>> AN ANNOUNCEMENT, AFTER THE
LECTURE TODAY, WE'LL BE GOING
OVER FOR THE PATHOLOGY COURT
TOUR SO IF ANY OF YOU WOULD LIKE
TO GO, I'LL BE WALKING PEOPLE
OVER AT 6:00.
AND DAVID CLINER WILL BE
DISCUSSING.
AND TODAY OUR SECOND SPEAKER AND
NEAL CAPP A ROSO.
HE WILL TALK ABOUT EPIDEMIOLOGY
AND OUR FIRST SPEAKER IS KAREN
BROUSSARD., SHE GOT HER GRADUATE
DEGREE AT PENN STATE.
AND HER TITLE IS STEM CELLS AND
CANCER INITIATING STEM CELLS.
THE KAREN.
>> CAN EVERYBODY HEAR ME OKAY.
I HOPE MY HAIR DOESN'T GET IN
THE WAY.
I'VE GOT A BUNCH OF SLIDES TO GO
THROUGH, SO WE'RE GOING TO GET
STARTED.
ALL RIGHT, SO CANCER STEM CELLS
AND STEM CELLS IN GENERAL, IT'S
A VERY, VERY YOUNG FIELD AND
HOPEFULLY THIS GENERATED RITES A
LOT OF INTEREST BUT JUST TO GIVE
YOU AN IDEA OF HOW YOUNG IT IS
THE FIRST 1 CAME OUT ABOUT STEM
CELLS IN 1968 AND JUST BETWEEN
1985 AND NOW THERE ARE ONLY 16
CITATIONS.
SINCE 2000, AND THE NUMBER OF
CITATIONS IS AT 39 FOLD.
THERE'S A LOT OF INTEREST
GENERATE INDEED STEM CELLS AT
THAT POINT AND JUST SINCE 1987,
THERE'S ALMOST BEEN 31,000
MUTATIONS THAT HAVE POPPED UP
AND IN THIS YEAR, 2011 ALMOST
3000 WORKS OF PUBLICATION VS
BEEN PUT OUT, SO A LOT OF OF
INTEREST IN STEM CELLS, AS WELL
AS CANCER STEM CELLS HAVE
CURRENTLY BEEN GOING ON.
SO JUST TO GIVE EVERYBODY
BACKGROUND ABOUT STEM CELLS AND
GET EVERYBODY ON THE SAME PAGE,
BECAUSE THERE'S A LOT OF
MISGUIDED INDIVIDUALS OUT THERE.
THEY DON'T KNOW QUITE WHAT'S
GOING ON WITH STEM CELLS BUT 2
MAIN THINGS YOU NEED TO KNOW
ABOUT STEM CELLS, THEY ARE
CAPABLE OF SELF-RENEWAL AND THEY
CAN ALSO DIVIDE, FORM
DIFFERENTIATED PROGENY, THERE'S
THE 2 MAIN THINGS TO KNOW ABOUT
STEM CELLS.
THERE'S A VARIETY OF STAGES THAT
A STEM CELL CAN GO THROUGH AND
WHAT I HAVE LISTED UP HERE, AND
WE'RE TALKING ABOUT THE CELLS
WITH THE MOST POTENTIAL.
THESE ARE THE LEAST
DIFFERENTIATED AND I'LL WORK MY
WAY DOWN TO THE CELLS THAT HAVE
THE MOST DIFFERENTIATED CELLS,
THESE ARE THE UNIPOTENT CELLS,
WE'LL TALK ABOUT THAT SO ON
SUBSEQUENT SIDES WE'LL GO
THROUGH DIFFERENT EFFECTS THAT
OCCUR BETWEEN EACH OF THESE
STAGES WHICH ALLOW A CELL TO
BECOME PLURIPOTENT CELLSY POTENT
STATE SPENT ALLOW A CELL TO BE
MULTIPLE AND WE'LL GO OVER THAT
IN THE NEXT COUPLE OF SLIDES.
BUT THE START, THE CELL WITH THE
MOST POTENTIAL, THAT IS THE
LEAST DIFREPRESENTIATED IS A
SELL THAT IS CALLED A TOTI
PUTTENT CELL, THIS IS CAPABLE OF
OF PRODUCING AN ENTIRE ORGANISM,
ALL RIGHT?
THIS INCLUDES THE PLACENTA, ALL
RIGHT?
THERE IS AN EVENT THEY WILL TALK
ABOUT IN THE NEXT SLIDE CALLED
COMPACTION WHICH DISCIPLINARY
LINEATES WHEN A CELL GOES FROM
BEING TOTI-POTENT TO PLURIPOTENT
PLURIPOTENT.
THE CELLS ARE CAPABLE OF DOING A
CELL, WHICH INCLUDES 3 GERM
LAYERS IT'S A BIT MORE
DIFFERENTIATED THAN A TOTI
POTENT CELL IT CANNOT MAKE THE
TROPOBLAST WHICH WILL FORM THE
PLACENTA SO IT'S DISTINGS
WISHING AGAINST THE CELLKS SO
THERE'S AN EVENT, I'LL GO OVER
IT IN THE NEXT COUPLE OF SLIDES
CALLED GASTROALATION WHICH
DELINEATES CELLS BEING
PLURIPOTENT FROM MULTIPOTENT
STATE POTENT, MULTIPOTENT CELLS,
AND THEY'RE INCAPABLE OF
PRODUCING CELL TYPES FROM 1 TO 3
DIFFERENT LAYERS.
THE MOST DIFFERENTIATED SELL
WITH THE LEAST POTENTIAL IS THE
UNIPOTENT CELL AND THAT CELL
TYPE IS CAPABLE OF PRODUCING 1
SPECIFIC CELL.
AS AN EXAMPLE, I HAD THE
HEPATOCYTE THERE, AND SO THOSE
ARE THE MOST DIFFERENTIATED, HAD
THE LEAST POTENTIAL OUT OF ALL
THE DIFFERENT CELLS THAT ARE
POSSIBLE.
SO AS I MENTIONED THERE ARE
SEVERAL EVENTS THAT OCCURRED
DISTINGUISHING TOTI AND
PLURIPOTENT CELLSY POTENT STATE
SPENT MULTIPOTENT CELLS WITHIN
THE STEM CELL HIERARCHY.
SO BEGINNING AT THE 1 CELL
STAGE, YOU HAVE THE FUSION OF
THE EGG AND THE SPERM, OKAY.
AND THAT CELL THEN WILL
DIFFERENTIATE OR DIFFERENTIATE
AND DIVIDE, PROLIFERATE.
AROUND APPROXIMATELY THE 8 AND
16 CELL STAGE, YOU WILL HAVE AN
EVENT AS I MENTIONED BEFORE
CALLED COMPACTION.
OKAY?
IT'S KIND OF VISIBLE HERE, YOU
CAN CHOIRLY SEE AT THE 16 CELL
STAGE, INDIVIDUAL CELLS IN THE
ZYGOTETHERE, ONCE IT OCCURS, AND
SEE WHICH YOU'VE ACTUALLY.
ON THESE STRUCTURES THAT WILL
YOU CAN UTILIZE--
IT WILL RESULT IN THE FORMATION
OF 2 DISTINCT CELL LAYERS, ALL
RIGHT, THE EXTERNAL CELLS AS I
JUST POINTED OUT WILL GIVE RISE
TO THE TROPOBLAST WHICH WILL
FORM THE PLACENTA THOSE INNER
CELLS WILL RISE TO BE INNER CELL
MASS, THEY WILL BE PLURIPOTENT
CELLSY POTENT STATE SPENT THESE
CAN FORM THE EMBRYO AND THE
ENTIRE STRUCTURE WITH THE INNER
CELL MASS AND THE TROPOBLAST IS
CALLED THE BLASTOCYST.
ALL RIGHT?
SO WE JUST MENTIONED THAT CELLS
ARE TOTI POTENT UP TO
APPROXIMATELY THE 16 CELL STAGE.
YOU HAVE AN EVENT CALLED
COMPACTION WHICH THEN OCCURS
RESULTING IN THE BLASTULA, ALL
RIGHT WITH THE TROPOBLAST, THE
CELLS THAT ARE LINING THAT
STRUCTURE AND THE INNER CELL
MASS, THE CELLS OF THE INNER
CELL MASS THEN WILL BE
PLURIPOTENT WHICH YOU TAKE THEM.
AND THEN THERE IS ANOTHER EVENT
WHICH THEN DISTINGUISHS
PLURIPOTENT TO MULTIPOTENT
STATANT CELLS CALLED
GASTROALATION, GASTROALATION IS
THEN FORMATION OF DIFFERENT GERM
LAYERS WITHIN THE CELL AS IT
DIFFERENTIATES.
GASTROALATION WILL OCCUR WHEN
HAVE YOU APPROXIMATELY 16 TO 100
CELLS AND YOU WILL THEN GET THE
FORMATION OF 3 DISTINCT GERM
LAYERS SPECIFICALLY ECTODERM
WHICH WILL RISE TO FORM THE
EPIDERMIS, ANY SORT OF NEURAL
CELLS, MESODERM, MUSCLE,
CARTILAGE, BLOOD AND BONES AND
THEN THE ENDODERM, SPECIFICALLY
LIKE INTERNAL ORGANS IN THE GUT.
ANYONE OF THESE CELLS ARE
CONSIDERED MULTIPOTENT.
OKAY?
SO AGAIN, TOTI POTENT CELLS WITH
THE FORMATION OF THE ZYGOAT,
THEN COMPACTION, THEN FORMATION
OF THE BLASTOCYST WITH THE
TROPOBLAST, INNER CELL MASS,
THESE CELLS ARE PLURIPOTENT
CELLSY POTENT STATE SPENT
COMPACTION WILL OCCUR AND THEN
GASTROALATION WILL OCCUR AND
THEN HAVE YOU FORMATION OF EACH
1 OF THE 3 DIFFERENT GERM LAYERS
AS WELL AS GERM CELLS.
THEY WILL BE AVAILABLE.
OKAY, AND THEN FINALLY AS I
MENTIONED, CELLS WITH THE LEAST
POETIC TECTIAL THAT ARE
MOST--POTENTIAL THAT ARE MOST
DIFFERENTIATED ARE UNIPOTENT
CELLS, THESE ARE CELLS WHICH
HAVE UNDERGONE DIFFERENTIATION
TO THE POINT WHERE THEY ARE VERY
SPECIFIC, THEY'RE VERY
SPECIALIZED.
EXAMPLES INCLUDE BONE CELLS AND
ENDOTHELIAL CELLS AND NERVE
CELLS, ALL RIGHT, EACH 1 OF
THESE CELL TYPE K'S ONLY MAKE
MORE OF THEIR KIND.
OKAY THAT,'S WHY THEY'RE
UNIPOTENT STATANT.
--UNIPOTENTENT.
SO AGAIN TOT-POTENT CELLS, THESE
CAN MAKE EVERY CELL TYPE IN THE
BODY INCLUDING THE PLACENTA, THE
TROPOBLAST, ONCE THOSE CELLS
UNDERGO COMPACTION AND THEY HAVE
FORMATION OF THEM, THE CELLS
WILL THEN BECOME PLURIPOTENT.
IF YOU TAKE THEM FROM THE INNER
CELL MASS, OKAY, GASTROALATION
OCCURS TO WHERE YOU HAVE
FORMATION OF 3 DISTINCT GERM
LAYERS AND THEY ARRIVE WITHIN
THE GERM LAYERS AND MORE
SPECIALIZED AND DIFFERENTIATED
TO BECOME SPECIFIC CELL TYPES
AND KERO10 O SIGHTS AND BONE
CELLS ET CETERA.
THESE ARE ALL UNIPOTENT.
SO I'M SURE MANY OF YOU ARE
FAMILIAR, THERE'S BASICALLY 2
DIFFERENT TYPES OF STEM CELLS
THAT ARE AVAILABLE TO
RESEARCHERS, SPECIFICALLY
EMBRYONIC AS WELL AS ADULT STEM
CELLS AND WHAT ARE THEY?
EMBRYONIC STEM CELLs AS I'VE
BEEN MENTIONING DEPENDING WHERE
YOU ISOLATE THEM FROM, AS YOU
ISOLATE THEM, IT'S PRIOR TO
COMPACTION OCCURRING, THESE
CELLS CAN GIVE RISE TO ANY CELL
WITHIN THE BODY IF YOU ISOLATE
THEM FROM THE INNER CELL MASS,
ALL RIGHT?
THESE WILL BE CONSIDERED PLUFFY
POTENT STATE SPENT THEY WILL NOT
BE ABLE TO FORM THE TROPOBLAST,
IF YOU'RE INTERESTED IN DOING
ANY RESEARCH WITH THEM.
BUT REGARDLESS OF IF THEY'RE
POTENT STATANT OR PLURIPOTENT,
THEY HAVE HIGH CLINICAL VALUE,
CAN BE USED FOR SPINAL CORD
INJURY, PARKINSON'S DISEASE,
ALZHEIMERS DISEASE AND OBVIOUSLY
AS MANY OF YOU ARE AWARE,
THERE'S ETHICAL CONCERNS
ASSOCIATE WIDE USING THEM.
BUT ON THE OTHER HAND, ADULT
STEM CELLS AS LONG AS HAVE YOU
THE CONSENT OF THE INDIVIDUAL,
THERE SHOULD BE NO PROBLEM WITH
USING THEM.
ALL RIGHT, TYPICALLY HARVEST
THEM FROM THE BONE MARROW, AND
THESE ARE MULTIPOTENT STATEINENT
NATURE, THEY'RE HEMEAT O POETEC
STEM CELLS, AND YOU IF YOU GET
THEM FROM A PERSON,---THEY ARE
LIMITED IN THE POTENTIAL THEY
HAVE, THEY CANNOT FORM EVERY
CELL TYPE IN THE BODY.
AS A RESULT OF THIS, THERE IS A
CELL TYPE, DOWN AT THE BOTTOM
HERE THAT I HAVE LISTED
INDUCIBLE PLURIPOTENT STEM CELLS
THAT THEY STARTED TO GENERATE TO
CIRCUMVENT THE PROBLEM WITH
LIMITED POTENTIAL WITH USING
MULTIPOTENT CELLS.
SO WHAT ARE THESE IPS CELLS?
WELL, THE IDEA BEHIND THEM IS TO
TAKE AN ADULT STEM CELL, ALL
RIGHT?
AND GENETICALLY REPROGRAM THEM
TO REDIFFERENTIATE THEM TO A
MORE EMBRYONIC LIKE STATE SO YOU
CAN MAKE OTHER CELL TYPES FROM
THEM.
TYPICALLY DONE USING EITHER
TRANSFECTION OR INFECTION INTO
WHATEVER CELL LINES ARE
INTERESTED IN USING.
, AND, AND IN PARTICULAR--AND
SOME OF YOU MAY NOTICE THAT
THERE'S C-MYC IN THERE AND THIS
IS A KNOWNONCHA GENE, AND THESE
ARE CANCER CAUSING PROBLEMS THAT
MAY RESULT FROM INFECTING CELLS
WITH C-MYC.
THERE'S A NEW GROUP THAT WAS
DISCOVERED SOX 2, NANOG, AND
LYNN 128.
AND, AND THOSE ARE COMMON, MORE
COMMON ARE THE KERATINOID.
>> YOU TAKE A VERY COMMON CELL,
AND AND THE HEMEAT O POETIC
CELLS, AND THERE ARE 4 EMBRYONIC
LIKE GENES AND AND WITH THE
KERO10 O SIGHTS SHE CAN
DIFFERENTIATE THEM THEM FROM THE
CARDIOMYOCYTES AND YOU USE THOSE
FOR DISEASE OR IMPLANTATION.
, THERE'S ANOTHER PROGRAM THAT
CAN BE USED IN THE LABORATORY
AND THE WAY THIS IS DONE IS YOU
TAKE A SOMEATIC CELL AND A
GENERIC CELL, ALL RIGHT, THAT
NUCLEUS THEN IS IMPLANTED INTO
AN ENUCLEATED OVUM AND I'LL SHOW
YOU HOW THIS WORKS IN A SECOND.
BUT YOU HAVE THE BLASTOCYST WITH
THE CELL WHICH IS WILL CONTAIN
DNA IDENTICAL TO THAT HOST AND
THIS IS THE METHOD BY WHICH THIS
WAS MADE.
THE PROBLEM WITH USING THIS IS
YOU DON'T REALLY GET A GOOD RATE
OF LIVE BIRTH, IT'S
APPROXIMATELY ONLY 1-2 PERCENT
THAT ACTUALLY WORK BECAUSE OF
FAULTY REPROGRAMMING, BUT THE
NICE THING ABOUT IT IS YOU CAN
GENERATE CELLS FOR THERAPEUTIC
CLONING IF YOU NEED TO DO
ANYTHING WITH IT.
SO HERE'S HOW SOMATIC CELL
NUCLEAR TRANSFER WORKS, SO I'LL
START AT THE BOTTOM LEFT,
BOTTOM, SO WE HAVE A RUN OF THE
MILL EGG THAT YOU JUST TAKE AND
THE CENTER OF THE NUCLEUS FROM,
AND YOU THEN HAVE WHATEVER CELL
TYPE THAT YOU'RE INTERESTED IN
STUDYING, THAT CELL TYPE IS
FUSED WITH YOUR EGG THAT YOU
REMOVE THE NUCLEUS, AND THEN
THAT THEN DEVELOPS INTO AN
EMBRYO AND YOU THEN IMPLANT THAT
CELL OR GROUP OF CELL INTO
FEMALE AND THEN HAVE YOU
WHATEVER CLONE YOU'RE INTERESTED
IN AND IT IS GENERATED.
THERE YOU GO.
SO HERE A A NICE LITTLE THAT YOU
MIGHT UTILIZE IN THE LABORATORY
TO STUDY STEM CELLS AND LOOK AT
THESE DIFFERENT TECHNIQUES.
SO AS KIND OF A BASELINE WITH
WHICH TO MODEL ALL THESE AFTER
ON THE VERY LEFT WE HAVE JUST
GENERIC INVITO FERTILIZATION,
OKAY SO YOU WOULD HAVE AN EGG
AND A SPERM BE FUSED AND YOU GET
THE RESULTING ZYGOTE, AGAIN, THE
CELLS HERE WOULD THEN HAVE
UNDERGONE COMPACTION, HAVE YOU
THE INNER CELL MASS, AND THEN,
AFTER YOU TAKE THAT OUT OF THE
PETRI DISH AND TILT PUT THAT IN
THE FEMALE, HAVE YOU THE BABY,
AND ON THE OTHER HAND IF YOU'RE
INTERESTED IN STUDYING ANY OF
THESE, ONCE YOU DO THAT HAVE YOU
THE RESULTS ZYG SOCIETY, YOU
TAKE THEM FROM THE PLURIPOTENT
CELLSY POTENT PLURIPOTENT
STAGE FROM COMPACTION OR YOU
COULD TAKE CELLS FROM THE INNER
CELL MASS, AGAIN THESE ARE
PLURIPOTENT AND TAKE ANY 1 OF
THESE, GROW IT UP IN A PETRI
DISH AND THEN USE IT FOR CELLS
FOR A LINE OR CLONING OVER
WHATEVER YOU'RE DOING.
SO THE TRANSFER IS COMPARABLE,
YOU HAVE A EGG, RUN OF THE MIG
EGG THAT YOU REMOVE THE NUCLEUS,
AND THEN TAKE WHATEVER CELL
YOU'RE TESTING IN, AND IN THIS
CASE, THAT IS THESE CELLS.
YOU THEN FUSE THOSE CELLS WITH
THE NUCLEATED EGG, AND YOU WOULD
THEN DEVELOP IN A ZYGOTE AND
UNDERGO COMPACTION, AND HAVE YOU
INNER CELL MASS, YOU TAKE THOSE
FROM EITHER 1 OF THESE STELLS
AND PUTçó THEM IN A PETRI DISH AND
DO WHATEVER YOU WANT TO DO WITH
THEM.
SO THEY'RE ALL VERY, VERY
SIMILAR, JUST COME FROM
DIFFERENT ANGLES.
SO THE MAIN QUESTION EVERYBODY
ASKS ME IS ARE THERE CLINICAL
TRIALS GOING ON WITH THE STEM
CELLS AND YES, THERE ACTUALLY
ARE.
>> AS OF RIGHT NOW, THERE ARE 3.
>> TWO DIFFERENT COMPANIES.
FIRST COMPANY THEY'LL GO OVER IS
CALLED GERON, AND THEIR TRIAL
STARTED A LITTLE OVER 2 YEARS
AGO, JANUARY 2009.
THE OTHER COMPANY, CURRENTLY HAS
2 TRIALS GOING ON.
THEY ARE CALLED ADVANCED CELL
TECHNOLOGIES, THEIR TRIAL
STARTED ALMOST A YEAR AGO.
NOVEMBER OF LAST YEAR AND THEN
THEY ALSO HAD ANOTHER TRIAL THAT
JUST STARTED IN JUNE OF THIS
YEAR.
BOTH OF THESE TRIALS ARE PHASE
1-2 TRIALS, IT'S TO MAKE SURE
THEY'RE OKAY TO USE WITH HUMANS
AND AT LEAST WITH GERON, THEY
WERE THE FIRST 1 TO GET
APPROVAL.
IT TOOK THEM 4 YEARS TO GET
APPROVAL TO DO THIS IN HUMANS
AND ALL RIGHT, SO I'LL JUST
BRIEFLY GO OVER EACH TRIAL, HAVE
YOU AN IDEA OF WHAT'S CURRENTLY
GOING ON OUT THERE.
GERIATRICKIZATIONON IS THE FIRST
GROUP THAT'S CURRENTLY WORKING
WITH HUMAN EMBRYONIC STEM CELL,
THEY'RE HOPING TO GET 8 TO 10
PATIENT WHO IS ARE PARAPLEGIC,
CAN YOU USE THEIR ARMS BUT NOT
THEIR LEGS SO SPECIFICALLY
DEALING WITH SPINAL CORD
INJURIES, THEY ARE CONDUCTING
THEIR STUDY ALL ACROSS THE
UNITED STATES AT MULTIPLE
LOCATIONS AND WHAT THEY'RE DOING
IS THEY HAVE A SPECIFIC TYPE OF
EMBRYONIC STEM CELL WHICH I'LL
MENTION INDEED A FEW SLIDES
WHERE THEY'RE GIVING TO PATIENTS
THAT, AND NOW LET'S LOOK THE
SITE OF INJURY AND IT'S LIMITIT
TO PATES WHO IS WITHIN THE AREA
OF THEIR SPINE AND FURTHER
INTERESTED IT'S PATIENTS WITH
COMPLETE AMERICAN SPINAL INJURY
ASSOCIATION PROCUREMENT GRADE A
THROUGH FINAL INJURY.
SO IF ANYONE'S A SPINAL PERSON
OUT THERE.
BUT THE PATIENTS ARE THEN GIVEN
ANTIREJECTION MEDS AND FOLLOWED
UP FOR ABOUT A YEAR.
AND PREVIOUSLY THEY CARRIED OUT
TRIALS IN RATS WITH THESE
INJECTIONS AND I SAW A VIDEO
TRIAL OF THESE AND IT WORKED
PRETTY GOOD.
THE FIRST PATIENT WAS INJECTED
ALMOST A YEAR AGO AND SINCE THEN
THEY HAVE 3 MORE PATIENTS WHICH
HAVE BEEN ENROLL INDEED THE
TRIAL AND IT TOOK THEM ALMOST 2
YEARS TO ACTUALLY GET PEOPLE
INTO THE TRIAL, YOU RECALL IT
WAS FIRST APPROVED BACK IN
JANUARY 09, VERY STRINGENT WITH
THE CRITERIA OF PEOPLE THEY'RE
LOOKING FOR.
SO THE FIRST PATIENT WAS
INJECTED IN THE SHEPHERD CENTER
IN THRAPT, GEORGIA, AGAIN SO
THEY HAVE MULTIPLE CENTERS
THROUGHOUT THIS AREA TO TRY TO
HELP PEOPLE GET THROUGH THESE
TRIALS.
AND THEY WERE INOCULATED WITH
THESE HUMAN EMBRYONIC STEM CELLS
ARRIVED AND THEY CALL GRN OPC 1
SO GERIATRICKIZATIONON, SITE
CELL 1.
THAT'S WHAT THAT STANDS FOR.
SO THESE GUYS, THESE PARTICULAR
CELLS, IT'S BEEN DEMONSTRATED IN
THE RATS THAT I MENTIONED
EARLIER, THEY HAVE REMILENNATING
AND STIMULATING PROPERTIES AND
AGAIN IT'S THAT EXPERIMENT THAT
THEY DID BEFORE, AND IT'S
SKINATTIC SCORES AND ANIMAL
SPINAL CORD INJURIES, AND SHOWED
THAT THERE WAS SUCCESSFUL
MILENNATION AROUND THOSE WHEN
THEY WERE INJUREDDED AND IT
TURNED OUT TO WORK GOOD IN THE
PRECLINICAL STUDIES.
THE TRIAL IS ALSO BEING DONE
WITH HUMAN EMBRYONIC STEM CELLS
BUT IT'S WITH THE TECHNOLOGY,
BOTH OF THOSE TRIALS THEY HAVE
GOING ON, BOTH DEAL WITH MACULAR
DEGENERATION OR MACULAR
DYSTROPHY, FIRST OF ALL MACULAR
DYSTROPHY IS FOR YOUNGER
INDIVIDUALS, CAUSES VISION LOSS
AND THEN AGE RELATED MACULAR
DEGENERATION IS FOR BLIPPEDNESS
IN ADULTS.
SIM--SAME KIND OF IDEA JUST WITH
DIFFERENT AGE GROUPS AND AGAIN
USING RETINAL CELLS DERIVE
FRIDAY HUMAN EMBRYONIC STEM
CELLS AND THIS 1 THANKFULLY WAS
APPROVED ABOUT A YEAR AFTER THE
APPLICATION WAS FIRST FILED SO
IT SEEMS LIKE THE FDA WAS TRYING
TO SPEED UP THE PROCESS AND STOP
TAKING SO LONG TO GET APPROVAL
FOR SOME OF THESE CLINICAL
TRIALS.
OKAY.
SO THE, SO THIS IS THE TOTAL
PATIENTS BETWEEN THE 2 DIFFERENT
STUDIES, AND SUPPOSED TO BE
OLDER, YOUNGER INDIVIDUALS, AND
AGAIN IT'S CONDUCTED ACROSS
MULTIPLE LOCATIONS AROUND THE
UNITED STATES TO MAKE IT EASY
FOR PATIENTS TO GET TO THE
TRIAL.
PREVIOUS STUDIES THAT WERE DONE
IN RATS SHOWED 100% IMPROVEMENT
OVER UNTREATED ANIMALS WITH NO
ADVERSE SIDE EFFECTS SO IT'S
VERY, VERY, PROMISING TO DO THIS
PARTICULAR INJECTION AND IT WAS
SHOWED THAT NEAR NORMAL FUNCTION
WAS ACHIEVE INDEED MICE BOTH
WITH [INDISCERNIBLE] AS WELL AS
DEGENERATION, SO IT SEEMS
PROMISING TO DO.
AND AS I POINTED OUT EARLIER,
ADVANCED CELL TECHNOLOGY HAS
DEVELOPED, AND IT WAS DETROYING
AN EMBRYO, AND WHAT THEY'RE
DOING THEN, PRIOR TO CELL
UNDERGOING COMPACTION IS TAKING
A CELL, HARVESTING A CELL FROM
THAT TOTI POTENT 1 AND THEN
DERIVE THE CELL LINE FROM USING
IT AND OBVIOUSLY THIS IS WHERE
IT HASN'T BEEN ABLE TO DO
EXTENSIVE LONG-TERM STUDY BUT AT
LEAST FROM WHAT THEY'VE SEEN SO
FAR, DOESN'T SEEM LIKE THERE'S
MUCH HARM IN REMOVING A CELL
FROM THIS EARLY STAGE EMBRYO, IT
SEEMS LIKE IT DEVELOPS FINE.
SO, THIS IS POTENTIALLY
SOMETHING THAT MIGHT BE ABLE TO
CIRCUMVENT ETHICAL ISSUES WITH
DESTROYING AN EMBRYO.
SO I'LL KIND OF SHIFT GEARS A
LITTLE BIT BECAUSE I'M NOW GOING
TO TALK MORE ABOUT CANCER STEM
CELLS, I WANT TO SHOW YOU SOME
GUYS SOME RESEARCH THAT'S GOING
ON IN THE LABORATORY JUST TO
GIVE YOU AN IDEA OF WHAT YOU CAN
DO USING STEM CELLS AND
REPROGRAMMING.
SO THE FIRST THING I'LL MENTION
TO YOU IS TRYING TO REPROGRAM
HUMAN CANCER CELLS USING THE
MOUSE MAMMARY GLAND AS A MODEL
SYSTEM FOR THAT.
SO SEVERAL YEARS AGO, IN THE
LABORATORY HERE AT THE NIH, WHAT
WE DID WAS ACTUALLY TAKE HUMAN
MOUSE SPERMATIA GONIA AND
IMPLANT THAT INTO A FEMALE MOUSE
MAMMARY GLAND AND WE SAW THAT
THOSE FEMALE MOUSE FROM MATTA
GONIA, SEE HERE WITH FISH, DONE,
SEE THE CELLS EXPRESSING THE Y
CHROMOSOME, NEXT TO THE 1S THAT
WERE FEMALE NEXT TO THE 1S THAT
WERE UNSTAINED, THESE CELLS WERE
ABLE TO RECAPITULATE A FEMALE
MAMMARY GLAND AND PATIENTS IN
THE CLINIC UPPER I HAVE SHOWN
HERE AND WE'RE CAPABLE OF HAVING
THOSE MALE CELLS TO SECRETE
MILK.
ALL RIGHT, SO I'LL GET INTO THIS
IN A COUPLE OF SLIDES BUT THIS
IS SHOWING THE POWER OF THE
MICRO ENVIRONMENT IN COUPLE WITH
STEM CELLS IN REPROGRAMMING
CELLS TO DO DIFFERENT FETES.
--FEATS.
SO IN ADDITION TO THOSE MAIL
MOUSE, WE DID A COMPARABLE
EXPERIMENT WITH NERVE CELLS,
NEWSPAPER O STEM CELLS AND THE
IMAGE SHOWN HERE THEN, IN RED,
ALL RIGHT, WE HAVE THESE MOUSE
NERVE CELLS THAT WE'VE
REPROGRAMMED USING SIGNALS FROM
THE MOUSE MAMMARY GLAND TO AGAIN
SECRETE MILK AND THIS IS A
RECAPITULATED MAMMARY GRAND
STRUCTURE HERE.
SO SINCE WE KNEW WE COULD DO
THAT WITH MALE MOUSE SPERMATIA
GONIA AND NEURAL CELLS WE WANT
TO THEN TAKE IT A STEP FURTHER
TO TRY TO INVOLVE MORE OF THE
STEM CELLS AS WELL AS CANCER
CELLS AND SEE IF WE COULD TAKE
HUMAN OR EXCUSE ME HUMAN
EMBRYONAL CARCINOMA CELLS AND
SEE IF WE COULD REPROGRAM THEM
LUESING THE MOUSE MAMMARY GLAND
AND SEE IF THEY COULD CONTRIBUTE
TO REGENERATION IN VIVO.
ALL RIGHT?
SO OUR MODEL SYSTEM AND THIS IS
WHAT WE USED IN SOME OF THE
OTHER EXPERIMENTS THAT I TALKED
ABOUT, WE HAVE 3 WEEK OLD MICE
WHERE WE SPECIFICALLY IMPLANT
OUR CELLS WITH WHATEVER WE'RE
DOING INTO THE NUMBER 4 AND THE
NUMBER 9 MAMMARY GLANDS, FAT
PADS AND THEY'RE BIG AND EASY TO
GET TO.
AND IT SEEMS LIKE EVERY TIME WE
IMPLANTED OUR CELLS WE NEED TO
IMPLANT NEM IN CONCERT WITH
MOUSE MAMMARY EPITHELIAL CELLS
TO GET THEM TO DO WHAT WE WANT
TO DO.
WE ALSO IMPLANTED OUR CANCER
CELLS BY CELLS AS WELL AS OUR
MAMMARY EPITHELIAL CELLS BY
THEMSELVES AS CONTROLS.
ALL RIGHT.
WHEN WE IMPLANTED THE CANCER
CELLS BY THEMSELVES, OKAY, WE
SAW NO OUTGROWTH FORMS AND WE
GOT TUMORS.
SO TUMOR FORMS AND THIS MAKES
SENSE.
>> BUT WHEN YOU PUT CANCER
CELLS, THESE HUMAN EMBRYONIC
STEM CELLS, THE CARCINOMA CELLS,
YOU PUT THEM IN CONCERT WITH
MAMMARY EPITHELIAL CELLS TO GIVE
THEM A PRIMER FOR WHAT THEY
SHOULD BE DOING.
YOU GOT OUTGROWTHS FORMING IN
NEARLY EVERY SINGLE CASE WITH NO
TUMORS.
ALL RIGHT?
SO HYPOTHETICALLY, WE THOUGHT
THAT WE HAD THESE HUMAN
EMBRYONAL CARCINOMA CELLS THAT
SEEM TO BE BEHAVING NORMALLY,
AND DID NOT FORM TUMORS IN THE
MICE.
SO WE WANT TO MAKE SURE THAT
THESE CANCER CELLS ARE ACTUALLY
THERE, THEY DIE OFF, WHAT
HAPPENED?
SO 1 OF THE THINGS WE USED WAS A
MARKER CALLED CD133, WHICH IS
SHOWN TO BE A MARKER FOR HUMAN
EMBRYONIC STEM CELLS AND WE TOOK
SECTIONS FROM OUR CHIMERIC
OUTGROWTH AND STAINED THEM FOR
CD133, ON THE LEFT HERE, YOU CAN
SEE THE RED STAINING CELLS ARE
ALL POSITIVE FOR CD133, HUMAN
CD133.
SO THESE SHOULD BE THOSE U MAN
EMBRYONAL CARCINOMA CELLS WE
IMPLANTED.
WE THEN TOOK IT A STEP FURTHER,
THESE HUMAN EMBRYONAL CARCINOMA
1S WERE MALE.
SO WE FORM THE CD133 CELLS,
PURIFIED THEM AND RAN DNA AND
RAN THE WORTHY Y CHROMOSOME AND
IT WOULD BE ON THE RIGHT HAND
SIDE THEN IS THE PC R THOUGHING
CD133 POSITIVE CELLS WERE ALSO
POSITIVE FOR THE Y CHROMOSOME
AND THEY WERE INDEED THOSE HUMAN
MALE CARCINOMA CELLS WE IMPLANT
THAD ARE NOW NOT TUMOR GENIC AND
BEHAVING LIKE MAMMARY EPITHELIAL
CELLS.
AND AGAIN, KIND OF THE PINNACLE
EXPERIMENT TO SEE IF WE COULD
TAKE THESE CELLS OR MALE CELLS
CANCEROUS MADE TO BEHAVE
NORMALLY AND GET THEM TO SECRETE
MILK AND INDEED WE COULD.
AND OVER ON THE RIGHT HAND SIDE,
WHAT YOU HAVE FOCUSED HERE, THE
BIG RED STAIN O GBA THE MIDDLE
IS MOUSE MILK, MOUSE CASING,
THIS IS A BIG LOBULE AND THE
GREEN, THE GREEN ARROW, THE
ALBUT MIN IS HUMAN MILK.
SO WE SEE THOSE HUMAN MALE
EMBRYONAL CARCINOMA CELLS ARE
REPROGRAMMED TO PRODUCE MILK.
SECRETE INTO THE SAME LOVUAL
THAT THE MOUSE GLAND IS THERE
AND IT'S BEHAVING NORMALLY AND
THE CANCER CELL.
SO IT'S POSSIBLE TO DO THINGS,
AND THOSE ARE THINGS FOR
EPITHELIAL SPECIFIC KERATINS,
OKAY?
CARATIN 8 AND 5.
AND YOU CAN SEE IN THE TOP LEFT
HAND CORNER, RED STAINING IS FOR
KERATIN 5, ALL RIGHT?
AND NEXT PANEL OVER, GREEN
STAINING IS FOR KERATIN 8 AND
THESE ARE FOR HUMAN KERATIN.
CRITERIA AND THOSE ARE NEW
EXPRESSING HUMAN KERATIN, AND
EXPRESSING THE MAMMARY GLAND.
AND WE WANTED TO SEE IF WE COULD
DO SIDE BY SIDE STAINING, AND
THERE'S SOME THAT CLEANS IT UP
AND MOUSE SPECIFIC ANTIBODIES
AND WE SHOW THAD WE HAD THESE
HUMAN STAINING CELLS.
AND THEY ARE WHERE, AND HAVE,
AND,5a AND EMBRYONIC CARC NOME
ACAN YOU USE THOSE, AND THEY CAN
BE REDIRECTED BY DEVELOPMENTAL
SIGNALS AND THE MOUSE MAMMARY
GLANDS.
--OF THAT GLAND THAT YOU'RE AND
FINALLY, WE ALSO SHOWED THAT
THOSE CELLS ARE CAPABLE OF
PRODUCING MILK SO COMPARABLE
CELL TYPE OF THAT GLAND IMPLANT,
AND ALSO THAT THOSE PROGENY ARE
CAPABLE OF DIFFERENTIATING
SPECIFIC PATHWAYS, SO FOR
CANCER, STEM CELLS WHICH I'LL
TALK ABOUT IN A BIT MORE DEATH
FOR THEM, SO CANCER AND SOME
PEOPLE CALL THEM CANCER
INITIATING STEM CELLS.
IT'S PRETTY CONTROVERSIAL TOPIC
BECAUSE NO 1 SO FAR HAS BEEN
CAPABLE OF GIVING A DEFINITIVE
DEFINITION FOR WHAT A CANCER
INITIATING CELL IS.
IS IT A NORMAL STEM CELL THAT'S
GONE ARRAY, A PROGENITOR CELL,
OR SELF-RENEWAL PROPERTY, IS IT
POSSIBLY CELL ORIGIN OF A TUMOR,
WHICH MIGHT BE THE SAME AS A
CANCER STEM CELL, WHICH IF
THAT'S THE CASE, IT MIGHT HAVE
IMPLICATIONS ON CANCER
PREVENTION AND PROTECTION.
SO ANY OF THESE ARE CANCER STEM
CELL MAY BE ABLE TO BE USED.
, AND IT'S DEVELOPED INTO
FORMING--
>> ONE, 2, 3, 4, 5, 6, 7, 8, 9,
10, 11, 12, 13, 14.
, IT WILL THEN EVOLVE INTO THE
STRANGE LOOKING STRUCTURES, NOT
COMPARABLE TO WHAT A NORMAL
BREAST WOULD DEVELOP INTO.
SO YOU WOULD THINK THEN TO
POSTULATE THAT CANCER STEM CELLS
SHOULD BE CAPABLE OF
SELF-RENEWAL JUST LIKE A NORMAL
STEM CELL WOULD BE SHOULD
RECAPITULATE ALL THE ORIGINAL 1S
IN THE TUMOR, SHOULD BE ABLE TO
YELLED A TUMOR IF YOU PUT IT IN
AN ANIMAL WITH JUST 1 SINGLE
CELL.
IF IT'S PUT IN THE RIGHT MICRO
ENVIRONMENT.
AS OF RIGHT NOW, THE ONLY TEST
TO DETERMINE THIS, A FUNCTIONAL
TEST, YOU HAVE TO TAKE WHATEVER
CANCER STEM CELL YOU PUT IT IN
AND SEE IF YOU GET A TUMOR FROM
IT.
THE PROBLEM NOW IS THAT WE HAVE
NO GOOD MARKER TO IDENTIFY
CANCER STEM CELL AS I'LL SHOW
YOU, THERE'S A VARIETY OF
DIFFERENT MARKERS PEOPLE ARE
USING AND THERE'S FOE 1 MARKER
THAT SAYS, A CELL IS A CANCER
STEM CELL.
SO HERE IS THE IDEA OF THE
PROBLEM BEHIND SO THE STEM CELLS
AND OTHER CELLS, YOU WOULD THEN
KILL OFF SOME DAUGHTER CELLS.
AND ANOTHER ROUND, 3 ROUNDS 4
ROUNDS WHATEVER IT TAKES, THAT
WILL HOPEFULLY DESTROY THE
REMAINING DAUGHTER CELLS, BUT
THE PROBLEM IS, THAT THE CANCER
STEM CELLS ARE STILL GOING TO BE
THERE.
AND NOW THE THERAPEUTICS AND
THEN THROW DIVIDE AND AS OF NOW,
WE HAVE NO IDEA HOW WIDE THESE
THINGS HAPPEN, TYPICALLY, AGAIN
I'M JUST USING THE BREAST AS AN
EXAMPLE.
OKAY, HAVE YOU YOUR MAMMARY STEM
CELL AGAIN WHICH YOU CAN SELL
FOR NEW AND DIVIDE TO GIVE
DIFFERENTIATED PROGENY, AT ANY 1
OF THESE STATES, THESE CELLS CAN
BECOME THEORETICALLY A CANCER
STEM CELL WHICH CAN THEN AGAIN
SELF-RENEW AND DIVIDE INTO FORMS
DIFFERENTIATED PROGENY.
BUT AGAIN, WHATEVER TUMOR THAT
IS DERIVED FROM THAT THAT
TUMOR'S GOING TO BE
HETEROGENEOUS, YOU WILL HAVE
DIFFERENT PROPERTIES OF CELLS
WITHIN THAT TUMOR OF WHICH YOU
WILL NEED SOME SORT OF
THERAPEUTIC TO GET AT THAT.
SO THAT'S THE MAINLIOR PROBLEM
WITH A LOT OF THERAPEUTICS OUT
THERE, RIGHT NOW.
SOME OF THE ISSUES ALSO WITH
CANCER STEM CELLS, JUST LIKE A
STEM CELL, THESE ARE GOING TO BE
VERY RARE.
THEY WILL BE HARD TO GET AT.
SO SOMETIMES THEY CAN BE
DORMANT.
THEY CAN LIE FOR YEARS WITHOUT
BEING FOUND, ALL RIGHT?
HOWEVER, IF YOU CAN FIGURE
THINGS OUT ENOUGH, SOME OF THEIR
PROPERTIES MAY ACTUALLY BE, CAN
YOU ACTUALLY HARNESS THEM.
THESE CELL SH'S BE CAPABLE OF
SELF-RENEWAL.
THEY SHOULD RECAPITULATE ALL
CELL TYPES WITHIN THE TUMOR.
ALL RIGHT?
AGAIN AS I MENTIONED YOU SHOULD
BE ABLE TO FORM A TUMOR FROM A
SINGLE CELL, IF YOU TAKE IT OUT
AND IMPLANT IT INTO A MOUSE.
OKAY?
AGAIN I MENTIONED THERE'S
PROBLEM WITH THERAPEUTIC
RESISTANCE.
CHEMO THERAPY AND RADIATION WILL
NOT GET AT THE CANCER STEM CELLS
AS OF RIGHT NOW.
IN THE LABORATORY THERE'S A FEW
WAYS CAN YOU ASSAY AND STUDY
THESE THINGS WHICH I WILL TALK
ABOUT IN THE NEXT FEW SLIDES.
THE MICHE ADAPTAISE AND CAN LOOK
AT SELF-RENEWAL AND LOOKING AT
STEMNESS OR GENE SIGNATURE AS
WELL AS ASYMMETRIC DIMENSION AND
RETENTION WHICH I'LL GO OVER IN
A FEW SLIDES TOO, THERE ARE SOME
SURFACE MARKERS WHICH PEOPLE ARE
UTILIZING BUT THIS' NO 1 THAT IS
CURRENTLY OUT THERE TO RAIRKS
DENTIFY CANCER STEM CELLS, ALL
RIGHT?
BUT IF YOU'RE LOOKING TO GET ANY
SORT OF PUBLICATIONS OUT THERE,
EVERYONE WILL TELL YOU YOU HAVE
TO HAVE MULTIPLE WAYS OF
IDENTIFYING THIS IN ORDER FOR
THE PAPER TO GET ACCEPTED.
YOU HAVE TO SHOW EVIDENCE WITH
BOTH PRIMARY TUMORS PLURAL
EFFUSIONS AS WELL AS IF YOU CAN
LOOK AT METASTATIC LESIONS IN
ORDER TO DEFINE WHATEVER CANCER
STEM CELL YOU WERE ATTEMPTING TO
DESCRIBE IN YOUR PUBLICATION.
SO AS AN EXAMPLE, 1 OF THE
METHODS YOU CAN IDENTIFY, CANCER
STEM CELL SYSTEM LOOKING AT 1
WAY OF RETENTION IN PARTICULAR
THE IMMORTAL STRAND HYPOTHESIS
AND WHAT IS THIS.
WELL, IT'S BEEN THOUGHT THAT
MOST STEM CELLS WILL SELECTIVELY
RETAIN THE TEMPLATE DNA STRAND
AND THIS WILL THEN--THESE PARENT
CELLS WILL YIELD DAUGHTER CELLS
WITH GENOMES THAT ARE REFLECTIVE
WITH THEIR PARENTS PARENTS AND WHY WOULD
THEY DO THIS, THEY OBVIOUSLY
WANT TO PROTECT THEIR TEMPLATE
DNA, FROM ANY SORT OF CHANGES,
ALL RIGHT, IN THE CASE OF NORMAL
CELLS THEY WANT TO PROTECT THEIR
TEMPLATE DNA FROM MUTATIONS
LEADING TO CANCER IN THE CASE OF
CANCER CELLS THEY WANT TO STAY
CANCEROUS, THEY WANT TO CONTINUE
TO DO DAMAGE.
ALL RIGHT?
SO HERE'S A SCHEMEATIC OF HOW
ASYMMETRIC DIVISION WORKS SO ON
THE LEFT-HAND SIDE, KIND OF KEEP
YOUR EYEOT BLACK BAR.
THAT'S THE TEMPLATE STRAND, THE
PARENT STRAND, SO AS THE CELL IS
UNDERGOING DIVISION, ANYTIME A
DAUGHTER CELL IS PRODUCED, IF
YOU'LL NOTICE THE TEMPLATE
STRAND SEES IN THE PARENT, THE
DAUGHTER CELL HAS A NEWLY
SYNTHESIZED STRAND THAT WILL
CONSIDER EVERY SINGLE TIME AND
PUT A NEW DAUGHTER CELL IS
PRODUCED, THE STRAND WILL BE
PRODUCED.
TELL HAVE ASYMMETRIC DIVISION.
IF YOU'RE INTERESTED IN STUDYING
THIS IN THE HABERATORY, THE NICE
THING ABOUT IT IS IT'S
INEXPENSIVE.
YOU CAN FIND THESE LABEL
RETAINING CELLS IN VARIOUS
TISSUES, ALL RIGHT?
PROBLEM WITH THAT IS, YOU NEED
TO FIX THE TISSUE WITH WHICH
YOU'RE INTERESTED IN STUDYING SO
OBVIOUSLY, THE TISSUE AND THAT
ORGANISM YOU CAN BE DEAD.
THEREFORE, IT'S VERY DIFFICULT
TO DO THIS, WITH A PATIENT, THIS
IS NOT GOING TO WORK.
SO JUST AS AN EXAMPLE AND SHOW
YOU WHAT WE'RE DOING IN THE
LABORATORY WE'LL SHOW YOU HOW
THIS LOOKS.
AS I MENTIONED YOU CAN FIND
THESE CELLS ACROSS DIFFERENT
SPECIES, IT'S BEEN FOUND ACROSS
DIFFERENT TISSUES AS WELL.
SO WE WANTED TO INVESTIGATE
THIS, SO AND THESE LONG LIVED
CELLS WERE PRESENT IN THE
POPULATION AND THEY WERE
MAINTAINING THE DNA STRANDS.
SO AGAIN, WE UTILIZE THESE 3
WEEK OLD MICE.
NUMBER 4 AND NUMBER 9 MAMMARY
GLANDS FOR ANY IMPLANTS WE WERE
DOING.
AND THE LABELS THATEE USE, WHAT
YOU TYPICALLY USE WHEN YOU
IMMORTALIZE THESE CELLS.
5 BRDU, AND AND THIS IS COMMONLY
USE INDEED IN CELL PROLIFERATION
AND IT CAN BE INCORPORATED INTO
DNA DURING S-PHASE SO IT IS
GOING TO IDENTIFY WHEN YOU LOOK
AT IT, THE IMMUNE HISTOCHEMISTRY
CELLS THAT ARE RETAINING THEIR
LABELS, THE CELLS THAT ARE LONG
LIVED.
YOU CAN ALSO THEN USE TREATY
THYMA DINE.
AND THIS WOULD BE A MARKER USED
TO MEASURE DNA SYNTHESIS.
SO WHEN YOU DETECT THIS FOR THE
RADIOGRAPHERY, THOSE CELLS ARE
ACTUALLY CYCLING.
AND WHAT DOES THIS LOOK LIKE AND
WHEN YOU HAVE THE TISSUE
TRANSSECTIONS, AND
INTERDISPURSED THROUGHOUT THE
TISSUE THAT ARE BROWN, AND AND
SO, A BROWN CELL WITH THE
SPECLED DOTS IS THE CELL THAT IS
LONG LIVED AND IT'S BEEN
RETAINING THE TEMPLATE DNA
STRAND.
AND IT IS ACTIVELY CYCLING WHICH
IS LITTLE BROWN DOTS, AND THOSE
SHOULD BE THE STEM CELLS THAT
ARE PRES EPT WITHIN THAT
POPULATION, TO KIND OF VISUALLY
GET IT AGAIN, AND IT WILL BE
APPARENT IDENTICAL SALES AND
WITH THOSE YOU'RE GOING TO SEE A
PARENT WITH 2 CELLS WITH BOTH
HAVING BROWN WITH THE BLACK DOTS
IN THEM.
UNDER ASYMMETRIC DIVISION, THAT
PARENT CELL WILL RETAIN THE
TEMPLATE DNA STRAND, SO THE
BRDU, WILL STILL BE BROWN, ANY
DAUGHTER CELL ITS GIVES OFF
WOULD BE CYCLING BUT NOT HAVE
THAT COUPLING THERE.
SO FUZZY HERE BUT YOU CAN SEE,
IT'S ASYMMETRICALLY DIVIDING AND
THIS WOULD BE THE PARENT CELL,
THE BROWN CELL, THE BRDU, THE
LONG LIVED TEMPLATE STRAND, IT'S
YIELDING A DAUGHTER CELL WHICH
IS ACTIVELY CYCLING WITH THE
THYMA DINE; THE BLACK DOTS SAME
OVER HERE, THE PARENTS CELL,
AGAIN, DIVIDING TO PRODUCE A
DAUGHTER CELL, THE TEMPLATE DNA
WILL BE RETAINED IN THE PARENT
CELL WHICH IS THE BROWN.
SO, IN OUR POPULATION THAT WE
WERE LOOKING AT, COMPARABLE TO
STEM CELLS, THESE LONG LIVED
IMMORTALIZED CANCER STEM CELLS
ARE POPULATION LESS THAN 1%,
RIGHT?
THEY'RE GOING TO BE ABLE TO
MAINTAIN THE ORIGINAL DNA,
ASYMMETRICALLY DIVIDE AND WE
SPECULATE WITHIN IMMORT ATIZED
CELLS--IMMORTALIZED CELLS THAT
THESE WILL MAINTAIN THE
DESTINATIONS AND THIS IS
SOMETHING TO THINK ABOUT WHEN
YOU STUDY CANCER STEM CELLS THAT
THERE IS GOING TO BE, AND AND
ANOTHER WAY THAT'S BEEN
TYPICALLY, AND THOSE ARE CANCER
STEM CELLS AND INTERESTINGLY
ENOUGH, TUMOR SPEARS OR SPEAR
FORMATION FIRST STARTED OUT
USING NEURAL STEM CELLS FOR SOME
REASON, I DON'T KNOW WHY, BUT
AND/OR YOU CAN TAKE THE CELLS
WHATEVER YOU'RE INTERESTED IN
STUDYING AND PUT THEM IN KNOTTED
HERE CONDITIONS THOSE WILL BE
ENRICHED STABLE IF YOU'RE
LOOKING AT CANCER CELLS THEY
WILL BE ENRICHED.
NICE THING ABOUT THIS, THEY'RE
INEXPENSIVE AND CELL CULTURE AND
AGAIN YOU CAN FIND SPEARS
FORMING ACROSS DIFFERENT SPECIES
AND TISSUES AND NOT SPECIFIC TO
BREAST CANCER OR PROSTATE CANCER
FOR ALL CANCERS.
AND AND AND AND THIS IS NOT
CONDITIONS, THE 1S THAT ARE
CAPABLE OF SURVIVE NOTHING THAT
ENVIRONMENT THEN ARE THEN GOING
TO START THE FORM SPEARS AND
THEN YOU GET THE PROLIFERATION
AND GOING 49%.
AND IT LOOKED LIKE VERY LARGE
BULB LOOKING CELLS WHICH ARE
ESSENTIALLY FUSIONS OF MANY
DIFFERENT SMALLER CELLS.
THOSE WERE UP TO APPROXIMATELY
200-MICRONS BIGGER THEY GET.
AND THEN COMPARED TO PARENTAL
CELL LINE, WHATEVER IT IS YOU'RE
STUDYING, AS YOU LEFT THESE,
WHAT YOU'RE GOING TO HAVE IS
THESE CELLS THEN ARE ENRICHED
FOR THEIR TUMOR PRODUCING
ABILITY SO YOUR MOUSE MODEL YOU
HAD INOCULATE THE TUMOR CELLS IN
SHOULD BE SHOULD BE DIFFERENT
THAN THE PARENTAL LINE YOU
INOCULATE THEM.
THE BAD THING ABOUT USING TUMOR
SPEAR SYSTEM YOU WILL GET
VARIABLE ENRICH MUCHMENT OF CELL
ACTIVITY, DEPENDING ON THE CELLS
THAT GET THE BIG CELL, IT MAY
PRODUCE A TUMOR, IT MAY NOT.
SO, IF YOU WERE TO TAKE ANY
GIVEN TOMB OAR SPEAR AND TRY TO
IMPLANT INTO A MOUSE, YOU MIGHT
NOT GET ANY SPORES THERE.
1 OTHER METHOD WHICH HAS BEEN
SHOWN IN THE LITERATURE IS
CALLED DEHYDROGENASE AND THIS
HAS BEEN AROUND FOR A COUPLE
YEARS NOW, AND THE DEHYDROGENASE
IS SPECIFICALLY EXPRESSED BY THE
HEMEAT O POETIC AND CELLS, YOU
CAN HIGHLY ENRICH FOR STEM CELL
ACTIVITY USING IT AND IT WORKS
ACROSS DIFFERENT SPECIES AND
THERE'S A SPECIALLY AVAILABLE
KID CALLED ATA FLOOR TO-GET FOR
IT AND HERE'S AN EXAMPLE OF WHAT
YOU WOULD GATE AND IN THE LEFT
HAND CORNER IS THE CONTROL CELL
GROUP WITH THAT, AND IN THE
MIDDLE, YOU THEN SEE KIND OF THE
MIDDLE GROUP HERE, THE
POPULATION, SIDE POPULATION IS
POSITIVE FOR THOSE DEHYDROGENASE
CELLS.
AND SAME THING OVER IN THE RIGHT
HAND SIDE.
ALL RIGHT, THESE CELLS
HYPOTHETICALLY ARE YOUR
CANCER--YOUR CANCER STEM CELLS
THAT ARE POSITIVE FOR THAT
DEHYDROGENASE.
PROBLEM WITH THIS IS, IT
REQUIRES FAX TO DO, IF YOU DON'T
HAVE A FAX IN YOUR LAB RAARE TOW
THERE'S--LABORATORY, THEY'RE
EXPENSIVE.
THERE ARE DIFFERENT FORMS OF
DEHIDE
DEHYDROGENASE, THERE'S BEEN
FORMS REPORTED AND IT ALLOW O
SINGLE 1 MARKER TO IDENTIFY
CANCER STEM CELL WHICH IS IS NOT
THE BEST IDEA IN THE WORLD.
SPEAKING OF MARKERS WE'LL TALK A
LITTLE BIT ABOUT WHAT'S BEEN
SHOWN IN THE LITERATURE.
THERE WAS A VERY POPULAR PAPER
OUT A FEW YEARS AGO IN
PARTICULAR LOOKING AT BREAST
CANC E-PRESCRIBING CELLS AND
THERE'S CD44 POSITIVE AND THAT
IS IDENTIFIED BREAST CANCER STEM
CELLS AND THE NICE THING ABOUT
THESE 2 MARKERS AGAIN FOR BREAST
CANCER STEM CELL SYSTEM THAT
IT'S HIGHLY ENRICHED FOR STEM
CELL ACTIVITY FOR SPECIFICALLY
BREAST CANCER CELLS.
IN THIS PARTICULAR EXPERIMENT
WHAT A DID AGAIN WAS TO USE
FACTS TO SORT FOR THE CD44
POSITIVES, CD24 NEGATIVE CELLS
WITHIN A PLURAL EFFUSION.
THEY AGAIN ISOLATED THESE CELLS,
GO THROUGH A MOUSE AND THAT
RESULTING XENOGRAFT THEY GOT WAS
A SMALL POPULATION RESULTED
THERE WERE OTHER CELLS THAT GREW
OUT FROM THAT CD24 NEGAATIVE
POSITIVE CELL POPULATION.
SO IF ANYBODY'S INTERESTED I'M
NOT GOING OVER IT.
BUT AGAIN, CD44 POSITIVE,
CDNEGMARKERS, ARE THERE.
ALPHA DEHYDROGENASE, ANDICANCY
STONES, AND BONE SARCOMA PEOPLE
ARE INVESTIGATING STROMAL LINES
AND CD185, CD44, SKY 1, CD5,
BLAH, BLAH, BLAH, ALL THEM HAVE
DIFFERENT MARKERS AND FOR ALL
THESE DIFFERENT TISSUES, THAT'S
THE COMPLICATED.
, AND USE THE FAX MACHINE, AND
USING ANTIBODIES WHICH IS THE
SAME, OTHER MARKERS THAT ARE NOW
IN THE LITERATURE FOR PEOPLE TO
LOOK AT, HERE'S A LIST OF ABOUT
10 TO 15 NEW 1S, PICK YOUR
MARKER, PICK YOUR FAVORITE
MARKER AND SEE IF IT WORKS.
OKAY?
WHAT'S GOING TO WIND UP
HAPPENING NOW NONE OF THE
CURRENT MARKERS, YOU WILL NEED
THEM TO IDENTIFY CANCER CELLS,
THERE WILL ALSO BE FUNCTIONAL
MARKERS THAT ARE NEEDED.
THE BEST WAY TO IDENTIFY THIS IS
TO TAKE WHATEVER TUMOR SPHERE OR
PET RIDISH THAT'S GOING SCUP AND
PUT IT INTO A MOUSE AND SOME
KIND OF FUNCTIONAL MARKER THAT
WILL ALSO BE NEEDED TO BE
SHOWING THAT YOU INDEED HAVE A
CANCER STEM CELL.
THE OTHER THING WHICH I HAVEN'T
TOUCHED ON AND I'LL GET INTO
THAT IN A FEW SLIDE SYSTEM VERY
BRIEFLY ABOUT THE NEARBY NICHE
STEM CELL CANCER ENVIRONMENT.
EACH ORGAN, EACH TYPE OF CANCER
WITHIN AN ORGAN, AND THEN EACH
PATIENT-SPECIFIC CANCER WILL
HAVE ITS OWN SIGNATURE SO THAT'S
SOMETHING TO THINK ABOUT.
WHAT HAPPENS AND IF A PERSON
GETS BREAST CANCER, THAT BREAST
CANCER MAY NOT BE THE SAME AS IF
THEY GET BRAIN CANCER OR
SOMETHING LIKE THAT, THEY ARE
ALL GOING TO BE DIFFERENT.
SO IT'S GOING TO GET COMPLICATED
VERY QUICKLY.
VERY BRIEFLY, I WANT TO GO OVER
THE IDEA OF A STEM CELL NICHE
AND HOW IT CAN AFFECT STEM
CELLS.
SO THE IDEA BETWEEN A STEM CELL
NICHE, THE NICHE IS GOING TO
WANT TO MINIMIZE ANY SORT OF
DIFFERENTIATION THAT OCCURS WITH
THAT STEM CELL.
MANY DIFFERENT FACTORS CAN BE
ACTING ON THAT STEM CELL, COMMON
1S INCLUDE THE WENT PATHWAY,
NOTCH PATHWAY, HEDGE HOG
PATHWAY.
DEPEBBLED O GBA WHERE THE STEM
CELL IS, TGF BETA, EGP, ET
CETERA.
OF SO ALL THIS ACT BEING ON THE
STEM CELL TO KEEP IT QUIESCENT,
KEEP IT FROM DIFFERENTIATING.
TYPICALLY YOU NEED 3 THINGS
WITHIN A NICHE.
FIBROBLAST, STROMAL CELLS,
WHATEVER, AS WELL AS EXTRAA
CELLULAR MATRIX THAT WILL
CONTROL THAT STEM CELL BEHAVIOR.
YOU WANT ALSO WANT TO HAVE A
RANGE OF SIGNAL TAG WILL OCCUR
AND THEN YOU WILL NAME YOUR STEM
CELL.
SO THERE IS A SCHEMEATIC THAT OF
HOW THIS WOULD OCCUR SO IN PART
A, THE TOP, YOU CAN SEE A
SPECIFIC NICHE WHERE YOU HAVE
THE STEM CELLS THAT ARE IN G-0,
THEORETICALLY BEING QUIESCENT,
OKAY, THAT NEARBY IS SEABEDDING
OUT SIGNALS EITHER BY CELL-CELL
CONTACT OR BY A PERRA TRINE
SIGNALING TO KEEP IT FROM
DIFFERENTIATING.
AND PART B, WHAT'S HAPPENED IS
THOSE STEM CELLS THEN HAVE
EITHER RECEIVED SIGNALS BECAUSE
THEY'VE GOTTEN A LITTLE TOO
CLOSE TO THE BOUNDARIES OF THE
NICHE HAS DEFERENTIATED INTO 1
PARTICULAR CELL TYPE OR HAS
DIFFERENTIATED AND GOTTEN
SIGNALS TO DEVELOP INTO A
DIFFERENT CELL TYPE.
ALL RIGHT?
SO THE EFFECTIVE RANGE OF THAT
NICHE, THOSE STEM CELL ARE
OUTSIDE OF THAT.
OKAY?
HERE'S AN EXAMPLE, JUST OF 2
DIFFERENT CELL TYPES ON THE TOP
IS THE HEMEAT O POETIC STEM
CELL, AND THE BOTTOM IS AN OFTIO
BLAST, JUST THESE 2 CELL TYPES
ALL THE DIFFERENT WAYS THESE
CELL TYPES CAN INTERACT, IT'S
VERY COMPLICATED VERY QUICKLY IF
YOU'RE INTERESTED IN EXAMINING
ANY PARTICULAR PATHWAY AS TO
WHAT CONTROLS THAT STEM CELL TO
BE THE WAY IT IS.
OKAY?
AND THEN 1 FINAL THING, BECAUSE
THIS IS SOMETHING THAT HAS BEEN
STARTING TO POP UP IN A LOST
CONFERENCES, AND AND WE DON'T
KNOW AT THIS POINT HOW CANCER
STEM CELLS AFFECT METASTASIS AND
ANOTHER 1 OUT THERE, ON CANCER
STEM CELLS AND METASTASIS, IT'S
POSSIBLE THAT A STEM CELL HAS
METASTASIZED.
AND IT'S POSSIBLE THAT THE
METASTATIC OR DIFREBTIATED CELL,
MAY HAVE DEVELOPED STEM LIKE
PROPERLY IN A SECONDARY
LOCATION, AND IT MAY BE THAT
THERE'S A METASTASIS OR
SECONDARY SITE INITIATING CELL,
ALL RIGHT, ANY OF THESE ARE
POSSIBLE, DON'T KNOW YET,
SURVIVAL AT THE SECONDARY SITE
IS KEY, OBVIOUSLY WITH ANY SORT
OF COLONIZATION AT THE SECONDARY
LOCATION AND THEN AS I JUST
SHOWED THE ROLE OF
MICROENVIRONMENT IS GOING TO
HAVE A MAJOR IMPACT ON HOW ALL
THESE CELLS ARE DEVELOPED.
OKAY.
AND JUST FINAL THOUGHTS AS I
MENTIONED, AND IF ANYBODY'S
INTERESTED IN STUDYING THEM
THERAPIST, THERE OF THIS OF THIS
STUDYING THESE, THEY ARE WELCOME
TO.
I WANT TO POINT OUT THE WORK
I'VE SHOWED, AND THE COLLEAGUES
THAT HELP TED ME.
THE WORK WAS SUPPORTED BY TEA
MONEY AND INTRAMURAL FUNDING AND
ANY QUESTIONS.
[ APPLAUSE ]
>> ANY QUESTIONS?
I DID SUCH A GOOD JOB
EXPLAINING.
>> [INAUDIBLE QUESTION FROM
AUDIENCE ] WE DIDN'T DO AND WE
HAVE NO WAY OF TAKING THEM BACK
OUT, SO I CAN'T ANSWER THAT
QUESTION, I DON'T KNOW ABOUT
THAT.
BUT WE--WHEN THEY WERE
REPROGRAMMING THE
MICROENVIRONMENT, AS LONG AS
THEY STAY WITHIN THE
MICROENVIRONMENT ARE GETTING
THOSE SIGNALS, THEY STAY.
YEAH.
>> [INDISCERNIBLE].
GENTLEMAN.
>> NOT YET.
NOT YET.
FINGERS CROSSED.
NOT YET.
IT LOOKS PROMISING.
>> [INDISCERNIBLE].
>> YOU CAN SEE IT WHEN THEY PUT
IT UNDER THE MICROSCOPE, YOU BUT
ESSENTIALLY WHEN YOU SEE THESE
TUMORS HERE, THEY LITERALLY FUSE
TOGETHER TO WHERE IT'S JUST 1
BIG BLOB IS THE BEST WAY TO
DESCRIBE IT AND IF YOU PUT IT
UNDER PHASE YOU CAN CLEARLY SEE
1 VERSES THE OTHER.
1 WILL BE BUMPY WITH THE RIDGES RIDGES
AND THE OTHER YOU WILL SEE
LITTLEBLES ALL OVER.
ANY OTHER QUESTIONS?
MY E-MAIL IS ON THE THING IF
ANYBODY THINKS OF SOMETHING
LATER ON.
SO FEEL FREE.
[ APPLAUSE ]
THANK YOU.
>> OKAY, SO AS YOU ALL KNOW,
CANCER ORIGINATES BECAUSE OF
GENETIC CHANGES AND AS A RESULT,
SOME PEOPLE HAVE GENES THAT ARE
AT HIGHER RISK OF GETTING CANCER
THAN OTHERS.
SO WE HAVE NEAL CAPP A ROSO, HE
GOT HIS MEDICAL DEGREE AT THE
UNIVERSITY OF NEW JERSEY MEDICAL
CENTER AND THEN HE CAME TO THE
NCI, TITLE OF THIS TALK,
EPIDEMIOLOGY AND INNICOLOGY,
NEAL.
>> MICKEY:  THANK YOU.
>> CAN YOU ALL HEAR ME?
OKAY WE'RE WONDERFUL WORLD OF
AND OF COURSE, IT'S MANY
INSTITUTES AND AMONG THEM IS
NCI.
AND I'M PART OF THE EPITHELIAL
RAMURAL PROGRAM, WHICH IS ABOUT
50% OF THIS DIVISION AND OUR
DIVISION IS THE DIVISION OF
CANCER EPIDEMIOLOGY AND GENETICS
AND WE'RE CONCERNED ABOUT THE
CAUSES EVER CANCER AND IN THE
POPULATION AND SO WE HAVE
BRANCHES THAT FOCUS ON
NUTRITION, HORMONES, INFECTIONS,
OCCUPATION, STATISTICAL METHODS
AND RADIATION AND I'M IN THE
GENETIC EPIDEMIOLOGY BRANCH SO
WE LOOK AT FAMILIES AND
POPULATIONS AND TRY AND FIGURE
OUT THE GENES THAT ARE CAUSING
PROBLEMS.
SO THE ROLE OF EPIDEMIOLOGY.
IS GENERALLY THE GOAL OF
EPIDEMIOLOGY ARE THE CAUSES OF
CANCER, WE LIKE TO QUANTIFY
RISKS, THOSE WOULD BE RISKS FOR
INDIVIDUALS BUT WE WOULD ALSO
LIKE TO IDENTIFY GROUPS.
WHAT ARE GROUPS AT ELEVATED
RISKS OF CANCER.
WE WANT TO UNDERSTAND MECHANISMS
BUT AND WE ACTUALLY TRY TO FOCUS
ON MECHANISMS, EPIDEMIOLOGY HAS
ALWAYS HAD A PUBLIC HEALTH
ORIENT ANTICIPATION, WE WANT TO
ENHANCE PUBLIC HEALTH AND
BECAUSE HEALTH SERVICES COST
MONEY, YOU WOULD LIKE TO KNOW
HOW TO SPEND THAT MONEY MOST
EFFICIENTLY.
AND IT'S TRYING TO DO THAT.
AND NOW THIS IS A LITTLE BIT
TONGUE IN CHEEK, BUT WE OFTEN
GET HALLED INTO A STUDY AT THE
LATE STAGE BECAUSE THERE MAY BE
A QUESTION ABOUT THE DESIGN OR
THE P-VALUE, NOW, AND THIS TIME
AGAIN, THIS IS TONGUE IN CHEEK
BUT THEY OFTEN DON'T ASK US WHAT
THE P-VALUE OF A STATISTICAL
QUESTION, BUT WHEN AN
EPIDEMIOLOGIST GETS CALLED IN TO
LOOK AT A STUDY, SOMEONE HAS A
MARKER THAT'S ASSOCIATE WIDE
CANCER.
THE EPIDEMIOLOGIST IS TYPICALLY
THINKING WHAT WAS YOUR STUDY
DESIGN, WHERE DID YOUR CONTROLS
COME FROM?
DID YOU CONSIDER BIAS?
DID YOU CONSIDER CONFOUNDING?
WHAT WAS THE ORIGINAL
HYPOTHESIS.
DID THE HYPOTHESIS CHANGE ASSED
STUDY WENT LONG THAT'S DATA
DREDGING.
DID YOU CONSIDER POWER?
THE NUMBERS THAT YOU HAD AND THE
STATISTICAL POWER OF THE STUDY?
DID YOU VALIDATE YOUR MARKER SO
THESE ARE THE KIND OF QUESTION
TAC EPIDEMIOLOGISTS THINK OF AND
EPIDEMIOLOGISTS FOCUS ON
POPULATIONS.
I'VE HEARD OF PEOPLE TALK ABOUT
THE EPIDEMIOLOGY OF CELLS.
TECHNICALLY WE DON'T DO THAT, WE
DO POPULATION.
SO OKAY, EPIY SPEAKS JUST A FEW
TERMS, EPIDEMIOLOGY, THE TERM
EPI, FROM THE IMREEK, THE PEOPLE
AND OTHERS TO TALK ABOUT.
SO 1 OF THOSE CLASSIC GREEK
WORLDS AND IT'S AN OBSERVATIONAL
SCIENCE.
CONTRASTING WITH EXPERIMENTAL.
WE DO NOT GET TO PICK WHOSE
EXPOSED AND UNEXPOSED.
THAT HAPPENS.
WE JUST GET TO LOOK AT GROUPS
AND EPIDEMIOLOGISTS HAVE A
NUMBER OF TECHNIQUES TO REDUCE
BIAS IN OUR STUDY GROUPS.
OKAY, RISKS, MEASURES OF THE
STRENGTH OF RELATIONSHIPS
BETWEEN A RISK FACTOR AND A
CANCER AND I'M REALLY NOT GOING
TO GO INTO THIS, I JUST WOULD
SAY THAT RELATIVE RISKS INVOLVE
COMPARISONS OF 2 GROUPS OF
INDIVIDUALS SO YOU OFTEN ABOUT
RISKS LIKE MEET IN ARE
YOUR--MEAT IN YOUR DIET WILL
INCREASE YOUR RISK OF CANCER IN
1.4.
SO THAT'S 40% INCREASED RISK BUT
YOU HAVE TO BE CAREFUL BECAUSE
RELATIVE RISKS CONTRAST WITH
ABSOLUTE RISK.
YOU CAN HAVE A FAIRLY
SUBSTANTIAL RELATIVE RISK AND
PARTICULARLY IF THE CANC SER
RARE, THE ABSOLUTE RISK REMAINS
VERY, VERY SMALL AND NOT
CLINICALLY SIGNIFICANT.
SO YOU REALLY NEED TO KNOW
WHETHER YOU'RE DEALING WITH AN
ABSOLUTE RISK OR A RELATIVE RISK
AND ODDS RATIO IS A SIMILAR TO A
RELATIVE RISK BUT IT'S TO DRIVE
FROM A CASE CONTROL STUDY AND
THE CAVEAT THERE IS THAT THE
DISEASE HAS TO BE RARE, SO
PREVALENCE REFERS TO THE TOTAL
NUMBER OF POPULATION AT A GIVEN
TIME AND TO STATE FROM INCIDENCE
WHICH ARE NEW CASES ASCERTAINED
DURING THE GIVEN TIME PERIOD, SO
IT CAN BE RELATED TO THE NUMBER
OF PEOPLE DIAGNOSED WITH CANCER
AND CURED AND LIVING WITH CANCER
AND CURRENTLY NOW, THE
PREVALENCE OF INDIVIDUALS WHO
HAVE BEEN DIAGNOSED WITH CANCERS
IS GREATER THAN 10 MILLION,
VERY, VERY, IMPORTANT FIGURE FOR
HEALTH PLANNING.
EPIDEMIOLOGISTS RIKE TO
EMPHASIZE PREVENTION.
OKAY?
SO THINK POLIO VACCINES,
SMALLPOX, SMOKING CESSATION,
CLEAN WATER, MEAT INSPECTION,
VACCINATION FOR HPV, THE REASON
IS, IT'S CHEAP, MUCH CHEAPER
THAN LATE STAGE INTERVENTION, SO
THIS IS A PUBLIC HEALTH
ORIENTATION, WE WANT TO
ELIMINATE DISEASE AT THE SOURCE.
THERE ARE A NUMBER OF REAL DOWN
SIDES HOWEVER TO EMPHASIZING
PREVENTION, 1 IS THAT WHEN YOU
DO AN INTERVENTION OF THAT TIME
IT TAKE AS A WHEEL TO SHOW THAT
IT HAD AN EFFECT.
SECONDLY, IT JUST DOESN'T HAVE
THE IMPACT WHEN YOU GO TO
CONGRESS THAT A CURE DOES.
A CURE IS JUST REALLY SEXY.
WHEREAS SAYING WE ARE GOING TO
REDUCE THE INCIDENCE OF LUNG
CANCER 20 YEARS FROM NOW, IT
DOESN'T HAVE THAT--PEOPLE KIND
OF HAVE THAT SHORT-TERM
ORIENTATION.
BECAUSE YOU DON'T HAVE THE
EMOTIONALLY GRIPPING STORIES OF
ALL THE DISEASE THAT YOU'VE
PREVENTED.
THERE'S LESS POLITICAL IMPACT
AND, UNLESS I'M MISTAKEN I DON'T
KNOW ANY EPIDEMIOLOGIST THAT
EVER GOT A NOBEL PRIZE.
YOU COULD ARGUE THAT IDENTIFYING
TOBACCO AS THE CAUSE OF LUNG
CANCER REALLY DESERVES SOME
SUBSTANTIAL RECOGNITION.
SO THERE'S PRIMARY, SECONDARY
AND TERTIARY, EVENT QUARTINARY
KINDS OF PREVENTION CAN YOU GO
INTO.
SO I A QUESTION EPIDEMIOLOGISTS
OFTEN GET, I HAVE A GRANDMOTHER
AND GRANDMA SMOKED, NOT ONLY
THAT, SHE NEVER DID ANY
EXERCISE, SHE NEVER USED A SEAT
BELT, SHATE BACON, HE DID ALL
SORTS OF UNHEALTHY THINGS AND
SHE WATCHED ALL OF HER DOCTORS
DIE.
OKAY, SO HOW DO YOU EXPLAIN THAT
EPIDEMIOLOGIST.
SO THE ANSWER IS THAT
EPIDEMIOLOGIST IS A PROBABLISTIC
SCIENCE AND THINK OF THAT
GASSIAN DISTRIBUTION, THERE'S
SOMEBODY AT THE END OF THAT
DISTRIBUTION AND WHO IS AT THE
END, GRANDMA.
SO YOU'RE ALWAYS GOING TO HAVE
SOMEONE OUT THERE.
AND WE ARE NOT DEINERMIVITYIC
AND I'LL TALK ABOUT A FEW OF
THEM IN A FEW MINUTESSA AS WE GO
ON.
AGAIN EPIDEMIOLOGISTS DON'T GET
TO DO EXPERIMENTS ON PEOPLE,
ALTHOUGH SOME OF US WOULD LIKE
TO, WE OBSERVE LARGE POPULATIONS
AND LOOK AT THEIR OUTCOMES AND
RELATE THEM BACK TO EXPOSURES.
AND THIS, THIS WEAKNESS, THIS
ALMOST PHILOSOPHICAL WEAKNESS
HAS BEEN EXPLOITED BY GROUPS
THAT DON'T WANT THEIR PARTICULAR
PRODUCTS IDENTIFIED AS BEING
RISKY SO TOBACCO COMPANIES FOR
YEARS SAID, WELL, THERE'S NO
EXPERIMENTAL EVIDENCE WHEN
LINKING CIGARETTES WITH LUNG
CANCER SO IT'S REALLY NOT
PROVEN.
SO IN RESPONSE, EPIDEMIOLOGISTS
PAY A LOT OF ATTENTION TO ISSUES
OF CAUSATION AND HAVE TRIED TO
IDENTIFY THE FACTORS THAT
ENHANCE A ARGUMENT AND
POPULATION DATA SO I'LL TOUCH
ON.
OKAY, EPIDEMIOLOGIST, AND AH
MAPS, OKAY, SO MAPS, SO IT'S
IT'S THE THING THAT STATE
REGISTRIES COULD NEVER EVER DO.
BUT YOU CAN SEE 1 LOOK AT THIS
MAP, AND IT MAY HAVE A LOT MORE
MELANOMA THAN THE NORTHERN AND
THIS IS A VERY COMPELLING
ARGUMENT, IT HAD SOMETHING THAT
REALLY HAS A LITTLE IMPACT IN
TERMS OF CONVINCING YOU THAT SUN
MAY BE A KEY FACTOR IN MELANOMA.
AND I WANT TO SHOW YOU THE MAP,
IS FOR LUNG CANCER, AND OVER 30
YEARS AGO, WITH THAT THERE'S A
GLOMERATION, AND AND THEY WERE
BUILDING SHIPS AND WHEN THEY
BUILT THE SHIPS THEY WERE USING
ASBESTOS SO THAT A WONDERFUL
THING THAT 1 LOOK TOOK MORE THAN
1 LOOK BI IT WAS A COMPELLING
AND QUICKLY IMPRELLSIVE ARGUMENT
SO THE EVOLUTION OF MAPS IS THE
GEOGRAPHIC INFORMATION SYSTEMS
OKAY, AND THESE ARE SALET AND
OTHER ADVANCED TECHNOLOGY BASED
SYSTEMS TO ASSESS EXPOSURES SO
THIS IS A WHOLE NEW AREA THAT'S
BEEN DEVELOPED AND YOU CAN
ESTIMATE NITRATES, PESTICIDE
LEVELS THERE ARE A MYRIAD OF
THINGS YOU CAN IDEBTIFY SO FOR
EXAMPLE, THERE WAS A LOT OF
POLITICAL PRESSURE IN THE 90S TO
EXPLAIN THE BREAST CANCER
EPIDEMNICK LONG ISLAND SO THERE
WAS A TON OF SATURDAY RELATED
DATA ON LONG ISLAND AND THE
ADJACENT NEW YORK AREA FOR
DIFFERENT PARAMETERS THAT THEY
CAN ASSESS VIA SATELLITE MPLET
SO THIS IS KIND OF AN EXCITING
NEW AREA OF RESEARCH, ANOTHER
TOOL THAT YOU'LL OFTEN SEE
EPIDEMIOLOGISTS SEE IS SEER,
SEER COMES OUT WITH A NEW
SUMMARY AND EVERY YEAR THEY TRY
TO MAKE THIS DATA MORE USER
FRIENDLY.
SO CAN YOU GO TO THE SEER WEB
SITE AND DOWNLOAD A LOT OF THESE
FACT SHEETS AND ALSO THE RAW
DATA AND THIS IS A WONDERFUL
THING IF YOU WANT TO KNOW
SOMETHING ABOUT CANCER, RATES
BROKEN OUT BY DIFFERENT CANCERS,
DIFFERENT ETHNICITIES, THERE'S
REALLY A TON OF WONDERFUL
INFORMATION AISLE SHOW YOU A
FEW--I'LL SHOW YOU A FEW
EXAMPLES.
THE SEER COVERS ABOUT A QUARTER
OF THE POPULATION AND HAS
INFORMATION ON DEMOGRAPHIC O
SINGLE TUMORS TUMOR MORPHOLOGY,
STAGE, THERAPY, SURVIVAL, SO
WHAT YOU SEE IS THAT RATES FOR A
NUMBER OF CANCERS TRENDED
DOWNWARD WHILE OTHERS GO UP AND
THIS IS USEFUL INFORMATION THAT
TELLS US A LOT AND THE EVEN
TERPRETATION AND OFTEN COMPLEX.
SO THERE ARE A LOT OF
INTERESTING FEATURES
INTERPRETING THIS DATA, SO FROM
1995-2000, YOU SEE A BIG
INCREASE IN INCIDENCE RATES AND
IN BOTH TEXT ACCIDENT IT'S A BIT
OF A BUMP BUT YOU DON'T SEE IT
IN WOMEN SO WHAT'S GOING ON
HERE.
AND TED CONSPIRE IS THAT YOU DO
PSA SCREENING AND SO, YOU
IDENTIFIED A LOT MORE CASES OF
PROSTASTY CANCER.
THE DEBATE G'S GOES ON WHETHER
IT'S AT ALL REAL BECAUSE IT GOES
BACK DOWN TO BASELINE AND A
TENANT OF EPIDEMIOLOGY IS WHAT
YOUICAL A CANCER DEPENDS ON YOUR
METHOD OF DIAGNOSIS.
HERE ARE CANCER RATES FOR WOMEN,
YOU CAN SEE THE INCIDENCES OF
LUNG CANCER AROSE, LAST QUARTER
OF THE CENTURY.
AND HERE YOU SEE SOME BREAK DOWN
BY GENDER AND RACE, AND HERE YOU
SEE, DEATH RATES AND MORTALITY
AND YOU HAVE BASICALLY A SLIGHT
DECREASE IN BOTH MEN AND WOMEN.
AND DOES ANYONE KNOW WHY THAT IS
THE CASE.
DRIVEN BY 1 CANCER.
THERE'S LONG CANCER.
AND THERE'S INCREASES AND WHAT
YOU FIND IS THAT ALTHOUGH THE
PUBLIC OFTEN THINKS THAT THE
[INDISCERNIBLE] CANCER RELATES
TO OUR EFFECTIVE TREATMENT AND
IN FACT MOST OF THE TIME IT
RELATES TO CHANGES IN THE
EPIDEMIOLOGY.
AND WE'LL COME BACK TO THAT.
SO, THE RATES FOR MEN, ROLLED
OVER, ABOUT 20 YEARS AFTER THE
DECLINE IN SMOKING STARTED AND
WOMEN STARTED LATER.
BECAUSE AS THE MARKET FOR
CIGARETTES FOR MEN DECLINED,
THEY WENT AFTER THE WOMEN, WITH
VIRGINIA SLIMS AND ALL SORTS OF
MARKETING CAMPAIGNS BUT THEN
EVENTUALLY THE POPULATION KINDS
OF MEASURES, THE SECULAR TREND
AND A DECLINE IN SMOKING ALSO
BEGAN TO EFFECT WOMEN IN THIS
RATE AND THIS ROLLED OVER FOR
WOMEN AS WELL, BUT NOT BEFORE
EXCEEDING BREAST CANCER SO LUNG
CAUSES MORE CANCER DEATHS THAN
BREAST CANCKENER WOMEN AND MORE
CANCER DEATHS OVERALL IN THE
UNITED STATES AND WORLD WIDE
THAN ANY OTHER CANCER.
JUST A NOTE IN CHILDREN, THE
DEATH RATES.
WHEN YOU SEE AN INCIDENCE RATE
THAT'S HIGHER THAN A MORTALITY
RATE, THAT OFTEN TELLS YOU THAT
AN EFFECTIVE TREATMENT EXISTS.
AND IN FACT, THERE'S REASONABLY
EFFECTIVE TREATMENTS FOR A
NUMBER OF CHILDHOOD CANCERS AND
FOR SOME IT'S VERY EFFECTIVE
LIKE ALL.
SO THERE'S THAT POINT.
OKAY, THIS IS JUST PROBABILITY
BY CANCER BY SITE AND THIS IS A
FEW YEARS OLD AND THE NEW 1
WON'T BE COMPARED BUT THESE ARE
KIND OF CRUDE BUT OVERALL YOUR
PROBABILITY OF DEVELOPING CANCER
IN MEN, THEY SAY 1 PUBLICITY 2
IN WOMEN, 1.3 REALLY IT'S
BETWEEN THOSE 2, BUT PRETTY HIGH
OVERALL.
GENERALLY HIGHER IN MEN THAN IN
WOMEN.
SO, WHAT'S THE CAUSE OF CANCER?
WELL, WE THINK WE KNOW A LOT
ABOUT THIS.
OF COURSE, AGE, ENVIRONMENT,
GENETICS AND COMBINATIONS ARE
THE GENERAL CAUSES AND THIS IS
AN OLD, OLD, SLIDE BUT YOU KNOW
IT USED TO BE DIVIDED INTO 3.
A THIRD TOBACCO, THIRD DIET AND
A THIRD EVERYTHING ELSE.
WE'VE GOTTEN A LITTLE MORE
REFINED THAN THAT.
AND TO TRY AND GIVE YOU A
GENERAL IDEA, I WOULD MAKE THE
ARGUMENT TO YOU THAT THE VAST
MAJORITY OF CANCER BASED ON
EPIDEMIOLOGY EVIDENCE IS DUE TO
THE ENVIRONMENT.
OKAY, WHY IS THAT?
BECAUSE THERE ARE DRAMATIC
DIFFERENCES IN CANCER RATES BY
GEOGRAPHY AND OVER TIME AND
THAT'S ONLY COMPATIBLE WITH
EXTREENSIC ENVIRONMENTAL CAUSES
AND THERE'S A VAST BODY OF DATA
THAT SUPPORTS THIS.
OF WHICH I WILL SHOW YOU A
LITTLE BIT.
1 IS THE CANCER VARIETY.
SO PICK YOUR CANCER, AND IT'S
THE COUNTRY WHERE IT'S VERY
HELPFUL.
A HUNDRED TIMES HIGHER IN OFF
THE RAILIA AND JAPAN.
NOW YOU MAY IMMEDIATELY RAISE
YOUR HAND AND SAY, WAIT A
MINUTE.
, FROM THOSE AND--ARE FROM
AUSTYALIA AND THOSE ARE FROM
ANOTHER.
FOR THE MOST PART MIGRATION
STUDIES WHEN INDIVIDUALS FROM 1
ETHNIC GROUP MIGRATE TO ANOTHER
ETHNIC GROUP, THEY TEND TO
ACQUIRE THE CANCER RATE OF THE
LOCATION.
SO THIS IS PRETTY TRUE FOR
PROSTATE COLON, GRASS, MOST OF
THE SOLID TUMORS, AND I'LL GIVE
YOU A FEW EXCEPTIONS LATER ON.
THESE ARE THE CANCER MAPS, WHEN
YOU LOOK AT THE MAP OF LUGE
CANCER IN THE MIDDLE OF MONTANA,
YOU HAVE A LITTLE RED DOT, AND
WHAT WAS IT 1 WAY IS EXTREMELY
HIGH ENS DENSE AREA AND IN CHINA
AND WHEN YOU GO TO CHINA AND YOU
LOOK AROUND THAT'S WHAT YOU SEE.
TERRIFIC INDOOR AIR POLLUTION.
LITTLE OVEN UNDERNEATH THE BED.
COOKING OIL.
AND RELATIVE RISK OF SMOKING.
AIR POLLUTION WAS TERRIFIC, HIGH
RATES OF LUNG CANCER.
SO BACK ON CIGARETTES,
CIGARETTES ARE THE BAD GUY AND I
MENTIONED EARLIER THAT
EPIDEMIOLOGISTS WERE FORCED
POLITICAL MEET BALL, AND FORCED
TO FIGHT THE BATTLE, AND,
AND--IT'S MORE LIKELY THE RISK
IS VERY HIGH, BUT YOU WOULD ALSO
LIKE IT TO BE CONSISTENT THE
STUDY, YOU WOULD LIKE TO SEE A
DOSE RESPONSE, IF YOU GET MORE
OF THE BAD EXPOSURE, YOU WANT TO
SEE MORE OF THE CANCER.
YOU WANT TO SEE SOMETHING THAT'S
TEMPORALLY PLAUSIBLE, YOU DON'T
WANT TO--YOU WANT TO SEE THE
CAUSE COME BEFORE THE CANCER AND
NOT VICE VERSA AND YOU THINK,
WELL THAT'S A TRIVIAL THING
THAT'S ACTUALLY NOT SO TRUE.
AND THEN YOU WOULD LIKE TO SEE
APPLAUSIBLE MECHANISM, YOU WANT
TO MAKE SURE THE BIOLOGY MAKES
SENSE, OKAY?
SO JUST HERE ARE SOME EXAMPLES.
AND THESE ARE 3 GIGANTIC COBRA
STUDIES THAT BEGAN IN THE 50S
IT'S A BEAUTIFUL BOAS--DOSE
RESPONSE AND SO THE MORE
CIGARETTE YOU SMOKE PERDAY, THE
MORE LUNG CANCER.
SO HAVE YOU CONSIEVENCY AND DOSE
RESPONSE AND SUBSTANTIAL ODDS
RATIO AT THE HIGHEST LEVEL OF
SMOKING SO THIS IS THE KIND OF
DATA THAT HIGHLY CONVINCING TO
EVERYONE EXCEPT A TOBACCO
EXECUTIVE.
SO HERE'S THE TEMPORAL ISSUE I
TOLD YOU ABOUT SO AS MALE MOKING
BEGAN, AFTER A SUITABLE LAG, YOU
SAW THE RATES OF MALE LUNG
CANCER RISE, SOCIALLY IT WAS
UNACCEPTABLE FOR WOMEN'S SMOKE
HOWEVER THEY BEGAN AROUND WORLD
WAR 22 WHEN THEY WENT INTO THE
WORKFORCE AND THEN LATER ON WHEN
TOBACCO WAS OFFERED TO THEM
SPECIFICALLY AND LATER ON, THE
RATES ROSE IN LUNG CANCER.
THEN YOU HAD THE PLAUSIBILITY TO
FIGURE THIS OUT WHO PUT IF ON
ON--PEOPLE ON SMOKING MACHINES
AND DEMONSTRATED THE
PATHOLOGICAL CHANGES IN LUNG
CANCER AFTER SMOKING SO YOU SAW
THE PROGRESSIVE CARCINOMA WITH
INSIGHTUE AND FRANK CARCINOMA
THAT YOU COULD SEE AND FINALLY
IF THERE WERE ENOUGH PEOPLE IN
THE SMOKING COHORTS TO DO THIS
YOU COULD CONVINCE PEOPLE TO
QUIT SMOKING, IT TOOK A WHILE
BUT THEIR RATE OF CANCER
DROPPED.
SO A YEAR SINCE QUITTING SMOKING
AS YOU GET FURTHER AND FURTHER
OUT.
THE RATES DROP, THEY NEVER HIT 1
EVEN THOUGH THIS LINE LOOKS LIKE
1 BUT THEY STEADILY GO DOWN.
SO AGAIN AN IMPRESSIVE DOSE
RESPONSE THAT'S VERY CONSISTENT
WITH THE KIND OF DATA THAT WAS
PRETTY--PRETTY CONVINCING, AND,
AND THE POPULATION OF SECULAR
CHANGE, AND IT TOOK A WHILE, IT
TOOK A WHILE ARE RECOGNITION IN
RECOGNITION THAT TOBACCO WAS BAD
TO EFFECT THE SOCIAL POLITICAL,
CHANGES THAT WERE NEEDED TO
REDUCE THE RATES OF SMOKING.
BUT LITTLE BY LITTLE IT'S
HAPPENING.
BUT IT'S IMPRESSIVE AND IT TOOK
DECADES TO DO THIS.
THE WORK OF EPIDEMIOLOGISTS IN
THIS PERIOD WAS ABSOLUTELY
CRITICAL TO DOING IT AND
ALTHOUGH IT TAKES TIME THE
EFFECTS ARE EXTREMELY POWERFUL
AND IF YOU WERE THE PERSON DOING
THIS WORK HERE AND YOU LIVED
DURING HERE, AND SO 1 OF THE
PLACES YOU GOT, WAS THAT LITTLE
BY LITTLE STUDIES OF
ENVIRONMENT, AND THAT'S
IMPORTANT BECAUSE ALTHOUGH THE
RISKS WERE SMALL 1.3 TO 1.7, YOU
ARE NOT [INDISCERNIBLE] SPOUSE
AND YOUR WIFE OR HUSBAND SMOKES,
YOU HAVE A 1.3 TO 1.7 FOLD
INCREASED RISK OF DYING OF LUNG
CANCER, AND BOTH RISKS KIND
BUT--STILL IT'S A SUBSTANTIAL
RISK OF THE POPULATION WHICH
TRANSLATES TO THAT THOUSANDS OF
DEATHS EVERY YEAR.
ALSO AS SOON AS YOU DEMONSTRATED
CONSISTENTLY, THAT PEOPLE WHO
WERE NOT A PRIMARY SMOKERS WERE
DYING OF OTHER PEOPLE'S TOBACCO
SMOKE, YOU SUDDENLY GOT A LOT
MORE POLITICAL PUSH TO PASS
CLEAN AIR LEGISLATION TO START
HAVING WORKPLACES FREE OF
SMOKING, I DON'T WANT TO GET ON
THEM TOGETHER AND BREATHE AND
PUT THE SMOKE NEXT TO ME AND THE
STEWART EASES DOESN'T WANT
TO--LITTLE BY LITTLE THEY CLEAN
UP RESTAURANTS OR PLAYING MOVIES
AND THAT HAD A DRAMATIC HEALTH
EFFECT AND AND THAT IF TURN
AFFECTED THE SOCIAL ENVIRONMENT
SO IT BECAME MORE DIFFICULT TO
SMOKE.
SO LITTLE BY LITTLE YOU'RE
MOVING THEM FURTHER AWAY AND
YOU'RE CREATING A SOCIAL
SITUATION WHERE, YOU'RE BECOMING
A BIG IMPACT.
SO IT'S FINDING ALTHOUGH IN THE
EARLY 80S LIKE A MINOR IT SHOULD
BE A BIG, BIG, RIPPLE EFFECT.
OKAY, SO TOBACCO IS STILL--WE
LOOK IN THE UNITED STATES AND WE
THINK WOW WE'VE DONE AÑi LOT.
IF YOU GO TO THE SOUTH OR THE
MIDWEST, YOU STILL SEE A LOT OF
PEOPLE, A LOTS MORE PEOPLE
SMOKING THAN HERE BUT IT STILL
ACCOUNTS FOR THE DEATHS,
MILLIONS OF DEATHS WORLD WIDE.
THE RATE OF SMOKING CONTINUES TO
BE HIGH IN CHINA, SO WORLD WIDE
INCREASE IN LUNG CANCER RATE
OVER THE NEXT DECADE OR 2.
AND MEDICAID AND MEDICARE ARE IN
THE 10S OF BILLIONS EACH YEAR
AND FRANKLY THE RATES OF SMOKING
IN ADOLESCENTS HADN'T REALLY
GONE DOWN MUCH, THEY'RE REALLY
TOUGH AND THE DECLINES IN ADULTS
RIGHT ABOUT 19% OF ADULTS IN THE
UNITED STATES DIE, AND THE WORRY
IS THAT THE SMOKES YOU HAVE LEFT
ARE PARTICULARLY GENETICALLY
RESISTANT GROUPS.
SO THEY ARE THE 1S WHERE THERE'S
JUSTICE A SUBSTANTIAL NICOTINE
DISCIPLINARY PENDENCY AND YOU'RE
GOING TO REALLY NEED SOME MORE
TARGETED INTERVENTION TO GET
THEM TO QUIT SMOKING.
SO THAT'S KIND OF A PROBLEM.
OKAY, I'M GOING TO HAVE TO STEP
ON IT A LITTLE BIT.
OKAY, SO I'M NOT GOING TO GO
THROUGH ALL THE RISK FACTORS SO
MUCH THIS IS STUFF TO READ ABOUT
AND I'LL CALL THE NUMBER 2,
GENETIC FACTOR SMOKING.
AND RADIATION IS STILL RIGHT UP
THERE, IONIZING RADIATION AND
IOINIZING RADIATION, THE
EVIDENCE IS PRETTY GOOD.
THE ELECTROMAGNETIC IS PRETTY
BAD.
IOINIZEING RADIATION IS THE
NUMBER OF TUMORS AND PROBABLY
THE NEWEST THING IN THE
ISOINIZING RADIATION AREA IS
CLL.
AND THE MOST COMMON LEUKEMIA IN
THE ACULTS IN THE UNITED STATES
AND IT USED TO BE ALWAYS BE
THOUGHT AT CLL.
THAT 1 IS NOT RELATED TO
RADIATION AND WHY WAS THAT THE
CASE BECAUSE THE BEST DATA IS
THE ATOMIC BOMB SURVIVORS IN
JAPAN ANDAZZIANS HAVE VERY LOW
RATES.
SO INSUFFICIENT POWER TO DETECT
AN INCREASE IN CL L.
HOWEVER, WITH THE RADIATION
EXPOSURE THAT OCCUR INDEED CHER
NOBLE AND FOLLOWING UP THAT DATA
IN RUSSIA, YOU NOW SEE THE
INCREASE IN C. L. L.
SO,--SO THERE'S ALL SORTS OF
DATA AND ALL SORTS OF LARGE
STUDIES.
EACH 1 OF THESE STUDY SYSTEM
LIKE A AN INCREDIBLE AMOUNT OF
WORK TO DEMONSTRATE THE
ASSOCIATION OF CANCER AND
IOINIZED RADIATION I'M NOT GOING
TO TALK ABOUT THAT.
NONIOINIZEING RADIATION IS
PARTICULARLY THE WORRY IS
[INDISCERNIBLE] AT MELLAGEOMA
BUT THE OTHER--MELANOMA BUT THE
OTHER WORRY IS THAT BECAUSE OF
CFCs, YOU HAVE--YOU STILL HAVE
THE OZONE HOLE WHICH RE APPEARS
OVER BOTH POLES EVERY YEAR AND
THE INCREASE IN U. V. EXPOSURE
THROUGH THAT HOLE IS POTENTIALLY
VERY DANGEROUS.
YOU COULD HAVE ALSO MADE THEM
WITH BROMINE AND WITH BROMINE
YOU WOULD HAVE COMPLETELY
DESTROYED THE OZONE LEVEL
BECAUSE IT WAS ABOUT 50 TIMES
MORE ADVAUNT THAN DESTROYING
OZONE, IT LASTS LONGER IN THE
ENVIRONMENT BUT IT'S BETTER AT
DESTROYING OZONE SO WHEN THEY
MADE THESE CHEMICALS, AT THE
FIRST TIME, NOBODY KNEW, NO 1
WAS WORRY BODY THE OZONE LEVEL,
WHO KNEW THAT THE CHEMISTRY
WOULD RIP A PART OZONE SOW YOU
WOULD HAVE ESSENTIALLY YOU KNOW
BROMINE HAD AND, AND THE YOU
WOULD ESSENTIALLY HAVE IT LIKELY
DESTROY LIFE ON THE PLANET.
EMPLOY--IT WOULD HAVE HAPPEN
HAPPEN--OKAY, SO THE RADIATION
IS NOT GOOD ALSO FOR NONCANCKER
END POINTS.
AND DIET IS AN INEDIBLY
INTERESTING AND VAST AREA THAT
WE DON'T HAVE TIME TO GO INTO,
BUT THERE'S LOTS OF HIGH RISK
AND IF WE HONE IN ON JUST 1 LONG
1, NOW THERE'S SOME OF THE
QUESTIONS--GREAT STUFF, WE
SHOULD USE IT, WELL, IT TURNED
OUT THAT THE RATES OF LUNG
CANCER WERE HIGHER IN THE BETA
CAROTENE GROUP SO IT GOES TO
SHOW THAT YOU NEED THOSE
RANDOMIZED TRIALS.
YOU NEED TO TEST IT.
A LOT OF INFORMATION ABOUT
OBESITY PARADOX, A LOT OF
CANCERS ARE ASSOCIATE WIDE
OBESITY AND NOT LUNG CANCER AND
THE ISSUE THERE IS THAT YOU CAN
STILL GET MORE CANCERS BY BEING
OVERWEIGHT AND MEAT AND
VEGETABLES WITH THESE DATA AND I
WILL SHOW THAT WE DID A
STUDY--THIS A TRICKY STUDY,
RESPIRATORY--IT MEANS A LITTLE
AND IT KEEPS BECAUSE THIS IS
WHAT WAS KNOWN ABOUT VIRUSES
WITH CANCERS 20 YEARS AGO AND
MORE RECENTLY, YOU KNOW I KIND
OF MADE THE SLIDE QUICKLY BUT
THERE'S A LOT OF NEW VIRAL
HYPOTHESIS.
NOT ONLY THAT, BUT THERE'S A LOT
OF NEW TECHNOLOGY TO INVESTIGATE
VIRUSES.
SO WE'RE DOING A STUDY WITH
CHRONIC LEUKEMIA, WHERE WE'RE
WORKING, WHERE WHAT YOU DO IS
YOU TAKE THE B-CELL WHICH IS ARE
THE TUMOR CELLS AND TAKE THE
T-CELLS WHICH ARE THE NONTUMOR
CELLS AND SEQUENCE THEM AND THEN
YOU TAKE OUT THE SUCCESSFUL
WAVES OF MATCHING THE GENETICS
SEQUENCES TO DATABASES, YOU TAKE
OUT THE NONHUMAN SEQUENCES AND
THEN, YOU LOOK AT THE NONHUMAN
SEQUENCES IN RELATION TO
DIFFERENT MICROBIAL DATABASES
AND YOU TRY AND MATCH THEM UP
AND THIS TECHNIQUE BEEN USED BY
MATT MIRE SON TO IDENTIFY A
NUMBER OF KNOWN VIRUSES FOR
DIFFERENT CONDITIONS.
SO THE HONEY BEE COLLAPSE
SYNDROME, THERE WAS A VIRUS
ASSOCIATE WIDE THAT PEOPLE ARGUE
WHETHER IT'S PRIMARY OR
SECONDARY.
THERE'S A GROUP OF LYMPHOMAS
WITH TRANSPLANT DEATHS AND
IDENTIFIED VIRUSES THERE.
SO WE'RE GOING TO TRY AND USE
THIS TECHNIQUE FOR A NUMBER OF
CANCERS WHERE THE ETIOLOGY IS
NOT KNOWN AND WE'RE TRYING IT
FIRST ON CLLL.
AND OKAY, BACTERIA AND STOMACH
CANCER.
H-PILORIC IS ASSOCIATE WIDE A
VARIETY OF DIFFERENT CONDITIONS
AND WE TOOK A LOOK AT H-PYLORY
IN LUNG CANCER BECAUSE THERE ARE
4 SMALL POORLY DESIGNED STUDIES
IN THE LITERATURE THAT ARGUED
THAT H-PYLORY WAS ASSOCIATE WIDE
ADENO CARCINOMA WHEN WE LOOKED
WE SAW NO EFFECT IN ANY OF THE
SCHEMIC OR ADENO CARCINOMA AND
CAN YOU SEE THERE ARE SMALL
RELATIVE RISKS BUT WHEN THE
KNIFE% CONFIDENCE INTERVALS
INCLUDE 1, THAT INDICATES THAT
THE RESULT IS NOT THERE.
BUT IF YOU WATCH THE STUDY, YOU
COULD SAY THAT IF YOU HAD MORE
POWER AND DISCOVER THAT THE TINY
ODDS RATIOS WERE TRUE.
BUT I DOUBT IT AND I ACTUALLY AM
PRETTY CONVINCE THAD H-PYLORY
HAS NOTHING TO DO WITH LUNG
CANCER.
OKAY OCCUPATIONAL CAR SIN O
GRENS ARE IMPORTANT AND YOU SRO
A SITUATION WITH THE TOBACCO
EXECUTIVES THAT--WHATEVER THESE
ARE ARGUES THAT YOUR STUDIES ARE
HIGHLY FLAWED AND THESE
CHEMICALS ARE TRACKED AND WE
SHOULD DO MORE OF THEM BECAUSE A
LITTLE BIT OF THEM STIMULATE
YOUR BODY TO BE DEFENSIVE AND
THEY'RE GOOD, THEY'RE GOOD FOR
YOU.
SO, AND EACH OF THESE ARE CAR
SIN O GENERATEDS SO THAT'S A
CONTINUING 1.
SO, I'M NOT GOING TO TALK A LOT
MORE ABOUT OCCUPATIONAL EXPOSURE
BECAUSE WE'RE RUNNING OUT OF
TIME.
SO, WHAT DON'T WE KNOW ABOUT
CANCER CAUSES FIRST FOR A
VARIETY OF CANCERS WE REALLY
KNOW, I DON'T WANT TO SAY
NOTHING BUT WE KNOW VERY, VERY
LITTLE ABOUT EXTREENSIC AND
ENVIRONMENTAL CAUSES.
SO I'LL COME BACK TO, AND
CLEARLY EXPLAIN MOST OF CLL.
EXPLAIN A FEW EXTRA CASES.
AND WE DID A DIET STUDY TO LOOK
AT THIS.
COULDN'T THERE BE DIETARY AGENTS
THAT CAUSE CLLAND WE LOOKED IN
PLCL.
WHICH IS 150,000 PEOPLE WITH
DIET RECORDS AND WE LOOKED IN
AARP.
THE AMERICAN ASSOCIATION OF
RETIRED PERSONS WHICH IS AN EVEN
LARGER COHORT WITH VERY GOOD
DIETARY DATA AND WHAT DID WE
FIND, EXPLORED EVERY SINGLE DIET
THAT WAS IN THE DATABASE AND WE
FOUND NOTHING WE COULD FIND NO
FOOD ASSOCIATE WIDE CLL.
COULD THERE BE A NUTRIENT OR
COMBINATION OF FOODS OR FOOD
GROUP?
YES.
BUT, WHATEVER IT IS, IT REMAINS
OBSCURE.
FOR THE CANCERS WHERE THE
GENERAL CAUSE IS UNDERSTOOD,
INDIVIDUALS SUSEPTIBILITY IS A
MYSTERY.
SO I CAN TELL YOU THAT YOU KNOW
WE CAN MAKE A BEAUTIFUL CURVE OF
SMOKING AND WE CAN GET MODELS
AND WE CAN FIT MODELS AND
PREDICT THE RISK OF GROUPS BASED
ON SMOKING, AGE, GENDER A FEW
OTHER FACTORS AND DO A RISK
MODEL BUT CAN WE TELL WHAT AN
INDIVIDUAL'S RAKE IS?
NO.
WE REALLY CAN'T.
HOW GENES AND ENVIRONMENT WORKED
TOGETHER IS XREAMLY POORLY
UNDERSTOOD-OF EXTREMELY POORLY
UNDERSTOOD.
IN ALL SCIENCE, THE RATIO OF
WHAT IS DISCUSSED TO WHAT IS
KNOWN HIGHEST FOR GENE
ENVIRONMENT.
OKAY, WE REALLY HAVE A RATHER
POOR UNDERSTANDING OF HOW GENES
AND ENVIRONMENT WORK TOGETHER
AND SOME POTENTIAL CAUSES ARE
POORLY UNDERSTOOD.
THERE'S SOME THAT WE LITERALLY
HAVEN'T QUANTITATED AT ALL YET.
1 IS SLEEP, WE DON'T KNOW HOW
ALTERATIONS IN THE SLEEP CYCLE
AFFECT PEOPLE AND ANOTHER 1 IS
DISRUPTION OF CIRCADIAN RHYTHM.
SO IT'S CLEAR IN ANIMAL MODELS
THAT WHEN YOU DISRUPT CIRCADIAN
RHYTHM THAT TUMORS THAT ARE
IMPLANTED DO BETTER.
AND WHY IT'S OPERATE NOTHING YOU
HAD--HUMANS, AND SO WHAT DOES
THIS DO.
YOU WOULD DO THIS MECHANISTIC
KINDS OF STUFF, WE'RE USING
ADVANCED TECHNOLOGY AND WE USE
CONSORTIA TO MAKE GIGANTIC
GROUPS TO IMPROVE OUR HEALTH.
SO, I TOLD YOU THAT CLL IS 1
WHERE WE DON'T HAVE AN
EXTREENSIC AND ENVIRONMENTAL
CAUSE AND NOW AFTER TELLING YOU
THAT CANCERS DUE TO ENVIRONMENT,
I'M GOING TO COME BACK TO MY
ORIGIN THAT'S GENETIC AT THE
IMUGOLOGY BRANCH AND TELL YOU,
NO, I LIED.
IN FACT ALL CANCERS DO TO GENES
OKAY, SO PRETTY MUCH EVERY
CANCER EXHIBITS SOMEATIC
MUTATIONS OF SOME KIND.
THAT ARE PASSED ON AND THAT
MAINTAIN THE MALIGNANT PHENOTYPE
SO WHILE YOU LOOK AT THE
ENVIRONMENT AND BLAME THAT,
INTERNALLY, WE'RE TALKING
GENETICS.
SO WE NEED TO FIND THAT AND HOW
DO YOU INVESTIGATE GENETICS TERM
PATHOLOGY?
YOU HAVE TO DETERMINE WHETHER
WE'RE TALKING ABOUT GERM LINE OR
SOMEATIC AND WE LOOK AT
INHERITED DEFECTS, BUT
INCREASINGLY WE'RE TRYING TO GET
OUR HANDS ON THE TUMOR SO WE
CAN'T INVESTIGATE THIS COMPENENT
AND YOU HAVE TO DECIDE WHETHER
YOU'RE LOOKING AT FAMILIES OR
POPULATIONS.
DAMAGELY IN THE POPULATION, THE
GENETIC RISK IS SMALL.
AND FINALLY, ARE WE USING A
CANDIDATE APPROACH OR AN
AGNOSTIC APPROACH.
SO THE PAST 10 YEARS, THE
AGNOSTIC APPROACH USING
HIGH-TECHNOLOGY TO BE HUNDREDS
OF THOUSANDS OF SNIPS IS
BECOMING MORE COMMON AND WE CAN
CLEARLY SEE THAT SEQUENCE
SUGGEST ON THE WAY OF TO BEING
THE METHOD OF CHOICE.
SO THIS IS THE FIELD OF GENETIC
EPIDEALIOLOGY AND REALLY THE
ORIGIN WAS IN FAMILY STUDIES AND
WE COLLECT FAMILIES LIKE THIS.
SO HERE WE HAVE AN NHL AND A CL
L AND 2 SIBLINGS, AND ALSO AN
NHL, AND THEN IN THE NEXT
GEBERATION HAVE ANOTHER CLL, AND
HAVE ANOTHER CLL.
AND SO THE KINDREDS IF YOU SEE
THE MENDELIAN PATTERN OF
INHERITANCE, IT'S CLEAR THERE
WILL BE A LOT MORE OF THE GENES
UNDER MOST GENETIC MODELS SO YOU
WANT TO STUDY FAMILIES LIKE
THIS.
THIS IS WHERE THE GENES ARE
HIDING, UNFORTUNATELY, THE
EXAMPLE SUFFICIENT CDK, AND 2A,
AND MUTATIONS IN MELANOMA.
AND YOU FIND THESE MUTATIONS IF
YOU ONLY HAVE 2 CASES IN THE
FAMILY, YOU FIND IT IN LESS THAN
5% BUT AS THE NUMBER OF CASES IN
THE FAMILY GOES HIGHER YOU ARE
MORE LIKELY TO FIND GENES
CANDIDATE GENES LIKE THIS.
AND HERE'S EXAMPLES OF GENES
THAT HAVE BEEN CLONED AND IT
GOES UP TO 96, BUT SINCE THEN,
THERE HAVE BEEN A FEW MORE, BUT
NOT MANY.
AND TO SOME EXTENT THERE'S BEEN
A LITTLE BIT OF A DIFFICULTY IN
THAT--THAT WE'VE DONE LARGER AND
LARGER GENETIC STUDIES IN
FAMILIES AND WE DON'T FIND THE
TRADITIONAL GENES THAT WE EXPECT
TO FIND SO A LOT OF FAMILIARIAL
MALIGNANCY REMAINS UNEXPLAINED.
OKAY, SO WHY BOTHER WITH LUNG
CANCER AND 1 OF THE REASONS OF
COURSE I TOLD YOU ABOUT THE
MORTALITY IS TREATMENT IS LOUSY,
AND SCREAMING IS REALLY
PROBLEMATIC.
YOU SAW THE SCREENING STUDIES IN
IDENTIFYING 20% AND ALL THE
MORTALITY BY 20% PROPORTIONATELY
SO IF YOU DO THE CALCULATIONS,
IT COSTS AS MUCH AS 2 MILLION
DOLLARS IN EACH CANCER CASE THAT
YOU PREVENT.
SO BEFORE YOU WANT TO INTRODUCE
THIS KIND OF MEASURE ON A
POPULATION LEVEL, YOU REALLY
NEED TO THINK VERY HARD AND MOST
EPIDEMIOLOGISTS THINK IT'S
REALLY NOT A GREAT IDEA.
AND SURVIVAL.
THE 13% IN THE 1970 AND NOW
WE'VE SOARED ALL THE WAY UP TO
16, MAYBE--I'LL GIVE YOU 20% 5
YEAR SURVIVAL SO CLEARLY WE
HAVEN'T MET THE CHALLENGE OF
LUNG CANCER YES.
EARLY ON WE DID A STUDY OF LUNG
CANCER RISK AND FAMILY HISTORY
AND THERE HAVE BEEN 20 STUDIES
LIKE THIS AND EVERY STUDY GIVES
A SIMILAR RESULT THAT IF YOU
HAVE A FAMILY MEMBER WITH LUNG
CANCER COMPARING TO CONTROLS AND
ADJUSTING FOR EVERYTHING YOU CAN
ADJUST FOR, YOU GET A FAIRLY
SUBSTANTIAL INCREMENT OF RISK
FOR HAVING FAMILY MEMBER MEANING
YOU'RE PROBABLY SHARING GENES.
WHAT ARE THOSE GENES?
WELL, WE DID CANDIDATE GENE
STUDIES, 10 AND 20 YEARS AGO
BECAUSE WE THOUGHT, THIS IS THE
CAUSE OF LUNG CANCER, THE
CARCINOGENS AND TOBACCO HAVE TO
BE METABOLICALLY ACTIVATED AND
THE GENES THAT DO THAT ARE UNDER
GENERATED THETIC CONTROL AND WE
KNOW 2 A6 AND THAT TOO SO WE
TESTED ALL THESE GENES WELL WE
DIDN'T REALLY FIND THAT MUCH AND
THERE WERE A LOT OF METHODS,
PROBLEMS WITH THOSE STUDIES AND
SO WE HAD TO AWAIT GWAS
TECHNOLOGY OVER THE LAST 4 OR 5
YEARS.
, AND SO IT'S THE ENVIRONMENT
AND THE GENES AND THEN MAYBE
THERE'S INTERACTIONS WE HAVEN'T
DISCOVERED MANY OF THEM AND IT'S
ONLY A HANDFUL OF EXAMPLES IN
CANCER.
SO HERE'S 1 OF THEM.
THE TRANSFER ACE, THIS
PARTICULAR GENE DETOXIFYS THESE
AMINES AND HALF THE POPULATION
HAS THE SLOW VERSION AND IF YOU
HAVE THE SLOW VERSION, YOU'RE A
SLOW ACETALATOR AND IT'S 1 OF
THOSE EFFECTS, THE
PHARMACOGENETIC TRAITS THAT
AFFECTS MULTIPLE GENES LIKE CAP
SUM, PROCANNA MID, IT'S ABOUT 15
OF THESE GENES, BUT, IT ALSO
METABOLIZES ARROWMATIC AMINS AND
IF YOU'RE A SLOW ACETALATOR, THE
ARROWMATIC AMINS SITS IN YOUR
SYSTEM FOR A LONGER PERIOD OF
TIME AND WHAT HAPPENS, YOU GET
BLADDER CANCER AND THIS WAS
SHOWN IN GERMAN DIE WORKERS IN
THE 1850S, SO THESE MEANS ARE
ALSO IN TOBACCO SMOKE AND GOOD
LUCK WAS FINALLY SHOWED THESE
PARTICULAR SNIP WAS A RISK
FACTOR FOR BLADDER CANCER AND IT
CONFIRMED 2 DECADES OF CANDIDATE
GENE STUDIES BUT THIS IS 1 OF
THE FEW, AND THE MORE YOU SMOKE,
THE MORE THIS GENE IS A RISK
FACTOR SO IT'S 1 OF THE FEW
EXAMPLES THAT'S OUT THERE.
OKAY, LIF YOU GO BACK IN A TIME
MACHINE ONLY 6 OR 7 YEARS AGO,
YOU SAW VERY ACTIVE ARGUMENTS
THAT SAID THESE GWAS STUDIES ARE
NOT GOING TO WORK, THEY'RE A
WASTE OF TIME, YOU'RE SPENDING
MILLIONS ON GENE WHEN IS YOU
COULD BE WORKING ON REAL CAUSES
OF CANCER, AND TOBACCO STUDYING
THOSE AND THINGS BUT YOU KNOW
PEOPLE MADE STRONG ARGUMENTS AND
IN FACT, GWAS STUDIES THAT NOW
NUMBER ABOUT 500 YOU CAN GO TO
THE NHGRI WEB SITE AND THEY HAVE
A VERY NICE LIST, EVERY WEB SITE
THAT COMES OUT THEY LIST THE
GENES FOUND PRETTY MUCH FOR
VIRTUALLY EVERY MEDICAL
CONDITION, HAVE YOU NOW E
DENTIFIED GENES OF MODEST EFFECT
AND THE PROBLEM IS THAT
VIRTUALLY BY EVERY CALCULATION
YOU CAN DO.
IT SHOULD BE THERE, BASED ON
OTHER APPROACHES, WHAT ARE THE
KINDS OF OTHER APPROACHES FAMILY
STUDIES, TWIN STUDIES, YOU CAN
CALCULATE THE AMOUNT OF GENETIC
BEARING, CAN'T EXPLAIN IT ALL.
OKAY, STUDY DESIGN AND I'LL
QUICKLY TELL YOU THAT
TRADITIONAL EPIDEMIOLOGY LEAVING
EXPOSURE TO IT, SO I COUNTED THE
NUMBER OF LUNG CANCER SKAS
CASES, I COUNTED HOW MUCH THEY
SMOKED, I USED THE STATISTICAL
MEASURE, TO SEE WHAT THESE
ASSOCIATION WAS AND I GIVE YOU A
RELATIVE RISK.
SO THAT'S WHAT EPIDEMIOLOGIST
WERE, AND YOU FOCUS ON SOMETHING
CALLED MOLECULAR AND MEASURE
INTERNAL DOSE.
ALL THE STRUCTURE AND FUNCTION
AND, SO WE DID A LUNG CANCER
STUDY AND INSTEAD OF ASKING
PEOPLE TO SMOKE WE ASKED THEM IF
THEY WERE DEPRESSED WHAT THEIR
PERSONALITY TYPE WAS AND IF THEY
HAD ATTENTION DEFICIT, HOW
NICOTINE DEPENDENT THEY WERE AND
WE DIDN'T JUST COUNT THE NUMBER
OF LUNG CANCERS, WE TRACKED HOW
WELL THEY SURVIVED.
SO THAT'S WHAT WE'RE DOING
THAT'S NEW.
WHEN YOU DO THAT, YOU CAN ASK
MORE QUESTIONS, CAN YOU MEASURE
YOUR GENE WHICH WE DO, AND IT'S
WITH LUNG CANCER AND WE ALSO
RELATED TO THE EXPOSURE.
SO WE'RE DOING THE STUDY
RELATING GENES TO SMOKING.
WHAT IS THE--WHAT IS IT ABOUT
SMOKING, WHAT GENES MAKE YOU
MORE OR LESS LIKELY TO SMOKE.
WE'RE ALSO RELATING IT TO
DIFFERENT INTERMEDIATE MARKERS,
WE GET TISSUE AND WE LOOK AND
SEE IF SOMEONE HAS P53 AND SAY
IF YOU HAVE OH P53, ARE YOU MORE
LIKELY TO HAVE A CERTAIN
INHERITED GENE.
THEN WE RELATE IT TO OUTCOME.
I'LL JUST TELL YOU, WHEN IT
COMES TO OUTCOMES, IN IS THE
EAGLE THIS IS OUR USUAL STUDY,
AND WE HAVE 2000 KIDS AND 2000
STUDIES AND GOOD POWER AND WE
COULD NOT FIND AN OUTCOME IN
OTHER WORDS WHICH IS THE
PROBABILITY, AND THESE IS
DISEASE STAGE 4 STHERE A GENE
PREDICTS HOW LONG YOU SURVIVE,
AFTER YOU TAKE INTO ACCOUNT AGE
GENDER.
WE'VE COMBINED WITH ONLY 2 OTHER
LUNG CANCER STUDIES IN THE WORLD
THAT CAPTURE THIS DATA THAT'S
MDANDERSON, AND DAVID CRISTIANY
AT HARVARD.
AND WE STILL CAN'T FIND IT.
SO, IF WE FIND IT, I'LL LET YOU
KNOW BECAUSE THAT WILL BE REALLY
INTERESTING.
AND IT'S PRETTY LATE, I'LL STOP
HERE IN CASE ANY OF YOU HAVE ANY
QUESTIONS.
>> THANK YOU FOR STAYING AWAKE.
>> [INDISCERNIBLE].
>> I'M REALLY HAPPY YOU ASKED ME
THAT.
WHEN IÑi WAS AN UNDERGRADUATE, I
WAS A [INDISCERNIBLE] MAJOR.
--GLOBAL WARMING.
WARM SUGGEST VERY REAL--WARMING
IS VERY REAL, IT'S A VERY TOUGH
DECISION ABOUT WHAT TO DO
BECAUSE OBVIOUSLY WE NEED ENERGY
AND WE HAVE TO--YOU KNOW WE HAVE
TO--IT HAS EFFECTS ON GROUND
WATER AND CLEARLY PRODUCES
HYDROCARBONS.
MOVE MORE TOWARDS NATURAL GAS
WHICH HAS A LOT OF OF BURDEN
THAN OIL, THAN PURE PETRESSABLE
TROLL TO THINK THAT
AND--PETROLEUM AND WE SHOULD BE
USING NONTRADITIONAL TYPES OF
POWER COURSES AND WHEN AND I
THAN THAT'S GOING TO BE TOUGH TO
GET A WINDMILL TO DRIVE A CAR
AND TOUGH TO GET A NUCLEAR
REACTOR TO DO THAT BUT WE
SHOULD.
WE SHOULD BE LOOKING AT THOSE
TECHNOLOGIES VERY HARD.
>> [INDISCERNIBLE].
>> THE FIRST ROUND OF STUDIES IN
LONG ISLAND DID NOT FIND A
PARTICULAR FEATURE ON--AND WHILE
I'M HAVING [INDISCERNIBLE]
AGRICULTURE AND A LOT OF
ENVIRONMENT WERE PARTICULARLY
WORRIED ABOUT THESE HORMONAL NEW
MAKING CHEMICALS CAUSING THIS
AND THOSE STUDIES TO BE DONE AND
THAT THE MORE STUDIES YOU DO,
YOU'LL FIND THAT SOME OF THE
TRADITIONAL HORMONAL FACTORS AND
GROWTH FACTORS RELATED TO
ENHANCED NUTRITION THAT CAUSE
EARLY AGE MEN ARCH SCHEENHANCED
NUMBER OFLES THAT AND--NUMBERS
OF AISLES AND GENERALLY CONSIDER
NOT ESPECIALLY A BIG DEAL AND
DEPARTMENT REALLY REVEAL A LOT
AND THE OVERALL THAT IT WAS THAT
POLITICAL PUNCH OF THAT
PARTICULAR THAT INSPIRED STUDIES
RATHER THAN TRUE EPIDEMIOLOGIC
IMPERATIVE RATES THAT THEY WERE
SO MUCH HIGHER.
SO--YES?
>> [INDISCERNIBLE]
>> SO WHAT ABOUT SMOKING
PARENTS?
SO OKAY, ENVIRONMENTAL TOBACCO
SMOKE TENDS TO COME IN 3 AREAS.
THERE'S CURRENT SMOKING BY YOUR
SPOUSE IN YOUR HOME WHICH IS
VERY WELL DOCUMENTED, THERE'S
SMOKING IN THE WORKPLACE, LESS
DOCUMENTED BUT ALSO DOCUMENTED
AND THEN, THERE'S SMOKING
EXPOSURE DURING CHILDHOOD.
IT'S PRETTY CLEAR THAT OVERALL
RESPIRATORY DISEASES ARE
ABSOLUTELY INCREASED BY
CHILDHOOD EXPOSURE.
THE STORY WITH LUNG CANCER IS
STILL NOT SO CLEAR.
IT'S VERY HARD TO SEPARATE THE
CHILDHOOD SMOKING EXPOSURE FROM
THE OTHER CATEGORIES AND YOU
KNOW WE'VE TRIED TO DO IT IN 1
STUDY AND WE FOUND WHAT WE
THINK, A STUDY WITH CLIFF HARRIS
THAT THERE WAS SOME RISK AND I
THINK THAT THE QUESTION IS STILL
OPEN.
>> [INDISCERNIBLE].
>> HE CAN GO TO THE SURGEON
GENERAL'S REPORT AND YOU CAN
READ A LOT ABOUT FORMATION OF
DNA ADDICTS AND A LOT OF THE
MECHANISMS ARE KNOWN BUT THERE
ARE ALSO BIG GAPS.
>> THERE ARE MECHANISMS ON
WHAT'S DIFFERENT FROM THE
[INDISCERNIBLE]
>> YEAH, OKAY, THAT'S LESS
KNOWN.
YEAH, YEAH, YEAH.
>> THAT'S NOT REALLY WELL KNOWN.
>> OKAY, THAT'LL DO IT.
WE HAVE TO GO ON OUR TOUR.