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8/12/2019 PENGENTAR BITEHNOLOGI HUTAN

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The History of

Biotechnology

http://www.i-s-b.org/wissen/timeline/englisch/


15/73

1859Charles Darwin publishes his

book ( On the Origin ofSpecies by Means ofNatural Selection ).

According to this bookevolution is life

s motor.The interplay of mutationand selection endows livingbeings with optimized traitsin order to survive. Theseprinciples are also valid forthe so-called 'chemicalevolution' of biomoleculesand are being used inlaboratories for in vitro optimizing of wantedqualities in molecules
http://www.literature.org/authors/darwin-charles/http://www.literature.org/authors/darwin-charles/http://www.literature.org/authors/darwin-charles/http://www.literature.org/authors/darwin-charles/http://www.literature.org/authors/darwin-charles/http://www.literature.org/authors/darwin-charles/


16/73

1865Gregor Mendel finds that

independent 'factors' areresponsible for the heredityof traits from one

generation to the nextaccording to a set of(Mendelian) priciples.


17/73

1869Friedrich Miescher discovers

an acidic substance in thenucleus of cells which henames 'nuclein'. By

elemental analysis he finds14 % nitrogen, 3 %phosphorus, and 2 % sulfur(from proteins). Since thesubstance cannot be

cleaved by the proteolyticenzyme pepsin Miescherconcludes that thissubstance is not a protein.


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1879

Walther Flemming observesthe separation ofchromosomes duringmitosis but fails to fully

understand its meaning. Hecounts 24 pairs ofchromosomes, a numberwhich will be corrected to23 later in 1956 by the

Indonesian scientist Joe-Han Tijo .
http://www.i-s-b.org/wissen/timeline/englisch/1956.htmhttp://www.i-s-b.org/wissen/timeline/englisch/1956.htm


19/73

1900William Bateson introduces

'genetics' as a scientificdiscipline

Hugo de Vries , Erich Tschermak

von Seysenegg and Carl Correns independently rediscover theMendelian principles

Hugo de Vries

defines themeaning of'mutations'


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1902

Walter Sutton observes ingrasshoppers' cells thatchromosomes carry theMendelian 'factors of

heredity', i.e. the geneticinformation.


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1909

Wilhelm Johansen coins theterms 'gene' , 'genotype' ,and 'phenotype' referring toMendel's 'factors' .

Archibald Garrod confirmsthe hereditary nature of fourmetabolic diseases . Hepublishes "Inborn Errors ofMetabolism"
http://www.people.virginia.edu/~rjh9u/garrod1.htmlhttp://www.people.virginia.edu/~rjh9u/garrod1.htmlhttp://www.people.virginia.edu/~rjh9u/garrod1.htmlhttp://www.people.virginia.edu/~rjh9u/garrod1.html


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1910

Thomas Hunt Morgan 'sstudies in the biology ofDrosophila melanogaster confirm that certain traits

are inherited sex-specifically. He also provesthat some phenotypesresult from several geneslocated on different

chromosomes.


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1927

Herman Muller finds thatenergetic radiation causesdefects in thechromosomes, i.e.

mutations.


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1928

Fred Griffith demonstratesthat material from killedbacteria of the pathogenicstrain Streptococcus

pneumoniae S ('smooth') istaken up from living ones ofthe non-pathogenic strainStreptococcus pneumoniaeR ('rough') which are

subsequently 'transformed'into the pathogenic S-strain.Pneumococcus pneumoniae


25/73

1944

Oswald Theodore Avery , Colin McLeod , and MaclynMcCarty find by careful analysis of Griffith' experimentsthat desoxynucleic acid (DNA) is the carrier of the'transforming principle'.


26/73

1945

Erwin Schrdinger proposesin his famous book 'What islife?' that genes must be'aperiodic crystals'

consisting of a successionof a small number ofisomeric elements whoseprecise sequenceconstitutes the heredity

code. Although these ideasdo nothing to identify theresponsible molecularstructures, they attractmany newcomers to the

field.


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1950

Erwin Chargaff observes the1:1 ratio of the nucleicbases adenine/thymine andguanine/cytosine. This will

be a decisive hint forWatson & Crick to thestructure of the DNAmolecule.


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1952Alfred Day Hershey 's and MarthaChase 's studies in bacteriophages

prove that only the nucleic acids carrythe genetic information; proteins aredefinitively excluded from playing thisrole.

Joshua Lederberg finds plasmids in

bacteria, small rings ofextrachromosomal DNA which can bereplicated autonomously.


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1953

James D. Watson and Francis H. C. Crick elucidate thestructure of the DNA molecule. It consists of two strandswhich are bound by hydrogen bonds bewtween oppositebasepairs of adenine-thymine and cytosine-guanine. Theirmodel is based on the results of many colleages, namelyRosalind Franklin who discovered the helical structure andthe outward position of the phosphate-sugar backbone.
http://www.accessexcellence.com/AB/BC/Rosalind_Franklin.htmlhttp://www.accessexcellence.com/AB/BC/Rosalind_Franklin.html


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1956..Arthur Kornberg reports the first in vitro

synthesis of a DNA molecule.

George Emile Palade locates proteinbiosynthesis to theribosomes, the'factories of the cell'.


32/73

1956Joe Han Tijo and Albert Levan correct

the number of the chromosome pairsin human cells to 23. Since the daysof Walther Flemming 24 was believedto be the true number.

Chromosomen einermenschlichen Zelle

protein chains are built at the ribosomes


33/73

1959T. Akiba , T. Koyama , Y.

Isshiki , S. Kimua , T.Fukushima , T. Watanabe and T. Fukusawa describe

the transfer of multipleresistance to antibiotics bybacterial plasmids.Plasmids turn out to beefficient vectors for

trafficking geneticinformation betweenbacteria of different strains.

bacterial plasmid (arrow)


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1960

Francois Jacob and Jaques Monod recognize the functionof the messenger RNA (mRNA). They develop the operonmodel of gene regulation in procaryotes.
http://esg-www.mit.edu:8001/esgbio/pge/lac.htmlhttp://esg-www.mit.edu:8001/esgbio/pge/lac.htmlhttp://esg-www.mit.edu:8001/esgbio/pge/lac.htmlhttp://esg-www.mit.edu:8001/esgbio/pge/lac.html


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1961

Sydney Brenner and Francis Crick claim that every amino acidcorresponds to a triplett ofnucleotides, called 'codons'.

Marshall Nirenberg andHeinrich Mathaei canprove that the codon UUUin mRNA codes for theamino acid phenyl alanineSydney Brenner

Marshall Nirenberg


36/73

1962John Gurdon claims to havereproduced frogs from the

epithelium cells of Xenopuslaevis . J. B. S. Haldane coins 'cloning' when

describing these debatedexperiments. Xenopus laevis South Africanclawed frogs

John Gurdon


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1966Mainly due to the work of Har

Gobind Khorana the'Genetic Code' iscompletely known.


38/73

1968Werner Arber discovers

enzymes, so-callednucleases, which digestDNA double strands fromthe ends.


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1969Jonathan Beckwith is

the first to isolate acomplete gene, in thiscase a gene from thebacterial sugarmetabolism.


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1970Hamilton Smith discovers an enzyme (HindII)

which specifically cleaves DNA doublestrands

Har Gobind Khorana synthesizesa complete gene (that of analanine t-RNA) in vitro .

David Baltimore and Howard Temin discover theviral enzyme reverse transcriptase. It translatesRNA sequences to DNA sequences and thustumbles the age old 'Central Dogma of Genetics'which defined the direction of the flow of thegenetic information to start from DNA via RNA tothe proteins.


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1971Paul Berg , Peter Loban , and

Dale Kaiser find enzymeswhich attach short singlestrands to the blunt ends ofdouble stranded DNA. Thesingle strands consist ofonly one sort of nucleotides.Complementary singlestrands (sticky ends) allowthe coupling of ds DNAfragments; the remaininggaps can be closed by theuse of ligases.


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1972

Janet Mertz and Ron Davis paste DNA fragments ofdifferent origin resulting from specific enzymaticrestriction. They close the gaps using ligases and thus

produce recombinant DNA.


43/73

1973Stanley Cohen and Herbert Boyer paste

enzymatically restricted DNA fragments intoplasmids which have been cleaved byrestriction enzymes. The resultingrecombinant plasmids can serve as vectorsfor the transfer of foreign DNA into bacteria.These experiments are generally regarded asthe beginning of the era of geneticengineering and modern biotechnology.


44/73

1975The first conference on safety issues of the new technology

is held at Asilomar in California.

Georges Khler and Cesar Milstein develop the 'HybridomaTechnology' for the production of monoclonal antibodies. Anantibody producing plasma cell (derived from a Blymphocyte) is fused with a tumor cell resulting in animmortal hybridoma cell which (as well as its daughters)continues to produce one kind of antibodies.


45/73

1976Herbert Boyer and Robert

Swanson found Genentechthe first biotech company.


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1977

Walter Gilbert and Frederick Sanger independentlydevelop two different methods for DNA sequencing.


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1978

Walter Gilbert discovers thatgenes of eucaryoticorganisms are composed ofcoding and non-codingparts. The non-codingsequences, named introns,are cut from the mRNAbefore translation leavingthe coding exons as thesource of information forprotein synthesis.


48/73

1979

Thomas Cech and Sydney Altman discover theautocatalytic activity of some RNA molecules tocleave themselves at well defined positions. Theycoin 'ribozyme' for this type of RNA.


49/73

1980

Jozef Schell and Marc van Montagu transferforeign DNA into plant cells by employing T-plasmids of Agrobacterium tumefaciens asvectors.


50/73

1981The first patent for a genetically modified organism is granted

to Ananda Chakrabarty of General Electric. It covers a P.aeruginosa strain which is equipped with genes of certainenzymes in order to metabolize crude oil.


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1982

The U.S. Food and Drug Agency (FDA) approvesrecombinant insulin formarketing.


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1984Alec Jeffreys develops 'genetic fingerprinting' allowing the

comparison of minute variations, the so-called restrictionlength fragment polymorphisms (RLFPs), in the genomesof two organsims.


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1985

Karry Mullis develops thepolymerase chain reaction(PCR). This powerful toolallows to copy andaccumulate extremely lowamounts of DNA fromvarious sources until a levelsufficient for analysis isreached.


54/73

1986Neal First develops protocols for

clonig cattle from bovineembryos by separating cells atearly embryonic stages. Theseexperiments resemble JohnGurdons earlier attempts at thecloning of frogs. The first cloningof an adult animal will bereported in 1997 by Ian Wilmut who succeeds in cloning asheep, Dolly.
http://www.i-s-b.org/wissen/timeline/englisch/1962.htmhttp://www.i-s-b.org/wissen/timeline/englisch/1962.htmhttp://www.i-s-b.org/wissen/timeline/englisch/1997.htmhttp://www.i-s-b.org/wissen/timeline/englisch/1997.htmhttp://www.i-s-b.org/wissen/timeline/englisch/1962.htmhttp://www.i-s-b.org/wissen/timeline/englisch/1962.htm


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1988

The first patent for atransgenicmammal is grantedto Harvard's PhilipLeder and Timothy

Stewart. It refers toa mouse which issusceptible totumors and servesas model organismfor studies incancer.


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1990

French Anderson successfully tries thefirst somatic gene therapy of a human.Patient

Ashanti DeSilva is cured

from an deficiency in theenzyme ADA, whichcauses severeimmunodeficiency.

German'GeneticEngineering

Act' passesparliament

Official kick-offof the HumanGenome Project(HGP)


57/73

1993

The German GeneticEngineering Act of 1990 isrevised, i.e. manyrestrictions of the 1990version are eased.

The BiotechnologyIndustry OrganizationBIO is created bymerging two smallertrade associations
http://www.uni-giessen.de/gfg/deutsch/g_tec_ge.htmhttp://www.uni-giessen.de/gfg/deutsch/g_tec_ge.htmhttp://www.i-s-b.org/wissen/timeline/englisch/1990.htmhttp://www.bio.org/http://www.bio.org/http://www.bio.org/http://www.bio.org/http://www.bio.org/http://www.bio.org/http://www.i-s-b.org/wissen/timeline/englisch/1990.htmhttp://www.uni-giessen.de/gfg/deutsch/g_tec_ge.htmhttp://www.uni-giessen.de/gfg/deutsch/g_tec_ge.htm


58/73

1994

Genetically modified tomatoes are on sale in the U.S. Canscontaining puree from transgenic tomatoes are on theshelves of british supermarkets.


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1995

The Institute for GenomicResearch (TIGR) publishes thefirst complete sequence of thegenome of a free-livingorganism, the bacterium

Haemophilus influenzae Germany launches the BioRegio

contest. 17 regions compete inpresenting the best blueprint for

the development of commercialbiotechnology to aninternational jury. The threewinning regions will share theprice of DM 150m.

1996
http://www.bioregio.com/http://www.bioregio.com/


60/73

1996The complete sequencing of the baker's yeast'genome is accomplished by close collaborationof laboratories in Europe, Japan, and the U.S.The Saccharomyces cervisiae genome ist thefirst eucaryotic genome completely sequenced.

Patrick Browne ofStanford Universitypresents the first'gene chip'containing 6116different genespecific sequencesof the baker's yeastgenome.

In the U.S.transgenic plantsgrow on more than1.9 million hectares


61/73

1997

Ian Wilmut (right) visits Dolly (center) the first mammalcloned from an adult cell.


62/73

1998Two research teams report embryonicstem cells differentiate to specializedtissue cells. The picture shows an earlydevelopmental stage, the blastocyst.

The first genome of amulticellular organism(Caenorhabditis elegans ) is

sequenced.

Craig Mello und Andrew Fire find that small double-strandedRNA molecules can selectively block gene expression inCaenorhabditis elegans , a phenomenon later referred to asRNA interference (RNAi)

1999


63/73

1999Pluripotent stem cells from tissues

can be reprogrammed to other celltypes.The sequence ofchromosome 22

is published.

The U.S. biotechcompany Celerastarts its ownhuman genomesequencingproject

2000


64/73

2000There are 1300 biotech companies on eachside of the Atlantic. About 400 are listed atstock exchanges.

The genome ofDrosophilamelanogaster issequenced. The fruitfly was introduced byThomas H. Morganinto geneticsresearch.

The Human Genome Organization andCelera present the first working draft of thehuman genome. The picture shows Celera'sCEO J. Craig Venter (left) and Francis

Collins, the speaker of the HGP.

2001


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2001 Less genes than expectedThe international Human Genome Project(HGP) and biotech company CeleraGenomics publish their versions of thesequence of the human genome. TheCelera team estimates the number of

genes to range from 26,000 to 39,000, HGPscientist' estimate is between 30,000 and40,000.

Rice genome

Syngenta (Basel, Switzerland), incollaboration with Myriad Genetics(Salt Lake City, UT), announced thecompleted sequencing of thegenome of Oryza sativa japonica

2001


66/73

2001

RNA interferenceThomas Tuschl isthe first todemonstrate thatRNA interference(RNAi) is alsoworking with

mammalian cells.

2002


67/73

2002Genomes of the malaria agent and its carrier sequencedResearchers of the Institute for Genomic Research (TIGR),the Sanger Institute (UK), and Stanford University publish thegenomic sequence of Plasmodium falciparum andPlasmodium yoelii . The protozoa P. falciparum causesmalaria.The genome of its carrier Anopheles gambiae is alsosequenced and published.

2003


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2003 Genome of SARS virussequencedWithin three weeks after itsdiscovery scientists of theMichael Smith GenomeSciences Centre in BritishColumbia (Vancouver, Canada)succeeded in sequencing thegenome of the virus causingsevere acute respiratorysyndrome (SARS). The RNA

virus remotely resemblescorona virus species andcontains roughly 30,000 genes.

2003


69/73

2003Germ cells from stem cellsKarin Hbner and Hans Schlerof the University ofPennnsylvania succeeded ingenerating oocytes from murinestem cells which were able togrow into further embryonicstages. The experimentdemonstrates the potential ofpluripotent stem cells to acquiretotipotency via a germ line cell

stage

2004


70/73

2004

99.999% accuracyThree years after the publication ofthe first draft a far more preciseversion of the sequence of the

human genome is published.

The number ofidentified genesdecreases againcompared with previousestimations.19,599 have beenconfirmed to encodeproteins, 2188 aresuspected to encode forproteins. 1183 geneshave been generatedthrough duplication ofgenes, 33 genesappear to have beendegenerated intodisfunctionalpseudogenes.

2004


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2004

Fatherless mouseTomohiro Kono of the TokyoUniversity of Agriculture presentedthe first mouse which was obtainedfrom oocytes only. His teamcombined the genomes of oocytes

from adult andnewborn mice andeventually one of460 experimentsresulted in a livinganimal, being 14month old at thetime of publication.Critical for successwas thesuppression of agene whichnormally controlsthe imprinting ofchromosomal DNAfrom mother andfather.

2004


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2004Mice from cancer cellsRudolph Jaenisch of MIT and Lynda Chin of the DanaFarber Cancer Institute generated cloned mice from cancercells by stuffing the nuclei of melanoma cells into de-nucleated mouse oocytes. The resulting blastocysts yieldedstem cells which were suitable for transplantation intonormal blastocysts which eventually developed into livinganimals. Some genetic markers of the melanoma cells werefound again in the animal, but the epigentic patterns hadgone lost - showing that epigenetic modifcations are bothreversible and late stage in the transformation of normalcells into melanoma cells.


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