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(applause)
>> WELL, HELLO TO EVERYBODY AND THANK YOU VERY MUCH
FOR GIVING ME THE OPPORTUNITY AND DR. CONNOR TO COME IN
AND SPEAK HERE AT GRAND RAPIDS COMMUNITY COLLEGE.
I'M HAPPY TO BE WITH YOU TODAY.
UM, I HAVE ONE RULE FOR MY PRESENTATIONS WHEN I GIVE THEM
AND THAT IS THAT WE KEEP THINGS INFORMAL.
SO, IF THROUGHOUT THE COURSE OF THIS PARTICULAR DISCUSSION,
YOU FEEL COMPELLED TO RAISE YOUR HAND
AND ASK A QUESTION OR INTERJECT OR WHATEVER,
I INSIST THAT YOU DO IT.
LET'S KEEP THIS AS DISCUSSIONAL AS POSSIBLE.
WE'VE GOT AN HOUR AND A HALF TOGETHER, AND, UH...
I HAVE ABOUT A MILLION SLIDES TO GO THROUGH.
SO, DEPENDING ON HOW MY NERVOUSNESS IS, THEY'LL BE DONE IN SIX MINUTES
OR, YOU KNOW, A COUPLE HOURS.
SO, WE'LL SEE HOW THIS GOES.
UH, SO, YEAH, IT IS QUITE A LONG TITLE TO MY PRESENTATION TODAY,
AND IT'S, "WILL YOU BE ABLE TO PREORDER THE SEX, HEIGHT, HAIR COLOR,
"PERSONALITY OF YOUR NEW BABY?
"AND IF YOU CAN, SHOULD YOU?"
SO... UH-OH.
THERE WE GO.
SO, I'VE KINDA CONDENSED THAT TITLE TO BE "GENOMICS & YOU."
SO, BEFORE WE GO REALLY FARTHER TODAY...
I HAVE TO GIVE THIS DISCLAIMER, AND THIS IS ACTUALLY IMPORTANT
AND THERE'S A REASON THAT I'M DOING IT.
SO, I WANT YOU ALL TO UNDERSTAND THAT I'M HERE TODAY
AND I'M NOT REPRESENTING MY COMPANY.
I'M REPRESENTING MYSELF AND MY EXPERIENCES,
AND ANYTHING THAT I SAY OR IMPLY COMES COMPLETELY FROM ME
AND NOT FROM ANYTHING THAT MY COMPANY DOES OR BELIEVES IN...
OR WHAT HAVE YOU.
SO, THIS IS ALL ME, NONE THEM.
AND THE REASON THAT I'M MAKING THIS DISCLAIMER
IS BECAUSE WE'RE GONNA HEAD INTO SOME MURKY WATERS...
AND A LOT OF PEOPLE FIND THE THINGS THAT I'M GONNA TALK ABOUT CONTROVERSIAL.
AND I WANT TO BE FREE TO TALK ABOUT THIS STUFF WITH YOU
AS AN INDIVIDUAL PERSON IN SOCIETY,
RATHER THAN A REPRESENTATIVE OF A COMPANY,
WHO MAY HAVE A DIFFERENT AGENDA AND SHAREHOLDERS TO ACCOUNT FOR.
SO, THIS IS ABOUT US TODAY.
UM, JUST TO EXTEND A LITTLE BIT ON THE INTRODUCTION,
SO THAT YOU CAN DECIDE FOR YOURSELF WHETHER OR NOT
YOU'D LIKE TO BELIEVE ANYTHING I HAVE TO SAY.
SO, I DID GET SOME TRAINING, EARLY ON, AT HILLSDALE COLLEGE.
I STUDIED BIOLOGY AND CHEMISTRY.
I WENT TO OHIO UNIVERSITY AND I GOT A PhD IN MOLECULAR BIOLOGY,
AND I STUDIED ONE PART OF MOLECULAR BIOLOGY
CALLED "POST-TRANSCRIPTIONAL PROCESSING,"
WHICH JUST BASICALLY HAS TO DO WITH THE ACTIVITY OF THE GENOME.
I WAS OF RESEARCH FELLOW AT THE DEFENSE DEPARTMENT
IN THE DIVISION OF EXPERIMENTAL THERAPEUTICS,
WHERE WE TRIED TO DEVELOP DRUGS TO FRONT-LOAD SOLDIERS WITH--
BEFORE THEY WENT INTO BATTLE,
SO THAT IF THEY WOULD WALK INTO A FIELD OF SARIN GAS,
THAT WE COULD GIVE THEM AN APPROPRIATE DRUG BEFOREHAND
AND THEY'D BE IMPERVIOUS TO THE DRUG.
ALL VERY SCI-FI MILITARY-TYPE STUFF...
BUT I ALSO WORKED AT THE NATIONAL CANCER INSTITUTE
DOING A BUNCH OF WORK AS A SCIENTIST, WITH CANCER.
BUT IT WAS ABOUT THAT TIME, IN MY EARLY 30s,
THAT I LEFT ACADEMIC RESEARCH
AND WENT OVER TO THE DARK SIDE OF BUSINESS,
AND I WORKED FOR A BIOTECH COMPANY CALLED AFFYMETRIX
AS AN APPLICATION SCIENTIST.
AND THEN, I HAD FIGURED IT WOULD BE A GOOD IDEA
TO START MY OWN COMPANY.
SO, YOU KNOW, THOSE SOMETIMES WORK OUT, SOMETIMES THEY DON'T,
AND WE DID OKAY WITH THAT,
BUT MY COMPANY, CALLED "TENEO SCIENCES"--
WE WORKED IN ARTIFICIAL INTELLIGENCE.
AND WHAT WE DID WITH THAT COMPANY
IS TRIED TO DEVELOP ARTIFICIAL INTELLIGENCES
THAT WOULD COMB THROUGH LARGE SETS OF GENETIC DATA
AND TRY TO MAKE SENSE OF IT.
AND YOU MAY UNDERSTAND WHY THAT'S IMPORTANT LATER,
BY THE END OF THIS TALK.
I'VE ALSO BEEN A CONSULTANT AND INVENTOR FOR SHADY GROVE CENTER
FOR PRE-IMPLANTATION GENETICS.
THIS IS A LARGE, EAST COAST IN VITRO FERTILIZATION CLINIC,
AND WE DEVELOPED TECHNOLOGIES TO INTERROGATE EMBRYOS
BEFORE THEY WERE IMPLANTED IN THE RECIPIENT FEMALE.
UM, I WAS A VICE PRESIDENT AT deCODE GENETICS,
WHICH IS AN ICELANDIC COMPANY, AND WHILE I WAS THERE,
WE WERE THE WORLD'S LARGEST GENETICS ANALYSIS COMPANY.
THEY'RE STILL QUITE LARGE.
AND THEY'VE BEEN SUPPLANTED BY COMPLETE GENOMICS,
WHERE I WORK RIGHT NOW,
WHERE WE DO WHOLE HUMAN GENOME SEQUENCING AND THAT'S IT.
THAT'S ALL WE DO.
THERE WE GO.
SO, I HAVE ONE MAJOR OBJECTIVE HERE.
(clearing throat)
IF I COULD BE ONE THING TODAY WITH ALL OF YOU,
I'D LIKE TO BRING WHOLE HUMAN GENOME SEQUENCING AND GENETICS
AND GENOMICS TO THE FOREFRONT OF YOUR MIND
AND GET YOU TO THINK ABOUT IT AND ITS IMPLICATIONS IN SOCIETY
AND IN YOUR LIFE AND PERHAPS EVEN IN YOUR CAREERS,
IF YOU ARE MOVING IN THE DIRECTION OF HAVING A CAREER.
AND TO DO THAT,
I'M GOING TO GIVE A VERY HIGH-LEVEL LOOK AT GENOMICS AND GENETICS.
I'M NOT GOING TO GET INTO THE WEEDS OF HOW ALL THAT STUFF'S PUT TOGETHER
OR ANALYSIS IS DONE.
AND I WANNA MAKE THIS AS REAL AS POSSIBLE FOR ALL OF YOU.
AND SO, TO DO THAT, I'M GONNA GIVE YOU REAL EXAMPLES FROM REAL PEOPLE,
AND SOME OF THESE EXAMPLES WILL TEND FROM THE MUNDANE--
THE STUFF IN THE BEGINNING OF THE TALK--
TO RATHER EXOTIC STUFF TOWARDS THE END OF THE TALK.
OKAY, SO, IN THE PROCESS, I WANT TO BE VERY CLEAR WITH YOU
ON THE DIFFERENCE BETWEEN FACT AND OPINION.
SO, I-- WHEN YOU WALK OUT HERE,
I WANT YOU TO BE ABLE TO SAY, "THESE ARE FACTS--
"THESE THINGS WE KNOW TO BE TRUE,
"AND THESE OTHER THINGS
"THAT GUY IN THE FRONT OF THE ROOM SAID WERE HIS OPINIONS,"
'CAUSE THEY ARE JUST THAT.
BUT MY OPINIONS HAVE BEEN FORMED ON THIS SUBJECT,
TRAVELING AROUND THE WORLD OVER THE LAST TEN YEARS,
TALKING TO WORLD LEADERS IN GENETICS AND GENOMICS,
AND MY OWN PERSONAL OPINIONS.
OKAY.
SO, TO START OFF-- THE CENTRAL DOGMA OF D.N.A.
ACTUALLY, BEFORE I GO ANY FURTHER,
I'D LIKE TO FIND OUT A LITTLE BIT ABOUT YOU.
HOW MANY STUDENTS IN HERE ARE IN PSYCHOLOGY MAJOR?
DON'T BE SHY.
HOW ABOUT SOCIOLOGY?
OKAY, HOW ABOUT BIOLOGY?
AND THAT WAS ONLY ABOUT, LIKE, HALF THE ROOM.
WHAT ARE THE REST OF YOU DOING?
NURSING?
OR WHAT ARE THE OTHER KINDS OF--
JUST GO AHEAD AND SHOUT OUT WHAT SOMEBODY ELSE IS DOING IN HERE.
>> PRE-MED. >> PRE-MED, GOOD.
>> CRIMINAL JUSTICE. >> CRIMINAL JUSTICE, EXCELLENT.
VERY GOOD.
ARCHITECTURE?
FANTASTIC.
YOU'RE GOING TO LIKE THE FIRST SLIDES.
OKAY, ALL RIGHT.
THAT'S GREAT.
AND I SEE THAT THERE'S SOME FACULTY IN HERE AS WELL.
IS THAT ALL FACULTY FROM GRCC?
YEAH?
OKAY.
OKAY...
SO, HERE IS THE VERY, VERY TRADITIONAL...
EXPLANATION OF D.N.A.
D.N.A. IS THE PLAN, RIGHT?
THIS IS HOW, FOR AGES, PEOPLE HAVE TALKED ABOUT IT.
IT'S THE ANALOGY THAT WE USE.
SO, IN OTHER WORDS, YOU KNOW, WHAT WE HAVE RIGHT HERE IS ON...
THE LEFT SIDE OF THE SCREEN, FOR ALL OF YOU--
IS SORT OF A BLUEPRINT RENDERING OF FRANK LLOYD WRIGHT'S "FALLING WATER."
THAT'S THE BLUEPRINT FOR HIS BEAUTIFUL HOME
IN PENNSYLVANIA, "FALLING WATER."
AND SO, THE ANALOGY WOULD GO
THAT THE D.N.A. ITSELF IS A SIMILAR PLAN,
AND THAT THAT PLAN CREATES AN ORGANISM-- IN THIS CASE, THE HUMAN.
SO, I THINK THAT-- I THINK THAT THAT IS...
AN OLD FASHIONED WAY TO THINK ABOUT D.N.A.
AND NOT REALLY TOTALLY CORRECT.
SO, MORE THAN JUST THE PLAN, D.N.A.-- YOUR GENOME--
IS A INSTRUCTION MANUAL.
IT DOES MORE THAN JUST LAY OUT WHAT THE STRUCTURE OF THINGS SHOULD BE.
IT IS THE SET OF DIRECTIVES THAT ARE REQUIRED
TO CREATE, GROW, MATURE,
OBSOLETE, AND KILL AN ORGANISM.
ALL THIS IS CONTAINED WITHIN IT.
AND WE PASS THIS INFORMATION FROM GENERATION TO GENERATION
THROUGH HERITABILITY.
SO, I THINK IT AS THE INSTRUCTION MANUAL, FULL OF DIRECTIVES.
(clearing throat)
SO, MANY OF YOU HAVE HAD THIS IN YOUR INTRODUCTORY BIOLOGY CLASSES,
PROBABLY FROM HIGH SCHOOL ONWARDS, BUT IT'S WORTH REVIEWING RIGHT NOW.
ESSENTIALLY, WHAT IS THE GENOME?
WHAT IS THE LOCATION AND ORGANIZATION OF THE GENETIC MATERIAL?
SO, EVERY SINGLE CELL IN YOUR BODY HAS-- EXCEPT FOR THE BLOOD CELLS--
HAS A NUCLEUS,
WHICH IS A SUB-CELLULAR ORGANELLE THAT HAS CHROMATIN--
CHROMOSOMES-- THAT MAKE UP THE GENOME.
THOSE CHROMOSOMES ARE COMPOSED OF D.N.A.
NOW, D.N.A. ITSELF IS A POLYMER
THAT HAS FOUR DIFFERENT BASES IN IT-- A, C, T, AND G--
AND THESE THINGS ARE STRUNG TOGETHER IN A CERTAIN SEQUENCE.
SO, THIS SEQUENCE OF A, C, Ts, AND Gs IS WHAT IS THE DIRECTIVE.
THAT'S THE BOOK, ESSENTIALLY,
THAT DECIDES HOW THINGS ARE GOING TO GO
FOR THE DEVELOPMENT AND USE OF AN ORGANISM.
SO, MY JOB-- MY COMPANY, AND WHAT MOST COMPANIES
ARE INTERESTED IN RIGHT NOW, IS TO DETERMINE, "WHAT IS THE SEQUENCE?
"WHAT IS THE ACTUAL ORDER OF THESE As, Cs, Ts, AND Gs,
"AND WHAT DOES THAT MEAN FOR DISEASE,
"HEALTHCARE, AGING, AND MANY OTHER THINGS?"
OKAY, I LOVE THIS PICTURE.
THIS IS A FALSE COLOR SCANNING ELECTRON MICROGRAPH
OF THE HUMAN CHROMOSOME NUMBER TWO.
I THINK IT'S ABSOLUTELY BEAUTIFUL, THAT WE GET TO SEE THESE THINGS.
SO, WHAT YOU'RE LOOKING AT HERE IS A SET OF MOLECULES, ESSENTIALLY.
IT'S THAT FINE OF RESOLUTION.
EVERY CELL IN YOUR BODY, ESSENTIALLY, HAS A FULL COMPLEMENT OF CHROMOSOMES...
JUST LIKE THIS.
AND SO, IN THE UPPER LEFT THERE
IS WHAT WE CALL A KARYOTYPE SPREAD,
AND THIS IS THE CHROMOSOMES THAT HAVE BEEN CONDENSED
AND ISOLATED FROM A CELL AND LAID OUT FOR MICROGRAPHY.
AND ESSENTIALLY, THERE ARE 23 CHROMOSOMES.
THERE'S 22 SETS OF CHROMOSOMES THAT ARE CALLED "AUTOSOMES."
MALES AND FEMALES HAVE AUTOSOMES-- 22 SETS OF THEM.
THEN, THERE'S SEX CHROMOSOMES-- "X" AND "Y"--
FEMALES HAVE TWO "X," MALES HAVE ONE "X" AND ONE "Y."
SO, COMPRISING THIS WHOLE GENETIC COMPLIMENT,
THE GENOME IS 6 BILLION NUCLEOTIDE PAIRS.
SO, WHEN I WAS GOING TO SCHOOL,
EVERYBODY SAID THAT THERE WERE 3 BILLION NUCLEOTIDE PAIRS, ALL RIGHT?
IS THAT THE NUMBER THAT MOST OF YOU HAVE HEARD?
THE TRUTH IS, THERE'S TWICE THAT MANY,
BECAUSE YOU HAVE PAIRS OF CHROMOSOMES.
YOU CAN SEE THAT EACH ONE OF THESE IS A CHROMOSOME PAIR,
WITH THE EXCEPTION OF THE SEX CHROMOSOMES RIGHT THERE.
SO, IT'S TWICE THAT MANY-- THERE'S 3 BILLION-- OR 6 BILLION PAIRS.
AND THERE'S ABOUT 23,000 GENES
THAT MAKE AROUND 400,000 DIFFERENT PROTEINS.
SO, IN ADDITION TO D.N.A. BEING THE DIRECTIVES--
SET OF DIRECTIVES, THE INSTRUCTION MANUAL--
I'D LIKE YOU TO THINK ABOUT D.N.A. AND THE GENOME
AS THE ULTIMATE INFORMATION REPOSITORY.
THIS SEQUENCE THAT'S PUT TOGETHER IN THE GENOME
IS ABLE TO ENCAPSULATE EVERYTHING THAT'S REQUIRED,
EVERYTHING THAT YOU ARE THINKING RIGHT NOW,
ALL OF YOUR MEMORIES, WITHOUT THE D.N.A. TO CONSTRUCT THAT BRAIN,
TO CONSTRUCT THE COMPUTERS--
THIS IS THE ULTIMATE INFORMATION REPOSITORY.
OKAY.
TRANSLATIONAL AND GENOMIC MEDICINE.
IS THERE ANYBODY IN HERE
WHO KNOWS THE DEFINITION OF "TRANSLATIONAL MEDICINE"?
ANYBODY BRAVE ENOUGH TO ADMIT IT?
OKAY, ALL RIGHT.
SO, THIS IS A BIG DEAL.
THIS IS, UM-- THIS IS SOMETHING THAT'S GOING TO AFFECT ALL YOUR LIVES.
IT'S GOING TO AFFECT MY LIFE...
BUT PARTICULARLY BECAUSE MOST OF YOU IN HERE ARE YOUNGER.
THIS IS SOMETHING THAT YOU'RE GONNA SEE MANIFEST THROUGHOUT,
YOU KNOW, THE NEXT FIVE TO FIFTY YEARS.
WE'RE-- BIG, BIG CHANGES IN MEDICINE ARE UNDERWAY,
AND THEY ARE THE CHANGES OF TRANSLATIONAL MEDICINE.
SO, ESSENTIALLY, TRANSLATIONAL MEDICINE IS AN INTEGRATED APPROACH
TO RESEARCH, DIAGNOSIS, AND TREATMENT OF MEDICAL AFFECTATIONS,
WHERE WE'RE LEVERAGING THE TOOLS OF SCIENCE, OKAY?
SO, WE'RE TRANSLATING THE TOOLS OF SCIENCE
DIRECTLY INTO CLINICAL PRACTICE.
MEDICINE ITSELF IS BECOMING MUCH MORE SCIENCE THAN IT USED TO BE
AND MUCH LESS ART.
SO, EVEN IN THE AREAS OF PSYCHOLOGY, PSYCHIATRY,
WHERE YOU'RE MAYBE NOT THINKING OF IT IN TERMS OF, LIKE,
"I'M GONNA CUT SOMEBODY OPEN WITH A SCALPEL,"
OR "CURE THEIR CANCER" OR WHATEVER--
TRANSLATIONAL MEDICINE WILL APPLY GENETIC AND GENOMIC TECHNOLOGIES IN ABUNDANCE.
SO, THIS IS COMMONLY REFERRED TO...
AS "BENCH TO BEDSIDE."
THAT'S HOW WE THINK OF IT--
FROM THE RESEARCH BENCH TO THE BEDSIDE OF THE PATIENT.
OKAY.
SO, I'M TAKING SOME TIME TO EXPLAIN THIS,
BECAUSE IT IS QUITE RELEVANT TO WHAT WILL BE HAPPENING IN THE FUTURE.
UM, SO, IF YOU WERE TO LOOK AT A SPECTRUM,
SAY BETWEEN RESEARCH ON ONE SIDE--
BEING A VERY, VERY SCIENTIFIC ENDEAVOR,
SOMETHING THAT HAPPENS PURELY IN THE LABORATORY,
YOU PUBLISH PAPERS IN ACADEMIC JOURNALS, THAT SORT OF THING--
TO CLINICAL PRACTICE ON THE EXACT OPPOSITE EXTREME OF THIS SPECTRUM.
THIS IS SOMETHING WHERE IT'S NOT QUITE AS SCIENTIFIC.
IT'S VERY WELL ESTABLISHED,
IT'S A CONSERVATIVE APPROACH TO DOING WHAT THEY'RE DOING,
IT'S INTERACTING DIRECTLY WITH PATIENTS.
UM, TRANSLATIONAL MEDICINE FALLS KIND OF IN THE MIDDLE.
OOP, THERE WE GO.
SORRY.
SO, TRANSLATIONAL MEDICINE, YOU KNOW, FIVE, TEN, SEVEN YEARS AGO,
WAS REALLY PRACTICED BY PEOPLE WHO ARE M.D. PhDs,
AND WHAT WE'VE SEEN OVER THE INTERVENING YEARS
IS THAT IT'S GAINED GREATER AND GREATER ADOPTION,
BUT NOT BY THE SCIENTISTS-- IT'S BY THE MEDICAL COMMUNITY,
WHO HAVE SEEN THESE SCIENTIFIC TOOLS
AND SAID, "WE NEED TO IMPLEMENT THESE THINGS IN OUR PRACTICE.
"WE NEED TO USE THESE TOOLS TO HELP US CARE FOR OUR PATIENT BASE."
SO, A COUPLE YEARS AGO, WE REALLY STARTED TO SEE,
YOU KNOW, TRANSLATIONAL MEDICINE COME TO THE FOREFRONT,
AND IN ANOTHER FEW YEARS, BY 2015,
THE TRANSLATIONAL MEDICINE TOOLS OUT THERE,
PARTICULARLY IN GENETICS AND GENOMICS,
WILL HAVE REALLY COME MUCH FARTHER INTO CLINICAL PRACTICE.
I THINK THAT PEOPLE THAT ARE PRACTICING PSYCHIATRY,
IN PARTICULAR, WHO ARE PRESCRIBING DRUGS,
WILL BE USING THE TOOLS OF TRANSLATIONAL MEDICINE.
SO, MORE TO THE POINT FOR US TODAY,
TRANSLATIONAL MEDICINE IS THIS--
IF YOU WERE TO THINK OF ALL THE TOOLS OF TRANSLATIONAL MEDICINE
THAT WOULD BE AVAILABLE--
THE TOOLS OF BIOLOGIST'S, WHICH IS, YOU KNOW, PROTEIN CHEMISTRY
AND GENETICS AND R.N.A. ANALYSIS-- ALL THAT SORT OF STUFF--
TRANSLATIONAL MEDICINE.
I'M GONNA FOCUS ON GENOMIC MEDICINE.
NOW, GENOMIC MEDICINE IS A TRANSLATIONAL MEDICINE.
IT'S A SUBSET OF TRANSLATIONAL MEDICINE,
AND THIS IS EXTRAORDINARILY POWERFUL.
AND IT'S NOT ONLY IMPORTANT IN TERMS OF IMPROVEMENT IN CLINICAL CARE.
IT'S ALSO IMPORTANT IN TERMS OF OUR UNDERLYING ECONOMY.
THERE'S A HUGE INVESTMENT THAT'S BEING MADE--
I MEAN, YOU'VE SEEN THE BUILDING THAT'S HAPPENED AROUND HERE,
IN GRAND RAPIDS, FOR RESEARCH.
YOU KNOW, THE VAN ANDEL INSTITUTE OVER THERE.
THAT'S HAPPENING ALL AROUND THE WORLD, AND IT'S LARGELY GENOMIC MEDICINE.
WHY?
WHY ARE THEY DOING THAT?
WHY IS EVERYBODY INVESTING IN GENOMIC MEDICINE?
WELL, IT'S BECAUSE OF THIS-- MOST PEOPLE, AT THIS POINT IN TIME,
BELIEVE THAT THE ROOT OF ALL DISEASE CAN BE TRACED BACK TO THE GENOME.
SO IT DOESN'T REALLY MATTER WHAT YOUR DISEASE IS--
PEOPLE OFTEN SAY TO ME, "WELL, RICK, WHAT ABOUT INFECTIOUS DISEASE?
"HOW DO TRACE THAT BACK TO THE GENOME?"
I MEAN, SOME THINGS ARE EASY TO EXPLAIN AWAY,
LIKE DEVELOPMENTAL DELAY, ALZHEIMER'S DISEASE--
THESE VERY CLEARLY HAVE GENETIC COMPONENTS-- CANCER.
SURE, THEY GET THAT, BUT WHAT ABOUT INFECTIOUS DISEASE?
WELL, THERE'S A THING CALLED A "HOST RESPONSE."
SO, YOUR ABILITY TO BE INFECTED OR NOT INFECTED IS, IN FACT,
DETERMINED BY YOUR GENOME AS WELL.
TRUE.
SO, I WILL STAND BY THIS STATEMENT-- AND IT'S PRETTY WELL ACCEPTED,
AND ANYBODY WHO'D LIKE TO GO TOE-TO-TOE WITH ME ON THIS, I'M READY.
(audience chuckling) NO TAKERS?
OKAY.
THIS IS...
THIS IS MENDEL'S EXPERIMENT RIGHT HERE.
GREGOR MENDEL WAS THIS OLD MONK-- KINDA THE FATHER OF GENETICS.
RAISE YOUR HAND YOU KNOW ABOUT GREGOR MENDEL-- HAVE SEEN IT.
OKAY.
SO, THIS IS LIKE THIS VERY TRADITIONAL, CLASSIC WAY TO THINK ABOUT GENETICS,
AND IN THIS EXPERIMENT--
MENDEL WAS A MONK, AND HE WATCHED HIS GARDEN GROW
AND HE WATCHED THESE PEA PLANTS
AND HE TRIED TO EXPLAIN AWAY THE VARIATION IN FLOWER COLOR,
AS THESE THINGS GREW EVERY SPRING, AND HE WOULD CROSS THE PLANTS.
AND HE FOUND...
THAT IF HE CROSSED A PLANT WITH A RED FLOWER ON IT
AND A PLANT WITH A WHITE FLOWER ON IT,
THAT THE RESULT WAS A PLANT WITH A PINK FLOWER,
KINDA HALFWAY BETWEEN RED AND WHITE.
AND HE FURTHER FOUND THAT IF HE TOOK THE PINK FLOWERS
AND HE TOOK TWO PINK FLOWERS AND HE CROSSED THEM TOGETHER,
THAT HE WOULD GET FLOWERS THAT RESULTED THAT WERE RED AND PINK AND WHITE,
AND MORE SPECIFICALLY, THAT THEY WERE IN A SPECIFIC RATIO--
25 PERCENT OF THE FLOWERS WERE RED, 50 PERCENT OF FLOWERS WERE PINK,
AND 25 PERCENT OF THE FLOWERS WERE WHITE.
AND SO, THIS IS THE KIND OF THING THAT WE ALL HAVE LEARNED IN GENETICS.
THIS IS, YOU KNOW, AS WE WENT TO SCHOOL, THIS IS HOW WE LEARNED GENETICS,
AND IT PROPAGATES THIS THOUGHT
THAT I SEE ALL THE TIME, WHICH IS...
"HEY, MY DAD HAD HEART DISEASE.
"THAT MEANS I'M GOING TO HAVE HEART DISEASE."
OR, "MY UNCLE WAS CRAZY.
"AM I GOING TO BE CRAZY?"
AND YOU KNOW, WHEN I SIT ON THE AIRPLANE,
WHICH IS WHAT I DO 90 PERCENT OF THE TIME,
AND I TELL PEOPLE WHAT I DO,
THEY ASK ME A LOT OF QUESTIONS ABOUT THIS SORT OF THING--
"AM I GOING TO GET SICK BECAUSE MY RELATIVE GOT SICK?"
WELL, THE TRUTH IS THAT GENETICS DOESN'T REALLY WORK THAT WAY VERY OFTEN.
THIS IS MENDELIAN GENETICS-- STRICTLY MENDELIAN GENETICS--
AND IT'S WHAT WE CALL "SIMPLE GENETICS."
AND THERE'S NOT VERY MANY HUMAN DISEASES...
THAT FALL INTO MENDELIAN GENETICS.
THEY'RE ACTUALLY ALL CATEGORIZED AT O.M.I.M.,
WHICH IS "ONLINE MENDELIAN INHERITANCE IN MAN."
THIS IS A WEBSITE FROM THE NATIONAL INSTITUTES OF HEALTH
AND JOHNS HOPKINS,
WHERE IT ACTUALLY TAKES ALL THE KINDS OF DISEASES
THAT FIT THAT CRITERIA OF, YOU KNOW, DOMINANT-RECESSIVE,
"MY DAD HAD IT, I'M GONNA HAVE IT," SORT OF PARADIGM,
AND LISTS THEM FOR YOU.
AND THERE'S NOT THAT MANY-- THERE'S ONLY LIKE 1,500.
SO, OUT OF ALL THE DIFFERENT KINDS OF HUMAN AFFLICTION THAT YOU CAN THINK OF,
ONLY A SMALL FRACTION OF THEM-- AND LARGELY NONE OF THEM--
ARE COMMON DISEASES.
YOU KNOW, YOU WON'T FIND SOMETHING LIKE HEART DISEASE IN THERE.
YOU WON'T FIND ANY OF THAT SORT OF STUFF.
IT'S OBSCURE THINGS.
SO, THERE IS THIS RELATIONSHIP THAT EXISTS
BETWEEN YOUR GENES AND DISEASE,
AND THE NUMBER OF GENETIC VARIANTS--
YOU'RE GONNA HEAR ME USE THIS WORD "GENETIC VARIANTS" ALL THE TIME TODAY.
AND IT GOES LIKE THIS...
BASICALLY, IT SAYS THAT THE FEWER NUMBER OF VARIANTS
THAT ARE RESPONSIBLE FOR PRODUCING A DISEASE,
THE STRONGER INFLUENCE OF THAT VARIANT ON THE DISEASE, OKAY?
SO, IN OTHER WORDS, AN EXAMPLE OF THAT WOULD BE
SOMETHING LIKE SICKLE CELL ANEMIA,
OR IF YOU HAVE A SINGLE-- SINGLE!-- NUCLEOTIDE VARIATION,
YOU'VE GOT SICKLE CELL ANEMIA.
VERY STRONG.
ON THE OTHER HAND, MORE COMPLEX STUFF--
STUFF THAT YOU ALL MIGHT BE DEALING WITH-- DISEASES OF THE MIND.
THEY HAVE MANY, MANY, MANY GENETIC VARIANTS THAT WORK TOGETHER
TO PRODUCE THIS PHENOTYPE, THIS PRODUCT THAT YOU SEE--
IF SOMEBODY'S SCHIZOPHRENIC OR WHAT HAVE YOU.
IT'S NOT ONE THING THAT PRODUCES IT, IT'S QUITE A NUMBER.
COMPLEX DISEASES.
OKAY, ANY QUESTIONS ON THAT?
THAT'S KIND OF AN IMPORTANT TOPIC,
SO MORE GENETIC VARIATION FOR COMPLEX DISEASES,
LESS GENETIC VARIATION FOR SIMPLE DISEASES.
OKAY, SO...
HERE'S THE DEAL-- WE'VE KNOW THIS FOR A LONG TIME,
THIS WHOLE PARADIGM ABOUT THE NUMBER OF VARIANTS REQUIRED
TO PRODUCE A GIVEN DISEASE.
WE'VE DONE THIS FOR A LONG, LONG TIME, AND BACK IN 1980s--
I'M SURE BEFORE ANY OF YOU WERE BORN--
THE GOVERNMENT MADE A DECISION, AND THEY SAID,
"WHAT WE'RE GONNA DO IS WE'RE GOING TO SEQUENCE THE HUMAN GENOME,"
AND THAT WAS THE BIRTH OF THE HUMAN GENOME SEQUENCING PROJECT.
AND THEY EMBARKED ON THIS THING
THAT WAS ESSENTIALLY LIKE THE MOON SHOT FOR GENETICS,
AND THAT'S, YOU KNOW, THIS BIT ABOUT SEQUENCING A GENOME IS NON-TRIVIAL.
THIS IS DIFFICULT.
YOU KNOW, 6 BILLION NUCLEOTIDE PAIRS HAVE TO BE READ AND UNDERSTOOD,
SO THAT THE DATA ANALYSIS ALONE IS VAST,
NOT TO MENTION THE MACHINERY AND PEOPLE REQUIRED TO DO THIS.
UM, AND THE REASON THAT THEY WANTED TO DO THIS
IS BECAUSE THEY WANTED TO GET A HANDLE ON HEALTHCARE
AND HOW DO WE TREAT PEOPLE?
HOW DO WE UNDERSTAND THE ROOTS OF DISEASE?
REMEMBER, I SAID THAT THE ROOT OF DISEASE IS GENETIC.
WELL, WE CAN'T GET AT IT UNTIL WE UNDERSTAND THE GENOME, RIGHT?
SO, THEY SAID, "FINE, LET'S GO AFTER THIS THING.
"WE'RE GONNA PUT SOME MONEY AT THIS AND SOME SMART PEOPLE,"
SO THEY STARTED IN 1985-1986.
THEY PUT THESE TWO GUYS TOGETHER IN A LABORATORY,
WHICH TURNED OUT TO BE A MISTAKE.
THEY SPENT $3 BILLION IN 15 YEARS.
WELL, SOME PLACE ALONG THE WAY, THOSE TWO GUYS GOT IN A FIGHT,
AND ONE GUY LEFT THE NATIONAL HUMAN GENOME RESEARCH INSTITUTE-- N.H.G.R.I.--
AND THAT WOULD BE THE GUY IN FRONT, CRAIG VENTER--
AND HE STARTED HIS OWN COMPANY CALLED "CELERA."
AND THEN, THERE BECAME A COMPETITION
TO SEE WHO COULD SEQUENCE THE HUMAN GENOME FIRST--
THE GOVERNMENT-FUNDED N.H.G.R.I. OR CELERA.
AND SO, THESE TWO GUYS WENT AT IT, AND THEY ULTIMATELY SEQUENCED THE GENOME.
AND THE FIRST DRAFT OF THE GENOME WAS COMPLETED IN ABOUT 2000,
THE FINAL DRAFT IN ABOUT 2003.
SO, THAT WASN'T THAT LONG AGO.
SINCE 2003-- YOU KNOW, IT'S LIKE LESS THAN TEN YEARS AGO,
$3 BILLION, 15 YEARS,
THOUSANDS OF SCIENTISTS TO DO ONE HUMAN GENOME SEQUENCE.
SO-- AND JUST A COUPLE YEARS AFTER THAT, BY 2006,
IT TOOK, STILL, YEARS TO SEQUENCE ANOTHER HUMAN GENOME.
AND THAT WAS, UH-- THAT GENOME WAS JAMES WATSON,
WHO WAS ONE OF THE GUYS WHO DISCOVERED THE STRUCTURE OF D.N.A.
AND THAT TOOK A FEW MILLION DOLLARS.
2007, FIRST COMPANY TOOK ITS FIRST CLIENT
TO SEQUENCE SOMEBODY FOR MONEY.
THAT'S (indistinct).
AND DID THAT FOR $350,000
AND IT STILL TOOK MONTHS TO DO JUST ONE SINGLE HUMAN GENOME.
AND THAT'S $350,000 AT NO PROFIT.
COUPLE OF YEARS LATER, 2009, IT'S DOWN TO $5,000
TO DO A WHOLE HUMAN GENOME AND THERE'S PROBABLY,
AT THIS POINT, 40 HUMAN GENOMES IN ALL OF HUMAN HISTORY
THAT HAVE BEEN SEQUENCED.
THAT'S TWO, THREE YEARS AGO, YOU KNOW?
TWO, THREE YEARS AGO, THERE'S ONLY 40 HUMAN GENOMES DONE.
AFTER ALL THIS.
NINE WEEKS-- LAST YEAR-- AT THE END OF LAST YEAR,
JUST A COUPLE OF MONTHS AGO, WE WERE DOWN TO ABOUT $3,000
TO DO A HUMANE GENOME SEQUENCE, AND IT TAKES LESS THAN TWO WEEKS--
ABOUT 15 DAYS.
SO, IF YOU THINK ABOUT THIS,
THERE'S A MILLION-FOLD DECREASE IN PRICE,
BETWEEN TEN YEARS AGO AND TODAY,
AND THE TIME TO DO IT HAS GONE FROM 15 YEARS TO ABOUT A WEEK.
ALL RIGHT, SO I'M TELLING YOU THIS
BECAUSE AS THE ECONOMICS OF THIS THING CHANGE
AND THE FEASIBILITY OF HAVING THE SEQUENCE DONE CHANGES,
IT WILL BEGIN TO COME INTO YOUR LIVES ON A DAILY BASIS.
AND SO, A LOT OF THIS TALK
IS GONE EXPLORE WHY THAT IS AND HOW IT CAN BE USED.
2015, DOWN TO ABOUT $100.
NOW, THAT'S THE ESTIMATE-- I PERSONALLY DON'T BELIEVE IT.
SO, LET'S JUST SAY THAT FROM HERE UP, THAT'S FACT.
FROM HERE DOWN, THAT'S OPINION.
OKAY, UM...
IT'S IMPORTANT TO UNDERSTAND GENOMIC VARIATION,
AND I SAID I WAS GONNA KEEP THIS TALK AT A HIGH LEVEL,
AND SO, I'VE TRIED TO PUT AN ANALOGY TOGETHER
THAT MAY HELP YOU UNDERSTAND WHAT GENETIC VARIATION IS.
SO, IF YOU THINK OF THE GENOME AS A DIRECTIVE,
AND THAT DIRECTIVE, LET'S SAY IN THIS CASE,
IS "POUR CREAM IN MY COFFEE."
THAT'S A DIRECTIVE, THAT'S A DIRECTION.
SO, THE GENOME HAS DIRECTIVES THAT ARE OBVIOUSLY NOT THAT COMPLICATED,
BUT YOU COULD THINK OF THIS DIRECTIVE AS A GENE OR A SET OF GENES,
AND THIS IS WHAT WE WOULD EXPECT TO BE A STANDARD CORRECT DIRECTIVE.
BUT IF YOU HAVE GENOME VARIATION--
THERE'S LOTS OF KINDS A VARIATION THAT OCCUR, RIGHT?
SO, THIS IS ONE KIND.
IF WE JUST CHANGE ONE LETTER-- IF YOU CHANGE THE "P" TO AN "S"--
IN OTHER WORDS, IF YOU WERE TO, LIKE, CHANGE ONE OF THOSE NUCLEOTIDES
FROM SAY, AN "A" TO A "C"--
JUST ONE LETTER CHANGE CAN CHANGE THE DIRECTIVE ENTIRELY.
I MEAN, YOU CAN SEE THE CONTEXT OF IT-- "SOUR CREAM IN YOUR COFFEE"?
I'M NOT SO INTO THAT, PERSONALLY.
(clearing throat)
SO, THAT FIRST THING WAS A SINGLE NUCLEOTIDE VARIATION.
THIS NEXT ONE WE'RE LOOKING AT IS WHEN YOU TAKE ENTIRE CHUNKS
AND CHANGE WHERE THEY'RE LOCATED INSIDE THE DIRECTIVE, OKAY?
THIS IS A TRANS-LOCATION.
SO, IN OTHER WORDS, "POUR COFFEE IN MY CREAM."
WELL, OKAY, THAT MAY WORK.
YOU MAY GET SOME OF WHAT YOU WERE AFTER THERE.
IT'S NOT QUITE CORRECT.
TRANS-LOCATIONS.
AND THERE'S ALL KINDS OF TRANS-LOCATIONS.
THIS, YOU WOULD NEED TO READ THIS IN A MIRROR, BUT IT'S INVERTED, OKAY?
SO, THAT'S CALLED "INVERSION," ANOTHER KIND OF VARIATION.
AND THEN, THERE'S SOMETHING LIKE THIS-- "POUR SUGAR MY COFFEE."
WELL, THIS IS A SUBSTITUTION.
IN THIS CASE, WE'VE SUBSTITUTED THE WORD "SUGAR" FOR "CREAM,"
AND YOU KNOW, THAT'S PROBABLY OKAY.
MAYBE IT'S AN OKAY SUBSTITUTION.
THE POINT HERE BEING THAT EVEN IF THERE ARE SUBSTITUTIONS IN THE GENOME,
IT MADE MAY STILL RESULT IN FUNCTIONAL PROTEINS,
FUNCTIONAL GENES, FUNCTIONAL ACTIVITIES FOR THE BODY,
THAT NOT ALL SUBSTITUTIONS ARE BAD, OKAY?
THIS IS HOW EVOLUTION KIND OF OCCURS BY THIS SORT OF MECHANISM.
AND I JUST STUCK THIS ONE IN HERE TODAY-- ER, YESTERDAY, ACTUALLY--
FOR ALL OF YOU, BECAUSE THIS IS ONE THAT YOU'LL NEED TO KNOW ABOUT,
SINCE THIS IS THE PSYCHOLOGY DEPARTMENT.
THIS KIND OF CHANGE, "POUR CREAM CREAM CREAM CREAM CREAM CREAM,"
AND ONWARD, "IN MY COFFEE."
THIS IS CALLED A "COPY NUMBER VARIATION."
SO, IN OTHER WORDS, IT'S THE NUMBER OF COPIES
OF THE GIVEN PART OF A DIRECTIVE
OR DIRECTIVE INSIDE OF A CELL CHANGES HOW THAT CELL FUNCTIONS.
SO, FOR INSTANCE, IF THAT DIRECTIVE IS TO MAKE A CERTAIN GLYCOPROTEIN,
AND YOU HAVE A COPY NUMBER VARIATION LIKE THIS,
WHICH IS AN AMPLIFICATION,
YOU MAY HAVE WANTED TO HAVE ONE COPY OF THE GLYCOPROTEIN.
YOU MAY HAVE ENDED UP WITH THOUSANDS OF COPIES OF THE GLYCOPROTEIN.
THAT CHANGES THE CELL SURFACE STRUCTURE OF THE BRAIN OR ANY OTHER KIND OF CELL,
WHATEVER IT MAY BE.
I'M JUST THROWING THINGS OUT HERE.
BUT THIS IS WELL KNOWN IN THE WORLD OF PSYCHOLOGY AND PSYCHIATRY--
THESE COPY NUMBER VARIATIONS-- TO CAUSE PROBLEMS.
AND SCHIZOPHRENIA IS ONE OF THE BIG DISEASES OF STUDY,
AS FAR AS COPY NUMBER VARIATION.
AND SO, THIS IS--
THESE ARE VERY IMPORTANT FOR PSYCHOLOGY, PSYCHIATRY.
UH, AUTISM, AS WELL-- COPY NUMBER VARIATION.
AND THERE ARE HUNDREDS OF MILLIONS OF DOLLARS THAT ARE BEING INVESTED
BY OUR COUNTRY AND OTHER COUNTRIES AROUND THE WORLD,
DIFFERENT KINDS OF INSTITUTIONS, WHETHER IT'S THE MILITARY,
WHETHER IT'S WHOLE COUNTRIES, NON-PROFITS LIKE "AUTISM SPEAKS"--
THEY'RE TRYING TO UNDERSTAND THIS QUESTION,
"WHAT ARE THE COPY NUMBER DIFFERENCES THAT PRODUCE THIS DISEASE?"
OKAY.
WE'RE DOING GOOD ON TIME.
SO, CLINICAL UTILITY.
ACTIONABLE INFORMATION.
SO, IN GENOMIC MEDICINE, REALLY THE IMPORTANT THING IS--
I DON'T CARE HOW MUCH VARIATION IS THERE IN THE GENOME,
WHAT I CARE ABOUT IS HOW MUCH OF THIS VARIATION IN THE GENOME CAN I ACT UPON?
IN OTHER WORDS, IF THERE IS A GENOMIC VARIANT,
IS THERE SOMETHING I CAN DO ABOUT IT?
OKAY.
SO, TO THAT POINT, GENOMIC MEDICINE TRIES TO DO THINGS
LIKE DIAGNOSE IDIOPATHIC DISEASE, PRESCRIBE APPROPRIATE MEDICATIONS--
THAT'S PHARMACOGENOMICS.
THAT'S VERY, VERY IMPORTANT, PARTICULARLY FOR PSYCHOLOGY, PSYCHIATRY.
UH, MAKE BETTER INFORMED TREATMENT DECISIONS FOR CANCER OR WHATEVER.
IDENTIFY SPECIFIC PERSONAL HEALTH RISKS EARLY...
AND THIS IS PERSONALIZED MEDICINE.
EVERYBODY RESPONDS DIFFERENTLY TO DRUGS.
YOU MAY HAVE HEARD OF PERSONALIZED MEDICINE--
THAT'S THE BIG WORDS THAT GET TOSSED AROUND IN PUBLIC THESE DAYS.
AND WHAT THAT MEANS IS THE RIGHT DRUG FOR THE RIGHT PERSON AT THE RIGHT TIME.
WE'RE GONNA TALK ABOUT THAT A LITTLE BIT.
OKAY.
THIS... REALLY BUMS ME OUT.
THIS GUY IS...
NICK VOLKER.
NICK VOLKER LIVES ACROSS THE LAKE IN MILWAUKEE--
RIGHT OUTSIDE MILWAUKEE.
AND NICK IS ABOUT SEVEN YEARS OLD RIGHT NOW.
I'M GONNA TELL YOU NICK VOLKER'S STORY TO HELP ILLUSTRATE
WHY GENOMIC MEDICINE IS SO IMPORTANT TO ALL OF US.
SO, NICK-- BEAUTIFUL LITTLE BABY BOY,
TO TWO LOVING PARENTS IN WISCONSIN.
BY THE TIME HE WAS TWO YEARS OLD, HE HAD FAILED TO THRIVE.
HE WASN'T GAINING WEIGHT, HE WASN'T GROWING,
AND THERE WAS DEVELOPMENT OF FISTULA.
SO, FISTULA ARE ESSENTIALLY LITTLE HOLES-- LITTLE FORAMEN--
THAT GO FROM THE COLON AND THE RECTUM TO THE OUTSIDE OF THE BODY
AND EXPEL FECES AND FECAL MATERIAL.
THEY CAUSE SEPSIS-- INFECTION.
THEY'RE VERY DAMAGING.
SO, HIS PARENTS, COMPLETELY DISTRAUGHT ABOUT THIS THING,
SET OFF ON WHAT IS COMMONLY CALLED "THE DIAGNOSTIC ODYSSEY,"
WHICH MEANS, "LET'S TRY THIS-- THAT DIDN'T WORK.
"WELL, LET'S TRY THIS-- THAT DIDN'T WORK."
AND SO ON AND SO FORTH.
AND IT'S KIND OF LIKE THROWING A BUNCH OF SPAGHETTI AT THE WALL
AND SEEING WHICH NOODLES STICK.
"THE DIAGNOSTIC ODYSSEY."
SO, NICK WENT THROUGH THE DIAGNOSTIC ODYSSEY,
AS THEY TRIED TO FIND OUT WHAT WAS WRONG WITH HIM.
AND IN THE PROCESS, BETWEEN THE AGE OF TWO AND FOUR,
HE WENT THROUGH A HUNDRED-- A HUNDRED!--
SEPARATE GENERAL ANAESTHESIA OPERATIONS,
TO REPAIR THE FISTULA THAT CONTINUED TO FORM BETWEEN HIS RECTUM
AND THE OUTSIDE OF HIS BODY.
AND IT WAS TOTALLY UNSUCCESSFUL.
AND BY THE TIME NICK WAS FOUR YEARS OLD-- FOUR YEAR OLD KID--
HE WEIGHED NINE KILOGRAMS.
THAT'S 20 POUNDS!
FOUR YEAR OLD WEIGHED 20 POUNDS, AND HE WAS FAILING.
LITERALLY, FAILING.
THE KID WAS JUST NOT GOING TO MAKE IT.
AND THE SURGERIES GOT MORE AND MORE RADICAL.
AT FIRST, THEY TRIED TO DO RE-SECTIONS ON HIS COLON.
THAT DIDN'T WORK.
MEANING, TAKE SECTIONS OUT OF HIS COLON.
AND ULTIMATELY, WHAT THEY HAD TO DO, WAS COMPLETELY REMOVE HIS COLON
FROM THE END OF THE SMALL INTESTINE, THROUGH THE RECTUM.
SO, HERE HE IS, FOUR YEARS OLD, STARTING OUT HIS LIFE LIKE THAT.
AND ABOUT THE AGE OF FOUR, WHEN HE WAS RECOVERING FROM THIS SURGERY,
HE BEGAN TO BE FED THROUGH A G-TUBE.
AND ALL HIS BROTHERS AND SISTERS AND FRIENDS
WERE OUT HAVING A GOOD TIME WITH HALLOWEEN AND EATING HALLOWEEN CANDY,
AND POOR NICK VOLKER COULD NOT EAT, HE COULDN'T DRINK.
HE WASN'T ALLOWED TO HAVE THESE THINGS.
AND AWARE OF HOW MUCH SICKNESS HE WOULD GET
EVERY TIME HE WOULD EAT AND DRINK,
HE WOULD CONTINUALLY BEG HIS MOTHER FOR FOOD AND WATER.
HE DIDN'T CARE IF HE GOT SICK.
HE JUST WANTED TO EAT.
I MEAN, THIS BREAKS MY HEART.
SO, FINALLY, THEY GOT WISE,
AND THEY SAID, "WE TRIED EVERYTHING ELSE."
SO, AT 100 SURGERIES, HE HAD CAPPED-OUT HIS MEDICAL EXPENSE.
MORE THAN $2 MILLION HAD GONE INTO DIAGNOSIS AT THIS POINT.
STILL DIDN'T HAVE ANY IDEA WHAT IT WAS.
THEY SAID, "FINE, LET'S TRY THIS ONE LAST THING.
"LET'S SEQUENCE HIS GENOME."
SO, THEY DID.
THEY DID THIS AT THE MEDICAL COLLEGE OF WISCONSIN.
THIS IS A VERY FAMOUS CASE-- YOU GUYS CAN LOOK THIS UP.
IT'S ALL OVER THE PLACE.
AND WHAT THEY FOUND WHEN THEY SEQUENCED HIS GENOME
WAS THAT THERE WAS A VARIATION
IN A PRO-INFLAMMATORY PROTEIN CALLED X.I.A.P.
AND THAT ONE VARIATION, BASICALLY, EXPLAINED AWAY THE DISEASE THAT HE HAD.
AND SO, WHAT THEY DID
IS THEY GAVE HIM A BONE MARROW TRANSPLANT.
SO, TO GIVE SOMEBODY A BONE MARROW TRANSPLANT
FOR SOME SORT OF DIGESTIVE DISORDER, THAT DIDN'T QUITE JIVE.
THEY WOULD NEVER REALLY HAVE KNOWN TO DO THAT,
HAD THEY NOT SEQUENCED HIS GENOME.
AND IT'S A RISKY THING IN A LITTLE KID, PARTICULARLY, SICK--
SOMEONE WHO IS AS SICK AS NICK WAS.
SO, THEY GAVE HIM THE BONE MARROW TRANSPLANT.
FORTY-TWO DAYS LATER,
HE WAS OUT OF THE HOSPITAL, GAINING WEIGHT, EATING AND DRINKING.
AND SINCE THAT TIME, HE HAS GROWN NORMALLY.
I FIND THIS TO BE COMPLETELY UNACCEPTABLE, AS A SOCIETY.
WE ARE BETTER THAN THIS.
WE KNEW THE RIGHT THING TO DO AHEAD OF TIME-- THE SMART THING TO DO.
WE SPENT $2 MILLION AND PUT THIS KID AND HIS FAMILY
ON A DIAGNOSTIC MEDICAL ODYSSEY THAT WAS PAINFUL AND EXPENSIVE.
WE COULD SPENT $30,000 WHEN WE FIRST SAW THE PROBLEM,
SEQUENCED HIS GENOME, SAVED HIS COLON, AND RECTIFIED HIS ENTIRE LIFE.
THIS IS WHY GENOMIC MEDICINE IS IMPORTANT.
THIS IS WHY YOU WILL SEE IT IN YOUR LIVES.
IT'S SO POWERFUL, THAT IT'S GONNA HELP A LOT OF PEOPLE
AND A LOT OF DIFFERENT DISEASES.
AND BY THE WAY, THAT DISEASE IS IDIOPATHIC AND CRYPTOGENIC,
MEANING THAT THE ANSWER IS HIDDEN INSIDE THE GENOME.
OKAY... PHARMACOGENOMICS.
(clearing throat)
SO, PHARMACOGENOMICS IS THE RELATIONSHIP BETWEEN YOUR GENOME--
AND THE VARIATIONS IN YOUR GENOME--
AND YOUR ABILITY TO METABOLIZE DIFFERENT DRUGS.
SO, LOTS OF PEOPLE ARE ON PRESCRIPTION DRUGS,
MANY PEOPLE IN THIS AUDIENCE ARE ON PRESCRIPTION DRUGS.
HAVE YOU EVER ASKED YOURSELF WHETHER OR NOT THAT DRUG WAS WORKING?
HAVE YOU EVER KNOWN SOMEBODY WHO WAS SICK AND PRESCRIBED DRUGS,
AND THE DRUGS DIDN'T SEEM TO WORK?
TURNS OUT THAT THIS HAPPENS ALL THE TIME...
AND IT'S BECAUSE EVERYBODY METABOLIZES THINGS SLIGHTLY DIFFERENT.
SO, RIGHT NOW, THERE IS ABOUT 125 DRUGS THAT ARE COMMERCIALLY MANUFACTURED,
FOR WHICH THERE ARE GENETIC VARIANTS KNOWN
THAT AFFECT THE METABOLISM AND ACTIVITY OF THOSE DRUGS.
SO, THIS IS A SMALL LIST, AND THERE'S THE REFERENCE AT THE BOTTOM,
IF YOU WANT TO CHECK THIS.
AND I'D LIKE TO FOCUS ON ONE OF THESE.
OKAY, SO THESE ARE REALLY THE TOP TWO PRESCRIBED DRUGS IN OUR COUNTRY--
THIS IS STATINS.
PEOPLE WHO HAVE HIGH CHOLESTEROL, TRIGLYCERIDES, THAT KIND OF THING.
AND THIS IS PLAVIX CLOPIDOGREL.
OKAY, SO IN THIS CASE, WHAT WE KNOW FOR CLOPIDOGREL--
THAT THERE IS A VARIANT IN A GENE CALLED CYP2C19,
AND THAT PARTICULAR VARIATION MAKES THE DIFFERENCE
BETWEEN BEING ABLE TO METABOLIZE THE PRO-DRUG
INTO ITS ACTIVE FORM OR NOT.
IF YOU HAVE ONE VARIATION, YOU SIMPLY CAN NEVER METABOLIZE THE DRUG,
YOU WILL DERIVE NO BENEFIT FROM THE DRUG.
SO...
THIS IS THE DRUG, CLOPIDOGREL-- PLAVIX.
NOW, FIRST OF ALL, I HAVE TO SAY
THAT MANY, MANY PEOPLE ARE HELPED BY THIS DRUG.
THIS DRUG IS AN ANTI-PLATELET.
SO, FOR PEOPLE WHO HAVE CARDIAC DISEASE
OR ANCILLARY-RELATED DISEASES LIKE STROKE,
THIS IS A VERY EFFECTIVE DRUG
AND IT HELPS MILLIONS AND MILLIONS OF PEOPLE, ALL AROUND THE WORLD.
I DON'T WANNA BASH THIS DRUG-- IT'S A GOOD DRUG.
BUT THE DRUG JUST ACTUALLY DOESN'T WORK ON EVERYBODY.
OKAY, SO...
WHEN I SAY APPROXIMATELY 30 PERCENT OF PEOPLE-- THIS IS GONNA--
REMEMBER THIS PART, FOR THE NEXT SECTION,
WHEN I TALK ABOUT EVOLUTION AND GLOBAL GENOGRAPHY.
HOW WELL THIS DRUG WORKS HAS SOMETHING TO DO, IN MANY CASES,
WITH WHAT YOUR ETHNICITY IS...
BECAUSE EVERYBODY'S ETHNICITY BRINGS WITH IT
A DIFFERENT SET OF GENOMIC INFORMATION,
AND SMALL LITTLE VARIATIONS CAN CHANGE HOW WELL YOU METABOLIZE DRUGS.
SO, 30 PERCENT OF THE PEOPLE, ON AVERAGE,
WHO ARE PRESCRIBED THIS DRUG, CANNOT USE IT-- CAN'T METABOLIZE IT.
OKAY.
THAT WE TALKED ABOUT.
SO, LET'S JUST TALK ABOUT THE BUSINESS OF THIS DRUG FOR A SECOND.
UH, PLAVIX IS MANUFACTURED GLOBALLY.
IT IS DISTRIBUTED GLOBALLY TO 125 COUNTRIES AROUND THE WORLD.
HUNDREDS OF MILLIONS OF PEOPLE TAKE THIS DRUG.
IN THE UNITED STATES, THE ANNUAL REVENUES-- AT LEAST IN 2009--
FOR PLAVIX WERE $6.6 BILLION.
OKAY, THAT'S A LOT OF MONEY.
NOW, ANY OF YOU, UNLESS YOU'VE BEEN LIVING UNDER A ROCK,
KNOW THAT OUR HEALTHCARE SYSTEM HAS GOT SOME FINANCIAL PROBLEMS, RIGHT?
OKAY, SO CHECK IT OUT.
YOU DO THE MATH ON THIS-- AND IT'S PRETTY SIMPLE MATH--
6.6 BILLION TIMES 30 PERCENT OF THE PEOPLE THAT CAN'T ACTUALLY USE IT,
THAT'S $2 BILLION WASTED, EVERY SINGLE YEAR.
THAT'S ONE DRUG, ONE COUNTRY, ONE YEAR.
IF YOU BEGIN TO EXTRAPOLATE THIS KIND OF THING OUT TO LOTS OF DRUGS
AND ALL COUNTRIES THAT COULD USE THIS SORT OF TECHNOLOGY,
YOU BEGIN TO SEE, THAT BY TARGETING PEOPLE WITH THEIR DRUG BETTER,
WE SAVE A LOT OF MONEY, NOT TO MENTION
THAT THERE ARE 30 PERCENT OF THE PEOPLE OUT THERE
THAT DERIVE NO BENEFIT FROM THIS DRUG!
IT'S NOT HELPING THEM!
AND SO, WHAT HAPPENS?
THEY GET SICK.
WHEN THEY GET SICK, WHAT DO THEY DO?
THEY GO TO THE HOSPITAL.
AND HOSPITALS ARE EXPENSIVE.
YOUR GOAL IS TO STAY OUT OF THE HOSPITAL.
OKAY, THIS IS JUST ONE EXAMPLE.
THERE'S, YOU KNOW, 125 THAT WE KNOW OF LIKE THIS.
NOW, THIS-- (chuckling) THIS DRIVES ME CRAZY,
AND FORGIVE ME FOR BEING PASSIONATE, BUT...
PLAVIX HAS ACTUALLY A WARNING ON THE BOX...
THAT THE F.D.A. MANDATES HAS TO BE ON THE BOX-- A BLACK BOX WARNING.
WHEN YOU LIKE-- IF YOU EVER BUY A PACK OF CIGARETTES,
THE BLACK BOX WARNING THAT SAYS, "WARNING-- IF YOU SMOKE THIS,
"YOU WILL GET CANCER AND DIE.
"IT WILL BE AWFUL." (audience laughing)
WELL-- RIGHT?
SO, PLAVIX HAS A BLACK BOX WARNING RIGHT ON THAT BOX THAT I SHOWED YOU
THAT SAYS, "TO TAKE THIS DRUG,
"YOU NEED TO TEST WHICH VARIANT OF CYP2C19 YOU ACTUALLY HAVE."
AND NOBODY DOES THE TESTING.
CRAZY.
OKAY.
PRENATAL GENETIC DIAGNOSTICS.
SO, IF YOU CAN SEQUENCE AN ADULT HUMAN
AND DETERMINE ALL THESE THINGS FOR AN ADULT HUMAN,
YOU OUGHT TO BE ABLE TO DO IT
FOR SOMEBODY THAT'S DEVELOPING TO BE AN ADULT,
ALL THE WAY IN THE EMBRYO.
SO, WE DO SOME OF THIS KIND OF STUFF RIGHT NOW
ON A LIMITED BASIS FOR DOWN SYNDROME OR CYSTIC FIBROSIS
OR VARIOUS OTHER THINGS.
UM...
USUALLY, WHEN I SHOW THIS SLIDE, PEOPLE'S FIRST REACTION IS,
"THE REASON WE'RE DOING PRENATAL DIAGNOSTICS
"IS TO DETERMINE WHETHER OR NOT THIS PARTICULAR INFANT
"HAS SOME SORT OF MAJOR MEDICAL PROBLEM
"AND DO WE WANT TO CONTINUE THIS PREGNANCY?"
I WOULD SUBMIT TO YOU THAT THERE ARE FAR LESS DARKER THINGS
THAT WE COULD BE GAINING FROM PRENATAL DIAGNOSTIC SCREENING.
FOR INSTANCE, JUST LIKE SOME ADULTS CANNOT METABOLIZE CERTAIN DRUGS,
YOU PROBABLY HAVE MET PEOPLE WITH FOOD ALLERGIES
OR HAVE PROBLEMS WITH CHOLESTEROL-- HYPERCHOLESTEROLEMIA.
MIGHT BE NICE TO KNOW, BEFORE THE BABY ACTUALLY COMES OUT OF THE MOM,
WHETHER OR NOT THEY HAVE, LIKE, A PROBLEM METABOLIZING CHOLESTEROL,
AND IF SO, WE MAYBE DON'T WANT TO BREASTFEED THE BABY,
OR MAYBE WE WANT TO MONITOR THE CHOLESTEROL LEVEL IN MOM,
WHILE SHE'S BREASTFEEDING, OR PUT HER ON STATINS.
THESE KINDS OF THINGS THAT WILL LEAD TO HEALTHCARE, YOU KNOW,
RIGHT FROM THE START, FROM THE FIRST BREATH.
AND SO, THIS INFORMATION, YOU KNOW, WHEN IT'S COLLECTED IN UTERO
CAN FOLLOW YOU FOR THE REST OF YOUR LIFE,
BECAUSE YOUR D.N.A. IS INVARIANT.
IT DOESN'T REALLY CHANGE.
THEY ONLY TIME IT REALLY CHANGES IS WHEN YOU GET CANCER, ALL RIGHT?
SO, ONE OF THE OTHER GREAT USES OF IN--
YOU KNOW, IN UTERO DIAGNOSTICS, IS THAT YOU HAVE A BASELINE
FOR THE REST OF YOUR LIFE.
YOU KNOW, BEFORE YOU HAVE BEEN EXPOSED TO ANY KIND OF ENVIRONMENTAL HAZARD,
YOU KNOW WHAT YOUR NASCENT GENOME SHOULD LOOK LIKE.
SO, EVERYBODY KNOWS THAT THERE'S THIS RELATIONSHIP
BETWEEN THE ENVIRONMENT AND THE GENOME, ALL RIGHT?
SO, SOME OF THE ST-- THIS IS JUST AN EXAMPLE RIGHT HERE--
IT TURNS OUT THAT FOR EVERY THREE CIGARETTES YOU SMOKE--
THE QUANTITATIVE ANALYSIS HAS BEEN DONE ON THIS--
AGAIN, FALLING IN THE CATEGORY OF FACT.
FOR EVERY THREE CIGARETTES YOU SMOKE,
YOU ACCUMULATE ONE SINGLE NUCLEOTIDE POLYMORPHISM MUTATION.
IN OTHER WORDS, YOU CHANGE ONE BASE IN YOUR GENOME.
WELL, SO THE PROBABILITY IS THAT EVERY TIME--
YOU GOT 6 BILLION BASES TO CHANGE.
YOU CHANGE ONE OF 'EM, PROBABLY THAT BASE CHANGE
IS NOT GONNA HAPPEN IN ANYTHING IMPORTANT, BUT THERE'S NO GUARANTEE.
AND SO, THIS IS THE KIND OF THING THAT LEADS TO CANCER PROGRESSION, RIGHT?
IT'S WHEN YOU GET THESE ACCUMULATED BASE CHANGES AND MODIFICATIONS
THROUGH TOXICOLOGY OF YOUR GENOME.
THAT'S ONE PART OF THE DISEASE.
RIGHT, SO I SAID I WAS GONNA MAKE HIS PERSONAL...
AND GIVE YOU ALL REAL EXAMPLES
OF WHAT I'M TALKING ABOUT WITH REAL PEOPLE.
AND RIGHT NOW, I'M GOING TO GIVE YOU AN EXAMPLE FROM ME.
SO, I'VE HAD MY GENOME ANALYZED,
AND I'M GONNA SHARE WITH YOU
THE ACTUAL RESULTS FROM MY GENOME ANALYSIS--
AT LEAST PARTS OF THEM-- I'M NOT HIDING ANYTHING.
I'M NOT AFRAID OF DISCRIMINATION BASED ON MY GENETIC MATERIAL.
MANY ARE.
(clearing throat) SO, MY GENOME WAS ANALYZED.
ABOUT 1.2 MILLION DATA POINTS WERE COLLECTED
FROM ALL THROUGHOUT MY GENOME,
AND THOSE WERE USED TO PROVIDE RISK ASSESSMENTS
FOR VARIOUS COMMON DISEASE,
FOR WHICH GENETIC INFORMATION IS CURRENT KNOWN.
IN OTHER WORDS, THESE ARE PROBABILITIES.
IN THIS PARTICULAR SLIDE, WHAT YOU'RE LOOKING AT IS THE GENETIC RISK
OR THE GENETIC PROBABILITY THAT I WILL GET A CERTAIN KIND OF DISEASE.
AND THESE ARE ACTUALLY, UM... RANKED.
AT LEAST THEY SHOULD BE RANKED IN TERMS OF GENETIC RISK, FROM HIGHEST TO LOWEST.
SO, RIGHT AT THE TOP-- CROHN'S DISEASE.
THAT'S A GASTROINTESTINAL DISORDER.
RIGHT BELOW IT, ULCERATIVE COLITIS-- ALSO GASTROINTESTINAL DISORDER.
NOW, I'VE NEVER BEEN DIAGNOSED WITH CROHN'S DISEASE,
BUT THAT'S PROBABLY BECAUSE I ABSOLUTELY HATE GOING TO THE DOCTOR
AND I NEVER GO, BUT I CAN TELL YOU THAT SOMETHING'S NOT RIGHT
AND I PROBABLY SHOULD GO TO THE DOCTOR.
AND SO, FOR ALL OF YOU WHO ARE DOING SOCIOLOGY AND PSYCHOLOGY,
THIS IS A BIG AREA OF RESEARCH IN THE FUTURE, STARTING RIGHT NOW,
AND THAT IS "WHAT DO PEOPLE DO WITH THE GENETIC INFORMATION,
"ONCE THEY HAVE IT?
"WHAT'S THEIR BEHAVIOR?"
IF I TOLD YOU THAT YOU HAD A PRETTY CHANCE GETTING DIABETES,
WOULD YOU PUT DOWN THE CHEESEBURGER?
WELL, THEY'RE TELLING ME THAT I HAVE A PRETTY GOOD, YOU KNOW, CHANCE
OF GETTING CROHN'S DISEASE.
DID I GO TO THE DOCTOR?
I DID NOT!
AND OSTENSIBLY, I AM SUPPOSED TO BE A SMART PERSON--
BRINGS THAT INTO QUESTION, I WOULD THINK.
SO, THAT'S THE GENETIC RISK.
THIS IS THE LIFETIME RISK.
AND SO, THE LIFETIME RISK IS A CALCULATION THAT GETS MODIFIED,
BASED ON MY ETHNICITY.
ALL RIGHT, SO I BROUGHT THIS THING UP ABOUT ETHNICITY
A COUPLE TIMES FOR DRUG METABOLISM, AND ALSO FOR DISEASES.
CERTAIN POPULATIONS AROUND THE WORLD
HAVE MORE OR LESS PROBABILITY