Biotech history

History of Biotech andHistory of Biotech and
Biotech ApplicationsBiotech Applications
BIT 120BIT 120
Source 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 thousandsTraditional biotechnology has been used for thousands
of years to produce improved food and health careof years to produce improved food and health care
products. Today, modern biotechnology enables us toproducts. Today, modern biotechnology enables us to
develop improved products more safely and moredevelop improved products more safely and more
rapidly than ever before.rapidly than ever before.
nn Biotechnology in one form or another has flourishedBiotechnology 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 theirthey 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 oror that milk could be converted into cheese or
yogurt, or that beer could be made by fermentingyogurt, or that beer could be made by fermenting
solutions of malt and hops began the study ofsolutions of malt and hops began the study of
biotechnologybiotechnology

Examples cont’dExamples cont’d
nn When the first bakers found that they could make aWhen 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 differentThe first animal breeders, realizing that different
physical traits could be either magnified or lost byphysical traits could be either magnified or lost by
mating appropriate pairs of animals, engaged in themating appropriate pairs of animals, engaged in the
manipulations of biotechnology.manipulations of biotechnology.

DefinitionDefinition
nn Definition:Definition: What then is biotechnology? the termWhat 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 rawscience to create new products from biologically based raw
materials, such as vaccines or foods. They also develop factorymaterials, 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 byBiotechnology 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 speculation
nn 18001800--1900: Significant advances in basic1900: Significant advances in basic
understandingunderstanding
nn 19001900--1953: Genetics1953: Genetics
nn 19531953-- 1976: DNA research, science explodes1976: DNA research, science explodes
nn 19771977-- present: modern biotechnologypresent: modern biotechnology

Biotechnology Time LinesBiotechnology Time Lines
nn 6000 BC6000 BC
nn Yeast was used to make beer by Sumerians and Babylonians.Yeast was used to make beer by Sumerians and Babylonians.
nn 4000 BC4000 BC
nn The Egyptians discovered how to bake leavened bread usingThe Egyptians discovered how to bake leavened bread using
yeast.yeast.
nn 420 BC420 BC
nn Socrates (470?Socrates (470? -- 399 BC), the Greek philosopher, speculated on399 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 BC
nn Aristotle (384Aristotle (384 -- 322 BC), told his students that all inheritance322 BC), told his students that all inheritance
comes from the father.comes from the father.

nn 1000 AD1000 AD
nn 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 thatis 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 AD
nn William HarveyWilliam Harvey concluded that plants and animals alikeconcluded that plants and animals alike
reproduce in a sexual manner:reproduce in a sexual manner:––egg isolated in 1800’segg isolated in 1800’s
nn 16601660--1675 AD1675 AD
nn MarcelloMarcello MalpighiMalpighi (1628(1628--1694) in this period used a microscope1694) in this period used a microscope
to study blood circulation in capillaries, described the nervousto study blood circulation in capillaries, described the nervous
system as bundles of fibers connected to the brain by the spinalsystem as bundles of fibers connected to the brain by the spinal
cord,.cord,.

nn 1673 AD1673 AD
nn Anton van Leeuwenhoek (1632Anton van Leeuwenhoek (1632 -- 1723), He was the first scientist1723), He was the first scientist
to describe protozoa and bacteria and to recognize that suchto describe protozoa and bacteria and to recognize that such
microorganisms might play a role in fermentation.microorganisms might play a role in fermentation.
nn 17011701
nn GiacomoGiacomo PylariniPylarini inin ConstantiopleConstantiople practiced "inoculation"practiced "inoculation"----
intentionally giving children smallpox to prevent a serious caseintentionally giving children smallpox to prevent a serious case
later in life. Inoculation will compete with "vaccination"later in life. Inoculation will compete with "vaccination"----anan
alternative method that uses cowpox rather than smallpox as thealternative 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

nn 18091809
nn NicolasNicolas AppertAppert devised a technique using heat to can anddevised a technique using heat to can and
sterilize foodsterilize food
nn 18271827
nn The worldwide search for the elusive mammalian egg ended withThe worldwide search for the elusive mammalian egg ended with
the first observation of canine eggs.the first observation of canine eggs. Remember 1630 andRemember 1630 and
William HarveyWilliam Harvey
nn 18501850
nn ONE OF MY FAVORITESONE OF MY FAVORITES IgnazIgnaz SemmelweisSemmelweis usedused
epidemiological observations to propose the hypothesis thatepidemiological observations to propose the hypothesis that
childbed fever can be spread from mother to mother bychildbed 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 bytheir hands after examining each patient. He became despised by
the medical profession and lost his job.the medical profession and lost his job.

nn 18561856
nn Karl Ludwig discovered a technique for keeping animal organsKarl 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 ofIn 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 (1809Charles Darwin (1809 -- 18821882) hypothesized that animal) hypothesized that animal
populations adapt their forms over time to best exploit thepopulations 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." As
he traveled in the Galapagos Islands,he traveled in the Galapagos Islands, he observed how thehe observed how the
finch's beaks on each island were adaptedfinch's beaks on each island were adapted to their foodto their food
sources.sources.

nn 18631863
nn Louis PasteurLouis Pasteur invented the process of pasteurization,invented the process of pasteurization,
heating wine sufficiently to inactivate microbes (thatheating 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 ofwine") while at the same time not ruining the flavor of
the wine.the wine.
nn Anton deAnton de BaryBary proved that a fungus causes potatoproved that a fungus causes potato
blight. A challenge for scientists during this period wasblight. A challenge for scientists during this period was
to discern whether a microbe was the cause of, or theto discern whether a microbe was the cause of, or the
result of, a disease.result of, a disease.

nn 18651865
nn Gregor MendelGregor Mendel (1822(1822 -- 1884), an Augustinian monk, presented1884), an Augustinian monk, presented
his laws of heredity to the Natural Science Society inhis laws of heredity to the Natural Science Society in BrunnBrunn,,
Austria. Mendel proposed that invisible internal units ofAustria. Mendel proposed that invisible internal units of
information account for observable traits, and that theseinformation account for observable traits, and that these
"factors""factors" -- which later became known as geneswhich later became known as genes -- are passed fromare 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 sensationallanguishing in the shadow of Darwin's more sensational
publication from five years earlier, until 1900, when Hugo depublication from five years earlier, until 1900, when Hugo de
VriesVries, Erich Von, Erich Von TschermakTschermak, and Carl, and Carl CorrensCorrens publishedpublished
research corroborating Mendel's mechanism of heredity.research corroborating Mendel's mechanism of heredity.
nn ..

nn PasteurPasteur investigated silkworm disease andinvestigated silkworm disease and
established that diseases can be transmitted fromestablished that diseases can be transmitted from
one animal to another.one animal to another.
nn Joseph Lister began using disinfectants such asJoseph Lister began using disinfectants such as
phenol (=carbolic acid) in wound care andphenol (=carbolic acid) in wound care and
surgery assurgery as PasteurPasteur developed the germ theory ofdeveloped the germ theory of
diseasedisease

nn 18681868
nn DavaineDavaine used heat treatment to cure a plant ofused heat treatment to cure a plant of
bacterial infection.bacterial infection.
nn FredrichFredrich MiescherMiescher, a Swiss biologist, successfully, a Swiss biologist, successfully
isolatedisolated nucleinnuclein, a compound that includes, a compound that includes
nucleic acid, from pus cells obtained fromnucleic acid, from pus cells obtained from
discarded bandages.discarded bandages.
nn 18701870
nn W.W. FlemmingFlemming discovered mitosis.discovered mitosis.

nn 18711871
nn DNA was isolated from the sperm of trout found inDNA was isolated from the sperm of trout found in thethe
Rhine River.Rhine River.
nn 18731873--66
nn Robert Koch investigated anthrax and developed techniques toRobert 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, andaided by Gram, Cohn, and WeigartWeigart..
nn 18801880
nn Studying fowl cholera,Studying fowl cholera, PasteurPasteur published his work onpublished 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 samecause disease but protected against severe forms of the same
disease.disease.

nn 1881 ANTRAX1881 ANTRAX
nn Robert Koch described bacterial colonies growing onRobert 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 pureNutrient agar became a standard tool for obtaining pure
cultures and for identifying genetic mutants. This iscultures and for identifying genetic mutants. This is
considered by T.D. Brock to be the single mostconsidered 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 againstPasteur 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 andthis 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.

nn 18841884
nn ROBERT KOCH STATED HIS "POSTULATES" FORROBERT KOCH STATED HIS "POSTULATES" FOR
TESTING WHETHER A MICROBE IS THE CAUSALTESTING WHETHER A MICROBE IS THE CAUSAL
AGENT OF A DISEASEAGENT OF A DISEASE..
nn PasteurPasteur developed adeveloped 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 thedied after 41 years of meticulously studying the
heredity "factors" of pea plants. Having received no scientificheredity "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 19001900 -- 19531953 -- Converging on DNAConverging on DNA
nn 1900 MENDEL’S WORK FINALLY TOOK ON1900 MENDEL’S WORK FINALLY TOOK ON
IMPORTANCEIMPORTANCE
nn The science of genetics was finally born whenThe science of genetics was finally born when Mendel'sMendel's workwork
was rediscovered by three scientistswas rediscovered by three scientists -- HugoHugo DeVriesDeVries, Erich Von, Erich Von
TschermakTschermak, and Carl, and Carl CorrensCorrens -- each one independentlyeach one independently
researching scientific literature for precedents to their ownresearching scientific literature for precedents to their own
"original" work."original" work.
nn 1902 HUMAN GENETICS BORN1902 HUMAN GENETICS BORN
nn WalterWalter StanboroughStanborough Sutton stated that chromosomes are pairedSutton stated that chromosomes are paired
and may be the carriers of heredity. He suggested that Mendel'sand may be the carriers of heredity. He suggested that Mendel's
"factors" are located on chromosomes."factors" are located on chromosomes.

nn 1905 X AND Y CHROMOSOMES RELATED TO1905 X AND Y CHROMOSOMES RELATED TO
GENDERGENDER
nn Edmund Wilson and Nellie Stevens proposed the idea thatEdmund Wilson and Nellie Stevens proposed the idea that
separate X and Y chromosomes determine sex. They showedseparate X and Y chromosomes determine sex. They showed
that a single Y chromosome determines maleness, and twothat a single Y chromosome determines maleness, and two
copies of the X chromosome determine femaleness.copies of the X chromosome determine femaleness.
nn 19051905--19081908
nn WilliamWilliam BatesonBateson and Reginaldand Reginald CrudellCrudell Punnett, along withPunnett, along with
others, demonstrated that some genes modify the action of otherothers, demonstrated that some genes modify the action of other
genes.genes.
nn 19061906
nn PaulPaul ErlichErlich investigatedinvestigated atoxylatoxyl compounds and discovered thecompounds and discovered the
beneficial properties ofbeneficial properties of SalvarsanSalvarsan -- the first chemotherapeuticthe first chemotherapeutic
agent.agent.

nn 19071907
nn Thomas Hunt Morgan began his work with fruit flies that willThomas 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 fundamentalestablish 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 ANIMALS
nn WilhelmWilhelm JohannsenJohannsen coined the terms 'gene' to describe thecoined the terms 'gene' to describe the
carrier of heredity; 'genotype' to describe the genetic constitucarrier of heredity; 'genotype' to describe the genetic constitutiontion
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 thewhich results from a combination of the genotype and the
various environmental factors.various environmental factors.

nn 1910 BASIS OF MODERN GENETICS1910 BASIS OF MODERN GENETICS
nn Thomas Hunt Morgan proved that genes are carried onThomas 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 fruitworkers, he pinpointed the location of various fruit
fly genes on chromosomes, establishing the use of Drosophilafly genes on chromosomes, establishing the use of Drosophila
fruit flies to study heredity..fruit flies to study heredity..
nn 19111911
nn Thomas Hunt Morgan explained the separation of certainThomas 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 thehe
breaking of chromosomes sometimes during the process of cellbreaking of chromosomes sometimes during the process of cell
division. Morgan began to map the positions of genes ondivision. Morgan began to map the positions of genes on
chromosomes of the fruit fly.chromosomes of the fruit fly.

nn 19121912
nn Lawrence Bragg discovered that XLawrence Bragg discovered that X--rays can be used torays 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 cellsHerbert M. Evans found (incorrectly) that human cells
contain 48 chromosomescontain 48 chromosomes..
nn 1924 EUGENICS IN THE UNITED STATES1924 EUGENICS IN THE UNITED STATES
nn Politicians encouraged by the eugenics movement passed thePoliticians encouraged by the eugenics movement passed the
U.S. Immigration Act of 1924, limiting the influx of poorlyU.S. Immigration Act of 1924, limiting the influx of poorly
educated immigrants from Southern and Eastern Europe on theeducated immigrants from Southern and Eastern Europe on the
grounds of suspected genetic inferiority.grounds of suspected genetic inferiority.

nn 19261926
nn Thomas Hunt Morgan published 'The theory of theThomas Hunt Morgan published 'The theory of the
gene', the culmination of work on the physical basis forgene', the culmination of work on the physical basis for
Mendelian genetics based on breeding studies andMendelian genetics based on breeding studies and
optical microscopy.optical microscopy.
nn Hermann Muller discovered that XHermann Muller discovered that X--rays inducerays induce
genetic mutations in fruit flies 1,500 times moregenetic mutations in fruit flies 1,500 times more
quickly than under normal circumstances.quickly than under normal circumstances. ThisThis
discovery provided researchers with a way to inducediscovery provided researchers with a way to induce
mutations, an important tool for discovering whatmutations, an important tool for discovering what
genes do on their own.genes do on their own.

nn 19281928
nn Fredrick Griffiths noticed that a rough type ofFredrick Griffiths noticed that a rough type of
bacterium changed to a smooth type when an unknownbacterium 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 identifiedpresent. 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 aAlexander Fleming noticed that all the bacteria in a
radius surrounding a bit of mold in aradius surrounding a bit of mold in a petriepetrie dish haddish 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 madewould be almost 15 years before it was made
available to the community for medicinal use.available to the community for medicinal use.

nn 19381938
nn 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 ENZYME
nn George Beadle and Edward Tatum experimented withGeorge 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 taskseach gene is translated into an enzyme to perform tasks
within an organism.within an organism.

nn 19431943
nn The Rockefeller Foundation, collaborating with theThe Rockefeller Foundation, collaborating with the
Mexican government, initiated the Mexican AgriculturalMexican government, initiated the Mexican Agricultural
Program. This was the first use of plant breeding asProgram. This was the first use of plant breeding as
foreign aid.foreign aid.
nn 19431943--19531953
nn Cortisone was first manufactured in large amounts.Cortisone was first manufactured in large amounts.
KIND OF A FIRST BIOTECH PRODUCTKIND OF A FIRST BIOTECH PRODUCT
nn 19441944
nn WaksmanWaksman isolatedisolated streptomycinstreptomycin, an effective antibiotic, an effective antibiotic
for TB.for TB.

nn 19451945
nn The U.N. Food and Agriculture OrganizationThe U.N. Food and Agriculture Organization (FAO)(FAO)
was formed in Quebec, Canada.was formed in Quebec, Canada.
nn 19451945 -- 19501950
nn CELLS GROWN IN LABCELLS GROWN IN LAB Isolated animal cellIsolated animal cell
cultures were grown in laboratories.cultures were grown in laboratories.
nn 19471947
nn Barbara McClintockBarbara McClintock first reported on "transposablefirst reported on "transposable
elements"elements" -- known today as "jumping genes." Theknown today as "jumping genes." The
scientific community failed to appreciate thescientific community failed to appreciate the
significance of her discovery at the time.significance of her discovery at the time.

nn 19501950
nn ErwinErwin ChargaffChargaff found that in DNA the amountsfound that in DNA the amounts
of adenine and thymine are about the same, asof adenine and thymine are about the same, as
are the amounts of guanine and cytosine. Theseare the amounts of guanine and cytosine. These
relationships are later known asrelationships are later known as "Chargaff's"Chargaff's
Rules"Rules" and serve as a key principle for Watsonand serve as a key principle for Watson
and Crick in assessing various models for theand 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 19531953 -- 1976: Expanding the Boundaries of DNA1976: Expanding the Boundaries of DNA
ResearchResearch
nn The discovery of the structure of DNA resulted in anThe 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 19531953
nn Nature magazine publishedNature magazine published James Watson'sJames Watson's and Francisand Francis
Crick's manuscript describing the double helix structureCrick's manuscript describing the double helix structure
of DNA.of DNA.

nn 19531953
nn GeyGey developed the HeLa human cell line.developed the HeLa human cell line.
HENRIETTA LACKSHENRIETTA LACKS-- DIED IN 1951 OFDIED IN 1951 OF
CERVICAL CANCERCERVICAL CANCER-- MOTHER OF 5MOTHER OF 5--
HER CELLS FIRST SHOWN TO GROWHER CELLS FIRST SHOWN TO GROW
OUTSIDE THE BODY FOR EXTENDEDOUTSIDE THE BODY FOR EXTENDED
PERIODSPERIODS-- USED TO DEVELOP THEUSED TO DEVELOP THE
POLIO VACCINEPOLIO VACCINE

nn 1957 CENTRAL DOGMA OF DNA1957 CENTRAL DOGMA OF DNA-- HOW DNAHOW DNA
MAKES A PROTEINMAKES A PROTEIN
nn Francis Crick and GeorgeFrancis Crick and George GamovGamov worked out theworked out the
"central dogma," explaining how DNA functions to"central dogma," explaining how DNA functions to
make protein.make protein.
nn 19591959
nn Francois Jacob and Jacques Monod established theFrancois Jacob and Jacques Monod established the
existence of genetic regulationexistence of genetic regulation -- mappablemappable controlcontrol
functions located on the chromosome in the DNAfunctions located on the chromosome in the DNA
sequencesequence -- which they named the repressor and operon.which they named the repressor and operon.

nn 19621962
nn Watson and Crick shared the 1962Watson and Crick shared the 1962 Nobel PrizeNobel Prize
for Physiology and Medicine with Mauricefor Physiology and Medicine with Maurice
Wilkins. Unfortunately,Wilkins. Unfortunately, Rosalind FranklinRosalind Franklin,,
whosewhose work greatly contributed to the discoverywork greatly contributed to the discovery
of the double helical structure of DNA, diedof the double helical structure of DNA, died
before this date, and the Nobel Prize rules dobefore this date, and the Nobel Prize rules do
not allow a prize to be awarded posthumouslynot allow a prize to be awarded posthumously

nn 1966 GENETIC CODE CRACKED1966 GENETIC CODE CRACKED
nn The genetic code was "cracked". MarshallThe genetic code was "cracked". Marshall
NirenbergNirenberg, Heinrich, Heinrich MathaeiMathaei, and, and SeveroSevero OchoaOchoa
demonstrated that a sequence of threedemonstrated that a sequence of three
nucleotide bases (a codon) determines each ofnucleotide bases (a codon) determines each of
20 amino acids.20 amino acids.

nn 19671967
nn ArthurArthur KornbergKornberg conducted a studyconducted a study using one strandusing one strand
of natural viral DNA to assemble 5,300 nucleotideof natural viral DNA to assemble 5,300 nucleotide
building blocks.building blocks. Kornberg'sKornberg's Stanford group thenStanford group then
synthesized infectious viralsynthesized infectious viral DNA.DNA.
nn 19701970
nn ONCOGENESONCOGENES PeterPeter DuesbergDuesberg and Peter Vogt,and Peter Vogt,
virologists at UCSF, discovered the first oncogene in avirologists at UCSF, discovered the first oncogene in a
virus. This SRC gene has since been implicated in manyvirus. This SRC gene has since been implicated in many
human cancershuman cancers

nn 1972 FIRST RECOMBINANT DNA MOLECULE1972 FIRST RECOMBINANT DNA MOLECULE
nn Paul BergPaul Berg isolated and employed a restriction enzyme to cutisolated and employed a restriction enzyme to cut
DNA. Berg used ligase to paste two DNA strands together toDNA. Berg used ligase to paste two DNA strands together to
form a hybrid circular molecule. This was the firstform a hybrid circular molecule. This was the first recombinantrecombinant
DNADNA molecule.molecule.
nn 1972 NIH GUIDELINES FOR RECOMBINANT DNA1972 NIH GUIDELINES FOR RECOMBINANT DNA
nn 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 guidelines
for DNA splicing.. Their concerns eventually led to the 1975for DNA splicing.. Their concerns eventually led to the 1975
AsilomarAsilomar Conference.Conference.

nn 1973 AMES TEST1973 AMES TEST
nn Bruce Ames, a biochemist at UC Berkeley, developed a test toBruce Ames, a biochemist at UC Berkeley, developed a test to
identify chemicals that damage DNA. The Ames Test becomes aidentify 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 MORITORIUM
nn A moratorium on recombinant DNA experiments was called forA moratorium on recombinant DNA experiments was called for
at an international meeting atat an international meeting at AsilomarAsilomar, California, where, California, where
scientists urged the government to adopt guidelines regulatingscientists urged the government to adopt guidelines regulating
recombinant DNA experimentation. The scientists insisted onrecombinant DNA experimentation. The scientists insisted on
the development of "safe" bacteria and plasmids that could notthe development of "safe" bacteria and plasmids that could not
escape from the laboratoryescape from the laboratory

nn 1976 MORE ABOUT ONCOGENES1976 MORE ABOUT ONCOGENES
nn J. Michael BishopJ. Michael Bishop andand HaroldHarold VarmusVarmus, virologists at, virologists at
UCSF, showed that oncogenes appear on animalUCSF, showed that oncogenes appear on animal
chromosomes, and alterations in their structure orchromosomes, 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 GUIDELINES
nn The NIH released the first guidelines for recombinantThe NIH released the first guidelines for recombinant
DNA experimentation. The guidelines restricted manyDNA experimentation. The guidelines restricted many
categories of experiments.categories of experiments.

nn 19771977 -- Present: The Dawn of BiotechPresent: The Dawn of Biotech
nn Genetic engineering became a reality when a manGenetic engineering became a reality when a man--made gene wasmade gene was
used to manufacture a human protein in a bacteria for the firstused 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 theand the world would never be the same again. In 1978, in the
laboratory oflaboratory of Herbert BoyerHerbert Boyer at the University of California at Sanat the University of California at San
Francisco, a synthetic version of the human insulin gene wasFrancisco, a synthetic version of the human insulin gene was
constructed and inserted into the bacteriumconstructed and inserted into the bacterium EscheriaEscheria colicoli. Since. Since
that key moment, the trickle of biotechnological developmentsthat 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 sequencingaccompanied by ever faster and more powerful DNA sequencing
and cloning techniques.and cloning techniques.

nn 19771977
nn GenentechGenentech,, Inc., reports the production of the first human proteinInc., 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, areleasing inhibitory factor. For the first time, a
synthetic, recombinant gene was used to clone a protein. Manysynthetic, recombinant gene was used to clone a protein. Many
consider this to beconsider this to be the advent of thethe advent of the Age ofAge of
BiotechnologyBiotechnology..
nn 19781978
nn RECOMBINANT INSULINRECOMBINANT INSULIN GenentechGenentech, Inc. and The City, Inc. and The City
of Hope National Medical Center announced the successfulof Hope National Medical Center announced the successful
laboratory production of human insulin using recombinant DNAlaboratory production of human insulin using recombinant DNA
technology.technology.

nn 1980 PATENTS ALLOWED1980 PATENTS ALLOWED
nn The U.S. Supreme Court ruled in that geneticallyThe U.S. Supreme Court ruled in that genetically
altered life forms can be patented a Supreme Courtaltered life forms can be patented a Supreme Court
decision in 1980 alloweddecision in 1980 allowed the Exxon oil company tothe Exxon oil company to
patent an oilpatent an oil--eating microorganismeating microorganism..
nn Kary MullisKary Mullis and others atand others at CetusCetus Corporation inCorporation in
Berkeley, California, invented a technique forBerkeley, California, invented a technique for
multiplying DNA sequences in vitro by, themultiplying DNA sequences in vitro by, the polymerasepolymerase
chain reactionchain reaction (PCR).(PCR). PCR POLYMERASE CHAINPCR POLYMERASE CHAIN
REACTIONREACTION

nn 19821982
nn GenentechGenentech, Inc., Inc. received approval from the Foodreceived approval from the Food
and Drug Administration to market geneticallyand Drug Administration to market genetically
engineered human insulin. 1982 The U.S. Foodengineered human insulin. 1982 The U.S. Food
and Drug Administrationand Drug Administration approves the firstapproves the first
genetically engineered drug, a form of human insulingenetically 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 preciseVancouver, developed a procedure for making precise
amino acid changes anywhere in a protein.amino acid changes anywhere in a protein. SITESITE
DIRECTED MUTAGENESISDIRECTED MUTAGENESIS

nn 19831983
nn Eli Lilly received a license to make insulin.Eli Lilly received a license to make insulin.
nn 19851985
nn Genetic fingerprinting enters theGenetic fingerprinting enters the court room.court room.
nn Cal Bio cloned the gene that encodes humanCal Bio cloned the gene that encodes human lunglung
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 performingThe NIH approved guidelines for performing
experiments inexperiments in gene therapy on humans.gene therapy on humans.

nn 19861986
nn The FDA granted a license for theThe 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 engineered
crop,crop, genegene--altered tobacco plants.altered tobacco plants.
nn 19871987
nn CalgeneCalgene, Inc. received a patent for the tomato, Inc. received a patent for the tomato polygalacturonasepolygalacturonase
DNA sequence, used to produce an antisense RNA sequenceDNA sequence, used to produce an antisense RNA sequence
that can extend thethat can extend the shelfshelf--life of fruitlife of fruit..

nn 19881988
nn Harvard molecular geneticists PhilipHarvard molecular geneticists Philip LederLeder andand
Timothy Stewart awarded the first patent for aTimothy Stewart awarded the first patent for a
genetically altered animal, a mousegenetically altered animal, a mouse that is highlythat is highly
susceptible to breast cancer.susceptible to breast cancer.
nn 19901990
nn UCSF and Stanford University were issued their 100thUCSF and Stanford University were issued their 100th
recombinant DNA patent license. By the end of fiscalrecombinant DNA patent license. By the end of fiscal
1991, both campuses had earned $40 million from the1991, both campuses had earned $40 million from the
patent.patent. PATENTS AND MONEYPATENTS AND MONEY

nn 19901990
nn The first gene therapy takes place, on a fourThe first gene therapy takes place, on a four--yearyear--old girl with anold girl with an
immuneimmune--system disorder called ADA deficiency. The therapysystem 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 bothh
in academia and in the media.in academia and in the media.
nn TheThe 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 novelPublication of Michael Crichton's novel Jurassic ParkJurassic Park, in which, in which
bioengineered dinosaurs roam abioengineered dinosaurs roam a paleontologicalpaleontological theme park; thetheme park; the
experiment goes awry, with deadly results.experiment goes awry, with deadly results.

nn 19921992
nn The U.S. Army begins collecting blood andThe U.S. Army begins collecting blood and
tissuetissue samples from all new recruits as part of asamples 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 19931993
nn Kary Mullis won the Nobel Prize inKary Mullis won the Nobel Prize in
Chemistry for inventing the technology ofChemistry for inventing the technology of
polymerase chain reaction (polymerase chain reaction (PCRPCR).).

nn 19941994
nn The first genetically engineered food product, theThe 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 genomeThe 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 19951995
nn AA new coalitionnew coalition of mainstream religions launched a campaignof mainstream religions launched a campaign
seeking to overturn current laws allowing the patenting of genesseeking to overturn current laws allowing the patenting of genes
used for medical and research applications. The group alsoused for medical and research applications. The group also
includesincludes Jeremy RifkinJeremy Rifkin, the controversial and outspoken critic of, the controversial and outspoken critic of
the biotechnology industry.the biotechnology industry. SHOULD PATENTS BESHOULD PATENTS BE
ALLOWED?ALLOWED?

nn 19961996
nn A new inexpensive diagnosticA new inexpensive diagnostic biosensorbiosensor test for the first timetest 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. colicoli
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 ANTRAXCAN IT BE DONE FOR ANTRAX
OR OTHER BIOTERRORISM AGENTS?OR OTHER BIOTERRORISM AGENTS?
nn The discovery of aThe discovery of a gene associated with Parkinson's diseasegene associated with Parkinson's disease
provides an important new avenue of research into the cause andprovides 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 off
the human genome and gene therapy with a combination ofthe human genome and gene therapy with a combination of fearfear
and mistrustand mistrust

nn 19971997
nn Researchers at Scotland'sResearchers at Scotland's RoslinRoslin Institute report thatInstitute report that
theythey have cloned a sheephave cloned a sheep----namednamed DollyDolly----from thefrom the
cell of an adult ewe.cell of an adult ewe. PollyPolly the first sheep cloned bythe first sheep cloned by
nuclear transfer technology bearing a human genenuclear transfer technology bearing a human gene
appears later.appears later. Nuclear transfer involves transferringNuclear transfer involves transferring
the complete genetic material (the DNA containedthe complete genetic material (the DNA contained
in a nucleus) from one cell into an unfertilized eggin 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 19981998
nn Two researchTwo research teams succeed in growingteams succeed in growing embryonicembryonic
stem cellsstem cells, the long sought grail of molecular, the long sought grail of molecular
biology.biology.
nn Scientists at Japan's Kinki UniversityScientists at Japan's Kinki University clone eightclone eight
identical calvesidentical calves using cells taken from a single adultusing cells taken from a single adult
cow.cow.
nn A rough draft of the humanA 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 19991999
nn MAD COW DISEASEMAD COW DISEASEA new medicalA new medical
diagnostic test will for the first time allow quickdiagnostic test will for the first time allow quick
identification ofidentification of BSE/CJDBSE/CJD a rare buta rare but
devastating form ofdevastating form of neurologicneurologic diseasedisease
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 companies
nn 1992: 80,000 employees, $8.1 billion in revenues;1992: 80,000 employees, $8.1 billion in revenues;
about same # companiesabout same # companies
nn Compensation in biotechnology companies isCompensation in biotechnology companies is
competitive and includes incentives, such as stockcompetitive and includes incentives, such as stock
option plans, 401K plans, companyoption plans, 401K plans, company--wide stockwide stock
purchase plans, and cash bonus plans.purchase plans, and cash bonus plans.

Approved Biotech ProductsApproved Biotech Products
nn 1938: Howard1938: 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 penicillin
nn 19431943--1953: Cortisone first manufactured in large1953: Cortisone first manufactured in large
amountsamounts
nn 1977:1977: GenentechGenentech producedproduced somatostatinsomatostatin (human(human
growth hormonegrowth hormone--releasing inhibitory factor),releasing inhibitory factor),
manufactured in bacteria. First time a recombinant genemanufactured 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 by1978: Harvard researchers produced rat insulin by
recombinant DNA.recombinant DNA.

nn 1982: FDA approves genetically engineered1982: FDA approves genetically engineered
human insulinhuman insulin
nn 1986:1986: OrthocloneOrthoclone OKT3 (MuromonabOKT3 (Muromonab--CD3)CD3)
approved for reversal of kidney transplantapproved for reversal of kidney transplant
rejection.rejection.
nn 1986: first recombinant vaccine approved1986: first recombinant vaccine approved--
hepatitishepatitis
nn 1987:1987: GenentechGenentech gets approval forgets approval for rtrt--PA (tissuePA (tissue
plasminogenplasminogen activatioractivatior) for heart attacks) for heart attacks

nn 1990:1990: ActimmuneActimmune (interferon 1b) approved for(interferon 1b) approved for
chronicchronic granulomatousgranulomatous diseasedisease
nn AdagenAdagen (adenosine(adenosine deaminasedeaminase) approved for) approved for
severe combined immunodeficiency diseasesevere combined immunodeficiency disease
nn 1994: first genetically engineered food the1994: first genetically engineered food the FlavrFlavr
SavrSavr tomato is approved.tomato is approved.
nn 1994:1994: Genentech’sGenentech’s NutropinNutropin is approvedis approved
(growth hormone deficiency)(growth hormone deficiency)

nn 1994:1994: Centocor’sCentocor’s ReoProReoPro approved (for patientsapproved (for patients
undergoing balloon angioplasty)undergoing balloon angioplasty)
nn GenzymesGenzymes Ceredase/CerezymeCeredase/Cerezyme approved forapproved for
Gaucher’sGaucher’s Disease (inherited metabolicDisease (inherited metabolic disease)disease)
nn Recombinant GMRecombinant GM--CSF approvedCSF approved
(chemotherapy induced(chemotherapy induced neutropenianeutropenia))
•• 1998:1998: Centocor’sCentocor’s RemicadeTMRemicadeTM approvedapproved
(monoclonal antibody for(monoclonal antibody for Crohn’sCrohn’s disease)disease)

Focus on “Famous” BiotechFocus 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 Nobelwon 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 pancreaticThey 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 typesNote 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 normalinsulin is produced in far greater amounts under normal
conditions making the simple approach used byconditions making the simple approach used by BantingBanting andand
Best quite successful.Best quite successful.

Properties of InsulinProperties of Insulin
nn Insulin is secreted by groups of cells within theInsulin 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 stomachThe pancreas is an organ that sits behind the stomach
and has many functions in addition to insulinand has many functions in addition to insulin
production.production.
nn The pancreas also produces digestive enzymes andThe pancreas also produces digestive enzymes and
other.other.
nn Without insulin, you can eat lots of food and actually beWithout insulin, you can eat lots of food and actually be
in a state of starvation since many of our cells cannotin a state of starvation since many of our cells cannot
access the calories contained in the glucose very wellaccess 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 preparationsThe first successful insulin preparations
came from cows (and later pigs)came from cows (and later pigs).. TheThe
pancreatic islets and the insulin proteinpancreatic islets and the insulin protein
contained within them were isolated fromcontained within them were isolated from
animals slaughtered for food in a similar butanimals slaughtered for food in a similar but
more complex fashion than was used by ourmore complex fashion than was used by our
doctor and meddoctor and med--student duo.student duo.

nn DiagnosticsDiagnostics
nn AntibodiesAntibodies
nn BiosensorsBiosensors
nn PCRPCR
nn TherapeuticsTherapeutics
nn Natural ProductsNatural Products
nn Foxglove:Foxglove:
nn digitalis: heart conditionsdigitalis: heart conditions
nn Yew treeYew tree-- cancer agent (taxol) breast and ovarian cancerscancer agent (taxol) breast and ovarian cancers
nn Endogenous Therapeutic agentsEndogenous Therapeutic agents –– proteins produced by theproteins produced by the
body that can be replicated by genetically engineered:body that can be replicated by genetically engineered: tPAtPA ––
tissuetissue plasminogenplasminogen factor (dissolves blood clots)factor (dissolves blood clots)

nn Biopolymers and Medical DevicesBiopolymers and Medical Devices-- naturalnatural
substances useful as medical devicessubstances useful as medical devices
nn hyaluronatehyaluronate-- an elastic, plastic like substance used to treatan elastic, plastic like substance used to treat
arthritis, preventarthritis, 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 DrugsDesigner Drugs –– using computerusing computer
modeling to design drugs without the labmodeling to design drugs without the lab--
protein structureprotein structure

nn Replacement TherapiesReplacement Therapies-- lack of productionlack of production
of normal substancesof normal substances
nn Factor VIIIFactor VIII-- missing in hemophiliamissing in hemophilia
nn InsulinInsulin
nn Use of Transgenic Animals and PlantsUse of Transgenic Animals and Plants

nn Gene TherapyGene Therapy –– replace defective genes withreplace defective genes with
functional onesfunctional ones
nn ADA (adenosineADA (adenosine deaminasedeaminase) deficiency) deficiency
nn cystic fibrosiscystic fibrosis
nn Immunosuppressive TherapiesImmunosuppressive Therapies –– used to inhibitused to inhibit
rejection (organ transplants)rejection (organ transplants)
nn Cancer TherapiesCancer Therapies --one method is antisenseone method is antisense
technologytechnology
nn VaccinesVaccines –– biggest break through inbiggest break through in
biotechnologybiotechnology-- prevention of diseaseprevention of disease

Biotech history

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