caption

Nobel Laureate Sir Richard Roberts PH.D.

[ MUSIC ] >> GOOD MORNING. SO, I HAD ALMOST A PAGE OF
INFORMATION FOR INTRODUCTION AND DOCTOR– AND SIR
RICHARD ROBERTS TOLD ME THAT I SHOULD JUST SO MUCH
OF IT, BECAUSE HE'S GOING TO TALK MORE ABOUT
HIS BIOGRAPHY FOR YOU. SO, THERE ARE JUST TWO
THINGS I WANT TO SAY, ONE WAS THAT AS I
WAS REMINISCING ABOUT NEW ENGLAND BIOLABS
OR NEB, WE WERE CHATTING, WHERE HE IS NOW AND HAS
BEEN FOR MANY YEARS, HOW NEB WAS OUR BIBLE AS
WE WERE IN GRADUATE SCHOOL. THE CATALOGUES WERE BETTER
THAN ANY BOOK AVAILABLE AND THEIR ENZYMES WERE MAGICAL.

SO, WE ARE THANKFUL
TO, YOU KNOW, ALL HIS LEADERSHIP
IN THAT COMPANY. AND THE SECOND THING I WANTED TO
BRUSH ON WAS THAT HIS DISCOVERY OF SPLIT GENES, AND HE'LL
DETAIL THAT MORE FOR YOU, WAS TRULY A PARADIGM SHIFT. IN FACT, IT WAS A TECTONIC
PARADIGM SHIFT AND HE WILL GO INTO IT BECAUSE THE DOGMA
AT THE TIME WAS THAT A UNIT OF HEREDITARY INFORMATION
THAT WE CALL A GENE WAS– THE DOGMA WAS THAT
IT WAS CONTINUOUS. SO THEIR FINDINGS WERE
SHOWING THAT IT WAS NOT, THAT THESE GENES WERE
SPLIT, THEY WERE SPLIT GENES AND THEY DID THAT IN ADENOVIRUS,
BUT EVENTUALLY, WE HAVE SEEN THAT MOST LIFE FORMS HAS
SPLIT GENES INCLUDING US AND THAT HOW DO A SPLIT GENE
INFORMATION IS EDITED IS VERY IMPORTANT AND IT'S IMPORTANT
FOR NORMAL DEVELOPMENT AND FOR– AS WELL AS FOR HEALTH. SO, FOR THEIR SEMINAL
DISCOVERY OF SPLIT GENES, SIR RICHARD ROBERTS AND DR.
PHILLIP SHARP SHARED THE 1993 NOBEL PRIZE IN PHYSIOLOGY
OR MEDICINE.

SO, PLEASE HELP ME IN
WELCOMING SIR RICHARD ROBERTS. [ APPLAUSE ] >> WELL, THANK YOU VERY MUCH. IT'S A PLEASURE TO BE HERE. NICE TO SEE THAT THERE
ARE LOTS OF YOU OUT THERE. WE HAVE A LITTLE BIT
OF REVERBERATION HERE, THAT SOMETHING YOU
CAN FIX PERHAPS. [ INAUDIBLE REMARK ] WELL, WE COULD SEE. IS THAT BETTER NOW? IS IT GONE? MAYBE YOU TURN THIS OFF. DID YOU? PERHAPS, THAT'S GOOD. I TEND TO WALK WHEN I TALK AND
THERE IS NO CLOCK AT THE BACK SO I'M GOING TO MAYBE WALK
AROUND HERE A LITTLE BIT. I HAVE A CLOCK UP HERE WHICH IF
I DON'T SEE THE ONE OVER HERE. SO I WILL DO THIS TO KEEP IN
TIME BUT IT'S ALWAYS A MISTAKE IF ANY OF YOU EVER GET US
TO SETUP A LECTURE THEATER, ALWAYS PUT THE CLOCK AT THE
BACK SO THE SPEAKER CAN SEE IT AND NEVER AT THE FRONT WHERE
THE STUDENTS CAN SEE IT BECAUSE THEY ARE JUST INTERESTED
IN WHEN IT'S ALL GOING TO END SO THEY GET ON WITH
THE NEXT THING.

SO, WHAT I WILL TRY TO DO DURING
THE COURSE OF THIS TALK IS TO GIVE YOU SOME IDEA OF HOW
I CAME TO WIN THE NOBEL PRIZE, KINDS OF THINGS THAT I FOUND
TO BE IMPORTANT, AND I'M HOPING THAT ALONG THE WAY, I
CAN HIGHLIGHT ONE OR TWO OF THE THINGS THAT I LEARNED
AS A RESULT OF BEING A STUDENT AND FOLLOWING THIS PATH THAT
I THINK CAN REALLY BE USEFUL TO A LOT OF PEOPLE
AND TO A LOT OF YOU. AND I HAVE A LITTLE SUMMARY
AT THE END BUT I'LL TRY TO GO INTO SOME OF THIS
A LONG THE WAY.

NOW, I GREW UP IN ENGLAND, I WAS BORN OVER HERE
IN THE TOWN OF DERBY. WHEN I WAS FOUR YEARS OLD,
MY PARENTS MOVED TO THE TOWN OF BATH IN THE SOUTH WEST. DERBY IS NOT A PARTICULARLY NICE
CITY ALTHOUGH IT'S A LOT NICE IN THERE THAN IT WAS. I WAS BORN DURING
THE SECOND WORLD WAR AND THE ROLLS-ROYCE FACTORIES
THAT WERE MAKING ALL THE ENGINES FOR THE SPITFIRES THAT
THE RAF WERE USING TO GO AND BOMB GERMANY WERE
BEING MADE IN THE FACTORY ABOUT 10 MILES AWAY
FROM WHERE I GREW UP. AND AS A RESULT, ALL GERMAN
BOMBING CAMPAIGNS COMING IN ALL THE TIME AND MORE THAN
HALF THE HAZARDS IN THE STREET IN WHICH I LIVE HAD BOMB DAMAGE. THERE WAS A CHURCH OVER THE
WAY THAT HAD BOMB DAMAGE AND SO IT WAS NOT
THE NICEST TO PLACES.

BUT ON THE OTHER
HAND, IT'S LOVELY. IF ANY OF YOU EVER GO TO
ENGLAND AND YOU'RE LOOKING FOR A NICE PLACE TO GO
AND VISIT AFTER LONDON, THEN I SUGGEST YOU
TAKE THE TRAIN TO BATH, IT'S ABOUT TWO HOURS. YOU CAN SPEND THE DAY
THERE, WALK AROUND, IT'S JUST A BEAUTIFUL,
BEAUTIFUL CITY. SO, I HAD A REALLY A
GREAT CHILDHOOD IN BATH AND I'LL TELL YOU A
LITTLE BIT ABOUT IT. SO, ONE OF THE THINGS
THAT HAPPENED WHEN I WAS QUITE
YOUNG WAS I WENT TO ST. STEPHEN'S SCHOOL SHOWN
UP HERE, VERY SMALL SCHOOL, IT HAD FOUR CLASSES, HAD
25 KIDS EACH CLASS, 25, 30 KIDS IN EACH CLASS. AND IT WAS JUST AN ABSOLUTELY
TYPICAL SMALL TOWN SCHOOL. IT WAS NOT RELIGIOUS EVEN THOUGH
IT WAS CALLED ST. STEPHEN'S. BUT OF COURSE, YOU
KNOW, IN ENGLAND, ALL OF THE SCHOOLS ENDED UP GETTING THIS CHRISTIAN
NAMES ASSOCIATED WITH THEM.

BUT I DISCOVERED A LOT OF
THINGS HERE, BUT IN PARTICULAR, THE HEAD MASTER TURNED OUT TO HAVE A TREMENDOUS
INFLUENCE ON MY LIFE. ONE THAT AT THE TIME, I DIDN'T
REALLY APPRECIATE BUT LATER DID AND HE MUST HAVE SEEN SOMETHING
IN ME, I DON'T KNOW WHAT IT WAS, BUT HE USED TO COME AFTER SCHOOL
AND WOULD GIVE ME PUZZLES TO DO AND USUALLY, THESE WERE
LITTLE MATHEMATICAL PUZZLES AND I JUST LOVE THEM. I FELL IN LOVE WITH
PUZZLES AND GAMES AND I FELL IN LOVE WITH MATHEMATICS. AND JUST AS A RESULT
OF THIS ONE TEACHER WHO PROBABLY HAD A
GREATER INFLUENCE ON ME THAN ANYBODY ELSE
WHO I RUN INTO. BY AGE 11, I READ A BOOK, MY
FATHER BOUGHT ME THIS BOOK WHICH SAID HOW I BECAME A
DETECTIVE AND IT WAS SORT OF A STORY OF A DETECTIVE
AND IT SOUNDED FANTASTIC.

I MEAN THIS WAS ONE
OF THESE THINGS HERE WHERE YOU'RE PRESENTED WITH
CRIME SCENES, YOU'D GO OFF AND YOU SOLVE THE PROBLEM. I USED TO LOVE AGATHA
CHRISTIE AND ALL OF THESE– THESE NOVELS, BUT THIS BOOK
REALLY TOLD YOU HOW YOU COULD BECOME A DETECTIVE. AND SO, I WAS DETERMINED
FROM AGE 11, I WAS PASSIONATE ABOUT THIS. I KNEW THAT THIS WAS
WHAT I WANTED TO DO AND I THINK THIS IS SOMETHING THAT IS ACTUALLY A VERY
GOOD LESSON FOR EVERYBODY. IT'S ALMOST GOOD TO HAVE
A PASSION TO DO SOMETHING. OK. BECAUSE THEN, YOU CAN HAVE
A GOOD FOCUS TO YOUR LIFE. IT DOESN'T MATTER WHAT IT IS. MAYBE YOU LOVE VIDEO
GAMES, MAYBE YOU SAY, I'M GOING TO MAKE MY
LIFE PLAYING VIDEO GAMES. WELL, DON'T PLAY THEM,
MAYBE WHAT YOU WANT TO DO IS WRITE THEM, DEVICE
THEM, FIND SOME NEW ONES AND MAKE THAT INTO A CAREER. AND SO, I'M VERY,
VERY KEEN ALWAYS ON FOLLOWING YOUR PASSION. IF YOU HAVE SOMETHING YOU LOVE
TO DO, TRY AND MAKE A CAREER OF IT, AND THE GREAT THING
ABOUT IT IS THAT AFTER TWO OR THREE YEARS, YOU
GET PASSIONATE ABOUT SOMETHING ELSE,
FOLLOW THAT.

DON'T THINK THAT BECAUSE YOU
STARTED IN A PARTICULAR PATH THAT YOU HAVE TO FOLLOW IT. SO AS I SAY, THIS TEACHER,
MR. BROOKS [ASSUMED SPELLING] AT ST. STEPHEN'S
SCHOOL MAY REALLY GOT ME IN LOVE WITH PUZZLES. I GO NOWHERE WITHOUT A PUZZLE. I LIKE SUDOKUS. I PLAY CHESS. I LIKE CROSSWORD
PUZZLES, I PLAY GO. I LOVE GAMES OF THIS SORT. BUT THEN, I DISCOVERED CHEMISTRY
AND I DISCOVERED CHEMISTRY BECAUSE AS A CHRISTMAS
PRESENT, I WAS GIVEN ONE OF THESE SIMPLE LITTLE CHEMISTRY
SETS AND THIS WAS IN THE DAYS WHEN CHEMISTRY SETS
REALLY WERE CHEMISTRY SETS. THEY WERE NOT THESE RATHER
FLACCID THINGS THAT YOU FIND AT THE MOMENT WHERE YOU CAN'T
REALLY DO ANYTHING INTERESTING WITH THEM. IN THOSE DAYS, YOU ACTUALLY
COULD DO INTERESTING STUFF WITH THEM. YOU COULD SORT OF MIX THINGS
UP AND THEY TURN YELLOW AND RED AND SO ON AND I QUICKLY WENT
THROUGH ALL THE EXPERIMENTS THAT WOULD GIVE THEM WITH THE
CHEMISTRY SET AND THEN I WENT DOWN TO LOCAL LIBRARY AND
STARTED READING ABOUT CHEMISTRY.

WE DIDN'T HAVE THOSE
SORTS OF AY BOOKS AT HOME. I GREW UP IN RATHER POOR FAMILY BUT I WAS NOT AWARE
THAT I WAS POOR. WE HAD A GREAT PUBLIC LIBRARY. I JUST GO DOWN THERE
AND GET WHAT I NEEDED AND I GOT ABSOLUTELY HOOKED
ON CHEMISTRY AND I DISCOVERED THAT I COULD MAKE FIREWORKS
WITH THE CHEMICALS THAT WERE IN THE SET THAT I'VE
BEEN GIVEN FOR CHRISTMAS. AND SO FROM THEN ON, IT
WAS FIREWORKS EXPLOSIVES. I JUST LOVE ALL THIS
STUFF, YOU KNOW, AND DIDN'T DO MOST
OF IT AT HOME. MOST OF IT, WE– I SORT OF
WE WENT DOWN TO LOCAL CANAL WITH COUPLE OF FRIENDS OF MINE
AND WE SET OFF VARIOUS THINGS.

BUT I REALLY LOVED THIS AND THE
CHEMISTRY AND WHAT YOU COULD DO AND HOW YOU COULD MAKE THE
COLORS AND FIREWORKS AND SO ON AND IT'S INTERESTING BECAUSE
I'VE BEEN DOING A LITTLE INFORMAL SURVEY AMONG A LOT
OF, YOU KNOW, THE LAUREATES IN SCIENCE AND MORE
THAN HALF OF THEM, THIS IS HOW THEY GOT
INTERESTED IN SCIENCE. AND NOWADAYS, YOU KNOW, INSTEAD
OF SELLING CHEMISTRY SETS WHERE YOU CAN ACTUALLY
DO SOMETHING USEFUL AND HAVE SOME FUN AND, YOU KNOW, MAYBE RISK BLOWING
OFF A FINGER OR TWO.

THE POLITICIANS HAVE DECIDED WE
CAN'T DO THIS ANYMORE, RIGHT. THEY MAKE THIS UNBELIEVABLY
MUNDANE CHEMISTRY SETS, THEY WERE ABSOLUTELY HOPELESS. IT SAYS THOUGH THEY REALLY
DON'T WANT YOUNG PEOPLE TO GET INTERESTED IN
STEM SUBJECTS AND FIND OUT ABOUT CHEMISTRY
IN THE REAL WORLD. SO, IF I WERE A POLITICIAN, THIS
IS ONE THING I WOULD CHANGE. THE FIRST THING I WOULD DO,
LET KIDS GET ON AND DO THINGS THAT ARE DANGEROUS, YOU KNOW,
DANGEROUS WITH GOOD THING. ALMOST EVERYTHING WORTH
DOING IN LIFE IS RISKY. I ALWAYS THINK ABOUT SKIING. YOU KNOW, SKIING IS A GREAT
SPORT, BUT IT'S NEXT IN WAITING TO HAPPEN AND YOU DO IT
UNTIL YOU HAVE YOUR ACCIDENT AND THEN YOU STOP AND
YOU DO SOMETHING ELSE. LIFE IS– ALMOST EVERYTHING IN LIFE REALLY WORTH DOING
IS A LITTLE BIT RISKY. SO, THIS WAS BATH. THIS WAS THE HIGH
SCHOOL I WENT TO. SO, THE CITY OF BATH
BOYS GRAMMAR SCHOOL. SO IN THOSE DAYS, THE
KIDS WHO WERE CONSIDERED TO BE A LITTLE BIT SMARTER
AND THE OTHERS WERE SENT OFF TO THE GRAMMAR SCHOOL. KIDS WHO TO LOOK TO SO
THEY MIGHT BE VERY GOOD AT MORE TECHNICAL
THINGS WERE SENT OFF TO A MORE TECHNICALLY ORIENTED
SCHOOL, BUT NOT SOMEONE WHO WAS GOING TO HAVE AN
ACADEMIC CAREER OF ANY SORT.

OK. AND SO, WHAT HAPPENED AT
THE SCHOOL AND I GOT THERE, I CAN TELL YOU WHY I GOT THERE, I GOT THERE BECAUSE I GOT THE
HIGHEST SCORE IN MATHEMATICS OF ANYBODY OF MY YEAR IN BATH. I DIDN'T FIND OUT THIS
UNTIL MANY YEARS LATER BUT THIS IS WHY THEY
SENT ME THERE. BUT OF COURSE BY THIS TIME, I STILL GOT A LITTLE BIT
MORE INTERESTED IN CHEMISTRY THAN I WAS IN MATH BUT I WAS
ALWAYS STILL GOOD AT MATH.

SO, I INCREASED MY
LOVE OF MATHEMATICS. WE HAD A VERY GOOD MATH TEACHER. ACTUALLY, WE HAD A COUPLE
WHO ARE REALLY GOOD. SO I LOVE THAT AND I
LEARNED TO PLAY THE VIOLIN, I WENT TO SCHOOL
ORCHESTRA AND SO ON. AND THAT'S FOR A WHILE WAS VERY
NICE BUT WHEN I LEFT SCHOOL AND WENT TO UNIVERSITY, I APPLIED TO JOIN THE UNIVERSITY
ORCHESTRA AND I WAS TOLD THAT UNLESS YOU WERE
MUSIC MAJOR, YOU COULDN'T JOIN
THEIR ORCHESTRA.

I MEAN, IT WAS APPALLING
AND SO FOR MANY YEARS, I ABANDONED THE VIOLIN ALL
TOGETHER AND I ONLY PICKED IT UP LATER WHEN MY OLDEST
DAUGHTER GOT INTERESTED IN DOING SOMETHING AND WE
DID IT TOGETHER FOR A WHILE. WE ALSO IN BATH, IS VERY CLOSE TO THIS LIMESTONE
ESCARPMENT CALLED THE MENDIPS, VERY NICE CAVES,
EXCELLENT CAVES THERE. AND I LOVE THIS BECAUSE
CAVING IS ALSO A FORM OF DETECTIVE WORK,
YOU KNOW, YOU GO DOWN AND YOU CAN MAKE DISCOVERIES.

YOU GO DOWN, YOU SEE A
LITTLE TUBE AND YOU THINK OH, LET'S GO THROUGH THERE
AND SEE WHAT'S THERE. AND SO I MADE A FEW DISCOVERIES
UNDERGROUND ON MENDIP. AND AGAIN, IT'S THIS IDEA THAT
BEING THE FIRST TO DO SOMETHING, BEING THE FIRST TO
FIND SOMETHING, THIS FOR ME IS ALWAYS
BEEN VERY EXCITING. I LOVE THIS FEELING WHEN
YOU DISCOVER SOMETHING FOR THE FIRST TIME. IT DOESN'T MATTER
WHAT IT IS, YOU KNOW, MAYBE IT'S JUST A TOURIST
DESTINATION BUT I LIKE THE IDEA OF FINDING STUFF AND I
ALSO DISCOVERED JAZZ, WHICH I LIKE VERY MUCH BUT
MORE TRADITIONAL JAZZ AND SORT OF ST. LOUIS STYLE OF JAZZ. BATH BECAME QUITE
FAMOUS FOR THAT AND WE HAVE THE FESTIVAL
EVERY YEAR AND THAT CONTINUOUS TO THIS DAY.

NOW, FOR UNIVERSITY, WHEN IT
CAME TIME TO GO TO UNIVERSITY IN ENGLAND, YOU HAVE TO TAKE
THESE EXAMS CALLED A LEVELS, ADVANCE LEVELS AND YOU TAKE
THIS NORMALLY WHEN YOU ARE 18 AND SO I TOOK THE EXAMS
AND FAILED PHYSICS. I HAD NEVER LIKE PHYSICS. I– THE TEACHER WAS AWFUL AND I JUST DIDN'T UNDERSTAND
A LOT OF WHAT WAS GOING ON. AND SO, I, YOU KNOW,
TRIED A LITTLE BIT BUT I JUST DIDN'T
DO WELL IN PHYSICS. AND SO BECAUSE OF THAT, I
COULDN'T GO TO UNIVERSITY AT 18 AS I NORMALLY WOULD HAVE DONE. I HAVE STAYED AT
SCHOOL FOR ANOTHER YEAR AND TAKE THE EXAMS AGAIN
AND THIS TIME, YOU KNOW, I ACTUALLY DID A BIT OF WORK
TO TRY TO GET THE PHYSICS RIGHT AND I MANAGED JUST TO SCRAPE
THROUGH AND AT THAT POINT, IT WAS NOT POSSIBLE FOR ME
TO GO OXFORD OR CAMBRIDGE BECAUSE THERE, THEY WOULD
ONLY TAKE THE VERY BRIGHT KIDS WHO WERE AGE 18 AND SO ON.

AND PLUS, THEY ACTUALLY
TURNED OUT NOT TO HAVE THE BEST CHEMISTRY
DEPARTMENTS IN ENGLAND. IT TURNED OUT THERE WERE
TWO UNIVERSITIES, SHEFFIELD AND SOUTHAMPTON, BOTH OF WHOM
HAVE REALLY HAVE CHEMISTRY DEPARTMENTS AND CHEMISTRY
WAS WHAT I WANTED TO DO AND SO I ENDED UP GOING TO
SHEFFIELD AND, YOU KNOW, THEY ACCEPTED ME AND I GOT A
STATE SCHOLARSHIP AND SO ON AND IT WAS ALL VERY GOOD. AND I LOVED THE CHEMISTRY THERE. IT WAS REALLY A CHANCE
TO BE A DETECTIVE BUT A DIFFERENT SORT
OF DETECTIVE. AND SO IN THIS CASE, YOU
COULD DO CHEMISTRY AND FIND OUT ABOUT THINGS AND
WE HAD A PROFESSOR, WD ALICE [ASSUMED SPELLING] WHO
WAS FANTASTIC AND HE THOUGHT IN A METHOD THAT IS VERY
DIFFERENT FROM THE WAY THAT MOST EVERYBODY ELSE HAS
THOUGHT FOR YEARS AND YEARS AND IN FACT, IS NOW THE METHOD THAT HE USES IS NOW BECOMING
FOUGHT OFF BY EDUCATORS AS A GOOD WAY TO DO
THINGS AND THAT IS INSTEAD OF TEACHING YOU HOW
TO REMEMBER STUFF SO THAT YOU COULD JUST
REGURGITATE IT IN AN EXAM, HE THOUGHT THE PRINCIPLES
OF THINGS AND HE THOUGHT YOU WHY
YOU NEEDED TO KNOW THIS AND HE PRESENTED CHEMISTRY AS A
PUZZLE BASICALLY AND THE EXAMS, EVERY EXAM THAT HE HAD WOULD
HAVE QUESTIONS OF THE FORM WELL, YOU GIVE– YOU WERE GIVEN THIS
COMPOUND AND YOU DID THIS TO IT AND GOT THIS RESULT
AND YOU DID THIS TO IT AND GOT THIS RESULT,
WHAT IS THE COMPOUND? AND SO, YOU COULDN'T SORT
OF LEARN THIS AHEAD OF TIME, YOU DIDN'T KNOW AND SO YOU
HAVE TO GO THROUGH THE BUSINESS OF LOGICALLY WORKING OUT,
WENT ON AND THIS TURNS OUT TO BE A GREAT
WAY TO TEACH PEOPLE.

AND FOR ME, THIS WAS
FANTASTIC, HAD A GREAT TIME. AND SO, WHEN I FINISHED
AS AN UNDERGRADUATE, I DECIDED I WAS GOING TO GO
INTO RESEARCH AND I CHOSE TO GO AND WORK IN HIS LAB. BUT IN FACT, WHAT
WAS INTERESTING WAS, IT WAS A TERRIFIC CHOICE
BUT NOT BECAUSE OF HIM, IT WAS A TERRIFIC CHOICE
BECAUSE IN HIS LAB, WE HAD A POST DOC CALLED
KAZU KUROSAWA FROM JAPAN AND HE IS PROBABLY THE
BEST TEACHER THAT I'VE COME ACROSS IN TERMS OF REALLY
TEACHING YOU HOW TO DO STUFF. HE WAS ONE OF THESE PEOPLE WHO
YOU GO TO HIM AND SAY, "WELL, YOU KNOW, I'VE BEEN TOLD
I'VE GOT TO DO THIS," AND SO HE WOULD SAY, "OH, YES,
YES," AND THIS IS HOW YOU DO IT, BUT HE'D EXPLAIN EXACTLY WHY YOU
WERE DOING WHAT YOU WERE DOING AND THEN WHEN YOU DID
IT, IT WOULD USUALLY WORK BUT YOU WOULD KNOW
WHY YOU'VE DONE IT. AND THIS IS SO IMPORTANT
ESPECIALLY WHEN YOU'RE DOING RESEARCH TO KNOW WHY YOU'RE DOING THE
THINGS YOU DO AND NOT JUST BECAUSE YOU'RE FOLLOWING
A RECIPE BUT BECAUSE YOU UNDERSTAND
WHAT IS GOING ON UNDERNEATH.

SO, HE WAS FANTASTIC AND
THAT WAS A VERY LUCKY BREAK IN MY LIFE. AND THE UNIVERSITY OF
SHEFFIELD WHO'S HAD A BUNCH OF NOBEL LAUREATES
ASSOCIATED WITH IT. UP HERE IS ONE OF THE
VERY FIRST HANS KREBS, THIS IS GEORGE PORTER, IT'S
HARRY KROTO WHO CAME ALONG JUST AFTER ME AND– SORRY, THIS
IS FLORY AND THIS IS KREBS. HERE IS ME. I TURNED OUT TO BE THE FIRST
STUDENT FORM SHEFFIELD EVER TO WIN A NOBEL PRIZE. THESE OTHER PEOPLE
WERE TEACHERS THERE. AND SO, WHEN THEY'VE DISCOVERED
THAT I'D WON THIS PRIZE, THEY MADE A GREAT FUZZ OF
ME WHICH WAS ALL VERY NICE, THERE'S ACTUALLY
A BUILDING THERE THAT THEY'VE NAMED
AFTER ME AND SO ON. BUT THEY WERE A GREAT
UNIVERSITY. I REALLY HAVE HAD
VERY GOOD INTERACTIONS FROM THE DAY I FIRST
WENT THERE UNTIL LATER. NOW, HARRY KROTO ALSO WAS
AT SHEFFIELD UNIVERSITY AND HE WAS THE SECOND
STUDENT TO WIN A NOBEL PRIZE. HE WON IT THREE YEARS
AFTER I DID BUT HE GONE THROUGH SHEFFIELD
THREE YEARS BEFORE ME, I NEVER ACTUALLY KNEW HIM
WHEN WE'RE IN SHEFFIELD BUT NEVERTHELESS, HE'S
A GREAT STORY TELLER.

HE'S WONDERFUL LECTURER AND SO HE ALWAYS MENTIONS
THE FACT THAT, YOU KNOW, THERE WAS THIS FELLOW, ROBERTS
WHO WON A NOBEL PRIZE BUT, YOU KNOW, HE WAS THREE
YEARS YOUNGER THAN HARRY AND SO HARRY THOUGHT
HIM EVERYTHING HE KNEW. AND SO, IN RECANTING THAT STORY,
I ALWAYS TELL EVERYBODY WELL, BUT, YOU KNOW, IT TOOK
HARRY ANOTHER THREE YEARS TO GET HIS NOBEL PRIZE. SO, THAT'S MAYBE
TELLING YOU SOMETHING. ANYWAY, WE'VE HAD A
LOT OF FUN ABOUT THIS.

HARRY IS A GREAT GUY. UNFORTUNATELY, HE HAS ALS AND
HE IS NOT IN VERY GOOD SHAPE, THAT'S LOU GEHRIG'S DISEASE. HE'S NOT IN VERY GOOD
SHAPE AT THE MOMENT, BUT HAS ONE OF THE
MOST WONDERFUL SENSES OF HUMOR EVEN NOW. SO, WHEN I WAS AT SHEFFIELD,
MY PHD THESIS PROJECT, I WAS GIVEN A PIECE OF WOOD
FROM A TREE IN BRAZIL AND ASK TO FIND OUT WHAT WAS IN IT. AND SO, THIS IS WHAT I
DID AND I WAS LOOKING FOR SOME PARTICULAR COMPOUND THAT MY CHEMISTRY PROFESSOR
HAD PREDICTED SHOULD EXIST AS A METABOLIC INTERMEDIATE
IN THE MAKING OF SOME COMPOUNDS
CALLED NEOFLAVONOIDS AND MANY OTHER STUDENTS HAD
BEEN GIVEN PIECES OF WOOD FROM DIFFERENT TREES AND NO
ONE HAD FOUND THIS COMPOUND THAT HE PREDICTED
SHOULD BE THERE.

AND IN MY TREE, IT WAS THERE. AND SO, HE THOUGHT THIS WAS
WONDERFUL, HE LET ME ALONE. I GOT EVERY SINGLE RESULT
I NEEDED FOR MY PHD THESIS AFTER ONE YEAR BECAUSE
OF THIS GUY KAZU KUROSAWA WHO MAKE SURE I DID ALL
THE RIGHT EXPERIMENTS. AND SO I ENDED UP AND
BECAUSE IN ENGLAND, YOU HAVE TO DO THREE YEARS
FOR PHD, I HAVE TWO YEARS TO REALLY DO WHATEVER
I WANTED TO DO. AND ONE OF THE THINGS THAT I
THOUGHT I WOULD DO WOULD BE TO SEE WHETHER I COULD ISOLATE
SOME OF THESE INTERMEDIATES IN THE SYNTHESIS OF
THIS NEOFLAVONOID. AND TO DO THAT, I LEARNED
SOME PLANT TISSUE CULTURE AND IT THOUGHT I COULD MAYBE DO. IT WAS A TOTAL FLOP,
IT WAS A DISASTER. NOT SOMETHING THAT
WAS GOOD FOR ME. BUT THE OTHER THING I DID
WAS I SPEND A LOT OF TIME IN THE LIBRARY AND
I WENT LOOKING AROUND THE LIBRARY LOOKING
FOR INTERESTING THINGS TO READ AND I CAME ACROSS THIS BOOK UP
HERE CALLED THE THREAD OF LIFE, AN INTRODUCTION TO
MOLECULAR BIOLOGY AND THIS WAS A BOOK WRITTEN
BY JOHN KENDREW WHO ALSO WENT ON TO WIN A NOBEL
PRIZE FOR THE STRUCTURE OF MYOGLOBIN, VERY
INTERESTING MAN.

BUT HE WROTE THIS BOOK THAT
DESCRIBED THE EARLY DAYS OF MOLECULAR BIOLOGY AND
IT WAS REALLY WRITTEN. HE WAS A CHEMIST AND
IT WAS REALLY WRITTEN FROM A CHEMICAL PERSPECTIVE AND
IT'S EITHER FANTASTIC, I MEAN, THIS MOLECULAR BIOLOGY STUFF, I
JUST COULDN'T GET ENOUGH OF IT. AND SO, BY THE TIME
I'D FINISH THE BOOK, I KNEW THIS WAS MY NEW PASSION. I WANTED TO BE A MOLECULAR
BIOLOGIST AND SO I WENT AND TALK TO MY PROFESSOR, ALICE, WHO
IMMEDIATELY SAID THERE'S NO SUCH THING AS MOLECULAR BIOLOGY
AND I STICK TO CHEMISTRY. AND IT TURNED OUT ALMOST
EVERYBODY IN THE DEPARTMENT OF CHEMISTRY IN SHEFFIELD
SAID THE SAME THING, YOU KNOW, THERE'S NO SUCH THING
AS MOLECULAR BIOLOGY, IT'S JUST CHEMISTRY
EXCEPT FOR ONE GUY, A GUY CALLED MIKE
BLAKBURN [ASSUMED SPELLING] WHO ENCOURAGED ME TO
SORT OF FOLLOW THIS LINE. SO, WHEN IT CAME TIME TO LOOK
FOR POST DOC, I APPLIED TO LABS THAT REALLY WOULD GIVE
ME THE OPPORTUNITY TO GET INTO MOLECULAR BIOLOGY AND
GET AWAY FROM CHEMISTRY.

I APPLIED TO SIC [PHONETIC]
LABS, THEY ALL TURNED ME DOWN EXCEPT FOR ONE
AND THE ONE PERSON WHO ACCEPTED ME WAS A GUY CALLED
STROMINGER, JACK STROMINGER. THAT'S THIS MAN HERE. HE AT THE TIME WAS A PROFESSOR
IN WISCONSIN AND HE HAD WORKED AT THE BASIC DETAILS BY WHICH
BACTERIA MAKE THEIR CELL WALLS. AND ONE OF THE THINGS HE
DISCOVERED ALONG THE WAY WAS THAT BACTERIA PUT AMINO ACIDS IN
AS A BRIDGE TO SORT OF CROSSLINK TO PEPTIDOGLYCAN THAT FORMS THE
BASIS OF THE CELL WALL TO SORT OF HOLD IT ALL IN PLACE AND I
WAS GIVEN THE TASK OF TRYING TO WORK OUT HOW THESE
AMINO ACIDS GOT IN. IT WAS KNOWN THEY USE TRNAS BUT NOT MUCH ELSE
WAS KNOWN ABOUT IT. SO, I GOT STARTED
ON THIS PROJECT. I WORKED WITH A MAN CALLED
TOM STEWART WHO WAS A POST DOC WHO OVERLAPPED WITH
ME FOR SIX MONTHS AND THE IDEA WAS
I WOULD JUST PICK UP HIS PROJECT AND
FOLLOW THROUGH. WELL, I GOT TO TELL YOU, WHEN I
GOT TO HARVARD AND SWITCH FIELDS AND I COULDN'T UNDERSTAND WHAT
ALL THESE PEOPLE WERE TALKING ABOUT, YOU KNOW, BECAUSE THEY
DIDN'T USE CHEMICAL TERMS, THEY ALL USED ACRONYMS.

YOU PROBABLY NOTICED THIS,
ANYBODY HERE WHO IS A BIOLOGIST, THERE ARE SO MANY ACRONYMS THAT
IF YOU ARE NEW TO THE FIELD, YOU HAVE NO IDEA WHAT
PEOPLE ARE TALKING ABOUT. AND I THINK THIS
IS ALSO SOMETHING THAT I'VE LEARNT ALONG THE WAY THAT COMMUNICATION IS INCREDIBLY
IMPORTANT THAT, YOU KNOW, WHENEVER YOU'RE TALKING
TO PEOPLE WHETHER THEY ARE IN YOUR FIELD OR OUT OF
YOUR FIELD, IT'S REALLY GOOD IF YOU CAN MAKE SURE THAT WHATEVER YOU TALK
ABOUT, THEY UNDERSTAND. AND I HAVE SOMETHING THAT I
ALWAYS MADE MY STUDENTS GO THROUGH WHICH I CALLED
THE GRANDMOTHER TEST. OK. NOW, THE GRANDMOTHER
TEST IS VERY SIMPLE ONE. THE STUDENT HAS TO
CONVINCE THEIR GRANDMOTHER THAT THE GRANDMOTHER
KNOWS WHAT THEY DO.

SO YOU GO THROUGH, YOU EXPLAIN
IT IN SUFFICIENTLY SIMPLE TERMS THAT AT THE END OF IT,
GRANDMOTHER GETS IT AND CAN THEN GO AND
TELL HER FRIENDS ABOUT HOW GREAT THE GRANDSON
OR GRANDDAUGHTER IS, RIGHT, BECAUSE THEY'VE ACTUALLY
UNDERSTOOD IT ALL AND I THINK THIS
IS SO IMPORTANT. I THINK WE SHOULD ALL DO THIS. IT'S VERY, VERY IMPORTANT
TO LEARN HOW TO COMMUNICATE WITH PEOPLE WHO ARE
NOT SPECIALISTS BECAUSE IT DOESN'T MATTER
WHETHER THEY ARE SPECIALIST OR NOT. YOU CAN USE THE SAME
LANGUAGE TO THE SPECIALIST TOO AND THEY'LL GET IT AS WELL. THAT WAS A LOT WITH SOMETHING
THAT I LIKE VERY MUCH. NOW, I WAS GIVEN THE TASK OF
SEQUENCING THIS GLYCYL-TRNA THAT WAS SPECIALIZED FOR
WORKING IN BACTERIAL CELL WALLS. AND AT THE TIME,
THIS WAS THE TIME WHEN THERE WERE ONLY A COUPLE OF METHODS AVAILABLE
TO SEQUENCE RNA.

IT WAS STILL VERY YOUNG
AND ONE GUY IN WISCONSIN, A GUY CALLED BOB HOLLY [ASSUMED
SPELLING] HAD DEVELOPED ONE METHOD OF DOING IT, WHICH
WAS UNBELIEVABLY TEDIOUS. I MEAN, IT REALLY WAS TEDIOUS
BUT BECAUSE TOM STEWART WHO HAD STARTED THE PROJECT THAT
COME FROM WISCONSIN TO HARVARD, HE WAS FOLLOWING THIS METHOD. WELL, I START– AFTER HE WENT,
I STARTED TO READ ABOUT IT AND DISCOVER IT WAS
A MUCH BETTER METHOD THAT WAS BEING PERFORMED BY
FRED SANGER IN CAMBRIDGE, THE MRC LAB IN CAMBRIDGE.

AND SO, THE FIRST THING I DID
WAS TO SAY WELL, YOU KNOW, I'M GOING TO ABANDON
THIS METHOD, THIS METHOD THAT HOLLY HAD
COME UP AND I WOULD GET GOING ON THIS SANGER METHOD. AND TO DO THAT, YOU HAD TO
MAKE VERY HIGHLY LABELED– P32 LABELED TRNAS. AND THIS WAS NOT SO EASY
BECAUSE I WAS WORKING ON ONE FROM A STAPHYLOCOCCUS AND
IT JUST WAS VERY DIFFICULT TO GET ENOUGH OF THE LABEL
TRNA IN ORDER TO THEN GO AND START DOING ALL THE METHODS. AND TO DO THAT, I HAD TO DO A
500 MILLICURIE PREP OF TRNA. SO I TOOK SOME STAPH AUREUS–
STAPH EPIDERMIDIS RATHER, GREW IT UP IN A VAT AND
WITH 500 MILLICURIE OF P32, 500 MILLICURIE OF P32
IS QUITE RADIOACTIVE. AT HARVARD, THERE WAS
SORT OF ONE WING OVER HERE AND ANOTHER WING FEW
HUNDRED FEET AWAY AND YOU COULD TAKE A
GEIGER COUNTER AND DETECT IT FROM ONE WING TO THE OTHER.

SO THIS WAS KIND OF FUN, YOU
KNOW, THIS WAS A SORT OF RISK THAT THE REGULATORS DON'T
LIKE YOU TO TAKE ANYWAY. SO, I– WE COULDN'T
DO IT AT HARVARD, THEY DIDN'T HAVE THE
APPROPRIATE FACILITIES, SO I WENT DOWN TO THE HOT LAB AT
MIT AND DID THE WORK DOWN THERE TO MAKE THIS TRNA AND
THEN WHEN IT HAD GOTTEN DOWN TO REASONABLE LEVELS, SUCH
THE HARVARD THOUGHT IT WAS OK TO HAVE A RENT [PHONETIC],
WE TOOK IT INTO THE COLD ROOM AND FINISHED OFF
THE PURIFICATION AND THE VERY FIRST BATCH,
THE FRACTION COLLECTORS STOCK OVER NIGHT AND EVERYTHING
WENT ON TO THE FLOOR OF THE FRACTION COLLECTOR. OK. SO THIS WAS– THIS WAS
PRETTY BAD, BUT JACK WAS KIND OF DECENT ABOUT IT, YOU KNOW,
HE SAID, OH, THIS WILL BE OK, WE'LL JUST GET ANOTHER BATCH
OF– AND THIS WAS NOT– THIS WAS AN EXPENSIVE
EXPERIMENT.

ANYWAY, SO WE GOT ANOTHER BATCH. SECOND TIME, I SAT UP ALL NIGHT AND WATCH THIS BLOODY
FRACTION COLLECTOR, YOU KNOW, TO MAKE SURE THAT WE DIDN'T
HAVE THE SAME PROBLEM. SO, MADE THE BATCH, TOOK IT
OVER AT FRED SANGER'S LAB, SPENT SIX WEEKS OVER THERE AND THOSE WERE INCREDIBLY
REWARDING WEEKS FOR MANY REASONS. SO, IN FRED SANGER'S LAB, HE HAD DEVELOPED PROTEIN
SEQUENCING TECHNIQUES AND WON THE NOBEL
PRIZE FOR THAT ALREADY AND HE SHARED THE DNA SEQUENCING
PRIZE WITH WALLY GILBERT. HE COULD EQUALLY HAVE HAD
A PRIZE FOR SEQUENCING RNA. THIS IS A MAN WHO
WHEN I FIRST MET HIM, I THOUGHT HE WAS A JANITOR. HE'S ONE OF THE MOST LOW KEY
PEOPLE YOU COULD IMAGINE. JUST UNBELIEVABLE AND YET A
TREMENDOUS TALENT, YOU KNOW, HE WAS JUST FANTASTIC,
OF COMING UP WITH IDEAS AND THEN TELLING YOU WELL,
YOU KNOW, MAYBE IT WOULD WORK AND VERY MODEST ABOUT
EVERYTHING.

BUT FOR ME, HE WAS
REALLY A MODEL SCIENTIST. I THINK THIS IS HOW ALL
SCIENCE SHOULD BE DONE. HE WAS A GREAT GUY. UNFORTUNATELY, WALLY
GILBERT [ASSUMED SPELLING] WHO SHARED THE PRIZE WITH HIM
IS A VERY DIFFERENT CUTTLEFISH AND WHAT HAPPENED IS THAT WALLY
CAME UP WITH A DIFFERENT METHOD WITH DNA SEQUENCING AND HE CAME OUT WITH A VERY DETAILED
PROTOCOL OF HOW TO DO IT AND FRED NEVER CAME
OUT UP WITH A PROTOCOL. AND THE BOTTOM LINE WAS THAT WALLY'S METHOD JUST
SPREAD EVERYWHERE AND IT WAS– HOWEVER YOU LOOK AT IT, IT
WAS DEMONSTRABLY INFERIOR TO FRED SANGER'S METHOD. AND SO I WAS THINKING,
YOU KNOW, WALLY, IF ANYTHING SET THE
FUEL BACK, YOU KNOW, HE SET DNA SEQUENCING BACK, IT WAS PROBABLY TWO YEARS BEFORE
FRED'S METHOD REALLY TOOK UP AT WHERE IT SHOULD HAVE GONE. AND ONE OF THE SADDEST
PARTS ABOUT THAT IS THAT IF WALLY HAD NOT
SHARED THE PRIZE WITH FRED, WALLY COULD HAVE GOTTEN
IT FOR SOMETHING ELSE. HE DISCOVERED THE LAC
OPERATOR AND WORK THAT, HAVE A LAC REPRESSOR-OPERATOR
INTERACTION WORKED, COULD HAVE SHARED THAT
PRIZE WITH MARK PTASHNE WHO DID THE SAME
THING FOR LANDER.

BUT THE NOBEL COMMITTEE,
THEY REALLY DON'T LIKE TO GIVE THE PRIZE
TO THE SAME PERSON TWICE IF THEY CAN AVOID IT AND SO, I
WAS TO SAYING THAT, YOU KNOW, IT WAS UNFORTUNATE
THAT BECAUSE OF THIS, MARK PTASHNE NEVER GOT
HIS PRIZE BUT, YOU KNOW, THE NOBEL PRIZE UNFORTUNATELY
IS FULL OF STORIES LIKE THAT OF PEOPLE WHO SHOULD
HAVE GOT IT AND DIDN'T. SO, WENT TO FRED'S LAB,
LEARNED HOW TO DO IT, LEARNED HOW TO SEQUENCE AND CAME
TO THE ATTENTION OF JIM WATSON AND ACTUALLY GOT TO KNOW
MARK PTASHNE VERY WELL BECAUSE I THOUGHT HIM HOW TO SEQUENCE USING
THE SANGER METHODS AND ALSO TOM [INAUDIBLE]
AND NUMBER OF PEOPLE.

I WAS THE FIRST PERSON IN THE
BOSTON AREA TO BE DOING THIS. I CAME TO YOUR ATTENTION
OF JIM WATSON. AND SO ONE DAY, I'M IN A SEMINAR
AND MARK PTASHNE COMES UP TO ME AND HE SAYS, YOU KNOW, JIM
WATSON IS LOOKING FOR SOMEONE WHO WILL SEQUENCE SP40 DNA
DOWN AT COLD SPRING HARBOR AND HE'S GOING TO COME UP
AND TALK TO YOU ABOUT THIS. SO, I SAID FINE, SO
I WAIT AND I WAIT AND I WAIT AND NO SIGN OF JIM. AND THEN MARK COMES UP TO ME
ABOUT TWO OR THREE WEEKS LATER IN ANOTHER SEMINAR AND SAYS, YOU
KNOW, JIM DOESN'T ACTUALLY KNOW WHO YOU ARE SO MAYBE YOU COULD
GO AND INTRODUCE YOURSELF. SO, I PROCEEDED TO DO THAT. WENT DOWN TO HIS OFFICE
BY 5 O'CLOCK AT NIGHT, 5:30 OR SOMETHING, KNOCKED ON
THE DOOR, WENT IN AND JIM SAYS TO ME, YOU KNOW, I SAY,
"I'M RICHARD ROBERTS" AND HE SAYS, "OH, YEAH, YEAH.

MARK TOLD ME ABOUT YOU." HE SAYS, "I WANT YOU TO COME DOWN AT COLD SPRING
HARBOR AND SEQUENCE SP40." AND THE WHOLE THING LASTED MAYBE
5, 10 MINUTES AND AT THE END OF IT, I'M JUST WALKING OUT OF
THE DOOR AND HE SAYS, "YOU KNOW, YOU PROBABLY SHOULD COME
DOWN AT COLD SPRING HARBOR AND GIVE A LITTLE TALK ABOUT BUT
YOU'RE DOING, BUT DON'T WORRY," HE SAID, "THE JOB IS YOURS." SO, YOU KNOW, THE SHORT
INTERVIEW, I GOT THIS JOB AT COLD SPRING HARBOR. SO I DID GO DOWN TO COLD SPRING
HARBOR AND DID GET THE JOB AND I SPEND 20 YEARS DOWN THERE.

I WAS FAIRLY HAPPY FOR
MOST OF THOSE YEARS UNTIL I BECAME ASSISTANT
DIRECTOR. THE PRIZE OF THAT
I COULD DO RESEARCH AND THEN MY RESEARCH KIND OF
DROPPED OFF AT THAT POINT. BUT I HAD A VERY GOOD TIME. HOWEVER, MOST OF THE TIME, I
WAS FIGHTING WITH JIM WATSON AND THE REASON IS THAT WHEN I
WENT DOWN THERE, I'VE BEEN HIRED TO SEQUENCE SP40 BUT I GET
DOWN THERE, I DISCOVERED THAT TWO MORE GROUPS
ALREADY SEQUENCING SP40. SO, YOU KNOW, WHY WOULD A
THIRD ONE WANT TO DO IT? AND SO I THOUGHT, WELL, WHAT
I'LL DO IS TRY TO DO SOMETHING THAT WILL SOUND AS THOUGH I'M
INTERESTED IN SEQUENCING SP40, BUT IN FACT, IT IS RATHER
DIFFERENT AND THAT WAS TO DEVELOP METHODS
FOR SEQUENCING DNA BECAUSE WHAT HAD HAPPENED IS THAT THE FIRST TYPE II
RESTRICTION ENZYMES HAD BEEN DISCOVERED BY HAM
SMITH AND IT WAS CLEAR THAT HERE WERE SOME
ENZYMES THAT WOULD TAKE DNA AND CUT IT UP INTO SMALL PIECES.

NOW, THE REASON THAT RNA
SEQUENCING WAS DEVELOPED BEFORE DNA SEQUENCING IS THAT
WHENEVER YOU'RE GOING TO PRODUCE NEW METHODS AND TRY
TO GET NEW METHODOLOGY GOING, YOU NEED SMALL THINGS
TO PRACTICE ON. CAN YOU COME PRACTICE ON
SOMETHING THAT IS SO BIG THAT YOU HAVE NO ALTERNATIVE WAY OF CHECKING WHETHER YOUR
ANSWER IS CORRECT OR NOT. AND IN RNA, THERE WERE
NICE SHORT RNA MOLECULES. YOU COULD DO IT BY SEVERAL
DIFFERENT METHODS AND KNOW THAT YOU WERE GETTING
THE RIGHT ANSWER. WITH DNA, THERE WERE
NO SMALL DNA MOLECULES. THAT'S ALL I THOUGHT THIS
RESTRICTION ENZYMES WERE GOING TO GIVE US THE OPPORTUNITY
TO MAKE THE SMALL DNAS THAT WE COULD USE TO BUILD
METHODS FOR SEQUENCING DNA. AND SO, ONE OF THE THINGS
I DID WHEN I GOT THEN AT COLD SPRING HARBOR,
I PURIFIED THE ONES THAT WERE KNOWN, THERE WERE
FIVE KNOWN AT THE TIME. AND THEN, DURING THE COURSE
OF PURIFYING, ONE OF THOSE, WE DISCOVERED THERE WERE
ACTUALLY TWO ENZYMES IN THERE, NOT JUST ONE AND I
BOUGHT THEM WITH ME FROM JACK'S LAB A
WHOLE BUNCH OF STRAINS BECAUSE I THOUGHT I MIGHT BE
END UP DOING A LITTLE WORK ON THE TRNAS INVOLVED
IN SOLE BIOSYNTHESIS.

AND SO I BROUGHT ABOUT 20
STRAINS FROM JACK'S LAB WITH ME IN CASE IF I WANTED
TO PURSUE THAT. AND SO, WE STARTED TO LOOK
THERE AND SEE WELL, YOU KNOW, DO THIS STRAINS HAVE RESTRICTION
ENZYMES IN THEM, LO AND BEHOLD, EVERYWHERE WE LOOKED, EVERY
STRAIN WE OPENED UP EXCEPT FOR JUST VERY FEW HAD
A RESTRICTION ENZYME AND THEY WERE ALL NEW, THEY ALL
RECOGNIZED DIFFERENT SEQUENCES. AND SO IT OCCURRED
TO BE THAT MAYBE, WE COULD USE THE SPECIFICITY OF
THE RESTRICTION ENZYMES IN ORDER TO WORK AT WHAT DNA
SEQUENCES WERE? AND SO, I WENT FULL
HEAD INTO THAT TO WHICH JIM WATSON
IMMEDIATELY CAME AND TOLD ME I WAS WASTING
MY TIME, THAT I WAS HIRED TO SEQUENCE SP40 AND WHY
DIDN'T I GET ON AND DO IT.

AND SO, WE HAD A FEW FIGHTS
ABOUT THAT, BUT I WAS CONVINCED THAT THESE RESTRICTION ENZYMES
WERE GOING TO BE USEFUL, NOT JUST FOR SEQUENCING DNA BUT
MORE GENERALLY FOR ALLOWING YOU TO MAKE SMALL PIECES OF
DNA THAT CARRY GENES, YOU COULD USE THEM FROM MAPPING. IT WAS JUST A MILLION
THINGS THAT COULD BE DONE. AND OF COURSE, THIS
LATER LED TO BE MET SOME OF THE MAJOR TOOLS
IN RECOMBINANT DNA.

AND SO WITH THAT, THESE ENZYMES, THE BIOTECH INDUSTRY WOULD
HAVE BEEN MUCH SLOWED IN ITS DEVELOPMENT. EVERYBODY WAS USING THIS. AND SO IN THE COURSE OF THIS,
WHAT HAPPENED WAS THAT I WENT TO JIM AND I SAID
LOOK, WE'VE GOT– IN THE TIME, WE HAVE 30 ENZYMES,
THEY WERE ALL DIFFERENT, ALL RECOGNIZED DIFFERENT
SEQUENCES, AND SO THEY START A COMPANY. LET'S SELL THIS ENZYMES
TO THE COMMUNITY INSTEAD OF GIVING THEM AWAY
WHICH WAS I WAS DOING. MAKE SOME PROFITS AND FEED THE
PROFITS INTO COLD SPRING HARBOR AND LET'S SUPPORT THE
RESEARCH AT COLD SPRING HARBOR IN THIS WAY TO WHICH JIM IN TYPICAL FASHION
SAID, "NOW YOU'RE CRAZY.

DON'T WANT TO DO THIS. IT'S VERY DIRTY TO BE
ASSOCIATED WITH INDUSTRY." AT FIRST, YOU KNOW, HE'S, "YOU
CAN'T MAKE MONEY ON DOING THIS," AND HE JUST– HE WAS
NOT INTERESTED AND YET HERE I AM WE'RE
GIVING ALL OUR STAFF AWAY. AND SO, I STARTED LOOKING AROUND
TO SEE IF THERE WAS SOMEONE ELSE WHO WOULD BE INTERESTED
IN THIS AND RUN INTO A FELLOW CALLED DON COMB WHO HAD STARTED NEW ENGLAND
BIOLABS, INVITED ME TO GO UP, I WENT UP AND DISCOVERED
THAT NEW ENGLAND BIOLABS AT THAT TIME WAS BASEMENT IN BEVERLEY [PHONETIC]
UNDERNEATH THE HAIRDRESSERS. THERE WAS DON COMB, HIS
WIFE AND ONE TECHNICIAN AND THEY WERE OPERATING ON
LITTLE MAKESHIFT BENCHES THAT THEY PUT TOGETHER AND
THEY HAD AN OLD CENTRIFUGE THAT THEY'D BOUGHT AS
A SPARE FROM HARVARD. HARVARD SELL OFF THEIR
OLD STUFF AND THIS IS WHERE THEY WERE STARTING
TO MAKE THESE THINGS.

AND IN 1974, THE
COMPANY GOT STARTED. IT WAS INCORPORATED IN '75 AND THEY MADE $200,000 SELLING
RESTRICTION ENZYMES IN 1975 AND THIS WAS A LOT OF MONEY AND FROM A JUST A VERY
SMALL MAKESHIFT OPERATION. AND SO I ALWAYS SAY, IF YOU'RE
GOING TO PUT UP AN INCUBATOR, YOU KNOW, EVERYBODY LIKES
TO INCUBATE COMPANIES. OK. YOU WANT TO PUT UP
THESE FANCY BUILDINGS. YOU WANT TO FIND BASEMENTS THEY
CAN GO INTO AND FIND GARAGES, YOU KNOW, YOU LOOK AT
BILL GATES AND MICROSOFT AND STEVE JOBS AND,
YOU KNOW, THESE PEOPLE WHO GET THIS COMPANIES GOING,
THEY DO IT ON THE CHEAP. THEY DON'T DO IT BY GOING
INTO THESE FANCY INCUBATORS. AND SO, I THINK THERE'S ANOTHER
LESSON THERE THAT'S WORTH DOING. SO ANYWAY, SO THAT
WAS SORT OF THE STORY OF RESTRICTION ENZYMES. THEY– THE NOBEL PRIZE
FOR THIS WAS GIVEN IN 1978 UNTIL DAN NATHANS, HAM
SMITH AND WERNER ARBER. WERNER ARBER DISCOVERED
THE VERY FIRST ONE, IT TURNED OUT IT
WASN'T VERY INTERESTING. HAM SMITH DISCOVERED HINDII. HE CALLED IT AND
IT ENDONUCLEASE, IT WAS ACTUALLY A MIXTURE OF TWO
ENZYMES WHICH I FOUND AS SOON AS WE STARTED TO TRY AND PURIFY
IT AND THIS WAS THE ENZYME THAT MADE ALL THE DIFFERENCE BECAUSE IT GAVE SPECIFIC
FRAGMENTS OF DNA AND HAM ONLY WAS
INTERESTED IN IT BECAUSE HE THOUGHT IT WAS
PROMOTING RECOMBINATION IN HAEMOPHILUS, HAVE NO IDEA
WHAT IT MIGHT BE USEFUL FOR, BUT FORTUNATELY, DAN NATHANS
WHO SHARED THE NEXT LAB TO HAM FIGURED OUT WHAT IT WAS
USEFUL FOR AND STARTED USING IT TO MAP SP40 AND THE
REST OF IT IS HISTORY IN TERMS OF MAPPING AND SO ON.

AND SO THESE THREE WERE
JUST A TREMENDOUS TRIO TO WIN THIS PRIZE,
IT WAS FANTASTIC. LET'S SEE WHERE WE
ARE GOING THERE. OK. SO THIS IS A SUMMARY
OF THINGS I DID WHILE I WAS AT COLD SPRING HARBOR. SO, IN THE FIRST TWO,
THREE YEARS I WAS THERE, WE FOUND 30 RESTRICTION ENZYMES, ALL BUT ONE OF WHICH
WAS DIFFERENT. I– IN '75, I BECAME SCIENTIFIC
ADVISER TO NEW ENGLAND BIOLABS, THEY'D ACTUALLY OFFERED ME A
PARTNERSHIP IN THE COUNTRY– IN THE COMPANY BUT I HAD
NO INTEREST IN THAT.. I, YOU KNOW, WAS JUST
A NEW INVESTIGATOR DOWN AT COLD SPRING HARBOR,
I WANTED TO DO RESEARCH.

I STILL HAD MY NOBEL
PRIZE WINNING WORK TO DO. SO, YOU KNOW, I COULDN'T
LEAVE AND GO TO A COMPANY. I PRODUCED THE FIRST RESTRICTION
ENZYME LIST WHICH WAS A LIST OF ALL THE KNOWN ENZYMES
THAT WE CIRCULATED WIDELY. THIS BECAME THE PRECURSOR
OF A DATABASE THAT I NOW RUN AND HAVE RUN, IT WAS ONE OF THE VERY FIRST
MOLECULAR BIOLOGY DATABASES. WE FOUND MANY RM SYSTEMS GENES,
WE DID A BUNCH OF CLONING AND BY 1978 THEN WE'D STARTED
DOING BIOINFORMATICS RELATED TO RESTRICTION ENZYMES AT
FIRST BUT LATER RELATED TO DNA SEQUENCES
AND RNA AND SO ON.

BUT OF COURSE, DURING
THIS TIME AND, YOU KNOW, JIM WAS CONSTANTLY TELLING
ME WHY I WAS WASTING MY TIME WORKING ON THIS RESTRICTION
ENZYMES AND SO ON AND EVENTUALLY GOT TO BE SO
WEARING THAT I THOUGHT WELL, MAYBE WE'LL TRY ANOTHER PROJECT
TOO AND SO I GOT A POST DOC TO COME DOWN RICHARD GELINAS. OH, I DON'T HAVE
HIS PICTURE YET. HE CAME DOWN AND WE DECIDED THAT
WHAT WE WOULD DO WOULD BE TO TRY TO MAP A PROMOTER ON
A EUKARYOTIC VIRUS, SOMETHING THAT WOULD
RESEMBLE A HUMAN PROMOTER OR A MASS PROMOTER OR SOME
HIGH ORGANISMS PROMOTER AND SEE IF THE SEQUENCES AT THE
5-PRIME END, WHICH WERE GOING TO DRIVE THE EXPRESSION
OF A GENE WITH THE SAME IN EUKARYOTES AND
IN PROKARYOTES.

WE ALREADY KNEW WHAT
THEY WERE IN PROKARYOTES. THANKS TO THE WORK THAT
HAD BEEN DONE AT HARVARD WITH WALLY GILBERT,
JIM WATSON'S LAB, MARK PTASHNE'S LABS AND SO ON. AND SO WE KNEW MORE OR LESS
WHAT WAS GOING ON THERE. BUT WE HAVE NO IDEA ABOUT WHAT
WAS GOING ON IN ADENOVIRUS WHICH WAS THE– THE VIRUS
WE CHOSE TO WORK ON. AND SO, WE HAD A VERY,
VERY SIMPLE IDEA. WHEN RNA IS FIRST MADE, THE 5-PRIME END HAS
A TRIPHOSPHATE ON IT. SO IT STARTS WITH ATP OR GTP, USUALLY ATP THAT HAS A
TRIPHOSPHATE ON IT, RUNS ALONG, YOU ADD ONE BASE AT A TIME WITH
THE RNA POLYMERASE UNTIL YOU GET TO THE 3-PRIME END AND THEN
3-PRIME END HAS POLY-A ON IT.

AND SO HERE, YOU'VE GOT
MOLECULES THAT IF YOU CUT THIS AND ALL THE G RESIDUES AND WHICH
YOU CAN DO WITH THIS ENZYME, A NUCLEASE CALLED RIBONUCLEASE
T1, YOU WOULD MAKE A SERIES OF OLIGONUCLEOTIDES AND THERE
WOULD BE BASICALLY JUST THREE KINDS OF OLIGONUCLEOTIDES
PRODUCED. ONE FROM THE INTERIOR PART
WHICH HAD A 5-PRIME PHOSPHATE AND A 3-PRIME HYDROXYL,
ONE FROM THE 3-PRIME END WHICH WOULD HAVE THE
BIG POLY-A TAIL ON IT AND SO YOU COULD ACTUALLY
GET RID OF THOSE VERY EASILY, JUST RUN THEM OVER AND
ALL AND GO DT COLUMN, IT WOULD CAPTURE THEM, YOU
COULD GET RID OF THOSE. BUT WHAT YOU WOULD HAVE WOULD
BE SOMETHING WITH A TRIPHOSPHATE ON IT AND IF WE COULD
FIND THE OLIGOS THAT HAD THE TRIPHOSPHATE,
THESE WOULD TELL US WHERE THE RNA STARTED AND THEN
WE COULD SEQUENCE UPSTREAM OF THAT ON THE DNA AND WORK
OUT WHERE THE PROMOTER WAS.

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