caption

Nobel Laureate Sir Richard Roberts PH.D.

VERY SIMPLE IDEA, VERY
SIMPLE EXPERIMENT. AND SO, RICHARD GOT STARTED
DOING THIS AND WE STARTED WITH ADENOVIRUS BECAUSE QUITE
A LOT, IT WAS ALREADY KNOWN ABOUT ADENOVIRUS IN TERMS
OF TRANSCRIPTION AND GENES AND WHERE THEY WERE AND WE
KNEW THAT EARLIER IN INFECTION, THERE WERE RNA TRANSCRIPTS
MADE COMING IN FROM THE ENDS OF THE VIRUS, ADENO
IS A LINEAR VIRUS. SO THERE WERE TRANSCRIPTS
COMING IN FROM THE END. AND SO, WE STARTED TRYING
TO FIND THOSE TRANSCRIPTS BUT THEY WERE PRESENT IN SUCH
LOW QUANTITIES WE COULD NEVER GET ENOUGH OF THEM. AND THEN WHILE WE WERE DOING
THAT, IT WAS DISCOVERED THAT RNAS MADE IN ADENOVIRUS AND OTHER SYSTEMS HAD
TRIPHOSPHATE CAPS ON THEM.

THEY HAD A 7 METHYL G, 7– 2-PRIME O METHYL G
AND THEN A G HOOKED UP IN A 3, 5 CONFIGURATION. THEY HAD A DIFFERENT
STRUCTURE, BUT WHAT IS MEANT WAS THAT THEY EFFECTIVELY HAD 2,
3 PRIME ENDS BECAUSE THE G THAT WAS ON THE CAP WAS
FACING IN THE WRONG DIRECTION. SO IT HAD A 3-PRIME DIHYDROXYL
GROUP, POLY-A HAD THAT TOO AND THAT ACTUALLY
GAVE US THE HOOK SO THAT WE COULD SEPARATE
THE CAPS OLIGONUCLEOTIDE, THE ONE FROM THE VERY
END FROM EVERYTHING ELSE.

AND I CAME UP WITH A
METHOD FOR DOING THIS THAT WAS BASED UPON
BORON CHEMISTRY, BORON TURNS OUT TO BE VERY
NICE FOR BINDING THINGS THAT HAVE [INAUDIBLE] DIOLES
THAT HAVE TWO HYDROXYL GROUPS ON THEM, CAME UP
WITH THIS METHOD AND SO RICHARD DID THE
EXPERIMENT AND WERE EXPECTING BECAUSE WE KNEW THERE WERE
ABOUT 20 DIFFERENT MESSAGES THAT WE WOULD SEE 20 DIFFERENT
OLIGONUCLEOTIDES CORRESPONDING TO THE START POINTS OF
ALL THE MESSENGER RNAS. WE DID THE EXPERIMENT AND HE ONLY FOUND ONE
CAT OLIGONUCLEOTIDE FROM THESE 20 MESSAGES. WELL IT JUST– IT
DIDN'T MAKE SENSE.

THIS WAS NOT WHAT WE WERE
EXPECTING AND SO, YOU KNOW, I HAD A LITTLE TALK WITH
HIM AND SAID, YOU KNOW, "WHY DON'T YOU GO BACK AND BE
A LITTLE MORE CAREFUL NEXT TIME AND DO THE EXPERIMENT PROPERLY." SO HE DID, HE WENT
BACK AND DID IT AGAIN AND GOT THE SAME RESULT. SO, WE HAD ANOTHER TALK AND
HE WENT AND DID IT AGAIN AND GOT THE SAME RESULT. AND SO I SAID, "YOU
KNOW, RICHARD, WHY DON'T YOU SIT
DOWN, LET ME DO IT. I'LL SHOW YOU HOW
TO DO IT PROPERLY." AND SO, I WENT AND DID
THE EXPERIMENT MYSELF AND SURE ENOUGH, I GOT THE
SAME RESULT AND AT THAT POINT OF COURSE I BELIEVED IT. YOU KNOW, ONE OF THE NICE
THINGS IS WHEN EXPERIMENTS FAIL IN THIS KIND OF SITUATION, IT'S ONE OF THE GREATEST
THINGS THAT CAN HAPPEN.

FAILURES ARE GREAT THING
BECAUSE IT'S TELLING YOU OF ONE OF TWO THINGS, EITHER
YOU SCREWED UP, YOU KNOW, MAYBE YOU DROPPED THE SAMPLE
ON THE FLOOR OR JUST DIDN'T LAY UP PROPERLY, BUT MAYBE NATURE
IS TRYING TO TELL YOU SOMETHING. AND IN THIS CASE,
NATURE WAS TRYING TO TELL US SOMETHING VERY
BIG AND SO I ALWAYS LOVE IT WHEN STUDENTS COME IN AND
SAY, YOU KNOW, "YOU SUGGEST THAT I DO THIS EXPERIMENT
AND IT DIDN'T WORK." YEAH, GREAT. MAYBE THERE'S A DISCOVERY HERE. SO, YOU DON'T– DON'T EVER
BE DISHEARTENED BY FAILURE. FAILURE IS A GOOD THING. ALL THE GREAT DISCOVERIES
ARE USUALLY MADE BY PEOPLE DOING AN
EXPERIMENT BUT IT DIDN'T WORK.

SO, RICHARD DID THE EXPERIMENT, IT TOOK US A WHILE
BEFORE WE COULD FIGURE OUT EXACTLY WHAT WAS GOING ON. SO, WE COULD SEE THAT THIS
ONE OLIGONUCLEOTIDE AT THE END OF THE MESSAGE CAME FROM
EVERY INDIVIDUAL MESSAGES, IF WE TRY TO PURIFY INDIVIDUAL
MESSAGES BY HYBRIDIZATION, THEY'LL ALL HAVE THE SAME
STRUCTURE AT THE END. AND I CAN TELL YOU,
MOST OF THE PEOPLE AT COLD SPRING HARBOR WHOM WE
TOLD THIS RESULT TO HAVE SAID "AH, IT'S AN ARTIFACT." OK, YOUR G IS NOT PULLING OUT WHEN YOU THINK
YOU'RE PULLING OUT, IT'S SOMETHING THAT'S VERY ODD. BUT WE KNEW THAT WE WERE ALREADY
DOING THE EXPERIMENTS CORRECTLY AND WE JUST WENT ON AND EVERY–
WE GOT INTO THIS MODE EVERY WEEK AND WE'D HAD A LITTLE
AUTOPSY ON A SATURDAY MORNING TO UNDERSTAND WHY LAST WEEK'S
EXPERIMENTS HADN'T WORK AND WHY NEXT WEEK, YOU KNOW,
WE COULD DO THE BIGGEST AND BEST EXPERIMENT NEXT WEEK. AND SO ONE ON ONE OF THIS
SATURDAY MORNINGS IN EARLY MARCH IN 1977, AND WE'RE SITTING
HAVING OUR SATURDAY MORNING AUTOPSY AND RICHARD IS THERE AND HE'S PROPOSING SOME
UNBELIEVABLY COMPLICATED EXPERIMENT AND SO FAR, I
JUST WASN'T PAYING ATTENTION AND THEN SUDDENLY
OUT OF THE BLUE, THE EXPERIMENT HE DO CAME TO ME.

AND SO, I SAID TO RICHARD,
"YOU KNOW, SIT DOWN, HERE'S WHAT WE SHOULD DO." AND SO THE EXPERIMENT
WAS ACTUALLY ENDED UP. IT WAS AN ELECTRON
MICROSCOPY EXPERIMENT, BUT NEITHER RICHARD NOR I
WERE ELECTRON MICROSCOPIST BUT WE WERE LUCKY BECAUSE JUST DOWN THE HALL WERE TWO
EXCELLENT MICROSCOPIST, TOM BROKER AND LOUISE CHOW. AND SO WE WENT DOWN INTO
THEM AND SAID, "YOU KNOW, WE'VE HAD THIS IDEA
FOR AN EXPERIMENT AND IF WE MAKE THE REAGENTS FOR
YOU, WILL YOU DO IT FOR US?" AND SO THEY LOOKED AND
THEY SAID, "WELL, YOU KNOW, IT'S NEVER BEEN DONE, NO ONE
HAS EVER QUITE DONE THIS THING BEFORE, BUT SURE AND THEY
SHOULD WORK AND WE'LL DO IT. AND SO, RICHARD MADE THE
APPROPRIATE SUBSTRATES THAT WE NEEDED FOR THE
EXPERIMENTS OVER THE WEEKEND AND ON TUESDAY MORNING,
LOUISE CHOW SPREAD THE RESULTS ON THE ELECTRON MICROSCOPE,
LOOKED AT THEM AND LO AND BEHOLD, SPLICING
WAS DISCOVERED.

EXACTLY WHAT WE HAD PREDICTED
HAPPENED SHOULD HAPPEN, HAD HAPPENED. IT WASN'T QUITE SO
STRAIGHTFORWARD AS THAT. WE ACTUALLY, THE EXPERIMENT
WAS BASED ON A FAULTS PREMISE BUT IT DIDN'T MATTER BECAUSE
THE FRAGMENTS THAT WE CHOSE TO LOOK UP WORKED ANYWAY. THE EXPERIMENT IS SORT
OF ILLUSTRATED UP HERE. I DON'T REALLY WANT TO TRY AND
GO INTO IT IN TOO MUCH DETAIL BUT THE IDEA OF THE
EXPERIMENT WAS THAT IF YOU CAN TAKE A MESSENGER
RNA, YOU CAN HYBRIDIZE IT TO DNA AND YOU GET A VERY NICE HYBRID. NOW, IF THERE ARE SEQUENCES
THAT DO NOT HYBRIDIZE TO THE DNA THAT THEY WILL STICK
OUT, THEY'LL BE STICKING OUT JUST THE POLY-A, IS
NOT COATED IN THE DNA, IT JUST STICKS OUT BECAUSE IT'S
ADDED POST TRANSCRIPTIONALLY AND YOU CAN DETECT IT
BY PUTTING IN OLIGO-DT AND THEN YOU GET A NICE SIGNAL
IN THE ELECTRON MICROSCOPE, GET SOMETHING NICE AND VISUAL.

WE WERE INTERESTED
IN THE OTHER END. WE WANTED TO KNOW WHAT
WENT ON AT THE 5-PRIME END. WE THOUGHT WE KNEW WHERE THE
STRUCTURE MIGHT BE COATED AND SO THAT WAS THE PROBE THAT
WE USED AND IT TURNED OUT THAT IT WAS THE RIGHT PROBE
BUT IT WAS FOR THE WRONG REASON. IT WAS THE WRONG SEQUENCE,
BUT IT DIDN'T MATTER BECAUSE THE RIGHT
SEQUENCES WERE ON THAT PROBE. AND AT THIS POINT,
SPLICING WAS DISCOVERED. WE HAD A PICTURE AND
EVERYBODY BELIEVED US. YOU KNOW, WE'D HAD ALMOST YEARS
WORTH OF BIOCHEMISTRY BEFORE THAT AND I REMEMBER, YOU KNOW,
I WENT UP TO JIM'S OFFICE AND TOLD HIM ALL ABOUT IT, I
TOLD EVERYBODY WOULD LISTEN ABOUT THIS EXPERIMENTS AND ALMOST NOBODY
WOULD BELIEVE THEM. ONE OF THE FEW PEOPLE WHO REALLY
BELIEVED THEM WAS A MAN CALLED GEORGE F. [ASSUMED
SPELLING] WHO WAS HEAD OF THE MOLECULAR BIOLOGY
INSTITUTE IN MOSCOW AND HE WAS AN INSTANT
COMBAT [PHONETIC], HE THOUGHT THIS WAS GREAT. BUT MOST OTHER PEOPLE
JUST DIDN'T BELIEVE IT UNTIL THEY SAW THIS
ELECTRON MICROSCOPIC PICTURE.

AND SO LATER, THAT'S HOW WE GOT
THE RESULTS, I DON'T KNOW, 10, 11 O'CLOCK IN THE MORNING. BY THE END OF THE DAY, EVERYBODY
WAS TALKING ABOUT NOBEL PRIZES BECAUSE THIS WAS
A HUGE DISCOVERY. IT OVERTHREW, AS
YOU HEARD EARLIER, ALL OF THE EXISTING PARADIGMS
ABOUT HOW RNAS WERE MADE AND WHAT GENES LOOK LIKE
IN HIGHER ORGANISMS OPPOSED TO LOWER ORGANISMS AND THIS
DIAGRAMIC [PHONETIC] TRIES TO EXPLAIN IT A LITTLE BIT. SO BASICALLY, THE GENE IS
DIVIDED IN A EUKARYOTE, IT SPREADS OVER HUGE DISTANCE
AND THERE ARE LITTLE BITS OF IT, THE CODE FOR THE PROTEIN BUT
THEY ARE SEPARATED AND THEY SIT ON SOME SEQUENCES THAT WE CALL
EXOMES AND THEN IN BETWEEN, THERE'S A REGION THAT JUST NEVER
CODES FOR ANYTHING THAT WE KNOW ABOUT IN TERMS OF
PROTEINS FOR THE MOST PART AND THAT'S CALLED INTRON.

THESE NAMES WERE INVENTED BY
WALLY GILBERT AND WE NOW KNOW THAT WHAT GOES ON IS
THAT YOU MAKE AN RNA THAT COPIES THE WHOLE THING AND THEN YOU TREAT IT THOUGH
IT WERE A MOVIE, YOU KNOW, YOU JUST SAW ALL THE OSCARS
AND THEY WERE GIVING OUT OSCARS FOR PEOPLE WHO WERE BUSY
EDITING TRANSCRIPTS– FILM TRANSCRIPTS THAT IS. THAT'S WHAT HAPPENS HERE. YOU BASICALLY MAKE THE
WHOLE RNA AND YOU TAKE IT TO THE CUTTING BLOCK
THEN YOU CUT AND SPLICE AND CUT AND SPLICE. YOU TAKE THE BITS THAT MAKE
SENSE, JOIN THEM TOGETHER, THE REST OF THEM, YOU THROW
AWAY IN JUST WHAT HAPPENS WHEN YOU MAKE A MOVIE SO THAT
EVENTUALLY, YOU'LL GET A MOVIE THAT LOOKS AS THOUGH IT WAS JUST
SHOCK CONTINUOUSLY ALL THE WAY THROUGH BECAUSE OF THE GOOD
EDITING JOB THAT'S DONE AND THAT'S WHAT HAPPENS
IN HIGHER ORGANISMS.

THIS IS HOW WE MAKE THE RNAS
THAT ARE ULTIMATELY GOING TO CODE FOR ALL OUR PROTEINS. IN BACTERIA, DON'T DO THAT, JUST
MAKE A DIRECT COPY OF THE DNA AND THEN YOU'VE GOT
WHAT YOU WANT. SO, IT WAS REALLY A VERY,
VERY NICE DISCOVERY TO BE MADE BECAUSE NO ONE HAD PREDICTED IT. YOU KNOW, VERY OFTEN
YOU MAKE A DISCOVERY, AND ALL YOU'RE DOING IS
CONFIRMING SOMEONE'S HYPOTHESIS. THIS WAS NOT HYPOTHESIS DRIVEN
SCIENCE, THIS WAS SCIENCE THAT WE WERE JUST LOOKING TO
SEE HOW SOMETHING WAS MADE AND AT ALMOST EVERY STAGE, A HYPOTHESIS WAS
SHOWN TO BE INCORRECT. SO IT WAS NICE. SO THIS WAS GOOD. AND OF COURSE, YOU KNOW, ONE OF
THE DISAPPOINTING THINGS HERE WHICH I THINK POINTS OUT
ONE OF THE PROBLEMS WE HAVE IN SCIENCE TODAY AND CERTAINLY
HAVE BACK THEN IS THAT AS SOON AS WE MADE THE DISCOVERY,
EVERYBODY WENT BACK, LOOK TO THEIR OWN DATA AND
DISCOVERED THEY HAD THE DATA IN THEIR NOTEBOOKS BUT SHOWED IN SOME OTHER SYSTEM EXACTLY
THE SAME THING WAS GOING ON.

I WENT TO A MEETING
AT COLD SPRING HARBOR AND WHICH THE RNA
VIROLOGISTS WERE THERE AND MIKE BISHOP STANDS
UP WHO LATER WENT ON TO WIN A NOBEL PRIZE
FOR THE RETROVIRUS WORK, SHOWED THE SLIDE IN WHICH HE
SHOWED CLEARLY HAD ALL THE DATA SHOWING THAT SPLICING WAS
GOING ON AND SO HE WAS ABLE TO EXPLAIN IT IN
TERMS OF SPLICING. AT LEAST HE DIDN'T TRY
TO CLAIM HE DISCOVERED IT BUT AN AWFUL LOT OF
PEOPLE AT THAT TIME DID TRY TO CLAIM THEY HAD DISCOVERED IT. AND THAT WAS KIND
OF DISAPPOINTING THAT SOMETHING LIKE
THAT GOES ON.

NOW, THE FIRST THING WE
DID AFTER THIS, YOU KNOW, YOU MAKE A BIG DISCOVERY,
YOU WANT TO CAPITALIZE ON IT. WHAT CAN YOU DO? WELL, MOST OF THE STUFF THAT REALLY NEEDED DOING
WAS ALL ELECTRON MICROSCOPY. AND OF COURSE AS I SAID,
NEITHER RICHARD NOR I WERE ELECTRON MICROSCOPISTS. AND SO TOM BROKER AND LOUISE
CHOW WERE ABLE TO GO ON AND PRODUCE JUST BEAUTIFUL
WORK SHOWING WHAT WAS GOING ON USING ELECTRON
MICROSCOPY TO WORK OUT WHERE ALL THE
MESSENGERS WERE COMING FROM.

RICHARD AND I DECIDED WE WOULD
TRY TO DO SOMETHING IN VITRO. MAYBE WE COULD WORK
OUT THE BIOCHEMISTRY OF THIS PROCESS BY
DOING IT IN VITRO. AND WE SET UP THE SYSTEM
AND STARTED TO DO SOME WORK BUT WE ACTUALLY, WE PICKED THE
WRONG RNA POLYMERASE IN ORDER TO MAKE THE RNA IN
VITRO AND TOM MANIATIS AT HARVARD PICKED THE RIGHT RNA
POLYMERASE AND SO HE WAS ABLE TO MAKE HAY ON IN VITRO
SPLICING, SET IT ALL UP, DISCOVERED LAUREATES– JUST
DISCOVERED A HUGE AMOUNT OF STUFF ABOUT HOW TO DO
IT WAS IMMENSELY SUCCESSFUL AND WE GOT NOWHERE.

SO, FOR US, THIS WAS A
GREAT DISAPPOINTMENT. SO, I SORT OF SETTLE
BACK AND DID MORE OF THE RESTRICTION ENZYMES WORK
WHICH IS REALLY BEEN A LOVE OF MINE FOR THE WHOLE
OF MY LIFE. SO, BUT ONE OF THE THINGS THAT
WE DID DO AT THIS TIME WAS TO REALIZE THAT IF IN FACT,
THERE WERE SIGNALS IN THE DNA THAT WOULD BE NECESSARY
TO TELL THE ORGANISM WHERE TO DO THE SPLICING
PROCESS, MAYBE BY LOOKING AT SEQUENCES, WE
COULD FIND THEM. AND SO ONE OF THE THINGS
WE GOT VERY INTERESTED IN WAS USING COMPUTER
PROGRAMS TO LOOK AT DNA AND RNA SEQUENCES. THIS WAS A TIME BEFORE
THERE WAS SUCH A TERM AS BIOINFORMATICS NOBODY
KNEW ABOUT ANYTHING OF THAT AND THERE WERE NO PROGRAMS TO
BE DOING THIS SORT OF STUFF. AND SO WE ENDED UP
WRITING A LOT OF SOFTWARE, I ENDED UP TEACHING
MYSELF HOW TO PROGRAM BECAUSE THIS WAS REALLY
SOMETHING THAT WAS VERY NEW AND THE TRADITIONAL
PROGRAM IS WHAT WE NEED TO DO WAS REALLY TRIVIAL STUFF
AND THEY WERE ONLY INTERESTED IN THE MORE DIFFICULT STUFF. AND ABOUT THAT TIME, ONE OF
THE PEOPLE THAT I INTERACTED WITH IS THE MAN CALLED
CARTER BURWELL WHO IS NOW– HE WRITES MUSICAL SCORES.

HE WAS A PROGRAMMER
AT COLD SPRING HARBOR AND ESSENTIALLY EVERY
TIME I HAVE PROBLEMS WHEN I WAS LEARNING HOW TO
WRITE PROGRAMS, I'D GO TO HIM AND HE PUT ME STRAIGHT
AND TOLD ME WHAT TO DO. HE WAS ACTUALLY UP FOR
AN OSCAR ON SUNDAY NIGHT. THEY DIDN'T WIN UNFORTUNATELY. THERE WERE A LOT OF US FROM COLD
SPRING HARBOR REALLY ROUTING FOR HIM. HE WAS JUST A GREAT GUY. HE WROTE THE MUSICAL
SCORE FOR CAROL, IF ANY OF YOU KNOW
HAVE SEEN THAT MOVIE. ANYWAY, HE'S REALLY A GREAT GUY. SO HE– I OWE HIM A GRATITUDE
OF THAT TOO BECAUSE ONE OF THE THINGS THAT I LOVE
IS COMPUTER PROGRAMMING, COMPUTER PROGRAMS,
BIOINFORMATICS AND A LOT OF WHAT I DO THESE
DAYS IS BIOINFORMATICS. SO, THIS IS RICHARD GELANIS,
THE GUY WHO DID THE BOOK OF THE EXPERIMENTAL WORK
ON THE BIOCHEMICAL SIDE OF SPLICING BETWEEN– BEFORE
TOM AND LUIS CAME ALONG.

HE IS NOW WORKING AT THE
INSTITUTE FOR SYSTEMS BIOLOGY THAT LEE HOOD SETUP IN SEATTLE. THIS WAS THE FIRST PAPER THAT
WE PUT AT ON THIS SHOWING ABOUT THIS LONG OLIGO
THAT WAS PRESENT ON ALL OF THE MESSENGER RNAS. OK. AND THEN THIS WAS THE
DISCOVERY OF RNA SPLICING. WE CALL THE PAPER– WE
HAD A LOT OF DISCUSSION ABOUT HOW WE SHOULD TITLE
THIS PAPER AND IN PARTICULAR, THE WORD AMAZING, YOU KNOW,
YOU CAN THINK OF MANY WORDS THAT YOU COULD PUT HERE. AND SO, I'D LIKED AMAZING. AND SO WE SENT IT IN AND
THREE REFEREES ALL WROTE BACK AND SAID AMAZING WAS AN
APPROPRIATE WORD TO USE IN THE TITLE OF A PAPER AND
BEN LEWIN WAS THE EDITOR AND HE WROTE A LETTER
AND SAID, "YOU KNOW, IF WE COULD CHANGE
THIS WORD AND DO ONE OR TWO MINOR REVISIONS,
WE'D BE OK." AND SO I CALLED HIM UP AND
STARTED TALKING AND I– DURING THE CONVERSATION I SAID,
"YOU KNOW, WHEN YOU FIRST HEARD ABOUT THIS, WHAT DID YOU THINK?" AND HE SAID, "OH, IT'S AMAZING." I SAID, "I REST MY CASE." SO, BY A LITTLE BIT OF TRICKERY,
I CONVINCED HIM THIS WAS OK.

SO, APPARENTLY, THIS
IS THE FIRST TIME THAT THE WORD AMAZING WAS
EVER USED IN THE TITLE OF A SCIENTIFIC PAPER. SO, I'M KIND OF PROUD
OF THAT TOO. SO THIS IS NEW ENGLAND BIOLABS AND WHEN I MOVED THERE WERE
JUST THREE PEOPLE WORKING THERE. IN 1992, AFTER I'VE BEEN AT
COLD SPRING HARBOR FOR 20 YEARS AND HAD BECOME ASSISTANT
DIRECTOR, I'M KIND OF GOT BORED WITH THE ADMINISTRATIVE
WORK THAT WAS INVOLVED THERE AND I DECIDED I WAS GOING TO
MOVE, I THOUGHT I MIGHT SETUP UP A SEQUENCING COMPANY,
THIS WAS AT THE TIME WHEN PEOPLE GOT INTERESTED IN
SORT HIGH TROOP OF SEQUENCING AND THEN WERE MACHINES
BEING MADE AND SO ON AND THEN NEW ENGLAND BIOLAB
HEARD THAT I MIGHT BE INTERESTED IN DOING SOMETHING ON THE
COMMERCIAL SIDE RATHER THAN JUST PURE RESEARCH.

AND SO THEY MADE ME AN OFFER
WHICH I FELT I COULDN'T REFUSE WHICH WAS BASICALLY THEY
SAID, "YOU KNOW, COME UP AND BE A RESEARCH DIRECTOR AND
YOU CAN DO WHATEVER YOU WANT ON THE RESEARCH FRONT," WHICH
SOUND PRETTY GOOD TO ME. SO THAT'S WHAT I DID,
I MOVED UP THERE. AND ONE YEAR LATER, OF
COURSE, I WON THE NOBEL PRIZE– OH LET ME– BEFORE
I DO THAT, LET'S– SO THIS WAS THE SECOND
BUILDING AFTER WE MOVED OUT OF THIS BASEMENT
UNDER THE HAIRDRESSER.

THIS WAS THE FIRST
BUILDING THAT WE PUT UP AND THEN THIS IS THE CURRENT
BUILDING THAT WE PUT UP IN 2005. WE'VE BEEN THERE
ABOUT 10 YEARS NOW. IT'S A BEAUTIFUL BUILDING. IF ANY OF YOU GET THE CHANCE
TO COME VISIT BIOLABS, YOU SHOULD CERTAINLY TAKE IT. IT'S ALMOST AN ART
GALLERY INSIDE. SO DON COMB IS VERY KEEN ON US. HE JUST LOVES ART
AND WE HAVE A LOT OF VERY INTERESTING ART INSIDE AND WE DO A LOT OF
RESEARCH THERE. NOW, SINCE MOVING TO BIOLABS,
THERE'S A BUNCH OF THINGS THAT I'VE DONE, GOT INVOLVED
IN CLONING RESTRICTION ENZYMES.

I'M NOT REALLY DOING A LOT
MYSELF BUT FINDING THINGS, EXPLORING THE LIMITS
OF BIOINFORMATICS AND THIS IS SOMETHING THAT
I'M REALLY VERY HEART ON, I'M KEEN ON BIOINFORMATICS
AT THE MOMENT AND MOST OF WHAT I DO THESE
DAYS IS ON A COMPUTER, ALTHOUGH I HAVE SMALL
WET LAB THAT FOLLOWS THROUGH ON THINGS I
SUGGEST THEY SHOULD DO. AND THEN WE DECIDED
THAT WHEN WE WERE TRYING TO CLONE ALL THE GENES FOR
OUR RESTRICTION ENZYMES THAT IT TURNED THAT
IT WAS NOT THAT EASY. RESTRICTION ENZYMES ARE
BIT DIFFICULT TO CLONE AND SO WE THOUGHT THE
THING TO DO WAS ACTUALLY TO JUST SEQUENCE THE
GENOMES FOR THESE THINGS. THIS WAS WHEN 454
SEQUENCING CAME ALONG.

AND SO FOR THE LAST 50
RESTRICTION ENZYME GENES, WE WANTED TO CLONE, WE SEQUENCE
THEM FIRST, USE BIOINFORMATICS TO FIND OUT WHERE THE
METHYLASES WERE AND THEN LOOKED AROUND TO SEE IF WE COULD FIND
THE RESTRICTION ENZYME GENES. AND THEN 48 OUT OF THE
50, WE WERE LOOKING FOR, WE WERE SUCCESSFUL IN
CLONING USING THAT METHOD. THE REASON I'M SO KEEN
ON BIOINFORMATICS IS THAT IF YOU LOOK AROUND, WHAT YOU SEE IS THERE'S
AN ENORMOUS AMOUNT OF SEQUENCING GOING ON. AND IF I JUST CLEAR ULTIMATELY,
WE'RE ONLY GOING TO KNOW ABOUT THE BIOLOGY ON THIS
PLANET BY SEQUENCING EVERYTHING. BUT IF YOU CAN'T
INTERPRET THAT SEQUENCE, WHAT'S THE POINT, WHY DO IT? AND SO, WE REALLY
FACED A BIG CHALLENGE.

WE'VE GOT TO UNDERSTAND HOW TO INTERPRET THIS SEQUENCES
PROPERLY AND AT THE MOMENT, THERE'S A TREMENDOUS AMOUNT OF
MONEY BEING SPENT ON SEQUENCING AND THERE IS MUCH LESS MONEY
BEING SPENT ON ACTUALLY TRYING TO WORK OUT WHAT
THE GENES ARE DOING. GIVE YOU AN EXAMPLE,
MYCOBACTERIUM TUBERCULOSIS. YOU KNOW, TUBERCULOSIS, NASTY
DISEASE, WE KNOW WHAT CAUSES IT, WE HAVE SEQUENCED
HUNDREDS OF ISOLATES OF MYCOBACTERIUM TUBERCULOSIS. HOW MANY OF THE GENES HAVE WE
ACTUALLY TRIED TO WORK OUT, WHAT THEY DO SINCE THE
FIRST SEQUENCE WAS DONE? THE ANSWER IS ABOUT A DOZEN.

OK. IT IS PATHETIC. IT IS ABSOLUTELY– HERE IS A
MAJOR KILLER, A REAL PROBLEM AND WE DON'T KNOW VERY
MUCH ABOUT THE GENOME AND WHAT THE GENES ARE
DOING AND HOW THEY ALL WORK AND WE HAVE TO DO MORE OF THIS. I THINK THERE ARE
SOME SERIOUS PROBLEMS. SO THIS WAS THE PRIZE WITH
PHIL SHARP AND MYSELF IN 1993. I HAVE TO TELL YOU I CAN TELL
YOU MORE LATER IF YOU WANT TO KNOW BUT THE SWEDES THROW
THE MOST MAGNIFICENT PARTY. IT IS JUST UNBELIEVABLE
WHAT THEY DO. YOU ARRIVE AT THE– WELL,
YOU GET ON THE PLANE TO GO OVER THERE AND THE FIRST THING
THEY DO IS ANNOUNCE THEY HAVE NOBEL PRIZE WINNERS ON
BOARD, THEY PROVIDE EVERYBODY WITH CHAMPAGNE AND THEY
ALL TOAST YOU, YOU KNOW.

AND THEN THIS IS WHY
YOU'RE STILL ON THE WAY. THIS WAS AT NEW YORK
AIRPORT PRETTY MUCH. YOU GET THERE, THEY GIVE YOU AN
ATTACHé AND YOU GO THROUGH FOR ABOUT 10 DAYS A SERIES OF
EVENTS IN WHICH IF ANYONE OF THESE EVENTS AT LUNCH TIME OR THE EVENING HAD BEEN THE
ONLY THING THAT HAPPENED TO YOU DURING THE COURSE
OF THAT YEAR, THIS WOULD BE ABOUT THE MOST MEMORABLE THING
THAT HAPPENED DURING THE YEAR. IT JUST GOES ON AND ON AND ON. IT'S FUN. I'LL RECOMMEND
IT TO EVERYBODY. [ LAUGHTER ] SO, ONE OF THE THINGS THAT WE
DID JUST BEFORE GOING TO SWEDEN, YOU KNOW, YOU HAVE TO
GIVE A NOBEL LECTURE.

AND YOU GOT TO GET THERE AND
YOU HAVE TO TELL EVERYBODY ABOUT ALL THIS WONDERFUL
THINGS THAT YOU'VE DONE SINCE YOU'VE MADE THE DISCOVERY. WELL AS I SAY, WE DIDN'T DO VERY
MUCH AND WE SEQUENCE ADENOVIRUS THAT WAS ABOUT IT BUT WE
REALLY DIDN'T DO ALL THAT MUCH AND IN MY RESEARCH HAD
SWITCHED COMPLETELY. AND WE WERE ACTUALLY INTERESTED
IN HHAI, A DNA METHYLASE AND WE HAD DISCOVERED ABOUT
THREE MONTHS BEFORE I HAD TO GO TO STOCKHOLM THAT THE WAY IN
WHICH THIS PROTEIN INTERACTS WITH DNA IS THE BASE THAT
IT'S GOING TO METHYLATE, IT FLIPS IT OUT OF THE HELIX, 180 DEGREES RIGHT
OUT OF THE HELIX. SO GOES INTO THE ACTIVE
SIDE OF THE PROTEIN, SO THE CHEMISTRY CAN BE DONE.

AND IF YOU IMAGINE, YOU KNOW,
ONCE YOU'VE GOT ALL THESE BASIS IN THE HELIX, IT'S
QUITE DIFFICULT TO DO CHEMISTRY ON THEM. AND SO WE HAD MADE THIS
DISCOVERY AND I WAS ABLE, AS MY NOBLE LECTURE, TO TALK
ABOUT THIS DISCOVERY, YOU KNOW, AND IF YOU MAKE A DISCOVERY,
THERE'S NO BETTER PLACE TO TALK ABOUT IT THAN IN STOCKHOLM, THIS
IS A LESSON WORTH LEARNING HERE. SO ANYWAY, SO THIS WAS
VERY GOOD AND WE PREDICTED THAT MANY ENZYMES THAT DID
CHEMISTRY WOULD DO THIS. WE NOW KNOW THAT THIS IS
TRUE, ALMOST EVERY ENZYME THAT DOES CHEMISTRY ON DNA
USES THIS SAME MECHANISM. AND NOT ONLY THAT,
IF YOU LOOK AT THIS, YOU CAN SEE HOW EASY
IT WOULD BE TO OPEN UP THE HELIX ONCE YOU FLIP ONE
OF THE BASIS AT AND WE NOW KNOW THAT RNA POLYMERASE WHEN
IT IS FIRST STARTING TO TRANSCRIBE DNA, IT
FLIPS OUT IN THE CASE OF E.

COLI BASE MINUS 11 TO THE
START POINT OF TRANSCRIPTION, THIS IS HOW IT BEGINS
OPENING UP THE HELIX. WE THINK THE SAME THING PROBABLY
HAPPENS FOR DNA REPLICATION TOO. SO THIS IS A– THIS WAS
A VERY NICE DISCOVERY. IT WAS SOMETHING GOOD TO BE
ABLE TO TALK ABOUT IN STOCKHOLM. NOW, AS I SAID RIGHT
FROM THE START, I'VE ALWAYS LOVE PUZZLES
AND GAMES AND SO ON. I SPENT MY NOBEL PRIZE MONEY
PUTTING A LOCAL CROQUET LAWN IN FRONT OF MY HOUSE. A GREAT EXPENSE I MIGHT ADD
AND I THINK EVEN TO THIS DAY, MY WIFE DOESN'T KNOW
QUITE HOW MUCH IT COST. BUT IT WAS VERY EXPENSIVE AND THE SCIENTIFIC AMERICAN
[INAUDIBLE] EXPLAINING HOW PEOPLE SPEND THEIR NOBEL PRIZE
MONEY AND THEY WERE TALKING ABOUT PEOPLE LIKE GUNTER
BLOBEL WHO GAVE HIS MONEY TO HELP REBUILD DRESDEN AND
THEY QUOTED ME AS SOMEHOW WHO SPENT IT IN A SOMEWHAT
LESS GOOD WAY AND SORT OF ESSENTIALLY THEY HINTED
THAT I'D WASTED THE MONEY BY PUTTING A CROQUET LAWN
IN FRONT OF MY HOUSE.

IN FACT, I HAVE THAT SO
MUCH ENJOYMENT OUT OF THIS. IT WAS WORTH EVERY PENNY
BUT WITHOUT THE PRIZE, I COULD NEVER HAVE AFFORDED IT. SO THAT WAS VERY NICE. I BECAME THE STUD MUFFIN OF SCIENCE ONE YEAR
IN THE 1997 CALENDAR. SOMEONE CAME AND APPROACHED
ME AND SAID WOULD I DO THIS, YOU KNOW, MOST OF THEM WERE– THE YOUNG GUYS, THEY HAD
HAIRY CHEST AND LOOK GOOD AND THE LADIES LIKED THEM. AND WHEN MY WIFE HEARD
ABOUT THIS AND HEARD THAT I'D SAID YES, AND THE
PHOTOGRAPHER WAS COMING, SHE LEFT THE HOUSE AND
SAID SHE DIDN'T WANT TO HAVE ANYTHING TO DO WITH IT. BUT LATER ON, SHE DECIDED IT WAS
ACTUALLY A LITTLE MORE TASTEFUL THAN SHE HAD IMAGINED. SO, THAT WAS VERY GOOD.

A FEW OTHER THINGS THAT HAVE
HAPPENED IN, WHENEVER IT WAS, 2005, THEY NAMED THIS
BUILDING AFTER ME AT SHEFFIELD. IN 2008, I WAS KNIGHTED
BY PRINCE CHARLES. THE CEREMONY IS SHOWN UP HERE. THIS IS ACTUALLY A VERY NICE
CEREMONY, YOU SORT OF GOING INTO BUCKINGHAM PALACE AND
YOU HAVE TO GO AND LAY SORT OF PRIME YOU AS TO WHAT
YOU'RE SUPPOSED TO DO. IT'S ALL INCREDIBLY FORMAL. BUT MY WIFE AND KIDS LOVED IT. THEY THOUGHT THIS WAS GREAT–
I THOUGHT IT WAS SORT OF OK. BUT THEY JUST LOVED IT
AND SO THAT WAS VERY NICE. AND ONE OF THINGS THAT
I'M RATHER PROUD OF IS THAT I'VE REALLY
HELPED TO ORGANIZE A LOT OF THE NOBEL LAUREATES
TO DO GOOD THINGS. AND THIS IS BECAUSE ONE
OF THE THINGS I FIND AS A NOBEL LAUREATE
IS THAT PEOPLE COME, THEY ASK FOR YOUR OPINION
ON THINGS, IRRESPECTIVE OF WHETHER YOU ACTUALLY KNOW
ANYTHING ABOUT IT OR NOT, BUT ANYWAY, THEY COME
AND ASK YOU YOUR OPINION AND THEY LISTEN. I'VE BEEN AMAZED AT
HOW MANY PEOPLE LISTEN. AND SO I THOUGHT WELL, YOU
KNOW, HERE IS AN OPPORTUNITY FOR THE NOBEL LAUREATES REALLY
TO TRY AND DO SOME GOOD.

AND SO HERE'S A FEW THINGS THAT I'VE GOTTEN
INVOLVED IN ORGANIZING. ONE WAS THE OPEN ACCESS
PUBLICATION INITIATIVE. THIS WAS SOMETHING THAT I
GOT QUITE A LOT OF LAUREATES, 49 SCIENCE LAUREATES TO SIGN ON
TO A PETITION THAT WE SENT OFF TO PUBLISHERS TO TRY AND
GET OPEN ACCESS GOING. IN 2006, THERE WAS AN ISSUE IN
THE BENGHAZI CHILDREN'S HOSPITAL WHERE MUAMMAR GADDAFI HAD
ACCUSED FIVE BULGARIAN NURSES AND ONE PALESTINIAN STUDENT
OF SPREADING HIV TO A LITTLE OVER 400 CHILDREN AND IT WAS
CLEAR AS THINGS DEVELOPED THAT THEY HAVEN'T DONE THIS. IT WAS JUST POOR MEDICAL
PRACTICE, YOU KNOW, IN LIBYA, I– MAYBE EVEN TODAY, THEY THOUGHT SHARING
NEEDLES WAS A GOOD THING. SO, YOU KNOW, YOU GET A VACCINE,
JUST GO VACCINATE EVERYBODY AND THEY SPREAD THE
VIRUS IN THIS MANNER. AND I ORGANIZED A
NUMBER OF LAUREATES. WE GOT 119 LAUREATES
TO SIGN A LETTER. I WENT TO THE LIBYAN EMBASSY
FOR THE UNITED NATIONS DOWN IN NEW YORK TALK TO THE
AMBASSADOR, I EVENTUALLY ENDED UP GOING OVER TO LIBYA
MEETING WITH GADDAFI'S SON AND WE GOT THE NURSES
ACT BASICALLY SO THAT WAS AN INTERESTING
THING OF SOMETHING WORTH DOING.

AUNG SAN SUU KYI IS THE PEACE
PRIZE WINNER WHO WAS IN– HAS ARREST IN BURMA
FOR A LONG TIME. WE GOT 219 LAUREATES
TO SIGN ON TO THAT AND WE TRIED TO DO
WHAT WE COULD. WE WERE NOT SUCCESSFUL
IN THAT ONE. LIU XIAOBO IS A CHINESE
PEACE PRIZE LAUREATE. HE IS IN JAIL IN CHINA AT THE
MOMENT AND WE'VE BEEN TRYING TO DO SOMETHING THERE. CAMP ASHRAF IS ANOTHER
THING I'VE BEEN INVOLVED IN. THIS IS A BUNCH OF
IRANIANS WHO ARE IN IRAQ AND CONSTANTLY BEING HARASSED. THE CIRCB IN CAMEROON WAS IN THE RESEARCH INSTITUTE
WORKING ON AIDS. AND IN THIS PARTICULAR
CASE, ONE OF OUR LAUREATES WHO WILL REMAIN NAMELESS
FOR THE PURPOSES OF THIS TALK REALLY DID SOME
VERY BAD THINGS AND HE WAS ABOUT TO BECOME DIRECTOR OF THIS
INSTITUTE WE GOTTEN THROWN AT. AND THE MOMENT, I'M VERY MUCH
STARTING A CAMPAIGN PRO GMOS, WHAT HAS BEEN GOING ON WITH
GENETICALLY MODIFIED ORGANISMS AND THE GREENPEACE AND THE OTHER
PARTIES WHO ARE AGAINST THESE AND TRYING TO GET GMOS AND
PRETEND THAT THEY'RE DANGEROUS WHEN THEY'RE CLEARLY NOT IS JUST
GETTING TOTALLY OUT OF CONTROL.

AND SO FAR, I HAVE 75
LAUREATES WHO SIGNED ON TO A LETTER THAT
WE'VE WRITTEN. WE'RE GOING TO LAUNCH A BIG
CAMPAIGN BEFORE TOO LONG. I HAVE A WEBSITE
ON PUTTING TOGETHER WHERE PEOPLE CAN JOIN US. I HOPE SOME OF YOU WILL
THINK THAT'S WORTHWHILE, BUT THIS IS ANTISCIENCE
OF THE VERY WORST KIND AND I THINK UNLESS WE CAN
GET SOMETHING DONE ABOUT IT, THE DEVELOPING WORLD ARE
GOING TO SUFFER TREMENDOUSLY. YOU KNOW, WE DON'T NEED GMOS. WE'RE FINE. WE HAVE PLENTY OF FOOD. BUT IN THE DEVELOPING WORLD,
IF THEY DON'T GET ACCESS TO THIS TECHNOLOGY,
THEY'RE GOING TO BE DEAD AND THAT ISN'T A GOOD THING. SO, JUST WANT TO FINISH TALK
ABOUT THE IMPORTANCE OF LUCK. OK. SO, ALMOST TIME. LET'S SEE HOW QUICKLY
I CAN GO THROUGH THIS. SO, I LEARNED MY FIRST LESSON
ABOUT LUCK PLAYING BILLIARDS. I WAS A VERY GOOD
BILLIARDS PLAYER, IN FACT, I ALMOST LOST A YEAR AT
SCHOOL BY PLAYING BILLIARDS AND SNOOKER INSTEAD OF
GOING TO SCHOOL AND I WENT TO AUDITION ACTUALLY TO BECOME
A PROFESSIONAL BILLIARDS PLAYER BECAUSE IT WAS PRETTY GOOD.

BUT ANYWAY THAT DIDN'T HAPPEN. THAT'S ANOTHER STORY BUT
THERE WAS AN OLD GENTLEMAN, ONE TIME HE WAS WATCHING
ME PLAY AND I HAD MADE A– I'D HAD A LUCKY SHOT AND I
JUST FLUFFED THE NEXT SHOT AND HE CAME UP TO ME AFTERWARDS
AND HE SAID, "YOU KNOW, THE IMPORTANCE OF LUCK
IS THAT EVERYBODY HAS IT AND WHEN YOU HAVE IT, IF
YOU DON'T TAKE ADVANTAGE OF IT, YOU'RE A FOOL." OK. BECAUSE MOST PEOPLE
WHEN THEY HAVE LUCK, THEY WILL TAKE ADVANTAGE OF IT. AND SO WHAT YOU HAVE TO DO WHEN
A LUCKY BREAK COMES YOUR WAY, CONCENTRATE EVEN HARDER ON THE
NEXT SHOT OR THE NEXT POINT IN YOUR CAREER OR
WHATEVER YOU'RE DOING.

EVERYBODY HAS LUCK, BUT YOU
DON'T WANT TO THROW IT AWAY. YOU HAVE TO MAKE THE
MOST OF IT AND I THINK THAT IS REALLY VALUABLE ADVICE. OH, SORRY. KAZU KUROSAWA WAS THE JAPANESE
POST DOC I TOLD YOU ABOUT. I ENDED UP AT HARVARD INSTEAD
OF GOING TO WISCONSIN WHICH IS WHERE I THOUGHT I WAS GOING
BECAUSE JACK MOVED JUST A COUPLE OF MONTHS BEFORE I HAVE TO GO. I'M LOOKING FOR EUKARYOTIC
PROMOTERS IN ADENOVIRUS. WELL, YOU KNOW, WE COULD
HAVE CHOSEN 100 PROJECTS, WE CHOSE THIS ONE. IT WAS LUCKY. HERE'S ONE THAT YOU
PROBABLY HAVEN'T HEARD ABOUT TAKING AN EARLY PLANE. YOU WILL KNOW WHAT HAPPENED
IN NEW YORK IN 9/11, THERE WERE TWO PLANES THAT
WENT INTO THE TWIN TOWERS.

THE FIRST OF THOSE
PLANES I WAS BOOKED ON. I– ABOUT A WEEK, 10 DAYS
BEFORE THAT HAPPENED, THE MEETING I WAS GOING TO
IN CALIFORNIA WAS CANCELLED AND MOVED A DAY EARLIER AND
SO I CHANGED MY RESERVATION ABOUT 10 DAYS BEFOREHAND
AND THEN I FLEW OVER TO CALIFORNIA ONE
DAY BEFORE THAT HAPPENED. BUT FOR THAT CHANGE IN MEETING,
I WOULD HAVE BEEN ON THAT PLANE AND I WOULDN'T BE
TALKING TO YOU TODAY. SO, LUCK IS UNBELIEVABLY
IMPORTANT AND EVERYBODY HAS IT, YOU KNOW, YOU JUST CAN'T BELIEVE
HOW IMPORTANT IT IS IN YOUR LIFE UNTIL IF YOU GO BACK AND START
LOOKING, YOU'LL FIND THERE A LOT OF LUCKY THINGS THAT
HAVE HAPPENED TO YOU. AND FINALLY, STUDYING BACTERIAL
RM SYSTEMS HAS JUST GIVEN ME SUCH A WEALTH OF FUN, ENJOYMENT,
BUT ALSO HAD A BIG IMPACT ON BIOLOGY, ON BIOTECH
INDUSTRY, GOT ME MY CURRENT JOB AND IT IS FUN AND I WILL TALK
TO YOU FOR THOSE OF YOU WHO WANT TO COME TO TALK LATER, I WILL TALK ABOUT WHAT I'M
CURRENTLY DOING WITH RM SYSTEMS WHICH I FIND INCREDIBLY
EXCITING.

SO, I SEE THE TIME
IS ALMOST GONE. WELL, LET ME JUST PUT
UP THIS LAST SLIDE. IT'S ABOUT HUMANS AND
BACTERIA, YOU KNOW, WE NOW KNOW THE METAGENOME
IS INCREDIBLY IMPORTANT. THE FUTURE OF MEDICINE IS
GOING TO BE HEAVILY INFLUENCED AS WE LEARN MORE
ABOUT THE METAGENOME. AND AN AWFUL LOT OF
BACTERIA THAT LIVE WITH US, A LOT OF VIRUSES THAT
LIVE WITH THE BACTERIA, WE KNOW ALMOST NOTHING
ABOUT THIS. AND SO I THINK HERE'S A GREAT
AREA FOR RESEARCH AND ONE THAT IS GOING TO HAVE A
MAJOR IMPACT ON MEDICINE. SO, I THANK YOU FOR
ALL YOUR ATTENTION AND IF YOU HAVE ANY QUESTIONS,
I'D BE HAPPY TO ANSWER THEM. THANK YOU. [ APPLAUSE ] I THINK THERE IS A MICROPHONE
CIRCULATING SOMEWHERE IF SOMEONE HAS A QUESTION. >> JUST OUT OF CURIOSITY, WHAT PROGRAMS DO YOU
USE OR LANGUAGES? >> WELL, I DON'T WRITE ANYMORE. I MEAN, I CAN TELL
YOU LITTLE ANECDOTES. SO I LEARNED FORTRAN. SO THIS WAS BACK IN THE LATE
1970S AND WHAT HAPPENED IS THAT ONE NIGHT, I WAS DEBUGGING
A PROGRAM, FINISHED IT, IT WORKED, LOOKED AT THE CLOCK,
IT WAS 8 O'CLOCK IN THE MORNING AND I HAVEN'T REALIZED
I'VE WORKED ALL NIGHT AND THE SAME THING HAPPENED
TO ME ABOUT THREE DAYS LATER AND I SAID, THIS IS IT, YOU
KNOW, I AM SO HOOKED ON THIS.

THIS IS GOING TO BE THE DEATH OF
ME AND SO I STOPPED PROGRAMMING AND NOW I HAVE OTHER
PEOPLE DOING IT. AND SO, ALL THE MODERN PROGRAMS
OR WHAT THE PROGRAM HAS WORKED FOR ME AND I'VE USED [INAUDIBLE]
SCRIPTS AND A VARIETY OF MODERN PROGRAMS
THAT ARE USEFUL. BUT I TRIED TO STAY AWAY FROM HAVING ALREADY
HAD THIS EXPERIENCE OF ALMOST OVERDOSING ON IT. >> I READ CRICK'S AUTOBIOGRAPHY
WITH GREAT INTEREST AND TOWARD THE END, HE SAID,
HUMANS WILL BECOME EXTINCT BUT WE AREN'T ANIMALS AND
WE WILL BECOME EXTINCT BUT WE WILL LIVE
ON IN ANOTHER FORM. CAN YOU ELABORATE
ANYMORE ON THAT? >> WELL YOU KNOW, I CAN'T BUT
I CAN TELL YOU WHAT I THINK OR THOUGHT ABOUT FRANCIS CRICK. HE WAS THE BRIGHTEST
HUMAN BEING I'D EVER MET. I MEAN, HE WAS ONE OF
THESE PEOPLE I MET FIRST WHEN I WAS A POST DOC AT
HARVARD AND I WAS EXPLAINING TO HIM WHAT I WAS DOING AND
HE MAPPED OUT ABOUT 20 YEARS OF RESEARCH FOR ME
DURING THE COURSE OF A HALF HOUR CONVERSATION.

HE WAS– AND I RUN INTO
HIM MANY TIMES AFTER THAT AND JUST AN INCREDIBLY
BRIGHT, SMART HUMAN BEING. SO MAYBE HAD SOME
INSIGHTS THAT I DON'T HAVE, BUT HE'S ONE OF MY GREAT HEROES. HE AND SYDNEY BRENNER,
VERY, VERY SMART PEOPLE. >> THANK YOU. >> SO IN YOUR TALK, YOU MENTIONED SEVERAL
INFLUENTIAL PEOPLE AND I'M CURIOUS HOW CAN YOU
DETERMINE WHETHER, YOU KNOW, SOMETHING IS GOING TO BE– SOMEONE IS GOING TO BE
A FRUITFUL COLLABORATOR OR IS GOING TO BE SORT OF GETTING A RESEARCH
MOVING FORWARD. HOW CAN YOU OR DO
YOU HAVE TO DETERMINE THAT OR YOU JUST USE LUCK? >> I MEAN, WHAT HAPPENS IS
THAT AS YOU MEET PEOPLE, YOU PRETTY SOON GET AN IDEA OF
WHO IS GOOD AND WHO IS NOT GOOD, RICHARD GELINAS FOR INSTANCE
WORKED IN AS A GRADUATE STUDENT IN [INAUDIBLE] LAB AND I
KNEW THAT EXPERIMENTALLY, HE WAS A VERY GOOD
EXPERIMENTALIST AND THIS WAS WHAT WAS NEEDED
FOR THIS KIND OF PROJECT.

AND WHAT I TYPICALLY LOOK FOR
IS PEOPLE WHO ARE ENTHUSIASTIC ABOUT WHAT THEY ARE DOING. SO, IF SOMEONE COMES AND
INTERVIEWS WITH ME FOR A JOB OR AS A STUDENT OR WHATEVER,
IF THEY ARE REALLY PASSIONATE ABOUT WHAT THEY WANT TO DO, I WILL TAKE THEM
ALMOST IRRESPECTIVE OF WHAT THEIR PREVIOUS
EDUCATIONAL BACKGROUND IS. I DON'T THINK EARLY EDUCATION
NECESSARILY TELLS YOU VERY MUCH ABOUT HOW GOOD SOMEONE IS
GOING TO BE IN THE LONG RUN. I MEAN, YOU KNOW, IF YOU LOOK
AT MY EDUCATIONAL BACKGROUND, YOU PROBABLY WOULDN'T
HIRE ME, SO. >> WHAT DO YOU CONSIDER
THE MOST UNDERRATED AND OVERRATED DISCOVERY OF MAYBE
THE PAST DECADE IN SCIENCE? >> OH GOSH. [ LAUGHTER ] >> WELL, YOU KNOW, ONE OF THE BIG DISCOVERIES IS
OBVIOUSLY CRISPR AND THE FACT THAT YOU CAN EITHER
GENOME EDITING WITH IT, IT IS QUITE POWERFUL.

WILL THAT BE THE BEST WAY
OF DOING GENOME EDITING? I DON'T KNOW. YOU KNOW, THIS CAME ALSO FROM STUDYING BACTERIAL
IMMUNE SYSTEMS. BACTERIA DO THE MOST
AMAZING THINGS. PROBABLY THE MOST
UNDERRATED DISCOVERY, I WON'T SAY THE LAST 10 YEARS
BUT THE FACT THAT THE DISCOVERY THAT THE DNA WAS A GENETIC
MATERIAL WHICH WAS MADE BY MCCARTY AND MACLEOD, THIS–
THEY NEVER GOT THE NOBEL PRIZE FOR THIS AND THEY
SHOULD HAVE DONE. I MEAN, THIS WAS AN
ABSOLUTELY MONUMENTAL DISCOVERY WHICH EVERYTHING ELSE FOLLOWED ON DNA REALLY DEPENDENT
UPON VERY HEAVILY. IN RECENT YEARS, I DON'T KNOW. IT'S REALLY HARD TO KNOW. I DON'T HAVE– I MEAN, I
CAN'T THINK OF A FEW THINGS THAT I DON'T THINK WAS SO GREAT
THAT HAVE BEEN LAUDED, THAT'S– ON THE WHOLE, I DON'T
WANT TO GO INTO THAT. >> YOU TALKED ABOUT
THE IMPORTANCE OF LUCK, WHAT ABOUT INTUITION
IN YOUR MIND, IS THAT PLAYING A PART FOR YOU? >> WELL, YOU KNOW, INTUITION
IS A VERY INTERESTING THING.

I DON'T KNOW IF YOU'VE READ
DANIEL KAHNEMAN'S BOOK. SO HE HAS A BOOK CALLED
THINKING, FAST AND SLOW. KAHNEMAN WAS A PSYCHOLOGIST
WHO WON THE ECONOMICS PRIZE. I HAD THIS BOOK CALLED THINKING,
FAST AND SLOW AND HE TALKS ABOUT THE WAYS IN WHICH
WE THINK ABOUT THINGS. AND THE THINGS THAT MOST PEOPLE AND CERTAINLY MOST LADIES
THINK OFF AS INTUITION IS SORT OF THIS FAST TRACK SOMEBODY
ASKED YOU A QUESTION OR YOU SEE SOME FACTS AND
YOU IMMEDIATELY THINK YOU CAN EXPLAIN THEM. AND THIS IS SORT OF
THE INTUITIVE THING. IT'S THE WAY THAT THE BRAIN
TYPICALLY REACTS TO THINGS, BUT THEN SOMETIMES,
YOU HAVE TO LOOK BACK AND YOU CAN'T IMMEDIATELY
SAY SOMETHING THEN YOU HAVE TO REALLY SIT AND
THINK AND ANALYZE IT.

AND A LOT OF PEOPLE WHO
USE INTUITION DON'T GO BACK AND DO THE ANALYTICAL STUFF
THAT IS REALLY NECESSARY. SO PERSONALLY, I'M NOT A
BIG BELIEVER IN INTUITION. I MEAN I THINK YOU CAN GET A GUT
FEELING THAT AN AREA IS GOING TO BE AN IMPORTANT OR THAT
SOMETHING IS WORTH DOING AS I JUST DID WITH METAGENOMICS. I MEAN I THINK THESE
BACTERIA THAT LIVED WITH US, THEY ARE GOING TO
BE VERY IMPORTANT AND WE ALREADY KNOW THEY ARE.

THERE ARE ALREADY ENOUGH
ANECDOTES OUT THERE TO SHOW YOU THAT THEY ARE GOING
TO BE VERY IMPORTANT. IF THAT'S INTUITION,
WELL, SO BE IT BUT I THINK IT'S REALLY
OBSERVATION LOOKING AROUND, SEEING WHAT'S GOING ON AND THEN
TRYING TO PUT THINGS TOGETHER AND SAY, WELL, THIS WOULD BE A
GOOD AREA TO GET INVOLVED IN. >> LOOKING AT THE SLIDE UP THERE
ABOUT HUMANS AND BACTERIA– >> UM-HMM. >> — WHAT DO YOU THINK IS
GOING TO HAPPEN WITH THE WAR BETWEEN HUMANS AND BACTERIA? >> WELL YOU KNOW, ULTIMATELY,
THE BACTERIA ALWAYS WILL WIN.

SO I ACTUALLY HAVE
A TALK THAT I GIVE ABOUT WHY YOU SHOULD
LOVE BACTERIA THAT KIND OF DEALS WITH, FIRST OF
ALL, HOW DIVERSE THEY ARE, HOW INTERESTING THEY ARE, HOW
THEY'VE GOTTEN REALLY BAD WRAP BECAUSE FOR 100 YEARS, THE
MICROBIOLOGIST HAVE ONLY FOCUSED ON THE PATHOGENS, WHEREAS, MOST BACTERIA ARE NOT
PATHOGENIC, THEY'RE FINE. BUT I HAVE A SLIDE I SHOW
AT THE END OF THAT TALK WHICH IS A PICTURE OF
MARS AND I SAY THAT I HOPE THAT BEFORE I DIE, WE WILL
DISCOVER THAT THERE IS A LIFE ON MARS THAT IT'S
BACTERIA LIVING, MAYBE SEVERAL MILES
BETWEEN THE SURFACE. BUT THEN WHEN WE
START SEQUENCING IT, WE DISCOVER IT'S ACTUALLY
OLDER THAN LIFE ON EARTH AND THAT WE CAME HERE BY
FRANCIS CRICK'S IN SPERMIA, IN WHICH CASE MEANS
WE'RE REALLY ALL MARTIANS AND THAT WOULD BE WONDERFUL. I WOULD LIKE THAT VERY MUCH. >> OK. SO WITH THAT, WE'RE GOING
TO END THE GENERAL PROGRAM.

IF YOU GUYS ARE FREE, PLEASE
ATTEND THE TECHNICAL LECTURE AT 4 TO 5 AND THANK YOU
ALL AGAIN FOR COMING. IF WE CAN GIVE ANOTHER
ROUND OF APPLAUSE FOR SIR RICHARD ROBERTS? [ APPLAUSE ] >> THANK YOU. [ APPLAUSE ].

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