SO I WENT TO AN IMMEDIATE CARE
FACILITY TO GET CHECKED OUT.
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THE DOCTOR NOTICED I HAD SWOLLEN
LYMPH NODES AND SHE SAID,
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"GEE, THAT SEEMS A
LITTLE SUSPICIOUS."
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AND I SAID, "WELL,
WHAT COULD THAT BE?"
00:04:31.956 --> 00:04:35.073
AND SHE SAID, "WELL, MAYBE
MONO OR IT COULD BE CANCER."
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I THOUGHT, "OKAY."
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SO SHE MADE AN
APPOINTMENT FOR ME TO GO
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SEE A SURGEON TO HAVE
THE LYMPH NODE BIOPSIED.
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SO I LITERALLY
WENT THE NEXT DAY.
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HE ACTUALLY GOT MY
BLOOD WORK AND, UH,
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THE WHITE CELL COUNT WAS 10
TIMES WHAT IT SHOULD'VE BEEN.
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BUT HE SAID, "WE PROBABLY
SHOULD TAKE THE LYMPH NODE OUT
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AND SEE WHAT'S GOING ON."
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HE SAID, "I COULD ACTUALLY
DO IT RIGHT NOW,"
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AND I SAID,
"OKAY, LET'S DO IT."
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TOOK THE LYMPH NODE OUT
AND I TOOK THE SAMPLE
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TO THE HOSPITAL AND I HANDED
IT TO THE PATHOLOGIST AND
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HE SAID, "IT'LL
PROBABLY BE OKAY."
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AND THEN HE LOOKED DOWN
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AT MY BLOOD WORK
AND HE SAYS,
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"ARE THESE, IS THIS
YOUR BLOOD WORK?"
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AND I SAID, "YEAH" AND I JUST
WATCHED HIS FACE CHANGE, LIKE,
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IT'S NOT GONNA BE GOOD NEWS.
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THEY SAID THERE'S THIS
NEW GUY, DAVID PORTER,
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WHO'S JUST DOWN FROM HARVARD.
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DR. DAVID PORTER: MY
NAME'S DAVID PORTER.
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I'M THE DIRECTOR OF THE BLOOD
AND MARROW TRANSPLANT PROGRAM
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HERE AT THE UNIVERSITY
OF PENNSYLVANIA IN
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THE ABRAMSON CANCER CENTER.
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UH, I'VE BEEN HERE A
LITTLE OVER 20 YEARS NOW.
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I TAKE CARE OF A LOT OF
PATIENTS WITH BLOOD CANCERS.
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AND MY RESEARCH INTEREST IS
PRIMARILY FOCUSED IN
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THE FIELD OF BLOOD AND BONE
MARROW TRANSPLANT AND
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IN IMMUNOTHERAPY
AND IN PARTICULAR,
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PARTICULARLY CELLULAR
IMMUNOTHERAPY.
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DOUG OLSON: SO THE NEXT WEEK,
I HAD AN APPOINTMENT WITH HIM.
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AND THAT'S WHEN HE
TOLD ME THAT I HAD CLL.
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HE DID HIS BEST TO TRY TO GET
ME TO THINK ABOUT IT MORE AS
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A CHRONIC DISEASE.
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BUT HAVING SAID THAT, THE
PROGNOSIS FOR CLL WAS LIKE
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SOMEWHERE BETWEEN SIX
AND FIFTEEN YEARS.
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ALL OF A SUDDEN, I'M
SEEING MY LIFE CUT SHORT.
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DR. DAVID PORTER: YEAH.
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DOUG OLSON: I MEAN, THAT,
THAT, THAT WAS REALLY THE,
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THE TOUGH PART ABOUT
HEARING IT'S NOT CURABLE.
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NARRATOR: CLL IS A FORM OF
LEUKEMIA THAT FOLLOWS YOU
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LIKE A STALKER IN THE NIGHT.
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IT CAN LAY LOW INSIDE YOUR
BLOODSTREAM FOR YEARS,
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SLOWLY SPREADING
UNTIL IT DEFEATS YOU.
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LEUKEMIA IS A
COMPLICATED DISEASE.
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IT IS A BLOOD CANCER THAT
LIVES IN THE BONE MARROW,
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WHERE BLOOD CELLS AND IMMUNE
CELLS ARE MANUFACTURED.
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MUTATIONS IN DNA PRODUCE
AN OVERABUNDANCE OF
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DEFECTIVE BLOOD CELLS.
00:07:07.394 --> 00:07:10.094
THE DEFECTIVE CELLS
COLLECT IN BONE MARROW AND
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THE LYMPH NODES, CLOGGING THE
PRODUCTION OF HEALTHY CELLS.
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IN TIME, THE PROLIFERATION OF
THESE CANCEROUS CELLS DAMAGES
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YOUR IMMUNE SYSTEM.
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WITH YOUR NATURAL
DEFENSES SHATTERED,
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PATHOGENS ARE FREE
TO RAVAGE YOUR BODY.
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IN MOST CASES,
CLL IS INCURABLE.
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IN MANY, IT CAN BE
MANAGED WITH CHEMOTHERAPY,
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OR IN EXTREME CASES, AN
IMMENSELY RISKY BONE MARROW
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TRANSPLANT CAN
OFFER REMISSION.
00:07:39.977 --> 00:07:42.227
HOWEVER, IF THE CELLS
CONTINUE TO MUTATE,
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THEY CAN BECOME
COMPLETELY RESISTANT
00:07:44.097 --> 00:07:46.982
TO TREATMENT, BECOMING FATAL.
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DOUG OLSON: THE FIRST CHEMO
WAS NOT ALL THAT VIOLENT.
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I DIDN'T LOSE MY HAIR.
00:07:58.662 --> 00:08:03.281
I HAD TWO ROUNDS AND BLOOD COUNT
WENT RIGHT DOWN TO NORMAL AGAIN.
00:08:05.035 --> 00:08:07.953
AND THEN IT WAS
ANOTHER FIVE YEARS.
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IT WAS 2006 WHEN I RELAPSED.
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PA: PROCEED WITH CAUTION.
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DON'T FORGET TO
ENJOY YOUR LIFE.
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DOUG OLSON: AND
DID THIS TREATMENT,
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THAT'S THE BENDAMUSTINE,
THAT DIDN'T WORK AT ALL.
00:08:33.063 --> 00:08:37.682
DAVID, HE SAID, "FRANKLY,
YOU HAVE THIS MUTATION."
00:08:38.485 --> 00:08:40.785
YOU KNOW, "THE CANCER
IS GONNA BECOME HARDER AND
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HARDER TO TREAT.
00:08:43.323 --> 00:08:45.740
WE'RE GONNA SWITCH
TO THIS NEW CHEMO.
00:08:45.826 --> 00:08:47.042
WE'LL SEE HOW THAT WORKS."
00:08:47.160 --> 00:08:48.860
AND WHEN IT DIDN'T,
SEVERAL TIMES,
00:08:48.962 --> 00:08:50.378
HE SAID, "YOU KNOW, WE'RE
GONNA HAVE TO START TALKING
00:08:50.497 --> 00:08:53.164
ABOUT BONE MARROW TRANSPLANT."
00:08:56.053 --> 00:08:58.587
HALF OF MY BONE
MARROW WAS CANCER.
00:08:58.672 --> 00:09:02.007
I MEAN, I, IT WAS, I
MEAN, LITERALLY, UM,
00:09:03.677 --> 00:09:05.760
IT WAS PRETTY SERIOUS
AT THAT POINT.
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DR. DAVID PORTER: THESE ARE
AWFUL CANCERS AND THERE ARE
00:09:10.017 --> 00:09:13.151
TIMES WHEN TREATMENTS JUST
DON'T WORK AND PATIENTS ARE
00:09:13.237 --> 00:09:15.270
SICK AND THEY FEEL
AWFUL AND PATIENTS DIE.
00:09:15.739 --> 00:09:19.524
AND THAT'S DEVASTATING.
00:09:19.610 --> 00:09:23.862
BUT HONESTLY, THE WORST WORSE
THING IS WHEN WE DON'T HAVE
00:09:23.947 --> 00:09:26.114
ANY OPTIONS FOR SOMEBODY.
00:09:26.199 --> 00:09:29.251
THAT'S THE MOST
FRUSTRATING PART FOR ME,
00:09:29.369 --> 00:09:32.203
WHEN WE DON'T EVEN HAVE
SOMETHING TO OFFER.
00:09:34.207 --> 00:09:35.740
NARRATOR: DR. CARL JUNE
DOES NOT BELIEVE IN
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RUNNING OUT OF OPTIONS.
00:09:40.013 --> 00:09:42.747
ALSO WORKING OUT OF THE
UNIVERSITY OF PENNSYLVANIA,
00:09:42.849 --> 00:09:46.268
DR. JUNE HAS BEEN DEVELOPING
A NEW TECHNOLOGY TO LEVERAGE
00:09:46.386 --> 00:09:48.937
THE IMMUNE SYSTEM'S
T CELLS TO FIGHT AND
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KILL LEUKEMIA IN MICE.
00:10:00.901 --> 00:10:02.767
DR. CARL JUNE: I'VE BEEN
THROUGH A LONG JOURNEY.
00:10:02.869 --> 00:10:05.570
SO I WAS A PHYSICIAN
AND THEN I GRADUALLY,
00:10:05.656 --> 00:10:07.939
I CAME TO A CONCLUSION THAT
I COULD PROBABLY HELP MORE
00:10:08.041 --> 00:10:11.793
PEOPLE THROUGH MY SCIENTIFIC
LABORATORY EFFORTS THAN
00:10:11.912 --> 00:10:14.713
ACTUALLY SEEING PEOPLE
ONE AT A TIME IN A CLINIC.
00:10:15.582 --> 00:10:17.832
DR. CARL JUNE: AND I TELL
MY FAMILY NOW THAT MY "MD"
00:10:17.918 --> 00:10:19.968
STANDS FOR MOUSE DOCTOR.
00:10:20.504 --> 00:10:22.053
NARRATOR: THE IMMUNE
SYSTEM PROTECTS YOU
00:10:22.139 --> 00:10:24.339
FROM OUTSIDE INVASION.
00:10:24.424 --> 00:10:27.625
IF A VIRUS, BACTERIA, OR
FUNGUS SLIPS INTO YOUR BODY,
00:10:28.595 --> 00:10:31.896
THE IMMUNE SYSTEM RESPONDS
WITH A COORDINATED ATTACK THAT
00:10:31.982 --> 00:10:35.066
KILLS THE INVADER,
AND ONLY THE INVADER.
00:10:36.687 --> 00:10:38.937
LEAVING YOUR BODY INTACT.
00:10:40.440 --> 00:10:42.657
THIS IS A T CELL.
00:10:42.776 --> 00:10:45.476
THIS IMMUNE CELL'S JOB IS TO
KILL INFECTED CELLS BEFORE
00:10:45.579 --> 00:10:47.195
THEY CAUSE MORE DAMAGE.
00:10:47.280 --> 00:10:49.814
IN THEORY, T CELLS CAN
BE EXTRAORDINARILY
00:10:49.916 --> 00:10:52.083
POTENT AGAINST LEUKEMIA.
00:10:52.169 --> 00:10:54.652
BUT THERE'S ONE PROBLEM.
00:10:54.755 --> 00:10:58.340
SINCE CANCER IS EFFECTIVELY
PART OF YOUR OWN BODY,
00:10:58.458 --> 00:11:01.325
THE IMMUNE SYSTEM SOMETIMES
IGNORES THESE ROGUE CELLS,
00:11:01.962 --> 00:11:04.295
ALLOWING THE CANCER
TO SPREAD UNCHECKED.
00:11:05.549 --> 00:11:08.266
JUNE AND HIS TEAM HAVE WORKED
TIRELESSLY TO FIND A WAY TO
00:11:08.352 --> 00:11:11.703
GET THE IMMUNE SYSTEM TO
RECOGNIZE AND DESTROY ALL
00:11:11.805 --> 00:11:13.605
OF THE CANCEROUS
CELLS IN THE BODY.
00:11:14.191 --> 00:11:15.673
DR. CARL JUNE: THE THERAPY
WE'RE DEVELOPING IS,
00:11:15.776 --> 00:11:17.675
IS MULTIDISCIPLINARY.
00:11:17.778 --> 00:11:20.562
IT INVOLVES
LEUKEMIA SPECIALIST.
00:11:21.114 --> 00:11:23.064
DAVID PORTER IS KNOWN AROUND
THE WORLD FOR HIS TREATING
00:11:23.150 --> 00:11:25.116
VARIOUS KINDS OF LEUKEMIA.
00:11:25.202 --> 00:11:27.402
IT INVOLVES
IMMUNOLOGY EXPERTISE,
00:11:28.622 --> 00:11:33.324
VIRAL VECTOR DESIGN EXPERTISE,
AND THEN THE CELL CULTURING
00:11:33.410 --> 00:11:36.360
EXPERTISE THAT BRUCE LEVINE
KNOWS MORE ABOUT THAN ANYONE
00:11:36.463 --> 00:11:37.545
IN THE WORLD.
00:11:37.664 --> 00:11:39.130
I'M QUITE SURE.
00:11:39.216 --> 00:11:40.799
DR. BRUCE LEVINE: OKAY.
00:11:40.884 --> 00:11:43.334
I'M A PROFESSOR IN
CANCER GENE THERAPY,
00:11:44.671 --> 00:11:47.055
AND I DIRECT THE
CLINICAL CELL AND
00:11:47.174 --> 00:11:49.224
VACCINE PRODUCTION FACILITY.
00:11:49.342 --> 00:11:52.894
AND WHAT WE DO IS TO
DEVELOP, MANUFACTURE,
00:11:53.013 --> 00:11:56.931
AND TEST CELL AND GENE
THERAPIES TO FIGHT CANCER
00:11:57.434 --> 00:12:00.185
USING THE PATIENT'S OWN
IMMUNE CELLS THAT
00:12:00.270 --> 00:12:02.687
HAVE BEEN GENETICALLY
TARGETED TO CANCER.
00:12:05.075 --> 00:12:07.492
DR. DAVID PORTER: A "CAR"
T CELL IS A T CELL THAT IS
00:12:07.577 --> 00:12:10.862
GENETICALLY MODIFIED IN A
WAY THAT ALLOWS IT TO SEE AND
00:12:10.947 --> 00:12:13.114
RECOGNIZE A CANCER CELL.
00:12:17.120 --> 00:12:20.004
A "CAR" STANDS FOR
CHIMERIC ANTIGEN RECEPTOR.
00:12:20.257 --> 00:12:22.907
IT'S A MOLECULE
THAT IS SYNTHETIC.
00:12:23.343 --> 00:12:26.344
WE CAN PUT IT INTO AN IMMUNE
CELL AND GENETICALLY CHANGE
00:12:26.446 --> 00:12:29.180
THE IMMUNE CELL TO
EXPRESS THE CAR MOLECULE.
00:12:30.550 --> 00:12:34.302
THAT FUNCTION OF BINDING
ACTIVATES THE T CELL AND IT
00:12:34.688 --> 00:12:37.472
ALLOWS IT TO BECOME ACTIVE,
TO BECOME A KILLER CELL,
00:12:37.557 --> 00:12:40.442
AND TO KILL THE LEUKEMIA.
00:12:47.984 --> 00:12:50.652
NARRATOR: THE UNLIKELY KEY TO
UNLOCKING THE POWER OF T CELLS
00:12:50.737 --> 00:12:56.274
AGAINST LEUKEMIA CAME FROM ONE
OF THE MOST FEARED VIRUSES, HIV.
00:12:58.612 --> 00:13:01.913
DR. CARL JUNE: BY USING A
GUTTED OUT HIV VIRUS AND
00:13:01.998 --> 00:13:03.882
MAKING IT SO IT'S
NON-PATHOGENIC,
00:13:03.967 --> 00:13:06.885
MEANING IT CAN'T
CAUSE HIV ANYMORE,
00:13:07.921 --> 00:13:11.956
IT STILL RETAINS ITS ABILITY
TO TRANSFER GENES INTO T CELLS.
00:13:12.642 --> 00:13:14.843
AND SO WE CAN REPURPOSE
THAT VIRUS AND
00:13:14.928 --> 00:13:16.961
USE IT FOR SOMETHING GOOD.
00:13:17.898 --> 00:13:19.797
NARRATOR: THE GENIUS OF
DR. JUNE'S GROUP WAS TO
00:13:19.900 --> 00:13:22.233
HARNESS HIV AS A
DELIVERY SYSTEM.
00:13:22.903 --> 00:13:26.304
THEY REPLACED HIV'S MALICIOUS
CODE WITH A BENEFICIAL ONE
00:13:27.040 --> 00:13:31.276
THAT REPROGRAMS T CELLS TO
IDENTIFY AND KILL CANCER CELLS.
00:13:32.279 --> 00:13:34.496
THIS BREAKTHROUGH
TRANSFORMS REGULAR T CELLS
00:13:34.614 --> 00:13:36.781
INTO CAR T CELLS.
00:13:37.834 --> 00:13:39.984
DR. CARL JUNE: IN 2004,
DAVID PORTER, AND I,
00:13:40.086 --> 00:13:42.954
AND BRUCE LEVINE
GOT A $1,000,000 GRANT
00:13:43.039 --> 00:13:46.124
TO DO THE CAR-19
THERAPY THAT WE HAD.
00:13:46.459 --> 00:13:49.511
AT THAT POINT, WE HAD IT
WORKING IN MICE AND WE WANNA
00:13:49.629 --> 00:13:51.513
DO ALL THE THINGS IT
WOULD TAKE TO TURN IT
00:13:51.631 --> 00:13:53.932
INTO A HUMAN TRIAL.
00:13:54.634 --> 00:13:57.852
NARRATOR: BUT WOULD THIS
EXPERIMENTAL TREATMENT GET THE
00:13:57.971 --> 00:14:01.272
SAME POSITIVE RESULTS
IN THE INFINITELY MORE COMPLEX
00:14:01.358 --> 00:14:03.808
HUMAN IMMUNE SYSTEM?
00:14:09.274 --> 00:14:11.391
NARRATOR: TOILING
FOR OVER A DECADE,
00:14:11.477 --> 00:14:15.061
DR. CARL JUNE'S RESEARCH
TEAM REPROGRAMMED HIV,
00:14:15.164 --> 00:14:18.398
ONE OF THE MOST TERRIFYING
MONSTERS OF THE 20TH CENTURY,
00:14:18.867 --> 00:14:21.785
AND TRANSFORMED IT INTO
A HERO OF THE 21ST.
00:14:22.204 --> 00:14:23.787
DR. CARL JUNE: IT'S A
TECHNOLOGY TRANSFER,
00:14:23.872 --> 00:14:27.040
THE KNOWLEDGE WE LEARNED ON
WHAT THE HIV VIRUS DOES AND
00:14:27.126 --> 00:14:29.259
ITS PATHOGENICITY
DISEASE CAUSING,
00:14:29.378 --> 00:14:31.812
LED TO A TREATMENT
FOR LEUKEMIA.
00:14:32.765 --> 00:14:35.515
NARRATOR: THIS BREAKTHROUGH
TRANSFORMS REGULAR T CELLS
00:14:35.601 --> 00:14:38.685
INTO SUPERCHARGED NEW
CELLS CALLED CAR T CELLS.
00:14:39.888 --> 00:14:42.139
DR. CARL JUNE: A CAR T CELL
THAT HAS AN ANTIBODY AGAINST
00:14:42.224 --> 00:14:45.108
A TUMOR CELL WILL
STICK LIKE FLYPAPER.
00:14:45.761 --> 00:14:48.161
AND THAT CAR T CELL WILL STAY
THERE ON THE CANCER CELL UNTIL
00:14:48.263 --> 00:14:49.930
THE CANCER CELL IS DEAD.
00:14:50.032 --> 00:14:53.900
IT CAN TAKE A FEW MINUTES TO
SOMETIMES AN HOUR FOR THE
00:14:54.002 --> 00:14:56.303
CAR T CELL TO KILL
THE TUMOR CELL.
00:14:56.405 --> 00:14:58.705
WHEN THE T CELL KNOWS THAT
THE TUMOR CELL IS DEAD,
00:14:58.807 --> 00:15:02.642
IT DISENGAGES AND LOOKS AND
FINDS OTHER CANCER CELLS.
00:15:04.580 --> 00:15:07.881
A CAR T CELL WILL GO FROM
ONE CANCER CELL, KILL IT,
00:15:07.983 --> 00:15:09.249
GO TO ANOTHER AND TO ANOTHER.
00:15:09.351 --> 00:15:11.885
SO THEY'RE CALLED
SERIAL KILLER CELLS.
00:15:22.531 --> 00:15:24.264
AND IT'S THE FIRST TIME
IN HISTORY THAT WE'VE
00:15:24.349 --> 00:15:26.766
HAD LIVING DRUGS.
00:15:32.741 --> 00:15:35.808
NARRATOR: UP UNTIL THIS POINT,
CAR T CELL THERAPY HAD ONLY
00:15:35.911 --> 00:15:39.779
BEEN ATTEMPTED IN PETRI
DISHES AND LABORATORY MICE.
00:15:40.282 --> 00:15:42.949
MAKING THE LEAP TO HUMANS
IS INFINITELY MORE
00:15:43.035 --> 00:15:45.619
COMPLEX AND TREACHEROUS.
00:15:47.172 --> 00:15:50.790
DR. CARL JUNE: CANCER IS MUCH
MORE COMPLEX IN HUMANS THAN
00:15:50.876 --> 00:15:52.425
IT IS IN MICE.
00:15:52.511 --> 00:15:53.960
LAB EMPLOYEE: I
MEAN, THIS IS ALL.
00:15:54.046 --> 00:15:56.046
DR. CARL JUNE: WHEN YOU START
FROM AN INITIAL TRIAL IN
00:15:56.131 --> 00:15:58.331
HUMANS, THERE'S A MUCH HIGHER
FAILURE RATE THAN THERE IS IN
00:15:58.433 --> 00:16:00.350
OTHER DISCIPLINES IN MEDICINE.
00:16:00.469 --> 00:16:02.502
LAB EMPLOYEE: THE PROBLEM IS
IT DOESN'T WORK AS WELL SO THE
00:16:02.604 --> 00:16:04.304
TUMOR GROWS AND THIS IS
A VERY RAPIDLY GROWING.
00:16:04.389 --> 00:16:05.856
DR. CARL JUNE: YEAH.
00:16:05.974 --> 00:16:08.225
DR. DAVID PORTER: IN 2006, IS
WHEN WE FIRST STARTED TO WRITE
00:16:08.310 --> 00:16:10.193
OUR FIRST CLINICAL
TRIAL USING THESE
00:16:10.312 --> 00:16:12.863
GENETICALLY MODIFIED T CELLS.
00:16:15.284 --> 00:16:17.684
FOLKS HERE AT PENN,
CARL JUNE, BRUCE LEVINE,
00:16:18.120 --> 00:16:20.370
WE'RE ALL DEVELOPING METHODS
WHERE THIS WAS GOING TO BE
00:16:20.489 --> 00:16:21.905
ABLE TO BE SCALED UP.
00:16:21.990 --> 00:16:25.242
THAT WE COULD DO THIS WITH
HUMAN T CELLS AND THAT WE WERE
00:16:25.327 --> 00:16:27.327
GOING TO BE ABLE TO GROW
ENOUGH OF THESE T CELLS TO
00:16:27.412 --> 00:16:30.497
ACTUALLY GIVE TO A, A PERSON.
00:16:31.300 --> 00:16:33.533
DOUG OLSON: MY GOAL FROM THE
BEGINNING WAS STAY ALIVE LONG
00:16:33.619 --> 00:16:36.386
ENOUGH FOR SOMEBODY TO COME
UP WITH A CURE FOR THIS THING.
00:16:36.505 --> 00:16:40.674
THAT'S WHAT I REALLY WANTED TO
DO IS TO JUST TRY TO STAY AS
00:16:40.759 --> 00:16:44.010
HEALTHY AS I COULD
AND, UM, YOU KNOW,
00:16:44.096 --> 00:16:47.180
TRY TO KEEP SURVIVING THIS
THING UNTIL THERE WAS A BETTER
00:16:47.266 --> 00:16:50.901
OPTION THAN BONE
MARROW TRANSPLANT.
00:16:51.019 --> 00:16:53.520
I MEAN, THIS LOOKED CURATIVE.
00:16:53.605 --> 00:16:56.389
YOU KNOW, IT WAS TARGETED
TO THE CANCER INSTEAD OF
00:16:56.491 --> 00:17:00.393
BLASTING, YOU KNOW, THE
BODY WITH POISON THAT,
00:17:00.495 --> 00:17:05.332
THAT PREFERENTIALLY KILLS
CANCER CELLS BUT ALSO WHACKS
00:17:05.417 --> 00:17:09.586
A LOT OF THE, UH,
HEALTHY TISSUE.
00:17:11.039 --> 00:17:13.456
SO I SIGNED UP.
00:17:14.543 --> 00:17:16.509
YOU KNOW, THEY TELL YOU ALL
THE THINGS THAT COULD GO WRONG
00:17:16.595 --> 00:17:18.244
AND THE, AND THE PROTOCOL
AT THE SAME TIME,
00:17:18.347 --> 00:17:19.629
AND YOU HAVE TO SIGN
FORMS, OF COURSE,
00:17:19.715 --> 00:17:21.181
THAT SAYS THAT YOU'RE
AWARE THAT, YOU KNOW,
00:17:21.266 --> 00:17:23.099
THINGS COULD GO BAD.
00:17:23.218 --> 00:17:26.853
BUT, YOU KNOW, IN A CLINICAL
TRIAL, IT'S, IT'S LITERALLY,
00:17:26.939 --> 00:17:30.056
YOU'RE MAKING A LEAP
FROM MICE TO HUMANS.
00:17:31.226 --> 00:17:33.226
NARRATOR: DOUG WAS ONE OF
THREE PATIENTS ENTERING
00:17:33.328 --> 00:17:35.462
UNCHARTED TERRITORY
IN THE EXPERIMENTAL
00:17:35.564 --> 00:17:38.098
CAR T CELL THERAPY.
00:17:38.200 --> 00:17:40.133
DOUG OLSON: TAKING THE
WHITE CELLS WAS THREE HOURS
00:17:40.235 --> 00:17:41.635
SITTING IN A CHAIR.
00:17:41.737 --> 00:17:44.938
THEN THE CELLS
GO OFF TO A LAB.
00:17:47.175 --> 00:17:49.743
DR. BRUCE LEVINE: WE GET A BAG
OF CELLS AND WE ISOLATE THE
00:17:49.828 --> 00:17:52.412
CELLS THAT WE
WANT, THE T CELLS.
00:17:55.751 --> 00:17:59.619
AND THEN AFTER A FEW DAYS, WE
LOAD THEM INTO THIS BIOREACTOR
00:17:59.921 --> 00:18:02.589
SO THIS IS EVERYTHING
THAT A CELL NEEDS.
00:18:03.759 --> 00:18:07.060
THE LIQUID END HAS NUTRIENTS
AND ALLOWS THE CELLS TO
00:18:07.145 --> 00:18:08.979
GROW AND DIVIDE.
00:18:09.097 --> 00:18:10.814
THEY LOVE THIS ENVIRONMENT.
00:18:10.932 --> 00:18:14.184
WE CAN PUT IN A FEW
TENS OF MILLIONS AND WE
00:18:14.269 --> 00:18:16.853
GET OUT BILLIONS.
00:18:17.572 --> 00:18:19.773
WE PUT THE GENE ENCODING THE
CHIMERIC ANTIGEN RECEPTOR
00:18:19.858 --> 00:18:21.491
IN THE T CELLS.
00:18:21.610 --> 00:18:23.943
WE'VE CROWD-PRESERVED THEM.
00:18:24.029 --> 00:18:26.613
AND I'LL SHOW YOU WHAT
THE CELLS LOOK LIKE.
00:18:27.282 --> 00:18:31.368
NOW THAT'S THE LIQUID NITROGEN
VAPOR AND IN HERE ARE
00:18:31.453 --> 00:18:33.820
RACKS WITH CANISTERS.
00:18:33.922 --> 00:18:39.158
IT IS IN HERE AND THEY'RE AT
MINUS 190 AND THEY'RE IN THESE
00:18:39.261 --> 00:18:41.628
BAGS IN THE CANISTERS.
00:18:42.798 --> 00:18:44.831
AND THEY HAVE A LABEL ON THEM.
00:18:44.933 --> 00:18:49.052
OKAY, SO NOW, YOU CAN SEE WHY
THEY CALL THEM WHITE CELLS.
00:18:50.472 --> 00:18:54.524
SO THIS TINY BAG HAS SEVERAL
HUNDRED MILLION CELLS.
00:18:56.311 --> 00:18:58.778
IN THE EYES OF
REGULATORY AUTHORITIES,
00:18:58.864 --> 00:19:01.398
IN THE EYES OF THE FDA,
WE REALLY ARE A PHARMACY.
00:19:01.700 --> 00:19:04.284
WE'RE MAKING A DRUG,
EVEN THOUGH IT'S THE
00:19:04.386 --> 00:19:06.486
PATIENT'S OWN CELLS.
00:19:07.155 --> 00:19:08.872
DOUG OLSON: THESE TWO YOUNG
WOMEN CAME INTO THE TREATMENT
00:19:08.990 --> 00:19:11.491
ROOM WITH A BIG
FLASK OF NITROGEN,
00:19:11.576 --> 00:19:14.994
WHICH HAD THIS LITTLE
PACKAGE OF MY CELLS.
00:19:15.914 --> 00:19:18.581
IT TURNS OUT THESE WERE THE
TWO PEOPLE THAT ACTUALLY WERE
00:19:18.667 --> 00:19:21.000
RESPONSIBLE FOR
MANUFACTURING THESE CELLS.
00:19:21.086 --> 00:19:25.138
AND I THINK, I THINK THEY WERE
AS EXCITED AS I WAS, YOU KNOW,
00:19:25.590 --> 00:19:28.508
'CAUSE THEY KNEW
HOW HUGE THIS WAS.
00:19:29.811 --> 00:19:32.345
THEN A NURSE, THEY
THAWED THE CELLS,
00:19:32.431 --> 00:19:35.148
AND HOOKED IT UP TO AN IV
AND TURNS THE VALVE,
00:19:35.233 --> 00:19:38.068
AND BAG EMPTIES.
00:19:39.187 --> 00:19:41.354
THEY KEPT ME AROUND FOR A
FEW HOURS TO SEE IF I HAD
00:19:41.440 --> 00:19:43.556
ANY REACTION TO IT.
00:19:43.658 --> 00:19:45.742
NOTHING HAPPENED.
00:19:56.004 --> 00:20:01.708
¶ ¶
00:20:03.512 --> 00:20:06.679
I CAN'T IMAGINE WHAT IT MUST
HAVE BEEN LIKE IN DAVID'S PART,
00:20:06.782 --> 00:20:09.081
AND CARL JUNE'S PART,
AND THE SCIENTIST THAT
00:20:09.184 --> 00:20:10.600
HAVE DONE THIS.
00:20:10.719 --> 00:20:12.552
ANYONE WHO STARTS A CLINICAL
TRIAL WILL TELL YOU THEY DON'T
00:20:12.637 --> 00:20:14.253
KNOW WHAT'S GONNA HAPPEN.
00:20:14.356 --> 00:20:15.421
THEY KNOW WHAT SHOULD HAPPEN,
00:20:15.524 --> 00:20:18.224
BUT THE BIOLOGICAL
SYSTEM'S VERY COMPLICATED.
00:20:21.363 --> 00:20:23.196
DR. CARL JUNE: ABOUT TWO
WEEKS AFTER HE WAS TREATED,
00:20:23.281 --> 00:20:25.115
THEN HE STARTED HAVING FEVERS.
00:20:25.233 --> 00:20:27.099
AND EVERY DAY, IT WOULD
CREEP UP A LITTLE BIT.
00:20:27.202 --> 00:20:29.819
DOUG OLSON: I LITERALLY WOKE
UP ON A MONDAY MORNING WITH
00:20:29.905 --> 00:20:33.606
FEVERS, AND, AND, AND CHILLS,
AND FELT LIKE I HAD THE FLU.
00:20:36.995 --> 00:20:39.412
DR. DAVID PORTER: SO I REMEMBER
THIS, THIS PART QUITE VIVIDLY.
00:20:39.748 --> 00:20:41.664
I WAS WALKING ACROSS CAMPUS.
00:20:41.750 --> 00:20:43.249
I HAD A PAGER AT THAT TIME.
00:20:43.351 --> 00:20:45.919
MY PAGER WENT OFF AND IT WAS
THE LABORATORY AND IT SAID,
00:20:46.021 --> 00:20:48.805
"WE HAVE SOME CRITICAL LABS ON
YOUR PATIENT, DOUG OLSON."
00:20:48.924 --> 00:20:50.256
THERE WERE A
WHOLE BUNCH OF THINGS
00:20:50.342 --> 00:20:51.975
THAT WERE OUT OF WHACK.
00:20:52.093 --> 00:20:55.812
UM, YOUR CALCIUM, YOUR,
YOUR KIDNEY TESTS.
00:20:55.931 --> 00:20:57.814
AND I WRITE IT DOWN AND SAID,
"THANK YOU," AND I HANG UP.
00:20:57.933 --> 00:21:00.099
AND I'M SITTING OUTSIDE
THIS RECEPTION ROOM
00:21:00.185 --> 00:21:01.434
JUST KIND OF LOOKING AT IT.
00:21:01.520 --> 00:21:03.653
AND I SAID, "YOU KNOW, THIS IS
WHAT YOU SEE IN A PATIENT WHO
00:21:03.772 --> 00:21:06.305
HAS TUMOR LYSIS SYNDROME."
00:21:06.408 --> 00:21:07.941
DR. CARL JUNE: THE CAR T CELLS
00:21:08.026 --> 00:21:10.643
WERE ATTACKING THE TUMOR SO
VIOLENTLY THAT THE PATIENTS
00:21:10.745 --> 00:21:14.113
COULD GET FEVERS OF 103
TO 106 DEGREES FAHRENHEIT.
00:21:14.749 --> 00:21:16.482
VERY HIGH FEVERS.
00:21:16.585 --> 00:21:18.785
DOUG OLSON: AND IT
TURNED OUT THAT THE,
00:21:18.870 --> 00:21:23.089
THE PROBLEM WAS THAT THERE'S
SO MANY TUMOR CELLS DYING,
00:21:23.175 --> 00:21:25.542
THEY'RE JUST DUMPING ALL OF
THEIR CELLULAR CONTENTS
00:21:25.627 --> 00:21:26.926
INTO MY BLOODSTREAM.
00:21:27.028 --> 00:21:28.511
DR. CARL JUNE: SO LATER,
WE WERE ABLE TO
00:21:28.630 --> 00:21:29.996
PUT THAT TOGETHER.
00:21:30.098 --> 00:21:31.664
THAT WHAT WE WERE SEEING
WAS ACTUALLY GOOD NEWS.
00:21:31.766 --> 00:21:33.416
DOUG OLSON: THEY ESTIMATED
SOMETHING ON THE ORDER OF
00:21:33.501 --> 00:21:35.051
THREE OR FOUR POUNDS
OF CELLS WERE BEING
00:21:35.136 --> 00:21:39.189
WIPED OUT IN A MATTER OF,
OF, OF PROBABLY A WEEK.
00:21:40.308 --> 00:21:43.693
DR. CARL JUNE: THAT WAS, UM,
BECAUSE, YOU KNOW, SO WE THEN,
00:21:43.812 --> 00:21:47.814
UM, WITNESSED WHAT WAS THE
CYTOKINE-RELEASE SYNDROME BUT
00:21:47.899 --> 00:21:51.684
IT WAS, IT GAVE US THE
PROOF THAT IT REALLY WORKS.
00:21:52.320 --> 00:21:55.187
SO BECAUSE WE HAD INFUSED
THESE CELLS THREE WEEKS
00:21:55.290 --> 00:21:56.923
BEFORE AND NOTHING HAPPENED.
00:21:57.025 --> 00:22:01.694
AND THEN THREE WEEKS LATER, HE
WAS NOW FULL OF THESE T CELLS.
00:22:01.796 --> 00:22:04.230
I MEAN, WE COULD MEASURE THAT.
00:22:05.917 --> 00:22:07.967
AND THEN HE GOT THE FEVER
AND THE TUMOR WENT AWAY.
00:22:08.053 --> 00:22:11.504
SO IT GAVE US THE SCIENTIFIC
MECHANISM OF ACTION.
00:22:12.257 --> 00:22:15.925
HE, IN THAT ONE PATIENT, GAVE
US THE PROOF THAT THIS WORKED.
00:22:16.511 --> 00:22:19.062
AND, AND SO THAT GAVE US A
REAL CONFIDENCE THAT THE,
00:22:19.180 --> 00:22:21.264
THE CELLS WERE WORKING
AS WE WOULD HOPE.
00:22:21.349 --> 00:22:23.883
THAT IT'S ASSOCIATED WITH
THEIR PROLIFERATION AND THEN
00:22:23.985 --> 00:22:28.104
THEIR, THEIR FUNCTIONS
AS CAR CELLS.
00:22:30.759 --> 00:22:33.726
WITHIN THREE PATIENTS, WE
KNEW IN ADULTS IT WORKED.
00:22:33.828 --> 00:22:35.862
DR. DAVID PORTER: AND IT
MIGHT HAVE BEEN THAT MORNING
00:22:35.947 --> 00:22:38.748
THAT I CAME TO SEE
YOU IN THE HOSPITAL.
00:22:38.867 --> 00:22:41.167
STARTED LOOKING FOR
SOME LYMPH NODES,
00:22:41.253 --> 00:22:43.202
THE ONES YOU ALWAYS FEEL
WHEN YOU'RE SHAVING.
00:22:43.288 --> 00:22:44.454
AND, AND THEY WEREN'T THERE.
00:22:44.539 --> 00:22:45.755
DOUG OLSON: UH-UH.
00:22:45.874 --> 00:22:47.290
DR. DAVID PORTER: RIGHT?
00:22:47.375 --> 00:22:48.875
THEY, THEY WERE,
THEY WERE GONE.
00:22:48.960 --> 00:22:51.210
DOUG OLSON: I FORGET THE,
THEY DIDN'T USE THE WORD CURE.
00:22:51.296 --> 00:22:54.080
THEY, UM, IT WAS SOMETHING
CLOSE TO IT THOUGH.
00:22:54.766 --> 00:22:58.084
SCIENTISTS, CANCER,
SCIENTISTS TEND TO,
00:22:58.186 --> 00:23:00.386
TEND TO BE AND NEED TO
BE VERY CONSERVATIVE
00:23:00.472 --> 00:23:03.106
ABOUT MAKING CLAIMS.
00:23:04.859 --> 00:23:07.860
YOU KNOW, THE NEXT
WEEK, I WENT BACK, UH,
00:23:07.946 --> 00:23:09.946
FOR MY CHECK UP WITH
DAVID AND, AND HE,
00:23:10.065 --> 00:23:11.597
THAT'S WHEN HE
TOLD ME, HE SAID,
00:23:11.700 --> 00:23:14.534
"WE CAN'T FIND A
CANCER CELL ANYWHERE.
00:23:14.619 --> 00:23:15.702
NOT IN YOUR BONE MARROW.
00:23:15.787 --> 00:23:17.937
NOT IN YOUR BLOOD."
HE SAID, "WE DID THIS,
00:23:18.039 --> 00:23:20.940
THIS REALLY SENSITIVE TEST."
00:23:21.042 --> 00:23:23.910
HE SAID, "THE CANCER'S
COMPLETELY GONE."
00:23:26.081 --> 00:23:29.615
SO I STILL HAVE
THESE CAR T-19 CELLS,
00:23:29.718 --> 00:23:31.968
UM, SO I'M SORT OF
IMMUNIZED AGAINST THE
00:23:32.087 --> 00:23:34.887
CANCER IF IT WERE
EVER TO COME BACK.
00:23:34.973 --> 00:23:40.343
IT, IT CAN'T, UM,
BECAUSE THESE, UM,
00:23:43.398 --> 00:23:45.398
WHAT THEY CALL THE KILLER
CELLS, THE T CELLS,
00:23:45.483 --> 00:23:48.985
RECOGNIZE THIS TYPE OF CELL
AND WILL KILL IT IMMEDIATELY.
00:23:55.360 --> 00:23:59.028
THIS SEPTEMBER 13TH WILL
BE SIX YEARS CANCER-FREE.
00:24:02.667 --> 00:24:05.034
ZERO CANCER.
00:24:15.130 --> 00:24:20.800
¶ ¶
00:24:20.885 --> 00:24:24.721
YOU KNOW, TO HAVE YOUR LIFE
SAVED IN THAT WAY IS JUST,
00:24:26.141 --> 00:24:28.608
IT'S HARD TO WRAP
YOUR HEAD AROUND IT.
00:24:28.693 --> 00:24:31.227
I STILL HAVEN'T, YOU KNOW.
00:24:42.824 --> 00:24:45.124
NARRATOR: DESPITE THESE
MIRACULOUS RESULTS,
00:24:45.210 --> 00:24:48.378
DR. JUNE'S RESEARCH
FACED AN UNCERTAIN FUTURE.
00:24:52.133 --> 00:24:54.000
DR. CARL JUNE: THAT WAS VERY
DIFFICULT TO GET FUNDING FOR
00:24:54.552 --> 00:24:56.753
AND IT WAS ONLY FROM
PHILANTHROPY THAT WE'RE
00:24:56.838 --> 00:24:58.221
GONNA MAKE ENDS MEET.
00:24:58.339 --> 00:25:01.674
WE HAD, BASICALLY, A MOM AND
POP OPERATION HELD TOGETHER
00:25:01.760 --> 00:25:04.977
BARELY BY, BARELY BY THE
SHOESTRING TO PAY FOR
00:25:05.063 --> 00:25:06.979
EVERYTHING FROM THE
CLINICAL TRIALS,
00:25:07.065 --> 00:25:08.848
TO MAKING THESE VIRAL VECTORS,
00:25:08.933 --> 00:25:12.101
TO THE CELL MANUFACTURING,
UH, FACILITY.
00:25:13.405 --> 00:25:18.191
DR. BRUCE LEVINE: IN 2010, WE
TREATED THREE PATIENTS WITH
00:25:18.276 --> 00:25:23.029
ADVANCED LEUKEMIA WITH CHIMERIC
ANTIGEN RECEPTOR T CELLS.
00:25:23.114 --> 00:25:27.450
WE SAW DRAMATIC RESPONSES
WHERE POUNDS OF LEUKEMIA
00:25:27.535 --> 00:25:29.869
MELTED AWAY OVER
SEVERAL WEEKS.
00:25:30.505 --> 00:25:31.570
AND WE RAN OUT OF MONEY.
00:25:31.673 --> 00:25:34.290
DR. CARL JUNE: SO DAVID PORTER
AND I MET ONE DAY IN THE
00:25:34.375 --> 00:25:36.626
COFFEE SHOP ACTUALLY DOWN
RIGHT BELOW THIS BUILDING.
00:25:36.711 --> 00:25:39.912
IT WAS IN JANUARY,
ABOUT THREE MONTHS,
00:25:40.014 --> 00:25:41.914
FOUR MONTHS AFTER THEIR
FIRST THREE PATIENTS HAD BEEN
00:25:42.016 --> 00:25:45.184
TREATED AND TO STRATEGIZE
WHAT COULD WE DO.
00:25:45.270 --> 00:25:47.603
DR. BRUCE LEVINE: AND MADE
A DECISION TO PUBLISH THE
00:25:47.722 --> 00:25:50.589
RESULTS OF THOSE
FIRST THREE PATIENTS.
00:25:51.192 --> 00:25:53.759
DOUG OLSON: NORMALLY, YOU
DON'T PUBLISH ON THREE PATIENTS.
00:25:53.862 --> 00:25:55.445
THAT'S UNUSUAL.
00:25:55.563 --> 00:25:58.281
UM, AND THEY WEREN'T SO SURE
THAT THE MANUSCRIPT WOULD
00:25:58.399 --> 00:25:59.982
EVEN BE ACCEPTED.
00:26:00.068 --> 00:26:01.934
DR. CARL JUNE: BUT OUR
REPORT WAS ACCEPTED BY THE
00:26:02.036 --> 00:26:03.569
NEW ENGLAND JOURNAL OF MEDICINE,
00:26:03.655 --> 00:26:06.622
WHICH IS ONE OF THE MOST
AUGUST AND RESPECTED JOURNALS.
00:26:06.741 --> 00:26:08.908
AND THEN IT TRIGGERED
A FIRESTORM.
00:26:08.993 --> 00:26:11.377
I HAD THOUSANDS AND
THOUSANDS OF INQUIRIES.
00:26:11.463 --> 00:26:14.497
PEOPLE OFFERING MONEY
TO NOW MAKE SURE THE TRIAL
00:26:14.582 --> 00:26:15.915
WOULD GO FORWARD.
00:26:16.000 --> 00:26:17.917
AND THEN EVERYTHING
COMPLETELY CHANGED.
00:26:18.419 --> 00:26:19.785
NEWSCASTER: THERE IS SOME
GOOD NEWS TO REPORT IN THE
00:26:19.888 --> 00:26:20.953
FIGHT AGAINST CANCER.
00:26:21.055 --> 00:26:23.306
AN EXPERIMENTAL TREATMENT
FOR LEUKEMIA IS HAVING
00:26:23.424 --> 00:26:26.676
EXTRAORDINARY RESULTS
BEYOND ANY EXPECTATIONS.
00:26:27.428 --> 00:26:29.562
HOW OFTEN DO WE
GET TO SAY THAT?
00:26:30.598 --> 00:26:32.315
PRESIDENT OBAMA: TODAY, THE
DISCOVERIES TAKING PLACE IN
00:26:32.433 --> 00:26:35.351
OUR FEDERALLY FINANCED LABS
AND UNIVERSITIES COULD LEAD TO
00:26:35.436 --> 00:26:38.020
NEW TREATMENTS THAT
KILL CANCER CELLS,
00:26:38.106 --> 00:26:40.439
BUT LEAVE HEALTHY
ONES UNTOUCHED.
00:26:40.525 --> 00:26:41.991
NEWSCASTER: HOW GOOD WERE
THOSE RESULTS COMPARED
00:26:42.110 --> 00:26:43.576
TO YOUR EXPECTATIONS?
00:26:43.661 --> 00:26:45.745
DR. CARL JUNE: THE RESULTS
EXCEEDED OUR EXPECTATIONS
00:26:45.830 --> 00:26:47.947
QUITE A BIT.
00:26:48.032 --> 00:26:49.749
DR. DAVID PORTER: THIS
THERAPY AS IT IS RIGHT
00:26:49.834 --> 00:26:53.085
NOW REMAINS COMPLICATED.
00:26:53.171 --> 00:26:56.589
EVERY DOSE IS UNIQUE FOR
AN INDIVIDUAL PATIENT.
00:26:57.125 --> 00:27:00.510
IT IS THE EPITOME OF
PERSONALIZED MEDICINE.
00:27:00.628 --> 00:27:03.546
AND SO UNLIKE SOME OTHER
DRUG THERAPIES THAT GET FDA
00:27:03.631 --> 00:27:06.382
APPROVAL AND THEN THEY'RE IN
THE PHARMACY FOR ANYBODY TO
00:27:06.467 --> 00:27:09.385
PRESCRIBE AND USE, I THINK
THESE ARE GOING TO BE
00:27:09.470 --> 00:27:13.556
THERAPIES THAT HAVE TO BE
USED BY SPECIALIST PROVIDERS.
00:27:14.809 --> 00:27:18.144
IF I HAD TO COMPLETELY GUESS
AT WHAT MIGHT BE COMING IN THE
00:27:18.246 --> 00:27:21.230
FUTURE, ONE COULD ENVISION
THAT THE MANUFACTURING
00:27:21.316 --> 00:27:24.033
PROCESS BECOMES MORE
AND MORE AUTOMATED.
00:27:24.152 --> 00:27:28.037
AND THERE IS A LOT OF INTEREST
IN TRYING TO DEVELOP THESE
00:27:28.156 --> 00:27:32.691
CAR T CELLS THAT ARE UNIVERSAL,
A MORE ONE SIZE FITS ALL,
00:27:32.794 --> 00:27:37.213
SO YOU COULD GENERATE A
LARGE NUMBER OF THESE CELLS,
00:27:37.332 --> 00:27:39.966
FREEZE THEM AWAY
IN THE PHARMACY,
00:27:40.051 --> 00:27:41.500
AND THEN WHEN A
PATIENT COMES IN,
00:27:41.586 --> 00:27:44.036
YOU WILL HAVE PREMADE
CELLS THAT COULD BE USED
00:27:44.138 --> 00:27:45.888
FOR MANY PATIENTS.
00:27:46.007 --> 00:27:47.974
NARRATOR: UNIVERSAL
DONOR T CELLS COULD HELP
00:27:48.076 --> 00:27:50.893
MILLIONS OF PEOPLE,
00:27:51.012 --> 00:27:53.479
ESPECIALLY CHILDREN
WHOSE CANCER TREATMENTS
00:27:53.565 --> 00:27:56.148
ARE OFTEN COMPLICATED.
00:27:57.101 --> 00:27:59.952
THE PROBLEM IS, RIGHT NOW,
T CELL THERAPIES ARE
00:28:00.054 --> 00:28:02.554
LIKE ORGAN TRANSPLANTS.
00:28:02.657 --> 00:28:05.608
THEY REQUIRE COMPATIBILITY
BETWEEN DONOR AND PATIENT,
00:28:06.661 --> 00:28:09.495
OR BOTH THE HOST BODY AND
THE DONATED CELLS WILL
00:28:09.581 --> 00:28:11.731
REJECT THE TRANSFUSION.
00:28:11.833 --> 00:28:14.733
IN THE WORST-CASE SCENARIO,
THE DONATED IMMUNE CELLS WILL
00:28:14.836 --> 00:28:18.237
MISTAKE EVERY CELL AND TISSUE
IN THE RECIPIENT'S BODY AS A
00:28:18.339 --> 00:28:21.407
FOREIGN PATHOGEN, AND THEY
WILL MELT THE PATIENT FROM
00:28:21.509 --> 00:28:23.342
THE INSIDE-OUT.
00:28:23.428 --> 00:28:26.295
BUT WHAT IF WE COULD
GENETICALLY REPROGRAM DONOR
00:28:26.381 --> 00:28:29.632
T CELLS SO THEY COULD
WORK ON ANYONE?
00:28:37.624 --> 00:28:42.644
[SCREAMING]
00:28:48.101 --> 00:28:51.770
[SCREAMING]
00:28:59.580 --> 00:29:03.198
NARRATOR: DR. ANDRE CHOULIKA
FOUNDED CELLECTIS IN 1999,
00:29:04.384 --> 00:29:05.951
WITH THE SOLE
PURPOSE OF CREATING
00:29:06.036 --> 00:29:08.453
A GENOME ENGINEERING TECHNOLOGY.
00:29:09.022 --> 00:29:12.357
AT THE TIME, IT WAS CONSIDERED
PURE SCIENCE FICTION.
00:29:27.641 --> 00:29:30.942
BY 2014, CELLECTIS HAD THE
TOOLS TO EDIT INDIVIDUAL
00:29:31.028 --> 00:29:33.111
SEQUENCES OF DNA.
00:29:33.197 --> 00:29:35.947
THEY CAN ADD, TURN OFF,
OR CORRECT ANY ATTRIBUTE
00:29:36.049 --> 00:29:37.649
IN A GENETIC CODE.
00:29:37.734 --> 00:29:40.318
SCIENCE FICTION HAD
BECOME SCIENCE FACT.
00:29:42.072 --> 00:29:43.738
DR. ANDRE CHOULIKA: WE
STARTED THE COMPANY AS A
00:29:43.824 --> 00:29:45.123
GENE EDITING COMPANY.
00:29:45.209 --> 00:29:47.659
GENE EDITING IS THE WAY
TO MODIFY GENES AND CELLS.
00:29:47.744 --> 00:29:50.745
IT MEANS YOU CAN GO, EDIT
A GENE LIKE YOU WOULD EDIT
00:29:50.831 --> 00:29:54.633
NORMAL TEXTS, TEXT, BUT THIS
IS DONE REAL UNDER MOLECULE OF
00:29:54.718 --> 00:29:57.586
LIFE INSIDE THE CELLS
WHERE WE CAN, FOR EXAMPLE,
00:29:57.671 --> 00:30:01.339
REMOVE PORTION OF THE DNA
THAT IS MALFUNCTIONING
00:30:01.425 --> 00:30:04.342
AND REPLACE IT BY
SOMETHING THAT WORKS WELL.
00:30:05.546 --> 00:30:08.063
WITH GENE EDITING, YOU CAN
MODIFY GENES TO UNDERSTAND
00:30:08.181 --> 00:30:09.648
HOW DNA FUNCTIONS.
00:30:09.733 --> 00:30:12.901
SO FOR RESEARCH PURPOSES, YOU
CAN MODIFY GENES TO CREATE NEW
00:30:13.020 --> 00:30:17.355
SPECIES LIKE NEW CROPS OR YOU
CAN MODIFY GENES FOR PEOPLE
00:30:17.441 --> 00:30:19.858
THAT ARE ILL, THAT
HAVE GENETIC DEFECTS.
00:30:20.527 --> 00:30:24.362
SO THE INITIAL CONCEPT
WAS DEFINITELY NOT CANCER.
00:30:24.781 --> 00:30:27.415
TEN YEARS AFTER WE
STARTED THE COMPANY,
00:30:27.534 --> 00:30:29.734
MY CHIEF SCIENTIFIC
OFFICER, FRED,
00:30:29.836 --> 00:30:31.620
CAME IN MY OFFICE AND SAID,
00:30:31.705 --> 00:30:35.239
"ANDRE, I DISCUSSED WITH TWO
VERY BRILLIANT SCIENTISTS.
00:30:35.342 --> 00:30:39.044
ONE WAS CALLED CARL JUNE,
FAMOUS GUY IN THE CAR T SPACE,
00:30:39.546 --> 00:30:42.764
AND THE SECOND ONE WAS,
IS CALLED MICHEL SADELAIN,
00:30:42.883 --> 00:30:45.767
ALSO ANOTHER VERY FAMOUS
SCIENTIST IN THE CAR T SPACE."
00:30:45.886 --> 00:30:48.603
AND ME AT THIS TIME,
2010, I'VE NEVER HEARD
00:30:48.722 --> 00:30:52.857
THE WORD CAR OR T, SO
FRED STARTED EXPLAINING,
00:30:52.943 --> 00:30:56.594
CAR IS CHIMERIC ANTIGEN
RECEPTOR PUT IN T CELLS AND
00:30:56.697 --> 00:30:59.364
YOU USE THE T CELLS TO
DESTROY CANCER CELLS.
00:31:00.000 --> 00:31:02.817
AND THE CAR DRIVES THE T
CELLS AGAINST CANCER CELLS.
00:31:04.404 --> 00:31:08.490
THIS IS THE THING WHERE GENE
EDITING CAN BE TRANSFORMATIVE
00:31:08.575 --> 00:31:12.777
BECAUSE YOU CAN CONVERT A CELL
INTO REAL THERAPY THAT CAN BE
00:31:12.879 --> 00:31:15.330
USEFUL AND UNIVERSAL.
00:31:15.415 --> 00:31:17.999
AND WE SIGNED UP FOR THIS.
00:31:18.085 --> 00:31:20.618
NARRATOR: IN A LEAP OF FAITH,
CELLECTIS PIVOTED THEIR GENE
00:31:20.721 --> 00:31:25.056
EDITING TECHNOLOGY TO RECODE
THE DNA OF DONATED T CELLS
00:31:25.142 --> 00:31:28.009
INTO UNIVERSAL CAR T CELLS
00:31:28.095 --> 00:31:31.513
THEORETICALLY FIT
FOR ANY RECIPIENT.
00:31:32.566 --> 00:31:35.299
AFTER THE INITIAL
EFFORT PROVED A SUCCESS,
00:31:35.402 --> 00:31:38.687
THEY PREPARED FOR YEARS
OF CLINICAL TRIALS.
00:31:40.657 --> 00:31:42.607
DR. ANDRE CHOULIKA: WE
DIDN'T HAVE ANY INTENTION OF
00:31:42.693 --> 00:31:45.810
INJECTING THESE TYPE OF VIALS
TO PATIENTS BECAUSE
00:31:45.912 --> 00:31:48.312
WE NEEDED A LOT OF VIALS
TO BE ABLE TO FILE
00:31:48.415 --> 00:31:50.031
OUR CLINICAL TRIAL APPLICATION.
00:31:50.117 --> 00:31:52.500
AND THIS WAS
PLANNED TO BE DONE
00:31:52.619 --> 00:31:55.253
WITH UNIVERSITY COLLEGE LONDON.
00:31:59.343 --> 00:32:01.543
NARRATOR: BEFORE ANY NEW
MEDICATION OR THERAPY IS
00:32:01.628 --> 00:32:05.263
CONSIDERED SAFE AND EFFECTIVE,
IT MUST FIRST BE RIGOROUSLY
00:32:05.349 --> 00:32:08.550
TESTED THROUGH CLINICAL TRIALS.
00:32:11.471 --> 00:32:13.671
THESE TRIALS ARE FUNDAMENTAL
IN DETERMINING AN
00:32:13.774 --> 00:32:16.841
EXPERIMENTAL TREATMENT'S
DOSAGE AND SAFETY AND
00:32:16.943 --> 00:32:20.228
TO IDENTIFY ANY
POSSIBLE SIDE EFFECTS.
00:32:20.731 --> 00:32:22.614
AT THE UNIVERSITY
COLLEGE LONDON,
00:32:22.699 --> 00:32:25.450
GREAT ORMOND STREET
INSTITUTE OF CHILD HEALTH,
00:32:25.535 --> 00:32:28.403
PROFESSOR WASEEM QASIM WAS
WORKING WITH CELLECTIS AS THE
00:32:28.488 --> 00:32:32.123
PRINCIPAL INVESTIGATOR, TAKING
THE UNIVERSAL CAR T CELLS
00:32:32.209 --> 00:32:34.876
FROM THE LAB TO TRIALS.
00:32:34.995 --> 00:32:37.328
NORMALLY, THIS PROCESS
CAN TAKE OVER A DECADE,
00:32:37.414 --> 00:32:40.198
WITH NEARLY ENDLESS
LAYERS OF APPROVAL.
00:32:40.584 --> 00:32:42.917
PROF WASEEM QASIM: SO OUR
QUESTIONS WERE WHAT DO YOU DO
00:32:43.003 --> 00:32:45.637
IF YOUR PATIENT IS ALREADY SO
UNWELL THAT YOU CAN'T COLLECT
00:32:45.722 --> 00:32:47.889
CELLS, HAS HAD SO MUCH
CHEMOTHERAPY THAT THERE'S NO
00:32:48.008 --> 00:32:50.308
WHITE BLOOD CELLS LEFT TO
COLLECT THAT YOU THINK
00:32:50.394 --> 00:32:51.709
ARE GONNA BE USEFUL?
00:32:51.812 --> 00:32:54.479
UM, HOW DO YOU DO THIS PROCESS
IN A WAY THAT
00:32:54.564 --> 00:32:57.215
CAN BE DONE QUICKLY AND
DELIVERED BACK TO THE PATIENT
00:32:57.317 --> 00:32:58.483
IN A TIMELY MANNER?
00:32:58.568 --> 00:33:02.937
AND THE ANSWER TO THAT IS
PERHAPS BEING ABLE TO USE A,
00:33:03.607 --> 00:33:07.442
A PRODUCT, TO SELL PRODUCT
THAT'S BEING MADE BEFOREHAND
00:33:07.527 --> 00:33:10.228
THAT CAN BE GIVEN BACK
TO MULTIPLE PATIENTS.
00:33:10.330 --> 00:33:12.113
NOW IN ORDER TO DO THAT,
WE HAVE TO OVERCOME
00:33:12.199 --> 00:33:14.232
THE BARRIER OF TRANSPLANTATION.
00:33:14.334 --> 00:33:19.421
WHICH MEANS, IF I PUT MY CELLS
INTO A NON-MATCHED INDIVIDUAL,
00:33:20.373 --> 00:33:23.425
THE CELLS, FIRSTLY, WILL
WANT TO REACT AGAINST THAT
00:33:23.543 --> 00:33:25.744
INDIVIDUAL BECAUSE THEY'LL
KNOW THE INDIVIDUAL'S FOREIGN,
00:33:25.846 --> 00:33:28.379
AND SECONDLY, THE PERSON
RECEIVING THE CELLS WILL TRY
00:33:28.465 --> 00:33:30.348
AND REJECT THEM BECAUSE
THEY KNOW THAT THE
00:33:30.434 --> 00:33:32.684
CELLS ARE NOT THEIR OWN.
00:33:32.769 --> 00:33:34.969
NARRATOR: IN AFFILIATION
WITH PROFESSOR QASIM,
00:33:35.055 --> 00:33:38.022
DR. PAUL VEYS WORKS ON THE
FRONTLINE WITH PATIENTS WHO
00:33:38.108 --> 00:33:41.259
DESPERATELY NEED NEW
CANCER TREATMENT OPTIONS.
00:33:41.361 --> 00:33:42.777
DR. PAUL VEYS: I'LL HAVE
TREATED WELL OVER
00:33:42.896 --> 00:33:46.397
3,000 PATIENTS AND AT LEAST 600
OF THOSE WILL HAVE GONE WRONG.
00:33:47.117 --> 00:33:49.818
SO THERE'S A LOT OF PATIENTS
THAT WE LOSE, IT'S UNSUCCESSFUL.
00:33:50.904 --> 00:33:54.072
AND YOU'VE GOT TO BE ABLE
TO COME IN THE NEXT DAY.
00:33:58.462 --> 00:34:02.497
EVEN FROM OUR FAILURES,
WE'VE LEARNED LOTS.
00:34:03.049 --> 00:34:06.000
AND IF WE HADN'T GONE
THROUGH THOSE FAILURES,
00:34:06.086 --> 00:34:08.586
WE WOULDN'T BE HAVING SOME OF
THE SUCCESSES WE HAVE TODAY.
00:34:08.672 --> 00:34:09.954
HAS YOUR CHEST
ALWAYS BEEN GOOD?
00:34:10.056 --> 00:34:11.339
YOU'VE NOT HAD ANY
BIG CHEST INFECTIONS?
00:34:11.424 --> 00:34:12.456
WOMAN: NO, NOT AT ALL.
00:34:12.559 --> 00:34:14.809
DR. PAUL VEYS: NO.
00:34:16.429 --> 00:34:17.628
LET'S WARM IT UP.
00:34:17.731 --> 00:34:20.515
SIT FORWARD AGAIN, PERFECT.
00:34:21.485 --> 00:34:24.402
OKAY, BIG BREATHS.
00:34:26.773 --> 00:34:29.240
NARRATOR: ONE OF THE MOST
TRYING CASES PAUL VEYS EVER
00:34:29.326 --> 00:34:31.943
FACED WAS 12-MONTH-OLD
LAYLA RICHARDS.
00:34:33.446 --> 00:34:34.863
MOTHER: WHEN SHE WAS
THREE MONTHS OLD,
00:34:34.948 --> 00:34:37.499
WE TOOK HER TO THE DOCTOR'S
AND JUST TOLD THEM,
00:34:37.617 --> 00:34:39.284
SHE JUST WASN'T HERSELF.
00:34:39.369 --> 00:34:41.619
HER HEARTBEAT WAS
A BIT FAST, HER,
00:34:41.705 --> 00:34:45.390
SHE HAD A HIGH PITCHED CRY,
AND SHE HAD GONE OFF OF
00:34:45.492 --> 00:34:46.891
HER MILK COMPLETELY.
00:34:46.993 --> 00:34:50.044
AND WITHIN HALF AN HOUR, WE
WERE TOLD SHE HAD LEUKEMIA AND
00:34:50.130 --> 00:34:52.163
THERE WAS A CATS AMBULANCE
COMING TO TAKE US TO GREAT
00:34:52.265 --> 00:34:55.049
ORMOND STREET HOSPITAL TO
START TREATMENT IMMEDIATELY.
00:34:55.969 --> 00:34:57.852
FATHER: THEY SAID IT WAS A
VERY AGGRESSIVE LEUKEMIA AND
00:34:57.971 --> 00:35:01.973
WE'RE GONNA TELL YOU
INFORMATION BIT BY BIT.
00:35:03.527 --> 00:35:06.177
DR. PAUL VEYS: SHE HAD
A TERRIBLE LEUKEMIA.
00:35:06.279 --> 00:35:10.148
WE CALL IT, UH, AN INFANT
LEUKEMIA AND INFANT LEUKEMIA
00:35:10.483 --> 00:35:12.183
IS ALWAYS BAD NEWS.
00:35:12.285 --> 00:35:14.819
AND HER DISEASE WAS
PARTICULARLY BAD NEWS BECAUSE
00:35:14.905 --> 00:35:18.489
EVEN BEFORE A MONTH HAD PASSED
AFTER HER TRANSPLANTS,
00:35:18.575 --> 00:35:21.859
UH, WE COULD SEE HER
DISEASE COMING BACK.
00:35:22.913 --> 00:35:25.630
SO WE WERE THEN IN A VERY,
VERY DIFFICULT POSITION AND
00:35:25.715 --> 00:35:28.883
WE'VE NEVER MADE
ANYBODY BETTER FROM
00:35:29.002 --> 00:35:31.252
THAT POINT PREVIOUSLY.
00:35:31.638 --> 00:35:34.538
SO IF YOU RELAPSE VERY
EARLY AFTER TRANSPLANTS,
00:35:34.641 --> 00:35:37.926
USUALLY THE RIGHT DECISION
IS TO TRY AND GET THEM HOME.
00:35:38.011 --> 00:35:40.311
SOMETIMES, WITH SOME
GENTLE TREATMENTS,
00:35:40.397 --> 00:35:43.815
BUT MAINLY TREATING THEIR,
THEIR PAIN OR THEIR SICKNESS.
00:35:43.900 --> 00:35:45.716
FATHER: FOR ME, AS A PARENT,
THAT'S NOT AN OPTION.
00:35:45.819 --> 00:35:47.602
MOTHER: DIDN'T AGREE WITH
GOING HOME TO DO NOTHING.
00:35:47.687 --> 00:35:49.220
WE WANTED TO TRY IT.
00:35:49.322 --> 00:35:50.989
IT WAS, WE DIDN'T
WANT NO WHAT IFS.
00:35:51.074 --> 00:35:53.858
WE WANNA KNOW THAT WE'VE
TRIED EVERYTHING FOR HER.
00:35:53.944 --> 00:35:55.994
DR. PAUL VEYS: AND WITH THE,
WITH THE PARENTS ABSOLUTELY
00:35:56.079 --> 00:36:00.114
REFUSING REPEATEDLY, I ASKED
OUR COLLEAGUES IN THE LAB,
00:36:00.200 --> 00:36:04.786
PROFESSOR QASIM, WHETHER HE
HAD ANY THIRD PARTY T CELLS
00:36:04.871 --> 00:36:07.755
THAT WE MIGHT BE ABLE TO
USE IN THIS SITUATION.
00:36:08.258 --> 00:36:09.507
DR WASEEM QASIM: AND SO
HE RANG ME AND SAID,
00:36:09.593 --> 00:36:12.243
"WELL, IS THAT NEW THERAPY
YOU GUYS ARE WORKING ON,
00:36:12.345 --> 00:36:15.296
THE UNIVERSAL THERAPY, HOW
LONG WILL IT BE BEFORE IT'S
00:36:15.382 --> 00:36:16.714
READY FOR USE?"
00:36:16.816 --> 00:36:18.349
I SAID, "WELL, LOOK,
ACTUALLY THE, THE,
00:36:18.435 --> 00:36:21.219
THE TRIAL IS PROBABLY STILL A
YEAR AWAY BECAUSE WE HAVE TO
00:36:21.304 --> 00:36:24.856
COMPLETE, UH, VARIOUS TESTING
ON THE PRODUCTS WE'VE MADE,
00:36:24.941 --> 00:36:27.591
WE HAVE TO GO TO THE
REGULATOR TO GET APPROVAL.
00:36:27.694 --> 00:36:30.612
REALISTICALLY, YOU'RE TALKING
12 MONTHS, MAYBE LONGER."
00:36:30.730 --> 00:36:32.096
DR. PAUL VEYS:
WE HAVE WHAT'S CALLED A
00:36:32.198 --> 00:36:34.532
SPECIALS LICENSE HERE,
WHICH IS FAIRLY UNUSUAL,
00:36:34.618 --> 00:36:36.200
WHICH ALLOWS US
TO DO THESE VERY,
00:36:36.286 --> 00:36:39.787
VERY EXPERIMENTAL PROCEDURES
OFF A FORMAL STUDY.
00:36:39.906 --> 00:36:43.607
IT ALLOWS YOU TO TREAT ONE OR
TWO PATIENTS OFF THESE STUDIES
00:36:43.710 --> 00:36:45.944
BECAUSE TO GET IT THROUGH
ON A FORMAL STUDY WOULD'VE
00:36:46.046 --> 00:36:47.462
TAKEN MANY MONTHS.
00:36:47.580 --> 00:36:51.182
AND LAYLA, YOU KNOW,
SHE HAD DAYS OR WEEKS.
00:36:51.284 --> 00:36:53.685
UH, SO I SAID, "LOOK, DO YOU
HAVE ANYTHING THAT'S EVEN
00:36:53.787 --> 00:36:58.256
VAGUELY CLOSE TO BEING USED
IN THE CLINICAL SITUATION?"
00:36:58.925 --> 00:37:01.309
AND THAT WAS JUST A
VERY SHORT EMAIL I SENT.
00:37:01.428 --> 00:37:03.845
EXPECTING OF COURSE,
DON'T BE SILLY.
00:37:04.264 --> 00:37:06.464
DR WASEEM QASIM: AND I, I
REMEMBER RESPONDING TO HIM AND
00:37:06.566 --> 00:37:08.232
SAYING, "ACTUALLY,
IT'S NOT A MAD IDEA.
00:37:08.318 --> 00:37:12.487
IT'S A VERY CALCULATED,
STRATEGIC WAY OF DOING THIS
00:37:12.605 --> 00:37:13.855
TYPE OF TREATMENT.
00:37:13.940 --> 00:37:16.741
AND AS IT HAPPENS, THE
CELLS WE'VE MADE ARE READY,
00:37:16.826 --> 00:37:20.745
BUT WE'LL NEED TO GO AND ASK THE
PERMISSION OF THE SPONSOR,"
00:37:20.830 --> 00:37:23.481
WHICH IS, WAS
CELLECTIS AT THAT TIME.
00:37:23.917 --> 00:37:24.999
DR. ANDRE CHOULIKA: SO
WE STARTED THINKING,
00:37:25.118 --> 00:37:26.451
WHAT SHOULD WE DO?
00:37:26.536 --> 00:37:28.536
HE TRIES IT AND WE'LL
KNOW IF IT WORKS OR NOT.
00:37:28.621 --> 00:37:30.204
MAYBE THE VIAL CAN BE TOXIC.
00:37:30.290 --> 00:37:32.490
MAYBE CAN KILL THE GIRL
BECAUSE OF COURSE ALL THE
00:37:32.592 --> 00:37:36.827
WARNINGS WERE YOU MIGHT INDUCE
THIS GRAFT-VERSUS-HOST DISEASE
00:37:36.930 --> 00:37:39.497
THAT CAN MELT DOWN THE PATIENT
FROM THE INSIDE AND KILL HIM.
00:37:39.599 --> 00:37:43.935
A NINE-MONTH-OLD BABY, IMAGINE
THIS, YOU DON'T WANNA DO THIS.
00:37:44.020 --> 00:37:45.053
DR. PAUL VEYS: THERE WERE
MANY OTHERS THAT SAID,
00:37:45.138 --> 00:37:46.187
"DON'T DO THIS.
00:37:46.306 --> 00:37:50.191
THIS IS TOO EXPERIMENTAL,
REPUTATIONS WERE AT RISK."
00:37:50.310 --> 00:37:52.777
DR. ANDRE CHOULIKA: WE'VE
BEEN INVESTING ALL OUR ENERGY.
00:37:52.862 --> 00:37:56.197
15 YEARS HERE TO
TRY TO SAVE PEOPLE.
00:37:57.117 --> 00:38:00.618
IF FOR THE FIRST
OCCASION WE SAY NO,
00:38:00.704 --> 00:38:03.020
THEN WHY ARE WE DOING THIS?
00:38:03.123 --> 00:38:04.288
SO I SAID YES.
00:38:04.374 --> 00:38:07.658
THE BOARD TOOK THE DECISION
TO BACK THIS UNANIMOUSLY
00:38:07.744 --> 00:38:09.026
IN THE COMPANY.
00:38:09.129 --> 00:38:11.662
EVERYONE WAS SAYING, "SURE,
THIS IS OUR MISSION IS
00:38:11.748 --> 00:38:13.297
TO TRY TO SAVE PEOPLE."
00:38:13.383 --> 00:38:14.999
DR. PAUL VEYS: SO BECAUSE THESE,
00:38:15.085 --> 00:38:18.086
THESE CELLS WERE COMPLETELY
UNIVERSAL AND NOT MATCHED TO
00:38:18.171 --> 00:38:20.888
LAYLA AT ALL, WE WERE
VERY WORRIED ABOUT THESE,
00:38:21.007 --> 00:38:22.590
THESE CELLS REJECTING
IMMEDIATELY WHEN WE
00:38:22.675 --> 00:38:23.891
PUT THEM IN.
00:38:24.010 --> 00:38:27.178
SO WE HAD TO REMOVE ANY REMNANTS
OF LAYLA'S IMMUNE SYSTEM.
00:38:27.680 --> 00:38:28.930
SHE DIDN'T HAVE MUCH
BECAUSE, OF COURSE,
00:38:29.015 --> 00:38:31.048
SHE'D JUST BEEN
THROUGH TRANSPLANTS AND
00:38:31.151 --> 00:38:32.049
SO MUCH TREATMENT.
00:38:32.152 --> 00:38:33.901
BUT THERE WAS STILL
PARTS ENOUGH LEFT THERE,
00:38:34.020 --> 00:38:36.270
SO WE HAD TO GIVE
SOME, SOME DRUGS,
00:38:36.356 --> 00:38:40.024
SOME CHEMOTHERAPY TO REMOVE
ANY REMAINING IMMUNITY
00:38:40.276 --> 00:38:41.359
THAT SHE HAD.
00:38:41.444 --> 00:38:43.694
THAT TAKES ABOUT A WEEK.
00:38:44.798 --> 00:38:47.115
THE IDEA WAS SHE
HAD NO RESISTANCE,
00:38:47.200 --> 00:38:50.568
AND THEN THE CELLS WERE
GIVEN, IT'S JUST ONE VIAL.
00:38:50.670 --> 00:38:53.788
COMES TO THE BEDSIDE,
IT'S DEFROSTED, GOES IN.
00:38:53.873 --> 00:38:56.457
UH, AND THEN WE WAIT.
00:38:57.544 --> 00:39:00.428
NARRATOR: THE TEAM WATCHED FOR
ANY SIGN OF THE HIGH FEVERS
00:39:00.547 --> 00:39:02.847
AND OTHER SIDE EFFECTS
THEY EXPECTED TO COME AFTER
00:39:02.932 --> 00:39:06.100
INJECTING THE
ENGINEERED T CELLS.
00:39:06.469 --> 00:39:08.469
BUT NOTHING HAPPENED.
00:39:08.555 --> 00:39:09.720
HAD IT FAILED?
00:39:15.270 --> 00:39:21.441
¶ ¶
00:39:25.831 --> 00:39:27.414
DR WASEEM QASIM: BEEN
QUITE A TENSE MONTH.
00:39:27.499 --> 00:39:31.785
BEEN TENSE BECAUSE WE WERE
EXPECTING SIDE EFFECTS.
00:39:31.870 --> 00:39:33.920
WE HAD ON OUR BLOOD TEST
EVIDENCE THAT WE COULD SEE THE
00:39:34.006 --> 00:39:36.322
CELLS IN THE BLOOD SYSTEM,
BUT WHY WASN'T
00:39:36.425 --> 00:39:37.657
SHE GETTING MORE UNWELL?
00:39:37.759 --> 00:39:39.960
SHE SHOULD BE
DEVELOPING TEMPERATURES.
00:39:40.045 --> 00:39:42.212
DR. PAUL VEYS: WE KNOW THAT
SOMETIMES IF CHILDREN HAVE
00:39:42.297 --> 00:39:45.515
THESE SORT OF THERAPIES
WITH A LOT OF DISEASE, UH,
00:39:45.634 --> 00:39:48.969
WITHIN FOUR, FIVE, SIX DAYS,
THEY CAN GET VERY SICK AS THE
00:39:49.054 --> 00:39:52.505
CELLS START TO ATTACK,
RASHES, FEEL VERY UNWELL.
00:39:53.442 --> 00:39:56.109
AND SOMETIMES REQUIRED TO
GO TO INTENSIVE CARE, UM,
00:39:56.562 --> 00:39:59.479
JUST TO GET OVER THAT WHAT
WE CALL CYTOKINE STORM.
00:39:59.565 --> 00:40:01.031
THAT DIDN'T HAPPEN IN LAYLA.
00:40:01.149 --> 00:40:02.399
DR WASEEM QASIM: UH, BECAUSE
NONE OF THAT HAPPENED,
00:40:02.484 --> 00:40:04.234
WE WERE ANXIOUS THAT
MAYBE THERE HADN'T BEEN
00:40:04.319 --> 00:40:05.518
AN ANTI-LEUKEMIC EFFECT.
00:40:05.621 --> 00:40:08.855
SO THE FIRST TIME POINT WE
WERE REALLY SURE THAT THE
00:40:08.957 --> 00:40:11.875
CELLS HAD REMOVED THE
REMAINING LEUKEMIA CELLS WAS
00:40:11.994 --> 00:40:14.661
WHEN WE LOOKED IN THE BONE
MARROW AT THE ONE MONTH MARK
00:40:14.746 --> 00:40:16.162
AND DIDN'T FIND ANY.
00:40:16.248 --> 00:40:18.331
DR. PAUL VEYS: WE, WE WERE
PRETTY EXCITED BY THAT POINT,
00:40:18.417 --> 00:40:21.301
UM, BECAUSE AS WELL AS
DETECTING NO DISEASE,
00:40:21.386 --> 00:40:23.870
WE ALSO COULD SHOW THAT THE
CELLS WERE STILL PRESENT.
00:40:24.590 --> 00:40:27.206
THEY HADN'T BEEN REJECTED,
AND IF THEY WEREN'T REJECTED,
00:40:27.309 --> 00:40:30.093
IT MEANS THEY WERE SORT
OF WHIZZING AROUND HER
00:40:30.178 --> 00:40:32.395
DOING THE JOB.
00:40:32.514 --> 00:40:37.567
FATHER: SHE WAS SO WEAK
BEFORE THIS TREATMENT AND
00:40:37.686 --> 00:40:38.818
IT'S JUST HORRIBLE.
00:40:38.904 --> 00:40:40.353
IT'S HORRIBLE AND
I'M JUST THANKFUL.
00:40:40.439 --> 00:40:41.821
IT'S A MIRACLE.
00:40:41.907 --> 00:40:43.907
DR. PAUL VEYS: THERE WERE
MANY, MANY CHALLENGES,
00:40:44.026 --> 00:40:45.909
BUT THINGS JUST
SEEM TO GO OUR WAY.
00:40:46.028 --> 00:40:48.945
AND LAYLA IS JUST SO TOUGH.
00:40:50.699 --> 00:40:54.200
SO I GUESS SHE ALSO HAS THE,
THE PARENTS' DETERMINATION
00:40:54.286 --> 00:40:55.252
AND WILL POWER.
00:40:55.370 --> 00:40:56.870
MOTHER: THERE'S ALWAYS
GOT TO BE A FIRST.
00:40:56.955 --> 00:40:58.288
WE BEGGED THEM
TO TRY SOMETHING.
00:40:58.373 --> 00:41:01.341
HOW WOULD YOU KNOW IF YOU
NEVER TRY AND HERE'S THE FIRST.
00:41:01.426 --> 00:41:03.209
YEAH.
00:41:05.514 --> 00:41:06.913
DR. ANDRE CHOULIKA:
IT BROUGHT ME TEARS.
00:41:07.015 --> 00:41:08.882
IT WAS SO MUCH, LIKE, EMOTION
FOR ME BECAUSE I SAID,
00:41:08.967 --> 00:41:10.433
"OKAY, WELL, WE TOOK
THE RIGHT DECISION."
00:41:10.552 --> 00:41:15.639
SHE'S HERE AND LIKE, UH,
LAUGHING AROUND AND, LIKE,
00:41:15.724 --> 00:41:17.941
REALLY IT'S AN
IMPORTANT THING FOR ME.
00:41:18.060 --> 00:41:20.393
AND SAY, "OKAY, WELL, EVEN
IF IT WORKED ONE TIME,
00:41:20.479 --> 00:41:23.363
I THINK THAT ALL MY LIFE WORTH
SOMETHING IF SHE HAVE A LIFE."
00:41:23.815 --> 00:41:25.649
TWO THINGS IMPORTANT IN LIFE.
00:41:25.734 --> 00:41:27.951
GOOD HEALTH, HAPPINESS, PERIOD.
00:41:28.320 --> 00:41:30.987
NOTHING ELSE.
00:41:33.241 --> 00:41:35.108
DR. CARL JUNE: AT THIS
POINT IN THE UNITED STATES,
00:41:35.210 --> 00:41:39.212
ONLY ABOUT 10% OF ADULTS GO
ON CLINICAL TRIALS FOR CANCER
00:41:40.215 --> 00:41:42.582
BECAUSE IT COSTS THEM
MONEY TO BE ON THE TRIAL.
00:41:42.684 --> 00:41:45.635
SOMETIMES PEOPLE COME ACROSS
COUNTRY AND THEY HAVE TO STAY
00:41:45.754 --> 00:41:47.971
HERE REALLY FOR A
MONTH ON OUR TRIAL.
00:41:48.090 --> 00:41:49.973
AND SOME OF THEM HAVE COME
IN RVS AND JUST SLEPT
00:41:50.092 --> 00:41:51.624
IN OUR PARKING LOT.
00:41:51.727 --> 00:41:58.098
IT'S, UM, UH, SO, UM, UM, BUT
THE SYSTEM DOESN'T HAVE
00:41:58.767 --> 00:42:00.317
TO BE THAT WAY.
00:42:00.435 --> 00:42:04.154
WHICH IS MOST PATIENTS ARE
NOT ON CANCER, UH, TRIALS, UM,
00:42:04.272 --> 00:42:06.305
EVEN THOUGH MOST PATIENTS
ARE DESTINED TO DIE.
00:42:06.692 --> 00:42:08.641
I MEAN, IF IT'S, YOU KNOW,
A METASTATIC TUMOR.
00:42:08.744 --> 00:42:11.578
SO THEY SHOULD BE ON TRIALS.
00:42:11.663 --> 00:42:13.479
NARRATOR: EVEN WITH
THE INITIAL SUCCESS OF
00:42:13.582 --> 00:42:16.616
PERSONALIZED AND
UNIVERSAL CAR T CELLS,
00:42:16.702 --> 00:42:19.619
THERE IS STILL THE CRUEL
REALITY THAT DELIVERING THESE
00:42:19.705 --> 00:42:22.956
TREATMENTS FROM THE LAB TO
PATIENTS IN CLINICAL TRIALS
00:42:23.041 --> 00:42:26.209
REMAINS MONUMENTAL,
BUT NOT IMPOSSIBLE.
00:42:28.380 --> 00:42:29.846
DR. CARL JUNE: I MEAN,
I HATE CANCER.
00:42:29.965 --> 00:42:32.832
I THINK ALMOST EVERYONE
HAS HAD SOME, YOU KNOW,
00:42:32.934 --> 00:42:36.136
INVOLVEMENT EITHER
FRIENDS OR LOVED ONES.
00:42:36.221 --> 00:42:38.171
MY DAD DIED OF LUNG
CANCER A FEW YEARS AGO,
00:42:38.273 --> 00:42:42.642
BUT MY FIRST WIFE AT AGE
41, UM, HAD OVARIAN CANCER.
00:42:43.612 --> 00:42:46.212
AND SO I, I ACTUALLY TOOK CARE
OF HER FOR ABOUT FIVE YEARS,
00:42:46.314 --> 00:42:49.249
UM, AND SHE PASSED
AWAY IN 2001.
00:42:50.569 --> 00:42:53.653
AND IT CHANGED MY LIFE
FOREVER, I'LL TELL YOU THAT.
00:42:54.289 --> 00:42:58.241
UM, IT, UH, AND
PROBABLY FOR THE GOOD.
00:42:59.327 --> 00:43:01.211
UM, THERE'S A BIG
SILVER LINING.
00:43:01.329 --> 00:43:04.130
UM, IT MADE ME
MORE COMPASSIONATE.
00:43:04.633 --> 00:43:07.333
BECAUSE AT THAT TIME,
I WAS WORKING ON CANCER
00:43:07.419 --> 00:43:11.054
IMMUNOTHERAPY AS WELL AS OUR
HIV THERAPY AND I FOUND OUT
00:43:11.173 --> 00:43:13.973
HOW HARD IT WAS TO GET THAT
INTO TRIALS THAT WOULD TREAT
00:43:14.059 --> 00:43:15.475
MY WIFE, CINDY.
00:43:15.560 --> 00:43:18.711
WHEN YOU ACTUALLY WANNA TREAT
A PATIENT AND DO THAT AS A
00:43:18.814 --> 00:43:21.681
TEST, DOES SOMETHING WORK
OR NOT, IT'S A LOT HARDER.
00:43:22.150 --> 00:43:23.650
WOMAN: SAMPLE, YOU CAN SEE.
00:43:23.735 --> 00:43:26.686
DR. CARL JUNE: THERE WERE
MANY, MANY BARRIERS TO
00:43:26.772 --> 00:43:27.854
EARLY STAGE TRIALS.
00:43:27.939 --> 00:43:31.191
IT TAKES A LOT OF COMMITMENT
AND YEARS OF LASER FOCUS.
00:43:35.247 --> 00:43:36.863
MICHAEL MROZ: SO I THINK
THE REGULATORY SYSTEM
00:43:36.948 --> 00:43:38.998
THAT WE'RE TRYING TO WORK ON...
00:43:42.621 --> 00:43:46.423
DR. DAVID PORTER: THERE ARE
LIKELY TO BE SOME CANCERS THAT
00:43:46.541 --> 00:43:49.426
RESPOND TO ACTIVATING
THE IMMUNE CELLS AND THERE ARE
00:43:49.544 --> 00:43:52.011
LIKELY TO BE SOME
CANCERS WHERE THAT'S,
00:43:52.097 --> 00:43:53.913
THAT'S NOT THE
WAY TO KILL THEM.
00:43:54.015 --> 00:43:57.267
THE IMMUNE CELLS AREN'T GOING
TO KILL EVERY TYPE OF CANCER.
00:43:58.303 --> 00:44:00.520
FOR THOSE WHERE IT'S EFFECTIVE,
00:44:00.605 --> 00:44:03.973
IT'S, IT'S BEEN JUST AN
INCREDIBLE ADVANCE.
00:44:04.609 --> 00:44:06.926
WE NOW HAVE EFFECTIVE
THERAPIES WHERE
00:44:07.028 --> 00:44:09.629
THERE WAS NOTHING.
00:44:09.731 --> 00:44:12.649
BUT IT WON'T WORK FOR EVERY
TYPE OF CANCER CERTAINLY.
00:44:13.869 --> 00:44:16.736
I DEAL WITH LEUKEMIA EVERY DAY
AND IT'S AWFUL AND IT'S LOUSY.
00:44:17.706 --> 00:44:18.872
WOMAN: GOOD?
00:44:18.957 --> 00:44:20.606
MAN: GRAB MY (INAUDIBLE)
IN HERE, PLEASE.
00:44:20.709 --> 00:44:22.608
MICHAEL MROZ: I TELL 'EM
FROM THE VERY BEGINNING,
00:44:22.711 --> 00:44:23.626
JUST BE FRANK WITH ME.
00:44:23.745 --> 00:44:24.627
JUST COME RIGHT OUT
AND TELL ME EVERYTHING.
00:44:24.746 --> 00:44:26.796
DON'T HOLD NO PUNCHES,
JUST GIVE IT TO ME.
00:44:27.415 --> 00:44:28.998
DR. DAVID PORTER: FEEL ANYTHING.
00:44:29.084 --> 00:44:31.634
I DEAL WITH PEOPLE WHO
ARE IN THIS VERY DARK PLACE.
00:44:31.753 --> 00:44:34.287
SOMETIMES THEY
FEEL VERY ALONE.
00:44:34.389 --> 00:44:36.306
NARRATOR: MICHAEL HAS BEEN
FACING THAT DARKNESS WITH
00:44:36.424 --> 00:44:39.225
CONVENTIONAL TREATMENT
FOR NEARLY TWO DECADES.
00:44:39.928 --> 00:44:42.979
HE IS NOT SICK ENOUGH FOR HIS
DOCTORS TO RISK GIVING HIM THE
00:44:43.098 --> 00:44:45.398
STILL EXPERIMENTAL
NEW T CELL THERAPIES.
00:44:46.601 --> 00:44:47.934
MICHAEL MROZ: YOU'RE, YOU'RE
THE ONLY ONE THAT KNOWS
00:44:48.019 --> 00:44:49.302
HOW YOU FEEL.
00:44:49.404 --> 00:44:52.939
IT, IT, IT CAN BE PRETTY BAD
WHEN YOU'RE CONSTANTLY SICK.
00:44:53.692 --> 00:44:55.158
YOU KNOW, WHEN YOU'RE
CONSTANTLY JUST
00:44:55.277 --> 00:44:56.776
SICK AND SICK AND SICK.
00:44:58.146 --> 00:44:59.496
DR. DAVID PORTER: HOLLER
IF YOU NEED ANYTHING, OKAY?
00:44:59.614 --> 00:45:00.980
MICHAEL MROZ: I SURE WILL,
THANK YOU.
00:45:01.082 --> 00:45:02.315
DR. DAVID PORTER:
TELL MONICA HI.
00:45:02.417 --> 00:45:04.200
MICHAEL MROZ: YOU KNOW,
I MEAN, HOPEFULLY, ONE DAY,
00:45:04.286 --> 00:45:05.451
THERE'LL BE AN
END TO ALL THIS.
00:45:05.537 --> 00:45:07.253
HOPEFULLY, YOU KNOW,
MAYBE ONE OF OUR PATIENTS,
00:45:07.339 --> 00:45:08.838
THEY MIGHT FIND SOMETHING
IN US AND BE LIKE,
00:45:08.957 --> 00:45:10.123
"OH, WE GOT A
BREAKTHROUGH, WE JUST,
00:45:10.208 --> 00:45:11.657
WE CAN TREAT THIS AND
CURE THIS."
00:45:11.760 --> 00:45:15.378
WE'LL, THEY'LL HAVE THAT 100%
CURE RATE FOR, YOU KNOW,
00:45:15.463 --> 00:45:17.630
EVERYBODY WILL BE
CURED OF IT ONE DAY.
00:45:18.300 --> 00:45:19.265
WOMAN: SEEMS LIKE THAT'S.
00:45:19.351 --> 00:45:21.217
MICHAEL MROZ: THEY'RE
GETTING THERE, YEAH.
00:45:21.303 --> 00:45:23.636
I BELIEVE THEY'RE
REALLY, REALLY CLOSE, I DO.
00:45:27.025 --> 00:45:29.192
DOUG OLSON: HOW CAN
ANYBODY BE SO LUCKY?
00:45:31.696 --> 00:45:37.483
YOU KNOW, TO ME, THE, THE,
THE MIRACLE IS, YOU KNOW,
00:45:42.123 --> 00:45:44.624
THREE OUT OF MILLIONS,
YOU KNOW, THAT,
00:45:44.709 --> 00:45:47.093
THAT GOT INTO THAT TRIAL.
00:45:47.996 --> 00:45:50.196
DR. DAVID PORTER: YOU KNOW,
THE IDEA THAT I CAN BE PART OF
00:45:50.298 --> 00:45:52.632
SOMETHING TO HELP DEVELOP
THESE NEW THERAPIES AND,
00:45:52.717 --> 00:45:56.302
AND MAKE THESE AVAILABLE TO
ALL THESE PATIENTS WHO REALLY
00:45:56.388 --> 00:45:59.505
HAVE NO OTHER TREATMENT
OPTIONS HAS BEEN, UM, GOSH,
00:45:59.591 --> 00:46:01.841
THE MOST ABSOLUTELY
REWARDING THING THAT
00:46:01.927 --> 00:46:03.760
I'VE DONE IN MY CAREER.
00:46:03.845 --> 00:46:06.646
AND IT'S EXCITING, IT'S EXCITING
TO COME TO WORK EVERY DAY,
00:46:06.731 --> 00:46:10.600
AND IT'S EXCITING TO,
TO SEE THESE TREATMENTS WORK,
00:46:10.719 --> 00:46:13.987
AND TO SEE THEM GET BETTER,
AND MODIFIED, AND ALTERED,
00:46:14.072 --> 00:46:16.906
UH, AND BECOME MORE
AND MORE EFFECTIVE.
00:46:17.025 --> 00:46:20.860
AND HOPEFULLY, WE CAN APPLY
THEM TO MORE AND MORE PEOPLE.
00:46:22.581 --> 00:46:27.283
[SCREAMING]
00:46:30.422 --> 00:46:36.376
¶ [MUSIC PLAYS
THROUGH CREDITS] ¶