Revolution in the Treatment of Disease

♪ [BEEPING] NARRATOR: BY THE 1980s, THE WORLD HAD ENTERED THE AGE OF THE GENE.

FROM HIGH SCHOOL BIOLOGY CLASSES TO CRIME FIGHTING, TO HOLLYWOOD MOVIES, THE IDEA OF THE GENE HAD CAPTURED THE POPULAR IMAGINATION.

PEOPLE BEGAN TO ASSUME THAT EVERYTHING THAT MADE THEM WHO THEY WERE-- HOW THEY LOOKED AND ACTED, EVEN HOW THEY FELL ILL AND DIED-- WAS INSCRIBED IN THEIR GENETIC CODE LIKE A SCRIPT HANDED THEM AT BIRTH.

MUKHERJEE: MANY OF THE FUNDAMENTAL QUESTIONS THAT ANY HUMAN BIOLOGIST WOULD SEEK TO ANSWER ULTIMATELY TRACK BACK TO THE GENOME.

WHY IS IT THAT WE AGE?

WHY IS IT THAT WE HAVE DISEASES?

THESE ARE QUESTIONS THAT WE'VE ASKED OURSELVES LITERALLY FROM THE MOMENT HUMANKIND WAS BORN.

NARRATOR: YET, EVEN AS EXCITEMENT AND TREPIDATION GREW ABOUT THE POTENTIAL OF USING GENETICS TO READ AND REWRITE THAT SCRIPT, SCIENTISTS HAD STILL UNCOVERED ONLY AROUND 100 ACTUAL GENES, AND IDENTIFYING EACH ONE HAD REQUIRED YEARS OF PAINSTAKING WORK.

IF SCIENTISTS WERE EVER GOING TO DETERMINE WHICH GENES CAUSE DISEASE, THEY WOULD NEED TO FIND THEM ALL, AND THAT SEEMED ALMOST IMPOSSIBLE.

LANDER: SOMETHING HAD TO BE DONE.

IT NO LONGER COULD BE LITTLE STEPS.

IT HAD TO BE THAT WE THOUGHT ABOUT THE HUMAN GENOME AS A WHOLE.

WE NEEDED TO SEE THE ENTIRE SEQUENCE, ALL 3 BILLION LETTERS OF THE HUMAN DNA LAID OUT.

BUT THE TRUTH WAS, WE HAD NO CLUE HOW IN THE WORLD TO PULL IT OFF.

♪ NARRATOR: IN MAY 1986, HUNDREDS OF BIOLOGISTS FROM AROUND THE WORLD CONVENED AT COLD SPRING HARBOR LABORATORY ON LONG ISLAND, NEW YORK.

THEY WERE THERE TO DISCUSS AN IDEA THAT WOULD HAVE SEEMED IMPOSSIBLE JUST A FEW YEARS BEFORE-- TO READ OUT THE ENTIRE HUMAN GENOME AND IDENTIFY EVERY GENE.

MAN: TO EVEN KNOW WE'VE GOT A DIGITAL GENETIC RECIPE IS VERY EXCITING, BUT TO BE ABLE TO READ THE WHOLE THING?

I MEAN, YOU KNOW, IT'S AS LONG AS 5,000 NOVELS.

IT'S AS LONG AS 800 BIBLES.

YOU KNOW, THIS IS A HUGE DOCUMENT.

HOW MANY GENES WERE THERE?

HOW WERE THEY ARRANGED?

HOW DO THEY MAKE OUR HAIR, OUR BRAINS, OUR HANDS, OUR CONSCIOUSNESS, OUR MEMORIES--US?

NARRATOR: THOUGH THE TECHNICAL CHALLENGES OF READING THE ENTIRE HUMAN GENOME SEEMED INSURMOUNTABLE, THE IDEA HAD GAINED THE SUPPORT OF A SURPRISING NUMBER OF TOP BIOLOGISTS, INCLUDING JAMES WATSON, ONE OF THE DISCOVERERS OF THE DNA DOUBLE HELIX.

FOR WATSON, IT HAD BECOME A MATTER OF PERSONAL URGENCY.

WATSON: I REALIZED MY SON WAS MENTALLY ILL. AND AT THE TIME OF THE COLD SPRING HARBOR MEETING, HAD RUN AWAY FROM THE HOSPITAL IN WHITE PLAINS.

AND I THOUGHT, "THERE'S NO CHANCE WE WILL EVER KNOW WHAT'S WRONG WITHOUT GENETICS."

BUT UNTIL YOU SEQUENCE THE HUMAN GENOME, WE COULDN'T LOOK FOR GENES.

[INDISTINCT CHATTER] NARRATOR: THE SCIENTISTS AT COLD SPRING DELIBERATED FOR 8 LONG DAYS.

HOW MANY RESEARCHERS, HOW MANY YEARS, HOW MUCH MONEY WOULD IT COST TO SEQUENCE THE ENTIRE HUMAN GENOME?

SOME SAID IT WAS PREMATURE AND IMPRACTICAL EVEN TO TRY.

THE TECHNOLOGY JUST WASN'T THERE YET.

BUT WATSON AND OTHERS PERSEVERED.

IF THE TECHNOLOGY DIDN'T EXIST, THEY'D INVENT IT.

IF THE MONEY WAS SHORT, THEY'D RAISE MORE.

WATSON WENT BEFORE CONGRESS SEEKING A MASSIVE COMMITMENT OF GOVERNMENT FUNDS.

SO THE PRIMARY AIM OF THE HUMAN GENOME PROGRAM IS TO IDENTIFY ALL THE HUMAN GENES AND TO, UH...SO WE CAN SEE WHAT THEY CAN DO.

NEWSCASTER: JAMES WATSON BELIEVES IT WILL REVOLUTIONIZE MEDICINE, GIVING PHYSICIANS A BETTER UNDERSTANDING OF THE GENETIC ROLE IN EVERYTHING FROM MUSCULAR DYSTROPHY TO CANCER.

I THINK THE SCIENTIFIC REWARDS WILL BE ENORMOUS.

I MEAN, WE'RE GOING TO FIND OUT THE PROGRAM FOR HUMANS, YOU KNOW, WHY WE'RE HUMAN, AND IT'S WONDERFUL.

COLLINS: WE ALL FELT LIKE, "WATSON SOMEHOW SAYS "IT'S GONNA TAKE 15 YEARS.

"I DON'T KNOW WHERE HE CAME UP WITH THAT "'CAUSE IT FEELS LIKE IT'S GONNA BE A LOT LONGER, BUT, OK, LET'S SEE WHAT WE CAN DO."

AND OFF WE WENT IN OCTOBER OF 1990.

ANNOUNCER: ...ZERO!

ALL ENGINES BURN.

NARRATOR: THE PROJECT, TO BE OVERSEEN BY THE NATIONAL INSTITUTES OF HEALTH, WAS SO BIG AND SO COSTLY THAT IT HAD ONLY ONE PRECEDENT IN THE HISTORY OF SCIENCE.

[INDISTINCT RADIO CHATTER] ANNOUNCER: TOWER CLEAR.

MUKHERJEE: IT'S AN INCREDIBLY BRAVE IDEA.

IT'S VERY MUCH BASED ON THE APOLLO MODEL, THE APOLLO PROGRAM MODEL, WHICH IS THAT MAYBE WE DON'T HAVE ALL THE TOOLS, BUT IF WE START THE APOLLO PROGRAM, WE'LL FIND THE TOOLS TO PUT HUMAN BEINGS ON THE MOON.

NARRATOR: SCIENTISTS SEEKING TO DECODE HUMAN DNA, LIKE THOSE WHO WORKED IN THE EARLY DAYS OF THE SPACE PROGRAM, FACED A WIDE GULF BETWEEN THEIR AMBITION AND THE TOOLS AT THEIR DISPOSAL.

SCIENTIST: A, G, C, A... NARRATOR: DNA SEQUENCING, FIRST DEVISED IN THE LATE 1970s BY BRITISH SCIENTIST FRED SANGER AND AMERICAN RESEARCHER WALLY GILBERT, WAS A PAINSTAKINGLY SLOW, MANUAL PROCESS.

COLLINS: THERE WAS A BEGINNING OF THE IDEA OF AN AUTOMATED DNA SEQUENCING MACHINE, BUT IT WAS PRETTY CLUNKY.

A REALLY GOOD LABORATORY MIGHT BE ABLE TO READ OUT A FEW HUNDRED LETTERS OF DNA IN A WEEK.

TO READ OUT 3 BILLION MEANT YOU'D HAVE TO GET TO THE POINT OF READING 1,000 LETTERS A MINUTE.

WE WERE SO FAR AWAY FROM THAT.

MAN: THERE WAS NO FUNCTIONAL INTERNET.

THERE WAS NO FUNCTIONAL E-MAIL.

WE WERE FAXING DNA SEQUENCE BACK AND FORTH TO ONE ANOTHER.

AND WHEN WE ACTUALLY GENERATED ANY SIGNIFICANT AMOUNT OF DNA SEQUENCE, DEFINED BY SIGNIFICANT BACK THEN, WHICH WASN'T MUCH, IT WAS BEING PUT ON CDs AND MAILED BY REGULAR MAIL.

WOMAN: WE ALL RECOGNIZED THAT THE HUMAN GENOME WOULD NOT BE SEQUENCED WITH 1987 TECHNOLOGY AND THAT THE MOST IMPORTANT THING THAT THE PROJECT HAD TO DO AT THE BEGINNING WAS TO IMPROVE THE QUALITY, THE EFFICIENCY, THE COST OF THE TECHNOLOGY.

NARRATOR: FORTUNATELY, THE EARLY YEARS OF THE GENOME PROJECT COINCIDED WITH A REVOLUTION IN THE SPEED OF COMPUTER PROCESSORS.

SCIENTISTS WERE SOON READING OUT LONGER AND LONGER SEQUENCES OF DNA BASES FASTER AND MORE CHEAPLY THAN EVER BEFORE.

AS THEY DID SO, SOME SAW THERE WAS MONEY TO BE MADE BY PATENTING CERTAIN DNA SEQUENCES AS SOON AS THEY WERE DISCOVERED IN CASE THEY CAME FROM DISEASE-CAUSING GENES.

THE IDEA WAS DEEPLY CONTROVERSIAL AMONG THOSE WHO BELIEVED IN FREE ACCESS TO THE HUMAN GENOME PROJECT'S DISCOVERIES.

COLLINS: THE WORDS "GOLD RUSH" WERE APPLIED IN THIS SITUATION.

WATSON ARGUED PASSIONATELY AS HE COULD THAT THIS WAS THE WRONG THING TO DO.

IT WAS CRAZY, IT WAS INSANE, AND ANYBODY WHO SUPPORTED IT WAS LIKEWISE CRAZY AND INSANE.

AS IT TURNED OUT, THE CURRENT NIH DIRECTOR AT THAT POINT, BERNADINE HEALY, SUPPORTED IT, SO SHE WAS ALSO CALLED INSANE IN FRONT OF OPEN MICROPHONES BY DR. WATSON, WHICH IS ONE OF THE REASONS THAT HE SUDDENLY RESIGNED UNDER A LOT OF PRESSURE.

NARRATOR: WATSON'S DEPARTURE IN 1992 WAS A MAJOR CRISIS FOR THE GENOME PROJECT.

HIS SUCCESSOR WAS FRANCIS COLLINS, A HIGHLY RESPECTED GENETICIST WHO'D DISCOVERED THE GENE FOR CYSTIC FIBROSIS.

BUT COLLINS HAD NO EXPERIENCE RUNNING A PROJECT ON SUCH A HUGE SCALE, LET ALONE ONE FACING SUCH A DAUNTING SCHEDULE.

COLLINS: IT WAS A SCARY TIME.

WE HAD LOST OUR LEADER, WHO HAD BEEN SUCH AN IMPORTANT CATALYST FOR GETTING THIS OFF THE GROUND, BUT IT WAS BARELY OFF THE GROUND.

THERE WAS STILL NO CERTAINTY AT ALL WE WERE GONNA MEET THOSE INCREDIBLY AMBITIOUS GOALS.

NARRATOR: GIVEN THE ENORMITY OF THE TASK, COLLINS BROUGHT TOGETHER OVER A DOZEN INSTITUTIONS WITH SEQUENCING CAPACITY IN THE UNITED STATES AND OVERSEAS.

COLLINS: WE BEGAN TO ACQUIRE ENOUGH SEQUENCING MUSCLE BY ABOUT 1996 TO MOVE ON FROM BACTERIA, WORMS AND FLIES, TO CONTEMPLATE HUMANS.

AND THAT WAS A MOMENT WHERE WE REALLY HAD TO DECIDE WHERE'S THE DATA GONNA GO?

NARRATOR: AT A MEETING IN BERMUDA IN 1996, COLLINS AND OTHER LEADERS OF THE PROJECT DECIDED THAT THEY WOULD IMMEDIATELY MAKE PUBLIC ALL THE DNA SEQUENCES THEY DISCOVERED, BECAUSE ONCE THE DATA WAS IN THE PUBLIC DOMAIN, IT COULD NOT BE PATENTED.

NOT EVERYONE ACCEPTED THE DECISION.

CRAIG VENTER WAS A RESEARCHER AT THE NIH AND AN EXPERT ON GENETIC SEQUENCING.

HE'D COME TO GENETICS AFTER SERVING AS A MEDIC IN VIETNAM, WHERE DAILY EXPOSURE TO THE SUFFERING OF SOLDIERS AND CIVILIANS MOTIVATED HIM TO DO MEDICAL RESEARCH WHEN HE GOT HOME.

KLAUSNER: WHEN CRAIG FIRST CAME TO THE NIH, HIS LAB WAS RIGHT NEXT DOOR TO MY LAB, SO I KNEW HIM.

HE HAD COME FROM VIETNAM.

HE HAD ALL THESE COLORFUL STORIES, AND THERE WAS SOMETHING MAVERICK ABOUT HIM.

NARRATOR: CREATIVE AND ENTREPRENEURIAL, VENTER SAW AN OPPORTUNITY TO WORK FASTER THAN THE HUMAN GENOME PROJECT.

HE CREATED A COMPANY CALLED CELERA GENOMICS IN 1998.

VENTER CLAIMED THAT BY USING A DIFFERENT STRATEGY AND MORE POWERFUL SEQUENCING MACHINES, HIS COMPANY WOULD BE ABLE TO READ OUT THE HUMAN GENOME AS MUCH AS 5 YEARS FASTER THAN THE PUBLIC PROJECT COULD.

KLAUSNER: HE CAME UP WITH AN ALTERNATIVE APPROACH CALLED SHOTGUN SEQUENCING... JUST BLOWING THE WHOLE GENOME UP INTO FRAGMENTS AND SEQUENCING LIKE MAD AND FIGURING OUT WITH COMPUTERS WHO WAS NEXT TO WHO BY WHERE THESE FRAGMENTS OVERLAPPED.

IT WAS A VERY CLEVER IDEA.

NARRATOR: VENTER ANNOUNCED THAT HE PLANNED TO PATENT POTENTIALLY VALUABLE DNA SEQUENCES AS SOON AS HIS TEAM FOUND THEM AND THEN LICENSE THEM TO OTHER RESEARCHERS AND DRUG COMPANIES.

SCIENTISTS FROM THE PUBLIC PROJECT WERE APPALLED.

VENTER WAS PROPOSING TO PROFIT FROM DATA THAT SHOULD BE IN THE PUBLIC DOMAIN.

WHAT WOULD HAPPEN IF GENES INVOLVED IN DISEASES SUCH AS BREAST CANCER OR SCHIZOPHRENIA BECAME AVAILABLE ONLY TO THE HIGHEST BIDDERS?

LANDER: CRAIG ARGUED THAT WE'D BE BETTER SERVED BY LETTING PRIVATE COMPANIES DO IT AND OWN IT AND SELL IT BECAUSE IT WOULD INCENT INVESTMENT.

AND THERE WERE A LOT OF FOLKS, MYSELF STRONGLY INCLUDED, WHO FELT THIS WAS COMPLETELY WRONG.

AND SO WE RAN THE CONTEST, WHICH WAS BETTER, AND THE BATTLE WAS MET-- A PUBLIC HUMAN GENOME PROJECT AND A PRIVATE EFFORT.

REPORTER: EVERY DAY, IT'S ROBOT VS.

ROBOT, PUBLIC COMPUTER VS.

PRIVATE COMPUTER.

NARRATOR: THE PUBLIC ASSUMED THAT THE WINNER OF THE RACE TO SEQUENCE THE HUMAN GENOME WOULD ALSO WIN THE DISPUTE OVER PATENTS.

ARE YOU GONNA WIN?

WE'RE NOT GONNA LOSE.

NARRATOR: OVERNIGHT, THE COMPETITION BECAME FRONT-PAGE NEWS-- PRIVATE PROFIT VS.

THE PUBLIC GOOD, CRAIG VENTER VS. FRANCIS COLLINS.

COLLINS: THE GOOD THING ABOUT THE RACE WAS IT BROUGHT ATTENTION TO THE HUMAN GENOME PROJECT.

AND NOW ALL OF A SUDDEN, IT'S EXCITING BECAUSE THERE ARE PERSONALITIES INVOLVED.

NARRATOR: CONFIDENT THAT THE PUBLIC EFFORT WOULDN'T BE ABLE TO KEEP UP, VENTER OFFERED COLLINS A CONSOLATION PRIZE.

I SAID, "I PLAN TO BE DONE WITH "THE HUMAN GENOME VERY QUICKLY, "WHY DON'T YOU GUYS SWITCH "AND PUT ALL YOUR EFFORTS AND SEQUENCE THE MOUSE GENOME?"

THAT WAS NOT WELL-RECEIVED.

WE DID WANT TO SEQUENCE THE MOUSE GENOME AND WE DID SEQUENCE THE MOUSE GENOME, BUT REALLY?

I UNDERSTAND IN RETROSPECT WHY IT WAS INSULTING, BUT I KIND OF LIKE THAT.

NEWSCASTER: CRAIG VENTER OF CELERA GENOMICS, A PRIVATE COMPANY, SAYS HE HAS A BIGGER COMPUTER THAN DR. COLLINS DOES.

NARRATOR: BY 1999, THE PUBLIC SNIPING BETWEEN THE TWO TEAMS THREATENED TO UNDERMINE THE WHOLE ENTERPRISE.

ARI PATRINOS, A GENETICIST AND FRIEND OF BOTH VENTER AND COLLINS, OFFERED TO BROKER A SOLUTION.

PATRINOS: IT WAS BECOMING A MUD WRESTLING MATCH.

SINCE I WAS PRETTY CLOSE TO BOTH OF THEM, I STARTED TO LOBBY THEM TO CONSIDER SOME SORT OF RAPPROCHEMENT, SOME SORT OF GET-TOGETHER THAT WOULD TAMP DOWN AT LEAST A LOT OF THIS ACRIMONY.

COLLINS: SO THAT WAS THE FAMOUS INVITATION TO COME TO ARI'S VERY SPARSE BASEMENT, CRAIG AND MYSELF AND HIM, OVER VERY BAD PIZZA TO TALK ABOUT WHETHER THERE IS A WAY FOR EVERYBODY TO WIN HERE AND NOT HAVE THIS BE A NASTY ENDING TO WHAT SHOULD HAVE BEEN A BIG TRIUMPH.

THE GOAL WAS TO ELEVATE SCIENCE BACK TO WHERE IT WAS OR SHOULD'VE BEEN IN THE FIRST PLACE, AND NOT NAME-CALLING AND ALL THE STUFF THAT WAS GOING ON.

I THINK IT DID HELP.

IT DIDN'T ELIMINATE IT, BUT I THINK IT HELPED QUITE A BIT.

NARRATOR: PATRINOS CONVINCED COLLINS AND VENTER TO SHARE PUBLIC CREDIT FOR THE PROJECT'S SUCCESS AND TO SET ASIDE THEIR DIFFERENCES OVER PATENTING.

ON JUNE 26, 2000, 10 YEARS AFTER THE INCEPTION OF THE HUMAN GENOME PROJECT, PRESIDENT BILL CLINTON GATHERED THE WORLD'S PRESS IN THE EAST ROOM OF THE WHITE HOUSE WITH BOTH MEN AT HIS SIDE.

WE ARE HERE TO CELEBRATE THE COMPLETION OF THE FIRST SURVEY OF THE ENTIRE HUMAN GENOME.

WITHOUT A DOUBT, THIS IS THE MOST IMPORTANT, MOST WONDROUS MAP EVER PRODUCED BY HUMANKIND.

NARRATOR: FOR THE FIRST TIME, VIRTUALLY THE ENTIRE SEQUENCE OF HUMAN DNA WAS LAID OUT FOR ALL TO SEE.

IT WAS JUST A DRAFT WITH SOME PARTS STILL LEFT TO BE SEQUENCED, BUT IT MARKED THE CULMINATION OF A JOURNEY THAT HAD BEGUN 135 YEARS BEFORE IN THE MORAVIAN MONASTERY WHERE GREGOR MENDEL DISCOVERED HOW TRAITS ARE PASSED FROM PARENTS TO OFFSPRING.

LANDER: IT WAS THE TURN OF THE 21st CENTURY, JUST ABOUT 100 YEARS AFTER THE REDISCOVERY OF MENDEL'S LAWS, AND WE'D GONE FROM REALIZING THAT THERE WERE LAWS OF HEREDITY THAT EXPLAINED TRAITS TO READING OUT THE ENTIRE BOOK OF HEREDITY OF THE HUMAN.

♪ NARRATOR: WITHIN THE VASTNESS OF TIME AND SPACE, IT IS THIS ONE TINY MOLECULE, DNA, COILED UP IN THE HEART OF ALL LIVING CELLS, THAT IS THE SCRIPT IN WHICH THE BOOK OF LIFE IS WRITTEN.

UNIQUE IN OUR UNIVERSE, AS FAR AS WE KNOW, DNA IS WHAT BINDS TOGETHER EVERY MEMBER OF THE HUMAN RACE WITH ALL OTHER ORGANISMS THAT HAVE EVER EXISTED AND WILL EVER EXIST ON OUR PLANET.

THE EFFORT TO DECODE ITS MEANING MARKED A STUNNING MILESTONE IN HUMAN HISTORY.

COLLINS: IT IS PROFOUND TO BE ABLE TO SEE YOUR OWN INSTRUCTION BOOK AND THAT OF ALL OF THE REST OF HUMANITY LAID OUT IN FRONT OF YOU AND TO REALIZE THAT NEVER WAS POSSIBLE UNTIL NOW IN THE WHOLE SWEEP OF HUMAN HISTORY AND PRE-HUMAN HISTORY.

EVERY LIVING THING ON THIS PLANET HAS BEEN DRIVEN BY THIS KIND OF DNA INSTRUCTION BOOK AND YET WE HAVE KNOWN ALMOST NOTHING, AND NOW WE DO.

♪ NARRATOR: 27-YEAR-OLD AUDREY WINKELSAS WAS BORN WITH A GENETIC DISEASE CALLED SPINAL MUSCULAR ATROPHY, SMA.

IT'S AN OFTEN FATAL DEGENERATIVE CONDITION.

AS HER MUSCLES WEAKEN, AUDREY RISKS LOSING HER ABILITY TO EAT AND BREATHE ON HER OWN.

OK, YOU READY?

WE GO THAT WAY.

NARRATOR: SHE AND HER MOTHER KEELY HAVE COME TO JOHNS HOPKINS HOSPITAL IN BALTIMORE, MARYLAND IN THE HOPE THAT A NEW GENETIC DRUG WILL STOP HER DISEASE FROM GETTING WORSE.

WOMAN: I'M BEING CAUTIOUSLY OPTIMISTIC.

EVEN IF IT JUST STOPS DISEASE PROGRESSION, THAT'S WORTHWHILE, AND ANY OTHER GAINS ARE A BONUS.

IT'S, I GUESS YOU COULD SAY, A RELIEF IN ONE SENSE, AND ALSO VERY EXCITING, BECAUSE WHO KNOWS WHAT'S TO COME.

ANY QUESTIONS FOR ME?

NO.

WE HAVE STUFF TO TALK ABOUT, NEW SCIENCE AND STUFF.

GOOD.

YEAH, INTERESTING THINGS GOING ON IN THE SMA WORLD, BUT YOU ALREADY KNOW MORE ABOUT THAT THAN I DO.

NARRATOR: THERE'S A TWIST IN AUDREY'S CASE.

SHE IS NOT ONLY AN SMA PATIENT... ALL RIGHT, SHALL WE GO?

SHE'S A MOLECULAR BIOLOGIST WHO HAS BECOME AN EXPERT IN THE SCIENCE OF SMA, AT THE FOREFRONT OF EFFORTS TO UNDERSTAND AND TREAT THE DISEASE THAT IS RAVAGING HER OWN BODY.

MAN: AUDREY IS A POISED, YOUNG WOMAN AND A CAREFUL SCIENTIST.

SHE'S AMAZING IN WHAT SHE CAN DO WITH WHAT SHE HAS, WHICH IS ALMOST NOTHING.

AND I'M QUITE CONCERNED THAT THAT LITTLE BIT IS SOMETHING THAT WE HAVE TO HOLD ONTO.

WINKELSAS: I FEEL VERY FORTUNATE TO BE LIVING IN A TIME WHERE, YOU KNOW, DEVELOPMENTS ARE HAPPENING SO QUICKLY, AND YEAH, IT'S CRAZY TO THINK HOW, YOU KNOW, WHEN I WAS BORN, THEY DIDN'T KNOW WHAT CAUSED SMA.

KEELY WINKELSAS, ON TAPE: HI.

WELCOME HOME, SWEETIE PIE.

KEELY WINKELSAS: WHEN AUDREY WAS ABOUT 6 MONTHS OLD, HER GODMOTHER, SHE SAID TO ME, "KEELY, WHAT'S WITH THE SHAKING?"

AND I SAID, "IT'S NOTHING."

NARRATOR: KEELY TOOK AUDREY TO A NEUROLOGIST, WHO IMMEDIATELY DIAGNOSED HER WITH SMA.

KEELY: HE SAID THAT THERE IS NO TREATMENT AND THAT AUDREY WOULD PROBABLY HAVE TO WEAR BRACES ON HER LEGS TO WALK.

AND MY THOUGHT WAS, "OK, THEY'RE NOT GONNA SHOW UNDER HER PROM GOWN."

NARRATOR: SMA IS A COMMON CHILDHOOD GENETIC DISEASE.

IT'S CAUSED WHEN A SINGLE GENE GOES WRONG.

SCIENTISTS FOUND THE GENE IN 1995 WHEN AUDREY WAS 3 YEARS OLD.

[CHEERS AND APPLAUSE] THEY ALSO DISCOVERED THAT THE DISEASE COMES IN DIFFERENT FORMS.

MOST CHILDREN WITH SMA HAVE A MORE SEVERE TYPE THAN AUDREY WITH AN EVEN MORE SERIOUS PROGNOSIS.

WOMAN: LET'S SEE IF WE CAN GET HER TO WAKE UP.

GOOD MORNING, ARI.

NARRATOR: ON DECEMBER 27, 2012, A BABY GIRL WAS BORN TO CHERYL AND JEREMY YODER IN BALTIMORE, MARYLAND.

THEY NAMED HER ARIEL.

WOMAN: WE HAVE A PICTURE OF US ON OUR BED WITH HER.

IT'S ONE OF MY FAVORITE PICTURES OF OUR FAMILY.

WE WERE ALL JUST SO HAPPY.

I THOUGHT THAT WE WERE GONNA HAVE 5 OR 7 KIDS AND THEY'RE ALL GONNA BE, YOU KNOW, TWO YEARS APART, AND WE'LL JUST DO THAT AND THEN WE'LL GO ON AND LIVE A LIFE WITH OUR TEAM, YOU KNOW, AND IT DIDN'T WORK OUT LIKE THAT.

NARRATOR: WHEN ARIEL WAS AROUND 4 WEEKS OLD, CHERYL STARTED WONDERING WHETHER SHE WAS DEVELOPING AS SHE SHOULD.

YODER: ONE DAY, I LAID A BLANKET ON THE TABLE AND PUT HER ON HER TUMMY AND SHE JUST LAID THERE AND LIKE, LOOKED A LITTLE BIT, BUT DIDN'T PICK HER HEAD UP AND THEN SHE JUST WENT TO SLEEP.

THERE WAS SOMETHING INSIDE OF ME THAT I DIDN'T SAY OUT LOUD THAT WAS BOTHERED BY THAT.

MAN: CHERYL WAS A NURSE, AND SHE HAD CONCERNS BEFORE I DID.

I JUST THOUGHT, YOU KNOW, SHE'S MY SWEET LITTLE DAUGHTER AND THERE'S NO PROBLEMS, YOU KNOW?

CHERYL YODER, ON TAPE: HA!

DO YOU SEE YOURSELF IN THERE?

YOU WANT IT?

AND THEN, AT A WELL VISIT AT 3 OR 4 MONTHS OLD, I SAID SOMETHING TO THE PEDIATRICIAN.

NARRATOR: THE YODERS WERE REFERRED TO A NEUROLOGIST.

TESTS REVEALED THAT ARIEL HAD THE MOST SEVERE FORM OF SMA.

CHUNG: BABIES WITH SPINAL MUSCULAR ATROPHY, WHEN THEY'RE BORN, IF YOU LOOK AT THEM, THEY LOOK PERFECTLY FINE.

THEY LOOK PERFECTLY HEALTHY, AND THAT'S IN MANY WAYS THE GREATEST TRAGEDY, BECAUSE THE ONES THAT ARE BORN WITH THE MOST SEVERE TYPE OF THIS WILL DIE, USUALLY BY THE END OF THEIR FIRST YEAR OF LIFE.

THE DISEASE IS ONE WHERE OVER TIME, THE MUSCLES ARE NO LONGER WORKING.

AND YOU NEED MUSCLES TO BE ABLE TO WALK, TO BE ABLE TO SIT UP, EVEN TO BE ABLE TO BREATHE.

NARRATOR: SMA IS A RECESSIVE CONDITION OCCURRING WHEN A CHILD INHERITS TWO COPIES OF A MUTATED GENE.

WITH NO SIGN OF IT IN THEMSELVES OR THEIR OLDER CHILDREN, THE YODERS HAD NO ADVANCED WARNING OF THIS TERRIFYING DIAGNOSIS.

ARIEL WAS ONLY 6 MONTHS OLD.

CHERYL YODER: I JUST REMEMBER LOOKING INTO HER EYES AND JUST BEING, LIKE, "OK, BABY, HERE WE GO.

"WE CAN'T CONTROL WHAT'S HAPPENING INSIDE OF YOU, "BUT WE CAN CONTROL OURSELVES TO LOVE YOU AND TO LOVE LIFE WITH YOU, YOU KNOW," AND THAT'S WHAT WE SET OUT TO DO.

[COOING] CHERYL YODER, ON TAPE: OH, MY GOODNESS!

YOU WANNA SHOW MOMMY HOW YOU'VE BEEN MOVING YOUR LEGS?

SO, I SET THEM UP LIKE THIS.

SHE'S ACTUALLY GONNA-- SHE USUALLY JUST FLOPS IMMEDIATELY OVER.

IT IS INTENSE TO SLOWLY JUST WATCH YOUR CHILD KIND OF FADING.

JEREMY YODER: THE LATTER WEEKS, I WOULD SAY EVEN MONTHS OF HER LIFE, WE, ON NUMEROUS OCCASIONS, THOUGHT WE HAD LOST HER.

♪ SHE SEEMED SO...ON THE EDGE.

WE'RE DESPERATE.

WE'RE NOT READY FOR HER TO GO.

WE'RE DOING EVERYTHING THAT WE CAN DO TO KEEP HER ALIVE.

AND YET, WHEN THAT MOMENT COMES, THAT MORNING, WE WAKE UP AND SHE'S GONE, IT'S, LIKE, COMPLETELY PEACEFUL.

CHERYL YODER: JER AND I WALKED DOWN TO THE CREEK, AND WE'RE LOOKING AT THE WATER, AND I JUST HAD THIS DESPERATE FEELING, KIND OF LIKE, COULD TIME JUST STOP, YOU KNOW?

LIKE, TIME JUST KEEPS RUSHING ON.

ALL OF A SUDDEN, IT WAS NOT EVEN TODAY THAT WE HAD HELD HER, YOU KNOW?

IT WAS, LIKE, YESTERDAY, AND THEN IT WAS QUICKLY TWO DAYS AGO, AND WE'RE STARTING TO THINK ABOUT WASHING THE LAUNDRY, AND IT'S LIKE HER LAUNDRY'S IN THERE.

NARRATOR: ARIEL DIED IN APRIL, 2014.

SHE WAS JUST 18 MONTHS OLD.

CHERYL YODER, ON TAPE: [LAUGHS] IS HE WHAT YOU THOUGHT HE'D LOOK LIKE?

JEREMY YODER: GIVE HIM A KISS.

HE WANTS A KISS.

NARRATOR: A YEAR LATER, THE YODERS HAD ANOTHER CHILD, A BOY NAMED JASE.

WHAT DO YOU THINK, MAX?

I LIKE HIM.

NARRATOR: NOW KNOWING THEY WERE BOTH CARRIERS OF SMA, THE YODERS TESTED JASE AS SOON AS HE WAS BORN.

CHERYL YODER: WE HAD HIM FOR A WEEK AND HE SEEMED STRONG, BUT THE WHOLE WEEK, WE'RE ON PINS AND NEEDLES JUST BECAUSE WE KNOW THAT THERE'S THIS BIG QUESTION THAT'S AT A LAB THAT WE'RE GONNA BE GETTING A CALL ABOUT.

NARRATOR: THE RESULTS CAME BACK WHEN JASE WAS 8 DAYS OLD.

HE, TOO, WAS POSITIVE FOR THE SMA MUTATION.

CHERYL YODER: WE WERE MAKING SANDWICHES, JUST THERE IN THE KITCHEN, AND THEY CALLED, AND IT WAS THE PEDIATRICIAN'S OFFICE.

IT WAS JUST--IT WAS A PUNCH IN THE GUT.

WITH ARIEL, WITH HER, IT SLOWLY CAME INTO OUR LIVES.

WITH JASE, IT WAS JUST, YOU KNOW, HERE IT IS.

IT JUST FELT SO DEVASTATING.

IT FELT LIKE WE'RE GONNA LOSE HIM AND THERE AREN'T OPTIONS AND [SIGHS] JUST THAT DISAPPOINTMENT AND...THE PAIN OF HEARING SOMETHING THAT YOU JUST DON'T WANT TO HEAR.

ARIEL WAS SWEET ENOUGH THAT IN SPITE OF LOSING HER AND HOW PAINFUL THAT WAS, FELT LIKE WE WOULD RATHER HAVE HAD THAT EXPERIENCE THAN TO NOT HAVE HAD HER AT ALL.

AND SO, WE LOOKED FORWARD TO JASE AND JUST... HOPED FOR THE BEST.

NARRATOR: BY THE EARLY 2000s, SCIENTISTS HAD IDENTIFIED VIRTUALLY THE ENTIRE SEQUENCE OF LETTERS IN THE HUMAN GENOME AND KNEW THAT CERTAIN SECTIONS WERE GENES-- THE INSTRUCTIONS FOR LIFE-- BUT THEY COULD NOT YET UNDERSTAND ITS FULL MEANING.

IT WAS AS IF THEY HAD DISCOVERED A SCROLL COVERED IN AN UNKNOWN LANGUAGE.

MUKHERJEE: WE ARE THE LANGUAGE.

WE ARE THE MANIFEST LANGUAGE OF THE GENOME.

BUT WHAT ARE THE WORDS?

HOW DO YOU WRITE A SENTENCE?

NARRATOR: SCIENTISTS WERE NOT EVEN CERTAIN ABOUT THE MOST BASIC INFORMATION-- HOW MANY GENES THERE WERE.

AT A MEETING IN 2000 THAT BROUGHT TOGETHER RESEARCHERS FROM AROUND THE WORLD, ONE DECIDED TO START A POOL.

GREEN: WE WOULD HAVE SCIENTIFIC PRESENTATIONS TALKING ABOUT DIFFERENT WAYS OF COUNTING GENES AND ACCOUNTING FOR GENES, AND AT SOME POINT SOMEBODY SAID, "YOU KNOW WHAT, WE NEED TO START PUTTING MONEY WHERE OUR MOUTH IS."

NARRATOR: SCORES OF BETS WERE PLACED.

GREEN: IF YOU HAD A NUMBER, YOU COULD WRITE THAT NUMBER DOWN AND PUT IT IN A JAR AND ALSO PUT MONEY IN THERE.

AND IT WAS SHOCKING THE RANGE THAT WAS BEING PREDICTED FROM THESE BETS.

NARRATOR: THE BETS STARTED AT AROUND 30,000 GENES AND RANGED UP TO MORE THAN 150,000.

RESEARCHERS HAD ALREADY SHOWN THAT MUCH SIMPLER ORGANISMS, SUCH AS YEAST, WORMS, AND FRUIT FLIES, HAD BETWEEN 5,000 AND 20,000 GENES.

SURELY, HUMANS, WITH OUR VASTLY SUPERIOR CAPABILITIES, MUST HAVE EXPONENTIALLY MORE.

GREEN: IT WAS STRIKING HOW MANY INCREDIBLY SMART PEOPLE WERE INCREDIBLY WRONG.

NOBODY GOT THE RIGHT NUMBER.

NOBODY GOT AS LOW AS IT TURNS OUT.

TURNS OUT WE'VE GOT ABOUT 20,000 PROTEIN-ENCODING GENES.

A FLY HAS ABOUT 13,000.

SHOCKING, SHOCKING.

HOW COULD THAT POSSIBLY WORK?

HOW COULD WE, AS COMPLICATED AND FANCY AS WE ARE, BE DRIVEN BY SUCH A SHORT LIST OF RECIPES?

20,000, REALLY?

NARRATOR: HOW COULD A MERE 20,000 GENES, FEWER THAN IN AN ONION, BUILD AN ORGAN AS COMPLEX AS THE HUMAN BRAIN?

THIS QUESTION OF HOW GENES CAN GENERATE THE COMPLEXITY AND IMMENSE DIVERSITY OF LIVING ORGANISMS HAD MYSTIFIED SCIENTISTS FOR MANY YEARS.

A HINT HAD COME FROM THE RESEARCH OF TWO REMARKABLE BIOLOGISTS WORKING IN PARIS IN THE 1950s AND '60s.

THEIR NAMES WERE FRANCOIS JACOB AND JACQUES MONOD.

BOTH HEROES OF THE FRENCH RESISTANCE, THE PAIR HAD FORGED A CLOSE SCIENTIFIC PARTNERSHIP.

TOGETHER, THEY TOOK ON ONE OF THE MOST PUZZLING QUESTIONS TO EMERGE FROM THE DISCOVERY OF DNA-- HOW CAN ALL THE CELLS IN A BODY DO SO MANY DIFFERENT THINGS WHEN EACH ONE CARRIES EXACTLY THE SAME GENETIC CODE?

HOW DO SOME CELLS KNOW TO COME TOGETHER AS A BRAIN, WHILE OTHERS FORM LUNGS, SKIN, OR HAIR?

MUKHERJEE: THE SIMPLEST EXAMPLE-- A CATERPILLAR AND A BUTTERFLY.

WE KNOW BOTH OF THEM HAVE THE SAME CODE, AND YET HOW IS IT POSSIBLE THAT THESE TWO ORGANISMS DON'T EVEN LOOK LIKE EACH OTHER?

THAT MUST BE BECAUSE IN TIME AND SPACE DIFFERENT ASPECTS OF THE CODE ARE ACTUALIZED SO THAT ONE ORGANISM CHANGES OVER TIME.

NARRATOR: JACOB AND MONOD'S CRUCIAL BREAKTHROUGH CAME IN 1961 WHILE OBSERVING A CURIOUS TRAIT IN BACTERIA.

FED WITH A CERTAIN TYPE OF SUGAR, THE BACTERIA RAPIDLY REPRODUCED, BUT WHEN THAT FOOD SOURCE WAS SWITCHED, THEY STOPPED MULTIPLYING FOR A PERIOD OF TIME BEFORE REPRODUCING AGAIN.

CLEARLY, THE BACTERIA WERE ADAPTING TO THEIR ENVIRONMENT BY CHANGING SOMETHING WITHIN THEMSELVES, BUT WHAT?

AFTER SOME INGENIOUS EXPERIMENTS, JACOB AND MONOD HAD THE ANSWER.

MUKHERJEE: WHAT THEY FIND IS THAT BACTERIA DEPLOY DIFFERENT GENETIC MACHINERY AT DIFFERENT TIMES IN RESPONSE TO THE ENVIRONMENT.

THEY ACTIVATE, AND LATER WE FIND THAT THEY ALSO REPRESS CERTAIN GENES.

BY SELECTIVELY ACTIVATING AND REPRESSING GENES, THEY CAN ACTUALIZE DIFFERENT PERMUTATIONS OF THE MASTER CODE THAT ALLOWS ORGANISMS TO BE DIFFERENT IN TIME AND SPACE.

[ORCHESTRA PLAYING CLASSICAL MUSIC] IT'S A LITTLE BIT LIKE AN ORCHESTRA, AND THERE'S A MASTER SCORE.

♪ AND THAT SCORE, OF COURSE, IS CODE.

♪ MONOD, HE IS A MUSICIAN.

HE UNDERSTANDS THE RELATIONSHIP BETWEEN SCORE AND MUSIC.

SCORE IS STATIC.

MUSIC IS ALIVE.

JACOB AND MONOD FIGURED OUT THAT GENES ARE BEING ACTIVATED, REPRESSED, TURNED ON, TURNED OFF.

SO THE GENOME IS THE LIVING SCORE GENERATING IN TIME AND SPACE, AND IN RESPONSE TO ENVIRONMENTS, THE KIND OF DIVERSITY THAT CHANGES DNA FROM A SEEMINGLY DEAD MOLECULE TO LIFE ITSELF.

GREEN: WE KNOW THAT SOME FUNDAMENTALS THAT JACOB AND MONOD LEARNED BACK THEN IN VERY SIMPLE ORGANISMS CLEARLY MUST APPLY TO WHAT GOES ON IN THE HUMAN GENOME, BUT IT JUST MUST BE ORDERS OF MAGNITUDE MORE COMPLICATED, AND SOMEHOW ALL THIS IS HAPPENING IN A HIGHLY CHOREOGRAPHED WAY.

NARRATOR: LATER, SCIENTISTS WOULD DISCOVER OTHER PROCESSES THAT ENABLED HUMANS AND OTHER HIGHER ORGANISMS TO GENERATE SUCH ENORMOUS COMPLEXITY WITH ONLY A MODEST NUMBER OF GENES.

THE DNA WITHIN EACH GENE, THEY FOUND, READ WHOLE OR IN PART, PRODUCING DIFFERENT RESULTS.

IT'S AS IF THE EXACT SAME PHRASES AND SENTENCES THAT PROVIDE THE INSTRUCTIONS FOR MAKING THE LEGS OF A CHAIR COULD BE REARRANGED TO MAKE THE SEAT OR THE ARMRESTS.

COBB: THE REALITY OF WHAT THOSE 20,000 GENES ARE DOING IS IN FACT AMAZINGLY COMPLICATED.

WE HAVEN'T JUST GOT 20,000 DIFFERENT INSTRUCTIONS.

MANY GENES CAN BE READ IN MORE THAN ONE WAY.

FROM THE SAME DNA SEQUENCE, YOU CAN READ 1/2 OF IT OR 3/4 OF IT OR TURN IT ON AT DIFFERENT POINTS IN YOUR DEVELOPMENT, AND THAT'S WHAT ACCOUNTS FOR THE AMAZING VARIETY AND WHY I DON'T LOOK LIKE KIND OF 2/3 FLY-- I LOOK LIKE ME.

NARRATOR: OF ALL THE REVELATIONS ABOUT THE HUMAN GENOME IN THE EARLY 2000s, POSSIBLY THE MOST SURPRISING WAS THAT THE GENES THEMSELVES COMPRISE ONLY A VERY SMALL PART OF IT.

LANDER: ALL THE FOCUS WAS ON THE GENES, THE PART OF HUMAN DNA THAT ENCODES THE PROTEINS, BUT IT TURNED OUT THAT INFORMATION WAS ONLY A LITTLE MORE THAN 1% OF ALL THE GENETIC CODE.

NARRATOR: AT FIRST, SCIENTISTS THOUGHT THOSE OTHER SEGMENTS OF DNA WERE USELESS DETRITUS DISCARDED ACROSS MILLENNIA OF HUMAN EVOLUTION.

BUT OVER TIME, THEY FOUND THAT SOME OF THE SEQUENCES WERE ACTUALLY SWITCHES THAT TURN GENES ON AND OFF.

LANDER: IN THE TEXTBOOKS, YOU DRAW A PICTURE WITH A BODY OF THE GENE CONTAINING THE PROTEIN INFORMATION AND IT TAKES UP MOST OF THE PICTURE, BUT IN THE GENOME, IT LOOKS LIKE A TINY FRACTION OF A WHOLE.

TURNS OUT THAT THERE WAS A LOT MORE INFORMATION THAT WASN'T THE PROTEIN CODING REGIONS OF THE GENOME.

IT WAS REGULATORY REGIONS SCATTERED ABOUT THE GENOME, AND IT WAS 3 OR 4 OR 5 TIMES AS MUCH INFORMATION, SO THE WHOLE TEXTBOOK PICTURE WAS TURNED ON ITS HEAD.

NARRATOR: STILL, THERE ARE STRETCHES OF THE HUMAN GENOME THAT SEEM TO HAVE NO FUNCTION-- OLD, DEFUNCT GENES SCATTERED LIKE SHIPWRECKS ON THE OCEAN FLOOR AND VAST, STRANGE SECTIONS OF REPEATING LETTERS THAT SEEM TO BE REMNANTS OF VIRUSES THAT LONG AGO EMBEDDED THEMSELVES IN OUR GENOME.

MORE IMPORTANTLY, THERE ARE OCCASIONAL ERRORS, SIMPLE MISTAKES IN COPYING THAT CAN HAVE CATASTROPHIC CONSEQUENCES.

AUDREY WINKELSAS: MITCHELL, COME.

YES.

NARRATOR: BORN WITH SPINAL MUSCULAR ATROPHY, BIOLOGIST AUDREY WINKELSAS HAS BEEN LIVING WITH ITS EFFECTS ALL HER LIFE.

AUDREY WINKELSAS: SO THIS WAS FROM MY VERY FIRST CHOIR CAMP.

KEELY WINKELSAS: THE VERY FIRST ONE.

THE FIRST ONE, WHICH WAS VERY COOL.

ONE OF THE PRACTICES.

EVER SINCE I STARTED SINGING IN CHOIR I LOVED IT, AND I THINK IT'S LIKE MY MAIN PASSION.

SO I THINK SCHOOL AND CHOIR ARE RIGHT UP THERE, BUT CHOIR PROBABLY TRUMPS SCHOOL.

[FEMALE SOLOIST SINGING] IT REALLY IS LIKE BEING PART OF SOMETHING GREATER THAN YOURSELF.

HAVING SMA, MY BREATHING WAS NEVER AMAZING FOR SINGING, SO I WOULD HAVE TO BREATHE A LITTLE BIT MORE OFTEN THAN YOU SHOULD.

BUT I HAVE NOTICED IT IS WORSE NOW.

SUSTAINING THE HIGH NOTES IS NOT AS GOOD AS IT USED TO BE, SO THAT IS FRUSTRATING, BUT IT'S OK, I STILL LOVE IT, SO... [FEMALE SOLOIST SINGING] NARRATOR: IN THE 1990s, SCIENTISTS DISCOVERED THE GENE THAT, WHEN MUTATED, LEADS TO SMA AND DETERMINED THAT IT CAUSES THE DISEASE BY NOT MAKING ENOUGH OF A PROTEIN ESSENTIAL FOR SUSTAINING MUSCLE STRENGTH.

SCIENTISTS ALSO UNCOVERED AN UNUSUAL FEATURE OF SMA.

CRAWFORD: THIS PARTICULAR DISEASE WAS PRETTY UNIQUE IN THAT IT ACTUALLY WASN'T ONE GENE.

THERE WAS A NEIGHBORING GENE THAT LOOKED ALMOST EXACTLY LIKE IT, AND WAY BACK IN HUMAN EVOLUTION, WE GOT TWO COPIES, SMN1 AND SMN2, BUT SMN2 IS KIND OF BROKEN DOWN.

IT JUST BARELY WORKS.

BUT IF YOU'RE MISSING THE SMN1 GENE, IT'S GOOD ENOUGH TO KEEP YOU ALIVE.

NARRATOR: SMA PATIENTS WHO LIVE LONGEST ARE THOSE WHOSE IMPAIRED SMN2 GENES MAKE MORE OF THE PROTEIN.

THAT GAVE RESEARCHERS AN IDEA-- FIND A WAY TO BOOST THE PERFORMANCE OF THE BACKUP SMN2 GENE.

CRAWFORD: SO THIS BECAME AN AMAZING SEARCH.

IS THERE SOME WAY WE CAN MAKE THIS BROKEN GENE WORK BETTER?

NARRATOR: THE SEARCH WAS LED BY ADRIAN KRAINER AT COLD SPRING HARBOR LABORATORY, WHOSE WORK FOCUSES ON RIBONUCLEIC ACID, RNA, THE MOLECULE THAT TRANSLATES DNA CODE INTO PROTEINS.

KRAINER: WE STUDIED THAT TYPE OF PROCESS IN OTHER GENES FOR MANY YEARS, AND SO WHAT WAS EXCITING IN THE SMA FIELD IS THAT IF YOU CAN UNDERSTAND WHAT'S WRONG WITH THE RNA FROM THE SMN2 GENE, IF YOU COULD FIX IT, POTENTIALLY, YOU'D HAVE A THERAPY THERE.

NARRATOR: AUDREY FOLLOWED KRAINER'S WORK CLOSELY AND BECAME FASCINATED BY THE IDEA THAT THE SMN2 GENE COULD BE SUPERCHARGED TO PRODUCE MORE OF THE PROTEIN THAT COULD SAVE HER LIFE.

THE SMN2 GENE IS ACTUALLY PRETTY LONG, AND ONLY PART OF THE GENE IS ACTUALLY WHAT MAKES THE PROTEIN, SO WE'LL PUT THAT IN THE MIDDLE HERE.

AND THAT'S WHAT WE CALL THE CODING SEQUENCE BECAUSE IT CODES FOR THE PROTEIN.

BUT THERE ARE THESE OTHER BITS ON EITHER END THAT DON'T DIRECTLY CODE FOR THE PROTEIN BUT THAT REGULATE HOW MUCH OF THE PROTEIN IS PRODUCED.

WE'RE LOOKING AT THIS REGION UPSTREAM TOWARD THE BEGINNING OF THE GENE, AND THIS AREA IS LIKE THE THERMOSTAT.

SO IT CAN BE TURNED UP OR TURNED DOWN TO REGULATE HOW MUCH OF THE SMN PROTEIN IS MADE.

NARRATOR: AUDREY HAS IDENTIFIED THE PRECISE SEQUENCE OF THE 164 GENETIC LETTERS THAT MAKE UP THIS THERMOSTAT.

♪ [FEMALE SOLOIST SINGING] MUCH OF THE PROCESS INVOLVED IN SWITCHING GENES ON AND OFF OR UP AND DOWN IS ORCHESTRATED BY LITTLE PIECES OF RNA.

♪ THIS FACT HAS GIVEN SCIENTISTS LIKE AUDREY HOPE THAT THEY CAN CREATE DRUGS THAT MIMIC THESE RNAs.

YES, GOOD BOY.

AUDREY WINKELSAS: EVERYONE KNOWS ABOUT DNA AND A LOT OF PEOPLE KNOW ABOUT PROTEINS, BUT FOR A WHILE IT WAS THOUGHT THAT RNAs WERE JUST KIND OF LIKE JUNK IN THE MIDDLE AND NOT THE CRITICAL COMPONENTS OF THE CELL.

BUT I WOULD ARGUE OTHERWISE.

KEELY WINKELSAS: MORNING, GEORGE.

♪ NARRATOR: NOW AT THE NIH, AUDREY IS STUDYING A NUMBER OF RNA COMPOUNDS THAT COULD PERHAPS TURN UP THE THERMOSTAT ON THE SMN2 GENE.

HER MOTHER KEELY HELPS HER RUN HER EXPERIMENTS.

AUDREY WINKELSAS: SO WE'LL LOAD THEM AS 31st AND GET THESE PRIMERS OUT, AND THEN PCR MASTER... MAN: AUDREY CONTACTED ME 2 OR 3 YEARS AGO WHEN SHE WAS LOOKING FOR A LAB TO WORK IN FOR A GRADUATE PROGRAM, AND SHE WANTED TO WORK ON SPINAL MUSCULAR ATROPHY.

AND I SAID SURE.

THEN I ASKED HER, "WELL, WHY DO YOU WANT TO WORK ON SPINAL MUSCULAR ATROPHY?"

AND SHE SAID, "WELL, I HAVE IT."

AND I SAID, "WELL, WE SHOULD TALK ABOUT THAT."

OK, SO I'M LOOKING FOR THE GS, GS OUTER.

FISCHBECK: IT'S A LITTLE UNUSUAL FOR SOMEONE TO WORK ON THEIR OWN DISEASE.

AND THE RISK IS THAT YOU LOSE YOUR OBJECTIVITY.

THAT'S FINE, YEAH.

FISCHBECK: BUT SHE'S REALLY TAKEN TO IT WELL.

SHE'S MAINTAINED OBJECTIVITY, A HIGH STANDARD OF SCIENCE, AND SHE'S BEEN GREAT.

RIGHT IN THE MIDDLE.

THIS?

YEP.

YEP.

KEELY WINKELSAS: AUDREY DIRECTS MY EVERY MOVE AT THE BENCH.

WE DO WESTERN BLOTS AND WE RUN GELS AND WE DO... WE DO PCRs, WE DO QPCRs.

AND THEN THE NEXT ONE HAS A C-DNA... KEELY WINKELSAS: THINGS I DIDN'T KNOW EXISTED UNTIL TWO YEARS AGO, THINGS I DIDN'T KNOW WERE A THING.

SO, IT'S THE SAME VOLUME FOR ALL OF THEM, SO .4 OK.

SO LET'S START WITH THE DNA.

♪ OK. ALL THE WAY DOWN INTO THE WATER.

[CHOIR VOCALIZING] ♪ GOOD.

♪ PERFECT.

SO THEN THAT'S EVERYTHING, SO IF WE CAN PUT THE LIDS ON THEM.

WE'RE GOING TO DO A GRADIENT, ACTUALLY, SO IF YOU... FISCHBECK: HAVING THE DISEASE, I THINK, HELPS AUDREY FOCUS ON WHAT SHE'S DOING.

IT CERTAINLY MOTIVATES HER.

IT KEEPS HER HERE NIGHTS AND WEEKENDS TO GET EXPERIMENTS DONE.

AND THEN 72 FOR 3 MINUTES.

FISCHBECK: SHE KNOWS HER STUFF VERY WELL.

SHE'S BEEN WORKING HARD ON IT AND HAS HAD SOME REALLY GOOD RESULTS.

MAYBE WE CAN GO AHEAD AND GET THE COMBS AND THE TRAY FOR THE GEL.

OK, SURE.

SURE.

NARRATOR: WITH ONE EXPERIMENTAL COMPOUND SHOWING SIGNS OF UPPING THE SMN2 GENE'S PRODUCTION OF PROTEIN, AUDREY WILL TAKE IT TO A LAB AT OXFORD UNIVERSITY IN ENGLAND SO SHE CAN TEST IT IN MICE.

OK, LET'S PUT THE PRIMERS AND STUFF AWAY AND THEN WE'LL POUR THE GEL.

♪ AUDREY WINKELSAS: [INDISTINCT] HELLO.

AUDREY WINKELSAS: AT THE NIH, WE TESTED THE DRUG ON HUMAN CELLS, BUT THERE ARE STILL SOME UNANSWERED QUESTIONS.

THIS IS THE FIRST TIME, HERE IN OXFORD, THAT WE ARE TESTING IT IN THE SMA MOUSE MODEL.

TRANSITIONING INTO THE MOUSE MODEL IS EXCITING, BUT IT'S ALSO KIND OF NERVE-WRACKING.

JUST BECAUSE SOMETHING WORKED PREVIOUSLY IN CELLS DOES NOT, BY ANY MEANS, MEAN THAT IT WILL WORK IN MICE.

...BUT WE COULD DO LIKE THE 120 MAYBE, AND DO LIKE, P0, P2, I DON'T KNOW.

OK. NO, I THINK THAT THOSE ARE TWO REALLY GOOD IDEAS, ACTUALLY, TO... NARRATOR: WITH TWO COLLEAGUES, AUDREY RECENTLY FILED A PATENT, HOPING TO ATTRACT INVESTMENT TO HELP DEVELOP HER EXPERIMENTAL COMPOUND INTO A USEFUL TREATMENT.

...WHICH IF--OR I DON'T KNOW HOW LONG, WE CAN... MAN: SHE'S DONE THIS WORK, WHICH ACTUALLY WILL TURN OUT TO BE TERRIFIC WORK.

EVEN IF IT DOES SOMETHING FOR SMA, IT'LL BE TERRIFIC.

IF IT'S A GENERAL MECHANISM, IT'LL BE STUNNING.

BUT, YOU KNOW, AUDREY IS A SUPERSTAR.

SHE'S A FORCE OF NATURE, SHE REALLY IS.

THE VISION AND THE EFFORT AND THE DEDICATION SHE'S BROUGHT TO THE PROJECT HAS BEEN EXTRAORDINARY, AND, YOU KNOW, I'VE NOT SEEN ANYBODY LIKE AUDREY IN A LONG, LONG TIME.

AUDREY WINKELSAS: IF EVERYTHING GOES AS WE HOPE IT MAY GO, THEN IT WOULD INVOLVE AROUND A YEAR OF EXPERIMENTS IN THE MICE, JUST BECAUSE UNLIKE CELLS, WHICH GROW VERY QUICKLY, IN MICE, YOU HAVE TO WAIT FOR THEM TO BE BORN.

YOU TRY, YOU KNOW, MULTIPLE DOSES TO SEE WHICH ONE MAY BE THE MOST EFFECTIVE AND LOOK AT MOUSE SURVIVAL TO SEE IF OUR DRUG, DOES IT EXTEND THEIR LIFESPAN AT ALL?

ANYWAY, IT'S A REALLY EXCITING TIME.

NARRATOR: BY THE MIDDLE OF THE FIRST DECADE OF THE 2000s, THE TASK OF FINDING THE MUTATED GENES THAT CAUSE A SPECIFIC DISEASE SEEMED FAR SIMPLER, JUST A MATTER OF COMPARING A NORMAL GENOME WITH AN ABNORMAL ONE AND IDENTIFYING THE DIFFERENCES.

CHUNG: THE END OF THE HUMAN GENOME PROJECT WAS REALLY THE BEGINNING FOR US.

IT GAVE US A ROADMAP.

IT GAVE US A SCAFFOLD, IN TERMS OF KNOWING JUST HOW MANY GENES WE HAD, WHERE THEY WERE LOCATED, AND STARTED TO ALLOW US TO THEN UNTANGLE AND MAKE ASSOCIATIONS BETWEEN THE GENES AND THE DISEASES THAT THEY CAUSE.

LANDER: YOU CAN COMPARE THAT ONE GENOME TO ANOTHER PERSON, TO A THIRD PERSON, A TENTH PERSON, TO A MILLION PEOPLE, AND ASK, SAY, DO THE PEOPLE WHO HAVE INHERITED A PARTICULAR RISK OF A GIVEN DISEASE HAVE SLIGHTLY DIFFERENT SEQUENCES THAN THOSE WHO DIDN'T GET THAT DISEASE?

NARRATOR: FOR GENETIC ILLNESSES LIKE SMA THAT ARE CAUSED BY DEFECTS IN A SINGLE GENE, FINDING AND TRACKING THE ANOMALY HAD BECOME A RELATIVELY STRAIGHTFORWARD PROCESS OF COMPARING GENOMES WITHIN FAMILIES.

BUT WHAT ABOUT COMMON DISEASES THAT SEEMED TO BE CAUSED BY DEFECTS IN MANY GENES AT ONCE?

KLAUSNER: COULD WE NOW EXPLAIN WHO GETS A COLD AND WHO DOESN'T, MENTAL ILLNESS, ALZHEIMER'S, HYPERTENSION, DIABETES, ON AND ON.

WE KNEW IT WAS GONNA BE MORE COMPLICATED, AND PART OF THE MORE COMPLICATED IS THAT IT WASN'T GONNA BE ABOUT RUNNING IN FAMILIES.

IT WAS GONNA BE LOOKING ACROSS POPULATIONS.

WE WERE GONNA HAVE TO LOOK AT LARGE NUMBERS OF PEOPLE.

NARRATOR: RESEARCHERS BEGAN TO COMPARE GENOMES OF PEOPLE WITH A CERTAIN DISEASE TO THOSE WITHOUT, HOPING TO FIND COMMON GENETIC ABNORMALITIES AMONG THEM.

WOMAN: WE STARTED TO SEE THAT THERE WERE CERTAIN SITES IN THE HUMAN GENOME THAT WERE OFTEN DIFFERENT BETWEEN ME AND MY NEIGHBOR, AND BY BEING ABLE TO LOOK AT JUST THESE SITES IN THOUSANDS AND THOUSANDS OF INDIVIDUALS, WE COULD START TO GET REAL ANSWERS ABOUT WHAT GENETIC VARIATION WAS IMPORTANT IN CERTAIN DISEASE.

THESE EXPERIMENTS WERE CALLED GENOME-WIDE ASSOCIATION STUDIES.

NARRATOR: WORKING WITH FASTER MACHINES, SCIENTISTS LAUNCHED A SERIES OF STUDIES TO UNCOVER WHICH GENES MIGHT BE CONTRIBUTING TO COMMON ILLNESSES.

ONE OF THE FIRST TARGETS WAS ALSO ONE OF THE MOST CONFOUNDING-- SCHIZOPHRENIA.

UNTIL THE MIDDLE OF THE 20th CENTURY, MANY SCHIZOPHRENICS HAD BEEN WAREHOUSED IN MENTAL HOSPITALS, THEIR DOCTORS AT A LOSS FOR HOW TO TREAT THE HALLUCINATIONS, DELUSIONS, AND CONFUSION SYMPTOMATIC OF THIS CRUEL DISEASE.

BUT BY THE 1990s, GENETICISTS KNEW THAT SCHIZOPHRENIA OFTEN RAN IN FAMILIES, A POWERFUL CLUE THAT IT MUST HAVE A GENETIC BASIS.

SCIENTISTS BEGAN SEARCHING FOR SIGNALS THAT WOULD LEAD THEM TO THE GENETIC MUTATIONS AT FAULT.

AT FIRST, THEY CAME UP EMPTY.

THERE DIDN'T SEEM TO BE ANY GENETIC ANOMALIES SPECIFIC TO PEOPLE WITH SCHIZOPHRENIA.

GABRIEL: WE FOUND ABSOLUTELY NO SIGNAL, BUT THEN WE GREW OUR COLLECTION OF INDIVIDUALS WITH SCHIZOPHRENIA AND WITHOUT THAT COULD BE STUDIED.

WE GOT TO TENS OF THOUSANDS OF INDIVIDUALS, AND FINALLY SOME SIGNALS EMERGED.

NARRATOR: BUT THE SIGNALS WERE WEAK, AND INSTEAD OF CLEAR EVIDENCE THAT JUST A FEW GENES WERE RESPONSIBLE FOR SCHIZOPHRENIA, INDICATIONS WERE THAT GENETIC MUTATIONS WERE SCATTERED ALL OVER THE GENOME.

MAN: NOW WE HAVE WELL OVER 100 DIFFERENT PARTS OF THE HUMAN GENOME THAT CARRY VARIANTS CLEARLY ASSOCIATED WITH RISK OF SCHIZOPHRENIA.

BUT UNFORTUNATELY, FOR ALMOST NONE OF THOSE HAVE WE ACTUALLY TRACKED DOWN TO THE EXACT RESPONSIBLE GENES.

NARRATOR: IT WASN'T ONLY SCHIZOPHRENIA.

ONE AFTER ANOTHER, GENOME-WIDE STUDIES TOLD THE SAME, FRUSTRATING STORY-- THE MOST COMMON DEBILITATING DISEASES TURNED OUT TO BE CAUSED BY COMBINATIONS OF DOZENS OR HUNDREDS OF GENES.

GOLDSTEIN: THE HOPE, OF COURSE, WAS THAT THE LEADS FROM THESE KINDS OF GENETIC STUDIES WOULD TEACH US SOMETHING THAT WOULD BE HELPFUL FOR DEVELOPING NEW THERAPIES.

AND IT'S FAIR TO SAY THAT IN THAT WAY GENOME-WIDE ASSOCIATION STUDIES HAVE WORKED LESS WELL THAN HOPED FOR.

NARRATOR: BUT JUST AS SCIENTISTS WERE LOSING FAITH IN GENOME-WIDE STUDIES, SOMETHING SURPRISING HAPPENED.

THEY BEGAN TO SEE THAT VERY DIFFERENT DISEASES SOMETIMES SHARED A FEW GENETIC ANOMALIES, LIKE FINGERPRINTS LEFT AT SEEMINGLY UNRELATED CRIME SCENES.

GABRIEL: WE KNOW THAT FROM GENOME STUDIES OF TYPE 2 DIABETES AND OF HEART ATTACK, THERE'S A REGION OF THE GENOME ON CHROMOSOME 9 THAT HAS THE EXACT SAME SET OF VARIATIONS THAT ARE LINKED TO BOTH OF THESE DISEASES.

IT'S NOT THAT THESE PEOPLE WHO HAD DIABETES ALSO HAVE HEART ATTACK.

IT'S ACTUALLY POINTING TO SOME BIOLOGY THERE THAT MUST BE VERY IMPORTANT BECAUSE CHANGES IN THIS REGION CONTRIBUTE TO BOTH OF THESE VERY SERIOUS OUTCOMES.

NARRATOR: IN THE LAST DECADE, RESEARCHERS AND PHARMACEUTICAL COMPANIES HAVE SEARCHED HARD TO FIND THESE SHARED MUTATIONS IN THE HOPE THAT THEY MIGHT EVENTUALLY BE ABLE TO TARGET MULTIPLE DISEASES WITH THE SAME DRUGS.

THE FOCUS OF THIS NEW APPROACH HAS BEEN CANCER.

WHILE THERE ARE MANY DIFFERENT TYPES OF CANCER, ALL BEGIN WHEN A GENE MUTATES IN A SINGLE CELL, CAUSING IT TO PROLIFERATE UNCONTROLLABLY, OFTEN LEADING TO A CASCADE OF OTHER MUTATIONS.

LANDER: MORE THAN ANY OTHER DISEASE, CANCER IS A DISEASE OF THE GENOME.

YOU CAN GO TO THE TUMOR AND SEQUENCE OUT THE TUMOR AND RECONSTRUCT THE PATTERN OF EVOLUTION THAT LED TO THAT TUMOR, AND YOU CAN COMPARE IT ACROSS MANY DIFFERENT PEOPLE WHO HAVE WHAT SEEMS LIKE THE SAME TUMOR, AND YOU CAN LEARN IN A TOTALLY UNBIASED WAY WHICH GENES HAVE MUTATIONS THAT DRIVE PARTICULAR KINDS OF LEUKEMIAS OR PARTICULAR KINDS OF BRAIN CANCERS OR SKIN CANCERS.

NARRATOR: IN 2005, SCIENTISTS SET OUT ON AN AMBITIOUS PROJECT TO IDENTIFY AS MANY CANCER-CAUSING GENES AS POSSIBLE.

TO THEIR DISMAY, THEY LEARNED THAT NO TWO CANCERS HAVE THE SAME COMBINATION OF GENETIC MUTATIONS.

MAN: CANCER ISN'T ONE DISEASE, NOT EVEN TWO DOZEN DISEASES.

IT'S THOUSANDS OF DISEASES, AND EACH OF THOSE DISEASES IS GONNA REQUIRE ITS OWN STRATEGY ON HOW TO TREAT AND, IF WE CAN'T TREAT, HOW DO WE DETECT IT SO EARLY THAT IT DOESN'T KILL YOU.

NARRATOR: BUT EVEN IF NO TWO CANCERS ARE EXACTLY ALIKE, THERE ARE KEY GENETIC MUTATIONS THAT MANY TYPES OF CANCERS SHARE, EVEN THOSE ARISING IN DIFFERENT PARTS OF THE BODY.

THIS MAKES TARGETING DIFFERENT CANCERS WITH THE SAME DRUG MORE FEASIBLE.

LANDER: CANCERS YOU MIGHT SAY WERE DIFFERENT, SOME BLOOD CANCER AND SOME SKIN CANCER, ACTUALLY SOMETIMES HAD EXACTLY THE SAME MUTATIONS, AND THAT'S COMPLETELY CHANGED THE WAY PEOPLE ARE ORGANIZING NEW KINDS OF CLINICAL TRIALS, BASED ON BIOLOGICAL MECHANISM, NOT SITE OF ORIGIN.

NARRATOR: 34-YEAR-OLD LETTIE LASSITER WAS DIAGNOSED WITH STAGE 4 GALLBLADDER CANCER IN 2013.

SHE WENT THROUGH 3 ROUNDS OF TRADITIONAL CHEMOTHERAPY, BUT THAT DID LITTLE TO HOLD HER TUMORS AT BAY.

THEN ONE AFTERNOON, SHE SUDDENLY COLLAPSED.

[SIREN] THE CANCER HAD SPREAD TO HER BRAIN.

WOMAN: METASTATIC GALLBLADDER CARCINOMA IS A FATAL DISEASE.

ONLY 2% OF PEOPLE LIVE BEYOND 5 YEARS.

WITH BRAIN METASTASES, THE PROGNOSIS BECOMES EVEN WORSE, AVERAGE LESS THAN 6 MONTHS.

HER BRAIN WAS SHIFTED, WHICH REQUIRED SURGERY, AND THEY WERE ABLE TO REMOVE, BUT OBVIOUSLY IT'S NOT A CURE.

LASSITER: I WAS DOWN A LOT.

YOU KNOW, I HAD THIS CANCER, AND I'M YOUNG.

YOU KNOW, GOT A HUSBAND, HAVE KIDS, HAVE GRANDKIDS, AND I'M LIKE, I'M NOT EVEN GONNA GET TO SEE THEM GRADUATE AND, YOU KNOW, THINGS LIKE THAT.

NARRATOR: THERE WERE NO OTHER DRUGS AVAILABLE TO TREAT HER TYPE OF CANCER, SO LETTIE'S DOCTORS SENT A SAMPLE OF HER TUMOR OUT FOR GENETIC TESTING.

THE TESTS REVEALED THAT HER GALLBLADDER CANCER HAD THE SAME GENETIC MUTATION AS A KIND OF BREAST CANCER KNOWN TO BE RESPONSIVE TO AN EXISTING DRUG.

...2, 3... NICE STICK.

PABBATHI: FOR HER, IT WAS PERFECT WHERE WE FOUND A GENOMIC ALTERATION, WE HAD DRUGS, WE HAD A CLINICAL TRIAL.

NARRATOR: LETTIE ENROLLED IN THE CLINICAL TRIAL IN MAY 2017, TAKING TWO DRUGS DESIGNED SPECIFICALLY TO TARGET A BREAST CANCER GENE.

IMMEDIATELY, HER TUMORS BEGAN TO SHRINK.

PABBATHI: SHE RESPONDED WELL IN HER LIVER, BUT A DRAMATIC RESPONSE IN HER PELVIS IN JUST A COUPLE OF MONTHS.

THE LAST SCAN WE DID IN DECEMBER CONTINUES TO SHOW ONGOING RESPONSE.

BUT MORE THAN RADIOGRAPHIC PICTURES, I THINK SHE'S FEELING A LOT BETTER.

NOW SHE COMES BACK, SHE LOOKS NORMAL, SHE'S UPBEAT, AND SHE'S LIVING HER LIFE.

HI THERE.

LASSITER: COME ON.

HOW ARE YOU?

HEY!

GOOD TO SEE YOU.

YOU DOING OK?

I'M DOING GOOD, DOING GOOD.

YOUR BLOOD WORK SHOWS YOUR COUNTS ARE LOOKING GOOD.

YOUR WHITE COUNT, YOUR HEMOGLOBIN, PLATELETS, NORMAL.

I THINK WE ARE READY TO CONTINUE WITH THE SAME PROGRAM.

ALL RIGHT?

CAN I CHECK YOU?

SURE CAN.

ALL RIGHT.

VERY GOOD.

LASSITER: I MEAN, WHEN THEY SAID IT HAD THE SAME CELLS AS BREAST CANCER, I'M LIKE, "BREAST CANCER AND GALLBLADDER?

YOU KNOW, HOW CAN THAT BE?"

AND I'VE BEEN ON THAT MEDICINE I THINK ALMOST TWO YEARS NOW, AND I JUST FEEL LIKE I GOT MY LIFE BACK NOW.

I FEEL LIKE LETTIE AGAIN.

MM-HMM.

YES, I DO.

PABBATHI: YOU QUALIFY FOR DRUGS BASED ON YOUR GENOMIC ALTERATIONS, RATHER THAN YOUR CANCER ORIGIN.

YOU DON'T GO BY BREAST CANCER, LUNG CANCER, G.I.

CANCER.

YOU GO BY, "THIS IS MY GENOMIC ALTERATION.

THIS IS MY TARGET.

THIS IS MY DRUG," AND THAT'S HOW WE SEE RESULTS.

[MACHINE BEEPS] NARRATOR: STORIES LIKE LETTIE LASSITER'S DEMONSTRATE THAT GENETICS CAN NOW PREDICT AND CHANGE THE COURSE OF SOME DISEASES.

IT'S STILL UNCLEAR EXACTLY HOW MANY GENETIC DISEASES CAN BE PREDICTED AND HEADED OFF BEFORE THEY DEVELOP.

THE COMPLEXITY OF THE GENOME AND THE DIFFICULTY OF ACCURATELY ASSESSING THE INFLUENCE OF ENVIRONMENTAL FACTORS PRESENT FORMIDABLE PROBLEMS.

BUT THE EXAMPLE OF BREAST CANCER SCREENING ILLUSTRATES WHAT WILL BECOME POSSIBLE.

THE DISCOVERY OF THE TWO MAIN GENES ASSOCIATED WITH FAMILIAL BREAST CANCER IN THE 1990s, BRCA1 AND BRCA2, WAS A MAJOR BREAKTHROUGH.

BUT AT LEAST A THIRD OF FAMILIES WITH A STRONG RISK OF THE DISEASE DON'T HAVE MUTATIONS IN THOSE TWO GENES, SO A NEW APPROACH WAS NEEDED.

WE HAVE BEGUN TO DECIPHER THE MULTITUDES OF GENES THAT CAUSE THE RISK FOR A WOMAN WHO DOESN'T HAVE A BRCA1 OR BRCA2 MUTATION.

NOW YOU COULD POTENTIALLY SCREEN THAT WOMAN, BECAUSE NOW YOU KNOW THAT SHE HAS A HEIGHTENED RISK.

YOU COULD SCREEN THAT WOMAN MORE AGGRESSIVELY FOR BREAST CANCER AND INTERVENE EARLY.

NARRATOR: GENETIC SEQUENCING IS LIKELY SOON TO BECOME A MAJOR PART OF DISEASE DIAGNOSIS AND PREVENTION.

IN FACT, IT MAY BE A REGULAR PART OF A DOCTOR'S VISIT.

THIS KIND OF INDIVIDUALIZED GENETIC SCREENING HAS BEEN GIVEN A NAME: PRECISION MEDICINE.

COLLINS: PRECISION MEDICINE IS THE IDEA OF BRINGING TOGETHER EVERYTHING YOU KNOW ABOUT THE INDIVIDUAL-- THEIR INHERITANCE, THEIR GENOME, BUT ALSO THEIR ENVIRONMENT, THEIR HEALTH BEHAVIORS, THEIR LIFESTYLE, THEIR DIET-- AND OPTIMIZING A MEANS OF PREVENTING DISEASE OR, IF DISEASE OCCURS, A MEANS OF TREATING IT IN A WAY THAT'S NOT ONE SIZE FITS ALL.

IT'S ACTUALLY PRECISE FOR THAT PERSON.

NARRATOR: AT THE NATIONAL INSTITUTES OF HEALTH IN BETHESDA, MARYLAND, A TEAM UNDER DIRECTOR FRANCIS COLLINS HAS LAUNCHED AN AMBITIOUS PRECISION MEDICINE PROJECT.

THEY ARE ENROLLING A MILLION PEOPLE, WHOM THEY PLAN TO TRACK FOR DECADES.

COLLINS: PEOPLE WALK AROUND WITH WEARABLE SENSORS THAT KEEP TRACK OF WHAT'S HAPPENING TO THEM.

THEY ANSWER LOTS OF QUESTIONNAIRES ABOUT THEIR HEALTH.

AND OVER THE COURSE OF MANY YEARS, WE ARE GOING TO LEARN MORE THAN WE HAD EVER DREAMED OF KNOWING ABOUT WHAT IT IS THAT PLAYS OUT IN PEOPLE'S ACTUAL HEALTH EXPERIENCE.

SOME OF THIS MAY BE THE ABILITY TO DO PREDICTION OF FUTURE ILLNESS SO THAT YOU MODIFY YOUR LIFESTYLE IN A WAY THAT'S SPECIFIC FOR YOU.

SOME OF IT MAY BE EARLY DETECTION.

IF YOU DO GET SICK AND YOU NEED A DRUG, WHAT DRUG?

WHAT DOSE?

THERE ARE MORE THAN 100 DRUGS FOR WHICH WE ACTUALLY KNOW THAT YOUR RESPONSE TO THAT WILL DEPEND ON SOMETHING WE COULD MEASURE IN YOUR DNA.

LANDER: THIS IS NO SMALL UNDERTAKING AND IT'S NOT GONNA HAPPEN OVERNIGHT, BUT IT IS CLEARLY GONNA BE A THEME OF MEDICINE IN THE 21st CENTURY.

NARRATOR: BUT EVEN AS THE AGE OF PERSONAL GENETIC DATA ARRIVES, SO DOES AN OLD SPECTER: EUGENICS.

IF AN INDIVIDUAL'S GENETIC MAKEUP IS MADE READILY AVAILABLE, WILL IT BE USED TO DISCRIMINATE IN EMPLOYMENT OR INSURANCE OR TO MAKE SUBJECTIVE JUDGMENTS ABOUT DIFFERENT RACES OR ETHNICITIES?

WOMAN: GENETICS, REALLY, BECAUSE OF IT BEING THE SORT OF CORE OF WHO WE ARE, OF COURSE, GETS MOBILIZED INTO IDEAS ABOUT HUMAN PERFECTION AND A KIND OF FANTASY ABOUT BEING ABLE TO PERFECT OURSELVES AND PERFECT OUR CHILDREN AND OUR CHILDREN'S CHILDREN.

NARRATOR: IT IS A TRAP THAT HAS ENSNARED EVEN PIONEERS IN THE FIELD.

JAMES WATSON HAS APPALLED THE SCIENTIFIC COMMUNITY WITH A SERIES OF UNFOUNDED REMARKS ABOUT THE GENETIC DIFFERENCES BETWEEN RACES AND GENDERS.

♪ IN FACT, EVIDENCE FOUND IN OUR GENOMES IN THE LAST FEW DECADES HAS REVEALED NOT HOW DIFFERENT WE ARE, BUT HOW ALIKE, AND HAS TOLD A COMPELLING STORY OF OUR SHARED HISTORY AS A SPECIES.

COBB: WE THINK ABOUT THE GENOME AS BEING ALL ABOUT MEDICINE AND THINGS ABOUT THE FUTURE, BUT FOR ME, THE MOST INTERESTING AND FASCINATING AND MIND-BOGGLING THING IS WHAT IT TELLS US ABOUT OUR PAST.

THE NEANDERTHALS, WHO WERE LONG THOUGHT TO BE THIS BRUTISH SPECIES OF HUMAN, THEY WENT EXTINCT ABOUT 35,000 YEARS AGO IN EUROPE, NOW TURNS OUT THAT BETWEEN THE NEANDERTHAL AND US, THERE ARE JUST 96 AMINO ACID DIFFERENCES, WHICH IS VIRTUALLY NOTHING.

AND, EVEN MORE, WE NOW KNOW THAT, BY COMPARING THIS ANCIENT DNA FROM NEANDERTHAL BONES AND OUR DNA, THAT, IN FACT, WE'RE NOT TECHNICALLY TWO SEPARATE SPECIES.

WE MATED WITH EACH OTHER.

EVERYBODY WHO IS NOT OF IMMEDIATE AFRICAN DESCENT HAS SOME NEANDERTHAL DNA IN THEM.

NARRATOR: LIKE THE RINGS IN A TREE, OUR GENOMES CONTAIN A RECORD OF OUR HISTORY AS A SPECIES.

BY COMPARING FOSSILIZED GENOMES, SCIENTISTS CAN SEE WHEN AND WHERE THE BRANCHES OF THE EVOLUTIONARY TREE DIVERGE AND THEREBY RECONSTRUCT THE HUMAN JOURNEY OUT OF AFRICA.

♪ COBB: BY LOOKING AT THE VARIATION THAT THERE IS BETWEEN DIFFERENT POPULATIONS, WE CAN READ BACK IN TIME.

AND WE KNOW THAT THE HUMAN POPULATION WENT DOWN TO 10,000 BREEDING PEOPLE ABOUT 80,000 YEARS AGO.

10,000, THAT'S IT.

THAT NARROWING OF OUR POPULATION TO THAT OF A SMALL TOWN.

WE WERE VERY, VERY LUCKY TO ESCAPE THAT PERIOD AND THEN TO COME TO DOMINATE THE PLANET.

THERE WAS NOTHING PREORDAINED ABOUT OUR SURVIVAL.

NARRATOR: WITH ALL PEOPLE ALIVE TODAY EVOLVING FROM SUCH A SMALL POPULATION OF FOUNDERS, IT IS NO SURPRISE THAT EVERY HUMAN BEING, NO MATTER WHERE THEY LIVE OR WHAT THEY LOOK LIKE, SHARES OVER 99% OF HIS OR HER DNA WITH EVERY OTHER HUMAN BEING.

MAN: WE'RE A NEW SPECIES THAT EXPANDED QUICKLY, AND WE ARE ALMOST GENETICALLY IDENTICAL TO EACH OTHER.

WE ARE MORE ALIKE, NO MATTER WHERE IN THE WORLD OUR ANCESTORS CAME FROM, THAN CHIMPANZEES IN THE SAME BAND IN A FOREST IN TANZANIA.

WE LOOK DIFFERENT BECAUSE OUR ANCESTORS ENCOUNTERED DIFFERENT ENVIRONMENTS, MORE OR LESS SUNLIGHT, MORE OR LESS HEAT OR COLD, THAT'S CHANGED OUR OUTSIDES.

THE OVERWHELMING REALITY OF HUMAN POPULATION GENETICS IS HOW SIMILAR WE ARE, NOT HOW DIFFERENT WE ARE.

NARRATOR: WHILE HUMAN MIGRATION HAS ALLOWED FOR SUPERFICIAL GENETIC DIFFERENCES TO EVOLVE, THERE IS NO EVIDENCE FOR GROUPING PEOPLE BY MORE COMPLEX TRAITS.

MAN: OUR SOCIALLY DEFINED NOTIONS OF RACE ARE NOT SUPPORTED GENOMICALLY.

THERE IS MORE GENETIC VARIATION WITHIN THE GROUPS THAT WE HAVE THOUGHT WERE BIOLOGICAL RACES THAN BETWEEN THEM, MEANING THAT THEY REALLY AREN'T RACES.

WE CAN CALL PEOPLE THIS, THAT, OR THE OTHER, BUT IF WE LOOK AT THE UNDERLYING BASIS OF WHAT MAKES PEOPLE PEOPLE, THOSE DISTINCTIONS, THOSE CATEGORIES SIMPLY DO NOT EXIST.

NARRATOR: WHERE GENETIC DIFFERENCE MATTERS IS NOT AT THE LEVEL OF LARGE GROUPS, BUT INDIVIDUALLY, AND HERE, A SINGLE GENETIC ABERRATION CAN MEAN THE DIFFERENCE BETWEEN LIFE AND DEATH.

♪ FOR CHERYL AND JEREMY YODER, THAT FACT WAS TRAGICALLY BROUGHT HOME WHEN THEY LOST THEIR DAUGHTER ARIEL TO SPINAL MUSCULAR ATROPHY IN APRIL 2014.

WHILE STILL GRIEVING, THEY LEARNED THAT THEIR NEWBORN SON JASE HAD ALSO TESTED POSITIVE FOR THE FATAL GENETIC DISEASE.

FEARING THAT NOTHING COULD BE DONE, BUT NOT WANTING TO LEAVE ANY STONE UNTURNED, THE YODERS TOOK JASE TO SEE THEIR NEUROLOGIST, WHO SURPRISED THEM WITH HIS REACTION.

CHERYL YODER: WE GOT TO THE ROOM AND HE SAID, "THIS BABY HAS SMA?

YOU HAVE THE GENETIC TEST?"

LIKE, "YOU HAVE THE PAPERS?"

AND WE HAD THEM THERE WITH US.

AND HE JUST GOT SO EXCITED AND WAS STARTING TO KIND OF PACE AROUND THE ROOM.

NARRATOR: THE YODERS' NEUROLOGIST TOLD THEM ABOUT AN EXPERIMENTAL DRUG THAT, FOR THE FIRST TIME, TREATED THE DISEASE BY INTERVENING DIRECTLY ON THE FUNCTIONING OF THE SMA GENE.

DEVELOPED BY A COMPANY IN CALIFORNIA, AND BASED ON YEARS OF PATHBREAKING WORK BY ADRIAN KRAINER AT COLD SPRING HARBOR, THE DRUG REPRESENTED A WHOLLY NEW WAY OF TREATING GENETIC DISEASE.

IT'S A LITTLE PIECE OF RNA THAT SEEKS OUT THE SMN2 GENE AND BLOCKS A MISTAKE IN IT.

THEY HOPED THIS WOULD MAKE IT PRODUCE MORE OF THE ESSENTIAL PROTEIN THAT JASE WAS MISSING.

THE YODERS' NEUROLOGIST WANTED TO ENROLL JASE IN THE TRIAL RIGHT AWAY.

ONCE HE SHOWED THE SLIGHTEST SIGN OF HAVING THE DISEASE, JASE WOULD NO LONGER BE ELIGIBLE.

♪ CHERYL YODER: WE WERE SHOCKED.

THAT'S NOT WHAT WE HAD EXPECTED TO HEAR.

WE WENT AWAY FROM THAT VISIT WITH JUST THIS KIND OF LIKE SURREAL LIKE, "PINCH ME.

IS THIS REALLY HAPPENING?"

THIS HOPE JUST SORT OF STARTING TO RISE IN OUR HEARTS, AND IT FELT WEIRD, AND IT FELT WONDERFUL.

NARRATOR: JASE GOT HIS FIRST DOSE OF THE EXPERIMENTAL TREATMENT, CALLED NUSINERSEN, THROUGH AN INFUSION INTO HIS SPINAL FLUID, WHEN HE WAS JUST 18 DAYS OLD.

CHERYL YODER: WE WERE ON A JOURNEY.

IT WAS KIND OF LIKE MIRACLE OR BUST, YOU KNOW?

WE'RE GONNA HAVE A MIRACLE OR WE'RE JUST GOING TO LOSE HIM.

OUR HOPE WAS THAT MAYBE OUR BABY WOULD BE ABLE TO AT LEAST SIT OR EAT NORMAL FOOD OR MAYBE HE WOULD WALK EVEN.

CHERYL YODER: WHAT ARE YOU DOING?

ARE YOU SITTING UP?

IT'S A MIRACLE!

IT'S JANUARY... JANUARY 24.

JEREMY YODER, VOICE-OVER: AS TIME GOES ON AND JASE BEGINS TO DO THINGS THAT ARIEL DIDN'T... CHERYL YODER: HE'S CRAWLING!

JEREMY YODER, VOICE-OVER: THERE'S THIS NEW HOPE, LIKE, HEY, IT LOOKS LIKE WE'RE GONNA GET TO RAISE HIM.

CHERYL YODER: I LOVE HOW YOU WALK WITH YOUR HANDS UP!

YES!

PERSON: OH!

CHERYL YODER, VOICE-OVER: WE WERE AT SOME FRIEND'S HOUSE FOR THE EVENING AND I SET JASE DOWN ON THE FLOOR... DADDY'S THERE.

CHERYL YODER, VOICE-OVER: AND JASE JUST TOOK A COUPLE STEPS AND IT WAS LIKE, "OH, MY GOODNESS, HE'S DOING IT.

LIKE, THAT'S MORE THAN HE'S EVER DONE BEFORE."

WOMAN: OH, GOOD JOB!

MAN: ARE YOU READY TO GO?

CHERYL YODER, VOICE-OVER: JASE WAS JUST GOING BACK AND FORTH BETWEEN US, AND WE KEPT BACKING UP AND HE WOULD GO FURTHER... COME TO DADDY.

YOU'RE DOING SO GOOD!

WHOA, THAT WAS AMAZING!

[CHEERING AND APPLAUSE] CHERYL YODER, VOICE-OVER: EVERYONE THAT WAS THERE WAS STANDING AROUND CHEERING, AND IT WAS AWESOME.

[CROWD CHEERING] THAT'S WONDERFUL.

CHERYL YODER, VOICE-OVER: AND THEN ON OUR WAY HOME IT WAS JUST QUIET AND WE WERE ALL JUST KIND OF LIKE, [SIGH] LIKE, "DID THAT REALLY...

THIS REALLY HAPPENED."

NARRATOR: JASE RECENTLY CELEBRATED HIS 3rd BIRTHDAY, UNAWARE THAT HE IS A MEDICAL PIONEER WHO REPRESENTS THE PROMISE OF A GENOMIC REVOLUTION DECADES IN THE MAKING.

I'M GONNA GET YOU!

NARRATOR: HE AND TWO DOZEN OTHER PRE-SYMPTOMATIC CHILDREN IN THE TRIAL ARE ALL DOING WELL.

THEY NEED SPINAL INFUSIONS OF THE DRUG EVERY FEW MONTHS.

YEAH, TREE!

NARRATOR: BUT WITHOUT THEM, THEY WOULD ALMOST CERTAINLY NO LONGER BE ALIVE.

[LAUGHS] I BET YOU CAN'T CATCH ME!

RAWR!

CHERYL YODER, VOICE-OVER: THERE'S JUST TIMES IN THIS JOURNEY WHERE THE FULL SERIOUSNESS OF IT HITS US AND WE'RE LIKE, WE'RE LOOKING AT SOMETHING AND WE'RE HOLDING A PERSON WHO, LIKE, EARTH HAS NEVER SEEN ANYTHING LIKE THIS BEFORE.

THIS HAS NOT BEEN POSSIBLE.

THIS IS AMAZING, AND YET IT'S ALSO REALLY NORMAL.

JEREMY YODER, VOICE-OVER: I'M A DREAMER.

I MEAN, HE'S JUST MY LITTLE SON, SO, I'M JUST TAKING THESE MOMENTS FOR WHAT THEY ARE AND LOVING HIM, LOVING LIFE, LOVING THE SEASON OF LIFE THAT WE'RE IN.

♪ COLLINS: I THINK EACH MOMENT WHERE THERE HAS BEEN A DRAMATIC SUCCESS DOESN'T JUST ENLIVEN THE PEOPLE WHO ARE WORKING ON THAT DISEASE.

IT HAS RIPPLES ACROSS THE FIELD.

IT'S ONE MORE REASON TO BELIEVE THAT THOSE DECADES OF REALLY HARD SLOGGING ARE FINALLY BEGINNING TO YIELD UP SOME REALLY REMARKABLE EVENTS AND THAT MAKES EVERYBODY INTERESTED IN WORKING HARDER AND PROBABLY RECRUITS NEW PEOPLE INTO THE FIELD WHO MAYBE WERE HOLDING BACK FOR FEAR THAT THIS WASN'T READY YET.

IT SEEMS TO BE READY NOW.

♪ NARRATOR: FOR ALL THE PROGRESS IN UNDERSTANDING DISEASE-CAUSING GENES, AND EVEN WITH THE SUCCESS IN SMA, DOCTORS KNOW THAT FAR MORE NEEDS TO BE DONE FOR THIS AND OTHER DISEASES.

BUT WHAT IF, RATHER THAN TRY TO FIX THE EFFECTS OF A BROKEN GENE, THEY COULD TREAT SOME DISEASES BY GIVING PATIENTS A HEALTHY GENE INSTEAD?

TILGHMAN: ONE OF THE IMPLICATIONS OF THE ABILITY TO ISOLATE GENES WAS THE IDEA THAT THEY COULD BE USED BASICALLY AS DRUGS, PARTICULARLY WHERE THE INDIVIDUAL HAD A MUTATION IN A SPECIFIC GENE.

SO, IF YOU COULD THEN REPLACE THE MUTANT GENE WITH A GOOD, INTACT GENE, COULD YOU THEN BASICALLY CURE THE DISEASE?

NARRATOR: FOR A LONG TIME, THE LOGISTICAL CHALLENGE HAD SEEMED INSURMOUNTABLE.

EVEN IF YOU COULD GET A NEW GENE INTO A STRAND OF DNA LOCATED DEEP INSIDE THE NUCLEUS OF A CELL, HOW WOULD YOU REPLACE ENOUGH OF THEM IN ENOUGH CELLS TO MAKE A DIFFERENCE?

WHAT WE'VE DISCOVERED IS THAT EVERYTHING IN BIOLOGY IS GENES.

WE THINK WITH GENES.

WE HAVE DISEASE WITH GENES.

AND, SO, FIGHTING DISEASE BY FIGHTING GENES MAKES SENSE.

PROBLEM IS THAT GENES ARE HARD TO GET AT.

NARRATOR: BUT IN THE 1980S, SCIENTISTS THOUGHT THAT THEY MIGHT HAVE FOUND A SOLUTION: SMUGGLING BILLIONS OF HEALTHY GENES INTO CELLS BY ATTACHING THEM TO THE ONE ORGANISM THAT HAD ALREADY FIGURED OUT HOW TO DO IT: VIRUSES.

VIRUSES INHABIT A UNIQUE PLACE IN BIOLOGY.

THEY ARE MADE PRIMARILY OF DNA, BUT THEY CAN'T REPRODUCE ON THEIR OWN.

SO, THEY HAVE EVOLVED THE ABILITY TO INVADE THE CELLS OF OTHER ORGANISMS AND HIJACK THEIR REPRODUCTIVE MACHINERY.

WHY NOT USE THEM, THEN, AS GENE DELIVERY VEHICLES?

THE IDEA WAS CALLED "GENE THERAPY."

THE FIRST WAVE OF GENE THERAPY TRIALS BEGAN AMID GREAT EXCITEMENT IN THE EARLY 1990S.

JOAN LUNDEN: SOMEDAY, OUR DOCTORS WILL SIMPLY DIAGNOSE OUR ILLNESSES, PRESCRIBE THE PROPER STRAND OF MOLECULES, AND SEND US HOME, CURED.

NARRATOR: AT THE CENTER OF IT ALL WAS JIM WILSON, A TALENTED YOUNG SCIENTIST, RECRUITED TO HEAD UP THE NATION'S NEWEST AND LARGEST GENE THERAPY CENTER AT THE UNIVERSITY OF PENNSYLVANIA IN PHILADELPHIA.

WILSON: THIS WAS GONNA CHANGE MEDICINE AND THEY WERE AHEAD OF THE CURVE.

THEY PUT SIGNIFICANT RESOURCES INTO RECRUITING ME FROM MICHIGAN TO BUILD A CAMPUS-WIDE INSTITUTE FOR GENE THERAPY.

NARRATOR: WITH A STAFF OF 200, WILSON HOPED TO BECOME THE FIRST SCIENTIST TO RUN A SUCCESSFUL GENE THERAPY TRIAL.

GENE THERAPY RESEARCH.

IT IS CREATING ENORMOUS EXCITEMENT.

IT'S GOING TO BE A WONDERFUL REVOLUTION.

IT'S GOING TO TURN OVER THE WAY WE MANAGE DISEASE AS DOCTORS.

UM, IT IS--IT'S THE BEST PARTS OF A BRAVE NEW WORLD.

NARRATOR: ONE OF WILSON'S FIRST TRIALS WAS DESIGNED TO TEST A GENE THERAPY TO CURE A RARE LIVER DISEASE CALLED OTC.

AFTER SUCCESSFULLY ATTACHING A HEALTHY COPY OF THE OTC GENE TO A VIRUS ASSOCIATED WITH THE COMMON COLD AND SHOWING IN ANIMAL TRIALS THAT IT COULD WORK, WILSON GAINED APPROVAL TO BEGIN TESTING THE THERAPY IN HUMANS.

IN SEPTEMBER 1999, A YOUNG MAN NAMED JESSE GELSINGER, SUFFERING FROM A MILD FORM OF THE DISEASE, CAME TO PHILADELPHIA FOR EXPERIMENTAL TREATMENT.

HIS FATHER PAUL SUPPORTED THE DECISION.

GELSINGER: IT WAS EXCITING TO THINK THAT THIS MIGHT ACTUALLY WORK.

THEY WERE ON THE PATH TO MAYBE FINDING A CURE, AND THERE WE WERE, WE WERE GONNA BE A PART OF IT.

NARRATOR: ON THE MORNING OF SEPTEMBER 13th, DOCTORS INFUSED JESSE WITH BILLIONS OF VIRUS PARTICLES CARRYING THE HEALTHY GENE.

IT TOOK TWO HOURS.

PAUL SPOKE TO HIS SON BY PHONE LATER THAT DAY.

GELSINGER: HE SOUNDED OK.

HE WAS, YOU KNOW, HE WASN'T FEELING WELL.

HE SAID, "I'M NOT FEELING TOO GOOD, DAD," AND IT WAS THE EXPECTED SIDE EFFECTS.

AND THEN AT THE END, WE GOT TO SAY GOOD-BYE, AND MY LAST WORDS WERE "JESSE, I LOVE YOU."

NARRATOR: OVERNIGHT, JESSE DEVELOPED A FEVER.

HIS CONDITION CONTINUED TO WORSEN THE FOLLOWING DAY.

HIS ORGANS FAILING, DOCTORS MOVED HIM ONTO LIFE SUPPORT.

HE DIED ON SEPTEMBER 17, 1999.

GELSINGER: HIS HEART HAD BEEN BEATING STRONG ALL ALONG, BUT THIS THING HAD JUST DONE SUCH CATASTROPHIC DAMAGE TO HIS BODY THAT THERE WAS NO RECOVERY POSSIBLE, AND... THAT'S MY KID WHO I HAD MADE SURE WAS OK ALL HIS LIFE, AND I PUT HIM IN THE HANDS OF OTHERS, AND HE WAS GONE.

NARRATOR: AN AUTOPSY SHOWED THAT THE VIRUS PARTICLES INJECTED INTO JESSE HAD TRIGGERED A MASSIVE REACTION FROM HIS OWN IMMUNE SYSTEM.

WILSON: THE INFLAMMATION STARTED AS SOON AS THAT VIRUS WENT INTO HIS BLOOD AND THE ONLY WAY THAT COULD BE THE CASE IS IF IT WAS THE DELIVERY VEHICLE, THE SHELL OF THE VIRUS, WAS ACTIVATING THE IMMUNE SYSTEM.

NARRATOR: IT WAS LATER DETERMINED THAT WILSON AND HIS TEAM HAD COMMITTED SERIOUS ETHICAL BREACHES.

WILSON HAD AN UNDISCLOSED FINANCIAL STAKE IN A COMPANY THAT STOOD TO PROFIT FROM A SUCCESSFUL TRIAL.

FURTHERMORE, HIS TEAM HAD FAILED TO WARN THE GELSINGERS OF PREVIOUS PROBLEMS IN ANIMAL TESTS.

WILSON WAS BANNED FROM CONDUCTING HUMAN TRIALS FOR 5 YEARS.

COLLINS: YOU KNOW, HUMAN BIOLOGY SHOULD NEVER BE UNDERESTIMATED FOR ITS COMPLEXITY.

THE SYSTEMS THAT HAVE BEEN SHAPED BY EVOLUTION OVER THESE HUNDREDS OF MILLIONS OF YEARS ARE VERY WELL DESIGNED TO TACKLE SOMETHING THAT'S UNEXPECTED COMING FROM THE OUTSIDE.

GENE THERAPY IS ONE OF THOSE THINGS COMING FROM THE OUTSIDE THAT IS UNEXPECTED AND ALL OF THOSE MECHANISMS THAT ARE PROTECTING US HUMAN ORGANISMS AGAINST BAD THINGS THAT ARE ALL AROUND US ARE GONNA KICK IN.

THEY'RE WHY WE'RE HERE.

THEY KEEP US GOING.

AND SOMETIMES, WHEN WE MIGHT NOT WANT THEM TO ACT, THEY'RE GOING TO ANYWAY.

THAT'S WHAT HAPPENED WITH JESSE.

♪ WILSON: REFLECTING ON WHAT HAPPENED, FOCUSING ON JESSE AND HIS FAMILY, IT'S A TRAGIC EVENT AND THE EXTENT TO WHICH WE DID ANYTHING THAT THEY WOULD HAVE FELT THAT WE LET THEM DOWN, UM, I TAKE RESPONSIBILITY FOR AND I DO NOT TAKE THAT LIGHTLY.

UM, AND I...RECOGNIZE ANY ISSUE OR CONCERN THAT THEY HAD IS LEGITIMATE AND ANYTHING THAT WE COULD HAVE DONE TO HAVE PREVENTED THAT WE SHOULD HAVE, AND WE HAVE LEARNED A LOT OF LESSONS ABOUT IT AND I THINK ABOUT IT FREQUENTLY, AND I'LL THINK ABOUT IT FREQUENTLY UNTIL THE DAY I DIE.

I DON'T KNOW WHAT ELSE TO SAY.

NARRATOR: WHEN JESSE DIED, GENE THERAPY ALL BUT DIED WITH HIM.

BUT THE IDEA THAT HAD SO CAPTURED THE SCIENTIFIC COMMUNITY REMAINED COMPELLING.

OVER THE NEXT DECADE, RESEARCHERS, INCLUDING WILSON HIMSELF, WORKED TO DEVELOP SAFER VIRUSES.

TODAY, NEW GENE THERAPY TRIALS ARE UNDERWAY ALL OVER THE WORLD.

ONE OF THE MOST EAGERLY WATCHED IS UNFOLDING IN BOSTON, MASSACHUSETTS.

ITS TARGET IS SICKLE CELL DISEASE, A DEBILITATING, AND SOMETIMES FATAL, BLOOD DISORDER.

ONE OF THE FIRST PATIENTS ON THE TRIAL IS 26-YEAR-OLD BRUNEL ETIENNE.

WOMAN: BRUNEL, HE NEVER CRIES ABOUT BEING SICK, BUT THE DAY THE DOCTOR TOLD HIM THAT YOU CAN'T DRIVE BECAUSE OF THIS DISEASE, BECAUSE OF HE HAD SO MANY STROKES, I REMEMBER HIM CRYING.

AND I HAD TO ASK THE DOCTOR, "PLEASE, CAN YOU GIVE US A MOMENT?"

BECAUSE THAT WAS, TO ME, THAT WAS THE MOMENT ALSO, IT WAS SO HARD FOR ME, YOU KNOW, JUST WATCHING MY KID, AND THERE'S NOTHING I CAN DO ABOUT IT.

DO YOU HAVE ANYTHING THAT'S ON YOUR MIND THAT YOU WANT ME TO ASK THEM?

BRUNEL: UM...

I STILL FEEL, LIKE, WEIRD AFTER, LIKE-- ARE YOU GONNA FEEL WEIRD AFTER?

YEAH.

OK. NARRATOR: THE SICKLE CELL MUTATION CAUSES RED BLOOD CELLS TO STRETCH AND STIFFEN, SO, THEY GET STUCK IN SMALL BLOOD VESSELS.

WOMAN: SICKLE CELL DISEASE IS ALWAYS THE SAME MUTATION IN THE GENE CALLED BETA GLOBIN, AND IT RESULTS IN A CHANGE IN A FUNDAMENTAL PART OF HEMOGLOBIN, WHICH IS THE PROTEIN INSIDE OF RED CELLS THAT HELPS US TO CARRY OXYGEN.

MUKHERJEE: THE DIFFERENCE IS IN ONE LETTER OF THE CODE.

JUST ONE LETTER, IT BECOMES ABNORMAL.

IT IS UNABLE TO CARRY OXYGEN PROPERLY.

AND IT RESULTS IN A DIFFUSE DISEASE.

MAN: PEOPLE KNOW ABOUT HEART ATTACKS, AND YOUR ARTERIES IN YOUR HEART CLOGGING UP AND HOW PAINFUL THAT IS.

IT'S SORT OF LIKE THAT, BUT IT'S ALL OVER THE BODY.

AND SO, THAT CAUSES BOTH PAIN, BUT IT ALSO, OF COURSE, DAMAGES WHATEVER ORGAN THAT YOU'RE, YOU'RE TALKING ABOUT, AND THAT LEADS TO THE LONG-TERM COMPLICATIONS OF SICKLE CELL DISEASE.

NARRATOR: BRUNEL SUFFERED HIS FIRST STROKE WHEN HE WAS 22 MONTHS OLD.

AND LIKE ALL SICKLE CELL PATIENTS, HE NEEDS REGULAR BLOOD TRANSFUSIONS TO SURVIVE.

CHUNG: WE'VE KNOWN ABOUT THE EXACT MOLECULAR DEFECT IN THIS CASE WELL BEFORE WE HAD THE HUMAN GENOME SEQUENCED.

THIS WAS ONE OF THE FIRST CONDITIONS THAT WE UNDERSTOOD VERY WELL, YET NOT BEING ABLE TO REALLY COME UP WITH A TREATMENT.

ONE WOULD THINK, SO SIMPLE, YET JUST DASTARDLY DIFFICULT IN TERMS OF COMING UP WITH A TREATMENT.

NARRATOR: FOR YEARS, THE ONLY LASTING REMEDY WAS A BONE MARROW TRANSPLANT, BUT BRUNEL DIDN'T HAVE A SUITABLE MATCH.

YOU OK?

YEAH.

GOOD JOB.

NARRATOR: SO, WHEN HE FIRST HEARD THAT THE GENE THERAPY TRIAL MIGHT RID HIM OF SICKLE CELL, HE LEAPT AT THE CHANCE.

BRUNEL ETIENNE, VOICE-OVER: I FEEL LIKE, IT'S LIKE A, A MONSTER... THAT'S INSIDE ME THAT WON'T GO AWAY.

MAKES YOU FEEL WEAK.

NARRATOR: BUT NOW BRUNEL HAS A CHANCE OF RECOVERY.

THE CLINICAL TRIAL, UNDER THE GUIDANCE OF DR. DAVID WILLIAMS AT DANA-FARBER HOSPITAL IN BOSTON, IS TAKING A NOVEL APPROACH.

RATHER THAN TRYING TO TREAT BRUNEL'S DISEASE BY GIVING HIM A NEW, HEALTHY BLOOD-PRODUCING GENE, WILLIAMS' TEAM IS LOOKING TO CURE HIS SICKLE CELL OUTRIGHT BY TARGETING A COMPANION GENE.

SCIENTISTS FOUND IT WHEN A GENOME-WIDE STUDY REVEALED WHY CERTAIN PEOPLE WITH SICKLE CELL WERE ACTUALLY SYMPTOM-FREE.

THE COMPANION GENE ACTS LIKE A SWITCH THAT CAN KEEP THEIR FETAL HEMOGLOBIN LEVELS HIGH AND THEIR SICKLE CELL DISEASE AT BAY.

UNTIL THEN, NO ONE HAD EVER CONNECTED THIS GENE WITH SICKLE CELL, BUT IT GAVE WILLIAMS AN IDEA.

WILLIAMS: WE REASONED, IF WE COULD REVERSE THAT SWITCH GENETICALLY, THEN WE COULD ALLOW FETAL HEMOGLOBIN TO COME BACK ON, AND WE COULD TURN DOWN ADULT BETA HEMOGLOBIN, AND THAT'S WHAT WE-- WE DESIGNED AND MANUFACTURED A VIRUS THAT DOES JUST THAT.

NARRATOR: AFTER EXTRACTING STEM CELLS FROM BRUNEL'S BLOOD, WILLIAMS' TEAM TAKES THEM TO A SPECIALIZED LABORATORY WHERE THEY ARE INFUSED WITH BILLIONS OF VIRUS PARTICLES CARRYING A HEALTHY COPY OF THE COMPANION GENE.

THE VIRUS TRANSPORTS THAT GENE STRAIGHT TO THE NUCLEUS OF BRUNEL'S STEM CELLS.

WILLIAMS: THEY'RE THE PATIENT'S OWN STEM CELLS, NOW GENETICALLY MODIFIED.

WE GIVE THOSE BACK TO THE PATIENT, AND WHEN WE DO THAT, WHEN THE RED CELLS ARE MADE FROM THOSE STEM CELLS, THAT ALLOWS THE FETAL HEMOGLOBIN TO COME BACK ON, AND THE REALLY COOL THING ABOUT THAT IS, WHEN THAT HAPPENS, IT TURNS OFF THE SICKLE GENE, TOO.

NARRATOR: TODAY, THE VIRUSES BEING USED IN BRUNEL'S TRIAL ARE SAFER, HAVING GONE THROUGH YEARS OF TESTING TO ENSURE THAT JESSE GELSINGER'S TRAGEDY IS NOT REPEATED.

8 WEEKS AFTER THE HEALTHY GENE WAS CARRIED BY VIRUSES INTO BLOOD CELLS TAKEN FROM BRUNEL, THE GENE THERAPY TREATMENT IS THAWED AND BROUGHT TO HIS BEDSIDE, READY TO BE INFUSED BACK INTO HIS BODY.

NURSES: HERE WE GO.

ALL RIGHT...WOO!

WOMAN: HE WAS ASKING, "WHERE'S MY SIGN?"

[SECOND WOMAN LAUGHS] ESTHER ETIENNE: OH, THIS IS IT?

NURSES: YES.

PEOPLE: 3-2-1... [CHEERING] WOMAN: THE CELLS ARE GOING IN THROUGH THE IV, AND THEN THEY CAN FIND THEIR WAY TO THE BONE MARROW, AND KIND OF SET UP SHOP.

ESTHER ETIENNE: MARCH 15.

YOU WILL ALWAYS REMEMBER THAT DAY, OK?

JUST LIKE YOU REMEMBER YOUR BIRTHDAY.

IT'S A NEW BIRTHDAY.

NARRATOR: IT'S A ONE-TIME TREATMENT THAT DOCTORS HOPE WILL LAST THE REST OF BRUNEL'S LIFE.

THEY WILL MONITOR HIM INTENSIVELY TO SEE IF BLOOD CELLS WITH THE NEW GENE WILL PROLIFERATE AND BLOCK HIS SICKLE CELL DISEASE.

WILLIAMS: WE DON'T CALL THIS A CURE, BECAUSE IT'S WAY TOO EARLY TO CALL THAT.

BUT IF EVERYTHING WORKS THE WAY WE THINK IT SHOULD WORK, THAT WILL BE A LONG-LASTING EFFECT.

NARRATOR: MUCH OF THE MEDICAL FIELD IS WATCHING THE TRIAL CLOSELY.

WITH A LONG HISTORY OF NEGLECT, AND A QUARTER OF A MILLION PEOPLE BORN WITH SICKLE CELL EACH YEAR, A SUCCESSFUL OUTCOME WOULD REPRESENT ONE OF THE BIGGEST AND MOST OVERDUE BREAKTHROUGHS IN GENETICS.

NOW THAT GENETIC SCIENCE APPEARS TO BE ON THE CUSP OF TRANSFORMING LIVES ON A GRAND SCALE, GOVERNMENTS, RESEARCHERS, AND PATIENTS WILL BE FORCED TO ADDRESS THE COMPLEX TOPIC OF COST.

WHO SHOULD PAY FOR THIS WORK AND FOR THE GENE-BASED MEDICINES THAT WILL FOLLOW?

THERE ARE OVER 5,000 GENETIC DISEASES.

SOME, LIKE SICKLE CELL OR SPINAL MUSCULAR ATROPHY, ARE RELATIVELY COMMON.

OTHERS AFFECT ONLY A HANDFUL OF PATIENTS.

WITH THE PRICES OF EACH OF THE FIRST GENETIC MEDICINES TOPPING A MILLION DOLLARS AND MANY SIMILAR DRUGS IN THE PIPELINE, THESE ISSUES WILL CERTAINLY BECOME MORE CONTROVERSIAL.

MUKHERJEE: I'M NOT GOING TO DEFEND THE PRICING FOR MOST DRUGS.

THE EXTRAORDINARY AND DIFFICULT THING FOR DEVELOPING DRUGS FOR RARE GENETIC DISEASES IS THAT THERE MIGHT BE ONLY 15 OR 20 PATIENTS WITH THAT DISEASE, BUT IF THE GENETIC THERAPIES ARE SUCCESSFUL, AND SOME OF THEM HAVE BEEN EXTRAORDINARILY SUCCESSFUL, THEY AVERT A LIFETIME OF RISK AND SUFFERING AND MEDICAL COST.

SO, HOW DO YOU BALANCE THESE TWO THINGS?

NARRATOR: IN ADDITION, GENETIC RESEARCH THAT CURRENTLY BENEFITS ONLY A FEW FAMILIES COULD ULTIMATELY BENEFIT THOUSANDS OR MILLIONS, WHICH FURTHER COMPLICATES THE ISSUE OF WHO SHOULD PAY.

MUKHERJEE: THERE CAN BE NO MORE CLASSIC EXAMPLE THAN THE FACT THAT THE ANTI-CHOLESTEROL PILLS THAT HUNDREDS OF THOUSANDS OF PEOPLE TAKE REALLY EMERGED FROM OBSERVATIONS OF A FAMILY WHERE THERE WAS A MUTATION IN A GENE FOR CHOLESTEROL METABOLISM.

THIS COULD BE TRUE FOR OBESITY.

THIS COULD BE TRUE FOR BREAST CANCER.

THIS COULD BE TRUE FOR ALZHEIMER'S DISEASE.

AND THAT SHOULD BE FOLDED INTO HOW SOCIETY PAYS FOR AND UNDERSTANDS MEDICINE IN GENERAL, BUT THERE'S NO SIMPLE MECHANISM--IT'S A CONUNDRUM.

THERE'S NO SIMPLE MECHANISM TO DO THAT.

♪ NARRATOR: BY ADDING A HEALTHY GENE TO A PATIENT'S GENOME, GENE THERAPY BROUGHT SCIENTISTS CLOSER TO THE SOURCE OF GENETIC DISEASE.

BUT THERE WAS ROOM TO DRAW STILL CLOSER, TO THE UNDERLYING CODE OF A MALFUNCTIONING GENE.

FOR DECADES, THE DREAM OF SCIENTISTS HAD BEEN TO EDIT THE CODE ITSELF, TO FIX THE SPELLING MISTAKES AT THEIR SOURCE.

THAT DREAM HAS PROVED ELUSIVE.

LANDER: SO, I REMEMBER IN THE 1990S AND THE 2000S, TALKING TO PEOPLE ABOUT GENETIC DISEASES, AND SOME LAYPERSON WOULD SAY, "WELL, WHY DON'T YOU JUST GO IN AND CHANGE THE LETTER OF THE DNA?"

AND I WOULD HAVE TO EXPLAIN THAT THERE WAS JUST NO WAY TO GET INTO A CELL AND RECOGNIZE THE EXACT SPOT OF THE SEQUENCE YOU WANTED TO CHANGE.

SO, IT TURNS OUT THAT WAS COMPLETELY WRONG.

THERE IS A WAY TO DO IT.

♪ NARRATOR: SCIENTISTS REALIZED THAT ONE KIND OF ORGANISM DID SEEM TO POSSESS THE ABILITY TO EDIT DNA.

IT WAS ONE OF THE SIMPLEST AND OLDEST ON EARTH: BACTERIA.

FOR AS LONG AS BACTERIA HAVE EXISTED, THEY HAVE BEEN LOCKED IN MORTAL COMBAT WITH VIRUSES, WHICH CONSTANTLY TRY TO INVADE AND DESTROY THEM.

IN 1987, A RESEARCHER DISCOVERED THAT SOME BACTERIA INCORPORATE SHORT PIECES OF VIRAL DNA INTO THEIR OWN.

THE UNIVERSITY OF CALIFORNIA'S JENNIFER DOUDNA WAS ONE OF THE SCIENTISTS WHO WONDERED WHY.

DOUDNA: I LOVE MYSTERIES AND I LOVE PUZZLES.

I MEAN, I THINK THAT'S WHY I BECAME A SCIENTIST.

I LOVE THE IDEA THAT I SPEND MY LIFE TRYING TO FIGURE THINGS OUT.

AND THE MYSTERY HERE WAS A LOT OF BACTERIA STORE PIECES OF VIRAL DNA IN THEIR CHROMOSOME, IN THEIR OWN DNA.

THEY GRAB THESE LITTLE BITS OF VIRAL DNA, INSERT IT INTO THE GENETIC MATERIAL OF THEMSELVES, AND THEN KEEP IT FOR FUTURE USE.

SO, WHY?

NARRATOR: DOUDNA AND OTHERS DETERMINED THAT THE BACTERIA ARE ACTUALLY USING THE VIRAL DNA TO RECOGNIZE FUTURE ATTACKS.

THE SYSTEM IS KNOWN BY ITS ACRONYM: CRISPR.

MAN: I KIND OF LIKEN CRISPRS TO BIOMETRIC IDENTIFICATION SYSTEMS, WHERE YOU MIGHT STORE FINGERPRINTS OR RETINAL SCANS AS A WAY TO BE ABLE TO RECOGNIZE SPECIFIC INDIVIDUALS IN THE FUTURE.

BACTERIA ARE DOING THE SAME THING, BUT THEY'RE STORING LITTLE SNIPPETS OF DNA FROM VIRUSES IN THEIR OWN GENETIC MATERIAL.

NARRATOR: BUT BACTERIA DON'T JUST IDENTIFY THEIR VIRAL ATTACKERS BY THOSE SNIPPETS OF DNA.

THEY ALSO DEVISED A WAY OF DESTROYING THEM.

AT A CONFERENCE IN PUERTO RICO, DOUDNA AND A FRENCH COLLEAGUE, EMMANUELLE CHARPENTIER, AGREED TO COLLABORATE AND, TOGETHER, THEY EVENTUALLY FIGURED OUT HOW BACTERIA DO IT.

CHARPENTIER, VOICE-OVER: CRISPR CAN BE REGARDED AS A PROGRAMMABLE MOLECULAR SCISSORS, SO, SCISSORS THAT WILL BE PROGRAMMED TO RECOGNIZE A CERTAIN SPECIFIC SEQUENCE ON THE GENOMES OF VIRTUALLY ANY CELL IN THE ORGANISM, WILL BE ABLE TO CUT THIS DNA AT A VERY SPECIFIC PLACE.

DOUDNA: THE CRISPR SYSTEMS IN BACTERIA ARE REALLY A SEEK-AND-DESTROY KIND OF SYSTEM.

THEY HAVE MOLECULES WHOSE JOB IS TO DETECT THAT FOREIGN DNA AND RECOGNIZE IT AS A VIRUS.

AND THEN, IN THE SECOND STEP, CRISPR MOLECULES CUT IT UP.

NARRATOR: IT WAS THEN THAT DOUDNA AND CHARPENTIER MADE A CONCEPTUAL LEAP THAT WOULD CHANGE THE HISTORY OF SCIENCE.

WOULD IT BE POSSIBLE, THEY WONDERED, TO EXTRACT CRISPR FROM BACTERIA AND TAKE CONTROL OF ITS GUIDANCE SYSTEM?

IN OTHER WORDS, COULD THEY RE-ENGINEER CRISPR INTO A SIMPLE TOOL FOR EDITING ANY KIND OF DNA, AT ANY SPOT THEY CHOSE?

AFTER YEARS OF TINKERING, THEY GOT THEIR IDEA TO WORK.

COBB: SO, EFFECTIVELY, THEY REALIZED THIS LITTLE MOLECULAR MACHINE, THEY COULD PROGRAM IT WITH ANY DNA.

AND BASICALLY, THAT'S WHY IT'S SO AMAZING.

IF YOU KNOW A DNA SEQUENCE IN AN ORGANISM, YOU CAN CHANGE THAT GENE.

GREELY: CRISPR IS BIOLOGY'S SUPER SWISS ARMY KNIFE.

IT SEEMS TO BE ABLE TO DO JUST ABOUT EVERYTHING.

AND IT CAN DO IT FASTER, CHEAPER, MORE ACCURATELY, MORE EASILY THAN ANYTHING THAT CAME BEFORE IT.

NARRATOR: BUT WOULD IT WORK IN HUMANS?

A RESEARCHER IN BOSTON DECIDED TO FIND OUT.

FENG ZHANG HAD BEEN FASCINATED BY MOLECULAR BIOLOGY SINCE HE WAS A BOY.

ZHANG: I WORKED IN A GENE THERAPY LAB WHEN I WAS A HIGH SCHOOL STUDENT.

I SPENT EVERY AFTERNOON THERE, GOING IN ON WEEKENDS...

I LEARNED HOW EXCITING IT CAN BE TO SEE NEW DATA, NEW DISCOVERIES, FOR THE FIRST TIME.

NARRATOR: IN 2011, ZHANG, NOW A WORLD-CLASS RESEARCHER HIMSELF, ATTENDED A MEETING IN BOSTON.

ZHANG: ONE OF THE RESEARCHERS WAS TALKING ABOUT THE BACTERIA THAT HE WAS STUDYING, AND HE JUST CASUALLY MENTIONED THAT THERE'S SOMETHING CALLED CRISPR.

I WAS INTRIGUED BY THAT AND WHEN I READ ABOUT IT, I THOUGHT, IF WE CAN TAKE THIS MACHINE OUT OF BACTERIAL CELLS AND PUT IT INTO HUMAN CELLS, MAYBE WE CAN MODIFY THE HUMAN GENOME.

NARRATOR: ZHANG'S EXPERIMENTS WITH HUMAN DNA PROVED SUCCESSFUL.

ZHANG: WE NOW HAVE A MACHINE THAT CAN SEARCH ALONG THE DNA IN A CELL TO FIND THE MUTATION.

AND THEN IT'S THE SAME AS A CURSOR IN MICROSOFT WORD.

WHEREVER YOU PLACE THIS CUT, WHEREVER YOU PLACE THE CURSOR, THAT'S WHERE YOU CAN START TO BACKSPACE TO DELETE AND YOU CAN ALSO TYPE IN NEW SEQUENCES.

NARRATOR: CRISPR IS TRANSFORMING THE FIELD OF FOOD PRODUCTION, MAKING IT POSSIBLE FOR THE FIRST TIME TO MODIFY PLANT GENOMES PRECISELY, WITHOUT INTRODUCING ANY FOREIGN DNA-- A SHORTCOMING IN PREVIOUS TECHNIQUES.

BUT IT WAS THE PROSPECT OF WHAT CRISPR COULD DO FOR HUMAN DISEASES THAT ELECTRIFIED THE SCIENTIFIC COMMUNITY.

FEMALE REPORTER: CRISPR COULD HELP RID US OF DISEASES LIKE CYSTIC FIBROSIS, MUSCULAR DYSTROPHY, AND EVEN HIV AND CANCER-- THINK ABOUT THAT.

STERNBERG: THE DREAM HERE IS THAT WE COULD USE CRISPR TO ACTUALLY ERASE THE MUTATIONS THAT CAUSE THESE DISEASES AT THEIR SOURCE.

SO, INSTEAD OF MANY KINDS OF MEDICINE WHERE A PATIENT MIGHT BE TAKING DRUGS EVERY DAY, EVERY WEEK, EVERY MONTH, DRUGS THAT ARE PROBABLY GOING TO BE VERY EXPENSIVE, THERE'S THE HOPE THAT WITH GENE EDITING, THERE'S NO NEED FOR ALL THOSE DRUGS.

WE CAN MAKE THE FIX ONCE, AND THE PATIENT WILL BE PERMANENTLY CURED OF THE DISEASE.

NARRATOR: BUT THE DREAM OF EDITING THE HUMAN GENOME WAS TEMPERED BY FEARS THAT SOME WOULD TAKE THE TECHNOLOGY TOO FAR.

JOHN OLIVER: IT'S LIKE CUT-AND-PASTE IN MICROSOFT WORD, AT WHICH POINT, PRESUMABLY, CLIPPY SHOWS UP AND SAYS, "HI!

"IT LOOKS LIKE YOU'RE TRYING TO PLAY GOD "AND ALTER THE BASIC BUILDING BLOCKS OF LIFE.

NEED SOME HELP?"

NARRATOR: SHORTLY AFTER HER DISCOVERY, JENNIFER DOUDNA RECEIVED A CALL FROM A BUSINESSWOMAN LOOKING TO DISCUSS A NEW VENTURE.

DOUDNA: SHE WAS AN ENTREPRENEUR WHO WANTED TO BE THE FIRST WOMAN TO GIVE BIRTH TO A CRISPR BABY.

AND SHE WANTED TO DO THIS BY CREATING A COMPANY THAT SHE WAS CALLING HAPPY, HEALTHY BABIES, THAT WOULD LITERALLY OFFER TO PEOPLE THE OPPORTUNITY TO EDIT THE DNA IN EGGS OR SPERM TO CREATE KIDS.

NARRATOR: DOUDNA HERSELF INITIATED AN INTERNATIONAL EFFORT TO PUT THE BRAKES ON CRISPR TECHNOLOGY.

[APPLAUSE] THIS RAISES A NUMBER OF ETHICAL QUESTIONS THAT WE HAVE TO CAREFULLY CONSIDER, AND THIS IS WHY I AND MY COLLEAGUES HAVE CALLED FOR A GLOBAL PAUSE IN ANY CLINICAL APPLICATION OF THE CRISPR TECHNOLOGY IN HUMAN EMBRYOS TO GIVE US TIME TO REALLY CONSIDER ALL OF THE VARIOUS IMPLICATIONS OF DOING SO.

NARRATOR: THE BIGGEST FEAR IS THAT CRISPR WOULD BE USED TO EDIT DNA IN EGGS AND SPERM, SO-CALLED "GERMLINE" DNA, WHICH IS PASSED DOWN FROM PARENT TO OFFSPRING.

CHANGING THE GERMLINE WOULD PERMANENTLY AFFECT THE EVOLUTION OF THE HUMAN RACE-- WHETHER IT WAS DONE ON PURPOSE OR NOT.

TILGHMAN: WHAT ARE YOU DOING IN MODIFYING THE GERMLINE?

ARE YOU ELIMINATING DISEASE, WHICH MANY OF US COULD LAUD, OR ARE YOU ENHANCING SOME TRAIT IN THE HUMAN POPULATION THAT YOU HAVE DECIDED IS PREFERABLE TO SOME OTHER TRAIT?

IT RAISES THE SPECTER OF 120 YEARS AGO OF EUGENICS.

COBB: GERMLINE MODIFICATION IS WHAT BIOETHICISTS ARE CONCERNED ABOUT.

AND THE ULTIMATE ARGUMENT IS, WELL, THIS WILL LEAD TO A FORM OF FASCISM, BECAUSE WE WILL CREATE A NEW SPECIES OF HUMAN WITH BLOND HAIR, BLUE EYES, OR WHATEVER PARTICULAR CHARACTERISTICS WE WANT.

MUKHERJEE: THE REAL FEAR THERE IS CONCERNS ABOUT ENHANCEMENT, ABOUT DRIVING RIFTS, GENETIC RIFTS IN SOCIETY, MUCH LIKE THE EUGENICISTS ONCE WANTED TO DRIVE GENETIC RIFTS BETWEEN SOCIETY, BREEDING ONLY THE...THE FIT AND...AND LEAVING THE UNFIT BEHIND.

WE DID PHILLY, NEW YORK, AND HERE.

WE HAVE TO DRIVE TO NEW YORK!

NARRATOR: FOR SOME PEOPLE, FEAR ABOUT THESE GENETIC RIFTS IS ALREADY FRONT AND CENTER IN THEIR LIVES.

DO YOU WANT TO GO TO NEW YORK CITY COMIC CON THIS NEXT YEAR?

CHILD: CAN WE STAY?

WOMAN: IN NEW YORK?

NARRATOR: REBECCA COKLEY WAS BORN WITH ACHONDROPLASIA, THE MOST COMMON FORM OF DWARFISM.

IT'S CAUSED BY A MUTATION IN A SINGLE GENE AND, THEREFORE, COULD CONCEIVABLY BE "CURED" BY CRISPR.

BUT COKLEY IS NOT INTERESTED IN BEING "CURED."

COKLEY, VOICE-OVER: WE SEE OUR DIAGNOSIS AS A THING OF PRIDE.

WE SEE IT AS A CULTURE.

IT'S NOT JUST A LINE OF CODE.

IT'S EMBEDDED IN WHO I AM.

THE PERSON I AM IS... IS DIRECTLY A RESULT OF ME BEING BORN A DWARF WOMAN.

FOR US, AND I THINK FOR ME, GROWING UP IN A FAMILY WITH PEOPLE LIKE ME, THERE WAS NEVER NORMAL OR DIFFERENT.

THERE WAS ALWAYS, LIKE, THE LITTLE PEOPLE SIDE AND THEN THE AVERAGES, YOU KNOW, MEANING PEOPLE LIKE THE REST OF YOU.

NARRATOR: WHEN STARTING HER OWN FAMILY, COKLEY WAS AWARE OF THE ODDS OF PASSING HER GENE ON.

AND HER FIRST TWO CHILDREN WERE BORN WITH ACHONDROPLASIA ALSO.

IN THE SUMMER OF 2018, DURING HER THIRD PREGNANCY, SHE WENT FOR A SCAN.

COKLEY: SO, WE'RE DOING THE SONOGRAM, AND I LOOK OVER AT MY DOCTOR AND I SAY, "HEY, JOANNE, HIS ARMS LOOK A LITTLE LONG," AND SHE'S LIKE, "OH, YEAH, YEAH, HIS ARMS ARE KIND OF LONG," AND I WAS LIKE, "NO, THEY'RE, LIKE, MASSIVE.

"WHAT'S WRONG WITH HIS ARMS?

ARE THOSE HIS LEGS?

"THEY'RE JUST INHUMAN, LIKE, WHAT AM I GONNA DO WITH "A CHILD THAT'S GOT THESE, LIKE, GINORMOUS ARMS AND LEGS?

LIKE, AM I HAVING A SPIDER BABY?"

[BABY FUSSING] [COKLEY SPEAKING INDISTINCTLY] NARRATOR: WITH THE ADVENT OF MORE PRECISE PRENATAL TESTING AND THE PROSPECT OF CRISPR GENE EDITING, COKLEY SEES A FUTURE IN WHICH PEOPLE LIKE HER COULD LITERALLY BE EDITED OUT OF THE PICTURE.

COKLEY, VOICE-OVER: YOU KNOW, THERE WAS DEFINITELY THAT THOUGHT THAT ONCE THE GENE WAS DISCOVERED ABOUT WHETHER OR NOT WE WOULD BE ON THE LIST OF PEOPLE TO FIX, UM, AND WHAT THAT FIX WOULD LOOK LIKE AND WHAT THAT FIX WOULD MEAN.

IN ICELAND, DOWN SYNDROME IS ON THE VERGE OF BEING ERADICATED AND IT'S DUE IN LARGE PART TO THE WIDESPREAD USE OF GENETIC TESTING.

COKLEY: IT'S HARD NOT TO THINK ABOUT IT EVEN IN THE CONTEXT OF WHAT WE'VE SEEN AROUND DOWN SYNDROME IN ICELAND.

THERE AREN'T BABIES BORN WITH DOWN SYNDROME ANYMORE IN ICELAND.

THAT'S PRETTY MUCH DONE, AND THAT COULD EASILY BE US, YOU KNOW, AND THAT'S A VERY PRECARIOUS FEELING.

NELSON: AS PEOPLE ARE PROCEEDING TO MAKE GENETIC CHANGES IN OFFSPRING AND FUTURE OFFSPRING, THESE ARE MOVES AND DECISIONS THAT ACTUALLY AFFECT ALL OF HUMANKIND.

I THINK THAT WE HAVEN'T COME TO REALLY GRASP THE WAY IN WHICH THE GENE, A KIND OF SMALL PHENOMENON, ACTUALLY IS THE THING THAT TIES US ALL TOGETHER AS A GLOBAL COMMUNITY, AND THAT THE DECISIONS THAT ARE MADE IN FAMILIES BY INDIVIDUALS POTENTIALLY HAVE PLANETARY IMPLICATIONS.

NARRATOR: BY 2018, AN INFORMAL CONSENSUS HAD BEEN REACHED AMONG SCIENTISTS AND GOVERNMENTS AROUND THE WORLD: FOR NOW, CRISPR TECHNOLOGY WOULD NOT BE USED IN GERMLINE RESEARCH.

BUT THE PROBLEM WAS: HOW TO ENFORCE IT?

BALTIMORE: YOU COULD SAY, "I WON'T DO A CERTAIN THING, AND MY FRIENDS WON'T DO IT," BUT HOW ABOUT THE WHOLE REST OF THE WORLD?

BECAUSE NOBODY HAS AUTHORITY OVER THE WORLD.

♪ NARRATOR: AT A SCIENTIFIC CONFERENCE IN NOVEMBER 2018, RUMORS BEGAN TO SWIRL AMONG DELEGATES THAT A CHINESE RESEARCHER-- DR.

HE JIANKUI-- WAS ABOUT TO MAKE A DRAMATIC ANNOUNCEMENT.

MAN: OK, SO, UM, JUST TO REMIND EVERYONE HERE THAT WE WANT TO GIVE DR.

HE A CHANCE TO EXPLAIN WHAT HE'S DONE.

NARRATOR: HE JIANKUI HAD CROSSED THE RED LINE FOR THE FIRST TIME.

HE HAD USED CRISPR TO EDIT THE GENOMES OF TWIN GIRLS WHILE THEY WERE STILL EMBRYOS, WITHOUT KNOWING WHAT UNINTENDED CONSEQUENCES HE MAY HAVE UNLEASHED ON THEM AND THEIR DESCENDANTS.

TWO BEAUTIFUL, LITTLE CHINESE GIRLS NAMED LULU AND NANA CAME CRYING INTO THE WORLD AS HEALTHY AS ANY OTHER BABIES A FEW WEEKS AGO.

NARRATOR: HE DESCRIBED HIS EXPERIMENT IN SLICK VIDEOS THAT HE RELEASED ONLINE.

HIS STATED GOAL WAS TO TARGET AND EDIT A SINGLE GENE IN EACH GIRL'S GENOME THAT HAS BEEN SHOWN TO OFFER PROTECTION AGAINST HIV/AIDS.

HE CALLED IT "GENETIC SURGERY."

NO GENE WAS CHANGED EXCEPT THE ONE TO PREVENT HIV INFECTION.

THE GIRLS ARE SAFE, HEALTHY AS ANY OTHER BABIES.

NARRATOR: AFTER A DAY OF ANTICIPATION, HE ARRIVED TO SPEAK BEFORE A TENSE GROUP OF FELLOW SCIENTISTS.

MODERATOR: ALL RIGHT... [APPLAUSE] HE: WE PERFORMED PGD WHOLE GENOME SEQUENCING ACROSS THE EMBRYO.

NARRATOR: HE GAVE A LENGTHY PRESENTATION, LAYING OUT THE SCIENCE BEHIND HIS EXPERIMENT.

THE SCIENTISTS IN THE AUDIENCE WERE SHOCKED.

FIRST, I JUST DON'T SEE THE UNMET MEDICAL NEED FOR THESE GIRLS.

THERE IS A CONSENSUS FOR, TO NOT ALLOW TO CONDUCT GENOME EDITING ON GERMLINE CELLS.

THIS IS CONSENSUS BETWEEN THE INTERNATIONAL COMMUNITY, INCLUDING CHINESE COMMUNITY.

I ASSUME YOU ARE VERY WELL AWARE OF THIS--THIS RED LINE.

WHY YOU CHOOSE TO CROSS THE LINE?

WHY SO MUCH SECRECY AROUND THIS PARTICULARLY WHEN YOU KNOW THE GENERAL FEELING AMONGST THE SCIENTIFIC COMMUNITY IS THAT WE SHOULDN'T GO AHEAD YET?

LANDER: THE ENTIRE EXPERIMENT FROM START TO FINISH SEEMED UNETHICAL, SCIENTIFICALLY ILL-CONCEIVED, SHODDILY DONE.

I MEAN, I WASN'T NECESSARILY SHOCKED THAT SOMEBODY WOULD DO SUCH A STUPID THING, BUT WHAT IT DID MAKE ME THINK WAS THAT IT WAS REALLY IMPORTANT NOW TO STOP AND SAY WE CAN'T GO FORWARD WITHOUT A SERIOUS FRAMEWORK, WE CAN'T GO FORWARD WITHOUT SERIOUS CONVERSATIONS ABOUT IT.

NARRATOR: AS THE CONDEMNATIONS MOUNTED, THE CHINESE GOVERNMENT LAUNCHED AN INVESTIGATION.

HE'S CRISPR EXPERIMENT ON HUMAN EMBRYOS WAS A WARNING TO THE WHOLE WORLD THAT THE GENIE IS ALREADY OUT OF THE BOTTLE.

TILGHMAN: THIS IS THE NATURE OF DISCOVERY-- THERE IS ALMOST NO SCIENTIFIC DISCOVERY OF ANY IMPORT THAT I CAN THINK OF THAT HASN'T HAD THE CAPACITY FOR BOTH GOOD AND ILL. AND IT'S GONNA TAKE, YOU KNOW, WISE SOCIETIES TO DIRECT THOSE DISCOVERIES DOWN THE RIGHT PATH AND AWAY FROM THE WRONG PATH.

LANDER: WE WILL SOON BE AT THE POINT WHERE FOR EVERY LIVING SPECIES ON THE PLANET, MAYBE MOST HUMAN BEINGS, WILL HAVE THAT GENETIC CODE AND IT'S SUDDENLY GIVEN US A TOTALLY DIFFERENT WAY TO THINK ABOUT BIOLOGY AS ENCODED IN DIGITAL INFORMATION, AND NOW NOT JUST TO LEARN ABOUT BIOLOGY, BUT TO MAYBE EVEN MAKE MEDICINES BASED ON THAT INFORMATION.

WE HAVE TO THINK CAREFULLY ABOUT HOW WE'RE GONNA USE THESE TOOLS TO MAKE SURE WE TRULY BENEFIT EVERYBODY.

MUKHERJEE: THE HUMAN GENOME IS THE MOST HUMAN THING WE POSSESS, AND THIS GENERATION WILL HAVE THE RESPONSIBILITY FOR THE STEWARDSHIP OF IT.

THEY WILL MAKE DELIBERATIONS ABOUT WHETHER OR NOT TO MAKE CHANGES IN IT, WHETHER OR NOT TO PREDICT FUTURES FROM IT.

THIS GENERATION HAS THE RESPONSIBILITY TO PROTECT AND TO UNDERSTAND AND TO INTERVENE ON THE MOST HUMAN THING THAT WE POSSESS IN COMMON.

IT'S AN AWESOME RESPONSIBILITY.

DO YOU FEEL LIKE ANYTHING'S GOTTEN TIGHTER?

NO.

NO?

ABOUT THE SAME.

OK, COOL.

NARRATOR: IT'S BEEN 6 MONTHS SINCE AUDREY WINKELSAS BEGAN HER TREATMENT WITH THE SMA DRUG NUSINERSEN.

JUST TELL ME IF I NEED TO STOP.

NARRATOR: HER PHYSICAL THERAPIST IS LOOKING TO SEE IF IT IS SHOWING ANY SIGNS OF SLOWING THE PROGRESSION OF AUDREY'S DISEASE.

DO YOU HAVE PAIN, LIKE, ON A DAILY BASIS?

NOT REALLY.

CAN YOU PULL IT BACK?

AHH, NICE.

LEFT LEG'S ALWAYS EASIER.

YEAH.

THAT'S GOOD.

READY, SET...GO.

[BUZZ] WOMAN, VOICE-OVER: SHE'S MAINTAINING HER DISEASE, AND IT SHOULD BE DECLINING, BASED ON THE NATURAL HISTORY STUDY.

SO, I THINK THE FACT THAT SHE'S KIND OF STAYING IN ONE LEVEL IS REALLY IMPORTANT, AND FOR HER, IT MIGHT NOT FEEL LIKE THAT BIG OF A WIN, BUT I THINK MAINTENANCE IS A BIG THING.

NICE.

GOOD JOB.

SO, LAST TIME YOU HAD AN 8 ON THE RIGHT AND A 6 ON THE LEFT... YEAH, FOR REAL.

SO, YOU GOT A 9 ON THE RIGHT AND AN 11 ON THE LEFT, SO, YOU WENT UP ABOUT 5 POINTS ON THE LEFT.

I KNOW.

THAT'S AMAZING.

AUDREY WINKELSAS, VOICE-OVER: I'M HAPPY WITH THE RESULTS FROM TODAY.

YOU KNOW, JUST NOT GETTING WEAKER IS A BIG BENEFIT OR IMPROVEMENT IN ITSELF, BECAUSE SOME THINGS ARE HARD TO DO, BUT I'M ABLE TO MANAGE DOING THEM NOW.

YOU KNOW, BEING A STUDENT, GOING TO THE LAB, DOING RESEARCH, WHICH IS WHAT I WANT TO DO.

SO, AS LONG AS I KNOW THAT THOSE THINGS KIND OF WON'T BE TAKEN AWAY, THEN THAT'S, THAT'S GREAT IN AND OF ITSELF.

THAT'S EXCITING.

GOOD JOB!

OR SHOULD WE DO OUR-- [IMITATES EXPLOSION] [LAUGHS] GOOD JOB.

[CHOIR SINGING INDISTINCTLY] ♪ NARRATOR: AUDREY CONTINUES TO TRAVEL BACK AND FORTH BETWEEN THE NIH AND OXFORD, WHERE SHE HAS JOINED A CHOIR AND IS SINGING AGAIN.

WHILE SHE FINISHES HER Ph.D. ON SMA, SHE IS LOOKING FOR HER NEXT LABORATORY POST AND RESEARCH PROJECT.

ESTHER ETIENNE: OK, NOW YOU KNOW I HAVE TWO CARDS... [LAUGHS] NARRATOR: FOR BRUNEL ETIENNE, THERE ARE ENCOURAGING SIGNS THAT THE GENE THERAPY TO TREAT HIS SICKLE CELL DISEASE IS WORKING.

WOMAN: OH, NO!

[LAUGHTER] NARRATOR: THOUGH IT IS STILL TOO SOON TO TELL IF HE WILL CONTINUE TO REQUIRE PERIODIC BLOOD TRANSFUSIONS, TESTS REVEAL THAT HIS OWN BLOOD IS LOOKING HEALTHIER THAN BEFORE.

HE, AND THE OTHER PATIENTS ON THE TRIAL, WILL CONTINUE TO BE MONITORED CLOSELY, AND THE GENE THERAPY IS NOW BEING EXTENDED TO YOUNGER PATIENTS.

[CHOIR SINGING INDISTINCTLY] ♪ ♪ ANNOUNCER: WATCH THE FULL FILM AND FIND ADDITIONAL INFORMATION AT PBS.ORG/THEGENE JOIN THE CONVERSATION WITH #THEGENEPBS TO ORDER "THE GENE: AN INTIMATE HISTORY," ON DVD, VISIT SHOPPBS.ORG.

OR CALL 1-800-PLAY-PBS.

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