>>> AND NEXT, TO A DISCOVERY THAT IS CHANGING THE WORLD.

MORE THAN A DECADE AGO, PIONEERING BIOCHEMIST JENNIFER DOWDNER CO-INVENTED THE GENE EDITING TECHNOLOGY WHICH EARNED HER A NOBEL PRIZE.

NOW THE VERY FIRST TREATMENT HAS BEEN APPROVED IN THE YOU CAN AND UNITED STATES, A LANDMARK DECISION FOR TREATING SICKLE CELL DISEASE AND FOR THE POSSIBILITIES OF THE RAPIDLY ADVANCING FIELD.

SHE JOINED WALTER ISAACSON TO DISCUSS ABOUT HER TECHNOLOGY AND THE POTENTIAL DANGERS OF ITS MISUSE.

>> JENNIFER, WELCOME BACK TO THE SHOW.

>> GREAT TO SEE YOU, WALTER.

>> YOU AND YOUR COLLEAGUES WON THE NOBEL PRIZE IN CHEMISTRY FOR THE DISCOVERY AND THE PERFECTION OF A TOOL KNOWN AS CRISPER THAT ALLOWS A MOLECULE THAT HAS RNA AND SORT OF A SCISSORS, AN ENSEEM THAT ACTS LIKE A SCISSORS THAT CAN CUT OUR DNA.

THE FDA HAS APPROVED THIS FOR TREATMENT OF SICKLE CELL ANEMIA.

FIRST OF ALL, EXPLAIN TO US HOW THAT WOULD WORK ON SICKLE CELL ANEMIA.

>> WELL, WALTER, IT'S AN AMAZING TIME.

WE ARE SEEING A REAL TRANSFORMATION IN MEDICINE WHERE NOW WE CAN EDIT THE ACTUAL CAUSE OF THE GENETIC DISEASE, LIKE SICKLE CELL DISEASE, TO PROVIDE PATIENTS WITH A DURABLE CURE.

AND IN THE CASE OF SICKLE CELL, WHAT HAPPENS IS THAT IT'S POSSIBLE NOW TO PERMANENTLY TURN ON THE PRODUCTION OF A SECOND PROTEIN, A PROTEIN THAT CAN PROTECT PEOPLE THAT HAVE THE SICKLE CELGENE FROM EXPERIENCING DISEASE PHENOTYPES.

SO THEY HAVE AN EXPERIENCE A LONG-TERM TREATMENT THAT MAY BE EFFECTIVELY A CURE FOR THIS DISEASE.

IT'S REALLY EXCITING.

>> IN THE BOOK I WROTE ABOUT YOU, THE CODE BREAKER, I HAVE A PICTURE OF VICTORIA GRAY WHO WAS THE FIRST PERSON ON WHICH YOU WERE TESTING THIS TECHNOLOGY, DOWN IN MISSISSIPPI.

YOU WENT AND YOU MET WITH HER NOT TOO LONG AGO.

TELL ME WHAT THAT WAS LIKE AND WHAT YOU LEARNED ABOUT HER.

THIS IS A REAL PERSON GETTING CURED OF A BAD DISEASE, BECAUSE OF A TECHNOLOGY YOU CREATED.

>> WHEN I MET VICTORIA GRAY, IT WAS TRULY AN EXCITING MOMENT FOR ME AS A SCIENTIST TO SEE THE IMPACT OF RESEARCH AND TECHNOLOGY ON A PERSON'S LIFE AND HOW IT CAN BE TRANSFORMATIVE.

SHE EXPLAINED HOW IN HER CASE, SICKLE CELL DISEASE HAD REALLY CONTROLLED HER LIFE AND MADE IT VERY DIFFICULT FOR HER TO WORK, TO BE A MOM TO HER FOUR KIDS, AND NOW WITH THIS DURABLE TREATMENT WITH CRISPER, SHE'S ABLE TO KICK BACK HER LEGS.

SHE CAN GO BACK TO SCHOOL, SHE'S ABLE TO WORK, AND FOR HER I THINK IT'S BEEN A LIFE-CHANGING EXPERIENCE.

>> TOTALLY LIFE CHANGING, BUT I THINK IT COSTS CLOSE TO $2 MILLION.

YOU HAVE TO EXTRACT THE STEM CELLS FROM THE HUMAN BODY AND THEN REINSERT THEM.

IT'S NOT SOMETHING SIMPLE.

HAVE YOU BEEN WORKING ON WAYS TO BRING DOWN THAT COST?

>> WELL, THAT'S RIGHT.

I MEAN, I THINK FOR SCIENTISTS LIKE ME, IT'S -- YOU KNOW, IT'S A MOMENT WHERE WE'RE BOTH VERY HOPEFUL ABOUT THE FUTURE, BUT WE RECOGNIZE HOW MUCH WORK THERE IS TO BE DONE.

AS YOU POINT OUT, THE TREATMENT RIGHT NOW IS OVER $2 MILLION A PATIENT.

IT ALSO REQUIRES A LONG-TERM TREATMENT THAT INVOLVES HOSPITALIZATION.

SO WE WOULD LOVE TO FIND WAYS TO BRING DOWN THAT COST BY MAKING IT EASIER TO DELIVER THE THERAPY INTO PATIENTS, MAYBE ONE DAY NOT REQUIRING HOSPITALIZATION AT ALL, BUT ALLOWING A ONE-TIME INJECTION.

AND ALSO MAKING IT POSSIBLE TO DISTRIBUTE THIS THERAPY MORE WIDELY AROUND THE WORLD.

>> DO YOU THINK INSURANCE COMPANIES ARE GOING TO PAY $2 MILLION EACH FOR EVERYBODY WITH SICKLE CELL?

>> WALTER, IT'S AN IMPORTANT QUESTION.

I THINK WE HAVE TO DO THE MATH AND ASK HOW MUCH IT COSTS TO TREAT A PATIENT OVER THEIR LIFETIME WITH A CHRONIC DISEASE LIKE SICKLE CELL, VERSUS HAVING A ONE AND DONE CURE FOR THAT TYPE OF DISEASE.

I THINK THIS IS A, YOU KNOW, A VERY IMPORTANT QUESTION THAT NOW HAS TO BE ADDRESSED.

>> WAIT, DO YOU THINK IT CAN BE DONE BY MATH?

WHAT HAPPENS IF THE MATH SAYS NO, LET THEM CONTINUE TO HAVE THE DISEASE?

>> IT CAN'T JUST BE MATH, IT HAS TO ALSO INVOLVE OUR TECHNICAL AND SOCIETAL EFFORTS.

WE'RE DOING THIS THROUGH THE INSTITUTE WHERE I WORK IN THE BAY AREA TO FIGURE OUT HOW TO ADDRESS THIS CHALLENGE TECHNICALLY AND HOW WE CAN WORK WITH PATIENT GROUPS TO HELP THEM UNDERSTAND THE THERAPY, HOW IT WORKS, WHETHER IT'S RIGHT FOR THEM.

AND ALSO TO ADVOCATE FOR LOWER COSTS AND BETTER DISTRIBUTION EFFORTS.

>> THE WAY TO LOWER THE COST IT WOULD SEEM WOULD BE JUST TO HAVE A PILL OR AN INJECTION IN WHICH THIS EDITING TOOL CAN GO RIGHT INTO HUMAN CELLS, WHERE YOU WANT IT TO.

WHAT'S THE PROBLEM WITH GETTING IT INTO HUMAN CELLS?

>> WELL, THAT'S RIGHT.

AND THE CHALLENGE THERE IS THAT CRISPER IS A BIG MOLECULE, AND WE ALSO HAVE TO FIGURE OUT HOW TO GET IT RIGHT TO THE CELLS THAT NEED EDITING AND NOT ANYWHERE ELSE.

AS YOU MENTIONED, THE SICKLE CELL THERAPY INVOLVES EDITING BLOOD STEM CELLS, CELLS THAT PRODUCE THE MATURE RED BLOOD CELLS IN OUR BODIES, AND LIVE IN OUR BONE MARROW.

SO RIGHT NOW, THE SICKLE CELL TREATMENT INVOLVES WHAT IS EFFECTIVELY A BONE MARROW TRANSPLANT.

BUT WE ENVISION A DAY WHEN IT WILL BE POSSIBLE TO PROVIDE A ONE-TIME INJECTION THAT TARGETS THE CRISPER MOLECULES DIRECTLY TO THOSE BLOOD STEM CELLS AND DOESN'T TOUCH ANY OTHER CELLS.

>> NOW, IF YOU DO IT, YOU'RE DOING IT IN A PATIENT RIGHT NOW, BUT YOU COULD, IN THEORY, AND IN FACT, IN PRACTICE, DO IT IN A DRUMLINE WAY, WHICH IS IN REPRODUCTIVE CELLS SO THAT YOU COULD MAKE EDITS THAT WOULD BE INHERTDED.

AND YOU WOULD GET SICKLE CELL WIPED OUT FROM WHOLE FAMILIES, AND MAYBE FROM THE HUMAN RACE.

YOU'VE BEEN A LITTLE -- VERY CAUTIOUS I SHOULD SAY ABOUT INHERITABLE EDITING.

DO YOU THINK WE'LL GET TO THE PLACE WHERE YOU SAY LET'S MAKE INHERABLE EDITS WHERE NOBODY WILL HAVE SICKLE CELL, NOT EVEN YOUR GRANDCHILDREN?

>> THAT WOULD BE AN APPROACH TO BE TAKEN IN THE FUTURE.

I THINK TODAY, THE TECHNOLOGY ISN'T THERE YET TO USE IT SAFELY THIS THAT FASHION.

AS YOU POINT OUT, THERE'S A VERY PRO-FOUND ETHICAL QUESTION TO BE ADDRESSED WHEN WE THINK ABOUT USING CRISPER IN A HERITABLE FASHION, BECAUSE IT DOES CHANGE DNA IN FUTURE GENERATIONS, SO WE HAVE TO BE CAUTIOUS ABOUT THAT TYPE OF USE.

>> WHEN WOULD YOU SAY WE SHOULD BE WILLING TO CROSS THAT LINE?

>> I THINK IT WOULD REQUIRE SEVERAL THINGS.

FIRST OF ALL, WE HAVE TO BE SURE THAT TECHNICALLY AND SCIENTIFICALLY THE TECHNOLOGY WOULD BE SAFE, AND WE'RE CERTAINLY NOT THERE TODAY.

SECONDLY, I THINK WE HAVE TO REALLY BE QUITE TRANSPARENT ABOUT THE APPLICATIONS OF HERITABLE GERMLINE EDITING, HOW WOULD WE DECIDE WHO IS GOING TO USE IT THAT WAY AND FOR WHAT TYPES OF END CASES.

SO THIS IS SOMETHING I'VE BEEN ADVOCATING FOR SEVERAL YEARS IN TERMS OF THINKING TOGETHER ABOUT HOW WE USE THE TECHNOLOGY RESPONSIBLY.

>> AS YOU KNOW FAR TOO WELL, A CHINESE SCIENTIST, WHO I THINK TOOK -- IT'S IN MY BOOK, TO BE A SELFIE WITH YOU, AND HE MADE INHERITABLE EDITS FOR AGAIN GIRLS IN CHINA, BUT NOW HE'S OUT OF HOUSE ARREST AND WORKING IN A LAB.

IS IT GOING TO BE POSSIBLE TO KEEP THIS JEANNIE IN THE MIDDLE?

>> WHAT'S IMPORTANT TO NOTE IS THAT THERE WAS A TRUE INTERNATIONAL BACKLASH AGAINST HIS ANNOUNCEMENT IN 2018, WHICH WAS THAT HE HAD USED CRISPER IN TWO HUMAN IMBREEIOS THAT WERE TRANSPLANTED INTO A WOMAN TO CREATE A PREGNANCY.

I THINK INTERNATIONALLY, IT WAS CLEARLY THE CASE THAT SCIENTISTS REJECTED THAT KEEP OF USE OF CRISPER, AND DECIDED THAT THIS SHOULD NOT BE SOMETHING TO BE ENCOURAGED.

SO I'M HEARTENED BY THAT EFFORT, AND I THINK THAT, YOU KNOW, THERE MAY BE A TIME IN THE FUTURE WHEN WE DECIDE THIS IS APPROPRIATE, BUT WE'RE NOT THERE TODAY.

>> YOU AND DAVID BALTIMORE AND A LOT OF PEOPLE, HAVE THE CHINESE BEEN COOPERATIVE ON THIS?

>> YES.

WE FOUND THE CHINESE SCIENTISTS HAVE BEEN QUITE ENGAGED AND INTERESTED IN WORKING TOGETHER ON THIS.

I THINK THERE'S AN APPRECIATION THAT WITH A POWERFUL TOOL LIKE CRISPER, WE HAVE TO WORK TOGETHER TO ENSURE THAT IT'S USED SAFELY IN THE FUTURE.

>> LET ME TALK ABOUT A HYPOTHETICAL, WHICH IS IF YOU CAN DO SOMETHING LIKE FIX THE ONE LETTER MUTATION EVENTUALLY THAT CAUSES SICKLE CELL OR DO WHAT YOU DID WITH BEETLE CELLS, YOU COULD ALSO ENHANCE IT.

SO I COULD DECIDE THAT MY BLOOD CELLS WILL CARRY MUCH MORE OXYGEN THAN ORDINARY PEOPLE'S, AND EVENTUALLY MAYBE MY KID, I COULD DESIGN A KID THAT WOULD HAVE BLOOD CELLS THAT CARRIED MORE OXYGEN, BE WONDERFUL ATHLETES, GREAT SPRINTERS.

SHOULD WE TRY TO DRAW A LINE BETWEEN WHAT'S TREATMENT FOR A PROBLEM, A DISEASE, AND WHAT'S ENHANCEMENT SO PEOPLE CAN DESIGN BETTER KIDS?

>> I WOULD FIRST LIKE TO POINT OUT FOR THE MOST PART, IT'S NOT VERY EASY TO DO THE THINGS THAT YOU MENTIONED TODAY OR MAYBE NOT POSSIBLE, BECAUSE WE DON'T KNOW THE GENETICS WELL ENOUGH TO CONTROL THOSE KINDS OF TRAITS.

BUT AS YOU'RE INDICATING, SOME DAY WE WILL.

SO WE DO HAVE TO BE GRAPPLING WITH THE CHALLENGE OF HOW WE USE CRISPER IN A SAFE AND ETHICAL FASHION GOING FORWARD.

I DON'T HAVE ANY EASY ANSWERS TO THAT, BUT I CERTAINLY THINK IT REQUIRES OPEN DISCUSSION AND REALLY INTERNATIONAL COORDINATION.

>> THERE IS A LOT OF GENETIC DISEASES THAT WE CAN DEAL WITH.

I GUESS THE ONES THAT CRISPER, THIS GENE EDITING TOOL WE HAVE BEEN TALKING ABOUT, COULD BE MOST USEFUL ON WERE JUST SIMPLE MUTATIONS, ONE OF THE SIMPLEST BEING SICKLE CELL, WHICH IS A ONE-LETTER MUTATION.

WHAT OTHER SYNDROMES AND MALADIES ARE SUSCEPTIBLE TO GENE EDITING NOW?

>> WELL, QUITE A FEW.

THERE'S A NUMBER OF DISEASES THAT HAVE A SINGLE GENE THAT'S KNOWN TO BE CAUSATIVE, AND ONES THAT COME TO MIND ARE CYSTIC FIBROSIS, MUSCULAR DYSTROPHY, HUNTINGTON DISEASE, AND THERE ARE MANY OTHERS.

SO I THINK THAT THERE ARE GREAT OPPORTUNITIES GOING FORWARD WITH CRISPER IF WE CAN FIGURE OUT THIS DELIVERY CHALLENGE, WHICH IS HOW WE GET THE CRISPER EDITING MOLECULES INTO THE RIGHT CELLS OF THE BODY.

>> YOU JUST MENTIONED HUNTINGTON'S.

JUST A GOD-AWFUL DISEASE.

PARTLY BECAUSE YOU DON'T KNOW YOU HAVE IT USUALLY UNTIL AFTER CHILD BEARING AIM.

SO IT JUST GOES DOWN IN THE FAMILIES AND IT'S JUST A DEATH SENTENCE.

WOULD THAT BE ONE OF THE FIRST CASES WHERE WE MIGHT SAY INHERITABLE EDITS MAKE MORAL SENSE?

>> I CERTAINLY THINK THAT WOULD BE THE KIND OF SITUATION WHERE WE MIGHT COME TO THAT CONCLUSION.

IF AND WHEN WE GET TO A POINT WHERE CRISPER IS TRULY KNOWN TO BE SAFE TO USE IN GERM CELLS.

>> SO TELL ME ABOUT THE OTHER DISEASES.

ARE THOSE ONES -- HOW WOULD THEY BE TREATED?

>> WELL, THEY WOULD BE TREATED USING EDITING APPROACH THAT MIGHT EITHER CORRECT THE DISEASE CAUSING MUTATION, OR MAKE A DIFFERENT CHANGE TO THE DNA THAT COULD MITIGATE DISEASE.

AND WHAT'S EXCITING IS THAT CRISPER IS NOT ONLY A TOOL THAT CAN BE USED AS THE THERAPEUTIC ITSELF, BUT IT CAN ALSO BE USED AS A RESEARCH TOOL.

SO WHAT WE ARE SEEING RIGHT NOW IN THE FIELD OF SCIENTIFIC RESEARCH IS THAT MORE AND MORE CRISPER IS INTEGRATED INTO MEDICAL RESEARCH PROJECTS WHERE WE CAN REALLY UNDERSTAND THE GENETICS OF DISEASE AT A LEVEL THAT WILL MAKE IT POSSIBLE ONE DAY TO PROBABLY ONE DAY TREAT THEM.

>> WHAT ABOUT ALZHEIMER'S?

>> WELL, YEAH.

THAT IS, AGAIN, A DEVASTATING DISEASE.

IT AFFECTS MANY FAMILIES.

I THINK ONE THING TO CONSIDER THERE IS THAT AS WE UNDERSTAND BETTER THE GENES THAT MAKE ANY OF US SUSCEPTIBLE TO A DISEASE LIKE ALZHEIMER'S, IT MAY IN THE FUTURE BE POSSIBLE TO PROVIDE PREVENTATIVE TREATMENT, PROTECTIVE GENES AGAINST A DISEASE LIKE ALZHEIMER'S.

>> I KNOW SOME EXPERIMENTS WERE DONE AT PENN INVOLVING THE EYE.

WHY IS THAT AN ORGAN WE CAN EDIT MORE EASILY, AND WHAT CAN BE DONE THERE?

>> THE EYE AND THE LIVER, AS WELL, ARE TWO ORGANS WHERE DELIVERY OF CRISPER MOLECULES IS RELATIVELY EASIER THAN OTHER PARTS OF THE BODY.

AND FOR THAT REASON, IT'S ATTRACTIVE TO TRY TO TREAT GENETIC EYE DISEASES OR LIVER DISEASES USING THE CRISPER TECHNOLOGY, BECAUSE WE HAVE STRATEGIES TODAY THAT ALLOW DELIVERY INTO THOSE ORGANS.

>> I NOTICE THAT YOU HAVE BEEN WORKING QUITE A BIT ON THE MICROBIOME.

TELL ME WHAT IT IS AND WHY CRISPER COULD BE USEFUL.

>> WELL, WE'RE ALL TRYING TO FIGURE OUT THE MICROBIOME AND HOW IT CONNECTS TO HUMAN HEALTH AND DISEASE.

BUT THERE'S INCREASING EVIDENCE THAT THE BACTERIA THAT LIVE IN OUR BODIES AND IN OUR ENVIRONMENT AS WELL, HAVE AN ENORMOUS INFLUENCE ON OUR HEALTH AND SUSCEPTIBILITY TO DISEASE.

SO WHAT WE'RE DOING TODAY WITH THE CRISPER TECHNOLOGY HERE AT THE INNOVATIVE GENOMICS INSTITUTE IS TO MAKE TARGETED CHANGES TO THE MICROBES THAT POPULATE THE HUMAN GUT TO REDUCE DISEASE SUSCEPTIBILITY AND WE HOPE TO PROVIDE DISEASE PROTECTION.

>> YOU SAID THAT BEFORE WE ENCOUNTER A WHOLE LOT OF CRISPER TECHNOLOGIES IN OUR DOCTOR'S OFFICE, WE'RE GOING TO ENCOUNTER IT A LOT MORE ON OUR FOOD PLATE.

TELL ME WHAT'S HAPPENING IN THE FIELD OF AGRICULTURE.

>> GENE EDITING WILL HAVE A HUGE IMPACT IN AGRICULTURE, NO QUESTION.

AND THE REASON IS THAT IT ESSENTIALLY GIVES PLANT BREEDERS A TOOL FOR MAKING PRECISE CHANGES IN PLANTS WITHOUT INTRODUCING A LOT OF OTHER ALTERATIONS TO GENES THAT DON'T NEED CHANGING.

AND AS A RESULT, WE HAVE NOW THE WAY TO CHANGE PLANTS TO PROVIDE DROUGHT RESISTANCE, TO INCREASE NUTRITIONAL VALUE, EVEN TO INCREASE YIELD OF CROPS.

ALL OF THESE THINGS ARE ALREADY HAPPENING USING CRISPER.

I THINK THIS WILL RAISE QUESTIONS ABOUT, YOU KNOW, HOW WE REGULATE OR DON'T REGULATE THAT KIND OF USE OF CRISPER.

AND THAT'S, AGAIN, A VERY ACTIVE AREA OF DISCUSSION CURRENTLY.

>> AND PEOPLE TALK ABOUT GENETICALLY MODIFIED ORGANISMS AND GMOs AND HOW THEY'RE AGAINST THEM.

ARE THEY DANGEROUS IF YOU EDIT THE GENES OF PLANTS AND ANIMALS WE EAT?

>> WELL, LET'S THINK ABOUT IT.

EVERYTHING WE NEAT IS GENETICALLY MODIFIED, GOING BACK THOUSANDS OF YEARS.

HUMANS HAVE BEEN BREEDING PLANTS FOR AS LONG AS WE'VE HAD AGRICULTURE.

AS A RESULT, EVERYTHING THAT WE CONSUME HAS MODIFIED GENES.

WHAT CRISPER DOES IS SIMPLY GIVES US THE TOOLS TO MAKE THOSE CHANGES PRECISELY RATHER THAN RANDOMLY AS IS CURRENTLY DONE.

>> SO THEY COULD BE SAFER ACTUALLY?

>> I FEEL THEY COULD, YES.

>> ONE OF THE DISHEARTENING THINGS THAT HAPPENED WITH COVID WAS -- ONE OF THE GREAT THINGS WAS WE FOUND ALL SORTS OF WAYS TO TREAT IT, WITH SCIENCE AND VACCINES.

BUT THEN THERE WAS A BACKLASH.

PEOPLE AFRAID OF THE SCIENCE OR PEOPLE SKEPTICAL ABOUT IT.

ONE OF THE REASONS, I THINK YOU COOPERATED WITH ME ON THE BOOK I WROTE, WAS WE WANTED TO EXPLAIN EXACTLY HOW THE SCIENCE WORKS, SO PEOPLE WOULDN'T BE AS MYSTIFIED OR AFRAID OF IT.

DO YOU THINK WE HAVE TO DO BETTER COMMUNICATIONS NOW THAT THERE'S BEEN, I THINK AN UNDERCURRENT OF ANTI-SCIENCE BACKLASH IN THIS COUNTRY.

>> I THINK IT'S INCREDIBLY IMPORTANT TO EXPLAIN WHAT SCIENCE IS GOING ON, HOW TAXPAYER MONEY IS USED TO SUPPORT RESEARCH AND WHAT BENEFIT IT PROVIDES TO SOCIETY.

I THINK MAYBE WE SCIENTISTS HAVEN'T DONE AS GOOD OF A JOB AS WE SHOULD HAVE OVER THE PAST FEW DECADES IN EXPLAINING THAT.

AND I THINK IT'S MAYBE EVEN MORE IMPORTANT NOW WITH SOCIAL MEDIA AND THE REPIDTY WITH WHICH MISINFORMATION CAN FLOOD THE INTERNET, FOR EXAMPLE.

WE REALLY NEED TO BE SURE THAT WE ARE PUTTING OUT THERE REAL INFORMATION, REAL DATA THAT'S TRUSTWORTHY SO THAT PEOPLE KNOW WHERE TO GET INFORMATION THEY CAN COUNT ON.

>> DR. JENNIFER DOWDNER, THANK YOU ONCE AGAIN FOR BEING WITH US.

>> THANK YOU, WALTER.