UNDERSTANDING
GENETICS
FROM THE 24 1/2 LECTURES BY DAVID SADAVA Ph. D. FOR THE TEACHING COMPANY - 2007
BIO-TECHNOLOGY - GENETIC ENGINEERING
QUOTE
OPENING STORY CONCERNS BILL, A STROKE VICTIM.
AS HE DROVE HOME FROM WORK HE FELT HIS FACE TWITCHING, THEN HIS SPEECH BECAME SLURRED, THEN HE GOT A REALLY REALLY BAD HEADACHE.
BILL IS ONE OF SEVERAL MILLION IN THE USA WHO HAVE A STROKE EACH YEARS.
A BLOOD CLOT FORMED IN AN ARTERY LEADING FROM THE HEART TO THE BRAIN. A COT OF THE BLOOD THAT CARRIES OXEGEN TO THE BRAIN - IRREVERSIBLE - CAN RESULT FROM BILL’S STROKE.
NOW WHEN YOU THINK OF BLOOD CLOTS, WELL THEY DO EVENTUALLY GO AWAY, BUT “GO AWAY” IS NOT A GOOD WAY TO SAY IT. NOT A GOOD BIOLOGICAL TERM, WE SAY, “DISSOLVES.”
AS THE WOUND IS HEALED, A HOLE IN THE SKIN FOR EXAMPLE, A SERIES OF CELLS HEALING THE WOUND, CREATES A SUBSTANCE CALLED “TISSUE PLASMINOGEN ACTIVATOR” [TPA].
AND TPA ACTIVATES THE BLOOD CLOTTING SYSTEM, THAT IS ALREADY TO GO IN THE BLOOD. A CLOT DISSOLVES.
THE TIME FACTOR IS IMPORTANT BIOLOGICALLY SPEAKING!
FOR IF THE CLOT DISSOLVED THE MINUTE IT WAS FORMED IT COULDN’T DO MUCH GOOD. THE BLOOD WOULD CONTINUE TO FLOW OUT AND YOU’D LOOSE ALL YOUR BLOOD. SO SLOW DISSOLVING OF THE CLOT IS A GOOD THING.
BUT NOT FOR BILL, WHO WAS HAVING A STROKE, A BLOOD CLOT FOR ANY LENGTH OF TIME WAS NOT GOOD FOR HIM. EVERY MINUTE THE BLOOD IS RESTRICTED TO THE BRAIN, IT’S HARMFUL.
BILL WAS CLOSE TO A HOSPITAL - HE DROVE TO EMERGENCY, LAY ON THE CAR’S HORN, AND GOT ATTENTION RIGHT AWAY. IMMEDIATELY THEY PUT A MEDICATION ON THE SPOT OF THE CLOT AND RIGHT AWAY IT DISSOLVED. BLOOD FLOW WAS RESTORED AND THERE WAS MINIMAL DAMAGE TO THE BRAIN; HE WAS HOME THE NEXT DAY AND WAS FINE.
THE DRUG THE EMERGENCY STAFF INJECTED WAS TPA. THIS IS THE PROTEIN THAT INITIATES THE CLOT DISSOLVING PROCESS.
NORMALLY THIS TAKES A LONG TIME, SURE BILL’S CLOT WOULD HAVE DISSOLVED, BUT OVER A LONG TIME, AND SO HIS BRAIN WOULD HAVE BEEN DAMAGED BEYOND REPAIR.
THIS SUBSTANCE APPLIED RIGHT THEN AND THERE ACTIVATED TO MAKE THE PROCESS TO DISSOLVED THE COT.
THE BAD THING IS IF WE WANT TO USE IT AS IN BILL’S CASE, WE NEED TO HAVE LOTS IF IT AROUND. IT’S VIRTUALLY IMPOSSIBLE TO GET ENOUGH OF IT FROM THE CELLS OF A PERSON, AND HAVE ON THE SHELVES READY FOR INJECTION.
ENTER—— RECOMBINANT DNA TECHNOLOGY!
FIRST— DNA WAS ABSTRACTED FROM HUMAN CELLS, AND THE GENE FOR TPA WAS ISOLATED BY THE PROCEDURE IN THE LAST LESSON. THIS DNA GENE WITH THE APPROPRIATE PROMOTER STIMULATING ITS EXPRESSION. THE FIRST TRY WAS IN BACTERIA CELLS - NOT A GOOD RESULT. SECOND - USED HAMSTER CELLS. IT WORKED WELL AND MUCH TPA WAS MADE, WAY MORE THAN COULD EVER BE MADE FROM BLOOD. A TPA PROTEIN WAS PURIFIED, PUT IN A BOTTLE AND SENT TO DOCTORS, HOSPITAL EMERGENCY ROOMS ETC.
THIS SCENARIO OF A GENE TO USEFUL PROTEIN BY GENETIC TECHNOLOGY, HAS BEEN PLAYED OUT FOR DOZENS OF PRODUCTS.
IT’S PART OF A REVOLUTION IN BIO-TECHNOLOGY.
BIOTECHNOLOGY—— THE MANIPULATION OF MICROBES, PLANTS, AND ANIMALS, TO MAKE PRODUCTS USEFUL TO PEOPLE.
AS SUCH BIOTECHNOLOGY IS NOT NEW, IT BEGAN A LONG TIME AGO; IT BEGAN IN AGRICULTURE.
AGRICULTURE—— THE HARVESTING, PLANTING, AND CULTIVATION OF PLANTS AND ANIMALS FOR FOOD AND FIBER.
ESTIMATES ARE AGRICULTURE BEGAN ABOUT 10,000 YEARS AGO [MAYBE 15, 20, OR MORE - Keith Hunt], WHAT IS NOW PRESENT DAY IRAQ.
WE HAVE EVIDENCE THAT SEMERITANS LIVING THERE AT THE TIME, LEARNT THAT BARLEY PLANTS GROWING NEAR TO WHERE THEY LIVED; THE BEADS OF BARLEY COULD BE MASHED UP TO MAKE BREAD AND ALSO BEER [THEY ALREADY HAD FERMENTATION DOWN AS A SKILL FROM OTHER THINGS IN NARUTE - Keith Hunt].
SO SEEDS FOR MASHING AND SOME FOR NEW GROWTH OF BARLEY.
IN EGYPTIAN HYRO-GRAFICS SHOW BEER AND BREAD AS STAPLE IN THEIR DIET.
WHY BEER? JUST TO HAVE A PARTY?
ANSWER— NO!
WHEN PEOPLE SETTLED IN VILLAGES AND TOWNS, THEY SOON CAME TO REALIZE WATER PURITY WAS A BIG PROBLEM. USING THE SAME WATER TO DRINK AND BATH AND USE OF TOILET, PEOPLE GOT SICK!
ALCOHOL DRINKS KILLED ANY BAD STUFF IN THE WATER.
FERMENTATION THROUGH YEAST PORE CELLS KILLS BAD BACTERIA IN WATER.
THE WORD FERMENTATION FROM THE LATIN “FERVERE” - TO BOIL. THE ‘V’ IS NOT PRONOUNCED. AFTER FOUR YEARS OF LATIN IN HIGH SCHOOL I CAN USE IT NOW.
BUBBLES FORM BECAUSE OF THE RELEASE OF CARBON-DIOXIDE.
FERMENTATION UNDER OTHER CONDITIONS PRODUCED OTHER PRODUCTS AS WELL, SUCH AS CHEESE, YOGURT, VINEGAR, LOTS OF THINGS.
BY THE MID-20TH CENTURY THERE WAS A WHOLE INDUSTRY CALLED BIO-TECHNOLOGY, SOME USING MICRO ORGANISMS IN HUGE VATS; THINGS LIKE ANTIBIOTICS, OILS, AMINO ACIDS, AND ENZYMES FOR THE FOOD INDUSTRY.
MODERN TECHNOLOGY IS NOT NECESSARILY THE BIO-TECHNOLOGY I’VE JUST DESCRIBED.
DNA BIOTECHNOLOGY
* GENERAL STRATEGIES OF USING recDNA
* THE FIRST MAJOR PRODUCT: HUMAN INSULIN
* OTHER MEDICALLY USEFUL PRODUCTS
* GENETICALLY ENGINEERED ANIMALS AND PLANTS TO MAKE PRODUCTS OF USE
WHAT PRODUCTS DOES recDNA MAKE FOR HUMAN USE?
TWO WAYS TO MAKE:
FIRST— EXISTING ORGANISMS COULD BE MODIFIED GENETICALLY TO BE MORE EFFICIENT; A NEW BIOTECH PATHWAY.
SECOND— NEW GENES COULD BE INSERTED INTO PRODUCTIVE ORGANISMS THAT HAVE NEVER HAD THEM BEFORE…. WE’RE HAVING BACTERIA MAKE THINGS THEY’VE NEVER MADE BEFORE, THE ACTIVATOR TPA FOR EXAMPLE.
THE KEY TO ALL OF THIS IS THE PROMOTER!
THE PROMOTER IS—— A DNA SEQUENCE BASED TO A GENE THAT ATTRACTS THE MOLECULES THAT EXPRESS THE GENE, MAKE RNA COPY, THE WHOLE COMPLEX OF MOLECULES THAT WILL BE INVOLVED IN DOING THAT.
PROMOTERS TURN OUT TO BE SPECIFIC FOR PLACE, THAT IS WHAT CELL TYPE IS GOING TO EXPRESS THE GENE, AND TIME; AS I’VE SAID BEFORE YOU DON’T HAVE HAIR GROWING OUT OF YOUR BONE MARROW, OR BLOOD CELLS GROWING OUT OF YOUR HEAD OF HAIR. THE PROMOTER IS THE REASON THE GENES ARE ALL THERE, THE PROMOTER IS DIFFERENT BESIDE THE GENES.
WE FOUND ALL THIS FROM PEOPLE WHO JUST WANTED TO KNOW HOW ALL THIS WAS DONE - BASIC RESEARCH LED TO THIS INDUSTRY.
PRODUCTION OF TPA
1. GENE [DNA] FOR TPA.
2. SLICED IN TO AN EXPRESSION VECTOR WITH SELECTABLE GENE AND PROMOTER.
3. PUT INTO, SAY A BACTERIAL CELL.
IT MAKES A LOT OF THE TPA WE ARE INTERESTED IN.
THE FIRST MAJOR PRODUCT FOR WIDE SPREAD USE WAS— HUMAN INSULIN; ABOUT 25 YEARS AGO [FROM 2007 WHEN THESE LECTURES WERE DONE - Keith Hunt].
INSULIN— COMES FROM A LATIN WORD FOR ISLAND— IT IS MANUFACTURED IN A VERY SMALL PART OF THE PANCREAS, CALLED ISLETS OF LANGERHANS.
INSULIN IS A PROTEIN THAT ACTS AS A HORMONE TO STIMULATE UPTAKE OF BLOOD SUGAR INTO TISSUES, SUCH AS THE LIVER AND MUSCLE.
IN DIABETES TYPE 1, PEOPLE ARE UNABLE TO PRODUCE INSULIN.
IN DIABETES 2 PEOPLE ARE NON-RESPONSIVE TO INSULIN.
PREVIOUSLY INSULIN CAME FROM SLAUGHTERED ANIMALS.
THE PROTEIN FOR INSULIN HAS 51 AMINO-ACIDS; IT FOLDS IN A CERTAIN WAY; IT GOES TO A CELL [LIVER, MUSCLE] AND SAYS, “SUCK UP THE SUGAR FROM THE BLOOD.”
BUT VERY OFTEN THERE IS A CONFLICT!
ANIMAL INSULIN HAS A FEW AMINO-ACIDS DIFFERENT FROM HUMAN INSULIN. OVER TIME THE HUMAN AMMUNE SYSTEM SAYS, “I DON’T KNOW YOU; YOU ARE NOT FROM ME.” SUCH PEOPLE WERE THEN IN A BIG PROBLEM; WE NEED HUMAN INSULIN, SO OUR AMMUNE SYSTEM FULLY ACCEPTS THE 51 AMENO-ACIDS— EVERY HUMAN MAKES THE SAME INSULIN.
THE PROBLEM IS THAT LITTLE AREA IN THE PANCREAS ONLY MAKES A TINY SMALL AMOUNT OF INSULIN.
IT NEEDS TO BE BOOSTED, AMPLIFYING THE EXPRESSION OF THE GENE.
HERE ARE THE STEPS THAT WERE DONE—
AT THE “CITY OF HOPE” MEDICAL CENTER, KEIICHI ITAKURA WENT INTO THE CHEMISTRY LAB AND MADE THE INSULIN GENE. NOW INSULIN HAS 51 AMINO-ACIDS AND 3 BASE PAIRS CODING FOR EACH AMINO-ACID, SO ABOUT 150 BASE PAIRS. IT TOOK TIME, NOW IT’S DONE BY MACHINE.
ITAKURA’S COLLEGE— ARTHUR RIGGS TOOK THIS INSULIN GENE AND PUT IT INTO AN EXPRESSING VECTOR NEXT TO A HIGH EXPRESSING PROMOTER.
IT WAS THEN PUT INTO A BACTERIA AND THE BACTERIA EXPRESSED HUMAN INSULIN.
THIS WAS ABOUT 7 OR 8 YEARS AFTER RECOMBINANT DNA WAS DONE.
A BIO-TECHNOLOGY COMPANY IN LARGE VATS ENABLED INSULIN TO BE MADE IN QUANTITY. IT WAS THEN DISTRIBUTED TO DOCTORS ETC.
THIS IS THE SOURCE OF ALL INSULIN MADE TO TREAT DIABETES #1.
IT’S A BIO-TECHNOLOGY MEDICATION.
OTHER USEFUL PRODUCTS HAVE BEEN MADE BY BIO-TECHNOLOGY.
* REPLACEMENT PROTEINS FOR ONES MISSING IN GENETIC DISEASES, LIKE INSULIN.
* BLOOD CLOTTING PROTEINS IN HEMOPHILIA— PEOPLE WHO HAVE NO BLOOD CLOTTING IN THEIR BLOOD AND CAN END UP DYING.
* PROTEINS USED TO TREAT DISEASES. THERE IS A PROTEIN CALLED “ERYTHROPOIETIN [EPO]. EPO IS A HORMONE LIKE SUBSTANCE MADE BY THE KIDNEYS; IT ENTERS THE BLOOD STREAM, IT GOES TO THE MARROW AND IN THE BONE MARROW IT STIMULATED THE RED BLOOD CELLS. NOW RED BLOOD CELLS ONLY LAST ABOUT 120 DAYS IN THE BLOOD, SO MUST BE CONSTANTLY REPLACED.
CONSIDER A PATIENT WITH KIDNEY FAILURE, MANY HAVE THIS PROBLEM. THEY CAN BE TREATED WITH DIALYSIS. TRANSPLANTS ARE LIMITED. DIALYSIS FILTERS OUT BAD THINGS BUT IT ALSO FILTERS OUT EPO. SO THEY ARE NOT MAKING EPO IN AFFECT. THEY HAVE SEVERE ANEMIA, TO GET AROUND THIS WOULD BE A MASSIVE TRANSFUSIONS, OR TREAT THEM WITH EPO.
SO THE EPO GENE WAS ISOLATED, EPO WAS MADE BY BIO-TECHNOLOGY, SO THIS IS WIDLY USED FOR PEOPLE UNDER DIALYSIS.
EPO WAS THE FIRST BIO-TECH TO BE ABUSED OR MIS-USED. ATHLETES FOUND EPO INCREASES RED BLOOD CELLS - IT STIMULATES PRODUCTION OF RED BLOOD CELLS BY ABOUT 10 PERCENT. HENCE GIVING AN ADVANTAGE OVER OTHERS. IT HAS BEEN ABUSED IN CERTAIN SPORTS.
PLANTS AND ANIMALS CAN BE GENETICALLY ENGINEERED TO MAKE PRODUCTS USEFUL FOR US.
GREAT EXAMPLE IS DAIRY ANIMALS, LIKE SHEEP, GOATS, AND COWS.
THEY PRODUCE A LOT OF MILK IN THEIR MAMERY GLANDS, WHICH ARE THEIR VERSION OF BREASTS.
BIOLOGY SCIENTISTS DISCOVERED THAT THE EXPRESSION OF GENES FOR THE MAJOR MILK PROTEINS, IS UNDER THE CONTROL, NOT SURPRISINGLY, OF A PROMOTER CAUSING TO BE EXPRESSED IN THE MAMERY GLANDS. IT’S CALLED “LACTOGLOBULIN PROMOTER.”
WELL THIS SETS UP A REAL NICE BIO-TECH.
YOU CAN TAKE THE GENE YOU WANT EXPRESSED IN MILK AND PUT IT INTO A DNA VECTOR, THAT HAS IN IT THIS LACTOGLOBULIN PROMOTER, AND YOU PUT THIS VECTOR INTO A SHEEP EGG CELL NUCLEUS, AND FERTILIZE THE EGG. LET IT DEVELOP IN THE LAB FOR A FEW DAYS, THEN INSERT IT INTO A SURROGATE MOTHER, WHICH NOW HAS THIS MODIFIED EMBRYO. THE OFFSPRING BORN WITH A NEW GENE. NOW WE HAVE SHEEP THAT MAKE MILK WITH THIS EXTRA PROTEIN YOU WANT.
THIS WAS WHAT WAS BEHIND CLONING “DOLLY” THE SHEEP.
THERE ARE SOME PEOPLE THAT LACK THE NORMAL AMOUNT OF GROWTH HORMONE, THEY ARE SHORT IN STATURE.
THE GROWTH HORMONE IS A PROTEIN WE GET FROM THE BODY, IN THE PITUITARY GLAND, BUT IN SMALL AMOUNTS, LIKE TPO.
WE HAVE TO GET IT BY RECOMBINANT DNA TECHNOLOGY.
SO THE GENE WAS ISOLATED, PUT INTO A VECTOR AND INTO COWS.
THERE IS A HERD IN ARGENTINA OF 10 COWS, THAT IN THEIR MILK WILL SUPPLY THE WORLD’S NEED FOR HUMAN GROWTH HORMONE EVERY YEAR. AND IT’S EASY TO GET THIS HORMONE OUT OF THE MILK, ALL EASIER THAN USING BACTERIA.
AMAZING! AND IT’S WORKING VERY WELL.
THIS IS CALLED “PHARMING” CONNECTED TO “PHARMACEUTICAL.”
PLANTS ALSO ENGINEERED TO PRODUCE PRODUCTS FOR US.
EASIER WITH PLANTS THAN WITH ANIMALS…. WE CAN TAKE ANY CELL OF THE PLANT, PUT A VECTOR IN AND GROW IT IN THE LAB.
PLANTS PRODUCE A LOT OF PROTEIN; PROTEIN IN THEIR LEAVES AND IN THEIR FRUIT.
SO FOR EXAMPLE:
TOBACCO PLANTS HAVE LARGE LEAVES, THEY CAN BE MODIFIED BY OUR KNOWLEDGE, TO CONTAIN TPA [CLOT DISSOLVING PROTEIN] IN THEIR LEAVES. THEY HAVE VERY LARGE LEAVES, SO MANYBE A NEW USE FOR TOBACCO LEAVES.
PLANTIBODY—— A PLANT THAT IS MAKING A HUMAN ANTIBODY; COULD BE USED FOR BACTERIAL MENINGITIS. SO USING PLANTS ESPECIALLY IN REMOTE AREAS— THE PLANT ITSELF HAVING ANTIBODY. A PLANT THAT IS GROWING WHERE PEOPLE LIVE.
WE CAN CREATE PLANTS WITH NEW CAPABILITIES.
FOR EXAMPLE:
A MAJOR COMPONENT OF DETERGENTS IS “LAURIC ACID”—— IN JUST ABOUT ALL DETERGENTS YOU WILL SEE IN STORES.
THE MOLECULE IS MADE IN A GENETIC PATHWAY IN TROPICAL PLANTS, PALM TREES, SO PALM CURNAL OIL.
SCIENTISTS PIN-POINTED A KEY COMPONENT. THEY FOUND THE GENE, PUT IT THROUGH THE STEPS ALREADY GIVEN.
CANOAL— CANOLA OIL, NO “LAURIC ACID” BUT WHEN BIO-TECHNOLOGY, GENETIC ENGINEERING WAS DONE, CANOLA PRESSED GIVES 60 PERCENT LAURIC ACID…..
I HAVE GIVEN YOU EXAMPLES OF BIO-TECHNOLOGY AND THE USEFUL PRODUCTS IT CAN GIVE US.
End Quote
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THERE ARE SOME THINGS THAT BIO-TECHNOLOGY IS GOOD FOR; MANY THINGS WE TAKE FOR GRANTED TODAY COME FROM BIO-TECHNOLOGY.
AS WE DELVE FURTHER AND FURTHER INTO THE BUILDING BLOCKS OF ALL LIFE, SCIENTISTS MUST BE CAREFUL IN HOW WE DO THINGS WITH WHAT WE HAVE LEARNT AND ARE ABLE TO DO.
SOCIETY AS A WHOLE MUST ALSO BE WATCHFUL; ACTUALLY OTHER SCIENTISTS MUST WATCH SCIENTISTS, BE A CHECK TO THE MIS-APPLICATION OF SCIENCE; AND SO MANY HAVE DONE THIS. ONE OF THE EARLIEST SCIENTISTS TO DO THIS WAS RACHEL CARSON IN THE 1960s AND HER FAMOUS BOOK “SILENT SPRING.”
WHAT YOU SHOULD BE MAINLY GETTING OUT OF ALL THESE LECTURES, IS THAT THE DEPTHS OF WHERE SCIENCE CAN NOW GO, SHOULD PROVE THAT A MASTER-MIND WAS BEHIND ALL THIS PHYSICAL CREATION OF LIFE ON THIS WONDERFUL BLUE PLANET CALLED EARTH.
INDEED THE APOSTLE PAUL WAS CORRECT WHEN WRITING TO THE CHURCH AT ROME IN THE BOOK CALLED “ROMANS”— PHYSICAL CREATION SHOULD PROVE TO US THERE IS A GOD BEING; ACTUALLY AS THE NEW TESTAMENT SAYS, A “GODHEAD”— THE FATHER AND SON, TALKED ABOUT OVER AND OVER AND OVER AGAIN IN THE NEW TESTAMENT HOLY BIBLE WRITINGS.
AND ALL THAT TRUTH, ABOUT THE GODHEAD, I’VE EXPOUNDED IN MANY STUDIES ON MY WEBSITE UNDER “GOD, CHRIST, AND THE HOLY SPIRIT.” Keith Hunt
GENETICS AND AGRICULTURE!
FROM THE 24 - 1/2 HOUR LECTURES PRODUCED FOR THE TEACHING COMPANY IN 2007.
Quote
THE NEXT TWO LECTURES DEAL WITH AGRICULTURE.
A NEWS PAPER ARTICLE IN CONNECTICUT DESCRIBED A NEW GENETIC WHEAT.
IT DEVELOPED QUICKLY, IT WOULD RESIST MOULD THAT WOULD GIVER LESS SEEDS.
IT WOULD GIVE A LOT OF GRAIN THAT WOULD NOT FALL OVER; ITS STEM WAS VERY STRONG, BECAUSE IT WAS ALSO SHORTER.
COMPARED TO OTHER WHEAT IT WAS MUCH BETTER.
BY THE END OF THE CENTURY IT WAS WELL KNOWN AND POPULAR.
THE DATE OF THIS ARTICLE WAS JUNE 30 1794.
FOR REASONS UNKNOWN THIS TYPE OF WHEAT WAS NOT USED IN THE 1800s WHEN THE WEST WAS SETTLED.
UNBEKNOWN TO THE AMERICANS THE JAPANESE WERE USING THIS SEMI-DWALF WHEAT - SHORT STRONG WHEAT GIVING A LOT OF SEEDS.
IT WAS THE STORY OF RANDOM MUTATION. IT HAPPENED IN AMERICA AND JAPAN.
THE JAPANESE WANTED TO GET A HIGHER YEALD. BY THE 20TH CENTURY THEY WERE CROSSING WHEAT WITH WHEAT, LONG WITH SHORT.
THEY WERE PRODUCING VERY HIGH WHEAT YIELDS— HOW MUCH WHEAT PER ACRE PER YEAR.
IT TOOK YEARS IN CROSSING UNTIL IN 1935 THEY WERE SATISFIED, AND IT TURNED OUT IT WAS PRODUCING ONLY SLIGHTLY BETTER THAN THE WHEAT PRODUCED IN CONNECTICUT 140 YEARS EARLIER.
A REMARKABLE ACCURANCE!
AFTER WW2 THE ALLIES SENT IN AN OCCUPATION ARMY— ONE MAN FROM THE USA WAS TO DO WITH FOOD PRODUCTION; THE USA WAS ESPECIALLY INTERESTED IN JAPAN FOOD, FOR THE ALLIES HAD DURING THE WAR BLOCKADED JAPAN FROM RECEIVING FOODS. THE USA WAS INTERESTED BECAUSE THEY COULD NOT FIGURE HOW JAPAN FED ITS PEOPLE DURING THE WAR.
WHAT THEY SOON FOUND OUT WAS THE JAPANESE HAD THIS SHORT WHEAT WITH HUGE YEALDS!
TO TAKE ADVANTAGE OF OTHERS THE USA SENT SOME OF THE SEEDS OF THIS WHEAT BACK TO THE USA.
THE USA HAD SUPPLANTED THAT KIND OF WHEAT 140 YEARS EARLIER, WITH OTHER WHEATS [KINDA DUMB RIGHT, YA YOU BET - Keith Hunt].
AFTER CROSSING IT THE FARMERS IN THE N.E. USA GOT BUMPER CROPS.
THIS IS BY NOW THE LATE 1940s.
A COUPLE OF YEARS PREVIOUSLY 1944, A RESEARCH PROGRAM IN MEXICO HAD BEEN SET UP BY THE ROCKEFELLA FOUNDATION. IT WAS A JOINT US-MEXICO VENTURE; IT’S GOAL WAS TO PRODUCE BETTER FOODS AS IT WAS A POOR COUNTRY AT THE TIME.
A YOUNG SCIENTIST NORMAN BORLAUG [B. 1914] HEADED THE PLANT BREEDING PROGRAM IN MEXICO.
IN 1953 BORLAUG RECEIVED SOME OF THIS SEMI-DWALF WHEAT DISCOVERED IN JAPAN.
BORLAUG SET OUT TO EXPERIMENT WITH THIS WHEAT.
BORLAUG PLANTED THIS WHEAT AT TWO LOCATIONS— ONE IN LOW LAND SUNNY AND HOT; THE OTHER IN HIGHER LANDS AND NOT AS HOT.
HE USED THESE TWO PLACES DELIBERATELY TO GET TWO CROPS A YEAR.
TWO CLIMATES—— PEOPLE IN DIFFERENT PARTS OF THE EARTH IN DIFFERENT CLIMATES.
BY 1961 BORLAUG REPEATED CROSSES—— HIT PAY DIRT!
TWO CROPS A YEAR - HOT CLIMATE AND NOT HOT CLIMATE.
SECOND: NEW STRAIN RESISTANT TO A WIDE VARIETY OF PESTS, INSECTS, MOULDS, AND BACTERIA.
THIRD: HIGH YIELDING, VERY HIGH, MORE THAN ANY OTHGER WHEAT. IT WAS STRONG SHORT STEMS, THE WIND COULD NOT BREAK.
IT WAS A HIT IN MEXICO—- 1950s AND 1960s—- IT TOOK OFF—- 12 YEARS IN MEXICO, AND THEIR WHEAT TRIPLED IN PRODUCTION. THEY NO LONGER HAD TO IMPORT WHEAT. THEY HAD ENOUGH TO FEED THEIR INCREASING POPULATION.
1964 BORLAUG VISITED INDIA. HE SENT THEM ABOUT 60 POUNDS OF WHEAT SEEDS. SO SUCCESSFUL IN 1965, THE NEXT YEAR, HE SENT 250 TONS.
IN 1966 INDIA WAS SENT 18,000 TONS OF WHEAT SEEDS.
SAME THING HAPPENED IN PAKISTAN!
OVER THE NEXT TWO DECADES WHEAT YIELDING RECORDS!
COUNTRIES EXPERIENCING FAMINE WERE IN SOME CASES, EXPORTING WHEAT.
1968— ONE “SPECIAL AID” GUY SAID IT WAS A “GREEN REVOLUTION.”
1970 BORLAUG WAS GIVEN THE NOBEL PEACE PRIZE— THERE WAS NO NOBEL PRIZE FOR AGRICULTURE— SUCH A PRIZE WAS NOT IN NOBEL’S WILL.
BUT BORLAUG HAD IN SOME WAYS BROUGHT PEACE.
HIS WORK PREVENTED MASS STARVATION AND POLITICAL TROUBLES.
ESTIMATES ARE THAT ONE BILLION LIVES WERE SAVED!
IT WAS “THE MOST IMPORTANT GENETICS EXPERIMENT OF THE 20TH CENTURY.”
I’LL REPEAT “IT WAS THE MOST IMPORTANT GENETICS EXPERIMENT OF THE 20TH CENTURY.”
[O WOW, I GET GOOSE-LUMPS THINKING OF IT; I MEAN ON A PHYSICAL SCALE, WHAT HE DID WAS BEYOND FANTASTIC, IT WAS MONUMENTAL IN SERVING OTHERS. I HAD NEVER READ ABOUT IT, SO THIS HISTORY WAS NEW TO ME AS I WATCHED THESE DVD LECTURES ON GENETICS - Keith Hunt]
I WANT TO TURN NOW TO AGRICULTURE AND AGRICULTURAL GENETICS.
PLANTS ARE OUR HOPE, FOR PLANTS ARE OUR MAIN SOURCE OF FOOD.
I’LL EXPLAIN WHAT IT’S ALL ABOUT AND OUR GENETIC HOPE AS WE SOW OUR FOODS.
THEN HOW WE BREED OUR PLANTS BY USING GENETICS.
FIRST: PLANTS AS HUMANITY’S MAIN SOURCE OF FOODS.
GROWTH OF POPULATION AND PLANT BREEDING IS A MAJOR ON GOING PROBLEM.
AGRICULTURE IS THE OLDEST BIO-TECHNOLOGY, IT BEGAN THOUSANDS OF YEARS AGO.
THIS THEN ALLOWED HUMAN SETTLEMENTS.
SOME OF THOSE PLACES WERE IN THE MIDDLE-EAST.
IN 1999, THE WORLD POPULATION REACHED 6 BILLION, ADDING 75 MILLION PER YEAR.
THE UN ESTIMATES ABOUT 1 IN 7 ARE CHRONICALLY UNDER FED.
THE 20TH CENTURY SAW THE GREATEST AGRICULTURAL PROGRESS EVER MADE.
DEMOGRAPHY— THE STORY OF HUMAN POPULATIONS. WE CAN SIMPLIFY IT IF WE FORGET ABOUT MIGRATION AND IMMIGRATION.
POPULATION GROWTH IS EQUAL TO THE BIRTH RATE [ADDITIONS] MINUS THE DEATH RATE [SUBTRACTIONS].
WHEN AGRICULTURE BEGAN AS A HUMAN PRACTICE THERE WAS A GREAT INCREASE IN BIRTH RATE. MORE CHILDREN BUT ALSO MORE DEATHS FROM INFECTIOUS DISEASES
BIRTH HIGH - DEATH RATE HIGH - GROWTH SLOW FOR THOUSANDS OF YEARS.
PEOPLE SETTLED, BETTER EDUCATION, BETTER SANITATION, BETTER SCIENCE, BETTER FOODS— DEATH RATE REDUCED. BIRTHS STILL HIGH, DEATHS REDUCED - POPULATION EXPLODES.
AFTER POPULATION RISES, BIRTH RATE WENT DOWN - COMPLEX REASONS.
MEDICINES INCREASED - BETTER HEALTH - NOT AS MANY CHILDREN NEEDED FOR A KIND OF INSURANCE FOR POPULATION.
DEMOGRAPHIC TRANSITIONS OVER DECADES.
HIGH BIRTH - HIGH DEATH
HIGH BIRTH - LOW DEATH
LOW BIRTH - LOW DEATH
EUROPE WENT THROUGH THIS OVER THE LAST TWO HUNDRED YEARS.
OTHER LESS DEVELOPED WORLD GOING THROUGH IT NOW.
FROM THE UN AND OTHER SOURCES, POPULATION WILL LEVEL OFF AT 10 BILLION BY 2050.
EVEN AT THAT THIS, POPULATION WILL PUT PRESSURE ON HUMAN FOOD PRODUCTION.
THE PRESENT [AS OF 2007 WHEN THESE DVDs WERE MADE - Keith Hunt] HUMAN DIET IS JUST BARELY ADEQUATE.
THE MAJOR SOURCE OF FOODS TO HUMANS ARE CROP PLANTS.
FOOD IS ANY SUBSTANCE THAT PROVIDES—
1. ENERGY— WORK OR AUTOMATIC STUFF LIKE HEART BEATING.
2. NUTRIENTS— THINGS WE CANNOT MAKE OF OUR INNER SELF, WE HAVE GENETIC LIMITATIONS. WE CAN’T MAKE VITAMIN C. WE DON’T MAKE IN OUR INNER SELVES 8 AMINO ACIDS, WE MUST EAT FOODS THAT CONTAIN THEM.
WORLDWIDE, THE DIRECT CONSUMPTION OF PLANTS AS FOOD ACCOUNTS FOR 75% OF WHAT WE EAT. THER REST IS FISH AND ANIMAL PRODUCTS.
PLANTS ARE USED TO FEED OUR FARMING ANIMALS.
3. PLANTS PROVIDE 2/3 OF HUMAN DIET.
RICE - WHEAT - CORN
THEY ARE KNOWN AS “STAPLE’ FOODS— USED OVER A LONG PERIOD OF TIME.
WE ARE RELIANT ON PRODUCTION, GROWTH, AND SEEDING OF THESE 3 PLANTS.
THE GROWTH OF A PLANT NEEDS THINGS IN THE ENVIRONMENT— SOIL, WATER, SUN.
FARMING IS— MODIFYING THE ENVIRONMENT TO FIT GROWTH.
THE SEEDS OF THE 3 PLANTS ARE LUNCH BOXES.
IT WILL GERMINATE, GROW, SPROUT UP ABOVE THE GROUND, BUT IN THE MEANTIME WHERE DOES IT GET ITS ENERGY?
PROTEINS— RICE, WHEAT, CORN
THEY HAVE LOW AMOUNTS OF 2 AMINO ACIDS.
PLANTS CAN MAKE ALL 20 AMMINO ACIDS.
WE CAN ONLY MAKE 12.
RICE, WHEAT, CORN— SOME VITAMINS FINE FOR THEM BUT NOT FOR US.
THESE THINGS ARE UNDER GENETIC CONTROL.
A MAJOR EFFORT IS TO IMPROVE THEM FOR GENETIC NEEDS FOR US.
FARMING— AGRICULTURAL— MAXIMIZE THE GENETIC POTENTIAL OF CROP PLANTS.
TWO WAYS TO INCREASE PRODUCTION—
FIRST: EXPAND THE LAND YOU GROW THEM ON.
SECOND: INCREASE THE PRODUCTION OF THE CROP THAT IS GROWN ON THE LAND.
SO WE HAVE—— EXPAND THE LAND; EXPAND THE YIELD.
LAND EXPANSION, WELL THAT WAS THE RISE OF MANY EMPIRES, CONQUEST, GET MORE LAND EVEN BY FORCE IF REQUIRED.
BAD NEWS— LAND LIKE THE WESTERN PLAINS OF NORTH AMERICA ALREADY USED. THE LAND LEFT, EITHER VERY DRY OR FOREST LAND. WOULD TAKE MUCH MANIPULATING TO GROW CROPS ON.
INCREASE CROP YIELD IS NOW THE WAY TO PRODUCE FOODS.
EXAMPLE OF JAPAN!
THEY INVADED CHINA - MORE LAND - CHINA REBUFFED THEM.
THEN— TRADED WITH OTHER NATIONS, BUT THAT WAS NOT DEPENDABLE.
SO BETTER IDEA— RELY ON SELF, INCREASE YIELD - SEMI-DWALF RICE AND WHEAT - THEIR HARVEST WAS 3 FOLD LARGER.
PROBLEM SOLVED!
WE ARE ADAPTING THE LAND FOR PLANTS TO GROW ON IT.
MANAGEMENT HAS FORMS:
1. MANAGE SOIL—— PLOW AND MANAGE SOIL. THERE’S A USA DEPARTMENT JUST DEVOTED TO SOIL. PREVENT SOIL RUNNING OFF INTO RIVERS; IMPROVE NUTRIENTS; ADD FERTILIZER.
2. WATER—— DISSOLVING SO PLANTS AND THEIR ROOTS FEED. WATER TOO DEEP OR COMES IN THE FORM OF RAIN BUT AT WRONG TIMES. SO HUGE DAMS, CANALS, DEEP WELLS THAT BRING UP WATER TO THE CROPS ABOVE.
3. PESTS—— REMEMBER “BIG THINGS HAVE LITTLE THINGS UPON THEIR BACK TO BITE ‘EM; AND LITTLE THINGS HAVE STILL LESSER THINGS AND SO INFINITUM.”
SO CROPS GET EATEN BY MOULDS, BACTERIA, INSECTS.
WE CONTROL BY HAND LIKE WEEDING; OR FUMIGATION, BUT WE HAVE TO BE VERY CAREFUL WITH SPRAYS, UNLESS THEY DAMAGE CROPS AND HUMANS.
PLANT BREEDING IS THE OTHER WAY TO IMPROVE CROP PLANTS.
MY MOTHER MAY FEED ME LOTS AND LOTS BUT I MAY GET WIDER, BUT NOT TALLER, AS THAT IS MY GENETIC CAPABILITY. SO WE NEED GOOD NOURISHMENT; PLANTS LIKEWISE.
3 THINGS TO HAVE FOR HEALTHY PLANTS WITH BETTER YIELDS.
PLANT GENETIC METHODS
1. PURE-LINE SELECTION
2. HYBRIDIZATION
3. DELIBERATE CROSSES
PURE-LINE SELECTION— THE WAY CROPS WERE DOMESTICATED.
THE EXAMPLE OF BARLEY THRESHING— BREAD AND BEER.
WHEAT AND ITS GENES - SEED DORMANCY - SEEDS BY PLANTS GERMINATE AT STAGGERED INTERVALS. FOR THE PLANT THIS IS TERRIFIC; ONE SEED MAY DIE, ANOTHER SPROUTS MONTHS LATER.
FOR FARMERS A BAD IDEA; THEY WANT TO PUT THE SEED IN THE GROUND AND HAVE SPROUTING ALL AT ONCE.
FARMER SELECTED PLANT STRAINS THAT DID NOT HAVE DORMANCY. DORMANCY WAS SELECTED OUT OF THE CROPS.
TAKES ABOUT 20 GENERATIONS TO BREED OUT WHAT YOU DO NOT WANT.
THERE ARE MANY OF THESE PLANTS/CROPS FOR A CERTAIN SELECTED GENES.
CORN—ALL KINDS OF VARIETIES - CORN COLORED, CORN THAT SPROUTS, TALL CORN AS HIGH AS AN ELEPHANT’S EYE— ALL KINDS FROM MILD TO VERY SWEET CORN.
FORT COLLINS, COLORADO, THE CAMPS OF COLORADO UNIVERSITY; THERE’S A BUILDING, A SEED STORAGE BUILDING— HALF A MILLION PURE LINE CROPS FROM ALL AROUND THE WORLD. 40 THOUSAND WHEAT VARIETIES ARE STORED THERE.
THEY ARE CONSTANTLY BEING TESTED FOR POTENCY.
A FARMER CAN WRITE IN FOR A PARTICULAR STRAIN OF WHEAT.
SOME VARIETIES FOR NUTRITIONAL PROPERTIES.
IN 1960s AT PERDU UNIVERSITY SCIENTISTS SCREENED THOUSANDS OF CORN IN SEED BANK SEEDS, WANTING TO HAVE ALL 8 AMINO ACIDS, WE HUMANS DO NOT MAKE, WE ONLY MAKE 12 OUT OF THE 20 AMINO ACIDS.
IN THE 1980s SURINDER VASAL FOUND ONE, BRED IT TO ADAPT TO DIFFERENT CLIMATES.
THERE IS ONE THAT GIVES QUALITY PROTEIN. IT WAS A GENETIC VARIETY - HIGH YIELDS - HIGH PROTEIN - BALANCED IN AMINO ACIDS.
THAT IS PURE-LINE SELECTION.
HYBRIDIZATION— CROSSES PURE-LINES
THE FIRST PERSON SCIENTIFICALLY TO DO SO WAS CHARLES DARWIN [1809-1882].
1910 GEORGE SHULL [1874-1954]. A PLANT GENESIS, WITH 2 LINES OF CORN; #1 GAVE 20 BUSHELS PER ACRE PER YEAR. ANOTHER #2 GAVE SAME. WHEN CROSSED THEY GAVE 80 BUSHELS - THE WHOLE GREATER THAN THE SUM OF THE PARTS.
IT’S CALLED HYBRID VIGOR. ALL CORN IN THE USA IS NOW HYBRID; YOU BUY THE SEED FROM A SEED COMPANY.
WHEAT AND RICE DOES NOT WORK WELL FOR HYBRID-ATION. THEY ARE STILL WORKING ON IT [AS OF 2007].
DELIBERATE CROSSES
CROSS ONE PLANT INTO ANOTHER TO GET A SINGLE PART INTO ONE PLANT.
HARD TO DO WHEN YOU HAVE CONTROLS OVER MANY GENES.
BORLAUG WANTED A GENE TO RESIST MOULD, IT’S CALLED WHEAT RUST. HE WANTED THE GENE IN A SEMI-DWALF PLANT. HE TOOK A VARIETY THAT WAS RESISTANT BUT HAD NO OTHER GOOD CHARACTERISTICS. HE GOT IT FROM THE SEED BANK CROSSED IT WITH THE SEDMI-DWALF WHICH HAD LOTS OF GOOD CHARACTERISTICS; THE OFFSPRING WERE A MISS, ALL TYPES OF GENES AND PHENO TYPES. HE CHOSE THE BEST OF THE SEMI-DWALF ONES, MODERATELY RESISTANT; THEN HE CROSSED AGAIN THIS VARIETY TO THE VERY RESISTANT PLANTS. AFTER ABOUT 6 GENERATION HE GOT WHAT HE WANTED INTO SEMI-DWALF PLANTS.
THESE METHODS OF PLANT BREEDING ARE WIDELY USED AND PRODUCE A HUGE WORLDWIDE EFFORT TO IMPROVE CROP PLANTS—— BUT THEY HAVE 4 LIMITATIONS.
LIMITATION TO TRADITIONAL PLANT BREEDING!
1. HIDDEN GENES
SCIENTISTS USE SOME GENES FOR THE CHARACTERISTICS THEY ARE INTERESTED IN BY CROSS AND PURE-LINE SELECTION, BUT WHEN DOING A CROSS YOU DON’T KNOW WHAT OTHER GENES THERE MAYBE, HIDDEN AWAY; UNDESIRABLE GENES THAT MAY BE TRANSFERRED.
MANY PURE-LINES IN THE SEED BANK HAVE LOW YIELDS BECAUSE IN ADDITION TO DISEASE RESISTANCE, FARMERS WERE UNAWARE OF GENES NOT SO GOOD. MIGHT BE CORN AS HIGH AS AN ELEPHANT’S EYERE, BUT ALSO HAD BAD CHARACTERISTICS AS WELL.
2. SECOND PROBLEM
SPECIES LIMITATION. THERE ARE MANY GENES OUT THERE THAT CANNOT BE CROSSED BECAUSE THEY ARE A DIFFERENT SPECIES.
3. IT’S SLOW
IT TAKES MANY GENERATIONS OF SELECTING AND CROSSING TO GET WHAT YOU WANT; IF DOING TRADITIONAL PLANT GENETICS.
4. THE ECOLOGICAL THRUST OF AGRICULTURE HAS BEEN TO USE GENETICS AND TECHNOLOGY TO ADAPT THE ENVIRONMENT TO THE PLANT.
THE NEXT LECTURE WE WILL SEE HOW MOLECULAR BIOLOGY AND BIO-TECHNOLOGY HAS BEEN APPLIED TO THESE 4 CHALLENGES.
End Quote
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SO WE HAVE SEEN THAT WORKING WITHIN A SPECIES, CROSS BREEDING ETC. CAN BE A GOOD THING, AND PEOPLE HAVE BEEN DOING IT FOR A LONG LONG TIME.
IT IS THE SAME WITH ALL THE DIFFERENT BREEDS OF HORSES, THAT CAN BE OF BENEFIT, AND AGAIN CAN BE A BAD THING FOR THE GREED OF MANKIND. FOR A WHILE THEY BRED THE THOROUGHBREDS TO HAVE THINNER BONES, TO MAYBE RUN FASTER; BUT IT WAS SOON SHOWN THERE WAS AN INCREASE IN HORSES THAT BROKE THEIR LEGS RUNNING ON THE RACE TRACK.
YES PEOPLE HAVE TO USE ALL THIS NOW KNOWN FARMING AND BREEDING WAYS, TO BRING BENEFIT AND NOT MORE PROBLEMS IN THE LONG RUN.
IT IS FORTUNATE WE DO HAVE DEDICATED AND MORAL SCIENTISTS, WHO WATCH FOR ABUSE AND WRONG RESULTS IN THE OVERALL WORKING OF THE SCIENCE COMMUNITY.
AGAIN WE MUST REMEMBER PEOPLE LIKE RACHEL CARSON IN THE 1960s AND HER WATCHFULNESS WHICH RESULTED IN HER FAMOUS BOOK SILENT SPRING.
GOD HAS GRANTED US THE KNOWLEDGE AND ABILITY TO WORK “WITH” WHAT HE CREATED.
WORKING “WITH” IS NOT WRONG; WORKING AGAINST FOR SELFISH REASONS IS VERY WRONG.
WE HAVE SEEN THE GREAT WONDERS AND SERVICE THAT WORKING “WITH” CREATION, CAN BRING TO MILLIONS OF PEOPLE.
WE SHOULD PRAY FOR MORE OF THOSE SCIENTISTS, AND PRAY THEY WILL ALSO BE A WATCHDOG FOR SCIENCE, KEEPING US FROM MISAPPLYING WHAT WE ARE NOW ABLE TO DO WITH OUR INCREASE OF KNOWLEDGE.
GOD HAS PUT IN HIS DNA CREATION A MOVING ABILITY; SOMETIMES IT MOVES ON ITS OWN TO CREATE, LIKE— THE PONY, THE REGULAR HORSE, AND THE DRAFT HORSE.
ALL CREATED LIFE FORMS ON EARTH ARE THE HAND OF THE MASTERMIND.
CREATION SHOULD PROVE TO YOU GOD DOES EXIST!
Keith Hunt
STUDY IN GENETICS——
From the DVDs I have from The Teaching Company— published in 2007 - Keith Hunt
BIOTECHNOLOGY and AGRICULTURE
I HAVE DESCRIBED HOW BIOTECHNOLOGY HAS DONE WONDERFUL THINGS FOR FARMING, OVER THE LAST CENTURY.
BUT I ALSO POINTED OUT THEY HAVE THEIR LIMITATIONS. WE HAVE CHALLENGES OVER THE NEXT 50 YEARS AS THE POPULATION OF THE WORLD LEVELS OUT AT ABOUT 10 BILLION. CAN BIOTECHNOLOGY HELP OUT?
I WANT TO BEGIN EITH A PROBLEM THAT’S EXISTED FOR MILLENNIUMS.
MOST PLANTS CAN’T GROW IN SALTY SOIL!
NOW WHEN SOIL IS IRRIGATED, WHEN WATER IS BROUGHT TO DRY SOIL, IN ORDER TO GROW CROPS, THE WATER COMES IN, AND SALT IN WATER COMES WITH IT; BUT RAIN WASHES IT DOWN TO LOWER LEVELS— IT’S CALLED PERCOLATION. THE SALT GOES DOWN TO LOWER LEVELS SO THE PLANTS ARE NOT HARMED. BUT IN DRY CLIMATES THERE’S NOT MUCH RAIN, SO SALT BUILDS UP.
THIS HAS ALWAYS BEEN A PROBLEM FOR SOCIETIES— THE MESOPOTAMIAN SOCIETY FELL PARTLY TO DO WITH SALT BUIL UP IN THEIR SOIL FOR GROWING CROPS.
IT IS ESTIMATED THAT TODAY 65,000 ACRES OF FARM LAND ARE LOST DAILY TO SALT BUILDUP.
THESE ACRTES ARE RENDERED USELESS BECAUSE OF SALT BUILDUP.
SALT IS TOXIC TO PLANTS IN TWO WAYS.
1. SALT IMPAIRS THE ROOTS FROM TAKING UP WATER.
2. SALT BLOCKS SEVERAL ENZYMES INVOLVED IN IMPORTANT CELLULAR PROCESSES.
HOW?
IT ALTERS THE WAY THESE PROTEINS FOLD— HENCE CANNOT FOLD THE CORRECT WAY AND SO IT DOES NOT DO ITS JOB, IT CANNOT FUNCTION CORRECTLY.
THE ENZYMES IN PLANTS ARE MAKING PROTEINS; IF NO PROTEINS, NO EXPRESSION IN PHENO TYPE.
Photosynthesis— THE PROCESS BY WHICH A PLANT CONVERTS SOLAR ENERGY INTO STORED ENERGY IN THE FORM OF SUGARS, CARBOHYDRATES.
FEW PLANTS IN THE WORLD CAN THRIVE IN VERY SALTY SOIL; AND CERTAINLY NOT THE MAJOR CROPS— RICE, WHEAT, CORN.
SO FIND A GENE IN THESE CROPS TO WITHSTAND SALTINESS IS VERY UNLIKELY. IF YOU GO TO THE SEED BANK IT IS VERY UNLIKELY YOU WILL FIND A MUTATION IN THESE 3 MOJOR CROPS, THAT CAN WITHSTAND SALT. THESE PLANTS AND RELATIVES DO NOT GROW IN SALTY SOILS.
I MENTIONED EARLIER IN THE COURSE THE MODEL ORGANISMS; THE TINY PLANT ARABIDOPSIS IS A MODEL GENOMES FOR THE MAJOR PLANTS. IT WAS SEQUENCED FIRST, BEFORE RICE AND OTHER CROPS.
IT IS A MODEL PLANT— IT DOES ALL THE THINGS THE MAJOR PLANTS DO; ROOTS, STEM, FLOWER, SEEDS, FRUITS, AND ALL OF THOSE THINGS.
SO IT’S USEFUL TO STUDY, WE CAN GROW IT QUITE READILY, IN A GREEN-HOUSE OR ROOM CLOSE TO THE LAB. WE KNOW ITS GENOME SEQUENCE.
IN THE 1990s EDUARDO BLUMWALD FOUND IN ARABIDOPSIS, A GENE THAT IS EXPRESSED AS A PROTEIN WHOSE JOB IS TO SUCK UP SALT AND PUT IT INTO STORAGE CELLS CALLED VACUALS. AND THESE CELLS ARE IN THE LEAVES OF THE PLANT. A GOOD WAY TO GET RID OF SALT, EVEN THE ROOTS ARE FREE, NO SALT STOPS THEM FROM DOING THEIR JOB. THE PLANT SURVIVES SALTY SOIL.
THE PROBLEM COMES WHEN THE SALT IN THE SOIL BECOMES VERY HIGH.
THERE’S NOT ENOUGH PROTEIN EXPRESSED SO THE SALT LEAKS OUT OF THESE VACUALS, GETS INTO THE PLANT AND IT WITHERS AND DIES.
USING BIOTECHNOLOGY, BLUMWALD ADDED A VECTOR, A VERY ACTIVE PROMOTER, BESIDES THE SALT GENE. SO THE EXPRESSION OF THIS GENE WILL BE ENHANCED.
THEN HE MADE TRANS-GENIC PLANTS USING THIS VECTOR. THEY WERE HIGH IN PROMOTING THIS PROTEIN AND EXPRESSION. THE PLANTS NOT ONLY SURVIVED VERY SALTY WATER, THEY THRIVED!
HIS OBJECTIVE WAS TO GET THIS INTO THE STAPLE PLANT CROPS OF RICE, WHEAT, AND CORN.
BIOTECHNOLOGY USES THE TRANSFER OF GENES. WHEN THE GENE WAS PUT INTO TOMOTO PLANTS, IT BECAME VERY SALT TOLERATE. A REGULAR TOMATO PLANT WOULD WITHER AND DIE IN SALTY SOIL. THE TOMATO PLANT WITH THE TOLERATE SALT GENE WOULD BE FINE. THE SALT WAS IN THE PLANT, IN THE LEAVES, BUT THE FRUIT WE EAT WAS JUST FINE.
AS TOMATOES ARE IMPORTANT THEY ARE NOT ARE IMPORTANT AS THE MAIN CROPS AND OTHERS.
SO THEY ARE BUSY GETTING THIS GENE THAT WITHSTANDS SALT INTO THE MAIN CROPS, BY USING BIOTECHNOLOGY, AS USED IN THE TOMATO PLANT. THIS THEN WOULD MAKE THE SALTY SOILS IN THE WORLD USABLE FOR CROP FARMING.
AS I’VE SAID TOO MUCH SALT IN THE SOILS OF THE MIDDLE EAST MADE IT UNTENABLE TO FARM. SALT RESISTANT PLANTS MAY MAKE THE DESERTS TAKE BLOOM AGAIN.
FIRST: BIOTECHNOLOGY IS A POWERFUL, SPECIFIC, AND RAPID WAY TO TRANSFER GENES FROM ONE ORGANISM TO ANOTHER, AND FROM ONE PLANT TO ANOTHER IN PARTICULAR.
SECOND: BIOTECHNOLOGY CAN LEAD TO A FUNDAMENTAL CHANGE IN THE RELATIONSHIP BETWEEN PEOPLE, CROPS, PLANTS, AND THE ENVIRONMENT.
UNTIL NOW WE HAVE SPENT TREMENDOUS EFFORTS TO ADAPT THE FARM TO THE ANIMALS. ADAPTING THE ENVIRONMENT TO THE GROWTH OF THE PLANT. NOW WE HAVE THE ABILITY TO ADAPT THE PLANT TO THE ENVIRONMENT.
I WANT TO TALK ABOUT AGRICULTURAL BIOTECHNOLOGY.
FIRST, ABOUT HOW AGRICULTURAL BIOTECHNOLOGY HAS DEVELOPED.
SECOND, EXAMPLE OF GENETICALLY MODIFIED PLANTS.
AS I WILL DISCUSS LATER THERE IS CONCERN ABOUT BIOTECHNOLOGY WITH PLANTS, AND WHAT SOME OF THOSE CONCERNS ARE.
FIRST, THE METHODS OF AGRICULTURAL TECHNOLOGY——
THE BEST SUMMERY I CAN GIVE IS THE METHODS OF AGRICULTURAL TECHNOLOGY ARE SIMILAR TO THOSE OF BIOTECHNOLOGY IN OTHER ORGANISMS. STARTING WITH BACTERIA TO ANIMALS. BUT WITH PLANTS WE ARE TOTIPOTENCY, MEANING— EVERY CELL HAS THE ENTIRE COMPLIMENT OF GENES FOR THE ENTIRE ORGANISM.
EVERY CELL CAN BE MANIPULATED TO GIVE AN ENTIRE PLANT.
CARROTS— FREDERICK STEWARD’S EXPERIMENT: TAKE A SINGLE CELL FROM THE ROOT, PUT INTO A GROWTH MEDIUM, GROWTH MEDIUM WILL TELL THE CELL TO MULTIPLY AND IT GROWS UP TO BE A FULL ROOT, STEM, LEAVES, AND FLOWER CARROT.
CLONING IS DONE WHEN UNIFORMITY IS REQUIRED.
IN FORESTRY TREES ARE CLONED - THE LITTLE PLANTLET IS GROWN INSIDE, TO THE SAME SIZE, THEN TRANSPLANTED AND GROWN FOR HARVESTING; VERY GOOD WAY OF CONSERVING THIS RESOURCE.
WE KNOW FROM TOTIPOCENCY A SINGLE CELL CAN BE TRANSFORMED BY VECTORS, SELECTED FOR VECTORS, AND THIS CAN BE CLONED. IT ALLOWED RAPID SCREENING OF THE PHENO-TYPE, AND GENE TYPE OF THESE SINGLE CELLS.
THERE ARE TWO WAYS TO GET PLANT DNA INTO PLANT CELLS FOR GENETIC TRANSCRIPTION.
PLANTS AND ANIMALS BASICALLY THE SAME.
GOING TO USE A CHROMOSOME - PIECE OF DNA; THE OTHER WAY IS MORE PHYSICAL.
WAYS TO GET PLANT DNA INTO CELLS
1. VECTOR
2. GENE-GUNS
FIRST, THE VECTOR.
THERE IS A DISEASE IN PLANTS CALLED “CROWN GALL TUMOR” YES PLANTS CAN GET CANCER, CELLS THAT REPRODUCE WITHOUT ANY CONTROL.
TURNS OUT THESE CROWN GALL TUMORS ARE CAUSED BY AN OUTSIDE AGENT, A BACTERIUM. WHEN THIS BACTERIUM AFFECTS THE BUD [THE TERMINAL REGION OF THE PLANT] THIS BACTERIUM INJECTS A SMALL CHROMOSOME INTO THE PLANT CELLS. THIS SMALL CHROMOSOME HAS DNA CODING FOR TWO TYPES OF PHENOTYPIC PROTEINS. ONE IS THAT THE DNA WILL GET INCORPORATED INTO THE PLANT GENOME AND EXPRESSED. THE OTHER, GENES STIMULATE THE CELLS TO DIVIDE— THE TUMOR FORMING GENES.
FOR THE BACTERIUM THIS IS A GOOD DEAL BECAUSE IT WANTS TO EAT THE SUGAR OF THE PLANT, AND PLANT CELLS PROVIDE MORE OF IT. FOR THE BACTERIUM THIS IS EXACTLY WHAT IT WANTS.
FOR BIO-TECH THIS IS GOOD IF WE GET RID OF THE GENE THAT CAUSES THE PLANT CELLS TO GROW AND REPRODUCE.
SO THIS VECTOR CAN BE REMOVED FROM THE BACTERIUM, THE GENES FOR INFECTION ARE ALLOWED TO REMAIN, AND THEN THE GENES FOR CAUSING THE PLANT CELLS TO GROW ARE REMOVED, AND THEN REPLACED BY YOUR FAVORITE GENE, THE GENE WE WANT TO MAKE THE PLANT TRANSGENIC.
IT TURNS OUT THIS SMALL PIECE OF DNA, THIS SMALL CHROMOSOME HAS A SINGLE RESTRICTION SITE FOR GENE INSERTION, AND IN ADDITION NUMEROUS PLANT PROMOTORS, GENE EXPRESSION. WE KNOW A LOT ABOUT SEED PROMOTORS, FRUIT PROMOTORS ETC.
SECOND WAY— GENE GUNS
YOU TAKE AN INNER PELLET AND YOU CODE IT WITH DNA, WHAT YOU WANT IN THE CELL— YOU SHOOT IT INTO THE CELL; THE CELL DOES HAVE A COAT THAT PROTECTS ITSELF, SO NOT AS EASY AS IT SOUNDS. THE PELLET DOES NOT GO THROUGH THE CELL, IT IS SLOWED DOWN.
THE REASON TO USE A GUN—
THE PLANT CELL IS OFTEN SURROUNDED BY CELEOS AND COMPLEX POLYMERS CALLED “THE CELL WALL” AND MAKES GETTING FOREIGN DNA AS A VECTOR INTO THE CELL QUITE DIFFICULT. SO A GUN SHOT TO GET THE STUFF IN.
PLANT BIOGENETICS OVERCOMES SOME OF THE PROBLEMS I LISTED IN THE PREVIOUS LECTURE.
PLANT BREEDING
TRADITIONAL BIOTECHNOLOGY
HIDDEN GENES SINGLE GENES
TRANSFERRED TRANSFERRED
GENES LIMITED GENES FROM ANY
TO THE SPECIES SPECIES
SLOW RAPID
ADAPT THE ADAPT THE PLANT
ENVIRONMENT TO ENVIRONMENT
TO THE PLANT
GENETICALLY MODIFIED PLANTS ARE IN GENERAL USE!
3 EXAMPLES OF THIS BIOTECHNOLOGY
1. INSECT-SPRAYS— SPRAYS THAT KILL INSECTS, BUT PROBLEM IS MANY ARE NOT SPECIFIC, THEY KILL MANY INSECTS NOT JUST THE PESTS, AND IN OTHER WAYS THEY ENDANGER OTHER THINGS IN NATURE.
WE OWE A GREAT DEBT TO RACHEL CARSON [1907-64] WHO IN THE EARLY 1960s WARNED THE USA OF DDT AND THE THINNING OF BIRD EGG SHELLS. HER NOW FAMOUS BOOK WAS CALLED “SILENT SPRING.”
THINGS LIKE CATERPILLARS EAT BACTERIUM AND NOT JUST LEAVES. THERE IS A BACTERIUM CALLED BACILLUS THURINGIENSIS [BT]— IT HAS A GENE THAT DEFENDS ITSELF AGAINST INSECT LARVI. IT CODES TO BIND THE INSIDE, THE GUT SHALL WE SAY, AND CAUSES DIARRHEA - THE INSECT DIES. GOOD FOR BACTERIUM, IT LIVES AND SURVIVES. THE GENE CODING FOR THIS TOXIN PROTEIN HAS NOW BEEN INTRODUCED TO CORN, COTTEN, SOYBEANS, TOMATO CELLS IN THE LABORATORY, THEN CLONED TO MAKE PLANTS AND EXPRESS THE TOXIN IN THE LEAF - THE CATERPILLAR EATS THE LEAF AND DIES. THE POPULATION OF THAT INSECT GOES WAY DOWN.
THIS TECHNOLOGY HAS REDUCED THE THE USE OF INSECT-SPRAYS BY 90%—— VERY IMPRESSIVE!
2. PESTICIDES, HERBICIDES— KILL WEEDS, BUT OFTEN GOOD CROPS THEMSELVES. GREAT CARE MUST BE USED TO USE HERBICIDES. BIOTECHNOLOGY HAS PUT IN THE CROPS RESISTANCE TO THESE HERBICIDES. SO THEY CAN BE USED WITHOUT DAMAGE TO THE CROPS.
THESE TWO EXAMPLES ARE IN WIDESPREAD USE ALL OVER THE WORLD!
3. RICE
RICE IS DEFICIENT IN AMINO ACID BALANCE— THEY ARE WORKING ON IT.
RICE IS ALSO DEFICIENT IN BATA-CAROTENE.
PEOPLE REQUIRE BC IN THEIR DIET; CARROTS HAVE IT AND IT GIVES THE REDISH COLOR. IT GETS CONVERTED TO VITAMIN A IN THE BODY.
RICE PLANTS DO NOT HAVE THE GENE TO MAKE BATA-CAROTENE.
AS A RESULT ABOUT 250,000 CHILDREN GO PARTIALLY BLIND EACH YEAR. THEY ARE EATING RICE AND DON’T GET ENOUGH BATA-CAROTENE IN THEIR DIET.
[A PROOF FROM THE LORD THAT ALL SHOULD BE EATING A BALANCED DIET. SEA-MEN WHEN DISCOVERING NORTH AMERICA WOULD GET SCURVY ON THE VOYAGE AND DIE. IT WAS DISCOVERED THAT EATING FRUIT WOULD PREVENT SCURVY— IT WAS A LACK OF VITAMIN C WHICH THE HUMAN BODY DOES NOT MAKE. THE ENGLISH WERE CALLED “LIMIES” BECAUSE THEY CARRIED TUBS OF LIMES FOR THE SAILORS TO SUCK ON - Keith Hunt]
OTHER PLANTS/FOOD DO HAVE BETA-CAROTENE - THERE ARE 3 ENZYMES ALONG THE WAY TO MAKE BC - OTHER PLANTS HAVE THEM AND SO HAVE BC.
INGO POTRYKUS [B. 1933] ISOLATED THESE ENZYMES; ONE FROM BACTERIA AND TWO FROM THE DAFFODIL PLANT. HE TOOK THESE AND INTRODUCED THEM TO THE RICE PLANT WITH A PROMOTOR, AND SO THE PATHWAY TO MAKE BC. THAT RICE IS GOLDEN IN COLOR AND HAS SUFFICIENT AMOUNTS OF BC.
[WHITE RICE LIKE WHITE BREAD IS NUTRITIONALLY VERY VERY LOW IN HEALTHY SUBSTANCES, AND SHOULD NOT BE A PART OF YOUR REGULAR DIET - Keith Hunt]
THESE PLANTS ARE NOW BEING CROSSED ALL OVER THE WORLD SO BC CAN BE THERE IN RICE EVERYWHERE.
SO THAT IS 3 WELL-KNOW AREAS WHERE BIOTECHNOLOGY IS USED.
THERE IS PUBLIC CONCERN ABOUT BIOTECHNOLOGY——
IN THE 1970s WHEN ALL THIS STARTED WE JUST DID NOT KNOW ENOUGH, SO NATURALLY CONCERNS, NATURALLY WORRIES; WHEN IT WAS ALL SHOWN TO BE SAFE CONCERNS ABATED.
PLANT BIOTECHNOLOGY AND GENERALLY MODIFIED FOODS ARE NOT NECESSARILY THE SAME——
NOT ALL PLANT BIOTECHNOLOGY CREATES A MODIFIED FOOD.
FOR EXAMPLE: IF YOUR WEARING SOMETHING OF COTTEN MADE IN AMERICA, YOU ARE WEARING COTTEN FROM A GENETICALLY MODIFIED PLANT— NO QUESTION ABOUT IT.
BUT PLANT BIOTECHNOLOGY THAT MAKES GENETICALLY MODIFIED FOODS IS A CONCERN, ESPECIALLY IN EUROPE.
THE OBJECTIONS TO BIOTECHNOLOGY IN AGRICULTURE ARE 3 FOLD——
FIRST: GENETICAL MANIPULATION IS UNNATURAL.
THE “YUCK” FACTOR; EATING FOODS WITH GENES FROM BACTERIA, IS GOING TOO FAR, JUST TOO MUCH TECHNOLOGY HERE.
THERE CAN BE NO RESPONSE TO THIS EMOTIONAL ARGUMENT.
WE MAY SAY, WELL CROPS HAVE BEEN MODIFIED WITHIN EACH OTHER FOR DECADES; CORN IS BREED SO WE HAVE ALL KINDS OF VARIETIES OF CORN TODAY. BUT TAKING GENES FROM ALL OVER AND SPLICING THEM TOGETHER IS A DIFFERENT SITUATION— THE YUCK FACTOR!
SECOND: GENETICALLY MODIFIED FOODS MIGHT BE UNSAFE TO EAT.
TAKING PROTEIN FROM HERE AND THERE, MIXING THEM, 3 DIMENSION STRUCTURE, MAY CREATE PROTEINS THAT SOME MAY BE ALLERGIC TO. AT THE PRESENT [2007] PLANTS ARE NOT BEING MODIFIED IN THE “FOOD” PART OF THE PLANT. BUT WE MUST BE CAREFUL, FOR CREATING FROM THE PERSPECTIVE OF ALLERGIC CONCERNS.
THIRD: GENETICALLY MODIFIED PLANTS ARE DANGEROUS TO THE ENVIRONMENT.
A GENE TRANSFERRED INTO A PLANT FROM SOMEWHERE ELSE, SAY TO RESIST PESTICIDES ETC. MIGHT BE INADVERTENTLY TRANSFERRED TO ANOTHER PLANT CLOSE BY, AND THIS HAS BEEN OBSERVED IN SOME AND NOT IN OTHERS. IT’S THE DANGER OF CREATING SUPER WEEDS.
TWO WAYS TO LOOK AT THESE PUBLIC CONCERNS——
PROCEED WITH CAUTION; TEST IN ALL WAYS WE CAN; PROCEED WITH CAUTION!
THE OTHER WAY TO LOOK AT IT IS THE PRECAUTIONARY PRINCIPLE— IF YOU CAN’T PROVE THIS WILL NEVER CAUSE A PROBLEM, DON’T DO IY!
IT’S LIKE “YOU NEVER KNOW WHAT’S GOING TO HAPPEN OVER A LONG PERIOD OF TIME”— THAT’S THE PRECAUTIONARY PRINCIPLE.
SO THERE’S THE TWO SIDES OF THIS ARGUMENT, ESPECIALLY VOICED IN EUROPE.
LESS SO IN OTHER PARTS OF THE WORLD, AND NOT AT ALL SO IN POOR PARTS WHERE BIOTECHNOLOGY IS USED TO IMPROVE PLANTS…….
SO WE HAVE COME FROM MENDEL AND HIS LAWS OF NATURE, TO DISCOVERING DNA AND HOW IT ALL FUNCTIONS.
I’VE COVERED HOW ALL THIS KNOWLEDGE HAS BEEN USED. IN MANY DIFFERENT WAYS TO SOLVING CRIMES, TO CLEANING UP THE ENVIRONMENT, TO STUDYING DISEASES— THE HOWS AND WHYS.
BIOTECHNOLOGY IS INCREASINGLY IMPORTANT.
IT IS RE-WRITING THE BOOK OF LIFE.
WE ARE FINDING OUT HOW ORGANISMS RELATE TO EACH OTHER.
GENETIC BIOLOGY IS HAVING A PROFOUND IMPACT IN MEDICINE, SCREENING AND MAKING SPECIFIC MEDICINE THAT ZERO IN ON THE PROBLEM CELLS AND NOT A SHOTGUN WAY LIKE CHEMOTHERAPY.
SO GENES, CLONING, STEM CELLS, ARE AT THE LEADING EDGE OF MODERN MEDICINES, AND HOLD GREAT PROMISE FOR THE FUTURE.
AGRICULTURE IS IMPORTANT FOR WE ALL MUST EAT. IT’S OFTEN TAKEN FOR GRANTED.
THE APPLICATION OF ALL THIS SCIENCE TO FEEDING THE WORLD IS ALREADY PROFOUND, AND AN EXCITING FUTURE IS POSSIBLE!
THE GENETIC GENI IS OUT OF THE BOTTLE!
…………………………………..
YES MAN CAN DO AND IS DOING WONDERFUL THINGS, BUT HE WILL NEED HAVE TO BE VERY CAREFUL TO USE SCIENCE CORRECTLY, OR HE COULD END UP WORSE OFF THAN BEFORE HE DISCOVERED AND KNEW ALL THE DEPTHS OF CREATION.
DAVID IN THE PSALMS SAID WE ARE WONDERFULLY MADE.
GOD SAID TO ANCIENT ISRAEL THAT IF THEY OBEYED HIS COMMANDMENT AND LAWS IN HOW TO LIVE CORRECTLY, AS GOD SET DOWN FOR THE PHYSICAL AND MENTAL SIDE OF THE HUMAN BODY, HE WOULD PUT NONE OF THESE DISEASES UPON US, THAT OTHER NATIONS HAD TO CONTEND WITH.
OUR BODY IS PHYSICAL AND SO GOD HAS GIVEN US PHYSICAL LAWS, THAT OBEYED WILL GIVE US AS NATIONS, WONDERFUL HEALTH.
BUT SADLY TOO MANY NATIONS ARE NOT FOLLOWING THOSE LAWS, NOR SEEKING THEM OUT.
THE LORD HAS GIVEN US DIET LAWS, THAT WAY TOO MANY CHRISTIANS THINK ARE ABOLISHED UNDER THE NEW COVENANT.
AND THERE ARE OTHER PHYSICAL LAWS, THAT COMMON SENSE WILL BRING YOU TO SEE SHOULD BE PRACTICED.
ONE OF THE GREAT TEACHERS OF THESE PHYSICAL LAWS IN THE LAST 100 YEARS WAS THE “HEALTH AND STRENGTH” MAN CHARLES ATLAS—— HIS COURSE IS STILL AVAILABLE, AND YOU CAN READ ALL ABOUT HIM ON THE INTERNET.
THERE ARE MANY LAWS TO HEALTH——
EXERCISE, REST AND SLEEP, PLAY TIME,
A STRESS FREE MIND, A POSITIVE HAPPY MIND, GIVING AND SERVING OTHERS, BEING FREE FROM ANGER, BITTERNESS
AND HOSTILITY. AND OF COURSE THE FOODS AND DRINKS YOU CONSUME.
GOD WOULD LIKE US TO BE HEALTHY IN MIND AND BODY, AND HE HAS GIVEN US THE LAWS TO FOLLOW THAT WILL BRING US HEALTH.
WE NEED TO GET IN HARMONY WITH THE FATHER’S COMMANDMENTS AND LAWS!
Keith Hunt
MOLECULAR MEDICINE——
THE IMMUNE SYSTEM
From the DVDs I have from THE TEACHING COMPANY— 2007
DAVID SADAVA Ph.D.
Quote:
MY OPENING STORY IS ABOUT SMALLPOX.
I’M GOIN G TO READ TO YOU FROM A LETTER——
FINDING SMALLPOX COULD BE SPREADING MUCH, AND FEARING THAT NO PRECAUTION COULD PREVENT IT FROM RUNNING THROUGH OUR ENTIRE ARMY, I DETERMINE THAT OUR TROOPS SHOULD BE INOCULATED. SHOULD THE DISEASE RAGE WITH IT’S USUAL VIRULENCE, WE SHOULD HAVE MORE TO DREAD FROM IT, THAN FROM THE SWORD OF THE ENEMY.
THIS LETTER WAS WRITTEN BY THE COMMANDER IN CHIEF OF THE USA CONTINENTAL ARMY TO HIS CHIEF PHYSICIAN, DATED JANUARY 6 - 1777.
IN THE PREVIOUS YEAR SMALLPOX HAD RAGED GENERAL GATE’S NORTHERN ARMY. OF 10,000 TROOPS, OVER HALF OF THEM GOT SMALLPOX, AND THE MILITARY CAMPAIGN HAD TO BE SUSPENDED FOR A MONTH.
THE LETTER FROM WASHINGTON KNEW WHEREOF HE WROTE.
AS A TEENAGER WASHINGTON TOOK HIS HALF BROTHER LAURENCE TO BARBADOS, HOPING IT WOULD HELP HIS BROTHER WITH HIS TURBOCAIOSIS.
WELL THE TRIP DID NOT DO MUCH FOR LAURENCE, BUT WASHINGTON CAME BACK WITH A MILD CASE OF SMALLPOX.
AS A SURVIVER OF THIS OFTEN LETHAL DISEASE, GEORGE HAD DEVELOPED A HIGH RESPECT FOR IT!
A CENTURY BEFORE SMALLPOX HAD DEVASTATED THE NATIVE POPULATION OF THE COLONIES.
IN 1775-76 IT HAD INCAPACITATED AN ARMY SENT TO LAY SEIGE ON QUEBEC, AT THE TIME A NON-INDEPENDENT COLONY, HOPING TO CONVINCE THE CANADIANS TO JOIN THE UNION.
WASHINGTON HAD HEARD ABOUT INOCULATION.
IN BOSTON - COTTEN MATHER [1663-1728] HAD WATCHED HIS 3 CHILDREN NEARLY DIE OF SMALLPOX.
THEN A SLAVE OF MATHER FROM AFRICA, NAMED ONESIMAS, TOLD HIM IN HIS COUNTRY PEOPLE WERE PROTECTED BY PUTTING SOME DRY PUSS OF THE POX ON A CUT IN THE SKIN.
IN 1721 SOME SAILORS INADVERTENTLY BROUGHT SMALLPOX TO BOSTOM. AN EPIDEMIC BEGAN. MATHER CONVINCED A PHYSICIAN ZABDIEL BOYLSTON [1676-1766] TO INOCULATE SOME NORMAL UN-DISEASED PEOPLE, IN THE WAY HIS SLAVE HAD DESCRIBED. BOYLSTON DID SO, FIRST ON TWO SLAVES AS WELL AS HIS OWN SON; WHEN IT WORKED HE DID IT ON MANY OTHERS. THE RESULT WAS THAT PARTICULAR SMALLPOX EPIDEMIC WAS GREATLY STEMED IN BOSTON.
THE OUTBREAK IN 1777, THE LETTER I READ TO YOU FROM WASHINGTON, WAS THE FIRST KNOWN INOCULATION OF AN ARMY AND IT WORKED PRETTY WELL.
THE COLONIST ARMY WON THE REVOLUTIONARY WAR.
SMALLPOX CLAIMED ABOUT 300 MILLION LIVES IN THE 20TH CENTURY.
IT’S ALWAYS TILL RECENTLY BEEN A SERIOUS DISEASE.
IN 1967 ALONE, 50 MILLION CASES WERE DETECTED AND 2 MILLION DEATHS.
[I WAS INOCULATED IN 1961 WHEN I CAME TO CANADA, IT WAS THE LAW. BUT I NEVER HEARD THAT SMALLPOX HIT CANADA IN THE 1960s - Keith Hunt]
1997 HOWEVER INOCULATION THAT HAD BEEN DONE WORLDWIDE SINCE THE 1960s LED TO THE ERADICATION OF SMALLPOX FROM PUBLIC HEALTH.
ONE OF THE GREAT SUCCESSES OF PUBLIC HEALTH.
NOW ONE OF A SERIES OF EVENS IN THE IMMUNE SYSTEM - THE SYSTEM THAT FIGHTS OFF DISEASE, IS INVOLVED IN THIS STORY OF GEORGE WASHINGTON AND SMALLPOX.
SMALLPOX IS CAUSED BY A VIRUS WITH GENOME OF DNA, AND ONLY INFECTS HUMANS.
SO STOPPING IT FROM TRANSFERRING FROM HUMAN TO HUMAN, IT COULD BE STOPPED.
IF EVERYONE WAS INOCULATED THE VIRUS WOULD HAVE NOWHERE TO GO.
WE KEEP SOME VIRUS ON HAND IN CASE SOME OTHER VIRUS MUTATES TO SMALLPOX.
THERE ARE SOME VIRUSES THAT AFFECT ANIMALS, SO WE WORRY ABOUT THAT.
THE VACCINE IS KEPT UNDER LOCK AND KEY.
BACK TO GEORGE WASHINGTON. HE PROBABLY CAUGHT IT FROM BEING AROUND A VICTIM OF SMALLPOX ON HIS TRIP TO BARBADOS, AND BREATHING IN DROPLETS WHICH CONTAIN THE VIRUS. IT IS QUITE CONTAGIOUS. AFTER 2 WEEKS HE PROBABLY GOT A SEVERE RASH, AND THE REMAINS OF IT PROBABLY SCARED HIM FOR LIFE - LITTEL SPOTS ON THE FACE. WE HAVE NO PAINTING OF A YOUNG GEORGE WASHINGTON. HE DID NOT BECOME FAMOUS UNTIL IN HIS 40s.
ABOUT 30% GET PNEUMONIA, SERIOUS INFECTIONS AND DEATH SOON FOLLOWS.
FOR WASHINGTON THE IMMUNE SYSTEM FOUGHT OFF THE VIRUS IN MANY STEPS.
[SO THE PROFESSOR ADMITS SOME PEOPLE FIGHT IT OFF THROUGH THEIR IMMUNE SYSTEM, AS DID GEORGE WASHINGTON - Keith Hunt]
THIS IS WHAT HAPPENS——
AFTER THE VIRUS ENTERS THE BODY SOME WHITE BLOOD CELLS CALLED “PHAGOCYTE” - “PHAGO” MEANS— EAT! IT ENGULFS THE VIRUS, DIGESTS IT INTO SMALL PIECES, CHOP IT UP. THEN THEY PRESENT SOME OF THESE SMALL PIECES ON THEIR OUTSIDE SURFACE. THEN OTHER “T CELL” RECOGNIZE THESE SMALL PROTEIN PIECES OF THE VIRUS, AND THIS SETS IN MOTION A SERIES OF EVENTS.
ANOTHER CELL CALLED “KILLER T CELLS” COME IN AND DESTROY THE LITTLE VIRUS PIECES AND ANY CELL CONTAINING THEM .
WE CALL THIS THE “T CELL IMMUNE SYSTEM.”
THEN STILL OTHER WHITE CELLS CALLED “B CELLS” MAKE ANTIBODY PROTEINS THAT WILL BIND UP ANY VIRUS CELLS OUTSIDE THE BODY LIKE IN THE BLOOD. THE B CELLS MAKE A HUGE ARMY THAT BINDS UP THE BAD GUYS.
A TWO PRONGED DEFENCE SYSTEM
FIRST: THE CELLULAR RESPONSE TO CHOP UP THE VIRUS AND KILLER T CELLS TO BIND AND DESTROY.
SECOND: THE B CELLS TO BIND UP THE VIRUS THAT MAYBE IN THE BLOOD.
AFTER THIS TWO PRONGED ATTACK ON THE VIRUS, THE JOB DONE, THE FIGHTING CELLS DIE, ALL BUT A SMALL CONTINGENT OF THE ARMIES REMAIN. THESE ARE SPECIFICALLY ARMED AGAINST SMALLPOX. THEY ARE READY TO BATTLE INCASE A NEW INFECTION COMES ALONG.
IT’S A STANDING ARMY OF T AND B CELLS.
THESE ARE CALLED MEMORY CELLS.
THEY WERE BEHIND THE INOCULATION OF THE CONTINENTAL ARMY. WHEN DEAD SMALLPOX PUSS WAS PUT ON THE CUT OF THE AMY SOLDIERS, AND IT LOOKED ENOUGH LIKE THE REAL LIVE VIRUS, IT PROVOKED THE IMMUNE SYSTEM TO SEND IN THE TWO ARMIES. SO THE ARMIES REPRODUCED ENOUGH OF THE T AND B CELLS TO FIGHT THIS IMAGINARY DISEASE. IT WAS NOT A REAL INFECTION AT THE TIME. ONCE THE ARMIES FOUGHT THIS IMAGINARY WAR THEY DIED OFF, BUT FOR A FEW “MEMORY” CELLS, READY TO MAKE WAR IF A NEW INFECTION OF SMALLPOX CAME ALONG. THE STANDING ARMY WAS READY TO DO BATTLE.
THAT’S MY INTRODUCTION TO THE IMMUNE SYSTEM.
I WILL TALK ABOUT THE CELLS IT HAS, T AND B AND THE MOLECULES IT HAS— ANTIBODIES.
THEN HOW IT IS CONTROLLED GENETICALLY— HIGHLY UNUSUAL FORM OF CONTROL.
THEN HOW WE CAN MANIPULATE THIS IN GENETICAL MEDICINE.
FIRST— THERE ARE TWO THINGS THE IMMUNE SYSTEM RECOGNIZES— NON BODY THINGS; THINGS NOT A PART OF THE HUMAN BODY. ANYTHING FROM THE OUTSIDE— CHEMICALS, VIRUSES, THAT ARE NOT YOU. IT RECOGNIZES NON-SELF AGENTS.
SECOND— IT THEN DESTROYS NON-SELF AGENTS BEFORE THEY CAN DO HARM.
THERE ARE THREE TYPES OF CELLS THAT ARE MAJOR PLAYERS— ALL WHITE CELLS.
FIRST “T” CELLS— THEY RECOGNIZE THE NON-SELF PIECES AND PUT OUT HANDS TO TAKE HOLD OF NON-SELF CELLS.
SOME OF THESE T CELLS SIGNAL OTHER T CELLS TO GO ATTACK AND KILL NON-SELF CELLS.
THEN THE THIRD TYPE OF CELLS ARE THE “B” CELLS.
AND B CELLS ARE STIMULATED TO MAKE PROTEINS THAT BIND UP THE INVADING NON-SELF CELLS IN THE BLOOD.
THERE ARE THREE TYPES OF MOLECULES THAT PLAY AN IMPORTANT PART IN THE IMMUNE SYSTEM.
THEY ARE ANTIGENS, ANTIBODIES, T CELL RECEPTORS.
FIRST— ANTIGENS
ANTIGENS ARE NON-SELF SUBSTANCES, NOT IN YOUR BODY. A VIRUS IS AN ANTIGEN. ANTI— AGAINST GENES. THE BODY IS THEN PROVOKED INTO ACTION TO DESTROY.
WHAT PROVOKES THE IMMUNE SYSTEM; SMALL CHEMICAL FORMATIONS, ONLY IN THE INVADER, NOT IN US. SO IT IS A PARTICULAR ARRANGEMENT WE DO NOT HAVE IN OUR BODY. A VIRUS MAY HAVE MANY OF THESE GROUPINGS OF ATOMS WE DON’T HAVE. A VIRUS MAY PROVOKE MANY DIFFERENT IMMUNE RESPONSES, BECAUSE OF THESE DIFFERENT GROUPING OF ATOMS IN THE VIRUS.
SOME OF THESE GROUPINGS MAY LOOK LIKE WHAT WE HAVE IN US. SO THAT PART OF THE VIRUS DOESN’T PROVOKE A RESPONSE FROM THE IMMUNE SYSTEM. BUT THE VIRUS WILL HAVE GROUPINGS UNIQUE TO THE VIRUS AND WILL PROVOKE A RESPONSE FROM OUR IMMUNE SYSTEM.
ANTIBODIES— ARE MADE BY THE B CELLS THAT BIND TO ANTIGENS.
SINCE ANTIGENS ARE A CHEMICAL GROUPING WITH CERTAIN SHAPES, THEN ANTIBODIES ARE A PROTEIN THAT FITS IT. A 3RD DIMENSIONAL SHAPE OF ANTIBODIES ARE DESIGNED TO FIT THE ANTIGENS.
SO LOCK AND KEY— THE B CELLS CAN ONLY MAKE ONE SPECIFIC ANTIBODY THAT FITS THE ANTIGEN.
EACH B CELL MAKES ITS OWN SPECIFIC TYPE ANTIBODY.
NOW WAIT A MINUTE; HERE’S THE PROBLEM, THERE ARE MILLIONS OF POTENTIAL ANTIBODIES, ONE FOR EVERY POSSIBLE GROUPING OF ANTIGENS, THAT WHICH IS NOT SELF.
T CELL RECEPTORS— THE 3RD MOLECULE I WANT TO INTRODUCE. THEY ARE PROTEINS LIKE ANTIBODIES, ON THE SURFACE OF A T CELL, AND THEY ARE GOING TO BIND TO A PIECE OF ANTIGEN ON THE SURFACE OF THE PHAGOCYTE [WHICH CHOPS UP THE VIRUS].
THERE HAS TO BE MILLIONS OF RECEPTORS TO CLAMP HOLD OF MILLIONS OF ANTIGEN FRAGMENTS PRESENTED BY THE PHAGOCYTE.
HOW DOES THIS SPECIFICALLY ARISE?
THE WAY IT HAPPENS IS FIRST OF ALL BY CLONAL SELECTION OF B AND T CELL SPECIFICITY. THERE ARE MILLIONS OF T CELLS MADE, AND MILLIONS OF B CELLS, EACH WITH THEIR OWN RECEPTORS TO BIND TO ANTIGENS. WHEN THE ANTIGEN IS PRESENTED THE ONLY RECEPTORS MADE IS THE ONE THAT WILL BIND TO THAT ANTIGEN.
PHAGOCYTE CHOPS UP THE VIRUS ANTIGENS AND STICKS A PIECE OUT FROM ITS SURFACE. THE T CELLS CRUISING AROUND HAS A RECEPTOR TO FIT THE ANTIGEN PIECE. NOW THE T CELL MAKES AN ARMY OF THE RECEPTOR WHICH FITS THE PIECE OF ANTIGEN.
CLONES ARE MADE OF THAT PARTICULAR T CELL.
BY THE SAME TOKEN MILLIONS OF B CELLS EXIST, AND WHICH MAKES A SPECIFIC ANTIBODY, THE ONE WHICH WILL FIT TO THE ANTIGEN, SO CLONING OF THAT PARTICULAR B WITH THAT SPECIFIC ANTIBODY.
THE REST OF THEM WILL HANG AROUND BUT ULTIMATELY THEY WILL DIE.
AFTER THE T AND B RESPONSE IS OVER, 90% WILL DIE OFF, AND A SMALL ARMY IS THERE IN STORAGE, IF THAT VIRUS AND ANTIGEN COMES BACK TO ATTACK THE HUMAN BODY. THEY ARE CALLED “MEMORY CELLS.”
[IF YOU’VE HEARD THIS ALREADY, WELL YES HE REPEATS HIMSELF, AND WILL AGAIN SHORTLY…. GUESS REPEATING DOES GET THE MESSAGE TO YOU - Keith Hunt]
HOW IS THIS UNDER GENETIC CONTROL?
THE GENETIC CONTROL OF THE IMMUNE SYSTEM IS HIGHLY UNUSUAL.
HERE’S THE CHALLENGE.
THERE ARE MILLIONS OF T AND B CELLS— EACH MAKING AN ANTIBODY FOR AN ANTIGEN— WHICH CAN ALSO BE IN THE MILLIONS. FOR EVERY ANTIGEN THERE MUST BE ANTIBODIES TO FIT THAT ANTIGEN.
SO GEORGE WASHINGTON AND YOU MAKE CONSTANT T AND B CELLS THAT WILL RESPOND TO SMALLPOX LONG BEFORE YOU ARE EVER EXPOSED TO THAT VIRUS.
[WOOOO….I’M A LITTLE OFF HIS TARGET HERE. IF THEY ARE ALREADY DOING STUFF WELL BEFORE THAT VIRUS HITS YOU, THEN WHY GET VACCINATED - Keith Hunt]
I AM MAKING ANTIBODIES, T CELL RECEPTORS THAT WILL BIND UP HIV — I’VE NEVER BEEN EXPOSED TO IT.
HERE’S THE PROBLEM WITH THAT TYPE OF MODEL:
THIS ASSUMES THERE ARE MILLIONS OF GENES, THEN EACH ONE OF THEM CODING FOR SPECIFIC T CELL RECEPTORS OR SPECIFIC B CELL RECEPTORS, AN ANTIBODY THAT WILL BIND UP THAT PARTICULAR ANTIGEN.
CAN’T BE, JUST CAN’T BE!
WE KNOW FROM HUMAN GENOME SEQUENCING WE HAVE A MEASLY 24,000 GENES. I SAID WE COULD DO MORE WITH THEM FOR REASONS I’VE GIVEN IN ANOTHER LECTURE.
BUT THAT NOWHERE COMES CLOSE TO MILLIONS AND MILLIONS OF CHEMICAL GROUPINGS THAT CAN COME FROM VIRUSES.
SO WE CAN’T HAVE ONE GENE FOR EACH PROTEIN— ONE GENE FOR EACH PROTEIN RECEPTOR— ONE GENE FOR ONE, TWO, THREE, FOUR, AND UP TO MILLIONS.
WE JUST DON’T HAVE ENOUGH DNA TO DO THAT.
THE SOLUTION IS VERY INTERESTING!
WE HAVE SUB-GENES THAT CODE FOR ANTIBODY OR T CELL RECEPTORS.
CONSIDER A PROTEIN THAT HAS 4 DIFFERENT REGIONS IN IT— REGION A, B, C, D.
IF WE WANT TO MAKE 16 DIFFERENT PROTEINS HERE——
SUBGENES A B C D
ALLELES 2 2 2 2 = 16
ALTERNATE SPLICING TOGETHER AT messengerRNA LEVEL FOR DIFFERENT PROTEINS.
NOW WE HAVE SPLICING AT DNA LEVEL.
ANTIBODY PROTEIN— TWO HEAVY CHAINS AND TWO LIGHT CHAINS.
IT’S A Y SHAPE.
THE ENDS ARE WHAT BINDS TO THE ANTIGEN.
HEAVY CHAIN
SUBGENES A B C D
ALLELES 300 10 5 2
DNA— COMBINE THEM— TOTAL POSSIBILITIES = 30,000
TOTAL NUMBER OF ALLELES IS 317
NOT MUCH DNA TO MAKE 30,000 PROTEINS.
LIGHT CHAIN
SUBGENES A B C D
ALLELES 300 1 5 2
TOTAL POSSIBLE = 3,000
CHAINS LIGHT HEAVY 3,000 X 30,000
TOTAL = 90 MILLION
DIFFERENT POSSIBLE PROTEINS CAN BE MADE FROM A TOTAL OF 625 ALLELES IN DNA.
SO A LITTLE DNA CUT AND SPLICED AND LOTS OF DIFFERENT ANTIBODIES!
THE SAME THING HAPPENS IN MAKING T CELL RECEPTORS.
A DNA SHUFFLE!
IT’S A GENETIC SHUFFLE— GOING ON ALL THE TIME TO MAKE T AND B CELLS TO BIND TO ANY POSSIBLE CHEMICAL GROUPING OF ANYTHING THAT IS NOT SELF.
WE ARE CONSTANTLY MAKING ANTIBODIES AND T CELLS, RECEPTORS, TO THINGS WE HAVE NEVER SEEN, OR NEVER EVEN BEEN INVENTED YET!
[WOW….SO IF THAT’S THE CASE WHY BOTHER WITH VACCINES? SEEMS LIKE FROM ALL THIS OUR IMMUNE SYSTEM IS PREPARING FOR ANYTHING THAT MAY COME ALONG, EVEN FOR THINGS NOT YET INVENTED - Keith Hunt]
VACCINES AND ANTIBODIES
VACCINES MAKE USE OF MEMORY CELLS. AFTER INFECTION THE T AND B CELLS DIE OFF, EXCEPT FOR A FEW, THEY STAY AROUND AND ARE MEMORY CELLS.
PEOPLE WHO HAVE HAD THE FLU WILL NOT GET IT AGAIN IN THE SAME YEAR. YOU HAVE BUILT UP MEMORY CELLS AGAINST THAT STRAIN OF FLU. IF IT TRIES TO INVADE YOU AGAIN, YOUR STANDING ARMY WILL KNOCK IT OUT - IT WILL NOT DO MUCH DAMAGE TO YOU.
A VACCINE IS DEFINED AS A DEAD ANTIGEN - IT PROVOKES AN IMMUNE RESPONSE TO BUILD AN ARMY TO FIGHT IMAGINARY INVADERS, SOMETHING NOT SELF. [HE’S REPEATING WHAT HE’S ALREADY TOLD US A FEW TIMES - Keith Hunt]
SOME GOOD ARMY CELLS REMAIN, TO FIGHT ANOTHER BATTLE SHOULD THE INVADING VIRUS COME AGAIN TO DO BATTLE [YA ABOUT 3 TIMES HE’S ALREADY TOLD US - Keith Hunt]
THE MEMORY CELLS STAND THERE TO FIGHT THE ANTIGEN IF IT COMES [WELL I GUESS REPEATING GETS THE MESSAGE ACROSS - Keith Hunt]
A VIRUS CAN MUTATE— NOW A NEW VARIANT COMING IN— MEMORY CELLS DON’T RECOGNIZE IT. THAT’S WHY WE GET A VACCINE SHOT EVERY YEAR.
[YES THERE ARE NOW AT LEAST 100 DIFFERENT FLU VIRUSES; THEY GUESS IN MAKING A VACCINE WHICH STRAIN WILL COME— OFTEN THEY ARE WRONG. MANY STILL DIE OF THE FLU EACH SEASON IT COMES. A STRONG IMMUNE SYSTEM IS THE ANSWER. I HAVE NEVER HAD A FLU SHOT IN MY ENTIRE LIFE OF 77 YEARS. I’VE HAD THE FLU ONCE AS A KID, AND ONCE AS AN ADULT IN JANUARY 1975— NEVER HAD IT SINCE. AND I ONLY GOT IT IN 1975 AFTER A VOAGE ACROSS THE ATLANTIC AND WAS SEA SICK FOR 5 DAYS— MY IMMUNE SYSTEM WAS WEAK - Keith Hunt]
THE FLU VIRUS MUTATES AND THE IMMUNE SYSTEM DOES NOT RECOGNIZE IT.
[NOW IF WE ARE MAKING MILLIONS OF T AND B CELLS, AS ALREADY EXPLAINED, FOR EVEN THINGS THAT HAVE NOT BEEN INVENTED YET, WHY BOTHER WITH VACCINES - Keith Hunt]
ANTIBODIES ARE SO SPECIFIC THEY WILL BIND TIGHTLY TO THEIR TARGET— ANTIGENS, IN ANY KIND OF CONTEXT OF CHEMICAL SOUP. WE COULD HAVE 5,000 ANTIGENS IN A GROUP AND THE ANTIBODY WILL ZERO IN ON THE SPECIFIC ANTIGEN THAT’S THERE— A LOCK AND KEY.
[YES HE’S EXPLAINED ALL THIS BEFORE, BUT I GUESS SAYING IT MORE THAN ONCE GETS IT ACROSS. ACTUALLY GOD DOES THE SAME THING IN HIS WORD— REPEATS GIVE IT ALL EMPHASIS. AGAIN IF WE ARE MAKING STUFF BY THE MILLIONS, WHY BOTHER WITH A VACCINE. I'M LOOSING HIM HERE - Keith Hunt]
ROSALYN YALOW AND SOLOMON BERSON USED THIS PROPERTY OF SPECIFICITY TO INVENT THE IMMUNOASSAY. IN THIS SYSTEM AN ANTIBODY IS TAGED WITH COLOR FOR DETECTION. AFTER THE ANTIBODY GLUES TO ITS TARGET— ANTIBODY TO ANTIGEN. THEY ARE SEPARATED. WE CAN MEASURE HOW MUCH IS THERE.
IT IS EXTREMELY SENSITIVE. WE CAN MEASURE HORMONES AS NEVER BEFORE.
FROM THIS WE HAVE DERIVED THE PREGNANCY TEST NOW USED REGULARLY BY WOMEN WHO WANT TO KNOW IF THEY ARE PREGNANT.
WHAT IS MADE BY A NEWLY FORMING EMBERO IS A SUBSTANCE CALLED “HUMAN CHORIONIC GONADOTROPIN” [HCG].
THIS UNIQUE HORMONE IS RELEASED IN BLOOD AND URINE, AND SO WE CAN TEST FOR IT WITH A HOME PREGNANCY KIT.
AMINOACA IS THE NAME GIVEN FOR SUCH TESTING.
AMINOACA IS USED FOR NEWBORNS FOR HYPOTHYROIDISM— ELIMINATING THEIR PROBLEM OF MENTAL RETARDATION.
ROSALYN AND SOLOMON WON THE NOBEL PRICE FOR DEVELOPING THIS TECHNOLOGY.
THESE ANTIBODIES CAN BE USED TO BIND ON CANCER CELLS. THEY CAN BE USED TO ZERO IN ON THE CANCER CELLS, A DIRECT TARGET TO HIT AND KILL.
WE HAVE NOW:
HERCEPTIN— BREAST CANCER
ERBITUX— COLON CANCEER
RITUXAN— LYMPHOMA CANCER
THEY ARE ANTIBODIES UNIQUELY BINDING TO CANCER TUMOR CELLS.
BINDING INITIATES CELL DEATH.
End Quote
[I STILL HAVE TO SAY AGAIN, A REPEAT TO GIVE EMPHASIS. IF WE ARE MAKING MILLIONS OF T AND B CELLS FOR THINGS THAT MAY COME AGAINST US AND FOR THINGS NOT YET INVENTED. WHY DO WE NEED VACCINES. HOW CAN WE CREATE A VACCINE AGAINST STUFF WE HAVE NOT YET HAD COMING AGAINST US, AND STUFF NOT YET INVENTED?
IN MY COMMENTS ON VACCINE I AM NOT TEACHING YOU NOT TO GET VACCINATED. THAT DECISION IS ENTIRELY YOUR DECISION. I’M JUST COMMENTING ON THINGS THE PROFESSOR HAS SAID, AND WONDERING HOW IT CAN ALL BE THOUGHT ABOUT IN THE CONTEXT OF VACCINES - Keith Hunt]
………………………………………
STUDY IN GENETICS
by DAVID SADAVA PH.D.
FROM THE TEACHING COMPANY— 2007
Quote
NOW I’D LIKE TO TURN TO CANCER.
MY OPENING STORY IS ABOUT ALLEN.
ALLEN FIRST NOTICED IT WHILE AT THE GYM. HE TIRED EASILY AND IT GOT WORSE OVER SEVERAL WEEKS. WHEN HE BEGAN TO HAVE SHORTAGE OF BREATH EVEN AT HOME WALKING FROM ROOM TO ROOM, HE DECIDED TO SEE HIS DOCTOR.
WHEN THE DOCTOR, LOOKING AT A DROP OF ALLEN’S BLOOD UNDER A MICROSCOPE, HE SAW MANY WHITE BLOOD SELL.
THIS IS UNSUAL BECAUSE WHITE BLOOD CELLS ARE USUALLY DWALFT IN NUMBER BY RED BLOOD CELLS.
A SAMPLE OF ALLEN’S BLOOD WAS SENT TO THE LABORATORY, AND THE LAB CONFIRMED HE HAD OVER 200,000 WHITE BLOOD CELLS TO A MILLIMETRE, WHICH IS ABOUT 1/5 OF A TEASPOON— 40 TIMES NORMAL.
IN THE NEXT FEW DAYS, A HEMATOLOGIST, SOMEONE WHO SPECIALIZES AND LOOKS AT BLOOD AND BONE MARROW; SHE FOUND A LOT OF IMMATURE WHITE BLOOD CELLS. IN ADDITION SHE SAW A FUNNY LOOKING ABNORMALITY, A CHROMOSOME CALLED “PHILADELPHIA CHROMOSOME.”
THE DIAGNOSIS WAS MADE AT THIS TIME— CHRONIC MYELOGENOUS LEUKAEMIA.
NO ONE KNOWS HOW, BUT IN THIS DISEASE OF WHITE BLOOD CELLS, THE DNA INSIDE TWO CHROMOSOMES INSIDE AN IMMATURE WHITE BLOOD CELL IS CUT AND SPLICED.
TWO CHROMOSOMES EXCHANGE MATERIAL; PARTS OF THE TWO GENES THAT ARE USUALLY ON SEPARATE CHROMOSOMES COME TO BE RIGHT BESIDE ONE-ANOTHER.
THINK OF IT THIS WAY— “THIS COURSE IS GOOD” AND “POLITICIANS ARE BORING.”
WE CAN CUT AND SPLICE AND GET TOTALLY DIFFERENT MEANINGS.
THE SHUFFLE CHROMOSOME AS SEEN IN ALLEN’S WHITE BLOOD CELLS WAS FIRST NOTICED BY SCIENTISTS, IN 1960 IN PHILADELPHIA, HENCE IT GOT ITS NAME.
THE WHITE BLOOD CELLS CARRYING THIS STRANGE CHROMOSOME ARE STIMULATED TO DIVIDE VERY RAPIDLY, SO YOU HAVE THIS HUGE NUMBER OF CELLS IN ALLEN.
FIRST, ALLEN WAS TREATED WITH CHEMOTHERAPY. DRUGS DESIGNED TO KILL ANY REPRODUCING CELLS, NOT JUST THE REPRODUCING CELLS IN HIS CANCER. SO OTHER GOOD REPRODUCING CELLS WERE ALSO KILLED— A SIDE EFFECT!
ONE OF THE DRUGS BOUND TO DNA; SECOND DRUG BLOCKS THER BUILDING BLOCKS ASSEMBLING DNA; A THIRD DRUG BLOCKS THE MECHANISM THAT PARTITIONS CHROMOSOMES TO NEW CELLS DURING CELL DIVISION.
AS MENTIONED THESE DRUGS HAD BAD AFFECTS ON OTHER DIVIDING CELLS.
BUT ALLEN STAYED THE COURSE FOR 6 MONTHS AND HIS WHITE BLOOD CELLS DROPPED TO 80,000 PER MILLIMETRE, STILL THIS IS 16 TIMES NORMAL.
THE DRUGS ALLEN TOOK BLOCKED CELL DIVISION ALL OVER THE BODY. THEY ARE NOT SPECIFIC FOR HIS CANCER.
NOW THE DOCTORS WOULD TRY A NEW APPROACH— A “PACIFIC DRUG.”
IN THE 1990s MOLECULAR BIOLOGY OF THIS DISEASE WAS STUDIED GREATLY. MOLECULAR BIOLOGY IS THE STUDY OF LARGE MOLECULES IN THE CELL OF DNA, AND THE PROTEIN WHICH IS THE EXPRESSION OF GENES.
THE NEW GENE, MADE BY THIS GENETIC SHUFFLING OF THIS PHILADELPHIA CHROMOSOME WAS SEQUENCED. AND ITS PROTEIN PRODUCT WAS STUDIED. AN EXAMPLE BY THE WAY OF REVERSE GENETICS— DNA SEQUENCE FIRST THEN FINDING THE PROTEIN.
AND INDEED THE PROTEIN TURNED OUT TO BE A TERRIFIC CELL DIVISION STIMULANT, IT CAUSES CELLS TO DIVIDE WITHOUT CONTROL.
THE NEXT STEP WAS THAT THE CHEMISTS AT A DRUG COMPANY, WENT INTO THE LAB AND DESIGNED A BRAND NEW SUBSTANCE, A CHEMICAL THAT WOULD SPECIFICALLY BIND TO AND INACTIVATE THIS NEW GENE PRODUCT IN THE TUMOR CELLS. UNQUE FOR THIS UNQUE TARGET.
AT THE UNIVERSITY OF ORAGON, DR. BRIAN DRUKER CO-ORDINATED A CLINICAL TRAIL WITH THIS DRUG, IN WHICH PATIENTS WITH CML WERE GIVEN THIS DRUG, FIRST TO TEST FOR SAFETY, AND THEN TO TEST FOR ITS AFFECTEDNESS. PATIENTS LIKE ALLEN WERE STALLING IN CONVENTIONAL TREATMENTS. PATIENTS WHERE WHITE BLOOD CELLS WERE STLL WAY TO HIGH; THEY WERE GIVEN THIS DRUG.
THE RESULTS WERE SPECTACULAR!
IN ALLEN’S CASE, THE COUNT FOR WHITE BLOOD CELLS WENT DOWN TO NORMAL—— 5,400 PER MIL.
IN FACT WHEN THE HEMATOLOGIST LOOKED IN HIS BLOOD AND BONE MARROW SHE FOUND NO ABNORMALITY, IN HIS CELLS, IN HIS CHROMOSOMES, IN HIS BLOOD AND BONE MARROW.
HE WAS CURED!
THE DEVELOPMENT OF THIS DRUG NOW CALLED “GLEEVIC” IS THE PROTO-TYPE; THE EXAMPLE— THE NEW MOLECULAR APPROACH TO CANCER TREATMENT.
THE AIM IS TO FIND OUT PRECISELY WHAT IS GOING WRONG IN A TUMOR CELL, AND DESIGN A RATIONAL TREATMENT ON THIS BASIS.
FOR THE REMAINING TIME IN THIS LECTURE I WANT TO DESCRIBE CANCER.
FIRST, CANCER DEVELOPS IN STAGES, THEN I’LL DESCRIBE HOW CANCER IS A GENETIC DISEASE. IT’S NOT USUALLY INHERITED; AND FINALLY THE WAYS WE TREAT CANCER.
CANCER DEVELOPS IN STAGES
WE KNOW CANCER CELLS ARE DIFFERENT THAN NORMAL CELLS. THERE ARE MANY HALLMARKS OF CANCER— CANCER CELLS LOOSE CONTROL OVER REPRODUCTION, THEY MULTIPLY WITH NO CONTROL.
NORMALLY CELLS CONTROL WHEN AND WHERE THEY REPRODUCE, AND THEY DO IT IN TWO WAYS.
THE FIRST IS INTERNAL CONTROL - THERE IS A CLOCK INSIDE A CELL. SCIENTISTS REFER TO IT AS A CELL CLOCK. IT TRIGGERS EVENTS IN A CELL TO CYCLE.
1. DUPLICATING DNA
2. PACKAGING DNA INTO COMPACT CHROMOSOMES.
3. SEPARATING THE CHROMOSOMES ONE FROM ANOTHER; EACH NEW CELL GETS A COMPLETE SET OF CHROMOSOMES.
4. WE WILL DIVIDE THE BIG CELL WITH THE TWO UNCLIE, BOTH WITH THE ENTIRE CHROMOSOME INTO TWO SMALLER CELLS.
EACH OF THESE FOUR ARE UNDER SEPARATE CONTROL. AND IT HAS TO DO WITH WHETHER AND HOW FAST CELL DIVISION WILL OCCUR.
NOW IN MOST MATURE PEOPLE LIKE ME, I TELL MY STUDENTS…. NO, NO - MATURE CELLS - A SPECIALIZED CELL THAT DOES NOT DIVIDE. A MATURE CELL, NOT ONES IN BONE MARROW - DOES NOT DIVIDE. IT’S OUT THERE, AND DOES ITS FUNCTION - NOT DIVIDING.
IT IS A FACT - A MAXIUM - IN BIOLOGY, MATURE CELLS DO NOT DIVIDE. IMMATURE CELLS ON THE OTHER HAND DIVIDE RAPIDLY. THINK OF AN EMBREO. OR BONE MARROW WHERE THERE ARE CELLS CONSTANTLY DIVIDING, TO REPLACE CELLS THAT DIE.
WHAT KEEPS CELLS DIVIDED IS A GROUP OF PROTEINS THAT STIMULATE THEM, TO NOT DIVIDE - PROTEINS THAT KEEP THEM FROM DIVIDING; THEY PREVENT TUMORS FROM FORMING. WE CALL THEM “TUMOR SUPPRESSORS.” THINK OF THEM AS THE BRAKES IN AN AUTOMOBILE.
THESE PROTEINS IN A CELL UNDER THE CONTROL OF GENES - DNA, ACT AT CONTROL POINTS - DNA DUPLICATION, SEPARATION, CHROMOSOMES ETC. FOR CELL DIVISION.
CANCER CELLS HAVE DEFECTIVE “TUMOR SUPPRESSORS.”
THEY HAVE MUTATION IN THEIR DNA THAT CAUSE PROTEINS TO NOT DIVIDE, TO NOT FUNCTION, IT’S LIKE HAVING BAD BRAKES IN A CAR; CAR MOVES REAL WELL IF YOU DON’T HAVE THE BREAKS ON.
NOW THOSE ARE THE INTERNAL CONTROLS OF CELL DIVISION.
THERE ARE EXTERNAL CONTROLS IN CELL DIVISION.
THE EXTERNAL CONTROLS, HORMONE SUBSTANCES CALLED “GROWTH FACTORS.”
THEY STIMULATE CELLS TO DIVIDE BY ACTING LIKE A GAS PEDAL IN A CAR, AT CERTAIN CONTROL POINTS. AT THE CONTROL POINTS THERE IS A GAS PEDAL TO GO FORWARD, AND A BRAKE PEDAL TO STOP GOING FORWARD.
HERE’S WHAT WE MEAN BY A GROWTH FACTOR.
I TALKED IN A PREVIOUS LECTURE ABOUT BLOOD CLOTS, AND GETTING RID OF BLOOD CLOTS; WE HAVE A NEW DRUG THAT DISSOLVES AWAY BLOOD CLOTS.
NOW I WANT TO TALK ABOUT BLOOD CLOT FORMATION.
A CLOT FORMS, AND THEN THE WOUND HEALS; AROUND THE BLOOD CLOT HEALS AND AS WE WOULD SAY, THE BLOOD CLOT GOES AWAY. NOW THESE CELLS THAT SURROUND THE BLOOD CLOT HAVE TO BE STIMULATED IN SOME WAY TO DO SO.
THOSE CELLS HAVE TO SURROUND THE BLOOD CLOT AND CLOSE UP ABOVE THE CLOT, THEN THE WOUND IS HEALED. THERE MUST BE A LOT OF CELL DIVISION GOING ON .
AND IT TURNS OUT AS THESE CELLS CLOSE THE WOUND THEY ALSO DISSOLVE THE CLOT. THE CELLS THAT FORM THE CLOT STIMULATE THE CELLS ABOVE IT TO HEAL.
THE CELLS THAT FORM THE CLOT MAKE A GROWTH FACTOR TO STIMULATE THE CELLS TO DIVIDE AND CLOSE THE WOUND.
GENES WHOSE PROTEIN PRODUCTS STIMULATE CELL DIVISION ARE CALLED “ONCOGENES” - ONCO MEANS “MASS” - GENES ARE GENES. AN ONCOLOGIST DEALS WITH A MASS - A TUMOR.
CANCER CELLS OFTEN MAKE THEIR OWN GROWTH FACTOR. THEY STIMULATE. THEY WILL HAVE THEIR OWN ONCOGENES - CONSTANTLY STIMULATING FOR CELL DIVISION. OTHER CANCER CELLS WILL HAVE MUTATED TO MAKE THEM HIGHLY SENSATIVE TO GROWTH FACTORS.
SO THESE ONCOGENES ARE THE GENES THAT TURN ON THE GAS PEDAL, OF CELL REPRODUCTION.
THE FEARSOME ASPECT IS THAT THESE CANCER CELLS CAN SPREAD TO OTHER PARTS OF THE BODY - IT IS CALLED “CANCER METASTASIS.”
VERY HARD TO TREAT; YOU CAN’T DO SURGERY IF THE CANCER IS ALL OVER THE PLACE.
THIS LEADS TO MUTABLE ORGAN FAILURE AND OFTEN LEADS TO PEOPLE DYING.
THINK OF METASTASIS IN THIS WAY—-
THE GLUE THAT CAUSES CELLS TO STICK TO ONE ANOTHER, THE GLUE IS SPECIFIC, THE SKIN CELLS. PINCH YOURSELF ABOVE SAY THE WRIST, THE CELLS STICK TOGETHER; THEY DO NOT STICK TO THE BONE.
SO THEY MUST HAVE A SPECIFIC SKIN CELL SURFACE; THEY ARE SPECIAL SKIN CELL PROTEINS TO STICK TOGETHER.
CANCER CELLS LOOSE THIS ADHESION.
THERE ARE SEVERAL STEPS TO METASTASIS, TO A TUMOR SPREADING.
FIRST, CANCER CELLS MUST LOOSE THEIR ADHESION TO STICK TOGETHER; AND DETACH FROM A GROWING TUMOR. THEN THE CELLS MAKE A B-LINE TO A BLOOD VESSAL. THE CHEW UP ADJACENT CELLS TO GET TO THE BLOOD STREAM. THEN THEY ENTER THE BLOOD SYSTEM. THEY GO THROUGH THE BLOOD AS A RED BLOOD CELL DOES. THEY COME TO ANOTHER ORGAN AND STOP! THEY WEASEL THEIR WAY OUT OF THE BLOOD AND INTO THE NEW ORGAN, AND MAKE A NEW TUMOR.
WE KNOW ALL OF THESE STEPS IN GREAT DETAIL AT THIS POINT.
DURING THE PROCESS OF GROWTH AS A TUMOR, METASTASIS MUST MAKE A NEW BLOOD VESSEL TO THE TUMOR. ALL PARTS OF THE BODY NEED BLOOD, FOR OXYGEN AND TO TAKE AWAY WASTE LIKE CARBON-DIOXIDE; IF YOU DON’T HAVE BLOOD AS A TISSUE YOU WILL DIE.
THE TUMOR NEEDS BLOOD. IT’S A BUNCH OF CELLS. IT SENDS OUT MESSENGERS TO THE BLOOD AND SAYS, “MAKE SOME BLOOD CANALS AND SEND BLOOD THIS WAY, OVER TO HERE - THE NEW TUMOR.
THIS PROCESS IS CALLED “ANGIOGENESIS” - IT MEANS “START NEW BLOOD VESSELS.”
THESE 4 EVENTS——
1. INACTIVATION OF TUMOR SUPPRESSORS
2. ACTIVATION OF ONCOGENES - TURN ON
3. METASTASIS - SPREADING
4. ANGEOGENESIS - GETTING BLOOD VESSELS
THESE OCCUR IN SEQUENCE
SO CANCER WE CAN DIFINE AS A MULTI-STEP DISEASE.
NOW I WANT TO TURN AND TALK ABOUT CANCER AS A GENETIC DISEASE - THE GENES INVOLVED IN THESE 4 PROCESSES.
THESE 4 EVENTS JUST DESCRIBED ARE OBVIOUSLY CONTROLLED BY GENES THEY ALL HAVE; AND THESE GENES ARE GETTING TURNED ON IN SOME WAY. TUMOR SUPPRESSORS, ONCOGENES, METASTASIS, ANGEOGENESIS — GENES, ARE ALL GETTING INAPPROPRIATELY EXPRESSED.
THERE ARE A COUPLE OF WAYS THEY GET INAPPROPRIATELY EXPRESSED.
ONE OF THEM IS TO BRING AN ACTIVE ONCOGENE INTO A CELL. IF THE ONCOGENE IS NOT BEING EXPRESSED A VIRUS CAN BRING IT INTO THE CELL.
[MY MOTHER DIED OF A VERY STRANGE CANCER, BROUGHT INTO HER BY A VIRUS; IT ATTACKS THE MUSCLES. IT IS A PAINLESS CANCER; YOU DO NOT KNOW YOU HAVE IT TILL IT IS TOO LATE. SHE COULD NOT GET OFF THE COUCH; MY DAD HAD TO CARRY HER TO THE CAR TO TAKE HER TO THE HOSPITAL. THEY TOOK A BLOOD TEST. THEY PULLED MY DAD OUT INTO THE HALL WAY, AND TOLD HIM ABOUT THIS STRANGE PAINLESS CANCER; THE LAST MUSCLE IT ATACKS IS THE HEART. THEY SAID SHE HAD ONLY A FEW DAYS TO LIVE; THEY WERE CORRECT, TWO DAYS LATER MY MOTHER DIED, SHE WAS 73 - Keith Hunt]
TUMOR VIRUSES WERE DISCOVERED IN A VERY INTERESTING WAY.
IN 1910 BY PEYTON ROUS [1879-1970] WORKING IN WHAT WAS THEN THE ROCKEFELLER INSTITUTE IN NEW YORK CITY, WHICH IS NOW THE ROCKEFELLER UNIVERSITY.
HE GOT A CALL FROM A CHICKEN FARMER IN LONG ISLAND; THE CHICKENS WERE GETTING A HORRIBLE TUMOLR ON THEIR KNEE. IT WAS SPREADING THROUGHOUT THE CHICKEN COOPS. HE THOUGHT MAYBE THIS IS A COMMUNICABLE DISEASE. HE WENT OUT AND INDEED HE THOUGHT IT WAS A VIRUS SPREADING AMONG THE CHICKENS. IT WAS EVENTUALLY CALLED “ROUS SARCOMA VIRUS” WHICH WAS CAUSING THIS TUMOR.
HE CAME TO THIS BY DOING THE KNOWN SCIENCE OF THE TIME - ISOLATE AND INFECT A LIVE CHICKEN THAT DIDN’T HAVE THE TUMOR; FROM THAT TUMOR IN THE ANIMAL HE ISOLATED AND REPEATED. YES A VIRUS.
ROUS WAS AWARDED THE NOBEL PRIZE IN 1966, 56 YEARS LATER!
WHY THAT LONG TO RECOGNIZE HIM?
PEOPLE THOUGHT WELL THIS IS SPECIALIZED - NO ONE WANTED TO BELIEVE CANCER COULD BE A COMMUNICABLE DISEASE. AND PEOPLE STARTED TO LOOK AT DNA AND PROTEINS; ATTENTION SHIFTED AND SO PUT ON THE BACK BURNER - IN 1950s AND 1960s IT WAS PUT ON THE FRONT BURNER.
IT’S GOOD FOR ALL SCIENTISTS TO KNOW THAT AFTER YOU’VE DONE YOUR WORK, IN THIS CASE 56 YEARS LATER, YOU CAN STILL WIN THE NOBEL PRIZE.
TUMOR VIRUSES HAVE ACTIVELY EXPRESSED ONCOGENES.
THE PROBE THAT SAYS I NEED BLOOD WILL THEN TO THESE TUMOR GENES AND STIMULATES CELL DIVISION.
APPROXIMATELY 10% OF CANCER IS BY VIRUSES. TWO MAJOR ONE—-
HEPATITUS B VIRUS - LIVER CANCER.
PAPILLOMAVIRUS - CERVICAL CANCER
THE GOOD NEWS IS AN ANTI-VIRAL VACCINE IS BEING USED SO PEOPLE CAN PREVENT GETTING THIS CANCER THAT IS COMMUNICABLE.
INHERITABLE—-
MUTATIONS IN THE TUMOR SUPPRESSING GENES THAT CAN CAUSE CELLS TO DIVIDE INAPPROPRIATELY. ABOUT 10% OF CANCERS ARE INHERITED.
THIS INCLUDES ABOUT 10% OF BREAST CANCER; 5% OF COLON-RECTAL CANCER, A LARGER PERCENTAGE OF TUMOR OF CHILDHOOD.
THIS IS ALL IN COMPARISON TO NON-INHERITED/VIRUS CANCER.
INHERITED USUALLY APPEARS EARLY IN LIFE - INHERITED BREAST CANCER IN WOMEN IN THIER 20s AND 30s, INSTEAD OF IN THEIR 50s AND AFTER. AND USUALLY TWO OT THREE PLACES IN THE BREAST OR BOTH BREASTS.
LOOKING AT THE DATA OF INHERITED AND SPORADIC CANCER WE’VE DESCRIBED——
ARTHUR KNUDSON PROPOSED THE “TWO-HIT” HYPOTHESIS INVOLVING TUMOR-SUPPRESSING GENES AND INHERITANCE. TUMOR SUPPRESSING GENES BLOCK CELL DIVISION.
RECALL FROM MENDELSON GENETICS MOST CELLS HAVE TWO COPIES OF EVERY GENE; KNUDSON PREPOSED THAT BOTH COPIES HAVE TO BE MUTATED SO PROTEINS MADE ARE INACTIVE ONES SO NO LONGER CAN BE BLOCKED.
IT’S LIKE TAKING YOUR FOOT OFF THE BRAKE AND RELEASING THE PARKING BRAKE ALSO, SO THAT YOUR CAR CAN MOVE FORWARD - BOTH ALLELES OF TUMOR SUPPRESSING GENES MUST BE OFF.
PEOPLE WITH INHERITED CANCER INHERITED ONE BAD ALLELE— SO LATER ON IF THEY GET A MUTATION IN THAT ALLELE, GIVING TWO BAD ALLELES THEY GET CANCER, AND IT HAPPENS RELATIVELY SOON.
PEOPLE WITH NON-INHERITED TWO MUTATIONS OF BAD ALLELES; THAT USUALLY IS LATER ON.
SPORADIC CANCER TAKES TWO MUTATIONS.
BUT OUR 4 SEQUENCE EVENTS STILL HAVE TO TAKE PLACE IN SEQUENCE.
THE MUTATIONS HAVE TO TAKE PLACE IN ALL 4 PROCESSES.
CELL MUTATION IN CANCER
CANCER CELL DIVISION
*
* *
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Fist Second Third Fourth
Mutation Mutation Mutation Mutation
UNCONTROLLED GROWTH!!!!
BERT VOGELSTEIN [B. 1949] AT THE JOHN HOPKINS UNIVERSITY AND HIS COLLEGES, SPENT A LOT OF TIME DURING THE 1990s LOOKING AT THE GENETIC CHANGES OF THE 4 TYPES I’VE DESCRIBED. SPECIFICALLY AT COLON-RECTAL CANCER, WHICH STARTS AS A SMALL CELL CALLED “POLYP” THEN THE GROUP OF CELLS GET LARGER, LARGER AND LARGER, OVER TIME. YOU CAN ACTUALLY FOLLOW THESE ON A CAMERA; YOU NEED TO REMOVE THE “POLYP” AND WHAT YOU HAVE IS CANCER CELLS.
VOGELSTEIN DOCUMENTED ALL THESE STAGES AS COLON-RECTAL CANCER WAS PROCEEDING.
WHAT HE FOUND WAS A SERIES OF DRAMATIC EVENTS. MUTATIONS IN SUPPRESSOR GENES, THEN IN ONCOGENES, THEN IN METASTASIS GENES, DETACHING, THEN LAST MUTATIONS IN ANGEOGENESIS GENES TO TURN THEM ON.
DESCRIBING CANCER IN SUCH DETAIL IS AN AMAZING ACHIEVEMENT IN MODERN BIOLOGY AND MEDICINE. AND WILL LEAD TO TREATMENTS AS WE HAVE SEEN IN SUCH A DRUG AS GLEEVIC.
ANYTHING THAT CAUSES CANCER MUST BE MAKING CHANGES IN THE CELLS - MUTATIONS.
1. SPONTANEOUS MUTATIONS——
CAN LEAD TO CANCER, BY THE FACT WE ARE MADE OF DNA; PEOPLE GET CANCER WITH NO RISK - NO BAD STUFF THEY ARE EXPOSED TO. AND THIS IS BECAUSE OF ERRORS IN DNA AS IT DUPLICATES, OR OTHER CHEMICAL REASONS. THIS IS A RARE EVENT BUT REMEMBER THE B ODY HAS TRILLIONS OF CELLS. AND CANCER CAN COME FROM ONE CELL THAT GOES BAD IN A NUMBER OF WAYS.
2. INDUCED MUTATIONS——
CAUSED BY SOMETHING ELSE, SOMETHING FROM OUTSIDE - KNOWN CARCINOGENS.
MOST CANCER MUTATIONS ARE CAUSED BY THE ENVIRONMENT, NO QUESTION ABOUT THAT; WE KNOW ENVIRONMENT FACTORS QUITE WELL.
CIGARETTE SMOKE, DAMAGES A SPECIFIC TUMOR SUPPRESSOR GENE, A GENE P53 IS DAMAGED; NO LONGER ACTS AS A TUMOR SUPPRESSOR GENE.
ULTRA VIOLET LIGHT FROM THE SUN CAN CAUSE SKIN CANCER.
[THE OZONE FILTERS OUT DAMAGING RAYS FROM THE SUN; UP TILL THE 1970s THE OZONE WAS IN TACT AND SUNBATHING WAS NOT A SERIOUS CONCERN. CHARLES ATLAS, THE FIRST MR. UNIVERSE, HAD A SUPERB SUN TAN, AND RECOMMENDED IT, IN HIS “HEALTH AND STRENGTH COURSE.” NOW THE OZONE HAS REPAIRED ITSELF, SUN BATHING IS FINE AGAIN BUT COMMON SENSE IS CALLED FOR. NEVER SHOULD YOU BURN YOURSELF. DARK HAIR PEOPLE SUNTAN MUCH EASIER THAN RED-HEADS AND BLONDS - Keith Hunt]
FOR MOST CANCER WE REALLY DON’T KNOW WHAT IS GOING ON [PROBABLY KNOW WAY MORE NOW IN 2020 - Keith Hunt]
CAUSES OF CANCER
TOBACCO
UNKNOWN
OTHER
THE BIGGEST PART OF THE PIE IS—— DIET!
WE KNOW THIS ABOUT DIET BECAUSE WHEN PEOPLE MOVE FROM ONE COUNTRY TO ANOTHER, IMMIGRATION, THEY AND THEIR OFF-SPRING WILL ADOPT THE COUNTRY’S CANCER RATE.
THERE ARE THREE WAYS TO TREAT CANCER
THOSE THREE WAYS ARE—— SURGERY, RADIATION, AND CHEMOTHERAPY.
FIRST— SURGERY— IT IS BY FAR THE MOST COMMON WAY. A TUMOR THAT IS IN ONE PLACE, YOU CAN REMOVE IT ALL BY SURGERY. THAT’S WHEN THE DOCTOR SAYS, “WE GOT IT ALL.” OTHER TREATMENT IS USED TO CLEAN UP SURROUNDING BAD CELLS, THAT ARE AROUND THE TUMOR.
SECOND— RADIATION— IS USED ON CANCER OF A LOCALIZED AREA, THAT CAN’T BE USED BY SURGERY; MIGHT BE USED FOR SURROUNDING AREAA OF A TUMOR, OR TO SHRINK A TUMOR THAT IS NEAR AN AREA WHERE SURGERY COULD BE TOO DANGEROUS TO USE.
RADIATION DAMAGES DNA; IT CAUSES BOTH STRAND OF DNA TO BE BROKEN. IT BREAKS THE BONDS OF BEADS ON DNA. THE AMOUNT USED ARE SMALL BUT LARGE IN COMPARISON TO THE TUMOR. THE LIFE TIME EXPOSURE TO RADIATION OF THE TYPICAL PERSON ON EARTH, FROM ALL CAUSES IS ABOUT 1/8 OF A GREY, DON’T WORRY ABOUT WHAT A GREY IS, REMEMBER 1/8.
DURING THE COURSE OF A TREATMENT THE TUMOR GETS ABOUT 50 GREY OVER 5 WEEKS. THAT’S 400 TIMES A LIFETIME DOSE OF RADIATION ON A LOCALIZED AREA. IT IS HIGHLY FOCUSSED ON A SPECIFIC AREA.
CHEMOTHERAPY— IT’S USED WHEN TUMORS SPREAD OVER THE BODY. YOU PUT A DRUG IN THE BLOOD SYSTEM IT WILL BE DISTRIBUTED EVERYWHERE. IT IS A DRUG THAT KILLS ALL DIVIDING CELLS, INCLUDING THE TUMOR. SO THERE ARE SIDE EFFECT WITH THIS, ANY DIVIDING CELLS ARE AFFECTED, AS IN BONE MARROW. SOME OF THE DRUG ARE FROM NATURAL PLANTS SOME ARE SYNTHETIC MADE IN THE LABORATORY.
PRECISE MOLECULAR DESCRIPTION OF THE CHEMICAL BIOLOGY ARE LEADING TO SPECIFIC MOLECULAR MEDICINES.
End Quote
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YES A LADY I KNOW WHO HAS CANCER IS RECEIVING A SPECIFIC DRUG THAT TARGETS THE CANCER SHE HAS. SO NO OTHER CELLS ARE AFFECTED.
THIS IS THE LATEST TECHNOLOGY TO FIGHT THE CANCER DISEASE, AND IT IS SHALL WE SAY, SPACE AGE MEDICINE.
THE WONDERS OF THE HUMAN BODY ARE MIND-BLOWING.
THE WONDER OF DNA AND ALL THAT IS CONNECTED WITH GENETICS IS TRULY ASTONISHING. WHAT WE HAVE DISCOVERED OVER THE LAST 70 YEARS IS AMAZING; ESPECIALLY SO IN THE LAST 20 YEARS.
TO THINK THAT THIS COULD ALL MATERIALIZE OUT OF NOTHING, AS SCIENCE NOW SAYS THE UNIVERSE CAME OUT OF NOTHING WITH A BIG BANG; TO BELIEVE THE WONDER OF GENETICS COULD JUST EVOLVE….. WELL FOR ME THAT IS A BELIEF FROM PLANET PLUTO.
THE MORE WE FIND OUT ABOUT THIS SUBJECT, THE MORE IT SHOULD GIVE US THE UNDERSTANDING THAT A MASTER-MIND IS BEHIND IT ALL—— THE MIGHTY ETERNAL GOD!
Keith Hunt
STUDY IN GENETICS——
GENE THERAPY
by David Sadava Ph. D.
For The Teaching Company— 2007
Quote:
NOW LET’S TALK ABOUT GENE THERAPY.
IT IS A DRAMATIC WAY OF IMPROVING A GENETIC DISORDER!
THE SKELETON MUSCLES THAT MOVE YOUR ARMS AND LEGS WITH TWO TYPES OF MUSCLE FIBRES - FAST AND SLOW TWITCH.
SLOW TWITCH FIBRES NEED A LOT OF OXYGEN FROM THE BLOOD, TO WORK WELL. THEY CONTAIN A LOT OF THE MIGHT OF THE CELL - CONDRAL DNA - MITOCHONDRIA = ENERGY PRODUCING FACTORIES IN THE CELL.
THESE PROVIDE A LONG LASTING POWER FOR MUSCLE CONTRACTION.
SLOW TWITCH FIBRES DON’T GET TIRED.
FAST TWITCH FIBRES ARE DIFFERENT - THEY DON’T NEED AS MUCH OXYGEN AS SLOW TWITCH FIBRES - AND FAR FEWER MITOCHONDRIAL - THEY GIVE QUICK BURSTS OF ENERGY - BUT GET TIRED EASILY.
LOOK AT SPRINTERS IN ATHLETICS - THEY HAVE MUCH MORE FAST TWITCH FIBRES THAN SLOW TWICH FIBRES.
DISTANCE RUNNERS HAVE MUCH MORE SLOW TWITCH FIBRES THAN FAST TWITCH FIBRES.
A LOT OF THIS FAST TO SLOW TWITCH FIBRES SEEMS TO BE GENETICALLY ENGINEERED.
YOU DON’T HEAR OF THE SAME PERSON WINNING THE MARATHON AND 100 METRE DASH, IN THE OLYMPICS.
DISTANCE RUNNERS SEEM TO BURN FAT DIFFERENTLY - MY FRIENDS WHO RUN MARATHONS CAN EAT TWICE WHAT I EAT BUT NEVER GAIN AN OUNCE - THEY DON’T GET FAT!
ENTER THE MARATHON MOUSE!
NO THIS IS NOT A VIDEO GAME, OR CARTOON CHARACTER - NO IT’S A MOUSE, TREATED TO CHANGE THE RATIO OF FAST TO SLOW TWITCH FIBRES - GENE THERAPY!
RON EVANS - SALK INSTITUTE IN CALIFORNIA, PRODUCED THIS MOUSE IN HIS LABORATORY.
HE WAS NOT LOOKING FOR A SUPREME ATHLETIC MOUSE; HE WAS LOOKING FOR THE BREAK-DOWN THAT CONTROLS FAT. HE IS AN ANTI-OBESITY RESEARCHER.
EVANS AND COLLEGES FOUND A PROTEIN - PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR [ PPARdelta]. I WILL REFER TO IT AS “PPARdelta.”
NOW THIS PROTEIN SEEMS TO BE ABLE TO BREAK DOWN FAT TISSUE IN STORED FAT - ADIPOSE TISSUE - TISSUE THAT STORES FAT.
PUT IT MILDLY THE DRUG COMPANIES GOT VERY INTERESTED IN WHAT EVANS WAS DOING.
PPARdelta IS A TRANSCRIPTION FACTOR, IT BINDS TO THE PROMOTER THAT PRODUCE THE GENES, THAT ARE INVOLVED IN FAT BREAKDOWN, PROMOTERS AND TRANSCRIPTION.
GENES ARE EXPRESSED AS PROTEINS, THE INTERMEDIATOR BETWEEN GENES BEING EXPRESSED AND messengerRNA - A COPY OF THE GENE, TO BE SENT OUT TO THE RIBOSOME TO BE TRANSLATED INTO A PROTEIN.
SO A GENE - PROMOTER - TRANSCRIPTION FACTOR = DNA TRANSCRIPTION.
TRANSCRIPTION FACTOR DO THE MAJIC - TURN GENES OFF AND ON.
PPARdelta BINDS TO THE PROMOTER AND A NUMBER OF AMINO-ACIDS TO BREAK DOWN FAT.
EVANS HAD ALREADY SHOWN ALL THIS WITH PPARdelta THAT CAUSED FAT TO BREAK DOWN.
NOW HE WONDERED WHAT WOULD HAPPEN IF PPARdelta WAS HIGHLY EXPRESSED IN MICE MUSCLES. MUSCLES NEED ENERGY AND FAT BREAKS DOWN INTO ENERGY.
HE THOUGHT WELL THE FAT STORED AROUND MICE MUSCLES WILL BREAK DOWN INTO ENERGY FOR THE MUSCLES, AND GET LEANER AS WELL, IF THE GENE WAS EXPRESSED IN FAT TISSUE.
SO EVANS DID GENE THERAPY ON THE MOUSE.
HE PUT THE GENE FOR PPAR - A PROTEIN BESIDE THE PROMOTER THAT WOULD BE EXPRESSED IN SKELETON MUSCLE, THIS RECOMBINANT DNA - PUT IT INTO A VECTOR, AND THE VECTOR WAS INJECTED INTO A FERTILIZED MOUSE EGGS.
ANIMALS WITH RECOMBINANT DNA WERE SELECTED WITH A DETECTABLE GENETIC MARKER, THAT YOU ALWAYS DO IN RECOMBINANT DNA WORK, THEN THESE ANIMALS WERE TESTED FOR—- WEIGHT GAIN, COMPOSITION OF MUSCLE AND PERFORMANCE.
NOW THE RESULTS——
AS HE HYPOTHESIZED, THE GENETIC MODIFIED MICE DID NOT GAIN WEIGHT ON A HIGH FAT DIET. THIS PPARdelta STIMULATED FAT BREAK-DOWN IN FAT STORES AND IN MUSCLE.
THE UNEXPECTED RESULT—— THE MUSCLE HAD CHANGED FROM A 50/50 RATIO OF SLOW/FAST TWITCH MUSCLES, TO A MARKED INCREASE IN SLOW TWITCH FIBRES.
WHEN HE PUT THE MICE ON AN EXERCISE-WHEEL THE PERFORMANCE CHANGED TO SLOW TWITCH FIBRES.
NORMAL MICE CAN RUN ABOUT 90 MINUTES OR 900 METRES BEFORE GETTING EXHAUSTED. THE GENETICALLY ALTERED MICE COULD GO TWICE AS LONG AND ABOUT TWICE AS FAR. THEY WERE NOW AS IF TRAINED TO BE LONG-DISTANCE ATHLETES.
CAN THIS LEAD TO HUMANS BEING ABLE TO DO MUCH BETTER IN LONG DISTANCE RACES? WELL IT’S UNCLEAR; BUT ATHLETIC AGENCIES ARE CONCERNED.
THIS IS AN EXAMPLE OF GENE THERAPY—
THE ADDITION OF GENES TO HUMANS FOR MEDICAL PURPOSES.
THERE ARE SEVERAL STRATEGIES FOR GENE THERAPY
GENE THERAPY IS BASED UPON A COUPLE OF FUNCTIONS.
1. WE KNOW THE GENES INVOLVED IN A DISORDER.
2. WE HAVE A NORMAL COPY OF THAT GENE.
3. WE KNOW WHEN AND WHERE THAT GENE IS NORMALLY EXPRESSED.
4. WE KNOW WHAT WILL HAPPEN WHEN THAT NORMAL GENE GETS EXPRESSED APPROPRIATELY.
ALL THIS KNOWLEDGE IS COMING TO US QUITE RAPIDLY THROUGH GENETIC MEDICINE. THE MORE WE DELVE INTO THE MORE WE LEARN THE HOWS AND WHENS.
GENE THERAPY MUST DO THE FOLLOWING——
1. GET THE GENE INTO THE APPROPRIATE CELLS.
2. GET THE GENE EXPRESSED IN THE CELL.
3. GET THE GENE INTEGRATED INTO THE GENOME OF THE TARGET CELLS.
4. IT MUST HAVE NO BAD SID EFFECTS.
GENE THERAPY HAS BEEN THE STUDY OF NUMEROUS “TRIALS” - EXPERIMENTS, IN VARIOUS HUMANS WITH DISORDERS.
THERE ARE MAJOR STRATEGIES FOR DOING GENE THERAPY, GOING FROM THE GENERAL TO THE PARTICULAR.
STRATEGIES FOR GENE THERAPY
1. GENE AUGMENTATION
2. TARGETED CELL KILLING
3. TARGETED MUTATION CORRECTION
GENE AUGMENTATION IS USED FOR DISEASES, WHERE A FUNCTIONAL GENE PRODUCT IS LOST.
THE IDEA IS TO INTRODUCE EXTRA COPIES OF THE NORMAL ALLELE THAT HAS BEEN MUTATED IN A PERSON. SO THE PROTEIN FUNCTION WILL BE RESTORED AND WORK NORMAL.
EXAMPLE: MUSCULAR DYSTROPHY IS A GOOD ONE.
WE KNOW PEOPLE WITH MD, THEIR MUSCLES LACK THE PROTEIN “DYSTROPHIN” AND NEED IT IN THE GENES.
TARGETED CELL KILLING USES A GENE THAT EITHER PRODUCES A POISEN THAT KILLS CERTAIN CELLS, OR STIMULATES THE IMMUNE SYSTEM TO DO SO.
SO TARGETED CELL KILLING IS USEFUL IN CANCER WHERE IT’S CALLED “SUICIDE CELL KILLING.” A GENE IS PUT INTO A CELL THAT PRODUCES A CHEMICAL KILLER OF THAT CELL. IT GOES INTO THE BODY, ALL OVER THE BODY, WHEN IT GOES INSIDE A CANCER CELL IT PRODUCES A CHEMICAL THAT IS A POISON FOR THAT CELL - THE CANCER CELL DIES.
COULD BE A GENE THAT REACTS WITH THE IMMUNE SYSTEM TO STRIKE AND KILL THE CANCER CELL. A GENE THAT PRODUCES OR MAKES A PROTEIN THAT MAKES “T” CELLS. THE CANCER CELL PUTS UP ITS HAND AND SAYS, “COME KILL ME NOW.”
TARGETED MUTATION CORRECTION REPLACES A BAD ALLELE WITH A GOOD ONE.
WE WANT TO TAKE A BAD ALLELE AND REPLACE IT WITH A GOOD ONE. WE DO NOT WANT JUST TO ADD A GOOD ALLELE; WE WANT TO TAKE THE BAD ONE OUT, RIGHT OUT, AND REPLACE IT WITH A GOOD ONE.
THIS IS GENE SHUFFLING.
WE NEED TO GET THE BAD ALLELE/GENE OUT AND NOT JUST ADD A GOOD ONE, AS THE BAD WILL KEEP WORKING.
THIS IS CALLED “DOMINANT NEGATIVE GENE PRODUCTION.”
IT’S NEGATIVE AND IT’S BAD - DOMINANT - NO MATTER WHAT YOU DO TO ADD GOOD ALLELES. THIS DOMINANT BAD ONE KEEPS MOVING ON. WE HAVE TO GET RID OF IT.
THIS IS THE BAD GAS PEDAL BEING MADE - TURN ME ON - KEEP GOING; YOU HAVE TO DESTROY THAT GENE.
THIS IS TARGETED MUTATION CORRECTION.
IT’S BEEN USED SUCCESSFULLY IN ANIMALS BUT NOT IN HUMANS [THIS WAS UP TO 2007 WHEN THIS LECTURE WAS PRODUCED, NOW IT IS USED IN HUMANS - Keith Hunt].
WE HAVE USED IN HUMANS THE FIRST TWO.
WE HAVE NOT DONE GENE THERAPY ON THE HUMAN EGG AND SPERM. IT WILL GO FIRST TO NON-SEX CELLS.
IT’S A LITTLE AMBITIOUS AT THIS TIME TO USE GENE THERAPY ON HUMAN SEX CELLS.
TWO WAYS TO PROCEED, I ZERO IN MORE.
1. EX VIVO GENE THERAPY - EX = OUTSIDE; VIVO = LIFE.
CELLS FROM TARGET ORGAN [SAY THE LIVER] - TAKEN OUT - NEW GENE IS ADDED TO CELLS IN THE LAB. THE CELLS THEN PUT BACK.
CELLS IN PARTS OF THE BODY, EASY TO REMOVE. CAN NOT DO SO WITH THE BRAIN, BONES AND THE LIKE. CAN’T REMOVE THE BRAIN AND CORRECT IT AND PUT THE BRAIN BACK.
2. IN VIVO GENE THERAPY - IN LIFE [VIVO = LIFE].
VECTOR WITH NEW GENE PUT IN AN INJECTOR NEEDLE AND PUT DIRECTLY INTO THE ORGAN. COULD DO IT SAY FOR THE SKIN, OR MUSCLE, OR ON A SOLID TUMOR.
SEVERAL VECTORS FOR GENE THERAPY——
A VECTOR, PIECE OF CHROMOSOME OR DNA THAT IS RECOGNIZED AND CAN GET INTO THE CELL, SO WE HAVE SOMETHING CARRYING THE NEW GENE INTO THE CELL.
THERE ARE 4 REQUIREMENTS FOR A GOOD VECTOR—-
1. EXPRESSION VECTORS WITH ACTIVE PROMOTERS. WE WANT OUR GENE TO BE EXPRESSED IN OUR THERAPEUTIC SETTING.
2. SMALL IN SIZE SO WE CAN HANDLE IN THE LAB. A SINGLE CELL HUMAN CHROMOSOME HAS A HUNDRED MILLION BASE PAIRS OF DNA - HARD TO CUT AND SPLICE WITH SOMETHING THAT BIG. WE NEED SOMETHING SMALLER.
3. A MARKER GENE, THAT WILL SHOW THE VECTOR GOT IN, INTO THE TARGET TISSUE, BUT HARMLESS - MIGHT BE GREEN COLOR PROTEIN OR SOMETHING LIKE ANTI-BODY RESISTANCE.
4. RESTRICTION ENZYME SITES - CUT DNA OPEN AND INSERT GENE DNA.
GENE VECTOR - VIRUS——
CAN MAKE A GOOD IVECTOR - IT IS A PIECE OF DNA - IT HAS A CODE - IT HAS GENES FOR INFECTING A CELL - WE REMOVE THOSE GENES AND PUT OURS IN. IT WILL SHOOT THEM INTO THE CELL NUCLEUS.
ALL OF THIS COMES BECAUSE OF OUR BIOLOGICAL GENETIC KNOWLEDGE.
THE COMMON GENE THERAPY VIRAL VECTORS——
1. ADENOVIRUS
2. ADENO-ASSOCIATED VIRUS
3. RETROVIRUS
ADENOVIRUS— IS LARGE - SOMETIMES CAUSES COLDS. THE DNA OF THIS VIRUS REMAINS OUTSIDE ITS CELL CHROMOSOMES AFTER INFECTION - NEGATIVE IN THAT THE DAUGHTER CELLS WILL NOT GET IT WHEN CELLS DIVIDE - BUT WILL HAVE TO BE REPEATED.
IT’S EASY TO ISOLATE AND EASY TO WORK WITH.
ADENO-ASSOCIATED VIRUS— IT’S SMALL - DOES NOT HARM HUMANS - IN THIS CASE THE DNA IS SPLICED INTO THE CHROMOSOME, AT A SPECIFIC SITE - WHICH IS CHROMOSOME 19, WITH OUR THERAPEUTIC DNA.
IT’S SMALL SO CAN’T PUT IN A LARGE NUMBER OF GENES BUT IT IS WIDELY USED.
RETROVIRUS— THEY HAVE RNA AS WELL AS DNA - THEY SPLICE IN THEIR DNA ANYWHERE ALONG THE GENOME - WELL AS 98% OF GENOME IS NOT GOING TO DO HARM, GUESS THAT’S OKAY. BUT WHAT IF YOU GO TO THAT 2% AND DISRUPT A FUNCTIONAL GENE, THAT’S NOT GOOD AT ALL. SO WE RUN A RISK SOMETIMES WHEN WE USE IT— RETROVIRUS GENE THERAPY.
SOME DNA AND RNA VIRUSES HAVE LED TO SUCCESSES [UP TO 2007 WHEN THESE LECTURE WERE DONE - Keith Hunt]
GOOD ON PAPER - GOOD IN MICE - BUT HUMANS, IT GETS MORE COMPLICATED.
SOME OF THE FAILURES IN HUMANS ARE THE FOLLOWING——
1. GENE THERAPY DOESN’T LAST LONG - TARGET CELLS OFTEN DIVIDE RAPIDLY - THE GENE DOESN’T GET INTO ALL THE CELLS - AND BE FAR OUT-NUMBERED SOON - SO SMALL MINORITY GET THE DNA GENE THERAPY.
2. PATIENT MAY MOUNT AN IMMUNE RESPONSE TO THE VECTOR.
ALL GENE THERAPY WAS STOPPED FOR A WHILE IN 1999 - A BOY WAS GIVEN GENE THERAPY AND DIED BY A MASSIVE IMMUNE RESPONSE AGAINST THE GENE VECTOR. IT WAS NOT EXPECTED AND NEVER FULLY EXPLAINED.
3. MANY DISEASES CANNOT BE CURED WITH A SINGLE GENE THERAPY.
WE HAVE TO KNOW WHAT THE GENE IS, THAT IS CAUSING THE PROBLEM - MULTITUDE OF GENES CAUSE HEART PROBLEMS. DIABETES #1 - MANY GENES INVOLVED. CANCER, ALZHEIMERS, AND OTHERS, HAVE MANY GENES INVOLVED.
NOBODY GIVES MASSIVE GENE THERAPY - NEVER DONE IN CLINICAL TRIALS - WAY TOO COMPLICATED.
SEVERE COMBINED IMMUNODEFICIENCY
THE IMMUNE SYSTEM DOES NOT WORK PERIOD!
THE FAMOUS “BUBBLE BOY” - KEPT ISOLATED TO EVERYTHING - LIVED IN A BUBBLE CONTAINER. THEY NEED BLOOD TRANSFUSIONS - WAS GIVEN ONE FROM HIS SISTER’S BLOOD - IT CONTAINED AN INFECTION NO ONE KNEW WAS THERE - THE BUBBLE BOY DIED - NO IMMUNE SYSTEM TO FIGHT IT OFF.
SCIENCE THEN TRIED GETTING THE PROTEIN AND GIVING IT THROUGH GENE THERAPY; IT WAS MODERATELY SUCCESSFUL.
[THERE ARE VARIATIONS OF IMMUNE DEFICIENCY PROBLEMS. WHEN I LIVED IN OSHAWA, ONTARIO, ONE YOUNG LADY CAME DOWN WITH AN IMMUNE DISEASE. SHE HAD NO IMMUNE SYSTEM TO FIGHT OFF PAINT, MAN MADE MATERIALS, AND ALL THE STUFF OUTSIDE. EVENTUALLY SHE HAD TO LIVE IN A COUNTRY HOUSE, WITH NO MAN MADE MATERIALS, BUT HARDWOOD FLOORS WAS OKAY. THE HOUSE HAD TO BE IN AN AREA WHERE FARMERS DID NOT USE ANY MAN MADE CHEMICALS. IN THIS ENVIRONMENT SHE WAS FINALLY ABLE TO TAKE WALKS OUTSIDE. I LEFT OSHAWA SHORTLY AFTER ALL THIS WAS ON THE NEWS, SO NEVER DID FIND OUT HOW SHE PROGRESSED FROM THAT SITUATION - Keith Hunt]
IN THE 1990s EX-VIVO GENE THERAPY WAS TRIED.
PATIENTS WHITE BLOOD CELLS WERE REMOVED; THE NORMAL ADA GENE VECTOR WAS PUT IN. CELLS THEN PUT BACK INTO THE PATIENT, HOPING TO DIVIDE AND FORM GOOD WHITE BLOOD CELLS. AND THEY DID - THE PATIENTS NEED FOR ADA WAS REDUCED - MODERATE SUCCESS. IT HAS BEEN REPEATED ON OTHER PATIENTS.
FAMILIAL HYPERCHOLESTOROLOMIA
FAMILY GROUP OF HIGH BLOOD CHOLESTEROL.
THE PATIENT CANNOT REMOVE CHOLESTEROL FROM THE BLOOD WHEN HE/SHE EASTS.
A PROTEIN THAT DOES THIS IS NON-FUNCTIONAL TO SEND IT TO THE LIVER TO BREAK DOWN. INSTEAD THE PROTEIN IS NOT THERE AND SO CHOLESTEROL STAYS IN THE BLOOD.
FIRST, A PIECE OF LIVER WAS REMOVED, CELLS SEPARATED IN THE LAB. A GENE FOR THIS RECEPTOR PROTEIN WAS ADDED TO THE NORMAL VECTOR, THEN PUT BACK IN PROTEIN. LIVER IS VERY PLASTIC AND SO ALL FUSSED TOGETHER. THE LIVER MADE ENOUGH RECEPTOR PROTEIN TO REMOVE CHOLESTEROL FROM THE BLOOD, THE PATIENTS CHOLESTEROL WENT DOWN. MODERATELY SUCCESSFUL.
ORNITHINE TRANSCARBANYLASE DEFICIENCY
PATIENTS CANNOT BREAK DOWN AMONIA WHEN BROKEN DOWN BY AMINO ACIDS WHEN DIGESTED. IT IS VERY TOXIC TO HUMANS, WHO USUALLY DIE WITHIN A YEAR OF BIRTH. MILDER CASES CAN LIVE FOR YEARS ON A SPECIAL DIET WITH AMONIA REDUCING DRUGS.
IN VIVO GENE THERAPY WAS DONE WITH A VECTOR NORMAL GENE INJECTED INTO THE ARTERY LEADING TO THE LIVER. THE VIRUS INFECTED THE LIVER CELLS - THE LIVER DID EXPRESS THE ENZYMES LOWERING AMONIA LEVELS. IT HAS ONLY BEEN DONE ON MIDER CASES [AS OF 2007].
CANCER
GENE THERAPY IS USED THE MOST ON CANCER.
TWO APPROACHES
1. IN VIVO - LUNG CANCER WITH P53 NOT FUNCTIONING DUE AS WE HAVE SEEN TO SMOKING. A GOOD P53 IS INJECTED AND PATIENTS HAVE LIVED LONGER.
2. EX VIVO - TARGET KILLING, BY THE REMOVAL OF WHITE BLOOD CELLS. “T” CELLS REMOVED AND THE ADDITION OF T CELL RECEPTOR - THEY HOME IN AND BIND TO AND KILL CANCER CELL TUMOR. SUCCESSFUL FOR MELANOMA.
MUSCLES
GRADUALLY STRENGTH GOES DOWN - FROM AGE 30 IT DECREASES UP TO 30% AS WE GO INTO OLD AGE. [AH YES THE PHRASE “THE STRENGTH OF YOUTH” IS A FACT OF LIFE - Keith Hunt]
THE DISABLED - NOT BEING ABLE TO USE MUSCLES THE BODY DOES NOT REPAIR MUSCLES NOT USED.
LEE SWEENEY AT THE UNIVERSITY OF PENNSYLVANIA IS STUDYING MUSCLE REPARE - WHAT GOES INTO MUSCLES AND THEIR REPARE MECHANISM.
HE’S FOUND TWO GENES INVOLVED AND THE PROTEIN CODED FOR THEM.
1. IGF-1 STIMULATES NEARBY CELLS TO PROMOTE MUSCLE BUILDUP.
2. MYOSTATIN STIMULATES MUSCLE BREAKDOWN.
SO HE’S BEEN DOING GENE THERAPY AND HE’S DOING IT ON MICE FIRST.
BY ADDING THE GENE FOR IGF-1 THE BUILDUP PROTEIN, TARGETED TO THE MUSCLES IN MICE BY GENETIC MODIFIED OR GENE THERAPY; AND LOW AND BEHOLD MUSCLES GOT BIGGER. THEN HE MAKES ANOTHER VECTOR AND IN IT WHAT BLOCKS MYOSTATIN. SO NO BREAKDOWN AND HENCE BIGGER MUSCLES STILL.
CLINICAL TRIALS ARE PLANNED ON PATIENTS WITH MUSCLE WASTING [AS OF 2007]
BUT WILL ATHLETES GET TO IT FIRST?
MORE CONCERN FOR PRO ATHLETIC COMPETITIONS SUCH AS THE OLYMPICS.
GENE THERAPY HAS POTENTIAL!
BUT SO DOES CLONING AND STEM CELLS.
End Quote
………………………..
SO WE HAVE SEEN IN THESE LECTURE STUDIES THE INTRICATE AND MIND-BENDING DETAILS OF THE HUMAN DNA AND MANY THINGS RELATED TO IT.
THE MORE MAN DELVES DEEPER INTO JUST ABOUT ANYTHING WE DELVE INTO TO LEARN ALL ABOUT IT, THE MORE AMAZING IT BECOMES.
TO THINK WE CAN JUST BRUSH THIS OFF AS MERE “EVOLUTION” AS IT SUPPOSEDLY CAME FROM A SINGLE CELL SOMEWHERE IN THE SEA MILLIONS OF YEARS AGO, TO DIVIDE AND EVENTUALLY DEVELOP INTO HUMAN BEINGS AS WE ARE TODAY OVER MILLIONS OF YEARS, IS TO ME THE SILLIEST AND CRAZIEST IDEA, FROM WAY OUT PLANET PLUTO IDEAS AND BEYOND.
THE BIBLE SAYS WE ARE WONDERFULLY MADE.
FOR A NORMAL HEALTHY PERSON TO LIVE IN A NORMAL HEALTHY PHYSICAL BODY, TAKES MILLIONS OF TINY THINGS ALL WORKING CORRECTLY AND IN HARMONY TOGETHER.
TRULY THE INNER WORKING OF THE HUMAN BODY, PROVES A MASTER MIND IS BEHIND IT ALL.
AND THAT IS JUST LOOKING AT THE HUMAN BODY; WHEN YOU LOOK AT ALL THE OTHER CREATED THINGS ON THIS PLUE PLANET, I SUBMIT TO YOU THERE WAS A MASTER MIND BEHIND IT ALL.
AS A KID OF 4, 5, 6, AND 7, I WAS FASCINATED BY ALL I COULD SEE AROUND ME, FROM THE LADY-BUG, TO THE CATERPILLAR, TO THE BUTTERFLY, TO THE BIRDS, TO CATS AND DOGS, TO THE HORSE, TO THE TREES, TO THE RIVERS, TO THE GEEN GRASS AND ETC.
MY FATHER SENT ME AT AGE 7 TO A CHURCH OF ENGLAND SCHOOL. THE VERY FIRST DAY WE WERE GIVEN A BIBLE. WE WERE TOLD TO OPEN IT TO PAGE 1. THE TEACHER READ— “IN THE BEGINNING, GOD CREATED THE HEAVENS AND THE EARTH…..”—— SHE CONTINUED TO READ…..
WOW, IT WAS LIKE A LIGHT SWITCH IN MY HEAD WAS TURNED ON—— AH THAT IS IT I SAID TO MYSELF; A BEING CALLED “GOD” MADE EVERYTHING I COULD SEE; YES THAT IS THE ANSWER I TOLD MYSELF—- THERE IS A GOD BEING BEHIND IT ALL.
I BELIEVED IN GOD FROM THAT DAY FORWARD.
I LOOK BACK NOW, AND I SEE IT WAS GOD’S HAND IN HAVING MY DAD SEND ME TO A CHURCH OF ENGLAND SCHOOL.
THE FIRST HALF HOUR OF EACH SCHOOL DAY WAS SPENT IN THE BIBLE.
I LOVED IT, I ATE IT UP AS THEY SAY.
IT WAS A GREAT AND WONDERFUL FOUNDATION. IT SERVED ME WELL AS I BECAME AN ADULT, AND GOD DECIDED TO REVEAL MORE AND MORE TRUTHS OF HIS WORD TO ME OVER DECADES.
MY WEBSITE IS THE CULMINATION OF ALL THOSE DECADES, OF READING AND STUDYING, SOMETIMES DAYS, WEEKS, MONTHS, YEARS, ON A BIBLE SUBJECT [MY BOOK ON “DIVORCE AND RE-MARRIAGE” TOOK ME 4 YEARS TO COMPLETE].
I AM BLESSED, THE LORD GAVE ME A CLEAR MIND, TO ACKNOWLEDGE THAT OTHERS HAVE WRITTEN A STUDY OR BOOK, THAT IS THE TRUTH OF THE MATTER ON THAT SUBJECT. MANY ARE ON MY WEBSITE, AND MY BLOG.
I HOPE THIS STUDY OF GENETICS - DNA - HAS BEEN AN EYE OPENER AND BLESSING TO YOU.
THIS SPACE-AGE SCIENCE, KNOWING ALL ABOUT GENES AND CELLS AND DNA, IS WHY SCIENTISTS AROUND THE WORLD HAVE BEEN ABLE TO BRING IN VACCINES AGAINST COVID, IN UNDER A YEAR. THEY ARE USING ALL THAT THE HUMAN BODY IS, AND HOW OUR CELLS AND DNA AND OUR IMMUNE SYSTEM WORK, WHEN AN INVADER FROM THE OUTSIDE, THAT IS NOT A PART OF US, ATTACKS US.
THERE IS NOTHING IN THESE VACCINES THAT ATTACK OUR DNA OR IMMUNE SYSTEM---- THEY WORK WITH OUR BODY, NOT AGAINST IT, TO HELP STIMULATE THE PRODUCTIONS OF T AND R CELLS VIA PROTEINS TO AMASS A FIGHTING ARMY QUICKLY, TO DESTROY OR GREATLY WEAKEN THE INVADERS FROM OUTSIDE.
THAT IS THE SCIENCE BEHIND THE VACCINES THAT CAN HELP OUR OWN IMMUNE SYSTEM BATTLE AND WIN AGAINST THE COVID VIRUS ENEMY.
Keith Hunt
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