Dr. Craig Venter – Life at the Speed of Light | NASA AMES TALK

[music playing] – IT–IT’S MY VERY, VERY GREAT HONOR TODAY TO–TO INTRODUCE THIS DIRECTOR’S COLLOQUIUM. YOU KNOW, IT’S BEEN KIND OF AN INTERESTING FEW YEARS. YOU KNOW, AND DEEP SPACE EXPLORATION AND SETTLEMENT– I’LL USE THAT WORD– IS GONNA REQUIRE AN IN-DEPTH UNDERSTANDING OF LIFE AND LIFE PROCESSES. AND, YOU KNOW, I’VE BECOME FIRMLY CONVINCED– WHICH IS AN AMAZING THING, ‘CAUSE I’M AN ASTROPHYSICIST– THAT BIOLOGY IS PROBABLY THE MOST IMPORTANT TECHNOLOGY FOR THIS CENTURY.

[applause] IN FACT, ASTROPHYSICS IS ABOUT LOOKING FOR LIFE, SO WE’RE BIOLOGISTS, TOO. AND, YOU KNOW, OF COURSE, AMES IS THE– IS THE LEAD CENTER FOR FUNDAMENTAL SPACE BIOLOGY AND FOR SYNTHETIC BIOLOGY FOR THE AGENCY. AND TODAY, WE HAVE THE– YOU KNOW, ONE OF THE NEATEST GUYS I HAVE EVER MET, AND HE’S THE LEAD SCIENTIST IN GENETIC– IN GENOMIC–PARDON ME– GENOMIC RESEARCH FOR THE 21ST CENTURY– J. CRAIG VENTER. AND HE’S GONNA SPEAK ABOUT THE PROFOUND IMPACTS THESE TOOLS WILL HAVE ON HUMANS’ EXISTENCE ON EARTH AND BEYOND. HE WAS LISTED ON “TIME” MAGAZINE’S 2007 AND 2008 100 LIST OF THE MOST INFLUENTIAL PEOPLE IN THE WORLD. IN 2010, THE BRITISH MAGAZINE “NEW STATESMAN” LISTED HIM AS 14TH IN A LIST OF THE 50– WORLD’S 50 MOST INFLUENTIAL FIGURES. HE BEGAN HIS FORMAL EDUCATION AFTER TOURS IN NAVY CORP– CORPSMAN IN VIETNAM FROM 1967/1968. AND AFTER EARNING BOTH A BACHELOR’S DEGREE IN BIOCHEMISTRY AND A PhD IN–IN PHYSIOLOGY AND PHARMACOLOGY FROM THE UNIVERSITY OF CALIFORNIA AT SAN DIEGO– A LOCAL BOY, SORT OF– HE WAS PERFORMED– APPOINTED PROFESSOR AT THE STATE UNIVERSITY OF NEW YORK AT BUFFALO IN THE ROSWELL PARK CANCER INSTITUTE.

TODAY’S TALK BY HIM IS ENTITLED “LIFE AT THE SPEED OF LIGHT.” PLEASE HELP ME WELCOME DR. CRAIG VENTER, WHO IS A COOL GUY AND A FRIEND, AND HE’S GONNA TELL YOU SOME REALLY COOL STUFF. CRAIG. [applause] [indistinct conversation] – THAT’S ONE OF THE BIGGEST CHALLENGES I’VE HAD NOW– I HAVE TO SAY SOMETHING COOL. [laughter] SO THAT’S A–THAT’S A CHALLENGE AT NASA AMES, WHERE SO MUCH OF THE STUFF HERE IS COOL. SO I’M EXCITED TO BE BACK HERE AGAIN. AND, PETE, THANK YOU– THANK YOU FOR INVITING ME, ONCE AGAIN, TO JOIN YOU. SO SEEING THAT MY BROTHER HAS SOMETHING TO DO WITH BUILDINGS HERE, I THOUGHT I’D SHOW A NICER BUILDING THAN YOU GUYS HAVE HERE. [laughter] SORRY, KEITH. THIS IS THE VENTER INSTITUTE BUILDING IN LA JOLLA, CALIFORNIA. IT’S ON THE UCSD CAMPUS, AND IT’S THE FIRST TRUE CARBON-NEUTRAL RESEARCH BUILDING. AND I HEAR EVEN NASA CAN MAKE CARBON-NEUTRAL OFFICE BUILDINGS, BUT GETTING A CARBON-NEUTRAL RESEARCH BUILDING WITH WET LABS AND MACHINERY AND FUME HOODS AND STUFF WAS A HUGE CHALLENGE, BUT– YOU CAN’T SEE IT IN THIS PICTURE, BUT THE ROOF IS A 1/2 A MEGAWATT POWER PLANT AND LOTS OF COOL INNOVATION.

BUT WE–WE TRY TO PRACTICE WHAT WE PREACH WITH OUR– WITH OUR ENTIRE ENVIRONMENT. I’M GONNA TALK MOSTLY ABOUT THE INNER CONVERSION OF THE DIGITAL AND BIOLOGICAL WORLDS. KIDS THAT GROW UP IN THE DIGITAL WORLD THINK NOTHING OF THIS, AND IT’S PRETTY OBVIOUS. IT TOOK A WHILE TO CONVINCE AN OLD GUY LIKE PETE THIS WAS IMPORTANT, BUT YOU SEE HE GETS IT NOW. [laughter] AND SO THAT’S REALLY IMPORTANT FOR THE– I THINK THE FUTURE OF–OF NASA. SO WHEN WE READ THE GENETIC CODE, WE CONVERT THIS 4-LETTER SYSTEM INTO THE 1s AND 0s IN THE COMPUTER, AND THIS HAS BEEN GOING ON FOR QUITE SOME TIME. IT REALLY STARTED WITH THE FIRST HUMAN GENE IN 1977, FIRST VIRUSES IN THE LATE ’70s, BUT IT WAS THE FIRST LIVING ORGANISM THAT MY TEAM SEQUENCED IN 1995 THAT STARTED TO CHANGE THE INFORMATION REVOLUTION, AT LEAST IN BIOLOGY. AND IT SCALED UP QUITE QUICKLY SO WE COULD GO FROM A MILLION BASE PAIR GENOME FIVE YEARS LATER TO DO THE FIRST DRAFT OF THE HAPLOID HUMAN GENOME AT 3 BILLION LETTERS. AND THE BREAKTHROUGHS WERE MOSTLY STRATEGY AND MATHEMATICAL, NOT NECESSARILY IN ANY TECHNOLOGY. BUT YOU’LL SEE, THE TOOLS HAVE CHANGED A LOT.

IN 1999, EVERYBODY THOUGHT A 1 1/2 TERAFLOP COMPUTER WAS BIG. AND IT TOOK BUILDING THIS UNIQUE COMPUTER TO BE ABLE TO ASSEMBLE THE FIRST VERSION OF THE HUMAN GENOME. AND YOU’LL SEE IN A MINUTE, IF YOU HAD TO PAY $50 MILLION FOR A 1 1/2 TERAFLOP COMPUTER– ANYBODY WANTS TO DO THAT, I’M HAPPY TO SELL YOU ONE– [laughter] BUT FORTUNATELY, COMPUTING HAS CHANGED AS RAPIDLY AS THE TECHNOLOGY IN THIS SPACE. AT CELERA, TO DO THE FIRST VERSION OF THE HUMAN GENOME, WE HAD AN ENTIRE BUILDING FILLED WITH MACHINES THAT LOOKED LIKE THIS. AND IT TOOK NINE MONTHS FOR THESE 350 MACHINES TO SEQUENCE THE FIRST VERSION OF THE HUMAN GENOME. SO THAT’S BARELY 15 YEARS AGO. OVER TIME WE SCALED THIS UP AND IN 2007 PUBLISHED THE FIRST DIPLOID GENOME. WE ALL HAVE TWO SETS OF CHROMOSOMES. WE GET HALF FROM EACH OF OUR PARENTS. AND IT WASN’T UNTIL 2007 THAT WE ACTUALLY SAW THE COMPLETE VERSION OF THE HUMAN GENOME. BUT THE–THE CHALLENGE GOES FAR FURTHER MATHEMATICALLY IN JUST ASSEMBLING THESE, AND WE’VE NOW SCALED THIS UP A WHOLE LOT MORE AT A NEW ENTERPRISE CALLED HUMAN LONGEVITY WHERE THE CHALLENGE IS TO SEE IF WE CAN PREDICT FROM YOUR GENETIC CODE ALMOST EVERYTHING ABOUT YOUR LIFE.

PETE AND I HAVE JOKED ABOUT THE MOVIE “GATTACA.” SOME PEOPLE THOUGHT THAT WAS A GREAT MOVIE, TRYING TO PREDICT FROM THE GENOME WHO SHOULD GO INTO SPACE AND WHO SHOULDN’T FOR LONG-TERM SPACE TRAVEL. AND THE HERO STOLE SOMEBODY ELSE’S GENETIC IDENTITY. HE WAS SOMEBODY WHO WAS LIKELY TO DIE IN SIX MONTHS FROM CARDIAC FAILURE, SO IF YOU’RE RUNNING A SPACE PROGRAM, YOU DON’T REALLY WANT THAT TO HAPPEN, AND YOU’D LIKE TO BE ABLE TO PREDICT THESE THINGS. BUT ALSO, YOU’D LIKE TO BE ABLE TO PREDICT THAT FOR YOURSELF, ESPECIALLY IF YOU CAN DO IT EARLY ENOUGH TO DO SOMETHING ABOUT IT. SO WHAT’S CHANGED? NOW, INSTEAD OF 300 MACHINES AND NINE MONTHS PER GENOME, WE HAVE THESE NEW MACHINES THAT EACH ONE CAN CRANK OUT, EVERY TWO DAYS, 16 GENOMES. UH… IT’S CALLED ILLUMINA HISEQ X TEN.

WE HAVE FOUR OF THESE, WHICH WILL ENABLE US TO DO ON THE ORDER OF 80,000 TO 100,000 GENOMES A YEAR INSTEAD OF ONE IN NINE MONTHS. SO THAT’S A PRETTY BIG CHANGE. AND THESE MACHINES GENERATE A LOT OF DATA JUST GETTING THESE LITTLE PIECES OF PRIMARY DATA THAT WE HAVE TO PUT TOGETHER TO REASSEMBLE THE GENOME. IT’S NOT ADEQUATE TECHNOLOGY RIGHT NOW FOR ALL THE THINGS WE WANT TO DO, BUT IT IS CHANGING. AND THAT GIANT ROOM ABOUT THE SIZE OF THIS AUDITORIUM FOR OUR 1 1/2 TERAFLOP COMPUTER CAN NOW BE REPLACED BY A CARD FOR YOUR PC AND KEEPS GETTING SMALLER AND FASTER. BUT IT’S STILL ONE OF THE BIGGEST COMPUTATIONAL CHALLENGES OF WAYS EVEN TO PUT AND SEPARATE YOUR PARENTAL CHROMOSOMES FROM EACH OTHER. ONE WAY WE DID THIS EARLY ON AT THE VENTER INSTITUTE– WE DEVELOPED SINGLE-CELL SEQUENCING. SO WE CAN DO A GENOME ON A SINGLE BACTERIAL CELL, A SINGLE HUMAN CELL, AND THIS DOES CELL SORTING TO DO THIS. AND TO SEPARATE THE GENOME INTO HAPLOTYPES, WE ACTUALLY SEQUENCED INDIVIDUAL SPERM CELLS.

WE JUST SIMPLY SEPARATED ONE, PULLED OUT INDIVIDUAL SPERM CELLS, AND SEQUENCED THE GENOME. YOU PROBABLY– EVEN THOUGH A LOT OF YOU ARE–ARE PHYSICISTS, YOU PROBABLY KNOW YOUR SPERM, IF YOU’RE MALES, ONLY HAS HALF THE GENOME, AND IF YOU’RE FEMALE, THE EGGS ONLY HAVE HALF THE GENOME. IF NOT, YOU JUST LEARNED SOMETHING REALLY IMPORTANT ABOUT THE NEXT STAGES OF YOUR LIFE. [laughter] BUT IT TURNS OUT, NO TWO SPERM CELLS OR TWO EGG CELLS HAVE THE SAME GENETIC CODE, AND IT’S BECAUSE THERE’S RANDOM BREAKS IN THE CHROMOSOMES AND CROSSOVERS. SO YOU HAVE TO SEQUENCE, YOU KNOW, SIX OR A DOZEN SPERM CELLS TO GET THE COMPLETE HAPLOTYPE PHASING OF HAVING THE CHROMOSOME SEPARATED. SO THAT’S A PHYSICAL WAY TO DO IT, REQUIRES A LOT MORE SEQUENCING. WE’RE TRYING TO FIND NEW MATHEMATICAL WAYS TO MAKE THIS HAPPEN EVEN FASTER FROM THE HIGH-THROUGHPUT GENOME SEQUENCING.

BUT IT’S IMPORTANT IN THE SENSE THAT EVERY ONE OF YOU, I’M SURE, HAS ASKED THE QUESTION– DID YOU GET THIS TRAIT OR THAT TRAIT FROM YOUR FATHER OR FROM YOUR MOTHER OR THEIR SIDE OF THE FAMILY? DID YOU… YOU KNOW, YOUR SPOUSE WAS THE ONE WHO CONTRIBUTED THE BAD TRAIT TO YOUR KIDS. YOU ONLY CONTRIBUTED THE GOOD ONES. SO EVERYBODY DOES TRACK THESE THINGS. BUT IT BECOMES IMPORTANT IN UNDERSTANDING YOUR GENETIC HISTORY AND YOUR GENETIC FUTURE TO, IN FACT, KNOW… BY KNOWING YOUR MOTHER’S GENETIC HISTORY AND YOUR FATHER’S GENETIC HISTORY AND WHICH PARTS CONTRIBUTED WHAT BECOMES PART OF THE BIG MATHEMATICAL PUZZLE FOR DE-CONVOLUTING THIS INFORMATION. AND IT TURNS OUT FOR ALMOST EVERY GENE YOU INHERITED DIFFERENT VARIANTS FROM YOUR FATHER AND FROM YOUR MOTHER. AND WHAT’S A GENE OF CONSEQUENCE FOR A UNIQUE TRAIT OR FOR A DISEASE– WHAT ARE CALLED COMPOUND HETEROZYGOTES– ARE FAR MORE PREDICTIVE OF REALITY THAN ANYTHING BEING DONE TODAY IN GENETICS JUST MEASURING SINGLE GENETIC POLYMORPHISMS.

SO WHEN WE LOOK AT COMPOUND HETEROZYGOTES WHERE YOU HAVE TWO INDEPENDENT CHANGES IN THE SAME GENE, ONE FROM EACH PARENT, IT’S FAR MORE PREDICTIVE OF THE PHENOTYPE PARTICULARLY FOR RISK ALLELES ASSOCIATED WITH DISEASE. SO IT’S NOT JUST OF THEORETICAL INTEREST, IT’S OF REAL CRITICAL INTEREST GOING FORWARD TO DO THIS. AND SO THE– THESE COMPOUND MUTATIONS OR COMPOUND HETEROZYGOTES ARE NOT BEING MEASURED AT ALL IN SCIENCE BECAUSE THERE’S BEEN NO WAY TO DO IT WITHOUT SEPARATING THE HAPLOTYPES OF THE GENOMES. WE’RE TRYING TO BUILD A DATABASE OF 1 TO 2 MILLION GENOMES OVER THE NEXT FEW YEARS, AS FAST AS WE CAN. WE ANNOUNCED THIS STARTING WITH THE MOORES CANCER CENTER IN SAN DIEGO, OF SEQUENCING THE GENOME OF EVERY PATIENT THAT COMES TO THAT HOSPITAL BUT ALSO SEQUENCING THE GENOMES ON THEIR TUMORS. AND TUMOR GENOME SEQUENCING, NOW TRACKING WHAT ARE CALLED DRIVER MUTATIONS, ARE PROBABLY THE MOST IMPORTANT THING YOU CAN KNOW IF YOU GET THE UNFORTUNATE DIAGNOSIS OF A DIFFERENT TYPE OF CANCER, FOR EXAMPLE, A LUNG CANCER.

THERE’S VARIATIONS IN AN ALK GENE THAT ROUGHLY 3% OF PEOPLE WITH LUNG CANCER HAVE THIS GENETIC VARIATION, THAT IF YOU HAVE THAT VARIATION, PFIZER HAS A DRUG THAT HAS A VERY HIGH CHANCE OF TREATING YOUR LUNG CANCER. [man coughs] SO OBVIOUSLY, IF YOU’RE COUGHING AND HAVE LUNG CANCER… [laughter] THE–THE MOST IMPORTANT THING YOU CAN KNOW IS YOUR GENOME, AND THIS IS NOW STARTING TO HAPPEN WITH MORE AND MORE TUMORS. AND IT’S CAUGHT ON JUST IN THE LAST ONE TO THREE YEARS BECAUSE THIS IS STARTING TO ACTUALLY CHANGE CLINICAL PRACTICE. THE COUNTER SIDE OF THIS IS THE PHARMACEUTICAL INDUSTRY FOUND HOW TO STILL TURN THESE INTO BLOCKBUSTERS BY CHARGING ALMOST $10,000 A MONTH FOR TREATMENTS, BECAUSE THEY HAVE A SMALLER NUMBER OF PATIENTS BUYING THESE. BUT IF YOU HAVE LUNG CANCER AND THEIR DRUG CAN CURE IT, YOU’RE PROBABLY HAPPY TO SEE THAT. NASA’S AN ORGANIZATION THAT IS FAMOUS FOR DOING PHENOTYPE SELECTION. THEY DON’T CALL IT GENETIC SELECTION, ‘CAUSE THAT– THAT WAS A WORD THAT PROBABLY SCARED THEM A LITTLE BIT, AND THEY DIDN’T PROBABLY REALLY KNOW THEY WERE DOING GENETIC SELECTION.

BUT WHEN YOU SCREEN ANY POPULATION FOR DIFFERENT TRAITS FOR SUCCESS– SUCH AS THE OLYMPICS, THE OLYMPICS IS THE ULTIMATE IN GENETIC SELECTION– PEOPLE WITH THE BEST GENOMES AND THE BEST TRAITS IN DIFFERENT FIELDS, DEPENDENT ON FAST MUSCLE TWITCH OR ACCELERATION GENES, ET CETERA, END UP BEING THE ONE TO EXCEL IN SPORTS, AND NASA HAD DIFFERENT SELECTION CRITERIA. BUT IF YOU’RE GONNA START SCREENING, THERE’S A NUMBER OF TRAITS– I JUST LISTED A FEW OF THEM HERE– THAT MIGHT BE IMPORTANT FOR LONG-TERM SPACE TRAVEL. FOR EXAMPLE, BEING ABLE TO DO VERY EFFECTIVE DNA REPAIR AFTER RADIATION DAMAGE MAKES THE DIFFERENCE IN WHETHER YOU GET CANCER OR DON’T GET CANCER.

OBVIOUSLY, A VERY STRONG IMMUNE SYSTEM. ALL THESE THINGS– LACK OF HAIR, I THINK IS ONE OF THE MOST IMPORTANT TRAITS… [laughter] BUT THESE ARE THINGS THAT CAN BE MEASURED IN THE FUTURE STRAIGHT FROM THE GENOME. AND SO IT’S– IT’S SOMETHING TO THINK ABOUT. BUT WE DON’T JUST HAVE OUR GENOME. WE HAVE, AND ARE DEPENDENT ON, A LARGE REPERTOIRE OF BACTERIA THAT LIVE ON AND WITHIN US. IT DOESN’T MATTER HOW OFTEN YOU WASH YOUR HANDS, YOU HAVE ABOUT 3,000 UNIQUE SPECIES CONTRIBUTING AS MANY AS 10 MILLION ADDITIONAL GENES TO OUR BIOLOGICAL REPERTOIRE. THIS IS CALLED THE MICROBIOME. AND JUST THINK ABOUT NEXT TIME YOU’RE– IT’S NOT A WORK-RELATED THING, HOPEFULLY. KISSING SOMEBODY OR SOMETHING ELSE, IT’S A THOUSAND DIFFERENT SPECIES THAT YOU HAVE OR THEY HAVE IN THEIR MOUTH. BUT THINK ABOUT EVERY ASTRONAUT THAT GOES UP TO THE SPACE STATION IS CARRYING ON THE ORDER OF 3,000 UNIQUE SPECIES WITH THEM, SOME THAT MIGHT INFECT THEIR COLLEAGUES, EVEN THOUGH THEY MAY NOT NECESSARILY INFECT THAT PERSON CARRYING THEM. AND THEY’RE AN IMPORTANT PART OF BIOLOGY. SO PART OF WHAT WE’RE DOING AT HUMAN LONGEVITY IS GOING TO BE SEQUENCING THE MICROBIOME ON AS MANY PEOPLE AS WE CAN.

THESE ARE JUST A FEW OF THE DISEASES THAT HAVE BEEN ASSOCIATED WITH CHANGES IN THE MICROBIOME. BUT ALSO THINGS LIKE ESOPHAGEAL CANCER, STOMACH CANCER, ALL ASSOCIATED VERY CLEARLY WITH CHANGES IN BACTERIA. SO WE USE A DIFFERENT ILLUMINA MACHINE AND WE CAN MULTIPLEX THESE SAMPLES BY LAYERING THEM ON EACH OTHER, SO A SINGLE MACHINE CAN PROCESS ABOUT 166 SAMPLES. SO YOU CAN SEE, JUST BY ADDING LOTS OF MACHINES ON, THIS ADDS UP QUITE QUICKLY. I ACTUALLY PROPOSED FOR THE FIRST TIME HERE FOUR YEARS AGO THAT WE MIGHT WANT TO THINK ABOUT DESIGNING A SYNTHETIC MICROBIOME. AND NOW THAT NASA’S BEEN INCREASING THE DISCUSSIONS ABOUT GOING TO MARS AND ELON MUSK IS GOING TO GO THERE… WE GOTTA THINK ABOUT THE IMPLICATIONS OF EACH PERSON CARRYING ALL THESE THOUSANDS OF UNIQUE SPECIES WITH THEM TO ANOTHER PLANET, ‘CAUSE ONCE THEY ESTABLISH THERE, WE WON’T GET RID OF THEM. WE MIGHT LIKE TO CHOOSE WHAT WE ESTABLISH THERE, AND–BUT IT TURNS OUT THE PHARMACEUTICAL INDUSTRY IS ALL OF A SUDDEN VERY INTERESTED IN SYNTHETIC MICROBIOMES, AS WELL.

AND BY CHANGING SPECIFICALLY THE MICROBES IN YOUR GI SYSTEM, ON YOUR SKIN, CAN VERY MUCH CHANGE YOUR BIOLOGY. SO WE MIGHT WANT TO THINK ABOUT HAVING A DEFINED MICROBIOME FOR EACH INDIVIDUAL BEFORE CONTAMINATING ENTIRE PLANETS WITH DISEASE-CAUSING MICROBES. AND EACH OF US HAS A DIFFERENT GENETIC REPERTOIRE FOR THE MICROBES THAT WE TOLERATE VERSUS CAUSE DISEASE. ABOUT 5% OF YOU ARE TOTALLY RESISTANT TO HIV INFECTIONS, JUST DUE TO A SINGLE LETTER CHANGE IN ONE GENE, BUT THAT DOESN’T MEAN YOU COULDN’T CARRY IT AND GIVE IT TO OTHERS. SO ASIDE FROM THE MICROBIOME, WE’RE ALSO MEASURING 2,400 CHEMICALS IN THE BLOODSTREAM. IT’S CALLED THE METABOLOME, AND WE’RE DOING THIS WITH A COMPANY CALLED METABOLOMICS IN NORTH CAROLINA. AND IT TURNS OUT, 2,400 IS ABOUT THE HUMAN REPERTOIRE. EACH OF US CAN SYNTHESIZE AROUND 2,400 DIFFERENT CHEMICALS. AND SO YOU CAN INFER BIOCHEMICAL PATHWAYS BY THE METABOLITES THAT YOU HAVE.

THE COMPLICATION IS WHEN YOU LOOK IN THE BLOODSTREAM OF PEOPLE AFTER A MEAL, ONLY ABOUT 60% OF THE CHEMICALS ARE OF HUMAN ORIGIN. 30% ARE FROM ALL THE DIFFERENT SPECIES YOU CONSUMED IN YOUR DIET. BUT 10%, OR ABOUT 50 CHEMICALS CIRCULATING THROUGH YOUR BRAIN RIGHT NOW, ARE FROM BACTERIAL METABOLITES OF THE CHEMICALS YOU CONSUMED IN YOUR DIET AND OF YOUR HUMAN CHEMICALS. SO IF WE WANT TO HAVE DEFINED ENVIRONMENTS IN SPACE, NOT ONLY DO YOU WANT TO DEFINE THE MICROBIOME, YOU WANT TO DEFINE THE CHEMICAL INPUTS BECAUSE THAT WILL DETERMINE THE OUTPUTS.

AND WE HAVE NO IDEA WHETHER THESE AFFECT, POSITIVELY OR NEGATIVELY, YOUR MENTAL CAPABILITIES. WE DO KNOW THEY CHANGE DISEASE OUTCOMES AND THERE’S LOTS OF DIAGNOSTICS BASED JUST ON MEASURING THESE CHEMICALS IN THE BLOODSTREAM. THESE ARE JUST A FEW OF THE THINGS WE’RE TRYING TO MEASURE AS PART OF THE HUMAN PHENOTYPE. WE’RE SETTING UP TO DO QUANTITATIVE MR– WHOLE-BODY MRI, AND A TEAM AT UC SAN DIEGO GOT THIS GOING NICELY WITH A BRAIN, WHERE WE CAN TAKE A QUANTITATIVE MRI, A SET OF IMAGES, AND REDUCE IT TO A TABLE OF VOLUMES OF DIFFERENT REGIONS OF THE BRAIN. THIS IS BEING USED TO DIAGNOSE ALZHEIMER’S DISEASE, FOR EXAMPLE, AND CAN BE DONE FAR MORE ACCURATELY THAN EVEN THE BEST PATHOLOGIST.

AND WE’RE GONNA BE LAYERING LAYER UPON LAYER OF ALL THIS INFORMATION USING THE GENOME AS THE ORGANIZING PRINCIPLES. THE GOALS ARE– CAN WE LEARN ENOUGH– SEE, ALL THESE THINGS, INCLUDING EPIGENETIC PHENOMENON, ALL START WITH YOUR GENETIC CODE– CAN WE LEARN ENOUGH TO ACTUALLY GO BACK AND START TO MAKE FUNDAMENTAL PREDICTIONS STRAIGHT FROM THAT PRIMARY CODE WITHOUT HAVING TO MEASURE ALL THESE OTHER CHANGES? AND SO THIS–IT’S THIS NEW INTEGRATIVE APPROACH TO MEDICINE, TRYING TO MAKE MEDICINE QUANTITATIVE FOR THE FIRST TIME EVER BASED ON ACTUAL, FACTUAL, MEASURABLE, ACCURATELY PREDICTABLE INFORMATION.

IT’S GONNA BE A BIG CHALLENGE, BUT THE TECHNOLOGY HAS ADVANCED ENOUGH, BOTH IN THE DNA SEQUENCING SIDE AND ON THE COMPUTE SIDE, TO PUT US RIGHT AT THE THRESHOLD OF MAKING THIS POSSIBLE. ALL THESE GET BACK TO THE QUESTION OF THE GENETIC CODE PREDICTING LIFE OUTCOMES AND PROGRAMMING LIFE OUTCOMES AND TRYING TO MEASURE HOW REAL THAT IS. SO ONE OF THE APPROACHES WE TOOK TO THIS EARLY ON WAS STARTING WITH THE 1s AND 0s ON THE COMPUTER TO SEE IF WE COULD RECAPITULATE LIFE BY GOING IN THE OTHER DIRECTION AND RE-CHEMICALLY MAKING THE GENETIC CODE BASED ON THE COMPUTER CODE.

JUST STRAIGHTFORWARD, BASIC ANSWERS. BIG QUESTIONS, YOU KNOW– DOES DNA CONTAIN ALL THE NECESSARY INFORMATION FOR CELLULAR LIFE? PEOPLE, FOR CENTURIES, HAVE BEEN LOOKING FOR SOME VITALISTIC MAGIC COMPONENT, AND EVEN THOUGH MOST MODERN SCIENTISTS THINK THAT VITALISM WAS DISPROVED CENTURIES AGO… THERE’S PROBABLY ABOUT 30 OR 40% OF THE BIOLOGICAL COMMUNITY ARE WHAT I DESCRIBE CLOSET VITALIST. THEY ACTUALLY WANT THERE TO BE SOMETHING MORE THAN THIS FACTUAL CHEMICAL INFORMATION. AND I THINK THEY’RE LARGELY DISAPPOINTED. YOU KNOW, SIMPLE QUESTIONS LIKE, YOU KNOW, WHAT IS THE SMALLEST NUMBER OF GENES FOR A SELF-REPLICATING CELL? AND THEN ULTIMATELY TO ANSWER THESE, COULD WE DESIGN AND CONSTRUCT SUCH A GENOME, SUCH A CELL? AND AS SOON AS WE STARTED DOWN THIS ROUTE, WE HAD NEW QUESTIONS, ‘CAUSE NOBODY HAD EVER DONE THIS BEFORE. WOULD CHEMISTRY EVEN PERMIT US TO WRITE LARGE STRETCHES OF GENETIC CODE? AND EVEN IF WE COULD DO THAT, COULD WE FIND A WAY TO BOOT UP THIS CHEMICAL SOFTWARE TO GET A LIVING CELL? WE STARTED, EARLY ON, WITH SOMETHING MUCH SMALLER.

WE DECIDED TO START WITH PHIX174, ‘CAUSE IT SOUNDS COOL. IS THAT–I DON’T KNOW IF THAT QUALIFIES AS COOL. BUT IT’S ACTUALLY– IT WAS THE FIRST DNA VIRUS GENOME SEQUENCE BY SANGER AND COLLEAGUES IN 1977 WHEN HE DEVELOPED WHAT WE REFER TO AS SANGER SEQUENCING. IT’S A SMALL GENOME OF A LITTLE BIT OVER 5,000 LETTERS OF GENETIC CODE. AND THE DNA IS INFECTIVE OF E. COLI, AND THIS IS A VIRUS SPECIFIC FOR THE BACTERIA E. COLI. SO BACTERIOPHAGE ARE VIRUSES THAT ONLY AFFECT BACTERIA. WE START WITH A GENETIC CODE IN THE COMPUTER. AFTER RESEQUENCING TO MAKE SURE WE HAD ACCURATE GENETIC CODE, AND WITH SOME NEW TOOLS WE DEVELOPED, ONLY TOOK TWO WEEKS TO SYNTHESIZE IT AND CORRECT THE ERRORS IN THE GENETIC CODE.

AND THEN WE FOUND WAYS JUST TO INSERT THAT IN E. COLI. AND THIS WAS THE FIRST EXPERIMENT. WHAT HAPPENS IS E. COLI STARTED TO READ THE SYNTHETIC DNA, STARTED TO MAKE THE PROTEINS. THE PROTEINS SELF-ASSEMBLED TO FORM THE VIRUS. THE VIRUS ACCUMULATED MILLIONS OF COPIES IN THE CELLS UNTIL THE CELLS BURST, AND THESE CLEAR SPOTS– THIS IS A LOT OF E. COLI, SO EVERY PLACE YOU SEE ONE OF THESE CIRCLES IS WHERE THE VIRUS HAS KILLED LARGE NUMBERS OF CELLS, REINFECTED ADDITIONAL CELLS, AND KILLED MORE. SO WE CALL THIS A SITUATION WHERE THE SOFTWARE BUILDS ITS OWN HARDWARE.

OBVIOUSLY COMPUTER SCIENTISTS WOULD LOVE IT IF YOU COULD JUST WRITE SOME COMPUTER CODE AND GET A NEW COMPUTER OUT OF IT. WE CAN AT LEAST GET INFECTIOUS PARTICLES OUT OF IT WITH THIS EXPERIMENT. BUT OUR GOAL WAS TO MAKE AN ENTIRE SELF-REPLICATING CELL, NOT A VIRUS THAT CAN JUST HIJACK CELLULAR MACHINERY. BUT WE KNEW WE COULD NOW ACCURATELY MAKE VIRAL-SIZE GENOMES. WE FIGURED IF WE COULD FIND A WAY LINK THEM ALL TOGETHER WE MIGHT BE ABLE TO BUILD A BACTERIAL CHROMOSOME, AND THAT’S WHAT WE SET OUT TO DO. AND WE STARTED WITH SOME VERY LABORIOUS MANUAL TECHNIQUES. WE DESIGNED THE GENOME IN THESE CASSETTES AROUND 5,000 TO 7,000 BASE PAIRS.

WE MADE EACH CASSETTE AND THEN WE STARTED PUTTING THEM TOGETHER IN SOMETHING THAT LOOKS LIKE A FINAL FOUR PLAYOFF. BUT AT EACH STAGE, TEAMS WERE WORKING ON DIFFERENT ONES OF THESE. AFTER EACH PIECE WAS MADE, THEY HAD TO CLONE AN E. COLI, GROW IT UP, SEQUENCE IT TO VALIDATE THAT WE HADN’T INTRODUCED ERRORS, AND THEN ONCE THAT WAS ALL DONE, WE WENT ON TO THE NEXT STAGE. THE LARGEST PIECE OF DNA AT THE TIME THAT IT WAS EVER SYNTHESIZED WAS ONLY ABOUT 30KB. SO ONCE WE WERE AT STAGE THREE, WE WERE WELL PAST THE LARGEST PIECES. AND WHEN WE GOT OVER 100,000 BASE PAIRS, CLONING E. COLI BECAME COMPLICATED. THE E. COLI DIDN’T LIKE THESE LARGE STRETCHES OF SYNTHETIC DNA, SOME OF WHICH CONTAINED BACTERIAL GENES THAT COULD ACTUALLY BE TOXIC TO E.

COLI. SO WE STARTED LOOKING AROUND FOR ANOTHER SYSTEM AND WE FOUND THAT MIRACLE BUG SACCHAROMYCES CEREVISIAE, THAT GIVES US BEER AND BREAD AND WINE– YOU KNOW, HUMIDITY WOULD NOT HAVE SURVIVED WITHOUT THIS ORGANISM. AND IT ALSO TAKES UP VERY LARGE PIECES OF DNA. IT CAN USE HOMOLOGOUS RECOMBINATION. THAT’S WHERE YOU JUST HAVE OVERLAPPING PIECES OF THE COMPLEMENTARY SEQUENCE AND THAT STITCHES THINGS TOGETHER. SO THAT’S WHAT WE DID. WE PUT THESE QUARTER-GENOME CHEMICALLY MADE PIECES WITH PROPER OVERLAPS INTO A YEAST WITH A SIMPLE VECTOR THAT HAS A SYNTHETIC YEAST CENTROMERE IN IT, AND YEAST IMMEDIATELY STITCHED THESE PIECES TOGETHER. WE ISOLATED AND SEQUENCED IT, AND THAT’S WHAT WE REPORTED IN 2008 AS THE–THE FIRST CHEMICALLY MADE BACTERIAL GENOME. CHEMISTRY CONTINUED TO IMPROVE– AND MANY OF YOU HERE KNOW THIS YOUNG MAN, DAN GIBSON– HE STARTED AS A POSTDOC IN THE LAB, AND HE TOOK WHAT WE WERE DOING IN THESE LABORIOUS STEPS, AND HE GREATLY SIMPLIFIED IT BY COMBINING THE ENZYMES AND THE OLIGONUCLEOTIDES IN A SINGLE REACTION AT 50 DEGREES CENTIGRADE, BECAUSE AT THAT TEMPERATURE, ONE OF THE KEY ENZYMES GETS KILLED OFF BEFORE IT CHEWS BACK TOO MUCH DNA. AND WE NAMED IT THE GIBSON ASSEMBLY AFTER DAN GIBSON.

AND HE CAME TO HAM SMITH AND I– HAM SMITH IS NOW 82– AND HE SAID, “I DON’T KNOW WHAT TOOK YOU OLD GUYS SO LONG.” BUT THE KEY THING ABOUT THIS, IT ALLOWS FOR COMPLETE AUTOMATION, SO WE CAN GO FROM THE DIGITAL CODE IN THE COMPUTER TO SYNTHETIC DNA IN AN AUTOMATED PROCESS. SO THE CHEMISTRY WAS GOING WELL. WE STARTED A BIOLOGICAL TEAM TO WORK OUT HOW TO BOOT UP THE CHROMOSOME. THAT WAS ACTUALLY MUCH HARDER. WE HAD A FRENCH POSTDOC AND JOHN GLASS AT THE INSTITUTE LEADING THE TEAM TO DO THIS. BECAUSE THIS PART OF THE BIOLOGY IS ESSENTIAL TO SYNTHETIC GENOMICS, I’M GONNA WALK YOU THROUGH WHAT WE DID, BECAUSE IT MAKES IT SORT OF UNIVERSAL IN HOW WE THINK ABOUT LIFE, AND HOPEFULLY HOW YOU WILL, AS WELL. WE HAD TWO SPECIES OF MYCOPLASMA– MYCOPLASMA MYCOIDES AND CAPRICOLUM. THEY WERE ABOUT THE SAME DISTANCE APART GENETICALLY AS WE ARE FROM MICE, SO ABOUT 10%. WE ISOLATED THE CHROMOSOME FROM M. MYCOIDES. WE ADDED HARSH ENZYMES TO CHEW UP ALL THE PROTEINS, ‘CAUSE WE NEEDED TO KNOW WHETHER WE COULD TRANSPLANT NAKED DNA.

WE ADDED A COUPLE CASSETTES TO IT, ONE, SO WE COULD SELECT FOR IT, AND ANOTHER, SO IT’D TURN THE CELLS BRIGHT BLUE IF IT WAS ACTIVATED. AND WE DEVELOPED TECHNIQUES FOR TRANSPLANTING THAT INTO THE CAPRICOLUM CELL, AND THIS IS WHAT TOOK SO LONG. BECAUSE YOU CAN’T PIPETTE THESE CHROMOSOMES. LARGE PIECES OF DNA ARE BRITTLE. IF YOU’RE PIPETTING THEM THEY FRACTIONATE INTO SMALLER PIECES.

SO WE ACTUALLY ISOLATE THE CHROMOSOMES IN GEL BLOCKS. WE CAN DO ALL THE CHEMISTRY IN THE GEL BLOCKS, AND THEN WE USE AN ENZYME AT THE LAST SECOND TO DISSOLVE THE GEL AS WE USE ELECTRIC CURRENT TO DRIVE IT INTO THE CELL. SO WE HAVE THIS LITTLE VIDEO TO SHOW YOU WHAT WE THINK HAPPENED. IT’S VERY SOPHISTICATED FOR NASA. SO I HOPE YOU’RE READY. BUT WE INSERTED THE NEW CHROMOSOME… [laughter] INTO THE CELL. NOW WE HAVE THE CELL– IT’S A PHENOTYPE– ALL THE CHARACTERISTICS OF ONE SPECIES, BUT IT NOW HAS TWO SETS OF GENETIC SOFTWARE. WHAT WE THINK HAPPENED IS THAT THE NEW CHROMOSOME STARTED TO BE READ, IMMEDIATELY STARTED PRODUCING ENZYMES AND PROTEINS. SOME OF THE EARLY PROTEINS WERE THE RESTRICTION ENZYMES THAT CHEW UP DNA THAT HAM SMITH DISCOVERED THAT LED TO HIS NOBEL PRIZE IN 1978. THESE ENZYMES RECOGNIZED THE CHROMOSOME IN THE CELL AS FOREIGN DNA AND CHEWED IT UP.

SO NOW WE HAVE THE BODY OF ONE SPECIES AND THE GENETIC SOFTWARE OF ANOTHER. SO WHAT HAPPENED? IN A SHORT PERIOD OF TIME, WE ENDED UP WITH THESE BRIGHT BLUE CELLS. AND WHEN WE INTERROGATED THEM, THERE WASN’T A SINGLE MOLECULE OF THE ORIGINAL CELL LEFT. EVERYTHING IN THE CELL DERIVED FROM THAT TRANSPLANTED CHROMOSOME. SO THIS IS SUCH A KEY PROCESS TO UNDERSTANDING THE GENETIC CODE AND HOW IT WORKS, BUT ALSO EVOLUTION. AND I THINK IT HELPS TO PROVE THAT LIFE IS A DNA SOFTWARE SYSTEM, AND IF YOU CHANGE THE SOFTWARE, YOU CHANGE THE SPECIES. AND IF YOU LOOK BACK AT EVOLUTION, WE SEE THIS HAPPENING OVER AND OVER AND OVER AGAIN.

IN FACT, EVOLUTION DIDN’T TAKE PLACE IN JUST WHAT PEOPLE THINK OF THESE POINT MUTATIONS AND YOU SELECT FOR SOMETHING. WE FIND IN THE BACTERIAL WORLD CELLS WITH TWO AND THREE CHROMOSOMES, AND WHEN WE LOOK AT THE CHROMOSOME STRUCTURE, THEY’RE CLEARLY DERIVED FROM DIFFERENT EVOLUTIONARY ORIGINS. SO THESE EVENTS OF XENOTRANSPLANTATION COULD BE FROM A CELL FUSION, AND IF THERE WAS A MISMATCH IN THE DNA RESTRICTION ENZYME SO DNA DIDN’T GET DESTROYED, YOU COULD ADD, IN ONE SINGLE STEP, A THOUSAND NEW TRAITS TO THAT CELL. WE SEE THIS WITH THE DEVELOPMENT OF THE ENTIRE PLANT WORLD WHERE A SMALL PROKARYOTIC PHOTOSYNTHETIC CELL GOT INCORPORATED INTO A EUKARYOTIC CELL, AND THAT GAVE US THE PLANT WORLD. AND IN OUR OWN BODIES, THE MITOCHONDRIAL GENOME WAS A BACTERIAL CELL THAT GOT INCORPORATED INTO YOUR EUKARYOTIC CELL, AND THAT GIVES US OUR ENERGY PLANT FORM FOR OXIDATIVE METABOLISM. BOTH IN THE CHLOROPLAST IN PLANTS AND IN OUR MITOCHONDRIA, THEY HAVE SEPARATE GENOMES.

THAT’S HOW ONE CAN TRACK THE MATERNAL GENOME FROM THE PATERNAL GENOME IN CELLS, BECAUSE THE MITOCHONDRIA COMES ALONG WITH THE EGG AND IS ONLY PASSED DOWN FROM MOTHER TO CHILD. AND SO WHEN YOU HEAR ABOUT DNA BEING USED FOR FORENSICS, IT’S QUITE OFTEN MITOCHONDRIAL DNA AND YOU CAN TRACK THE MATERNAL LINEAGES. SO ALL THIS CHEMISTRY WAS WORKING SO MUCH BETTER, WE DECIDED TO MAKE A MUCH LARGER CHROMOSOME. AND WE’D BEEN DOING ALL THIS WORK ON M. MYCOIDES SO WE DECIDED TO USE THE GIBSON ASSEMBLY TOOLS TO MAKE THIS MILLION BASE PAIR GENOME. WE STARTED WITH 1,000 BASE PAIR PIECES, PUT TEN OF THOSE TOGETHER TO GET 10KB PIECES. THEN WE PUT 10 OF THOSE TOGETHER TO GET 100KB PIECES. THEN WE PUT 11 OF THOSE INTO YEAST, AND IT ASSEMBLED THE ENTIRE CHROMOSOME. WE DID THE TRANSPLANTATION, AND IT DIDN’T WORK. SO THOSE OF YOU WHO WORK IN THE SOFTWARE WORLD HAVE DEBUGGING SOFTWARE. WE HAD TO CREATE A BIOLOGICAL VERSION OF THE DEBUGGING SOFTWARE TO FIND WHETHER IT WAS AN ERROR IN OUR DESIGN AND OUR SYNTHESIS, ET CETERA.

AND WE BASICALLY SUBSTITUTED THESE 100KB PIECES IN THE NATURAL CELL, AND WE FOUND TEN OF THEM WORKED AND ONE DIDN’T. WE RESEQUENCED THE ONE, AND WE FOUND A SINGLE BASE PAIR DELETION IN AN ESSENTIAL GENE, THAT IT CLEARLY MADE ALL THE DIFFERENCE BETWEEN LIFE AND NO LIFE. WE CORRECTED THAT ONE BASE PAIR, DID THE TRANSPLANTATION, AND WE GOT THE FIRST SYNTHETIC CELL WE DEFINED AS BEING POWERED COMPLETELY BY A CHEMICALLY MADE GENOME. SO THIS HAS NOW BEEN FOUR YEARS SINCE WE REPORTED THIS IN SCIENCE AND TO THE WORLD. AND MANY OF YOU REMEMBER THE WAY THAT WE COULD PROVE IT WAS TOTALLY SYNTHETIC DNA IS WE BUILT WATERMARKS INTO THE GENETIC CODE. WE DEVELOPED A CODE WHERE WE CAN WRITE THE ENTIRE ENGLISH LANGUAGE WITH NUMBERS AND PUNCTUATION IN THE FOUR LETTERS OF DNA.

AND WE INCLUDED THE NAMES OF 46 SCIENTISTS, NAMES OF THE INSTITUTIONS, AND I CAME UP WITH THREE QUOTATIONS FROM LITERATURE THAT I THOUGHT MIGHT BE APPROPRIATE. THE FIRST IS FROM JAMES JOYCE– “TO LIVE, TO ERR, TO FALL, TO TRIUMPH, TO RE-CREATE LIFE OUT OF LIFE.” THAT SEEMED TO FIT WHAT WE WERE DOING. THE SECOND SOME OF YOU PROBABLY RECOGNIZE, IT’S FROM OPPENHEIMER’S BIOGRAPHY “AMERICAN PROMETHEUS,” TOLD TO HIM BY AN EARLY TEACHER– “SEE THINGS NOT AS THEY ARE, BUT AS THEY MIGHT BE.” AND THE THIRD FROM RICHARD FEYNMAN– “WHAT I CANNOT BUILD, I CANNOT UNDERSTAND.” ONCE–AND ALSO, THERE’S A URL BUILT INTO THIS, AND WE CREATED SORT OF A CONTEST FOR PEOPLE TO DECODE THIS.

THEY SENT AN E-MAIL TO THE SPECIES, AND ONCE A NUMBER OF PEOPLE DECODED IT, WE MADE IT AVAILABLE. AND ONE OF THE FIRST RESPONSES WE GOT WAS A LETTER FROM JAMES JOYCE ESTATE ATTORNEY… [laughter] ASKING US IF WE HAD COPYRIGHT PERMISSION. BUT UNDER AMERICAN LAW, YOU CAN USE UP TO A PARAGRAPH AS LONG AS IT’S WITH ATTRIBUTION. AND THEN WE STARTED GETTING E-MAILS FROM A CALTECH SCIENTIST SAYING WE HAD MISQUOTED RICHARD FEYNMAN. JAMES JOYCE WAS DEAD AND SO WAS RICHARD FEYNMAN AT THE TIME. I THINK THEY STILL ARE, BUT… [laughter] IF YOU GO ON THE INTERNET, THIS IS THE MAIN QUOTE THAT YOU FIND DOING GOOGLE SEARCHES. AND IT TURNS OUT HIS BIOGRAPHER MADE AN ERROR IN WRITING ABOUT THIS. AND HERE’S THE–AS PROOF, THEY SENT A PHOTO OF THE CALTECH– A BLACKBOARD– SO THE ORIGINAL QUOTATION IS– “WHAT I CANNOT CREATE, I DO NOT UNDERSTAND.” SO WE’VE GONE BACK AND CHANGED THE GENETIC CODE SO FEYNMAN WILL REST PEACEFULLY.

[laughter] SO WHAT’S HAPPENED IN THE LAST FOUR YEARS? WE’VE BEEN LEARNING HOW TO DESIGN A CELL FROM SCRATCH. AND YOU’D THINK THIS WOULD BE REALLY STRAIGHTFORWARD TO DO. THERE’S NOT– THERE’S ONLY ABOUT 900 GENES IN THIS GENOME, AND YOU’D THINK THAT YOU COULD KNOCK THEM OUT ONE AT A TIME AND FIND OUT WHICH ONES WERE ESSENTIAL FOR LIFE AND WHICH ONES AREN’T, AND WE’VE BEEN DOING THAT FOR A LONG PERIOD OF TIME. THIS IS– WHEN YOU CONVERT THE GENOME INTO GENES IN M. MYCOIDES, THIS IS WHAT IT LOOKS LIKE, AND IT’S TRYING TO WORK OUT WHICH OF THOSE GENES ARE ESSENTIAL FOR LIFE IN THE CONTEXT OF THE OTHERS. THE ANALOGY WE USE IS WITH A SEVEN TRIPLE SEVEN.

IF YOU’RE DOING PARTS KNOCKOUT TO FIND OUT WHAT’S ESSENTIAL, YOU CAN REMOVE ONE ENGINE AND THE AIRPLANE WILL STILL FLY AND LAND SAFELY. IF YOU REMOVE THEM BOTH, IT WON’T. AND THAT’S SORT OF WHAT HAPPENS WITH BIOLOGY. THERE’S REDUNDANCY BUILT IN, BUT THE REDUNDANCY IS NOT OBVIOUS. IT’S NOT THE SAME STRUCTURE. IT’S NOT THE SAME PROTEIN FAMILIES. AND WHEN WE GET DOWN TO SORT OF OUR MINIMAL GENOME, ABOUT 1/4 OF THE GENES IN THIS CELL ARE OF UNKNOWN FUNCTION. THE ONLY THING WE KNOW IS THAT IF YOU REMOVE THAT GENE YOU CAN’T GET A LIVING SELF-REPLICATING CELL.

MY UNCLE IS 91. HE DESIGNED THE BOEING 757 AND 767. AND I SAID, “IMAGINE IF YOU WERE DESIGNING THESE AIRPLANES AND YOU DIDN’T KNOW WHAT 20% OF THE PARTS DID.” HE SAID, “WHAT MAKES YOU THINK WE KNEW?” [laughter] IN FACT, THE AIRLINE– THE AVIATION HISTORY IS HAVING FAILURES AND THEN GOING BACK AND DISSECTING WHAT THE FAILURE WAS AND CORRECTING IT NEXT TIME. IT’S KIND OF AN EXPENSIVE WAY TO GO, BUT THAT’S WHAT WE’VE BEEN DOING WITH THE GENOME. BUT WHEN 1/4 OF YOUR PARTS ARE OF UNKNOWN FUNCTION, IT’S HARD TO WORK OUT AND DO DESIGN ON FIRST PRINCIPLES, BUT WE’RE VERY CLOSE NOW ON THIS FIRST CELL DESIGNED COMPLETELY IN THE COMPUTER.

WE THINK IT’S GONNA WORK, AND WE’LL FIND OUT IN JUST A FEW WEEKS. THE NEXT STAGE WE’VE BEEN WORKING ON IS TO DEFRAG THE GENOME. YOU KNOW, EVOLUTION IS MESSY. THERE’S ALL KINDS OF REARRANGEMENTS. DNA CAN BE CODED ON EITHER STRAND. IT TURNS OUT, DIRECTIONALITY IS IMPORTANT FROM THE ORIGIN OF REPLICATION. SO THERE’S A HIGHER ORDER, BUT IF WE’RE GONNA DO DESIGN, WE WANT TO HAVE CASSETTES BY FUNCTION THAT WE CAN SORT OUT. SO WE’VE BEEN DOING THIS DEFRAGGING PROCESS. AGAIN, IT’S DIFFICULT TO DO WITH 1/4 OF THE GENES OF UNKNOWN FUNCTION.

SO THAT CREATES CHALLENGES. WE’RE USING THIS TECHNOLOGY IN OTHER AREAS. WE RECENTLY ANNOUNCED THIS PROGRAM WITH UNITED THERAPEUTICS WITH OUR GOAL TO HUMANIZE THE PIG GENOME TO MAKE PIG ORGANS FOR TRANSPLANTATION. THERE’S ABOUT 1/4 OF A MILLION DEATHS JUST FROM PEOPLE THAT NEED LUNG TRANSPLANTS AND CAN’T GET THEM. MOST OF YOU KNOW THIS HAS BEEN DONE WITH HUMANIZING MONOCLONAL ANTIBODIES. SO YOU CAN MAKE MONOCLONAL ANTIBODIES IN MICE, BUT THERE ARE ACTUAL HUMAN MONOCLONAL ANTIBODIES, AND THAT’S WHERE A LOT OF THE HUMAN THERAPEUTICS COME FROM. AND WE’RE NOW UNDERTAKING TO REWRITE THE PIG GENOME. AND WE’RE STARTING– FIRST, WE HAVE TO GENERATE A SUPERACCURATE VERSION OF THE PIG GENOME. SO WE’RE DOING THIS WITH SOME NEW TECHNOLOGY USING A COMBINATION OF PACBIO AND ILLUMINA SEQUENCING. BECAUSE THERE’S A HUGE DIFFERENCE BETWEEN READING THE GENETIC CODE AND WRITING THE GENETIC CODE. YOU CAN INFER, EVEN AS MUCH AS 10% ERRORS, WHAT THE GENOME IS. IF YOU’RE WRITING THE GENETIC CODE, AS I SHOWED WITH MYCOIDES SYNTHETIC GENOME, ONE BASE PAIR BEING WRONG CAN MAKE THE DIFFERENCE BETWEEN LIFE AND NO LIFE.

SO THE ACCURACY WHEN YOU’RE RE-CREATING LIFE HAS TO BE SUBSTANTIALLY HIGHER. WE’LL WORK ON DESIGNING WHICH PARTS OF THE GENOME WE HAVE TO CHANGE TO HUMANIZE. AND THE GOAL AT SYNTHETIC GENOMICS IS TO ACTUALLY DESIGN AND BUILD A NEW CELL. WE’LL GIVE THAT CELL TO UNITED THERAPEUTICS. THEY’RE GONNA, INSTEAD OF DOING GENOME TRANSPLANTATION WITH EUKARYOTIC CELLS, YOU CAN JUST TRANSPLANT THE NUCLEUS. SO THEY’RE GONNA TAKE OUR ENGINEERED CELL, TRANSPLANT THAT, GENERATE PIG EMBRYOS, AND GENERATE PIGS THAT THEN, AS THE PIGS ARE OLDER, THEY’LL USE THOSE ORGANS FOR TRANSPLANTATION. THIS HAS ACTUALLY BEEN EFFECTIVE JUST CHANGING FIVE GENES. THEY’VE GOTTEN TRANSPLANTS TO HAVE LASTED OVER A YEAR IN BABOONS. BUT TO GET IT SO IT’S REALLY EFFECTIVE FOR HUMAN TRANSPLANTATION ON A ROUTINE BASIS, WE HAVE TO MAKE A SUBSTANTIAL NUMBER OF CHANGES. BUT THE TOOLS ARE NOW READY TO START REWRITING THE GENETIC CODE. IT’S A–PETE WARNED ME AHEAD OF TIME, HE HAD TO LEAVE, BUT THIS IS THE PART HE LIKES IN TERMS OF THE INTER-CONVERSION OF DNA AND THE COMPUTER. AND WE TESTED IT IN A PROJECT WITH A TEAM HERE AT NASA OUT IN THE MOJAVE DESERT, TESTING OUR– OUR SENDING UNIT FOR THE BIOLOGICAL TRANSPORTER.

WE WENT OUT TO THE NASA TEST SITE IN THE MOJAVE DESERT, TOOK SAMPLES OF SOIL. A ROBOT WEARS THESE NICE GLOVES. [laughter] YOU KNOW? BUT IT WAS VERY EFFECTIVE. AND THEN WE SEQUENCED THEM IN OUR LAB BUS RIGHT ON-SITE, SO THAT–THAT’S PETE UP THERE RUNNING ONE OF THE MACHINES WHILE HE WAS THERE. SO IT GENERATED TREMENDOUS DIVERSITY OF ORGANISMS. IT WASN’T JUST A SIMPLE COLONY, EVEN THOUGH IT LOOKED LIKE THAT BIOLOGICALLY. WE JUST SEND IT UP TO THE CLOUD, DOWNLOADED THAT AT THE INSTITUTE, AND DID ALL THE ANALYSIS. SO THAT’S THE SENDING UNIT. THE RECEIVING UNIT IS BASED ON TAKING IN A DIGITAL SIGNAL AND CONVERTING IT BACK INTO BIOLOGY. SO WITH HELP FROM DARPA, WE ACTUALLY BUILT A PROTOTYPE OF THIS MACHINE. AND IT’S BEEN THOROUGHLY TESTED NOW FOR FUNCTIONALITY OF BEING ABLE TO SEND A DIGITAL SIGNAL TO IT. AT FIRST, WE HAD TO DO DNA ASSEMBLY AND ACCURATELY PRODUCE LARGE PIECES OF DNA. THEN WE HAD TO SHOW THAT IT COULD ACTUALLY MAKE PROTEINS. AND WE HAD TO MAKE RNA, AND THEN WE ACTUALLY MADE THE– A FLU VIRUS AND GOT IT SO THE NEW VACCINE COULD BE RESCUED FROM THAT, AND THE FINAL STAGE IS JUST SENDING A DIGITAL SIGNAL.

IT PRODUCED PHIX174 BACK TO OUR ORIGINS OF THE VERY FIRST EXPERIMENT WE DID, WHICH WAS THEN ABLE TO INFECT E. COLI AND KILL THE BACTERIA. SO WE’RE ABLE TO ACTUALLY SEND BIOLOGY THROUGH THE INTERNET. WE CAN MAKE DNA, RNA, PROTEINS, AND PHAGE AND SIMPLE SELF-REPLICATING CELLS. THE FUTURE WE’VE– TO SEND FAR MORE THROUGH THAT. SYNTHETIC GENOMICS HAS THE FIRST GN–DNA ASSEMBLY ROBOT. THAT’S GONNA BE ON THE MARKET LATER THIS YEAR. THIS IS NOT THE COMPLETELY AUTOMATED VERSION. THIS TAKES INPUT OF OLIGONUCLEOTIDES AND IT AUTOMATICALLY ASSEMBLES IT INTO LARGE PIECES OF DNA. THE NEXT VERSIONS WILL ALSO HAVE THE SYNTHETIC CAPABILITY. BUT JUST THINK ABOUT SOME OF THE PROBLEMS YOU GUYS ARE FACING OF TRYING TO GET SAMPLES, FOR EXAMPLE, BACK FROM MARS. USING LIFE AT THE SPEED OF LIGHT AND SENDING DIGITAL DNA INFORMATION WHEN EARTH AND MARS ARE AT THEIR CLOSEST, IT COULD BE AS LITTLE AS MINUTES TO GET A SAMPLE BACK HERE.

WE COULD SEND IT TO A SPACE SUIT LAB INSTEAD OF SPLASHING IT DOWN IN THE MIDDLE OF THE OCEAN. AS YOU– MANY OF YOU ARE AWARE, SAMPLE RETURN IS FRAUGHT WITH POLITICAL ISSUES ALTHOUGH, YOU KNOW, WHEN THE ASTRONAUTS FIRST CAME BACK FROM MAR–FROM THE MOON AND SPLASHED DOWN INTO THE OCEAN AND THEN PARADED AROUND THE DECK OF AN AIRCRAFT CARRIER AND THEN GOT INTO THE DECONTAMINATION UNITS FOR TWO WEEKS, OBVIOUSLY, NASA NEEDS SOME PEOPLE THAT HAVE WORKED IN STERILE ENVIRONMENTS AND SURGICAL UNITS TO KNOW WHAT YOU CAN CONTAMINATE AND HOW YOU CONTAIN IT, SO…

BUT WE COULD– WE COULD SEND IT DIGITALLY RIGHT BACK TO A SPACE SUIT LAB AND REBUILD THE– THE ALIEN LIFE THERE, IF ONE SO WANTED TO. WE’VE BEEN TALKING ABOUT EXPERIMENTS, SENDING BIOLOGY DIGITALLY TO AND FROM THE SPACE STATION AS PERHAPS ONE OF THE NEXT STEPS. AND THIS HAS IMPLICATIONS IN WHAT WE CAN DO WITH MEDICINE. WE’VE BEEN WORKING ON VACCINES FOR A LONG TIME. WE WERE WORKING WITH NOVARTIS, AND OUR FIRST GENOME-BASED VACCINE JUST GOT APPROVED IN EUROPE AND WILL BE APPROVED, WE THINK, IN THE U.S. IT’S AGAINST MENINGITIS B. THOSE OF YOU WHO HAVE– YOU’RE EITHER COLLEGE-AGE KIDS OR YOU HAVE KIDS THAT AGE, SHOULD DEFINITELY PAY ATTENTION TO THIS WITH THE OUTBREAKS IN PRINCETON AND UC SANTA BARBARA AND ALSO SOME CASES IN RIVERSIDE. BASICALLY, THE CDC AND THE FDA ARRANGED FOR IMMEDIATE USE OF THE NEW MENINGITIS B VACCINE TO STOP THOSE– STOP THOSE POTENTIALLY– INFECTIONS FROM SPREADING FURTHER. BUT MENINGITIS IS ONE OF THOSE DISEASES THAT’S TOTALLY PREVENTABLE WITH A VACCINE, BUT BY THE TIME YOU CAN DIAGNOSE IT, IT’S TOO LATE FOR PEOPLE.

SO IF YOU’RE THAT AGE OR HAVE KIDS THAT AGE, I HIGHLY RECOMMEND IT, AND IT SHOULD BE AVAILABLE SOON IN THE U.S. INFLUENZA IS A VACCINE THAT HAS TO BE MADE ANNUALLY. THE BIG FEAR, GOING BACK TO 1918, WHERE ABOUT 3% OF THE WORLD’S POPULATION WERE KILLED FROM THE 1918 FLU VIRUS. IT TURNED OUT SOME PEOPLE BURIED IN THE PERMAFROST AND SOME SAMPLES IN ARMY FREEZERS IN–IN WASHINGTON, D.C., THE TISSUE STILL CONTAINED LIVE VIRUS. IT WAS ISOLATED AND SEQUENCED AND THE CDC REPRODUCED THE VIRUS SO WE COULD UNDERSTAND MORE ABOUT IT, AND SO WE CAN RECOGNIZE DANGEROUS COMPONENTS OF THIS. AND THIS HAPPENED IN REAL TIME WITH H7N9. IN A COURSE OF SIX DAYS FROM MARCH 31ST, THE FIRST H7N9 CASES BEING REPORTED IN CHINA.

A CHINESE GROUP SEQUENCED THE GENOME. WE WERE ABLE TO DOWNLOAD THE SEQUENCE DIGITALLY. WE STARTED THE SYNTHESIS ON APRIL 1ST. AND ON APRIL 6TH, THE FIRST VACCINE ISOLATES WERE RECOVERED. NOVARTIS AND THEIR NEW CELL LINE FACILITY IN NORTH CAROLINA SCALED UP THE PRODUCTION, WENT INTO CLINICAL TESTING, AND NOW THE U.S. IS STOCKPILING THIS VACCINE, WHICH IS OUR FIRST SYNTHETIC DNA-BASED VACCINE. AND IT’S ALSO THE FIRST TIME WE’VE HAD A FLU VACCINE BEING STOCKPILED AND READY IN THE U.S. BEFORE THERE’S EVER AN INFECTION IN THE U.S. THEY’VE BEEN IN HONG KONG, CHINA, MALAYSIA, AND THEY WILL SHOW UP HERE SOONER OR LATER, BUT NOW THAT THE VACCINE IS READY, HOPEFULLY A PANDEMIC CAN BE TOTALLY PREVENTED. SO THE NEXT STEPS IS MAYBE COMBINING THESE THINGS. WE CAN ACTUALLY SEND THE FLU VACCINE AROUND THE WORLD AT THE SPEED OF LIGHT IN A FRACTION OF A SECOND. AND SO IF YOU HAD RECEIVING UNITS EVEN ON YOUR HOME COMPUTER, YOU COULD DOWNLOAD INSULIN, YOU COULD DOWNLOAD OUR, UH, VACCINES OR A FLU VACCINE.

AND IF WE HAVE THESE DISTRIBUTED ENOUGH, IT SHOULD TOTALLY PREVENT ANY FUTURE PANDEMICS. SO FOR NASA, A COMBINATION OF THESE THINGS MAY– CERTAINLY USING GENOMICS TO IDENTIFY AND PREVENT DISEASE RISK IN THE FUTURE BOTH HERE ON EARTH AND ON OTHER PLANETS. AND OBVIOUSLY, DESIGN IS AN OPEN ISSUE. MAYBE WE WANT TO MAKE PHOTOSYNTHETIC ANIMALS OR EVEN PHOTOSYNTHETIC HUMANS IF THEY ARE BALD AND HAVE ENOUGH SKIN AVAILABLE. SO THANK YOU VERY MUCH. [applause] – THANK YOU, DR. VENTER. – SURE. – SO WE HAVE TIME FOR A COUPLE OF QUESTIONS. IF YOU HAVE A QUESTION, PLEASE RAISE YOUR HAND, WAIT FOR THE MICROPHONE, AND PLEASE STAND WHEN YOU ASK THE QUESTION. – I HAVE A QUESTION BACK HERE. – WHERE? – CRAIG, I HAVE A QUESTION OVER HERE. – OH, OKAY. – I THINK THIS IS AMAZING THAT YOU WERE ABLE TO MAKE A SYNTHETIC ORGANISM, I.E. SYNTHESIZED DNA, BUT I’M A LITTLE BIT SURPRISED THAT YOU’RE SURPRISED THAT IT WORKED. I MEAN, WHAT WOULD HAVE HAPPENED OTHERWISE? I MEAN, YOU MADE THE DNA. IT WAS CHEMICALLY IDENTICAL TO DEOXYRIBONUCLEIC ACID. HOW COULD IT NOT HAVE WORKED? – I’M NOT SURPRISED THAT IT WORKED IN THE END. IN FACT, IF YOU LOOK AT MY BOOK, THE FIRST THIRD OF IT IS THE HISTORY OF THIS FIELD.

AND A FRENCHMAN WROTE A BOOK A HUNDRED YEARS AGO SAYING THAT SYNTHETIC LIFE WAS OBVIOUS AND WAS GOING TO HAPPEN ONCE OUR IMPROVED KNOWLEDGE OF MACROMOLECULES OCCURRED AND THAT IT WAS– HE WAS SO CERTAIN, HE SAID PEOPLE SHOULD NOT BE SURPRISED WHEN IT HAPPENED. HE WAS IN THE POINT OF VIEW OF DEALING WITH ALL THE TECHNICAL DETAILS OF DOING THIS. THE TRANSPLANTATION OF GETTING THE GENOME INTO THE CELL UNDER THE RIGHT CONDITIONS, IT MADE ME APPRECIATE HOW AND WHY RESTRICTION ENZYMES EVOLVED. IF YOU HAD A MEAL OF FISH AND ABSORBING BILLIONS OF COPIES OF THE FISH GENOME, YOU STARTED TO REARRANGE YOUR OWN GENOME, WHICH IS WHAT HAPPENS IN THE BACTERIAL WORLD IF THEY DON’T HAVE THE RIGHT RESTRICTION ENZYMES, EVOLUTION WOULD BE VERY SURPRISINGLY DIFFERENT. WE’D PROBABLY BE A LOT MORE CAREFUL ABOUT WHAT WE EAT. [laughter] SO IT’S NOT SURPRISING THAT IT WORKED IN THEORY. WHEN YOU WORK ON TEN YEARS TO OVERCOME THE PRACTICAL LIMITATIONS OF MAKING IT HAPPEN, THAT WAS THE SURPRISING PART. – LET ME ASK A FOLLOW-UP QUESTION, AND THAT HAS TO DO WITH NOT ONLY RESTRICTION ENZYMES BUT ALL THE DIFFERENT TYPES OF RNAs THAT ARE INVOLVED AND ALL THE DIFFERENT CONTROL FACTORS, PROMOTERS, ALL THE DIFFERENT SILENCERS THAT ARE IN A COMPLEX GENOME THAT WE MOVE BEYOND A YEAST GENOME OR A SINGLE-CELL PROKARYOTIC GENOME INTO SOMETHING COMPLEX– DO YOU REALLY SEE A FUTURE THERE IF YOU’RE JUST DABBLING IN DNA? – WELL, THOSE PEOPLE WHO MEASURE EPIGENETIC PHENOMENON, I HAVE A SAYING FOR THEM– EPIGENETICS IS STILL GENETICS.

IT STARTED WITH THE GENOME, AND ALL THESE EPIGENETIC PHENOMENON CAME FROM MOLECULES PRODUCED FROM THAT BASIC GENETIC CODE. THAT’S WHAT OUR CHALLENGE IS WITH THIS GIANT COMPUTE OF GETTING SO WE CAN PREDICT FROM THE PRIMARY CODE– ‘CAUSE THAT’S HOW YOUR CELLS WORK, YOU KNOW? YOU HAVE 100 TRILLION CELLS. THEY READ YOUR GENETIC CODE, AND THEY PRODUCE VIRTUALLY EVERYTHING ABOUT YOU. WE’VE BEEN REDUCED IN MEDICINE TO MEASURING A FEW OF THE LIMITED GROSS CHANGES FROM THAT. WE WANT TO GET SO WE CAN PREDICT ALL OF THOSE FROM UNDERSTANDING THE GENETIC CODE ITSELF. YES. – YES, I HAD A QUESTION REGARDING WHEN YOU’RE SENDING THE DNA INFORMATION, SAY, FROM MARS OR SO THAT PEOPLE CAN USE IT, YOU KNOW, TO DOWNLOAD IN THE FUTURE– – WE HAVEN’T DONE THAT YET, BUT… [laughs] – [laughs] BUT YOU HAD–YOU HAD DONE SAMPLES IN THE DESERT, YOU HAD SAID… – YEAH. – THAT ACTUALLY DID WORK. WHAT KIND OF INFORMATION LOSS WAS THERE WHEN– WHEN IT WAS SENT? WAS THERE ANY SORT OF– YOU KNOW, WHEN YOU THINK ABOUT COPYING SOMETHING, THERE’S ALWAYS JUST A LITTLE BIT THAT–THAT MIGHT BE LOST THERE.

– YEAH. WITH THE SEQUENCING THAT WE WERE DOING IN THE DESERT, THERE WAS SO MUCH REDUNDANCY THAT WASN’T AN ISSUE. ACTUALLY, A BIGGER PROBLEM WAS THE BIOLOGICAL DIVERSITY SO THAT WE WOULD NOT– FROM THE SAMPLING WE DID IN THE DESERT AND THE AMOUNT OF SEQUENCING WE DID THERE, WE DIDN’T EXPECT THIS TREMENDOUS DIVERSITY OF EUKARYOTES AND PROKARYOTES THAT LOOK, ON THE BACK OF THIS QUARTZ ROCK, LIKE A SIMPLE ALGAE COLONY. SO WE WOULD HAVE HAD TO SEQUENCE IN GREATER DEPTH TO BE ABLE TO RECONSTRUCT THE GENOMES FROM ALL THOSE DIFFERENT SPECIES THERE.

SO IF WE’RE EVER SAMPLING– IF WE’RE SAMPLING ON MARS AND THERE’S GREAT BIOLOGICAL DIVERSITY, AND THERE’S NO REASON TO EXPECT THERE WOULDN’T BE, WE HAVE TO HAVE A MASSIVE AMOUNT OF SEQUENCING IF WE ACTUALLY WANT TO RE-CREATE THOSE ORGANISMS. IF YOU ISOLATE THEM AND THEN SEQUENCE THEM, THEN IT’S MUCH SIMPLER, BUT THERE WAS REALLY NO LOSS OF SIGNAL THAT WE COULD HAVE SEEN. IT’S JUST SENDING DNA UP TO THE CLOUD AND THEN RECAPTURING IT. YES. – YOU MENTIONED THAT ONE OF YOUR GOALS WAS–YOU’D HAVE IN THE NEXT FEW WEEKS– YOU’RE REORGANIZING THE GENOME TO COMPARTMENTS BASED ON FUNCTION. I WAS WONDERING, IF BY DOING THAT, ARE YOU AVOIDING–ARE–ARE YOU REMOVING SOME OF THE– ARE YOU–ARE YOU CAUSING A PROBLEM WITH THE RANDOM RECOMBINATION THAT MIGHT CALL– OR THAT HAPPENS BETWEEN– DURING SEQUENCING THAT– BY–BY HAVING THE–THE–THE GENE– GENOME IN A RANDOM SITUATION OR RANDOM ORGANIZATION AROUND THE GENOME, THEN IF THERE IS RANDOM RECOMBINATION, THEN YOU HAVE– STILL HAVE SOME GENES THAT ARE STILL REPLICATING THE SAME THINGS.

– IN MOST OF THESE BACTERIAL SPECIES, THERE’S NOT A LOT OF RECOMBINATION, BUT IT CERTAINLY CAN OCCUR, BUT I DON’T THINK THAT WOULD LEAD TO IT. THE BIGGEST CHALLENGE IS THERE ARE THESE HIGHER ORDER STRUCTURES. FOR EXAMPLE, ON A CIRCULAR GENOME, THERE’S AN ORIGIN OF REPLICATION AND THE GENETIC CODE GETS READ OUT FROM THERE IN A CIRCLE. AND IF YOU MOVE THAT ORIGIN OF REPLICATION AROUND TOO MUCH OR DON’T HAVE SYMMETRY AROUND IT, IT GETS SO YOU DON’T HAVE LIFE.

WHERE ARE WE? – AS GENETIC MATERIAL BECOMES SYNTHESIZABLE AND TRANSMISSIBLE, WHAT ISSUES DO YOU SEE ARISING IN TERMS OF OWNERSHIP? – DEPENDS WHAT YOU MEAN BY OWNERSHIP. YOU JUST LEFT YOUR FINGERPRINTS AND A LOT OF DNA ON THE MICROPHONE. WE COULD SEQUENCE YOUR GENOME FROM THAT. YOU DON’T OWN THE MICROPHONE, UM… YOU KNOW, SO I THINK THESE ARE CONCEPTS THAT ARE GONNA BE RAPIDLY OUTDATED BY THE PROGRESSION OF THE INFORMATION UNIVERSE THAT WE’RE IN. WHAT YOU WANT IS NOT OWNERSHIP. YOU WANT TO HAVE SOME DEGREE OF CONTROL WHAT CAN BE DONE WITH YOUR DNA. THAT’S FAR MORE IMPORTANT THAN OWNERSHIP. – SO IF YOU WANTED TO SEND ONE OF THESE MACHINES OF YOURS TO MARS TO SEQUENCE DNA, HOW BIG IS IT, HOW HEAVY IS IT? IS IT FEASIBLE TO DO IT WITH YOUR CURRENT TECHNOLOGY? – IT’S A GREAT QUESTION.

I THINK YOU’D WANT TO SHRINK THEM DOWN A WHOLE LOT MORE, AND THAT SHOULDN’T BE THAT MUCH OF A CHALLENGE. SEQUENCING BACTERIAL AND SMALL EUKARYOTIC GENOMES IS VERY DIFFERENT THAN– IF THERE’S MARTIANS WITH HUMAN-SIZE GENOMES, THEN WE NEED MUCH BIGGER TECHNOLOGY, UM… THINGS LIKE THE… THE LIFE TECHNOLOGIES, TECHNOLOGY WHICH MEASURES pH CHANGES ASSOCIATED WITH ONE BASE BEING ADDED AND IS BASICALLY DONE ON A COMPUTER CHIP IS, BY DEFINITION, VERY MINIATURIZED AND DOESN’T RELY ON ANY OPTICS FOR READING IT. THE ILLUMINA SEQUENCERS, WE ACTUALLY HAD TO HAVE A TECHNICIAN COME OUT TO THE MOJAVE DESERT TO REALIGN THE OPTICS JUST AFTER ROAD TRAVEL OUT THERE. SO THOSE INSTRUMENTS WOULD NOT BE VERY GOOD FOR SPACE TRAVEL. UH… THERE’S NO REASON ANY OF THESE TECHNOLOGIES COULDN’T BE REDUCED TO CHIP-BASED AND MICROCHANNEL-BASED THINGS. WE’RE, AT THE PROOF OF CONCEPT STAGE, JUST GETTING THEM TO WORK. HOPEFULLY, YOU’LL TAKE THAT ON. – OKAY, SO YOU TALKED ABOUT A SYNTHETIC MICROBIOME WITH, LIKE, THE CONTEXT OF SPACE EXPLORATION WHICH I IMAGINE IS LIKE AS ISOLATED AS AN ENVIRONMENT AS YOU CAN GET.

BUT IF YOU WERE TO ATTEMPT TO HAVE ENGINEERED CELLS, LIKE, LIVING IN A HUMAN GUT ON EARTH, HOW DO YOU PREVENT NATURAL CELLS FROM OUTCOMPETING AND REPLACING THOSE ENGINEERED CELLS? – SO IT’S A VERY GOOD QUESTION. AND I THINK IT ALL GETS INTO CELLULAR DESIGN, YOU KNOW? I THINK THAT’S GONNA BE ONE OF THE BIGGEST, MOST CHALLENGING FIELDS GOING FORWARD, BUT IT’S GONNA HAPPEN STARTING WITH HAVING ALL THIS DIGITAL INFORMATION AND TRYING TO UNDERSTAND WHAT IT’S TELLING US TO BE ABLE TO GO BACK AND DO THE DESIGN. SO SOME OF THE SYNTHETIC MICROORGANISMS MAY BE, YOU KNOW– WE CAN MAKE CELLS GROW MUCH FASTER AND OUTCOMPETE OTHER ORGANISMS, AS WELL. THE GOAL IS TO ELIMINATE THEIR PATHOLOGICAL POTENTIAL AND JUST HAVE THEM HAVE THE BENEFICIAL METABOLISM. SO WE HAVE A WAYS TO GO WITH A DEGREE OF UNDERSTANDING BUT I THINK THERE’S GONNA BE– JUST LIKE THE 767 AND OTHER AIRPLANES, THERE’LL BE A FEW FAILURES BEFORE WE HAVE IT ALL SORTED OUT.

– THERE WAS A QUESTION SAYING HOW YOU TRANSMITTED ALL THIS DNA INFORMATION FROM MARS OR “SIMULATED” MARS. IT MAY BE A FUTURE TRANSPORTER, LIKE A “STAR TREK” TRANSPORTER, OR IS IT A WAY OF WE COULD EVENTUALLY SEND HUMANS INTO FAR DEPTHS OF SPACE AT THE SPEED OF LIGHT, NOT BY PEOPLE, BUT BY OUR SPECIALIZED CODE OF DNA AND MAYBE BEING REASSEMBLED SOMEWHERE ELSE? – WELL, PEOPLE ARE A LITTLE BIT CONCERNED WITH THAT, ‘CAUSE MY GENOME’S BEING BROADCAST FOR ABOUT 15 YEARS OUT THERE, SO YOU MIGHT GET A LOT OF CRAIG VENTERS COMING BACK IF PEOPLE DO THAT EXPERIMENT. [laughter] BUT NO, YOU KNOW, YOU CAN EASILY– IF IT’S REALLY DISTANT SPACE TRAVEL, YOU COULD JUST SEND EITHER SOME STEM CELLS THAT ARE SHIELDED IN LEAD AND ASSUME THAT SOMEBODY, IF THEY REACH THE RIGHT ENVIRONMENT, WOULD BE ABLE TO DO THE TRANSPLANT AND BOOT THEM UP, OR POTENTIALLY JUST SEND CODE.

UH… ONCE WE’RE IN DIFFERENT PLACES AND HAVE THINGS TO READ THE CODE AND BOOT IT UP, OR IF WE HAVE MORE ADVANCED MACHINES, WE CAN JUST SEND THOSE AND BOOT IT UP. IT WOULDN’T BE HARD TO DO THAT IN TERRAFORMED PLANETS. SENDING HUMANS IS A LOT MORE CHALLENGING. OKAY. – SO PLEASE JOIN ME IN THANKING DR. VENTER AGAIN FOR AN EXCELLENT PRESENTATION. [applause] [musical tones] [electronic sounds of data].

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