History of Biotech and Biotech Applicationsfaculty.mc3.edu/lrehfuss/bit120/history.pdf · History of Biotech and Biotech Applications BIT 120 Source for History Information: ... ray

History of Biotech and History of Biotech and Biotech ApplicationsBiotech Applications

BIT 120BIT 120Source for History Information:Source for History Information:

www.accessexcellence.orgwww.accessexcellence.org

History of BiotechnologyHistory of Biotechnology

nn The term "The term "biotechnologybiotechnology" was coined in 1919 by Karl " was coined in 1919 by Karl ErekyEreky, an Hungarian engineer, an Hungarian engineer

nn Traditional biotechnology has been used for thousands Traditional biotechnology has been used for thousands of years to produce improved food and health care of years to produce improved food and health care products. Today, modern biotechnology enables us to products. Today, modern biotechnology enables us to develop improved products more safely and more develop improved products more safely and more rapidly than ever before. rapidly than ever before.

nn Biotechnology in one form or another has flourished Biotechnology in one form or another has flourished since prehistoric times. since prehistoric times.

ExamplesExamples

nn Examples:Examples:nn they could plant their own crops and breed their they could plant their own crops and breed their

own animals, they learned to use biotechnology. own animals, they learned to use biotechnology. nn The discovery that fruit juices fermented into wine, The discovery that fruit juices fermented into wine,

or that milk could be converted into cheese or or that milk could be converted into cheese or yogurt, or that beer could be made by fermenting yogurt, or that beer could be made by fermenting solutions of malt and hops began the study of solutions of malt and hops began the study of biotechnologybiotechnology

Examples cont’dExamples cont’d

nn When the first bakers found that they could make a When the first bakers found that they could make a soft, spongy bread rather than a firm, thin cracker, soft, spongy bread rather than a firm, thin cracker, they were acting as fledgling biotechnologists. they were acting as fledgling biotechnologists.

nn The first animal breeders, realizing that different The first animal breeders, realizing that different physical traits could be either magnified or lost by physical traits could be either magnified or lost by mating appropriate pairs of animals, engaged in the mating appropriate pairs of animals, engaged in the manipulations of biotechnology.manipulations of biotechnology.

DefinitionDefinitionnn Definition:Definition: What then is biotechnology? the term What then is biotechnology? the term

"biotechnology" refers to the use of living organisms or their "biotechnology" refers to the use of living organisms or their products to modify human health and the humanproducts to modify human health and the human environment.environment.

nn Other definitions: 1. Other definitions: 1. •Biotechnologists use engineering and •Biotechnologists use engineering and science to create new products from biologically based raw science to create new products from biologically based raw materials, such as vaccines or foods. They also develop factory materials, such as vaccines or foods. They also develop factory processes to reduce pollution or treat waste products.processes to reduce pollution or treat waste products.

nn ••2.2. Biotechnology uses living cells and materials produced by Biotechnology uses living cells and materials produced by cells to create pharmaceutical, diagnostic, agricultural, cells to create pharmaceutical, diagnostic, agricultural, environmental, and other products to benefit society. environmental, and other products to benefit society.

Periods of Biotechnology History:Periods of Biotechnology History:

nn PrePre-- 1800: Early applications and speculation1800: Early applications and speculationnn 18001800--1900: Significant advances in basic 1900: Significant advances in basic

understandingunderstandingnn 19001900--1953: Genetics1953: Geneticsnn 19531953-- 1976: DNA research, science explodes1976: DNA research, science explodesnn 19771977-- present: modern biotechnologypresent: modern biotechnology

Biotechnology Time LinesBiotechnology Time Linesnn 6000 BC6000 BCnn Yeast was used to make beer by Sumerians and Babylonians. Yeast was used to make beer by Sumerians and Babylonians. nn 4000 BC4000 BCnn The Egyptians discovered how to bake leavened bread using The Egyptians discovered how to bake leavened bread using

yeast. yeast. nn 420 BC420 BCnn Socrates (470? Socrates (470? -- 399 BC), the Greek philosopher, speculated on 399 BC), the Greek philosopher, speculated on

why children don't always resemble their parents. why children don't always resemble their parents. nn 320 BC320 BCnn Aristotle (384 Aristotle (384 -- 322 BC), told his students that all inheritance 322 BC), told his students that all inheritance

comes from the father. comes from the father.

Biotechnology Time LinesBiotechnology Time Linesnn 1000 AD1000 ADnn Hindus observed that certain diseases may "run in the family." Hindus observed that certain diseases may "run in the family."

Spontaneous GenerationSpontaneous Generation is the dominant explanation that is the dominant explanation that organisms arise from nonorganisms arise from non--living matter. Maggots, for example, living matter. Maggots, for example, were supposed to arise from horsehair. were supposed to arise from horsehair.

nn 1630 AD1630 ADnn William HarveyWilliam Harvey concluded that plants and animals alike concluded that plants and animals alike

reproduce in a sexual manner:reproduce in a sexual manner:––egg isolated in 1800’segg isolated in 1800’snn 16601660--1675 AD1675 ADnn Marcello Marcello MalpighiMalpighi (1628(1628--1694) in this period used a microscope 1694) in this period used a microscope

to study blood circulation in capillaries, described the nervousto study blood circulation in capillaries, described the nervoussystem as bundles of fibers connected to the brain by the spinalsystem as bundles of fibers connected to the brain by the spinalcord,. cord,.

Biotechnology Time LinesBiotechnology Time Linesnn 1673 AD1673 ADnn Anton van Leeuwenhoek (1632 Anton van Leeuwenhoek (1632 -- 1723), He was the first scientist 1723), He was the first scientist

to describe protozoa and bacteria and to recognize that such to describe protozoa and bacteria and to recognize that such microorganisms might play a role in fermentation. microorganisms might play a role in fermentation.

nn 17011701nn GiacomoGiacomo PylariniPylarini in in ConstantiopleConstantiople practiced "inoculation"practiced "inoculation"----

intentionally giving children smallpox to prevent a serious caseintentionally giving children smallpox to prevent a serious caselater in life. Inoculation will compete with "vaccination"later in life. Inoculation will compete with "vaccination"----an an alternative method that uses cowpox rather than smallpox as the alternative method that uses cowpox rather than smallpox as the protecting treatmentprotecting treatment----for a century. for a century.

nn Gave too much and some children diedGave too much and some children died

Biotechnology Time LinesBiotechnology Time Linesnn 1809 1809 nn Nicolas Nicolas AppertAppert devised a technique using heat to can and devised a technique using heat to can and

sterilize foodsterilize foodnn 18271827nn The worldwide search for the elusive mammalian egg ended with The worldwide search for the elusive mammalian egg ended with

the first observation of canine eggs. the first observation of canine eggs. Remember 1630 and Remember 1630 and William HarveyWilliam Harvey

nn 18501850nn ONE OF MY FAVORITES ONE OF MY FAVORITES IgnazIgnaz SemmelweisSemmelweis used used

epidemiological observations to propose the hypothesis that epidemiological observations to propose the hypothesis that childbed fever can be spread from mother to mother by childbed fever can be spread from mother to mother by physiciansphysicians. He tested the hypothesis by having physicians wash . He tested the hypothesis by having physicians wash their hands after examining each patient. He became despised by their hands after examining each patient. He became despised by the medical profession and lost his job. the medical profession and lost his job.

Biotechnology Time LinesBiotechnology Time Linesnn 1856 1856 nn Karl Ludwig discovered a technique for keeping animal organs Karl Ludwig discovered a technique for keeping animal organs

alive outside the body, by pumping blood through them. alive outside the body, by pumping blood through them. nn In contrast to the ideas of In contrast to the ideas of JustisJustis LiebigLiebig, , Louis PasteurLouis Pasteur (1822 (1822 --

1895)1895) asserted that microbes are responsible for fermentation. asserted that microbes are responsible for fermentation. 18591859

nn Charles Darwin (1809 Charles Darwin (1809 -- 18821882) hypothesized that animal ) hypothesized that animal populations adapt their forms over time to best exploit the populations adapt their forms over time to best exploit the environment, a process he referred to as "natural selection." Asenvironment, a process he referred to as "natural selection." Ashe traveled in the Galapagos Islands, he traveled in the Galapagos Islands, he observed how the he observed how the finch's beaks on each island were adaptedfinch's beaks on each island were adapted to their food to their food sources. sources.

Biotechnology Time LinesBiotechnology Time Lines

nn 18631863nn Louis PasteurLouis Pasteur invented the process of pasteurization, invented the process of pasteurization,

heating wine sufficiently to inactivate microbes (that heating wine sufficiently to inactivate microbes (that would otherwise turn the "would otherwise turn the "vinvin" to "" to "vinvin aigreaigre" or "sour " or "sour wine") while at the same time not ruining the flavor of wine") while at the same time not ruining the flavor of the wine. the wine.

nn Anton de Anton de BaryBary proved that a fungus causes potato proved that a fungus causes potato blight. A challenge for scientists during this period was blight. A challenge for scientists during this period was to discern whether a microbe was the cause of, or the to discern whether a microbe was the cause of, or the result of, a disease. result of, a disease.

Biotechnology Time LinesBiotechnology Time Linesnn 18651865nn Gregor MendelGregor Mendel (1822 (1822 -- 1884), an Augustinian monk, presented 1884), an Augustinian monk, presented

his laws of heredity to the Natural Science Society in his laws of heredity to the Natural Science Society in BrunnBrunn, , Austria. Mendel proposed that invisible internal units of Austria. Mendel proposed that invisible internal units of information account for observable traits, and that these information account for observable traits, and that these "factors" "factors" -- which later became known as genes which later became known as genes -- are passed from are passed from one generation to the next. Mendel's work remained unnoticed, one generation to the next. Mendel's work remained unnoticed, languishing in the shadow of Darwin's more sensational languishing in the shadow of Darwin's more sensational publication from five years earlier, until 1900, when Hugo de publication from five years earlier, until 1900, when Hugo de VriesVries, Erich Von , Erich Von TschermakTschermak, and Carl , and Carl CorrensCorrens published published research corroborating Mendel's mechanism of heredity. research corroborating Mendel's mechanism of heredity.

nn ..


nn PasteurPasteur investigated silkworm disease and investigated silkworm disease and established that diseases can be transmitted from established that diseases can be transmitted from one animal to another. one animal to another.

nn Joseph Lister began using disinfectants such as Joseph Lister began using disinfectants such as phenol (=carbolic acid) in wound care and phenol (=carbolic acid) in wound care and surgery as surgery as PasteurPasteur developed the germ theory of developed the germ theory of diseasedisease


nn 18681868nn DavaineDavaine used heat treatment to cure a plant of used heat treatment to cure a plant of

bacterial infection. bacterial infection. nn FredrichFredrich MiescherMiescher, a Swiss biologist, successfully , a Swiss biologist, successfully

isolated isolated nucleinnuclein, a compound that includes , a compound that includes nucleic acid, from pus cells obtained from nucleic acid, from pus cells obtained from discarded bandages. discarded bandages.

nn 18701870nn W. W. FlemmingFlemming discovered mitosis. discovered mitosis.

Biotechnology Time LinesBiotechnology Time Linesnn 18711871nn DNA was isolated from the sperm of trout found inDNA was isolated from the sperm of trout found in the the

Rhine River. Rhine River. nn 18731873--66nn Robert Koch investigated anthrax and developed techniques to Robert Koch investigated anthrax and developed techniques to

view, grow, and stain organisms. He then photographed them, view, grow, and stain organisms. He then photographed them, aided by Gram, Cohn, and aided by Gram, Cohn, and WeigartWeigart. .

nn 18801880nn Studying fowl cholera, Studying fowl cholera, PasteurPasteur published his work on published his work on

"attenuated" or weakened strains of organisms that could not "attenuated" or weakened strains of organisms that could not cause disease but protected against severe forms of the same cause disease but protected against severe forms of the same disease. disease.


nn 1881 ANTRAX1881 ANTRAXnn Robert Koch described bacterial colonies growing on Robert Koch described bacterial colonies growing on

potato slices, on gelatin medium, and on agar medium. potato slices, on gelatin medium, and on agar medium. Nutrient agar became a standard tool for obtaining pure Nutrient agar became a standard tool for obtaining pure cultures and for identifying genetic mutants. This is cultures and for identifying genetic mutants. This is considered by T.D. Brock to be the single most considered by T.D. Brock to be the single most important discovery in the rise of microbiology. important discovery in the rise of microbiology.

nn Pasteur used attenuation to develop vaccines against Pasteur used attenuation to develop vaccines against the bacterial pathogens of fowl cholera and anthrax; the bacterial pathogens of fowl cholera and anthrax; this was a founding moment in immunology and this was a founding moment in immunology and opened new areas in the field of preventive medicine. opened new areas in the field of preventive medicine.

Biotechnology Time LinesBiotechnology Time Linesnn 18841884nn ROBERT KOCH STATED HIS "POSTULATES" FOR ROBERT KOCH STATED HIS "POSTULATES" FOR

TESTING WHETHER A MICROBE IS THE CAUSAL TESTING WHETHER A MICROBE IS THE CAUSAL AGENT OF A DISEASEAGENT OF A DISEASE. .

nn PasteurPasteur developed a developed a rabies vaccinerabies vaccine. . nn Christian Gram described the differential staining technique forChristian Gram described the differential staining technique for

bacteria known as the Gram stain. bacteria known as the Gram stain. nn Gregor MendelGregor Mendel died after 41 years of meticulously studying the died after 41 years of meticulously studying the

heredity "factors" of pea plants. Having received no scientific heredity "factors" of pea plants. Having received no scientific acclaim during his lifetime, he said not long before his death, acclaim during his lifetime, he said not long before his death, "My time will come." "My time will come."


nn 1900 1900 -- 1953 1953 -- Converging on DNAConverging on DNAnn 1900 MENDEL’S WORK FINALLY TOOK ON 1900 MENDEL’S WORK FINALLY TOOK ON

IMPORTANCEIMPORTANCEnn The science of genetics was finally born when The science of genetics was finally born when Mendel'sMendel's work work

was rediscovered by three scientists was rediscovered by three scientists -- Hugo Hugo DeVriesDeVries, Erich Von , Erich Von TschermakTschermak, and Carl , and Carl CorrensCorrens -- each one independently each one independently researching scientific literature for precedents to their own researching scientific literature for precedents to their own "original" work. "original" work.

nn 1902 HUMAN GENETICS BORN1902 HUMAN GENETICS BORNnn Walter Walter StanboroughStanborough Sutton stated that chromosomes are paired Sutton stated that chromosomes are paired

and may be the carriers of heredity. He suggested that Mendel's and may be the carriers of heredity. He suggested that Mendel's "factors" are located on chromosomes. "factors" are located on chromosomes.

Biotechnology Time LinesBiotechnology Time Linesnn 1905 X AND Y CHROMOSOMES RELATED TO 1905 X AND Y CHROMOSOMES RELATED TO

GENDERGENDERnn Edmund Wilson and Nellie Stevens proposed the idea that Edmund Wilson and Nellie Stevens proposed the idea that

separate X and Y chromosomes determine sex. They showed separate X and Y chromosomes determine sex. They showed that a single Y chromosome determines maleness, and two that a single Y chromosome determines maleness, and two copies of the X chromosome determine femaleness. copies of the X chromosome determine femaleness.

nn 19051905--19081908nn William William BatesonBateson and Reginald and Reginald CrudellCrudell Punnett, along with Punnett, along with

others, demonstrated that some genes modify the action of other others, demonstrated that some genes modify the action of other genes. genes.

nn 19061906nn Paul Paul ErlichErlich investigated investigated atoxylatoxyl compounds and discovered the compounds and discovered the

beneficial properties of beneficial properties of SalvarsanSalvarsan -- the first chemotherapeutic the first chemotherapeutic agent. agent.

Biotechnology Time LinesBiotechnology Time Linesnn 19071907nn Thomas Hunt Morgan began his work with fruit flies that will Thomas Hunt Morgan began his work with fruit flies that will

prove that chromosomes have a definite function in heredity, prove that chromosomes have a definite function in heredity, establish mutation theory, and lead to a fundamental establish mutation theory, and lead to a fundamental understanding of the mechanisms of heredity. understanding of the mechanisms of heredity.

nn 1909 MENDEL’S LAWS TO ANIMALS1909 MENDEL’S LAWS TO ANIMALSnn Wilhelm Wilhelm JohannsenJohannsen coined the terms 'gene' to describe the coined the terms 'gene' to describe the

carrier of heredity; 'genotype' to describe the genetic constitucarrier of heredity; 'genotype' to describe the genetic constitution tion of an organism; and 'phenotype' to describe the actual organism,of an organism; and 'phenotype' to describe the actual organism,which results from a combination of the genotype and the which results from a combination of the genotype and the various environmental factors. various environmental factors.

Biotechnology Time LinesBiotechnology Time Linesnn 1910 BASIS OF MODERN GENETICS1910 BASIS OF MODERN GENETICSnn Thomas Hunt Morgan proved that genes are carried on Thomas Hunt Morgan proved that genes are carried on

chromosomes, establishing the basis of modern geneticschromosomes, establishing the basis of modern genetics. . With his coWith his co--workers, he pinpointed the location of various fruit workers, he pinpointed the location of various fruit fly genes on chromosomes, establishing the use of Drosophila fly genes on chromosomes, establishing the use of Drosophila fruit flies to study heredity.. fruit flies to study heredity..

nn 1911 1911 nn Thomas Hunt Morgan explained the separation of certain Thomas Hunt Morgan explained the separation of certain

inherited characteristics that are usually linked as caused by tinherited characteristics that are usually linked as caused by the he breaking of chromosomes sometimes during the process of cell breaking of chromosomes sometimes during the process of cell division. Morgan began to map the positions of genes on division. Morgan began to map the positions of genes on chromosomes of the fruit fly. chromosomes of the fruit fly.

Biotechnology Time LinesBiotechnology Time Linesnn 19121912nn Lawrence Bragg discovered that XLawrence Bragg discovered that X--rays can be used to rays can be used to

study the molecular structure of simplestudy the molecular structure of simple crystalline substances. crystalline substances. 19181918

nn Herbert M. Evans found (incorrectly) that human cells Herbert M. Evans found (incorrectly) that human cells contain 48 chromosomescontain 48 chromosomes. .

nn 1924 EUGENICS IN THE UNITED STATES1924 EUGENICS IN THE UNITED STATESnn Politicians encouraged by the eugenics movement passed the Politicians encouraged by the eugenics movement passed the

U.S. Immigration Act of 1924, limiting the influx of poorly U.S. Immigration Act of 1924, limiting the influx of poorly educated immigrants from Southern and Eastern Europe on the educated immigrants from Southern and Eastern Europe on the grounds of suspected genetic inferiority. grounds of suspected genetic inferiority.


nn 19261926nn Thomas Hunt Morgan published 'The theory of the Thomas Hunt Morgan published 'The theory of the

gene', the culmination of work on the physical basis for gene', the culmination of work on the physical basis for Mendelian genetics based on breeding studies and Mendelian genetics based on breeding studies and optical microscopy. optical microscopy.

nn Hermann Muller discovered that XHermann Muller discovered that X--rays induce rays induce genetic mutations in fruit flies 1,500 times more genetic mutations in fruit flies 1,500 times more quickly than under normal circumstances.quickly than under normal circumstances. This This discovery provided researchers with a way to induce discovery provided researchers with a way to induce mutations, an important tool for discovering what mutations, an important tool for discovering what genes do on their own. genes do on their own.


nn 19281928nn Fredrick Griffiths noticed that a rough type of Fredrick Griffiths noticed that a rough type of

bacterium changed to a smooth type when an unknown bacterium changed to a smooth type when an unknown "transforming principle" from the smooth type was "transforming principle" from the smooth type was present. Sixteen years later, Oswald Avery identified present. Sixteen years later, Oswald Avery identified that "transforming principle" as DNA. that "transforming principle" as DNA.

nn Alexander Fleming noticed that all the bacteria in a Alexander Fleming noticed that all the bacteria in a radius surrounding a bit of mold in a radius surrounding a bit of mold in a petriepetrie dish had dish had dieddied. The age of penicillin thus began, although it . The age of penicillin thus began, although it would be almost 15 years before it was made would be almost 15 years before it was made available to the community for medicinal use.available to the community for medicinal use.


nn 19381938nn Proteins and DNA were studied in various labs with XProteins and DNA were studied in various labs with X--

ray crystallography. ray crystallography. nn The term "molecular biology" was coined. The term "molecular biology" was coined. nn 1941 ONE GENE ONE ENZYME1941 ONE GENE ONE ENZYMEnn George Beadle and Edward Tatum experimented with George Beadle and Edward Tatum experimented with

NeurosporaNeurospora, a mold that grows on bread in the tropics, , a mold that grows on bread in the tropics, developing the "onedeveloping the "one--genegene--oneone--enzyme" hypothesis: enzyme" hypothesis: each gene is translated into an enzyme to perform tasks each gene is translated into an enzyme to perform tasks within an organism. within an organism.


nn 19431943nn The Rockefeller Foundation, collaborating with the The Rockefeller Foundation, collaborating with the

Mexican government, initiated the Mexican Agricultural Mexican government, initiated the Mexican Agricultural Program. This was the first use of plant breeding as Program. This was the first use of plant breeding as foreign aid. foreign aid.

nn 19431943--19531953nn Cortisone was first manufactured in large amounts. Cortisone was first manufactured in large amounts.

KIND OF A FIRST BIOTECH PRODUCTKIND OF A FIRST BIOTECH PRODUCTnn 19441944nn WaksmanWaksman isolated isolated streptomycinstreptomycin, an effective antibiotic , an effective antibiotic

for TB. for TB.


nn 19451945nn The U.N. Food and Agriculture Organization The U.N. Food and Agriculture Organization (FAO)(FAO)

was formed in Quebec, Canada. was formed in Quebec, Canada. nn 1945 1945 -- 19501950nn CELLS GROWN IN LAB CELLS GROWN IN LAB Isolated animal cell Isolated animal cell

cultures were grown in laboratories. cultures were grown in laboratories. nn 19471947nn Barbara McClintockBarbara McClintock first reported on "transposable first reported on "transposable

elements" elements" -- known today as "jumping genes." The known today as "jumping genes." The scientific community failed to appreciate the scientific community failed to appreciate the significance of her discovery at the time. significance of her discovery at the time.


nn 19501950nn Erwin Erwin ChargaffChargaff found that in DNA the amounts found that in DNA the amounts

of adenine and thymine are about the same, as of adenine and thymine are about the same, as are the amounts of guanine and cytosine. These are the amounts of guanine and cytosine. These relationships are later known as relationships are later known as "Chargaff's "Chargaff's Rules" Rules" and serve as a key principle for Watson and serve as a key principle for Watson and Crick in assessing various models for the and Crick in assessing various models for the structure of DNA. structure of DNA. AT ABOUT THE SAME; AT ABOUT THE SAME; GC ABOUT THE SAMEGC ABOUT THE SAME


nn 1953 1953 -- 1976: Expanding the Boundaries of DNA 1976: Expanding the Boundaries of DNA ResearchResearch

nn The discovery of the structure of DNA resulted in an The discovery of the structure of DNA resulted in an explosion of research in molecular biology and genetics, explosion of research in molecular biology and genetics, paving the way for the biotechnology revolution. paving the way for the biotechnology revolution.

nn 19531953nn Nature magazine published Nature magazine published James Watson'sJames Watson's and Francis and Francis

Crick's manuscript describing the double helix structure Crick's manuscript describing the double helix structure of DNA. of DNA.


nn 19531953nn GeyGey developed the HeLa human cell line. developed the HeLa human cell line.

HENRIETTA LACKSHENRIETTA LACKS-- DIED IN 1951 OF DIED IN 1951 OF CERVICAL CANCERCERVICAL CANCER-- MOTHER OF 5MOTHER OF 5--HER CELLS FIRST SHOWN TO GROW HER CELLS FIRST SHOWN TO GROW OUTSIDE THE BODY FOR EXTENDED OUTSIDE THE BODY FOR EXTENDED PERIODSPERIODS-- USED TO DEVELOP THE USED TO DEVELOP THE POLIO VACCINEPOLIO VACCINE


nn 1957 CENTRAL DOGMA OF DNA1957 CENTRAL DOGMA OF DNA-- HOW DNA HOW DNA MAKES A PROTEINMAKES A PROTEIN

nn Francis Crick and George Francis Crick and George GamovGamov worked out the worked out the "central dogma," explaining how DNA functions to "central dogma," explaining how DNA functions to make protein. make protein.

nn 19591959nn Francois Jacob and Jacques Monod established the Francois Jacob and Jacques Monod established the

existence of genetic regulation existence of genetic regulation -- mappablemappable control control functions located on the chromosome in the DNA functions located on the chromosome in the DNA sequence sequence -- which they named the repressor and operon. which they named the repressor and operon.


nn 19621962nn Watson and Crick shared the 1962 Watson and Crick shared the 1962 Nobel Prize Nobel Prize

for Physiology and Medicine with Maurice for Physiology and Medicine with Maurice Wilkins. Unfortunately, Wilkins. Unfortunately, Rosalind FranklinRosalind Franklin, , whosewhose work greatly contributed to the discovery work greatly contributed to the discovery of the double helical structure of DNA, died of the double helical structure of DNA, died before this date, and the Nobel Prize rules do before this date, and the Nobel Prize rules do not allow a prize to be awarded posthumously not allow a prize to be awarded posthumously


nn 1966 GENETIC CODE CRACKED1966 GENETIC CODE CRACKEDnn The genetic code was "cracked". Marshall The genetic code was "cracked". Marshall

NirenbergNirenberg, Heinrich , Heinrich MathaeiMathaei, and , and SeveroSevero Ochoa Ochoa demonstrated that a sequence of three demonstrated that a sequence of three nucleotide bases (a codon) determines each of nucleotide bases (a codon) determines each of 20 amino acids. 20 amino acids.


nn 19671967nn Arthur Arthur KornbergKornberg conducted a study conducted a study using one strand using one strand

of natural viral DNA to assemble 5,300 nucleotide of natural viral DNA to assemble 5,300 nucleotide building blocks. building blocks. Kornberg'sKornberg's Stanford group then Stanford group then synthesized infectious viralsynthesized infectious viral DNA. DNA.

nn 19701970nn ONCOGENESONCOGENES Peter Peter DuesbergDuesberg and Peter Vogt, and Peter Vogt,

virologists at UCSF, discovered the first oncogene in a virologists at UCSF, discovered the first oncogene in a virus. This SRC gene has since been implicated in many virus. This SRC gene has since been implicated in many human cancers human cancers

Biotechnology Time LinesBiotechnology Time Linesnn 1972 FIRST RECOMBINANT DNA MOLECULE1972 FIRST RECOMBINANT DNA MOLECULEnn Paul BergPaul Berg isolated and employed a restriction enzyme to cut isolated and employed a restriction enzyme to cut

DNA. Berg used ligase to paste two DNA strands together to DNA. Berg used ligase to paste two DNA strands together to form a hybrid circular molecule. This was the first form a hybrid circular molecule. This was the first recombinant recombinant DNADNA molecule. molecule.

nn 1972 NIH GUIDELINES FOR RECOMBINANT DNA1972 NIH GUIDELINES FOR RECOMBINANT DNAnn In a letter to Science, Stanford biochemist Paul Berg and othersIn a letter to Science, Stanford biochemist Paul Berg and others

called for the National Institutes of Health to enact guidelinescalled for the National Institutes of Health to enact guidelinesfor DNA splicing.. Their concerns eventually led to the 1975 for DNA splicing.. Their concerns eventually led to the 1975 AsilomarAsilomar Conference. Conference.

Biotechnology Time LinesBiotechnology Time Linesnn 1973 AMES TEST1973 AMES TESTnn Bruce Ames, a biochemist at UC Berkeley, developed a test to Bruce Ames, a biochemist at UC Berkeley, developed a test to

identify chemicals that damage DNA. The Ames Test becomes a identify chemicals that damage DNA. The Ames Test becomes a widely used method to identify carcinogenic substances. widely used method to identify carcinogenic substances.

nn 1975 RECOMBINANT DNA MORITORIUM1975 RECOMBINANT DNA MORITORIUMnn A moratorium on recombinant DNA experiments was called for A moratorium on recombinant DNA experiments was called for

at an international meeting at at an international meeting at AsilomarAsilomar, California, where , California, where scientists urged the government to adopt guidelines regulating scientists urged the government to adopt guidelines regulating recombinant DNA experimentation. The scientists insisted on recombinant DNA experimentation. The scientists insisted on the development of "safe" bacteria and plasmids that could not the development of "safe" bacteria and plasmids that could not escape from the laboratory escape from the laboratory


nn 1976 MORE ABOUT ONCOGENES1976 MORE ABOUT ONCOGENESnn J. Michael BishopJ. Michael Bishop and and Harold Harold VarmusVarmus, virologists at , virologists at

UCSF, showed that oncogenes appear on animal UCSF, showed that oncogenes appear on animal chromosomes, and alterations in their structure or chromosomes, and alterations in their structure or expression can result in cancerous growth. expression can result in cancerous growth.

nn 1976 RELEASE OF NIH GUIDELINES1976 RELEASE OF NIH GUIDELINESnn The NIH released the first guidelines for recombinant The NIH released the first guidelines for recombinant

DNA experimentation. The guidelines restricted many DNA experimentation. The guidelines restricted many categories of experiments.categories of experiments.

Biotechnology Time LinesBiotechnology Time Linesnn 1977 1977 -- Present: The Dawn of BiotechPresent: The Dawn of Biotechnn Genetic engineering became a reality when a manGenetic engineering became a reality when a man--made gene was made gene was

used to manufacture a human protein in a bacteria for the first used to manufacture a human protein in a bacteria for the first time. Biotech companies and universities were off to the races, time. Biotech companies and universities were off to the races, and the world would never be the same again. In 1978, in the and the world would never be the same again. In 1978, in the laboratory of laboratory of Herbert BoyerHerbert Boyer at the University of California at San at the University of California at San Francisco, a synthetic version of the human insulin gene was Francisco, a synthetic version of the human insulin gene was constructed and inserted into the bacterium constructed and inserted into the bacterium EscheriaEscheria colicoli. Since . Since that key moment, the trickle of biotechnological developments that key moment, the trickle of biotechnological developments has become a torrent of diagnostic and therapeutic tools, has become a torrent of diagnostic and therapeutic tools, accompanied by ever faster and more powerful DNA sequencing accompanied by ever faster and more powerful DNA sequencing and cloning techniques. and cloning techniques.

Biotechnology Time LinesBiotechnology Time Linesnn 19771977nn GenentechGenentech, , Inc., reports the production of the first human protein Inc., reports the production of the first human protein

manufactured in a bacteria: manufactured in a bacteria: somatostatinsomatostatin, a human growth , a human growth hormonehormone--releasing inhibitory factor. For the first time, a releasing inhibitory factor. For the first time, a synthetic, recombinant gene was used to clone a protein. Many synthetic, recombinant gene was used to clone a protein. Many consider this to be consider this to be the advent of the the advent of the Age of Age of BiotechnologyBiotechnology. .

nn 19781978nn RECOMBINANT INSULINRECOMBINANT INSULIN GenentechGenentech, Inc. and The City , Inc. and The City

of Hope National Medical Center announced the successful of Hope National Medical Center announced the successful laboratory production of human insulin using recombinant DNA laboratory production of human insulin using recombinant DNA technology. technology.


nn 1980 PATENTS ALLOWED1980 PATENTS ALLOWEDnn The U.S. Supreme Court ruled in that genetically The U.S. Supreme Court ruled in that genetically

altered life forms can be patented a Supreme Court altered life forms can be patented a Supreme Court decision in 1980 allowed decision in 1980 allowed the Exxon oil company to the Exxon oil company to patent an oilpatent an oil--eating microorganismeating microorganism. .

nn Kary MullisKary Mullis and others at and others at CetusCetus Corporation in Corporation in Berkeley, California, invented a technique for Berkeley, California, invented a technique for multiplying DNA sequences in vitro by, the multiplying DNA sequences in vitro by, the polymerase polymerase chain reactionchain reaction (PCR). (PCR). PCR POLYMERASE CHAIN PCR POLYMERASE CHAIN REACTIONREACTION


nn 19821982nn GenentechGenentech, Inc. , Inc. received approval from the Food received approval from the Food

and Drug Administration to market genetically and Drug Administration to market genetically engineered human insulin. 1982 The U.S. Food engineered human insulin. 1982 The U.S. Food and Drug Administrationand Drug Administration approves the first approves the first genetically engineered drug, a form of human insulin genetically engineered drug, a form of human insulin produced by bacteria. produced by bacteria.

nn Michael Smith at the University of British Columbia, Michael Smith at the University of British Columbia, Vancouver, developed a procedure for making precise Vancouver, developed a procedure for making precise amino acid changes anywhere in a protein. amino acid changes anywhere in a protein. SITE SITE DIRECTED MUTAGENESISDIRECTED MUTAGENESIS


nn 19831983nn Eli Lilly received a license to make insulin.Eli Lilly received a license to make insulin.nn 19851985nn Genetic fingerprinting enters the Genetic fingerprinting enters the court room.court room.nn Cal Bio cloned the gene that encodes human Cal Bio cloned the gene that encodes human lung lung

surfactant proteinsurfactant protein, a major step toward reducing a , a major step toward reducing a premature birth complication. premature birth complication.

nn Genetically engineered plants resistantGenetically engineered plants resistant to insects, to insects, viruses, and bacteria were field tested for the first time. viruses, and bacteria were field tested for the first time.

nn The NIH approved guidelines for performing The NIH approved guidelines for performing experiments in experiments in gene therapy on humans.gene therapy on humans.

Biotechnology Time LinesBiotechnology Time Linesnn 19861986nn The FDA granted a license for the The FDA granted a license for the first recombinant vaccinefirst recombinant vaccine

(for hepatitis) to Chiron Corp. (for hepatitis) to Chiron Corp.

nn The EPA approved the release of the first genetically engineeredThe EPA approved the release of the first genetically engineeredcrop, crop, genegene--altered tobacco plants. altered tobacco plants.

nn 19871987nn CalgeneCalgene, Inc. received a patent for the tomato , Inc. received a patent for the tomato polygalacturonasepolygalacturonase

DNA sequence, used to produce an antisense RNA sequence DNA sequence, used to produce an antisense RNA sequence that can extend the that can extend the shelfshelf--life of fruitlife of fruit. .


nn 19881988nn Harvard molecular geneticists Philip Harvard molecular geneticists Philip LederLeder and and

Timothy Stewart awarded the first patent for a Timothy Stewart awarded the first patent for a genetically altered animal, a mousegenetically altered animal, a mouse that is highly that is highly susceptible to breast cancer. susceptible to breast cancer.

nn 19901990nn UCSF and Stanford University were issued their 100th UCSF and Stanford University were issued their 100th

recombinant DNA patent license. By the end of fiscal recombinant DNA patent license. By the end of fiscal 1991, both campuses had earned $40 million from the 1991, both campuses had earned $40 million from the patent. patent. PATENTS AND MONEYPATENTS AND MONEY

Biotechnology Time LinesBiotechnology Time Linesnn 19901990nn The first gene therapy takes place, on a fourThe first gene therapy takes place, on a four--yearyear--old girl with an old girl with an

immuneimmune--system disorder called ADA deficiency. The therapy system disorder called ADA deficiency. The therapy appeared to work, but set off a fury of discussion of ethics botappeared to work, but set off a fury of discussion of ethics both h in academia and in the media. in academia and in the media.

nn The The Human Genome ProjectHuman Genome Project, the international effort to map all , the international effort to map all of the genes in the human body, was launched. Estimated cost: of the genes in the human body, was launched. Estimated cost: $13 billion. 1990 Formal launch of the international Human $13 billion. 1990 Formal launch of the international Human Genome Project.Genome Project.

nn Publication of Michael Crichton's novel Publication of Michael Crichton's novel Jurassic ParkJurassic Park, in which , in which bioengineered dinosaurs roam a bioengineered dinosaurs roam a paleontologicalpaleontological theme park; the theme park; the experiment goes awry, with deadly results. experiment goes awry, with deadly results.


nn 19921992nn The U.S. Army begins collecting blood and The U.S. Army begins collecting blood and

tissuetissue samples from all new recruits as part of a samples from all new recruits as part of a "genetic dog tag" program aimed at better "genetic dog tag" program aimed at better identification of soldiers killed in combat.identification of soldiers killed in combat.

nn 19931993nn Kary Mullis won the Nobel Prize in Kary Mullis won the Nobel Prize in

Chemistry for inventing the technology of Chemistry for inventing the technology of polymerase chain reaction (polymerase chain reaction (PCRPCR).).

Biotechnology Time LinesBiotechnology Time Linesnn 19941994nn The first genetically engineered food product, the The first genetically engineered food product, the FlavrFlavr SavrSavr

tomato, gained FDA approval.tomato, gained FDA approval.nn The first crude but thorough linkage map of the human genome The first crude but thorough linkage map of the human genome

appears.(Seeappears.(See Science, v.265, Sep.30, '94, for the full color pullScience, v.265, Sep.30, '94, for the full color pull--out). out).

nn 1995 1995 nn AA new coalitionnew coalition of mainstream religions launched a campaign of mainstream religions launched a campaign

seeking to overturn current laws allowing the patenting of genesseeking to overturn current laws allowing the patenting of genesused for medical and research applications. The group also used for medical and research applications. The group also includes includes Jeremy RifkinJeremy Rifkin, the controversial and outspoken critic of , the controversial and outspoken critic of the biotechnology industry. the biotechnology industry. SHOULD PATENTS BE SHOULD PATENTS BE ALLOWED?ALLOWED?

Biotechnology Time LinesBiotechnology Time Linesnn 19961996nn A new inexpensive diagnostic A new inexpensive diagnostic biosensorbiosensor test for the first time test for the first time

allow instantaneous detection of the toxic strain of E. coli E. allow instantaneous detection of the toxic strain of E. coli E. coli coli strain 0157:H7, the bacteria responsible for several recent foodstrain 0157:H7, the bacteria responsible for several recent food--poisoning outbreaks. poisoning outbreaks. CAN IT BE DONE FOR ANTRAX CAN IT BE DONE FOR ANTRAX OR OTHER BIOTERRORISM AGENTS?OR OTHER BIOTERRORISM AGENTS?

nn The discovery of a The discovery of a gene associated with Parkinson's diseasegene associated with Parkinson's diseaseprovides an important new avenue of research into the cause and provides an important new avenue of research into the cause and potential treatment of the debilitating neurological ailment. potential treatment of the debilitating neurological ailment.

nn Surveys indicate the public regards research into the workings oSurveys indicate the public regards research into the workings of f the human genome and gene therapy with a combination of the human genome and gene therapy with a combination of fear fear and mistrustand mistrust


nn 19971997nn Researchers at Scotland's Researchers at Scotland's RoslinRoslin Institute report that Institute report that

they they have cloned a sheephave cloned a sheep----named named DollyDolly----from the from the cell of an adult ewe. cell of an adult ewe. PollyPolly the first sheep cloned by the first sheep cloned by nuclear transfer technology bearing a human gene nuclear transfer technology bearing a human gene appears later. appears later. Nuclear transfer involves transferring Nuclear transfer involves transferring the complete genetic material (the DNA contained the complete genetic material (the DNA contained in a nucleus) from one cell into an unfertilized egg in a nucleus) from one cell into an unfertilized egg cell whose own nucleus has been removed.cell whose own nucleus has been removed.

nn ..


nn 19981998nn Two research Two research teams succeed in growing teams succeed in growing embryonic embryonic

stem cellsstem cells, the long sought grail of molecular , the long sought grail of molecular biology. biology.

nn Scientists at Japan's Kinki University Scientists at Japan's Kinki University clone eight clone eight identical calvesidentical calves using cells taken from a single adult using cells taken from a single adult cow. cow.

nn A rough draft of the human A rough draft of the human genome mapgenome map is produced, is produced, showing the locations of more than 30,000 genes.showing the locations of more than 30,000 genes.


nn 19991999nn MAD COW DISEASEMAD COW DISEASEA new medical A new medical

diagnostic test will for the first time allow quick diagnostic test will for the first time allow quick identification of identification of BSE/CJDBSE/CJD a rare but a rare but devastating form of devastating form of neurologicneurologic disease disease transmitted from cattle to humans.transmitted from cattle to humans.

Biotechnology StatsBiotechnology Stats

nn Some biotech statistics:Some biotech statistics:nn 2001: 200,000 employees, $30 billion in revenues; 2001: 200,000 employees, $30 billion in revenues;

1450 total companies and 350 public companies1450 total companies and 350 public companiesnn 1992: 80,000 employees, $8.1 billion in revenues; 1992: 80,000 employees, $8.1 billion in revenues;

about same # companiesabout same # companiesnn Compensation in biotechnology companies is Compensation in biotechnology companies is

competitive and includes incentives, such as stock competitive and includes incentives, such as stock option plans, 401K plans, companyoption plans, 401K plans, company--wide stock wide stock purchase plans, and cash bonus plans. purchase plans, and cash bonus plans.

Approved Biotech ProductsApproved Biotech Products

nn 1938: Howard 1938: Howard FloreyFlorey/Ernst Chain, Oxford U., /Ernst Chain, Oxford U., England isolated penicillinEngland isolated penicillin

nn 19401940--1945: Large scale production of penicillin1945: Large scale production of penicillinnn 19431943--1953: Cortisone first manufactured in large 1953: Cortisone first manufactured in large

amountsamountsnn 1977: 1977: GenentechGenentech produced produced somatostatinsomatostatin (human (human

growth hormonegrowth hormone--releasing inhibitory factor), releasing inhibitory factor), manufactured in bacteria. First time a recombinant gene manufactured in bacteria. First time a recombinant gene was used to clone a protein.was used to clone a protein.

nn 1978: Harvard researchers produced rat insulin by 1978: Harvard researchers produced rat insulin by recombinant DNA.recombinant DNA.


nn 1982: FDA approves genetically engineered 1982: FDA approves genetically engineered human insulinhuman insulin

nn 1986: 1986: OrthocloneOrthoclone OKT3 (MuromonabOKT3 (Muromonab--CD3) CD3) approved for reversal of kidney transplant approved for reversal of kidney transplant rejection.rejection.

nn 1986: first recombinant vaccine approved1986: first recombinant vaccine approved--hepatitishepatitis

nn 1987: 1987: GenentechGenentech gets approval for gets approval for rtrt--PA (tissue PA (tissue plasminogenplasminogen activatioractivatior) for heart attacks) for heart attacks


nn 1990: 1990: ActimmuneActimmune (interferon 1b) approved for (interferon 1b) approved for chronic chronic granulomatousgranulomatous diseasedisease

nn AdagenAdagen (adenosine (adenosine deaminasedeaminase) approved for ) approved for severe combined immunodeficiency diseasesevere combined immunodeficiency disease

nn 1994: first genetically engineered food the 1994: first genetically engineered food the FlavrFlavrSavrSavr tomato is approved.tomato is approved.

nn 1994: 1994: Genentech’sGenentech’s NutropinNutropin is approved is approved (growth hormone deficiency)(growth hormone deficiency)


nn 1994: 1994: Centocor’sCentocor’s ReoProReoPro approved (for patients approved (for patients undergoing balloon angioplasty)undergoing balloon angioplasty)

nn GenzymesGenzymes Ceredase/CerezymeCeredase/Cerezyme approved for approved for Gaucher’sGaucher’s Disease (inherited metabolic Disease (inherited metabolic disease)disease)

nn Recombinant GMRecombinant GM--CSF approved CSF approved (chemotherapy induced (chemotherapy induced neutropenianeutropenia))

•• 1998: 1998: Centocor’sCentocor’s RemicadeTMRemicadeTM approved approved (monoclonal antibody for (monoclonal antibody for Crohn’sCrohn’s disease)disease)

Focus on “Famous” Biotech Focus on “Famous” Biotech Product: InsulinProduct: Insulin

nn Insulin: Insulin: nn Insulin is a hormone, and therefore, a protein.Insulin is a hormone, and therefore, a protein.nn Insulin was the first hormone identifiedInsulin was the first hormone identified (late 1920's) which (late 1920's) which

won the doctor and medical student who discovered it the Nobel won the doctor and medical student who discovered it the Nobel Prize (Prize (BantingBanting and Best).and Best).

nn They discovered insulin by tying a string around the pancreatic They discovered insulin by tying a string around the pancreatic duct of several dogs.duct of several dogs.

nn Note that there are other hormones produced by different types Note that there are other hormones produced by different types of cells within pancreatic islets (of cells within pancreatic islets (glucagon, glucagon, somatostatinsomatostatin, etc, etc) but ) but insulin is produced in far greater amounts under normal insulin is produced in far greater amounts under normal conditions making the simple approach used by conditions making the simple approach used by BantingBanting and and Best quite successful.Best quite successful.

Properties of InsulinProperties of Insulin

nn Insulin is secreted by groups of cells within the Insulin is secreted by groups of cells within the pancreas called islet cells. pancreas called islet cells.

nn The pancreas is an organ that sits behind the stomach The pancreas is an organ that sits behind the stomach and has many functions in addition to insulin and has many functions in addition to insulin production. production.

nn The pancreas also produces digestive enzymes and The pancreas also produces digestive enzymes and other. other.

nn Without insulin, you can eat lots of food and actually be Without insulin, you can eat lots of food and actually be in a state of starvation since many of our cells cannot in a state of starvation since many of our cells cannot access the calories contained in the glucose very well access the calories contained in the glucose very well without the action of insulin. without the action of insulin.

Insulin (cont’d)Insulin (cont’d)

nn The first successful insulin preparations The first successful insulin preparations came from cows (and later pigs)came from cows (and later pigs).. The The pancreatic islets and the insulin protein pancreatic islets and the insulin protein contained within them were isolated from contained within them were isolated from animals slaughtered for food in a similar but animals slaughtered for food in a similar but more complex fashion than was used by our more complex fashion than was used by our doctor and meddoctor and med--student duo.student duo.

Biotech ApplicationsBiotech Applications

nn DiagnosticsDiagnosticsnn AntibodiesAntibodiesnn BiosensorsBiosensorsnn PCRPCR

nn TherapeuticsTherapeuticsnn Natural ProductsNatural Productsnn Foxglove: Foxglove: nn digitalis: heart conditionsdigitalis: heart conditions

nn Yew treeYew tree-- cancer agent (taxol) breast and ovarian cancerscancer agent (taxol) breast and ovarian cancersnn Endogenous Therapeutic agents Endogenous Therapeutic agents –– proteins produced by the proteins produced by the

body that can be replicated by genetically engineered: body that can be replicated by genetically engineered: tPAtPA ––tissue tissue plasminogenplasminogen factor (dissolves blood clots)factor (dissolves blood clots)


nn Biopolymers and Medical DevicesBiopolymers and Medical Devices-- natural natural substances useful as medical devices substances useful as medical devices

nn hyaluronatehyaluronate-- an elastic, plastic like substance used to treat an elastic, plastic like substance used to treat arthritis, prevent arthritis, prevent postsurgicalpostsurgical scarring in cataract surgery, scarring in cataract surgery, used for drug deliveryused for drug delivery

nn adhesive substances to replace stitchesadhesive substances to replace stitches

nn Designer Drugs Designer Drugs –– using computer using computer modeling to design drugs without the labmodeling to design drugs without the lab--protein structureprotein structure


nn Replacement TherapiesReplacement Therapies-- lack of production lack of production of normal substancesof normal substances

nn Factor VIIIFactor VIII-- missing in hemophiliamissing in hemophiliann InsulinInsulin

nn Use of Transgenic Animals and PlantsUse of Transgenic Animals and Plants


nn Gene Therapy Gene Therapy –– replace defective genes with replace defective genes with functional onesfunctional ones

nn ADA (adenosine ADA (adenosine deaminasedeaminase) deficiency) deficiencynn cystic fibrosiscystic fibrosis

nn Immunosuppressive Therapies Immunosuppressive Therapies –– used to inhibit used to inhibit rejection (organ transplants)rejection (organ transplants)

nn Cancer Therapies Cancer Therapies --one method is antisense one method is antisense technologytechnology

nn Vaccines Vaccines –– biggest break through in biggest break through in biotechnologybiotechnology-- prevention of diseaseprevention of disease

Documents

History of Biotech and Biotech Applicationsfaculty.mc3.edu/lrehfuss/bit120/history.pdf · History of Biotech and Biotech Applications BIT 120 Source for History Information: ... ray