CAREER THAT HAS BRIDGED BOTH 
ACADEMIC AND INDUSTRIAL 
RESEARCH.
CURRENTLY DR. CORN IS THE 
FOUNDING SCIENTIFIC DIRECTOR OF 
INNOVATIVE GENOMICS INSTITUTE, 
WHICH IS A UNIQUE COLLABORATION 
BETWEEN UC BERKELEY AND UC SAN 
FRANCISCO.
ADDITIONALLY, HE IS AN ASSISTANT
 PROFESSOR OF MOLECULAR BIOLOGY 
AND BIOPHYSICS -- OH, MOLECULAR 
AND CELL BIOLOGY UNIVERSITY OF 
BERKELEY.
PREVIOUS TO THIS, HE WAS A GROUP
 LEADER AT GENENTECH.
INCORPORATING MULTIPLE FIELDS IN
 THE DEVELOPMENT OF NEW 
THERAPEUTICS.
THE CURRENT AIM OF HIS RESEARCH 
IS TO END GENETIC DISEASE, SUCH 
AS SICKLE CELL DISEASE, THROUGH 
THE DEVELOPMENT OF 
NEXT-GENERATION GENOME EDITING 
TECHNOLOGIES.
THESE TOOLS, SUCH AS 
CRISPR/Cas9, HAVE ALLOWED NOVEL 
DISCOVERIES ABOUT THE 
FUNDAMENTAL WORKINGS OF CELLS 
AND ALSO THE MECHANISMS OF 
DISEASES.
ADDITIONALLY, DR. CORN HAS BEEN 
PUBLICLY -- HAS PUBLICLY SPOKEN 
ABOUT POTENTIAL ETHICAL 
CHALLENGES POSED BY WIDESPREAD 
APPLICATIONS OF THESE 
TECHNOLOGIES.
PLEASE WELCOME DR. CORN TO THE 
STAGE.
[ APPLAUSE ]
>>> THANKS VERY MUCH FOR HAVING 
ME HERE
>>> THANKS VERY MUCH FOR HAVING 
ME HERE TODAY.
GOOD AFTERNOON.
THIS CONFERENCE HAS BEEN REALLY 
FANTASTIC.
I THINK IT IS ONE OF THE 
WONDERFUL THINGS ABOUT A LIBERAL
 ARTS EDUCATION, I DID MY 
UNDERGRADUATE AT A SMALL LIBERAL
 ARTS COLLEGE, UNIVERSITY OF 
PUGET SOUND IN THE NORTHWEST.
THIS IS ONE OF THE THINGS THAT I
 THINK IS SEW GREAT ABOUT THESE 
-- SO GREAT ABOUT THESE 
ENVIRONMENTS, MERGING QUESTIONS 
ABOUT SCIENCE WITH QUESTIONS 
ABOUT HOW DO WE THINK ABOUT 
THESE THINGS, YOU KNOW, NOT JUST
 WHAT CAN WE DO, BUT WHAT SHOULD
 WE DO.
I AM GOING TO START BY GETTING A
 POLL FROM THE AUDIENCE.
I DIDN'T WARN YOU IN ADVANCE I 
WAS GOING TO DO THIS, SO THERE 
IS NO CLICKER OR ANYTHING LIKE 
THAT THAT YOU CAN DO, BUT THIS 
IS AN EASY POLL.
HOW MANY OF YOU HAVE READ A BOOK
 OR SEEN A MOVIE THAT 
INCORPORATES GENETIC 
ENGINEERING?
LIKE "JURASSIC PARK," ANYTHING 
LIKE THAT.
DID IT END WELL?
[ LAUGHTER ]
SO TYPICALLY THIS IS THE WAY WE 
THINK ABOUT GENETIC ENGINEERING.
POPULAR CULTURE, IT IS VERY 
OFTEN THIS WARNING SIGN, SCIENCE
 TISS GO OFF -- SCIENTISTS GO 
OFF IN A LAB, MAKE DINOSAURS, 
AND THE DINOSAURS END UP EATING 
THE SCIENTISTS.
IT IS NOT GREAT.
BUT THERE IS ANOTHER SIDE TO NEW
 POSSIBILITIES IN GENETIC 
ENGINEERING, AND THAT'S 
POTENTIALLY SOMEDAY BEING ABLE 
TO CURE GENETIC DISEASES.
THAT'S ONE OF THE THINGS THAT I 
AM VERY PASSIONATE ABOUT.
GENETIC DISEASES ARE CAUSED BY 
MUTATIONS THAT ARE IN PEOPLE'S 
DNA.
YOU CAN TREAT GENETIC DISEASES 
RIGHT NOW, BUT IT IS PALLIATIVE 
CARE.
YOU TREAT SYMPTOMS, BUT THE 
UNDERLYING CAUSE REMAINS THE 
SAME.
WHAT THE HOPE IS FOR GENETIC 
DISEASE, IS TO GIVE PEOPLE THE 
POSSIBILITY, IF THEY WANT, TO BE
 ABLE TO TREAT THE MUTATION IN 
THEIR GENOME.
SO THAT'S WHAT I WANT TO TALK 
ABOUT.
WHERE ARE WE, AND NOT IN SOME 
SORT OF SCIENCE FICTION WAY, BUT
 REALLY WHERE IS THE TECHNOLOGY,
 WHAT IS ACTUALLY REALISTIC, 
WHAT CAN WE DO TODAY, WHAT WILL 
WE DO IN THE FUTURE.
AND I PROMISE NO DINOSAURS.
SO LET'S START OFF BY TALKING 
ABOUT WHAT ARE WE REALLY TALKING
 ABOUT.
WE ARE TALKING ABOUT GENES.
AND GENES ARE THINGS INSIDE ALL 
ORGANISMS THAT REALLY SHAPE 
LIFE.
SO BACTERIA HAVE GENES, AND IN 
FACT THE RISE OF RESISTANT TO 
ANTIBIOTICS IS CAUSED BY 
MUTATIONS IN GENES THAT ARE IN 
THE BACTERIA THAT ALLOW THEM TO 
PROCESS THOSE ANTIBIOTICS.
WHENEVER YOU LOOK AT, YOU KNOW, 
YOUR FAVORITE FURRY FRIEND, YOU 
CAN SEE GENES AT WORK.
ALL DOGS ARE RELATED TO EACH 
OTHER, AND JUST SMALL CHANGES IN
 A COUPLE OF GENES GIVE THE HUGE
 DIVERSITY BETWEEN DOGS.
OF COURSE IF YOU LOOK AT YOUR 
NEIGHBOR, YOU CAN LOOK LEFT, 
LOOK RIGHT, TRY TO FIGURE OUT, 
ARE THEIR EARS ATTACHED, ARE 
THEY SEPARATE, THAT'S A GENETIC 
TRAIT.
BUT GENES CAN ALSO GO WRONG.
SO MUTATIONS IN GENES CAN CAUSE 
GENETIC DISEASE.
THIS IS A PICTURE OF THE 
SO-CALLED BUBBLE BOY, THE PERSON
 WHO WAS BORN WITH SEVERE 
COMBINED IMMUNODEFICIENCY OR 
SCID.
THE END RESULTS OF SCID, PEOPLE 
ARE BORN WITH NO FUNCTIONING 
IMMUNE SYSTEM SO HE NEEDS TO BE 
ISOLATED FROM THE ENVIRONMENT 
BECAUSE THEY GET SICK VERY, VERY
 EASILY AND VERY BADLY.
THE THING ABOUT SCID IS THAT 
THERE ARE MANY, MANY DIFFERENT 
MUTATIONS THAT CAN LEAD TO THIS.
AND ALL OF THEM RESULT IN HAVING
 NO FUNCTIONAL IMMUNE SYSTEM.
BUT THERE ARE OTHER TYPES OF 
GENETIC DISEASES WHERE THERE'S A
 SINGLE MUTATION THAT CAN CAUSE 
THAT DISEASE.
AN EXAMPLE OF THAT WOULD BE 
SICKLE CELL DISEASE.
SO EVERYONE WITH SICKLE CELL 
DISEASE HAS THE SAME MUTATION.
OKAY?
AND IT IS IN A PROTEIN CALLED 
HEEM OWE GLOBIN THAT NORMALLY 
CARRIES OXYGEN.
THE MUTATION INSTEAD CAUSES THE 
HEMOGLOBIN TO ENCLOSING UP 
CAPPELLERIS.
RED BLOOD SHELLS, ENCLOSINGS -- 
CLOGS UP CAPPELLERIS AND LEADS 
TO PAIN.
ALSO LEADS TO GREATLY DECREASED 
LIFESPAN.
IN THE DEVELOPING WORLD, PEOPLE 
LIVE UNTIL MAYBE 45.
IN SUB-SAHARAN AFRICA WHERE IT 
IS MOST PREVALENT PEOPLE 
ACTUALLY DIE AROUND AGE 5.
SO THIS IS A GENETIC DISEASE.
SICKLE CELL DISEASE IS VERY 
PREVALENT IN TROPICAL OR OTHER 
COUNTRIES WHERE MALARIA IS 
PRESENT.
SO IN THE U.S., THE TRAIT IS 
MOST OFTEN FOUND IN INDIVIDUALS 
OF AFRICAN DESCENT.
BUT IT ALSO POPS UP THROUGHOUT 
THE WORLD.
LIKE I SAILED, THERE ARE PLENTY 
OF PEOPLE IN THE U.S. THAT HAS 
IT, BUT THERE ARE MILLIONS OF 
PEOPLE IN AFRICA.
SO WHAT WE ARE REALLY TALKING 
ABOUT HEAR IS A HUGE AMOUNT OF 
GENETIC INFORMATION IN SOMEONE'S
 BODY.
SO IF YOU THINK ABOUT YOUR BODY 
AS SORT OF EACH CELL CONTAINS A 
LIBRARY OF GENETIC INFORMATION.
AND THAT INFORMATION GETS READ 
OUT, MOST OF THE TIME WHEN YOU 
HAVE MUTATIONS, THOSE MUTATIONS 
CAUSE A TYPO, BUT YOU CAN STILL 
FIGURE OUT WHAT THE SENTENCE 
SAYS.
SO YOU CAN THINK ABOUT MAYBE YOU
 ARE READING THROUGH A BOOK, AND
 THERE'S SOMETHING THAT CHANGES,
 A WORD A LITTLE BIT.
CAN YOU STILL FIGURE OUT WHAT 
THAT MEANS.
THAT WOULD BE A NEUTRAL 
MUTATION.
ACTUALLY, BETWEEN YOU AND THE 
PERSON SITTING NEXT TO YOU, 
THERE ARE THOUSANDS OF NEUTRAL 
MUTATIONS.
AND THEY ARE BASICALLY BENIGN, 
THEY DON'T REALLY DO ANYTHING.
EVERY ONCE IN A WHILE THERE IS A
 MUTATION THAT CHANGES THE 
MEANING OF A WORD.  
AND IT CAN CHANGE THE MEANING OF
 THE WORD VERY, VERY, VERY 
SERIOUSLY.
SO SIMPLE EXAMPLE MIGHT BE, IF 
YOU THINK ABOUT THE WORD DANCER,
 THAT'S ONE LETTER AWAY, A C 
FROM THE WORD CANCER.
SO IF YOU CAN IMAGINE, THAT IN 
THE ENTIRE BOOK, IT'S THE WORD 
DANCER GETS CHANGED TO CANCER IN
 JUST THE RIGHT WAY, IN JUST THE
 WRONG PLACE, THAT CAN BE REALLY
 BAD.
SO WHAT DO WE HOPE IN TERMS OF 
GENETIC ENGINEERING, THE HOPE IS
 REALLY BE ABLE TO TAKE THIS 
HUGE AMOUNT OF GENETIC 
INFORMATION, AND PUT THINGS 
BACK, TO BE ABLE TO TAKE 
MUTATIONS THAT HAVE ARISEN, AND 
PUT THEM BACK INTO A STATE THAT 
DOES NOT CAUSE DISEASE.
ONE OF THE REASONS WHY PEOPLE 
ARE REALLY EXCITED ABOUT GENETIC
 ENGINEERING RESEARCH RIGHT NOW,
 IS BECAUSE IN THE LAST COUPLE 
YEARS, WE'VE NOW UNDERSTOOD MUCH
 MORE ABOUT OUR OWN GENOME.
SO WHEN IT COMES TO READING 
GENOMES, SEQUENCING GENOMES, 
SEQUENCING PEOPLE, UNDERSTANDING
 WHAT MUTATIONS ARE OUT THERE, 
THERE HAVE BEEN HUGE, HUGE 
STRIDES OVER THE LAST DECK ATD.
-- DECADE.
IT IS NOW ACTUALLY POSSIBLE FOR 
INDIVIDUAL PATIENTS TO HAVE 
GENOMES COMPLETELY SEQUENCED.
THE PROCEDURE IS TOTALLY 
NON-INVASIVE, AND IT REALLY ONLY
 COSTS ABOUT A THOUSAND DOLLARS 
WHEN YOU GET DOWN TO IT.
IT IS QUITE CHEAP.
AND IT GETS DONE ON A RELATIVELY
 ROUTINE BASIS.
THE PROBLEM IS, WHAT DO YOU DO 
WITH ALL THAT INFORMATION.
BECAUSE WHAT I TOLD YOU IS THAT 
IF YOU TAKE ANY TWO INDIVIDUALS 
AND YOU SEQUENCE THEM, THERE 
WILL BE THOUSANDS OF CHANGES.
MOST OF THEM DON'T REALLY DO 
ANYTHING.
SO THERE'S A BIG QUESTION ABOUT 
HOW DO YOU KNOW WHAT MUTATIONS 
CAUSE PROBLEMS.
THEN OF COURSE, ONCE YOU FIGURE 
OUT WHICH ONE CAUSES THE 
PROBLEM, YOU NEED TO BE ABLE TO 
DO SOMETHING ABOUT IT.
AND THAT'S WHERE GENOME 
ENGINEERING COMES IN.
GENE EDITING.
THE PROBLEM IS, WE ARE MUCH 
BETTER AT READING THAN WE ARE AT
 WRITING.
SO WE HAD TOOLS TO BE ABLE TO 
CHANGE GENOMES FOR ABOUT TWENTY 
YEARS.
THINGS ARE STARTING TO 
ACCELERATE.
CRISPR IS ONE EXAMPLE OF THAT, 
BUT WE ARE VERY NEW AT THIS.
SO LIKE I SAID, GENOME EDITING 
HAS BEEN AROUND FOR TWENTY 
YEARS.
THAT MIGHT BE A SURPRISE TO 
PEOPLE IN THE AUDIENCE, YOU 
KNOW, WHY AM I ONLY HEARING 
ABOUT THIS NOW, WHEN IT COMES TO
 SCIENCE, WHY HAVEN'T I HEARD 
ABOUT THIS 20 YEARS AGO?
IN PART IT IS BECAUSE IT WAS 
PRETTY HARD TO DO.
SO THE FIRST GENE EDITING TOOLS 
WERE CALLED -- IT MIGHT SURPRISE
 YOU TO KNOW THESE ARE IN THE 
CLINIC RIGHT NOW.
THERE IS A COMPANY THAT IS USING
 ZINC TOOLS TO CURE DISEASES.
THEY HAVE PRETTY PROMISING 
RESULTS, TO TRY TO CURE HIV.
SO THE IDEA HERE, HIV ATTACKS A 
CERTAIN CELL IN YOUR BLOOD, AND 
IT DOES SO BY BINDING ONTO A 
CERTAIN THING THAT'S ON THE 
SURFACE OF THAT CELL.
AND THAT THING THAT'S ON THE 
SURFACE OF THE CELL DOESN'T SEEM
 TO DO MUCH ELSE.
SO WHAT DO THESE GENE EDITORS 
DO?
DELETE THE THING ON THE SURFACE 
OF THE CELL, AND THUS THE HIV 
HAS NOWHERE TO GO AND YOU CAN 
CLEAR IT OUT.
SO THIS IS ACTUALLY IN PHASE 2 
CLINE CAL TRIALS FOR -- CLINICAL
 TRIALS FOR HIV, HAS BEEN SHOWN 
TO CURE PEOPLE OF HIV.
BUT, AGAIN, IT IS HARD TO USE, 
SLOW TO DEPLOY, YOU REALLY HAVE 
TO BE A SPECIALIST IN THE ART TO
 USE THEM.
SO WHAT HAS REALLY CHANGED GENE 
EDITING RESEARCH IS THE 
DEVELOPMENT OF SO-CALLED 
CRISPR/Cas9, AND THE FUNDAMENTAL
 ADVANCE HERE IS NOT THE IDEA OF
 GENE EDITING IN AND
 OF ITSELF, BUT THE 
DEMOCRATIZATION OF GENE EDITING.
RESEARCH AND HOPEFULLY FOR 
THERAPY.
WHAT IS Cas9?
LET'S TAKE A GEEK OUT MOMENT TO 
TALK ABOUT HOW THIS WORKS.
I AM GOING TO PRESENT A BLOB.
IN THIS BLOB WE HAVE Cas9 THE, 
WHICH IS THE PROTEIN, AND IT IS 
RECOGNIZING THE PIECE OF DNA, 
OPENING UP THAT PIECE OF DNA.
Cas9 THEN USES A PIECE OF RNA 
WHICH IS ANOTHER PIECE OF 
SO-CALLED KNEW CLAY IK ACID -- 
NUCLEIC ACID.
WHEN I TALK ABOUT DNA AND RNA, 
THINK ABOUT A, T, G, C, 
HOPEFULLY YOU HAVE HEARD ABOUT 
BEFORE.
ONE THING YOU MIGHT REMEMBER 
ABOUT DNA IS THAT YOU HAVE PAIRS
 OF THESE BASES, THESE NUCLEIC 
ACIDS.
A ALWAYS GOES WITH T, AND G GOES
 WITH C.
THAT'S THE FUNDAMENTAL THING 
ABOUT CRISPR/Cas9.
IF YOU KNOW A GOES WITH T, G 
GOES WITH C, WHICH I JUST TOLD 
YOU, THAT'S IT.
THAT'S ALL YOU NEED TO KNOW TO 
DESIGN A GENE EDITING.
YOU NO LONGER HAVE TO FIGURE OUT
 HOW FINGERS WORK, AND WHAT 
CASES DO THEY WORK, WHAT CASES 
DON'T THEY WORK.
IF YOU KNOW THAT A GOES WITH T 
AND G GOES WITH C, YOU CAN 
DESIGN A GENE EDITING AGENT.  
THAT ALLOWS PEOPLE TO INSTEAD OF
 FOCUSING ON THE INS 0 AND OUTS 
OF THE TOOLS, INSTEAD THEY CAN 
FOCUS ON JUST MAKING THE TOOLS, 
REPROGRAMMING THOSE TOOLS AND 
USING THEM.
ALSO MEANS THAT REPROGRAMMING 
THIS IS SIMPLE AND EASY, AND AS 
YOU WILL HEAR IN A BIT, THAT 
MEANS YOU CAN ACCESS MANY MORE 
PROBLEMS.
YOU CAN ACCESS MANY MORE 
DIFFERENT DISEASES, AND ASK 
DIFFERENT QUESTIONS YOU COULDN'T
 GET TO BEFORE.
SO THE WAY GENOME EDITING 
ACTUALLY WORKS IS YOU MAKE THAT 
CHANGE ON THE RNA, THE A, T, G, 
C PART.
AND THAT BRINGS Cas9 TO AN AREA 
OF THE GENOME.
THEN Cas9 CUTS THAT PART OF THE 
GENOME.
THAT MIGHT SOUND SURPRISING.
WE ARE TALKING ABOUT EDITING.
WHY ARE WE SUDDENLY DOING 
CUTTING WHEN WE WANT TO DO 
EDITING?
THE REASON THIS WORKS IS THAT 
ALL ORGANISMS THAT ARE OUT THERE
 HAVE EVOLVED GREAT WAYS TO 
PROTECT THEIR GENOMES.
SO IF YOU GET A CUT INSIDE A 
GENOME, YOUR CELLS WILL REPAIR 
THAT CUT.
YOUR CELLS HAVE DEFENSES AGAINST
 DNA DAMAGE.
AND IN YOUR CELLS, THIS HAPPENS 
IN ONE OF TWO WAYS: ON THE ONE 
HAND, YOU HAVE ERROR REPAIR, 
WHICH LEADS TO DELETIONS AND 
INSERTIONS AT A REGION.
AND ON THE OTHER HAND, YOU HAVE 
THE OPPORTUNITY TO PUT AN EXTRA 
INFORMATION, WHICH THE CELL WILL
 THEN COPY OFF OF, AND 
INCORPORATE THAT INFORMATION.
SO WHAT DOES THAT MEAN?
WHEN YOU GET THE INSERTIONS AND 
DELETIONS, THAT WILL DISRUPT 
WHATEVER IS THERE.
SO IF THERE WAS INFORMATION THAT
 WAS DOING SOMETHING, LET'S SAY 
SOMETHING SAID DANCER.
NOW IT MIGHT SAY D-A-X-Q, IT 
BREAKS WHATEVER WAS THERE, OKAY?
FROM A RESEARCH POINT OF VIEW, 
THE WAY WE DO RESEARCH IN 
BIOLOGY, TAKING SOMETHING THAT 
WORKS ALREADY, SAY, IN A CULTURE
 STYLE OR A MODERN ORGANISM AND 
TRY TO BREAK IT IN PRECISE WAYS 
AND SAYING HOW DOES BREAKING 
THIS THING IN THIS PRECISE WAY 
CHANGE THE OUTCOME.
THAT'S THE WAY WE LEARN THINGS 
ABOUT THE WORLD AROUND US.
THAT'S IMPORTANT BECAUSE THE 
WORLD AROUND US IS VERY 
COMPLICATED.
SO INSTEAD OF SAYING BUILD A CAR
 ENGINE FROM A WHOLE BUNCH OF 
PARTS LYING AROUND, WE START 
WITH WORKING CAR ENGINES AND 
TAKE OUT ONE PIECE AT A TIME AND
 ASK WHAT DOES THIS DO.
SO Cas9 THE ON THE ONE HAND IS A
 WAY TO ASK FUNDAMENTAL 
QUESTIONS ABOUT HOW DO THE EDGE 
INCHES THAT ARE OUR CELLS 
ACTUALLY WORK.
FROM AN EDITING POINT OF VIEW, 
SORT OF MORE SURGICAL WAY OF 
DOING THINGS, WE CAN SWAP 
MUTATIONS IN AND OUT IN A VERY 
PRECISE WAY.
INSTEAD OF PUTTING IN THAT 
WEIRD, CRAZY XQZ IN THE MIDDLE 
OF DANCER, WE CAN TAKE THE 
SEQUENCE THAT SAYS CANCER ADD BE
 CHANGE IT BACK INTO DANCER.
SO IT IS VERY PRECISE AND VERY 
SURGICAL.
SO THERE'S USES FOR FUND THE AL 
RESEARCH -- FUNDAMENTAL RESEARCH
 AND POTENTIAL TO CURE GENETIC 
DISEASES.
BUT ONE OF THE THINGS IS THE 
CONTEXT REALLY MATTERS.
TURNING OUT THAT NOT EVERY CELL 
IN YOUR BODY HAS THE SAME TYPES 
OF REPAIR MECHANISMS AS EVERY 
OTHER CELL.
SO ONE OF THE THINGS THAT PEOPLE
 ARE TRYING TO FIGURE OUT RIGHT 
NOW IS WHEN YOU TRY TO MAKE 
THESE FIXES IN, SAY, A BRAIN 
CELL VERSUS A BLOOD CELL, HOW DO
 WE BETTER CONTROL AND GET THE 
OUTCOMES THAT WE WANT.
SO I REALLY WANT TO STRESS THAT 
WE'RE NOT AT THE SCIENCE FICTION
 FUTURE NOW, WE ARE JUST, YOU 
KNOW, ABLE TO PUT THESE KINDS OF
 CHANGES INTO CELLS AND PATIENTS
 RIGHT AWAY.
WE ARE STILL IN THE, WE HAVE NEW
 TOOLS, WE NEED TO UNDERSTAND 
HOW THEY WORK, AND WE NEED TO 
UNDERSTAND HOW THEY INTERSECT 
WITH OUR OWN BODIES.
SO LET'S ZOOM IN A LITTLE BIT 
MORE FROM THE BLOB.
WHAT I AM SHOWING YOU HERE IS A 
3-D MODEL OF Cas9.
SO THIS IS ACTUALLY -- THIS IS 
ACTUALLY WHAT Cas9 LOOKS LIKE.
THIS IS BASED ON A SO-CALLED 
CRYSTAL STRUCTURE THAT'S BEEN 
SOLVED RELATIVELY RECENTLY.
SO THIS IS ACTUALLY PHYSICALLY 
WHAT Cas9 LOOKS LIKE.
Cas9 IS THE PROTEIN THAT'S IN 
WHITES, THE GENE THAT IT'S 
RECOGNIZING IN BLUE, AND WHAT 
GETS USED TO PAIR THE GENE, THE 
A, T, G, C PAIR IS IN ORANGE.
WE CAN POP AWAY PAST OF Cas9, IT
 WRAPS AROUND THE TARGET GENE, 
WHEN IT DOES SO, IT LEADS TO 
THESE BREAKS.
ONCE THOSE BREAKS GET PUT IN, 
THAT'S THE SIGNAL FOR THE CELL 
TO SAY, I HAVE A BREAK IN THE 
GENOME, I NEED TO REPAIR IT.
I NEED TO DO SOMETHING WITH IT.
REALLY Cas9 IS A LITTLE GENOME 
EDITING MACHINE.
I WON'T GET INTO THE DETAILS OF 
HOW Cas9 AND CRISPR SYSTEMS WERE
 DISCOVERED, OTHER THAN TO SAY A
 QUICK ASIDE TO SAY CRISPR/Cas9 
IS ONE OF THE REALLY AMAZING 
STORIES OF HOW FUNDAMENTAL 
RESEARCH CAN HAVE HUGE 
IMPLICATIONS FOR APPLICATION AND
 POTENTIALLY TREATING THERAPY.
Cas9 AND CRISPR ARE ACTUALLY 
BACTERIAL SYSTEMS.
THE BACTERIAL MACHINES, THEY 
WERE DISCOVERED BY PEOPLE NOT 
LOOKING FOR GENOME EDITING 
MACHINES, THEY WERE JUST TRYING 
TO ASK HOW IS IT THAT BACTERIA 
WORKS.
IT TURNS OUT THEY HAVE HUGE 
IMPLICATIONS FOR TREATING 
DISEASE.
SO I THINK ONE OF THE LESSONS 
THAT WE HAVE IS IT IS IMPORTANT 
TO, MAYBE A BETTER WAY TO PUT 
IT, FORTUNE FAVORS PREPARED 
MINDS.
YOU NEED TO ASK QUESTIONS ABOUT 
THE WORLD, BUT IT HELPS TO JUST 
BE CURIOUS, AND TO ASK THOSE 
QUESTIONS WITHOUT SAYING I WANT 
TO FIND A GENOME EDITING 
MACHINE, TO JUST ASK GENERALLY 
HOW DOES THE WORLD AROUND ME 
WORK.
SO LET ME COME BACK TO THE IDEA 
OF DEMOCRATIZATION.
I TOLD YOU THERE IS AN EASY WAY 
OF DOING THE EDITING, BUT THAT 
DOESN'T CHANGE THE WAY WE THINK 
ABOUT USING GENOME EDITING 
TOOLS.
IT USED TO BE THAT A WHOLE BUNCH
 OF PEOPLE WOULD HAVE A WHOLE 
LOT OF DIFFERENT QUESTIONS.
AND IF YOU WANTED TO ASK THOSE 
QUESTIONS, USING GENOME EDITING 
YOU WOULD HAVE TO GO TO YOUR ONE
 GENOME EDITING EXPERT, AND THEN
 EVERYTHING WOULD BOTTLENECK 
AROUND THAT.
SO THINGS SLOWED DOWN A LOT.
ACTUALLY, THEY ENDED UP BEING 
QUITE EXPENSIVE.
WITH Cas9, WHAT HAPPENED 
INSTEAD, EVERYBODY NOW CAN USE 
THESE TOOLS THEMSELVES.
SO THAT'S ONE OF THE THINGS THAT
 I WANT TO PUT 0 -- OUT THERE, 
USING Cas9, CRISPR SYSTEMS TO 
CURE GENETIC DISEASE IS VERY 
EXCITING, BUT ONE OF THE HUGE 
POSSIBILITIES HERE IN GENERAL 
FOR THERAPY IS THE ABILITY TO 
ASK AND ANSWER QUESTIONS THAT 
ARE MORE FUNDAMENTAL, MUCH MORE 
RAPIDLY.
AND THAT'S REALLY, I THINK, SO 
SORT OF THE SNOWBALL EFFECT THAT
 WILL HAVE AN EFFECT ON OUR 
LIVES.
SO CURING GENETIC DISEASE IS A 
REALLY IMPORTANT PART OF 
CRISPR/Cas9, BUT NOW BEING ABLE 
TO ASK THE HUNDREDS OF QUESTIONS
 THAT PEOPLE MIGHT HAVE AND NOT 
HAVE ALL THAT RESEARCH 
BOTTLENECKED IN ONE LITTLE AREA 
I THINK IS GOING TO LEAD TO A 
HUGE ACCELERATION IN FUNDAMENTAL
 UNDERSTANDING, WHICH WILL 
EVENTUALLY LEAD TO MORE CURES 
FOR EVEN NON-GENETIC DISEASES.
TO GIVE YOU AN IDEA HOW QUICKLY 
THINGS ARE MOVING, THIS IS A 
CHART SHOWING HOW MANY 
PUBLICATIONS MENTIONED GENOME 
EDITING.
I TOLD EUGENE OEM EDITING WAS 
AROUND FOR -- GENOME EDITING WAS
 AROUND FOR 20 YEARS, SO IN THE 
90s.
BUT THE MENTIONS OF GENOME 
EDITING IN THE LITERATURE, IN 
SCIENTIFIC LITERATURE WERE SO 
SMALL BEFORE THE INVENTION OF 
Cas9, YOU CAN'T EVEN SEE THEM ON
 THIS GRAPH.
FEW PEOPLE WERE WORKING IN Cas9,
 RIGHT WHEN Cas9 GOT DISCOVERED,
 CRISPR SYSTEMS GOT DISCOVERED 
AND DEPLOYED, THE MENTIONS OF 
GENOME EDITING EXPLODED.
AT THIS POINT THERE ARE ABOUT 
4,000 Cas9 PUBLICATIONS IN THE 
PAST FOUR YEARS ALONE.
THERE ARE ABOUT FOUR PAPERS 
PUBLISHED EVERY DAY.
THE FIELD IS MOVING AT AN 
INCREDIBLE PACE.
AND I THINK THAT JUST GIVES YOU 
AN IDEA OF HOW EXCITING PEOPLE 
FIND THIS.
SO THE USE OF CRISPR CAST 9 IS 
-- Cas9 IS REALLY TRANSFORMING 
BIOLOGY BY LETTING PEOPLE ASK 
DEMOCRATIZED QUESTION.
SO MODEL ORGANIZE NIMS, IT TURNS
 OUT IT -- ORGANISMS, IT WORKS 
IN NON-HUMAN PRIMATES, TO ASK 
QUESTIONS THAT MIGHT BE EVEN 
CLOSER TO HUMAN HEALTH, IT WORKS
 IN AGRICULTURAL SPECIES, SUCH 
AS WHEAT, CORN, THINGS LIKE 
THAT, IN MY LAB WE TEND TO USE 
IT IN HUME APP CELLS.
SO -- HUMAN CELLS.
IN -- THIS MEANS NOT ONLY CAN WE
 ASK FUNDAMENTAL QUESTIONS FOR 
RESEARCH, BUT POTENTIALLY HOPE 
TO APPLY IT FOR GENETIC DISEASE.
AS A QUICK ASIDE, IT COULD HAVE 
IMPACTS BEYOND THAT.
SO PEOPLE HAVE SHOWN GENOME 
EDITING USING Cas9 WORKS IN 
AGRICULTURAL SPECIES, GOATS, 
COWS, CHICKENS, ET CETERA.
AND PEOPLE HAVE SHOWN THAT IT 
WORKS IN MOSQUITOS AND THE 
MALARIA PARASITE.
PEOPLE ARE STARTING TO THINK 
ABOUT WAYS OF POTENTIALLY 
ERADICATING MALARIA USING GENOME
 EDITING TOOLS.
THAT'S A TOPIC FOR ANOTHER DAY, 
BECAUSE I THINK WE WANT TO FOCUS
 ON THE POSSIBILITY FOR, SAY, 
GENOME EDITING AND REPRODUCTION.
LET'S GIVE A CONCRETE EXAMPLE 
HOW GENOME OWED -- EDITING WOULD
 CHANGE THE WAY PEOPLE TREAT 
DISEASE.
FOCUS ON SICKLE CELL DISEASE.
A BLOOD DISORDER.
IT IS CAUSED BY SICKLING OF RED 
BLOOD CELLS.
BUT THAT EVENTUALLY COMES ALL 
THE WAY BACK TO BONE MARROW.
YOUR BONE MARROW IS THE SOURCE 
OF ALL THE BLOOD COMPONENTS YOU 
HAVE.
NOW, SICKLE CELL DISEASE CAN BE 
CURED PERMANENTLY THROUGH A 
SO-CALLED ALOGENIC TANS PLANT.
YOU TAKE BONE MARROW FROM A 
HEALTHY INDIVIDUAL AND 
TRANSPLANT IS INTO SOMEONE WITH 
SICKLE CELL DISEASE, AND THAT 
THEN RENDERS THEM HEALTHY.
THEY NO LONGER HAVE THE BONE 
MARROW WITH THE MUTATION, THEY 
HAVE HEALTHY BONE MARROW, AND 
THAT CURES THEM.
BUT THERE ARE A LOT OF PROBLEMS 
WITH THIS.
NUMBER ONE, IT CAN BE VERY HARD 
TO FIND A DONOR.
NUMBER TWO, THE ACT OF DOING 
THIS BONE MARROW TRANSPLANT, YOU
 HAVE TO OBLATE THE BONE MARROW.
THAT RENDERS THE PERSON WHO GETS
 THE BONE MARROW TRANSPLANT 
INFERTILE.
NUMBER THREE, THERE IS A SMALL 
CHANCE, ABOUT A 1% CHANCE, THAT 
PEOPLE WHO GET THIS BONE MARROW 
TRANSPLANT WILL REJECT THE 
GRAPH.
THEY MAY HAVE TO GET ANOTHER 
BONE MARROW TRANSPLANT TO 
REPLACE THE BONE MARROW, GIVING 
THEM THE DISEASE BACK AGAIN.
THIRD, THERE IS THE POSSIBILITY 
THEY MAY NEVER WAKE UP FROM THE 
OPERATING TABLE.
FROM A GENE EDITING POINT OF 
VIEW, INSTEAD WE WANT TO TURN 
THIS TOWARDS A TRANSPLANT, MAKE 
PEOPLE THEIR OWN BONE MARROW 
DONORS.
SO WE WANT TO TAKE SOMEONE'S 
BONE MARROW, WHICH HAS THE 
SICKLE CELL MUTATION, TAKE IT 
OUT, EDIT THE GENE TO PUT IT 
BACK AND THEN TRANSPLANT IT BACK
 INTO THE PERSON.
SO IN THIS WAY, RATHER THAN 
TAKING BONE MARROW FROM A 
HEALTHY PERSON, PUTTING IT INTO 
SOMEONE WITH A DISEASE, WE TAKE 
SOMEONE'S OWN BONE MARROW WITH 
THE DISEASE AND TURN IT HEALTHY 
AND PUT IT BACK IN.
SICKLE CELL DISEASE IS JUST ONE 
EXAMPLE OF THIS.
THERE ARE ABOUT A HUNDRED 
THOUSAND PEOPLE IN THE U.S. THAT
 HAVE SICKLE CELL DISEASE, WHICH
 IS ACTUALLY A PRETTY LARGE 
NUMBER.
BUT WORLDWIDE THERE ARE ABOUT 
350 MILLION PEOPLE THAT HAVE 
SOME FORM OF GENETIC DISEASE.
AT LEAST THAT HAVE BEEN 
IDENTIFIED.
THERE ARE 7,000 DIFFERENT 
MONOJENIC DISORDERS, CAUSED BY 
MUTATIONS IN A SINGLE KRISTINE 
THAT WE -- GENE THAT WE KNOW OF.
PART OF THE REASON THAT PEOPLE 
ARE EXCITED ABOUT CRISPR/Cas9 
FOR GENE EDITING, EXACTLY WHAT I
 TOLD YOU PREVIOUSLY.
IT IS VERY EASY TO MAKE NEW 
REAGENTS.
SO IF IT IS HARD TO TAKE A 
GENOME EDITING AGENT, A YEAR FOR
 EACH ONE, IMAGINE IF THERE WERE
 7,000 DIFFERENT DISEASES AND IT
 TAKES A LONG TIME TO MAKE EACH 
ONE, IT WOULD TAKE FOREVER TO DO
 THIS, EVEN LEAVING ASIDE ALL 
THE CHALLENGES AROUND DOING 
REGULATION, AND SAFETY AND 
THINGS LIKE THAT.
EVEN JUST FINDING THE FIRST 
REAGENT TO DO THE EDITING IS 
GOING TO TAKE FOREVER.
BUT Cas9 IS VERY FAST, VERY 
EASY, AND SO AT LEAST ON PAPER, 
IT COULD BE POSSIBLE TO MAKE A 
DIFFERENT GENOME EDITING REAGENT
 FOR EACH INDIVIDUAL MUTATION, 
WHICH BRINGS UP THE IDEA OF 
PERSONAL CURES.
AND THE REASON I THINK THIS IS 
SO POWERFUL IS SOMETHING THAT IS
 ACTUALLY NOT PRIVATE TO GENETIC
 DISEASE, THE IDEA OF THE LONG 
TAIL.
THE LONG TAIL MAY BE 
RECOGNIZABLE TO YOU IN A CONTEXT
 OF SOMETHING LIKE AMAZON, OR 
DOING GOOGLE SEARCHES, OR THINGS
 LIKE THAT.
THE IDEA HERE IS THAT WHEN MOST 
PEOPLE GO OUT, THEY LOOK FOR, 
SAY, TWO OR THREE THINGS.
TWO OR THREE PRODUCTS.
AND IN A -- THAT COVERS A LOT OF
 SPACE, MAYBE 50% OF THINGS ARE 
COVERED BY 2 OR 3 PRODUCTS.
SO THINK ABOUT THIS IN THE 
CONTEXT OF GENETIC DISEASE, A 
BUNCH OF PATIENTS HAVE TWO OR 
THREE DIFFERENT GENETIC 
DISEASES.
AND THE REST OF THE 50% IS 
COVERED UP BY A HUGE SMATTERING 
OF A WHOLE BUNCH OF DIFFERENT 
STUFF.
THAT'S THE LONG TAIL.
OKAY?
SO TWO OR THREE THINGS CAPTURE 
THE FIRST 50%, AND THE LAST 50% 
IS COVERED BY THOUSANDS.
SO THAT'S A PROBLEM IF YOU HAVE 
A TOOL OR REAGENT TO MAKE A CURE
 THAT IS VERY SLOW TO DEVELOP.
YOU WOULD ONLY BE AIL TO DO 
SOMETHING -- ABLE TO DO 
SOMETHING FOR 50% OF PEOPLE, 
THAT HAVE THE TWO TO THREE 
DISEASES.
TO REALLY AFFECT THE LONG TAIL, 
THE OTHER 50%, YOU NEED 
SOMETHING THAT'S FAST AND EASY.
AND SO THE HOPE, BUT WE ARE NOT 
THERE YET, IS THAT Cas9 MIGHT BE
 ABLE TO ADDRESS THE LONG TAIL.
NOW, THERE ARE A LOT OF 
CHALLENGES HERE BEYOND JUST 
MAKING THESE REAGENTS.
WHEN YOU START THINKING ABOUT 
PERSONAL CURES, YOU HAVE TO 
START THINKING ABOUT HOW YOU 
SHOW THAT THIS IS SAFE.
HOW DO YOU RUN A CLINICAL TRIAL,
 IF THERE ARE ONLY FIVE PEOPLE 
IN THE WORLD THAT HAVE THIS 
DISEASE.
I AM NOT GOING TO ADDRESS THAT, 
BECAUSE YOU COULD PROBABLY DO, 
YOU KNOW, AN HOUR-LONG 
DISCUSSION ABOUT JUST THAT ONE 
ISSUE.
I AM GOING TO FOCUS ON JUST -- I
 AM GOING TO SAY IT'S 
POTENTIALLY THERE, AND SO I 
THINK ONE OF THE THINGS WE NEED 
TO DO IS START TALKING ABOUT 
WHAT IS THE REGULATION LANDSCAPE
 LOOK LIKE NOW THAT THE 
POSSIBILITY IS THERE FOR THE 
LONG TAIL.
SO I HAVE BEEN TALKING ABOUT 
GENE EDITING IN GENERIC TERMS.
I AM GOING TO MAKE A SPLIT 
BETWEEN SO-CALLED SEMATIC AND 
GERMLINE EDITING.
SEMATIC, YOU MAKE A MUTATION NOT
 PASSED DOWN TO DIFFERENT 
GENERATIONS.
AN EXAMPLE WOULD BE THIS BONE 
MARROW TRANSPLANT I TALKED 
ABOUT.
YOU TAKE BONE MARROW OUT, EDIT, 
PUT IT BACK IN.
IF THE PERSON WHO GOT THAT EDIT 
HAS A CHILD, THEIR CHILD MAY 
STILL HAVE THE MUTATION PASSED 
DOWN TO THEM.
THE DIFFERENCE IN GERMLINE 
EDITING IS THAT YOU EDIT, WHEN 
YOU EDIT THE SO-CALLED GERMLINE,
 MIGHT BE EDITING THE EGGS OR 
SPERM OR EVEN THE EMBRYO, AND 
THAT CHANGE WOULD BE, THEN, 
PASSED DOWN THROUGH GENERATIONS.
SO THAT WOULD MEAN, SAY, IF 
SOMEONE HAD A GENETIC DISEASE, 
YOU WOULD NOT -- YOU WOULD CURE 
IT IN THEM, AND YOU WOULD THEN 
CURE IT IN THEIR CHILD AND CURE 
IT IN, SAY, THEIR GRANDCHILD.
SO LET'S TALK FIRST ABOUT WHAT 
ISSUES THERE MIGHT BE.
I TALKED ABOUT THE PROMISE, HOW 
EXCITED PEOPLE ARE ABOUT THIS.
SOME OF THESE CONCERNS CAME UP 
IN THE PREVIOUS DISCUSSION, I 
THINK THEY WERE WELL COVERED.
I JUST WANT TO GO OVER THEM 
REALLY QUICKLY.
THE FIRST OFF, BEING ACCESS TO 
TREATMENT.
NOW, I WANT TO POINT OUT THIS IS
 NOT A PRIVATE PROBLEM TO 
GENETIC DISEASE TREATMENT.
IN FACT, THE GRAPHIC THAT I AM 
SHOWING HERE THAT SHOWS PROBLEMS
 WITH STIGMA, DRUGS COST TOO 
MUCH, NO CONFIDENTIALITY, ALL OF
 THESE THINGS APPLY TO THE 
TREATMENT OF GENETIC DISEASE.
THIS IS A GRAPHIC FROM W.H.O. 
HANDBOOK ON TREATMENT FOR HIV 
AND AIDS.
EVERY SINGLE ONE OF THESE 
PROBLEMS, ACCESS TO CLINICS THAT
 CAN DO GENE EDITING, PROBLEMS 
OF CONFIDENTIALITY, YOU KNOW, 
HOW DO YOU PROTECT SOMEONE, IF 
SOMEONE GOT AN EDIT, DID NOT GET
 AN EDIT.
HOW WILL IT COST.
ALL OF THE SUPPLIES, NEW 
TECHNOLOGY LIKE GENOME EDITING.
THERE IS ANOTHER PROBLEM WHICH I
 THINK HAS NOT BEEN COVERED YET,
 BUT IS NO LESS IMPORTANT, WHICH
 IS PART OF THE CHALLENGE OF 
THESE GENETIC DISEASES, THAT 
THEY OCCUR IN MINORITY 
POPULATIONS.
AND ESPECIALLY WHEN IT COMES TO 
SICKLE CELL DISEASE, THESE 
POPULATIONS HAVE NOT BEEN 
TREATED WELL BY THE MEDICAL 
ESTABLISHMENT.
AND SO WHEN I GO AND I TALK TO 
PATIENTS WITH SICKLE CELL, HALF 
OF THEM ARE EXCITED, BECAUSE 
THEY SAY IT IS REALLY GREAT THAT
 YOU ARE FOCUSING ON A DISEASE 
THAT AFFECTS US, WHO HAPPENS TO 
BE A MINORITY POPULATION, AND 
THE OTHER HALF SAYS, WHY ARE YOU
 GIVING US THIS EXPERIMENTAL 
MEDICINE YOU DON'T ACTUALLY KNOW
 IS NOT GOING TO HAVE SOME 
TERRIBLE SIDE EFFECTS?
THAT'S A REALLY IMPORTANT 
MESSAGE TO TAKE HOME, AND ONE 
WHICH I DON'T HAVE A VERY GOOD 
ANSWER FOR.
LIKE WE TALKED ABOUT DURING THE 
DISCUSSION, I'M TRYING TO 
PROVIDE OPTIONS FOR PEOPLE, BUT 
I THINK THAT WE DO HAVE TO THINK
 HARD ABOUT WHERE DO WE TEST 
THESE MEDICINES, HOW DO WE SHOW 
THEY ARE AFTER SAFER AND DO SO 
IN A WAY THAT'S RESPONSIBLE FOR 
THE POPULATIONS THAT WE ARE 
TRYING TO TREAT.
THIS IS ESPECIALLY BECOMES THE 
CASE WHEN WE START MOVING INTO 
CONTEXT FOR THESE GENETIC 
DISEASES, ARE SO RARE THAT, TAY 
-- SAY, 10 PEOPLE IN THE WORLD 
HAVE THE DISEASE, SO HOW DO YOU 
ACTUALLY RUN A TRIAL WHEN 
RUNNING A TRIAL MEANS AFFECTING 
EVERYONE.
THE THIRD CHALLENGE, EVEN WITH 
SEMATIC EDITING, PUBLIC 
ACCEPTANCE IS MODEST.
SO THIS IS A POLL DONE BY PEW 
RESEARCH, FINISHED A COUPLE 
MONTHS AGO THEY ASKED PEOPLE, 
WOULD YOU WANT SEMATIC EDITING.
REMEMBER, NOT PASSED DOWN.
WOULD YOU WANT IT FOR YOUR BABY,
 IF IT HAD A CHANCE OF IMPROVING
 THAT BABY'S HEALTH.
YOU CAN SEE THAT IT'S ABOUT 
50/50 SPLIT.
OKAY?
SO THESE ARE PEOPLE THAT SAY MY 
BABY ISN'T IN TROUBLE, BUT I 
WOULD NOT WANT TO HAVE EDITING 
DONE.
AND I THINK IT IS VERY TELLING 
THAT IN FACT THERE'S A SPLIT 
BETWEEN WHETHER OR NOT PEOPLE 
HAVE KIDS OR NOT.
AND IT GOES AT LEAST TO ME, IT 
WENT OPPOSITE THE WAY I THOUGHT 
IT WOULD.
IF PEOPLE HAVE A CHILD, THEY ARE
 LESS LIKELY TO THINK THAT 
SEMATIC EDITING WOULD BE A GOOD 
CHOICE FOR THAT CHILD.
THIS IS IN CONTRAST TO SOMETHING
 THAT I SEE A LOT WHEN I WORK 
WITH PATIENTS WHO HAVE CHILDREN 
WITH GENETIC DISEASE.
I WORK WITH A COUPLE OF PATIENT 
GROUPS.
SOME OF THOSE PATIENT GROUPS ARE
 VEHEMENTLY FOR SEMATIC EDITING.
THEY WANT TO ABOLISH THE FDA, I 
DON'T WANT SAFETY TRIALS ANY OF 
THAT, GIVE ME THE MEDICINE RIGHT
 NOW, BECAUSE THEIR CHILDREN ARE
 SUFFERING.
I THINK THIS IS ANOTHER ONE OF 
THOSE THINGS THAT WOULD BE 
REALLY INTERESTING TO DISCUSS IN
 THE FUTURE, IS, YOU KNOW, TO 
WHAT EXTENT DO WE EMPOWER 
PATIENTS TO GIVE THEM ACCESS TO 
THINGS WHEN WE CANNOT GUARANTEE 
THAT THEY WILL BE SAFE.
NOW LET'S TALK ABOUT GERMLINE 
EDITING.
PEOPLE TALK A LOT ABOUT GERMLINE
 EDITING WHEN IT COMES TO 
GENETIC DISEASE.
I ACTUALLY WANT TO START ABOUT 
TALKING ABOUT THE RESEARCH 
APPLICATIONS.
THIS IS KATHY, SHE HAD A PAPER 
COME OUT, SHE ASKED A 
FUNDAMENTAL QUESTION USING 
GERMLINE EDITING.
THE QUESTION SHE WANTED TO KNOW,
 WHY IS IT THAT PREGNANCIES 
SOMETIMES FAIL.
YOU MIGHT ASK YOURSELF, WELL, 
SURELY WE MUST KNOW THIS BY NOW.
THE ANSWER IS NO.
WE KNOW ALMOST NOTHING ABOUT IT.
PART OF THE REASON IS, WE HAVE 
HAD NO TOOLS TO BE ABLE TO ASK 
ANYTHING ABOUT DEVELOPING 
EMBRYOS IN HUMANS, AND THERE'S 
BEEN VERY LITTLE APPETITE TO DO 
THAT RESEARCH.
SO KATHY IN THE THE U K. DID A 
NICE SET OF EXPERIMENTS TRYING 
TO ASK ONE PART OF THE 
FUNDAMENTAL QUESTION.
I THINK THAT'S ONE OF THE THINGS
 WE WANT TO MAKE SURE WE DO WHEN
 WE TALK ABOUT GERMLINE EDITING.
WE DON'T WANT TO THROW THE BABY 
OUT WITH THE BATH WATER.
WE WANT TO ENABLE PEOPLE TO 
ANSWER FUNDAMENTAL QUESTIONS 
THAT WILL AFFECT A LOT OF 
PEOPLE'S LIVES, EVEN IN CASES 
THAT DO NOT IMPACT GENETIC 
DISEASE.
NOW, THERE ARE CASES WHERE 
GERMLINE EDITING MIGHT BE USEFUL
 FOR THERAPY, SO CASES WHERE NOT
 JUST EDITING THE PERSON WHO IS 
AFFLICTED WITH THE PARTICULAR 
DISEASE, BUT MAKING SURE THAT IF
 THEY DON'T WANT TO, THEY DON'T 
HAVE TO TREAT DOWN TO THEIR 
CHILDREN, THERE ARE CASES WHERE 
AT THAT THAT MIGHT BE 
APPLICABLE.
ONE EXAMPLE OF THAT WOULD BE 
HUNTINGTON'S DISEASE.
THE DISEASE, THE SO-CALLED 
REPEAT EXPANSION DISEASE.
YOU HAVE CERTAIN REPEATS IN THE 
GENE, AND FOR REASONS I WON'T GO
 INTO, OVER TIME, OVER 
GENERATIONS, THEY EXPAND OUT.
WHAT THAT MEANS IS THAT IF THE 
PARENT IS A LITTLE BIT AFFECTED,
 THE CHILD MIGHT BE MORE 
AFFECTED, THE GRANDCHILD WILL BE
 MORE AFFECTED THAN THAT, AND 
THE GREAT-GRANDCHILD MIGHT BE 
AFFECTED MOST OF ALL.
SO PATIENTS SAY, LOOK, I AM 
GOING TO GET A CURE FOR MYSELF, 
BUT MY KID I KNOW IS IS GOING TO
 HAVE THIS DISEASE, AND THEY ARE
 IN FACT GOING TO HAVE IT WORSE 
THAN I DO.
WHY CAN'T I DO GERMLINE EDITING 
TO STOP THIS DISEASE WHERE IT 
STARTS.
AND SO I THINK, AGAIN, THIS 
DISCUSSION NEEDS TO BE A LITTLE 
BIT MORE SUBTLE THAN JUST LIKE 
GERMLINE SEMATIC, BAD OR VICE 
VERSA, WE NEED TO TALK ABOUT 
THESE THINGS IN TERMS OF 
SPECIFIC DISEASES, SPECIFIC 
PATIENTS AND SPECIFIC 
APPLICATIONS.
I THINK WE HAVE A LITTLE BIT OF 
TIME TO DO THIS BECAUSE IT TURNS
 OUT GERMLINE THERAPY, EVEN IF 
WE HAD ALL AGREED IT WOULD BE 
FINE, IT'S NOT YET READY FOR THE
 CLINIC.
SO NUMBER ONE, THERE IS A 
CONCEPT OF SAFETY, HOW DO YOU 
KNOW THAT YOU ARE HITTING JUST 
WHAT YOU WANT TO HIT, EDITING 
JUST WHAT YOU WANT TO EDIT AND 
NOT SOMETHING ELSE.
IT TURNS OUT THAT THESE EDITING 
REAGENTS CAN HAVE EFFECTS, THAT 
MEANS THEY CAN HIT WHERE YOU 
WANT TO GO, THEY CAN ALSO HIT 
SOMEWHERE ELSE.
UNTIL WE GET IT ONLY HITTING 
WHAT WE WANT IT TO HIT, YOU 
OBVIOUSLY WOULD NOT WANT TO PASS
 THESE OFF TARGETS THROUGH 
GENERATIONS.
THERE'S A MORE SUBTLE PROBLEM, 
WHICH IS ONE CALLED 
MOSIASISM, WHICH MIGHT BE MORE 
FUNDAMENTAL.
THAT'S WHEN DIFFERENT CELLS IN 
THE BODY RECEIVE DIFFERENT 
TRAITS, AND THIS CAN HAPPEN IN 
HUMANS, IT HAPPENS ACTUALLY, 
EVERYONE IN THE AUDIENCE 
FAMILIAR WITH A CASE OF 
MOSIASISM.
A TORTOISE SHELL CAT.
ALL THOSE DIFFERENT COLORS COME 
BECAUSE THOSE CATS ARE MOSAIC.
EACH CELL IN THE COAT HAS A 
SLIGHTLY DIFFERENT TRAIT.
OKAY?
WHEN YOU GO IN AND YOU DO 
GERMLINE EDITING, EVEN IN MODEL 
ORGANISM, SUCH AS IN THESE MICE,
 WHICH ARE A REAL-LIFE EXAMPLE.
IN THESE MICE, SOME ARE WHITE, 
SOME OF THE MICE ARE BLACK, SOME
 ARE MOTTED -- MOTTLED.
THAT'S BECAUSE NOT ALL THE CELLS
 IN THE INITIAL MOUSE EMBRYO GOT
 THE SAME EDIT.
AND THIS HAS BEEN THE CASE WITH 
GERMLINE EDITING SINCE PEOPLE 
STARTED TO USE IT.
IT'S A SEVERE PROBLEM, AND, 
AGAIN, WE NEED TO UNDERSTAND 
MORE ABOUT WHY MOSAISISM HAPPENS
 TO FIGURE OUT A WAY AROUND 
THIS.
A THIRD AND POSSIBLY THE BIGGEST
 REASON TO NOT YET PUT GERMLINE 
EDITING IN THE CLINIC IS REALLY 
JUST DO WE REALLY WANT TO DO 
THIS.
AND I THINK THIS IS ACTUALLY THE
 BIGGEST BARRIER.
I THINK FOR GOOD REASON.
WHEN WE THINK ABOUT THE PREVIOUS
 THINGS SAFETY, MOM -- MOSAISM, 
THOSE ARE HURDLES.
PUBLIC SENTIMENT IS NOT 
SOMETHING TO BE OVERCOME, THAT'S
 SOMETHING TO BE SUSED.
THAT'S -- DISCUSSED.
THAT'S A QUESTION, DO WE REALLY 
WANT TO DO THIS, HOW FAR DO WE 
WANT TO GO, WHAT IS APPROPRIATE,
 WHAT IS NOT.
AND I THINK IT IS TELLING THAT 
IN THIS SAME PEER RESEARCH 
STUDY, PEOPLE ASK, WOULD YOU BE 
MORE OR LESS LIKELY TO BE IN 
FAVOR OF GENE EDITING IF 
SOMETHING WAS PASSED ON TO KIDS 
OR NOT PASSED ON TO KIDS.
AND YOU CAN SEE THAT IF SOMEONE 
MADE AN EDIT THAT WOULD BE 
PASSED ON TO THE WHOLE 
POPULATION, VERY, VERY FEW 
PEOPLE FIND THAT ACCEPT BL A -- 
ACCEPTABLE.
THAT'S SOMETHING WE NEED TO TALK
 ABOUT, AND I THINK WE NEED TO, 
AS SOCIETY, DECIDE IS THIS 
SOMETHING WE WANT TO ALLOW.
IF IT IS SOMETHING WE WANT TO 
ALLOW, ARE THERE SPECIFIC CASES 
WE WANT TO ALLOW IT IN.
WHY DO PEOPLE EVEN CONSIDER 
THIS?
THERE'S THE DISEASE POINT OF 
VIEW.
THERE'S ALSO THE QUESTION OF 
ENHANCEMENT.
SO I WANT TO BRING THIS SPECTRA 
IN THE ROOM, BECAUSE I THINK 
THIS IS SOMETHING THAT WE WANT 
TO TALK ABOUT.
BECAUSE IF WE JUST TALK ABOUT 
GENE EDITING FOR GENETIC 
DISEASE, THE QUESTION BECOMES 
RELATIVELY EASY.
SOMEONE HAS A DISEASE, AND WE 
WANT TO CURE THEM, THERE ARE A 
LOT OF SUBTLE AT THISES THERE WE
 DID DISCUSS A LITTLE BIT AGO, 
BUT IT IS A LITTLE BIT EASIER 
THAN SAYING, WELL, WHAT ABOUT 
PREVENTION OF DISEASE?
FOR EXAMPLE, THERE ARE GENES YOU
 CAN EDIT IN THE BODY THAT WILL 
PREVENT HEART ATTACKS, 
BASICALLY.
OKAY?
SO THERE ARE PEOPLE THAT ARE 
NATURALLY BORN THAT HAVE THESE 
MUTATIONS, AND THEIR CHOLESTEROL
 IS BASICALLY ZERO, THEY ARE 
INCREDIBLY HEALTHY.
THE QUESTION IS, WELL, SHOULD 
EVERYBODY GET THIS, RATHER THAN 
TAKING STATINS, SHOULD EVERYBODY
 GET THIS?
THERE ARE MUTATIONS YOU CAN MAKE
 THAT CAN MAKE PEOPLE MORE 
MUSCULAR, LIKE I SAID 
PREVIOUSLY, MUTATIONS THAT CAN 
RENDER PEOPLE HIV RESISTANT.
SO YOU MIGHT ASK YOURSELF, YOU 
KNOW, THERE ARE QUESTIONS ABOUT 
ENHANCEMENT, WHERE PEOPLE TALK 
ABOUT HAIR COLOR, AND 
INTELLIGENCE.
THOSE ARE NOT REALLY ON THE 
TABLE RIGHT NOW.
WE DON'T UNDERSTAND WHAT MAKES 
SOMEONE, YOU KNOW, MORE 
INTELLIGENT, OR TALLER OR 
ANYTHING LIKE THAT.
WE DO KNOW SINGLE GENES THAT 
COULD BE EDITED THAT WOULD 
RENDER SOMEONE HIV-RESISTANT, 
ARE THOSE THINGS THAT SHOULD BE 
ON THE TABLE?
I WANT TO BRING THAT UP, BECAUSE
 I THINK THAT'S ONE OF THOSE 
THINGS WHERE IF WE SAY YES TO 
ONE, THE QUESTION IS IS HOW DO 
WE KEEP PEOPLE FROM DOING THE 
OTHER.
ONE OF THE THINGS THAT PEOPLE 
HAD ACTUALLY STARTED AT THAT -- 
TO TALK ABOUT IS MAKING HE HAD 
ITS THAT WILL -- EDITS THAT WILL
 ENABLE PEOPLE TO GO TO SPACE.
THIS IS SOMETHING THAT I THINK, 
THIS SOUNDS VERY SCIENCE 
FICTION, BUT IT IS ONE OF THOSE 
THINGS THAT PEOPLE ARE THINKING 
ABOUT FOR THE LONG RUN.
SO IT TURNS OUT HUMANS ARE NOT 
ADAPTED WELL TO SPACE.
>> THEY GET OSTEOPOROSIS, THEY 
HAVE -- I AM NOT TALKING ABOUT 
THE BREATHING IN SPACE.  
NO AMOUNT OF GENE EDITING WILL 
FIX THE BREATHING IN SPACE 
PROBLEM.
[ LAUGHTER ]
FOR EXAMPLE, YOU DEVELOP HEART 
PROBLEMS, THINGS LIKE THAT.
SO SOME PEOPLE HAVE SAID, LOOK, 
IF WE ARE REALLY, REALLY SERIOUS
 ABOUT LONG-TERM SPACE TRAVEL, 
SENDING SOMEONE TO MARS, WE 
DON'T WANT THEM TO ARRIVE ON 
MARS AND EVERYBODY ON THE CRAFT 
HAS HAD A HEART ATTACK AND 
BRITTLE BONES.
RIGHT?
WE NEED TO DO SOMETHING ABOUT 
THIS.
SO I THINK THIS IS ONE OF THOSE 
THINGS THAT YOU WOULD THINK 
WOULD ONLY COME UP IN A SCIENCE 
FICTION BOOK, BUT PEOPLE ARE 
STARTING TO TALK ABOUT THIS.
PEOPLE ARE STARTING TO SAY, 
LOOK, IF WE ARE REALLY SERIOUS 
ABOUT THIS AS A PROGRAM, WE NEED
 TO BE HAVING THESE DISCUSSIONS.
SO I BRING THIS UP SORT OF IN 
THE IDEA OF VIGOROUS DEBATE, FOR
 THE FURTHER LONG FUTURE.
FINALLY, WHY WOULD YOU CONSIDER 
GERMLINE EDITING?
I THINK THE FUNDAMENTAL REASON 
IS ACTUALLY THE HARDEST TO ARGUE
 ABOUT, AND COMES UP THE MOST 
OFTEN WITH PATIENTS IS PATIENTS 
SAY, LOOK, YOU COULD DO SEMATIC 
EDITING AND IT WILL AFFECT JUST 
ME.
I WANT MY KIDS TO HAVE A BETTER 
LIFE THAN I HAD.
I THINK THAT'S SOMETHING THAT 
PERSONALLY I FIND IT VERY HARD 
TO ARGUE WITH PATIENTS ABOUT 
THAT.
HOW DO YOU TELL SOMEONE NO, 
THAT'S NOT RIGHT.
YOU KNOW, YOU WANT YOUR KIDS TO 
HAVE A BETTER LIFE THAN YOU DID.
I THINK THAT'S SOMETHING THAT WE
 NEED TO REALLY GRAPPLE WITH.
I THINK IT'SING THAT -- 
SOMETHING THAT WE NEED TO 
INVOLVE PATIENTS IN.
WHAT IS GENOME EDITING GOING TO 
LOOK LIKE?
I TOLD YOU HOW THE SCIENCE WORKS
 SHALL AND WHAT SOME OF THE TECH
 NICKAL AND ETHICAL PROBLEMS 
ARE.
RIGHT NOW WE CAN DO RESEARCH AND
 FIGURE OUT WHAT GENES DO, WE 
CAN USE THAT TO UNDERSTAND MORE 
ABOUT HOW WE WORK, AND HOW THE 
WORLD AROUND US WORKS.
AND THAT REALLY MAKES RESEARCH 
MUCH FASTER, MUCH BETTER.
IN THE MEDIUM TERM, I THINK WE 
WILL SEE REALLY THE RISE OF 
SO-CALLED SYNTHETIC BIOLOGY.
PEOPLE WILL BE ABLE TO USE 
GENOME EDITING TOOLS TO, SAY, 
MAKE BETTER FUELS, TO MAKE 
BETTER MEDICINES, AND IN THE 
MEDIUM TERM, WE ARE ACTUALLY 
GOING TO SEE THERAPIES FOR THESE
 BLOOD DISORDERS.
FOR EXAMPLE, SICKLE CELL 
DISEASE.
THERE ARE SEVERAL GROUPS, MY LAB
 INCLUDED, BUT SEVERAL COMPANIES
 WORKING ON CURES FOR SICKLE 
CELL DISEASE SHALL AND SEVERAL 
OF THEM HAVE GONE ON PAPER TO 
SAY WE ARE GOING TO BE IN THE 
CLINIC BY 2018-2019.
NOT AVAILABLE FOR SALE, BUT 
STARTING TRIAL.
I THINK IN THE MEDIUM TERM, WE 
WILL START TO SEE SEMATIC 
THERAPIES FOR BLOOD DISORDERS.
IN THE LONG-TERM DREAMS, HERE 
THE QUESTION IS WHAT DO WE WANT.
I LEARNED A WHILE AGO THAT IT'S 
VERY DANGEROUS TO PROGNOSTICATE 
WHAT IS GOING TO HAPPEN IN 20 
YEARS, BECAUSE EVERYTHING WILL 
BE DIFFERENT IN 20 YEARS.
BUT YOU MIGHT SAY, WELL, MAYBE 
THERE IS A WAY TO DO THERAPIES 
COMPLETELY IN VITRO.
YOU JUST DO AN INJECTION AND 
TREAT SICKLE CELL DISEASE THAT 
WAY.
THERE IS A POSSIBILITY BROUGHT 
UP OF PERSONAL CURES, WHERE, 
SAY, TWO PEOPLE IN THE WORLD 
HAVE A GENETIC DISEASE, OR ONE 
INDIVIDUAL PERSON HAS A GENETIC 
DISEASE, YOU COULD DEVELOP 
SOMETHING THAT CURES JUST THAT 
ONE PERP -- PERSON.
SO THIS IS THE DISRUPTIVE 
SCIENCE FICTION THAT I THINK WE 
REALLY NEED TO START TALKING 
ABOUT.
PART OF THE REASON WE NEED TO 
START TALKING ABOUT IT IS THAT 
EVEN THOUGH THINGS ARE EARLY 
DAYS, AND EVERYTHING IS KIND OF 
CHAOTIC, AND WE ARE SORT OF 
BUILDING THIS CAR WHILE WE ARE 
DRIVING, THE CAR REALLY IS A 
RACE CAR.
THINGS ARE MOVING REALLY, REALLY
 FAST.
SO WE HAVE TO CONSIDER HOW ARE 
WE GOING TO USE THIS NEW 
ABILITY.
WE ARE ON THE BRINK OF THESE 
CURES FOR DISEASES.
WE COULD USE IT FOR THINGS LIKE 
DESIGNER BABIES.
I GET ASKED QUESTIONS ABOUT 
DESIGNER BABIES ALL THE TIME.
AND, YOU KNOW, THERE ARE THESE 
BOMBASTIC HEADLINES ABOUT THE 
END OF "LIFE AS WE KNOW IT" FROM
 JUST EDITING ALL THE THINGS, 
BECAUSE OF THESE KINDS OF 
HEADLINES, YOU KNOW, THE 
SCIENTIFIC COMMUNITY TO -- 
TOGETHER WITH SOCIOLOGISTS AND 
HAD A MEETING OF THE NATIONAL 
ACADEMY OF SCIENCES, YOU WILL 
HEAR SOME OF THE PEOPLE WHO WERE
 AT THIS MEETING, I THINK TO 
REALLY SUMMARIZE THE OUTCOME OF 
THIS MEETING, IT WAS A BIG 
YELLOW LIGHT.
SO WHAT THEY BASICALLY SAID WAS 
GERMLINE EDITING IS OKAY IN SOME
 RESTRICTED SETS OF THINGS.
AND I THINK THAT IS AN 
INTERESTING -- IT'S AN 
INTERESTING DISTINCTION TO DRAW,
 GERMLINE EDITING IS OKAY, BUT 
ONLY OKAY IN SOME SITUATIONS, 
WHEN IS IT NOT OKAY, WHEN IS IT 
OKAY.
I THINK ARE MOVING TARGETS, I 
THINK AT LEAST FOR ME.
THINGS ARE MOVING REALLY 
QUICKLY.
I WANT TO GIVE YOU AN IDEA HOW 
QUICKLY THINGS ARE MOVING, 
ESPECIALLY ON THE GERMLINE 
EDITING FRONT.
JUST IN THE LAST MONTH, THREE 
PAPERS CAME OUT ON EDITING IN 
HUMAN EMBRYOS, TO EITHER CORRECT
 MUTATIONS, TO REVERSE 
POTENTIALLY PATHOGENIC 
MUTATIONS, OR TO JUST LEARN MORE
 ABOUT FUNDAMENTAL RESEARCH.
SO THERE WAS A LULL.
PEOPLE WERE TRYING TO FIGURE OUT
 IS THIS OKAY, THE DECISION CAME
 DOWN THAT, YES, THIS MIGHT BE 
OKAY IN SOME SITUATIONS, AND 
THINGS ARE STARTING TO GO REALLY
 FAST.
LIKE I SAID, THERE ARE A LOT OF 
TECHNICAL HURDLES, BUT THERE ARE
 ALSO, I THINK THAT IT'S 
POSSIBLE THOSE WILL BE OVERCOME.
THE NEXT QUESTION FOR US, WHAT 
DO WE WANT TO DO.
SO I AM GOING TO LEAVE WITH JUST
 A COUPLE OF QUESTIONS.
REALLY, WHAT DO YOU THINK IN THE
 AUDIENCE.
SOME THINGS TO SPARK DISCUSSION,
 HOPEFULLY IN THE PANEL 
 JUST ASK YOURSELF IF YOU HAD A 
GENETIC DISEASE, WOULD YOU EDIT 
YOURSELF SEMATICALLY, KNOWING 
THAT WOULD CHANGE YOUR DNA.
WOULD YOU EDIT TO PREVENT THE 
DISEASE?
LET'S SAY YOU DIDN'T HAVE A 
GENETIC DISEASE, BUT YOU HAD A 
MUTATION THAT PREDISPOSED YOU TO
 SOMETHING THAT WOULD HAPPEN 
LATER IN LIFE.
WOULD YOU EDIT YOURSELF TO 
PREVENT THAT SDEZ -- DISEASE?
AND WOULD YOU UNDERGO GERMLINE 
EDITING IN EITHER CASE.
IF YOU EITHER HAD A GENETIC 
DISEASE, WOULD YOU UNDERGO GERM 
LYON EDITING TO -- GERMLINE 
EDITING TO PREVENT PASSING IT 
DOWN TO YOUR KIDS, OR IF THAT 
MUTATION JUST GAVE YOU A HIGHER 
CHANCE OF GETTING SOMETHING, 
WOULD YOU GET PREVENTIVE 
GERMLINE EDITING TO AVOID 
PASSING THAT DOWN TO YOUR 
CHILDREN.
AND FINALLY, HOW WOULD YOU 
BALANCE YOUR OWN PERSONAL FAMILY
 PRIORITIES, RIGHT?
YOUR OWN SENSE OF SELF AND YOUR 
OWN SENSE OF YOUR OWN HEALTH AND
 CONTROL OF YOUR OWN HEALTH, AND
 YOUR DESIRES TO HAVE YOUR KIDS 
HAVE A BETTER LIFE, VERSUS 
SOCIETAL ACCEPTANCE.
I ASK THIS, BECAUSE IN SEVERAL 
OF THE PATIENT POPULATIONS THAT 
I TALKED TO, THEY SAID, LOOK, I 
KNOW THIS IS NOT ACCEPTED, I 
FRANKLY DON'T CARE.
MY KID'S IN A WHEELCHAIR, THEY 
ARE GETTING WORSE.
I DON'T CARE WHAT ANYONE ELSE 
THINKS, I WANT THIS TO GO 
FORWARDITE -- RIGHT NOW.
SO I AM NOT GOING TO SAY THAT I 
COME DOWN TO ONE SIDE OR THE 
OTHER, IT IS A VERY COMPLE 
INDICATED QUESTION.
I WOULD -- COMPLICATED QUESTION.
I WOULD ENCOURAGE EVERYBODY IN 
THE AUDIENCE, THOSE PARTICULAR 
PATIENTS HAVE COME DOWN ON ONE 
SIDE, BUT I HAVE TALKED TO 
PATIENTS WHO SAY EVEN THOUGH I 
HAVE THIS DISEASE, IT IS A SCARY
 THING, I DON'T WANT THIS 
EDITING AT ALL.
I ENCOURAGE YOU TO THINK FOR 
YOURSELF, WHAT WOULD YOU DO IN 
THAT SITUATION, AND LET'S 
HOPEFULLY TALK ABOUT THAT OVER 
THE DAY.
WITH THAT, I AM GOING TO FINISH 
UP.
THANKS VERY MUCH FOR YOUR 
ATTENTION.
[ APPLAUSE ]
DISCUSSION?
NO?
I
I THINK WE GO TO THE PANEL 
