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Page 1: History of Biotech and Biotech Applications

History of History of Biotech and Biotech and

Biotech Biotech ApplicationsApplicationsBIT 120BIT 120

Source for History Source for History Information:Information:

www.accessexcellence.orgwww.accessexcellence.org

Page 2: History of Biotech and Biotech Applications

History of BiotechnologyHistory of Biotechnology

The term "The term "biotechnologybiotechnology" was coined in " was coined in 1919 by Karl Ereky, an Hungarian engineer1919 by Karl Ereky, an Hungarian engineer

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

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

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ExamplesExamples

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

breed their own animals, they learned breed their own animals, they learned to use biotechnology. to use biotechnology.

The discovery that fruit juices The discovery that fruit juices fermented into wine, or that milk could fermented into wine, or that milk could be converted into cheese or yogurt, or be converted into cheese or yogurt, or that beer could be made by fermenting that beer could be made by fermenting solutions of malt and hops began the solutions of malt and hops began the study of biotechnologystudy of biotechnology

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Examples cont’dExamples cont’d

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

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

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

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

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

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

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Periods of Biotechnology Periods of Biotechnology History:History:

Pre- 1800: Early applications and Pre- 1800: Early applications and speculationspeculation

1800-1900: Significant advances in 1800-1900: Significant advances in basic understandingbasic understanding

1900-1953: Genetics1900-1953: Genetics 1953- 1976: DNA research, science 1953- 1976: DNA research, science

explodesexplodes 1977- present: modern biotechnology1977- present: modern biotechnology

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Biotechnology Time Biotechnology Time LinesLines

6000 BC6000 BC Yeast was used to make beer by Sumerians and Yeast was used to make beer by Sumerians and

Babylonians. Babylonians. 4000 BC4000 BC The Egyptians discovered how to bake leavened The Egyptians discovered how to bake leavened

bread using yeast. bread using yeast. 420 BC420 BC Socrates (470? - 399 BC), the Greek philosopher, Socrates (470? - 399 BC), the Greek philosopher,

speculated on why children don't always resemble speculated on why children don't always resemble their parents. their parents.

320 BC320 BC Aristotle (384 - 322 BC), told his students that all Aristotle (384 - 322 BC), told his students that all

inheritance comes from the father. inheritance comes from the father.

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Biotechnology Time Biotechnology Time LinesLines

1000 AD1000 AD Hindus observed that certain diseases may "run in Hindus observed that certain diseases may "run in

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

1630 AD1630 AD William HarveyWilliam Harvey concluded that plants and animals concluded that plants and animals

alike reproduce in a sexual manner:–alike reproduce in a sexual manner:–egg isolated in egg isolated in 1800’s1800’s

1660-1675 AD1660-1675 AD Marcello Malpighi (1628-1694) in this period used a Marcello Malpighi (1628-1694) in this period used a

microscope to study blood circulation in capillaries, microscope to study blood circulation in capillaries, described the nervous system as bundles of fibers described the nervous system as bundles of fibers connected to the brain by the spinal cord,. connected to the brain by the spinal cord,.

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1673 AD1673 AD Anton van Leeuwenhoek (1632 - 1723), He was the Anton van Leeuwenhoek (1632 - 1723), He was the

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

17011701 Giacomo Pylarini in Constantiople practiced Giacomo Pylarini in Constantiople practiced

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

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

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1809 1809 Nicolas Appert devised a technique using heat to can Nicolas Appert devised a technique using heat to can

and sterilize foodand sterilize food 18271827 The worldwide search for the elusive mammalian The worldwide search for the elusive mammalian

egg ended with the first observation of canine eggs. egg ended with the first observation of canine eggs. Remember 1630 and William HarveyRemember 1630 and William Harvey

18501850 ONE OF MY FAVORITES ONE OF MY FAVORITES Ignaz Semmelweis used Ignaz Semmelweis used

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

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1856 1856 Karl Ludwig discovered a technique for keeping Karl Ludwig discovered a technique for keeping

animal organs alive outside the body, by pumping animal organs alive outside the body, by pumping blood through them. blood through them.

In contrast to the ideas of Justis Liebig, In contrast to the ideas of Justis Liebig, Louis PasteurLouis Pasteur (1822 - 1895) (1822 - 1895) asserted that microbes asserted that microbes are responsible for fermentation. are responsible for fermentation. 18591859

Charles Darwin (1809 - 1882Charles Darwin (1809 - 1882) hypothesized that ) hypothesized that animal populations adapt their forms over time to animal populations adapt their forms over time to best exploit the environment, a process he referred best exploit the environment, a process he referred to as "natural selection." As he traveled in the to as "natural selection." As he traveled in the Galapagos Islands, Galapagos Islands, he observed how the finch's he observed how the finch's beaks on each island were adaptedbeaks on each island were adapted to their food to their food sources. sources.

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18631863 Louis PasteurLouis Pasteur invented the process of invented the process of

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

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

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18651865 Gregor MendelGregor Mendel (1822 - 1884), an Augustinian monk, (1822 - 1884), an Augustinian monk,

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

..

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

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

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18681868 Davaine used heat treatment to cure a Davaine used heat treatment to cure a

plant of bacterial infection. plant of bacterial infection. Fredrich Miescher, a Swiss biologist, Fredrich Miescher, a Swiss biologist,

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

18701870 W. Flemming discovered mitosis. W. Flemming discovered mitosis.

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18711871 DNA was isolated from the sperm of trout DNA was isolated from the sperm of trout

found infound in the Rhine River. the Rhine River. 1873-61873-6 Robert Koch investigated anthrax and developed Robert Koch investigated anthrax and developed

techniques to view, grow, and stain organisms. He techniques to view, grow, and stain organisms. He then photographed them, aided by Gram, Cohn, and then photographed them, aided by Gram, Cohn, and Weigart. Weigart.

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

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

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1881 ANTRAX1881 ANTRAX Robert Koch described bacterial colonies Robert Koch described bacterial colonies

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

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

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18841884 ROBERT KOCH STATED HIS "POSTULATES" ROBERT KOCH STATED HIS "POSTULATES"

FOR TESTING WHETHER A MICROBE IS FOR TESTING WHETHER A MICROBE IS THE CAUSAL AGENT OF A DISEASETHE CAUSAL AGENT OF A DISEASE. .

Pasteur developed a Pasteur developed a rabies vaccinerabies vaccine. . Christian Gram described the differential Christian Gram described the differential

staining technique for bacteria known as the staining technique for bacteria known as the Gram stain. Gram stain.

Gregor Mendel died after 41 years of Gregor Mendel died after 41 years of meticulously studying the heredity "factors" of meticulously studying the heredity "factors" of pea plants. Having received no scientific acclaim pea plants. Having received no scientific acclaim during his lifetime, he said not long before his during his lifetime, he said not long before his death, "My time will come." death, "My time will come."

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1900 - 1953 - Converging on DNA1900 - 1953 - Converging on DNA 1900 MENDEL’S WORK FINALLY TOOK ON 1900 MENDEL’S WORK FINALLY TOOK ON

IMPORTANCEIMPORTANCE The science of genetics was finally born when The science of genetics was finally born when

Mendel'sMendel's work was rediscovered by three work was rediscovered by three scientists - Hugo DeVries, Erich Von Tschermak, scientists - Hugo DeVries, Erich Von Tschermak, and Carl Correns - each one independently and Carl Correns - each one independently researching scientific literature for precedents to researching scientific literature for precedents to their own "original" work. their own "original" work.

1902 HUMAN GENETICS BORN1902 HUMAN GENETICS BORN Walter Stanborough Sutton stated that Walter Stanborough Sutton stated that

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

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1905 X AND Y CHROMOSOMES RELATED TO 1905 X AND Y CHROMOSOMES RELATED TO GENDERGENDER

Edmund Wilson and Nellie Stevens proposed the Edmund Wilson and Nellie Stevens proposed the idea that separate X and Y chromosomes determine idea that separate X and Y chromosomes determine sex. They showed that a single Y chromosome sex. They showed that a single Y chromosome determines maleness, and two copies of the X determines maleness, and two copies of the X chromosome determine femaleness. chromosome determine femaleness.

1905-19081905-1908 William Bateson and Reginald Crudell Punnett, along William Bateson and Reginald Crudell Punnett, along

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

19061906 Paul Erlich investigated atoxyl compounds and Paul Erlich investigated atoxyl compounds and

discovered the beneficial properties of Salvarsan - discovered the beneficial properties of Salvarsan - the first chemotherapeutic agent. the first chemotherapeutic agent.

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19071907 Thomas Hunt Morgan began his work with fruit Thomas Hunt Morgan began his work with fruit

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

1909 MENDEL’S LAWS TO ANIMALS1909 MENDEL’S LAWS TO ANIMALS Wilhelm Johannsen coined the terms 'gene' to Wilhelm Johannsen coined the terms 'gene' to

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

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1910 BASIS OF MODERN GENETICS1910 BASIS OF MODERN GENETICS Thomas Hunt Morgan proved that genes are Thomas Hunt Morgan proved that genes are

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

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

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

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19121912 Lawrence Bragg discovered that X-rays can Lawrence Bragg discovered that X-rays can

be used to study the molecular structure of be used to study the molecular structure of simplesimple crystalline substances. crystalline substances. 19181918

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

1924 EUGENICS IN THE UNITED STATES1924 EUGENICS IN THE UNITED STATES Politicians encouraged by the eugenics Politicians encouraged by the eugenics

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

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19261926 Thomas Hunt Morgan published 'The theory Thomas Hunt Morgan published 'The theory

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

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

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

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

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

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19381938 Proteins and DNA were studied in various Proteins and DNA were studied in various

labs with X-ray crystallography. labs with X-ray crystallography. The term "molecular biology" was coined. The term "molecular biology" was coined. 1941 ONE GENE ONE ENZYME1941 ONE GENE ONE ENZYME George Beadle and Edward Tatum George Beadle and Edward Tatum

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

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19431943 The Rockefeller Foundation, collaborating The Rockefeller Foundation, collaborating

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

1943-19531943-1953 Cortisone was first manufactured in Cortisone was first manufactured in

large amounts. KIND OF A FIRST large amounts. KIND OF A FIRST BIOTECH PRODUCTBIOTECH PRODUCT

19441944 Waksman isolated Waksman isolated streptomycinstreptomycin, an , an

effective antibiotic for TB. effective antibiotic for TB.

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19451945 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. 1945 - 19501945 - 1950 CELLS GROWN IN LAB CELLS GROWN IN LAB Isolated animal Isolated animal

cell cultures were grown in laboratories. cell cultures were grown in laboratories. 19471947 Barbara McClintockBarbara McClintock first reported on first reported on

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

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19501950 Erwin Chargaff found that in DNA the Erwin Chargaff found that in DNA the

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

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1953 - 1976: Expanding the Boundaries 1953 - 1976: Expanding the Boundaries of DNA Researchof DNA Research

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

19531953 Nature magazine published Nature magazine published James Watson'sJames Watson's

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

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19531953 Gey developed the HeLa human cell Gey developed the HeLa human cell

line. line. HENRIETTA LACKS- DIED HENRIETTA LACKS- DIED IN 1951 OF CERVICAL CANCER- IN 1951 OF CERVICAL CANCER- MOTHER OF 5- HER CELLS MOTHER OF 5- HER CELLS FIRST SHOWN TO GROW FIRST SHOWN TO GROW OUTSIDE THE BODY FOR OUTSIDE THE BODY FOR EXTENDED PERIODS- USED TO EXTENDED PERIODS- USED TO DEVELOP THE POLIO VACCINEDEVELOP THE POLIO VACCINE

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1957 CENTRAL DOGMA OF DNA- HOW 1957 CENTRAL DOGMA OF DNA- HOW DNA MAKES A PROTEINDNA MAKES A PROTEIN

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

19591959 Francois Jacob and Jacques Monod Francois Jacob and Jacques Monod

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

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19621962 Watson and Crick shared the 1962 Watson and Crick shared the 1962

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

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1966 GENETIC CODE CRACKED1966 GENETIC CODE CRACKED The genetic code was "cracked". The genetic code was "cracked".

Marshall Nirenberg, Heinrich Marshall Nirenberg, Heinrich Mathaei, and Severo Ochoa Mathaei, and Severo Ochoa demonstrated that a sequence of demonstrated that a sequence of three nucleotide bases (a codon) three nucleotide bases (a codon) determines each of 20 amino acids. determines each of 20 amino acids.

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19671967 Arthur Arthur KornbergKornberg conducted a study conducted a study using using

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

19701970 ONCOGENESONCOGENES Peter Duesberg and Peter Peter Duesberg and Peter

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

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1972 FIRST RECOMBINANT DNA MOLECULE1972 FIRST RECOMBINANT DNA MOLECULE Paul BergPaul Berg isolated and employed a restriction enzyme isolated and employed a restriction enzyme

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

1972 NIH GUIDELINES FOR RECOMBINANT 1972 NIH GUIDELINES FOR RECOMBINANT DNADNA

In a letter to Science, Stanford biochemist Paul Berg In a letter to Science, Stanford biochemist Paul Berg and others called for the National Institutes of Health and others called for the National Institutes of Health to enact guidelines for DNA splicing.. Their concerns to enact guidelines for DNA splicing.. Their concerns eventually led to the 1975 Asilomar Conference. eventually led to the 1975 Asilomar Conference.

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1973 AMES TEST1973 AMES TEST Bruce Ames, a biochemist at UC Berkeley, Bruce Ames, a biochemist at UC Berkeley,

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

1975 RECOMBINANT DNA MORITORIUM1975 RECOMBINANT DNA MORITORIUM A moratorium on recombinant DNA experiments A moratorium on recombinant DNA experiments

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

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1976 MORE ABOUT ONCOGENES1976 MORE ABOUT ONCOGENES J. Michael BishopJ. Michael Bishop and and Harold Harold VarmusVarmus, ,

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

1976 RELEASE OF NIH GUIDELINES1976 RELEASE OF NIH GUIDELINES The NIH released the first guidelines for The NIH released the first guidelines for

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

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1977 - Present: The Dawn of Biotech1977 - Present: The Dawn of Biotech Genetic engineering became a reality when a man-Genetic engineering became a reality when a man-

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

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19771977 GenentechGenentech, , Inc., reports the production of the first Inc., reports the production of the first

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

19781978 RECOMBINANT INSULINRECOMBINANT INSULIN Genentech, Inc. and Genentech, Inc. and

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

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1980 PATENTS ALLOWED1980 PATENTS ALLOWED The U.S. Supreme Court ruled in that The U.S. Supreme Court ruled in that

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

Kary Mullis and others at Cetus Kary Mullis and others at Cetus Corporation in Berkeley, California, Corporation in Berkeley, California, invented a technique for multiplying DNA invented a technique for multiplying DNA sequences in vitro by, the sequences in vitro by, the polymerase chain reactionpolymerase chain reaction (PCR). (PCR). PCR PCR POLYMERASE CHAIN REACTIONPOLYMERASE CHAIN REACTION

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19821982 Genentech, Inc. Genentech, Inc. received approval from the received approval from the

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

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

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

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

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

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

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19861986 The FDA granted a license for the The FDA granted a license for the first first

recombinant vaccinerecombinant vaccine (for hepatitis) to Chiron (for hepatitis) to Chiron Corp. Corp.

The EPA approved the release of the first genetically The EPA approved the release of the first genetically engineered crop, engineered crop, gene-altered tobacco plants. gene-altered tobacco plants.

19871987 Calgene, Inc. received a patent for the tomato Calgene, Inc. received a patent for the tomato

polygalacturonase DNA sequence, used to produce polygalacturonase DNA sequence, used to produce an antisense RNA sequence that can extend the an antisense RNA sequence that can extend the shelf-life of fruitshelf-life of fruit. .

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19881988 Harvard molecular geneticists Philip Harvard molecular geneticists Philip

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

19901990 UCSF and Stanford University were issued UCSF and Stanford University were issued

their 100th recombinant DNA patent license. their 100th recombinant DNA patent license. By the end of fiscal 1991, both campuses had By the end of fiscal 1991, both campuses had earned $40 million from the patent. earned $40 million from the patent. PATENTS AND MONEYPATENTS AND MONEY

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19901990 The first gene therapy takes place, on a four-year-old The first gene therapy takes place, on a four-year-old

girl with an immune-system disorder called ADA girl with an immune-system disorder called ADA deficiency. The therapy appeared to work, but set off deficiency. The therapy appeared to work, but set off a fury of discussion of ethics both in academia and in a fury of discussion of ethics both in academia and in the media. the media.

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

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

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19921992 The U.S. Army begins collecting The U.S. Army begins collecting

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

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

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

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19941994 The first genetically engineered food product, The first genetically engineered food product,

the Flavr Savr tomato, gained FDA approval.the Flavr Savr tomato, gained FDA approval. The first crude but thorough linkage map of the The first crude but thorough linkage map of the

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

1995 1995 A new coalition of mainstream religions launched A new coalition of mainstream religions launched

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

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19961996 A new inexpensive diagnostic biosensor test for the A new inexpensive diagnostic biosensor test for the

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

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

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

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19971997 Researchers at Scotland's Roslin Institute Researchers at Scotland's Roslin Institute

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

..

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19981998 Two research Two research teams succeed in growing teams succeed in growing

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

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

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

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19991999 MAD COW DISEASEMAD COW DISEASEA new medical A new medical

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

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Biotechnology StatsBiotechnology Stats

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

revenues; 1450 total companies and 350 revenues; 1450 total companies and 350 public companiespublic companies

1992: 80,000 employees, $8.1 billion in 1992: 80,000 employees, $8.1 billion in revenues; about same # companiesrevenues; about same # companies

Compensation in biotechnology companies is Compensation in biotechnology companies is competitive and includes incentives, such as competitive and includes incentives, such as stock option plans, 401K plans, company-wide stock option plans, 401K plans, company-wide stock purchase plans, and cash bonus plans. stock purchase plans, and cash bonus plans.

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Approved Biotech Approved Biotech ProductsProducts

1938: Howard Florey/Ernst Chain, Oxford 1938: Howard Florey/Ernst Chain, Oxford U., England isolated penicillinU., England isolated penicillin

1940-1945: Large scale production of 1940-1945: Large scale production of penicillinpenicillin

1943-1953: Cortisone first manufactured in 1943-1953: Cortisone first manufactured in large amountslarge amounts

1977: Genentech produced somatostatin 1977: Genentech produced somatostatin (human growth hormone-releasing (human growth hormone-releasing inhibitory factor), manufactured in bacteria. inhibitory factor), manufactured in bacteria. First time a recombinant gene was used to First time a recombinant gene was used to clone a protein.clone a protein.

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

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Approved Biotech Approved Biotech ProductsProducts

1982: FDA approves genetically 1982: FDA approves genetically engineered human insulinengineered human insulin

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

1986: first recombinant vaccine 1986: first recombinant vaccine approved- hepatitisapproved- hepatitis

1987: Genentech gets approval for rt-1987: Genentech gets approval for rt-PA (tissue plasminogen activatior) for PA (tissue plasminogen activatior) for heart attacksheart attacks

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Approved Biotech Approved Biotech ProductsProducts

1990: Actimmune (interferon 1b) 1990: Actimmune (interferon 1b) approved for chronic granulomatous approved for chronic granulomatous diseasedisease

Adagen (adenosine deaminase) approved Adagen (adenosine deaminase) approved for severe combined immunodeficiency for severe combined immunodeficiency diseasedisease

1994: first genetically engineered food 1994: first genetically engineered food the Flavr Savr tomato is approved.the Flavr Savr tomato is approved.

1994: Genentech’s Nutropin is approved 1994: Genentech’s Nutropin is approved (growth hormone deficiency)(growth hormone deficiency)

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Approved Biotech Approved Biotech ProductsProducts

1994: Centocor’s ReoPro approved (for 1994: Centocor’s ReoPro approved (for patients undergoing balloon angioplasty)patients undergoing balloon angioplasty)

Genzymes Ceredase/Cerezyme approved Genzymes Ceredase/Cerezyme approved for Gaucher’s Disease (inherited for Gaucher’s Disease (inherited metabolic disease)metabolic disease)

Recombinant GM-CSF approved Recombinant GM-CSF approved (chemotherapy induced neutropenia)(chemotherapy induced neutropenia)

1998: Centocor’s RemicadeTM approved 1998: Centocor’s RemicadeTM approved (monoclonal antibody for Crohn’s disease)(monoclonal antibody for Crohn’s disease)

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

Insulin: Insulin: Insulin is a hormone, and therefore, a protein.Insulin is a hormone, and therefore, a protein.     Insulin was the first hormone identifiedInsulin was the first hormone identified (late (late

1920's) which won the doctor and medical student 1920's) which won the doctor and medical student who discovered it the Nobel Prize (Banting and who discovered it the Nobel Prize (Banting and Best).  Best). 

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

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

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Properties of InsulinProperties of Insulin Insulin is secreted by groups of cells Insulin is secreted by groups of cells

within the pancreas called islet cells. within the pancreas called islet cells. The pancreas is an organ that sits behind The pancreas is an organ that sits behind

the stomach and has many functions in the stomach and has many functions in addition to insulin production. addition to insulin production.

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

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

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Insulin (cont’d)Insulin (cont’d)

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

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Biotech ApplicationsBiotech Applications DiagnosticsDiagnostics

AntibodiesAntibodies BiosensorsBiosensors PCRPCR

TherapeuticsTherapeutics Natural ProductsNatural Products Foxglove: Foxglove: digitalis: heart conditionsdigitalis: heart conditions

Yew tree- cancer agent (taxol) breast and ovarian Yew tree- cancer agent (taxol) breast and ovarian cancerscancers

Endogenous Therapeutic agents – proteins Endogenous Therapeutic agents – proteins produced by the body that can be replicated by produced by the body that can be replicated by genetically engineered: tPA – tissue plasminogen genetically engineered: tPA – tissue plasminogen factor (dissolves blood clots)factor (dissolves blood clots)

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Biotech ApplicationsBiotech Applications

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

hyaluronate- an elastic, plastic like substance hyaluronate- an elastic, plastic like substance used to treat arthritis, prevent postsurgical used to treat arthritis, prevent postsurgical scarring in cataract surgery, used for drug scarring in cataract surgery, used for drug deliverydelivery

adhesive substances to replace stitchesadhesive substances to replace stitches

Designer Drugs – using computer Designer Drugs – using computer modeling to design drugs without modeling to design drugs without the lab- protein structurethe lab- protein structure

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Biotech ApplicationsBiotech Applications

Replacement Therapies- lack of Replacement Therapies- lack of production of normal substancesproduction of normal substances

Factor VIII- missing in hemophiliaFactor VIII- missing in hemophilia InsulinInsulin

Use of Transgenic Animals and Use of Transgenic Animals and PlantsPlants

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Biotech ApplicationsBiotech Applications

Gene Therapy – replace defective Gene Therapy – replace defective genes with functional onesgenes with functional ones

ADA (adenosine deaminase) deficiencyADA (adenosine deaminase) deficiency cystic fibrosiscystic fibrosis

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

Cancer Therapies -one method is Cancer Therapies -one method is antisense technologyantisense technology

Vaccines – biggest break through in Vaccines – biggest break through in biotechnology- prevention of diseasebiotechnology- prevention of disease