Guide To Biotechnology

8/7/2019 Guide To Biotechnology

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industrial & environmentalfood & agriculture

health


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The Guide to Biotechnologyis compiled by the

Biotechnology Industry Organization (BIO)

Editors

Roxanna Guilford-Blake

Debbie Strickland

Contributors

BIO Staff


3/112Biotechnology Industry Organization i

table ofContents

Biotechnology: A Collection of Technologies 1

What Is Biotechnolog? .................................................. 1

Cells and Biological Molecules ........................................ 1

Biotechnology Industry Facts 2

Market Capitaliation, 19942006 .................................. 3

U.S. Biotech Industr Statistics: 19952006 ................... 3

U.S. Public Companies b Region, 2006 ........................ 4

Total Financing, 19982007 (in billions o U.S. dollars) .... 4

Biotech Industr Financing .............................................. 5

Time Line 6

Biotechnolog Polic Milestones ................................... 15

Technologies and Tools 18

Bioprocessing Technolog ............................................ 18

Recombinant DNA Technolog ..................................... 18

Monoclonal Antibodies ................................................. 19

Cloning ......................................................................... 20

Protein Engineering....................................................... 20

Biosensors ................................................................... 21

Nanobiotechnolog ...................................................... 21

Microarras ................................................................... 22

From Biotechnology to Biology: Using BiotechTools to Understand Life 23

Research Applications o Biotechnolog ....................... 23

Putting the Pieces Together: Omics and Related Tools .... 27

The Next Step: Using New Knowledge

to Develop Products ................................................ 29

Health Care Applications 32

Diagnostics ................................................................... 32

Therapeutics ................................................................. 32

Personalied Medicine .................................................. 35

Regenerative Medicine ................................................. 36

Vaccines ....................................................................... 37Plant-Made Pharmaceuticals ........................................ 37

Therapeutic Development Overview .............................. 38

Agricultural Production Applications 41

Crop Biotechnolog ...................................................... 41

Forest Biotechnolog .................................................... 44

Animal Biotechnolog ................................................... 45

Aquaculture .................................................................. 51

Global Area o Transgenic Crops, 19952007: Industrialand Developing Countries (million acres) .................. 53

Global Area o Transgenic Crops

in 2006 and 2007 b Countr (million acres)............. 53

Agricultural Biotech Products on the Market 54

Food Biotechnology 60

Improving the Raw Materials ......................................... 60

Food Processing .......................................................... 61

Food Saet Testing ...................................................... 62

Industrial and Enironmental Applications 63

Industrial Sustainabilit.................................................. 63

Biocatalsts .................................................................. 64

Biouel .......................................................................... 64

Existing and Planned U.S. Cellulosic

Ethanol Bioreneries .................................................. 66

Green Plastics .............................................................. 67

Nanotechnolog ........................................................... 67Environmental Biotechnolog ........................................ 68

Industries That Benet .................................................. 69

Consumer Goods Made With Industrial Biotech 70

Examples of Industrial Enzymes 71


4/112ii Guide to Biotenology

Industrial BiotechRelated Sales inChemicals, 2005: $95.5 Billion 72

Preparedness for Pandemics and Biodefense 73

A Strategic Asset .......................................................... 73

Other Approaches ........................................................ 74

Other Uses 75

DNA Fingerprinting ....................................................... 75

Intellectual Property 77

What Is a Patent? ......................................................... 77

The Purpose o a Patent ............................................... 77

Patentable Inventions ...............................................78

Patent Requirements .................................................... 78

The Patent Application.................................................. 79

Patenting Organisms .................................................... 79

Patent Licensing ........................................................... 80Recent Patent Developments ....................................... 80

Ethics 81

Ethical Issues................................................................ 82

BIO Statement of Ethical Principles 86

Biotechnology Resources 88

Periodicals, Headline Services and Web Sites ...........88

General Science Journals ............................................. 89

Biotech Education and Careers .................................... 89

Selected Recent Reports on Biotechnolog .................. 89

Glossary of Biotech-related Terms 93


5/112Biotechnology Industry Organization 1

What Is Biotechnolog?

A is simples, bioechnology is echnology based on biology. Fromha perspecive, he use o biological processes is hardly noeworhy.We began growing crops and raising animals 10,000 years ago oprovide a sable supply o ood and clohing. We have used he biologi-cal processes o microorganisms or 6,000 years o make useul oodproducs, such as bread and cheese, and o preserve dairy producs.

Crops? Cheese? Ta doesn sound very exciing. So why doesbioechnology receive so much atenion?

Te answer is ha in he las 40 years weve gone rom pracicingbioechnology a a macro levelbreeding animals and crops, orexampleo working wih i a a micro level. I was during he

1960s and 70s ha our undersanding o biology reached a poinwhere we could begin o use he smalles pars o organismshebiological molecules o which hey are composedin addiion ousing whole organisms.

An appropriae modern deiniion o bioechnology would behe use o cellular and biomolecular processes o solve prob-lems or make useul producs.

We can ge a beter handle on he meaning o he word biotechnol-ogy by hinking o i in is plural orm, biotechnologies. Tas becausebioechnology is a collection o echnologies ha capialize on heatribues o cells, such as heir manuacuring capabiliies, and pu

biological molecules, such as DNA and proeins, o work or us.

Cells and Biological Molecules

Cells are he basic building blocks o all living hings. Te simplesliving hings, such as yeas, consis o a single, sel-sucien cell. Com-plex creaures more amiliar o us, such as plans, animals and humans,are made o many dieren cell ypes, each o which perorms veryspecic asks.

In spie o he exraordinary diversiy o cell ypes in living hings,wha is mos sriking is heir remarkable similariy.

I urns ou ha all cells have he same basic design, are made ohe same maerials and operae using essenially he same process-es. Almos all cells have a nucleus, which conains DNA ha di-recs cell consrucion and operaion. Cells share oher srucuresas well, including hose ha manuacure proeins. Tis uniy olie a he cellular level provides he oundaion or bioechnology.

WHAT IS DNA?

DNA, or deoxyribonucleic acid, is he herediary maerial inhumans and almos all oher organisms. Nearly every cell in a

persons body has he same DNA. Mos DNA is locaed in he cellnucleus (where i is called nuclear DNA), bu a small amoun o

DNA can also be ound in anoher par o he cell called he mio-chondria (miochondrial DNA or mDNA).

Te inormaion in DNA is sored as a code made up o our chemicalbases: adenine (A), guanine (G), cyosine (C) and hymine (). Hu-man DNA consiss o abou 3 billion bases, and more han 99 perceno hose bases are he same in all people. Te order, or sequence, ohese bases deermines he inormaion available or building andmainaining an organism, similar o he way in which leters o healphabe appear in a cerain order o orm words and senences. Nowo people, excep or idenical wins, share he exac same DNAsequences.

DNA bases pair up wih each oher, A wih and C wih G, o ormunis called base pairs. Each base is also atached o a sugar moleculeand a phosphae molecule. ogeher, a base, sugar, and phosphaeare called a nucleoide. Nucleoides are arranged in wo long srandsha orm a spiral called a double helix. Long, coninuous srands oDNA are organized ino chromosomes. Human cells (excep or hesex, or germ, cells) have 46 chromosomes, arranged in 23 pairs. Halcome rom he moher, hal rom he aher.

Specic secions o DNA ha carry he code or paricular proeins arecalled genes. When a paricular proein is needed, he DNA base pairsspli, and NA (ribonucleic acid) bases atach o he open DNA bases,orming a srand o mNA (messenger NA). Te mNA ravels o

oher pars o he cell where he sequence o he mNA is read byoher cell srucures ha make he proein.

Te NIH provides a well-illusraed primer on DNA and geneics,Help Me Undersand Geneics. You can download i a htp://ghr.nlm.nih.gov/.

WHy IS DNA THE CORNERSTONE OF BIOTECHNOLOGy?

Because virually all cells speak he same geneic language, DNA romone cell can be read and aced on in anoher oneeven a dierencell ype rom a dieren species. Tis eaure is wha makes DNA hecornersone o modern bioechnology. Scieniss can,or example, use

a yeas cell o make human insulin by insering he human insulin geneino he yeas.

DNA is also he oundaion or hundreds o diagnosic ess orgeneic diseases and predisposiion o disease. Some new esscan even ideniy which reamen, and wha dosage, is bes or aparicular paien.

Because DNA and relaed cellular processes are so specic, bioech-nology producs can oen solve problems wih ewer uninended con-sequences han oher approaches. In ac, he bes words o describeodays bioechnology are specic, precise andpredictable.

A Collection of Technologies


6/1122 Guide to Biotenology

Te bioechnology indusry emerged in he 1970s, based large-ly on a new recombinan DNA echnique whose deails were

published in 1973 by Sanley Cohen o Sanord Universiyand Herber Boyer o he Universiy o Caliornia, San Fran-cisco. ecombinan DNA is a mehod o making proeinssuch as human insulin and oher herapiesin culured cellsunder conrolled manuacuring condiions. Boyer wen on oco-ound Genenech, which oday is bioechnologys largescompany by marke capializaion.

Bioechnology has creaed more han 200 new herapies andvaccines, including producs o rea cancer, diabees, HIV/AIDS and auoimmune disorders.

Tere are more han 400 bioech drug producs and vac-

cines currenly in clinical rials argeing more han 200diseases, including various cancers, Alzheimers disease, heardisease, diabees, muliple sclerosis, AIDS and arhriis.

Bioechnology is responsible or hundreds o medical diagnos-ic ess ha keep he blood supply sae rom HIV and deecoher condiions early enough o be successully reaed. Homepregnancy ess are also bioechnology diagnosic producs.

Agriculural bioechnology benes armers, consumersand he environmenby increasing yields and arm income,decreasing pesicide applicaions and improving soil and waerqualiy, and providing healhul oods or consumers.

Environmenal bioech producs make i possible o cleanup hazardous wase more ecienly by harnessing polluion-eaing microbes.

Indusrial bioech applicaions have led o cleaner processesha produce less wase and use less energy and waer in such in-dusrial secors as chemicals, pulp and paper, exiles, ood, energy,and meals and minerals. For example, mos laundry deergensproduced in he Unied Saes conain bioechnology-basedenzymes.

DNA ngerprining , a bioech process, has dramaically im-

proved criminal invesigaion and orensic medicine. I has also ledo signican advances in anhropology and wildlie managemen.

Te bioech indusryis regulaed by he U.S. Food and DrugAdminisraion (FDA), he Environmenal Proecion Agency(EPA) and he Deparmen o Agriculure (USDA).

As o Dec. 31, 2006, here were 1,452 bioechnology compa-nies in he Unied Saes, o which 336 were publicly held.*

Marke capializaion , he oal value o publicly raded bio-ech companies (U.S.) a marke prices, was $360 billion as olae April 2008 (based on socks racked byBioWorld).

Te bioechnology indusry has mushroomed since 1992, wihU.S. healh care bioech revenues rom publicly raded compa-nies rising rom $8 billion in 1992 o $58.8 billion in 2006.*

Bioechnology is one o he mos research-inensive indusriesin he world. U.S. publicly raded bioech companies spen$27.1 billion on research and developmen in 2006.*

Tere were 180,000 employed in U.S. bioech companies in2006.*

Te op ve bioech companies invesed an average o$170,000 per employee in &D in 2007.

In 1982, recombinan human insulin became he rs bio-ech herapy o earn FDA approval. Te produc was devel-oped by Genenech and Eli Lilly and Co.

Corporae parnering has been criical o bioech success.According o BioWorld, in 2007 bioechnology companiessruck 417 new parnerships wih pharmaceuical companiesand 473 deals wih ellow bioech companies. Te indusryalso saw 126 mergers and acquisiions.

Mos bioechnology companies are young companies devel-oping heir rs producs and depend on invesor capial orsurvival. According o BioWorld, bioechnology atraced morehan $24.8 billion in nancing in 2007 and raised more han$100 billion in he ve-year span o 20032007.

Te biosciencesincluding all lie-sciences aciviies em-ployed 1.2 million people in he Unied Saes in 2004 andgeneraed an addiional 5.8 million relaed jobs.**

Te average annual wage o U.S. bioscience workers was

$65,775 in 2004, more han $26,000 greaer han he averageprivae-secor annual wage.**

Te Bioechnology Indusry Organizaion (BIO) was oundedin 1993 o represen bioechnology companies a he local, sae,ederal and inernaional levels. BIO comprises more han 1,200members, including bioech companies, academic ceners, saeand local associaions, and relaed enerprises.

biotechnologyIndustry Facts

* New data are expeted in mid-2008 rom Ernst & Young, wi publises an annual global oeriew o te biotenology industry.** Te data are rom a BIO-sponsored Battelle Memorial Institute report, Growing the Nations Biotech Sector: State Bioscience Initiatives 2006. A new,

updated report is expeted to be released in 2008.



Year 2006 2005 2004 2003 2002 2001 2000 1999 1998 1997 1996 1995 1994

Sales 45.3 39.7 28.1 28.4 24.3 21.4 19.3 16.1 14.5 13 10.8 9.3 7.7

Reenues 53.5 48.5 43.8 39.2 29.6 29.6 26.7 22.3 20.2 17.4 14.6 12.7 11.2

R&D Expense 22.9 16.6 19.6 17.9 20.5 15.7 14.2 10.7 10.6 9.0 7.9 7.7 7.0

Net Loss 3.5 1.4 6.8 5.4 9.4 4.6 5.6 4.4 4.1 4.5 4.6 4.1 3.6

No. of PublicCompanies

336 331 331 314 318 342 339 300 316 317 294 260 265

No. of Companies 1,452 1,475 1,346 1,473 1,466 1,457 1,379 1,273 1,311 1,274 1,287 1,308 1,311

U.S. Biotech Industry Statistics: 19942006*

Source:

Ernst & Young LLP, annual biotenology industry reports, 19952006. Finanial data based primarily on sal-year nanial statements o publilytraded ompanies.**

*Amounts are U.S. dollars in billions.

Market Capitalization, 19942006*

Sources:

Ernst & Young LLP**

450

400

350

300

250

200

150

100

50

01994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006

45 41 52

8393

137.9

353.5

330.8

225206

336.8

408392

Year

** New data are expeted in mid-2008 rom Ernst & Young, wi publises an annual global oeriew o te biotenology industry.



REGION NO. PUBLIc cOS. MARkET cAP.* REvENUE* R&D*

San Franiso Bay Area 69 $145,553 $17,668 $7,485

New England 60 $62,936 $10,384 $3,919

San Diego 38 $20,916 $3,252 $1,432

New Jersey 28 $28,556 $1,747 $802

Mid-Atlanti 23 $17,111 $2,061 $1,270

Souteast 19 $5,301 $544 $271

New Yor State 17 $8,893 $1,373 $685

Mid-West 8 $1,161 $121 $90

Pai Nortwest 15 $4,928 $196 $521

Los Angeles/Orange county 11 $81,585 $14,692 $4,898

Nort carolina 9 $2,017 $328 $191

Pennsylania/Delaware valley 12 $7,140 $2,078 $603

Texas 11 $1,495 $160 $170

colorado 6 $1,847 $296 $195

Uta 2 $1,454 $160 $170

Oter 8 $1,526 $384 $107

U.S. Public Companies by Region, 2006

* Amounts are in millions o U.S. dollars.

Source:

Ernst & Young LLP

Total Financing, 19982007 (in billions o U.S. dollars)

40

35

30

25

20

15

10

5

0

5.4

11.8

38

15.1

10.5

16.9

20.8 20.1 20.3

24.8

1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

Source:

BioWorld



Other fnancings

o public companies:

$13,418.7

(54.2%)

Public oerings:

$5,125.0

(20.7%)

Biotech Industry Financing

Venture unding:

$6,230.1

(25.1%)

Total: $24,773.8 Mi llion

(all gures in millions)

Source:BioWorld



8000 B.C.

Humans domesicae crops and livesock.

Poaoes are rs culivaed or ood.

40002000 B.C.

Bioechnology is rs used o leaven bread and ermen beerwih yeas (Egyp).

Producion o cheese and ermenaion o wine begin (Sum-eria, China and Egyp).

Babylonians conrol dae palm breeding by selecively pollina-ing emale rees wih pollen rom cerain male rees.

500 B.C.Te rs anibioic is pu o use: moldy soybean curds used orea boils (China).

A.D. 100

Powdered chrysanhemums are he rs insecicide (China).

1322

An Arab chieain rs uses aricial inseminaion o producesuperior horses.

15901608Te compound microscope is invened in he Neherlands.Tere is some dispue abou who exacly should be crediedwih he invenion; Hans Jansen, his son Zacharias Jansenand Hans Lippershey has each been credied wih he break-hrough.

1663

English physicis ober Hooke discovers exisence o he cell.

1675

Duch scienis Anonie van Leeuwenhoek discovers baceria.

1761

German boanis Joseph Koelreuer (also spelled Jose Klreu-er and Kohlreuer) repors successul crossbreeding o cropplans in dieren species.

1797

English surgeon Edward Jenner pioneers vaccinaion by inocu-laing a child wih a viral vaccine o proec him rom smallpox.

18301833

1830Proeins are discovered.

1833Te rs enzyme is discovered and isolaed.

18351855

German scieniss Mahias Schleiden and heodorSchwann propose ha all organisms are composed o cells,and German pahologis udol Virchow declares, Everycell arises rom a cell.

1857

French chemis and microbiologis Louis Paseur proposesmicrobes cause ermenaion.

1859

English nauralis Charles Darwin publishes he heoryo evoluion by naural selecion. Te concep o careullyselecing parens and culling he variable progeny grealyinuences plan and animal breeders in he lae 1800s despieheir ignorance o geneics.

1865

Te science o geneics begins: Ausrian monk Gregor Mendelsudies garden peas and discovers ha geneic rais are passedrom parens o ospring in a predicable wayhe laws oherediy. Mendels discoveries were largely ignored unil heearly 20h cenury.

18701890

Using Darwins heory, plan breeders crossbreed coton, de-veloping hundreds o varieies wih superior qualiies.

Farmers rs add nirogen-xing baceria o elds o improveyields.

American boanis William James Beal produces rs experi-menal corn hybrid in he laboraory. Beal also sared he

worlds longes-running (and sill ongoing) sudy o seedviabiliy.

1877A echnique or saining and ideniying baceria isdeveloped by German physician and early baceriologis oberKoch.

1878Te rs cenriuge is developed by Swedish engineerand invenor Gusa de Laval.

1879Walher Flemming, a physician and one o he ound-ers o he sudy o cyogeneics, discovers chromain, he

time line



rod-like srucures inside he cell nucleus ha laer came obe called chromosomes.

1897

German biochemis Eduard Buchner discovers ha special-ized proeins (enzymes) are responsible or converingsugar o alcohol.

1900

Frui ies ( Drosophila melanogaster) are used in early sudieso genes. Te rui y remains an imporan model organismoday.

American agronomis and invenor George Washingon

Carver seeks new indusrial uses or agriculural eedsockssuch as peanus and soybeans.

1902

Te erm immunology rs appears.

1906

Te erm genetics is inroduced.

1911

American pahologis Peyon ous discovers he rs cancer-

causing virus.

1914

Baceria are used o rea sewage or he rs ime in Man-cheser, England.

1915

Phages, or bacerial viruses, are discovered.

1919

Te word biotechnology is rs used in prin.

1920

American scieniss Herber McLean Evans and Joseph Longisolae human growh hormone.

1928

Scotish scienis Alexander Fleming discovers penicillin.

A small-scale es o ormulaed Bacillus thuringiensis (B) orcorn borer conrol begins in Europe. Commercial produciono his biopesicide begins in France in 1938.

ussian scienis Georgii Karpechenko crosses radishes and

cabbages, creaing erile ospring beween plans in dier-en genera.

German boanis Friedrich Laibach rs uses embryo rescueo obain hybrids rom wide crosses in crop plansknownoday as hybridizaion.

1930

U.S. Congress passes he Plan Paen Ac, enabling he prod-ucs o plan breeding o be paened.

1933

Hybrid corn, developed by Henry Wallace in he 1920s, iscommercialized. Growing hybrid corn eliminaes he opiono saving seeds. Te remarkable yields ouweigh he increasedcoss o annual seed purchases, and by 1945, hybrid corn ac-couns or 78 percen o U.S.-grown corn.

1938

Te erm molecular biology is coined.

1941

Te erm genetic engineeringis rs used, by Danish microbiolo-gis A. Jos in a lecure on reproducion in yeas a he echni-

cal insiue in Lwow, Poland.

1942

Te elecron microscope is used o ideniy and characerize abaceriophagea virus ha inecs baceria.

Penicillin is mass-produced in microbes.

1943

German boanis Friedrich Laibach proposes Arabidopsisthaliana as a model organism or plan geneic research.



1944

Canadian-born American baceriologis Oswald Avery and

colleagues discover ha DNA carries geneic inormaion.

Ukranian-born American biochemis Selman Waksman iso-laes srepomycin, an eecive anibioic or uberculosis.

1946

Scieniss discover ha geneic maerial rom dieren v irusescan be combined o orm a new ype o virus, an example ogeneic recombinaion.

1947

American plan cyogeneicis Barbara McClinock discovers

ransposable elemens, or jumping genes, in corn.

1949

American chemis Linus Pauling shows ha sickle cell anemiais a molecular disease resuling rom a muaion in he pro-ein molecule hemoglobin.

1951

Aricial inseminaion o livesock using rozen semen isaccomplished.

1953Te scienic journal Nature publishes James Wason and Fran-cis Cricks manuscrip describing he double helical srucure oDNA, which marks he beginning o he modern era o geneics.

1955

An enzyme involved in he synhesis o a nucleic acid is iso-laed or he rs ime.

1956

American biochemis and physician Arhur Kornberg discov-ers he enzyme DNA polymerase I, leading o an undersand-

ing o how DNA is replicaed.

1958

Sickle cell anemia is shown o occur due o a change o a singleamino acid.

DNA is made in a es ube or he rs ime.

1959

Sysemic ungicides are developed. Te seps in proein bio-synhesis are delineaed.

ALSO IN THE 1950s

Inererons are discovered.

Te rs synheic anibioic is creaed.

1960

Exploiing base pairing, hybrid DNA-NA molecules are cre-aed.

Messenger NA is discovered.

1961

USDA regisers he rs biopesicide: Bacillus thuringiensis, or B.

1963

New whea varieies developed by American agriculural scien-is Norman Borlaug increase yields by 70 percen.

1964

Te Inernaional ice esearch Insiue in he Philippinessars he Green evoluion wih new srains o rice hadouble he yield o previous srains i given sucien erilizer.

1965

Henry Harris and John Wakins a he Universiy o Oxordsuccessully use mouse and human cells.

1966

Te geneic code is cracked, demonsraing ha a sequence ohree nucleoide bases (a codon) deermines each o 20 aminoacids. (wo more amino acids have since been discovered.)

1967Te rs auomaic proein sequencer is pereced.

1969

An enzyme is synhesized in vitro or he rs ime.

1970

Norman Borlaug receives he Nobel Peace Prize (see 1963).

Scieniss discover resricion enzymes ha cu and splicegeneic maerial, opening he way or gene cloning.



1971

Te rs complee synhesis o a gene is compleed.

1972

American biochemis Paul Berg publishes he resuls o hiswork creaing he rs DNA molecules ha combine genesrom dieren organisms.

Te DNA composiion o humans is discovered o be 99 per-cen similar o ha o chimpanzees and goril las.

Iniial work is done wih embryo ranser.

1973

American biochemiss Sanley Cohen and Herber Boyer

perec echniques o cu and pase DNA (using resricionenzymes and ligases) and reproduce he new DNA in baceria.

1974

he Naional Insiues o Healh (NIH) orms a ecom-binan DNA Advisory Commiee o oversee recombinangeneic research.

esearch using geneically enhanced microbes or indusrialapplicaions begins.

1975

Te rs monoclonal anibodies are produced.

1976

Te ools o recombinan DNA (rDNA) are rs applied o ahuman inheried disorder.

Molecular hybridizaion is used or he prenaal diagnosis oalpha halassemia.

Yeas genes are expressed in E. coli baceria.

Te sequence o DNA base pairs or a specic gene is deermined.

Firs guidelines or recombinan DNA experimens released:Naional Insiues o Healhecombinan DNA AdvisoryCommitee.

ecombinan DNA pioneer Herber Boyer co-ounds Genen-ech, he rs company based on he echnology.

1977

A human gene is expressed in baceria or he rs ime.

Procedures are developed or rapidly sequencing long secionso DNA using elecrophoresis.

1978

Te high-level srucure o a virus is rs idenied.

ecombinan human insulin is rs produced.

Norh Carolina scieniss show i is possible o inroduce spe-cic muaions a specic sies in a DNA molecule.

1979

Human growh hormone is rs synhesized.

ALSO IN THE 1970s

echniques or rapid sequencing o nucleoides are pereced.

1980Te U.S. Supreme Cour, in he landmark case Diamond v.Chakrabarty, approves he principle o paening organisms,which allows he Ex xon oil company o paen an oil-eaingmicroorganism.

Te U.S. paen or gene cloning is awarded o American bio-chemiss Sanley Cohen and Herber Boyer.

Te rs gene-synhesizing machines are developed.

esearchers successully inroduce he human gene or iner-eron ino a bacerium.

Paul Berg, Waler Gilber and Frederick Sanger receive heNobel Prize in Chemisry or creaion o he rs recombinanmolecule.

1981

Scieniss a Ohio Universiy produce he rs ransgenic ani-mals by ranserring genes rom oher animals ino mice.

A Chinese scienis becomes he rs o clone a sha goldencarp.

1982

Applied Biosysems, Inc., inroduces he rs commercial gasphase proein sequencer, dramaically reducing he amoun oproein sample needed or sequencing.

Te rs recombinan DNA vaccine or livesock is developed.

Te rs bioech drug is approved by FDA: human insulinproduced in geneically modied baceria. Genenech and EliLilly developed he produc.

he irs geneic ransormaion o a plan cell occurs, usinghe peunia.



1983

American biochemis Kary Mullis invens he polymerase chainreacion (PC) echnique. PC, which uses hea and enzymeso make unlimied copies o genes and gene ragmens, laerbecomes a major ool in bioech research and produc develop-men worldwide.

Te rs geneic ransormaion o plan cells by I plasmids isperormed.

Te rs aricial chromosome is synhesized.

Te rs geneic markers or specic inheried diseases are

ound.

Bioechnology is used o grow a whole plan, he peunia. Tepeunia passes is new rais o ospring.

1984

Te DNA ngerprining echnique (using PC) is developed.

Te enire genome o he human immunodeciency virus(HIV) is cloned and sequenced.

1985

Geneic markers are ound or kidney disease and cysic brosis.

Geneic ngerprining is enered as evidence in a courroom.

ransgenic plans resisan o insecs, viruses and baceria areeld-esed or he rs ime.

Te NIH approves guidelines or perorming gene-herapyexperimens in humans.

1986

Te rs recombinan vaccine or humans is approved, a vac-cine or hepaiis B.

Inereron becomes he rs anicancer drug produced hrough bioech.

Scieniss a he Scripps Insiue and he Universiy o Calior-niaBerkeley describe how o combine anibodies and enzymes(abzymes). Abzymes show poenial o break chemical bonds,including proein pepide bonds, wih grea precision.

Te rs eld ess o ransgenic plans (obacco) are conduced.

Te Environmenal Proecion Agency approves he release ohe rs ransgenic cropgene-alered obacco plans.

Te Organizaion o Economic Cooperaion and Develop-men (OECD) Group o Naional Expers on Saey in Bio-

echnology saes: Geneic changes rom rDNA echniqueswill oen have inherenly greaer predicabiliy comparedo radiional echniques and risks associaed wih rDNAorganisms may be assessed in generally he same way as hoseassociaed wih non-rDNA organisms.

Microbes are rs used o clean up an oil spil l. (Te rs indus-rial bioech paen ever issued was or a microbe o clean upoil spills; see 1980.)

1987

Te rs eld es or a bioech cropvirus-resisan oma-

oesis approved.Frosban, a geneically alered bacerium ha inhibis rosormaion on crop plans, is eld-esed on srawberry andpoao plans in Caliornia, he rs auhorized oudoor ess oa recombinan bacerium.

1988

Harvard molecular geneiciss are awarded he rs U.S. paenor a geneically alered animala ransgenic mouse.

A paen or a process o make bleach-resisan proease en-zymes o use in deergens is awarded.

Juries in he U.S. and he U.K. deliver he rs murder convic-ions based on DNA evidence.

1989

Te rs eld es or bioech cotonan insec-proeced (B)varieyis approved.

Te Plan Genome Projec begins.

Te rs DNA ngerpriningbased exoneraion occurs. As oApril 2008, 216 people had been exoneraed hrough DNA,according o Te Innocence Projec.

ALSO IN THE 1980s

Sudies o DNA are used o deermine evoluionary hisory.

A recombinan DNA animal vaccine is approved or use inEurope.

ibozymes and reinoblasomas are idenied.



1990

Chy-Max, an aricially produced orm o he chymosin

enzyme or cheese-making, is inroduced. I is he rs produco recombinan DNA echnology in he U.S. ood supply.

Te Human Genome Projecan inernaional eor o mapall he genes in he human bodyis launched.

Te rs experimenal gene herapy reamen is perormedsuccessully on a 4-year-old girl suering rom an immunedisorder.

Te rs ransgenic dairy cowused o produce human milkproeins or inan ormulais creaed.

Te rs insec-proeced bioech corn is produced: B corn.

Te rs ood produc o bioechnology is approved in U.K.:modied yeas.

Te rs eld es o a geneically modied verebraerouis iniiaed.

1992

American and Briish scieniss unveil a echnique or es-ing embryos in vitro or geneic abnormaliies such as cysicbrosis and hemophilia.

Te FDA declares ha ransgenic oods are no inherenly

dangerous and do no require special regulaion.

1993

Merging wo smaller rade associaions creaes he Bioechnol-ogy Indusry Organizaion (BIO).

FDA approves recombinan bovine somaoropin (rBS) orincreased milk producion in dairy cows. Te produc (rBS)is commercialized as POSILAC.

FDA approves Beaseron (inereron bea-1a), he rs o sev-eral bioech producs ha have had a major impac on muliplesclerosis reamen.

1994

FDA approves he rs whole ood produced hrough bioech-nology: FLAVSAV omao.

Te rs breas-cancer gene is discovered.

Pulmozyme (dornase ala), a recombinan version o humanDNase, is approved. Te drug breaks down proein accumula-ion in he lungs o cysic brosis paiens.

1995

Te rs baboon-o-human bone marrow ransplan is per-

ormed on an AIDS paien.

Te rs ull gene sequence o a living organism oher han avirus is compleed, or he bacerium Haemophilus inuenzae.

Gene herapy, immune-sysem modulaion and recombinanlyproduced anibodies ener he clinic in he war agains cancer.

1996

Te discovery o a gene associaed wih Parkinsons disease pro-vides an imporan new avenue o research ino he cause andpoenial reamen o he debiliaing neurological ailmen.

Farmers plan bioech saple cropscorn, soybeans andcotonor he rs ime.

Te genome sequence o he microorganism Methanococcusjannaschii conrms ha here is a hird main branch o lieon Earh, along wih baceria and eukaryoes (ungi, proiss,plans and animals). Te hird branch is called Archaea.

1997

Dolly he sheep is unveiled in Scoland as he rs animalcloned rom an adul cell.

Te rs weed- and insec-resisan bioech crops are commer-

cialized: oundup eady soybeans and Bollgard insec-proeced coton.

Bioech crops are grown commercially on nearly 5 millionacres worldwide. Te crops are grown in Argenina, Ausralia,Canada, China, Mexico and he Unied Saes.

iuxan (riuximab) is he rs anicancer monoclonal ani-body o win FDA approval.

A group o Oregon researchers claims o have cloned wohesus monkeys.

Te rs indusrially relevan gram-posiive microorganism

(Bacillus subtilis) genome is sequenced.

DHA and ALA oil produced rom bioech-enhanced microal-gae are inroduced ino worldwide markes.

1998

Human embryonic sem cell lines are esablished.

Te FDA approves he breas cancer drug Hercepin (ras-uzumab) or paiens whose cancer overexpresses he HE2



recepor. I is widely considered he rs pharmacogenomic (orpersonalized) medicine.

Te Perkin-Elmer Corp. enliss American biologis Craig Venero a head a new company called Celera Genomics whose goal iso sequence he human genome aser han he Human GenomeProjec. (Celera has since been absorbed by Applera Corp.)

Universiy o Hawaii scieniss clone hree generaions o micerom nuclei o adul ovarian cumulus cells.

Scieniss a Japans Kinki Universiy clone eigh idenicalcalves using cells aken rom a single adul cow.

Te rs complee animal genome, or he C. elegans round-worm, is sequenced.

An early rough dra o he human genome map is produced,showing he locaions o housands o genes.

Five Souheas Asian counries orm a consorium o developdisease-resisan papayas.

Te rs gene chip or ranscripional proling o an indusrialorganism is designed.

1999

Te U.K.s Wellcome rus joins orces wih 10 large pharma-ceuical companies o creae Te SNP Consorium, whose

goal is o nd and map 300,000 common single nucleoidepolymorphisms (SNPs) in he human genome.

Te Human Genome Projec complees he rs nished,ull-lengh sequence o a human chromosome, chromo-some 22. Te HGP moves up he dae or a complee humangenome dra o 2000.

For he rs ime, invesors pu more han $10 billion ino he bio-ech indusry. Invesmen has never since dipped below ha level.

A new diagnosic es allows quick idenicaion o BovineSpongiorm Encephalopahy (BSE, also known as mad cowdisease) and Creuzeld-Jakob Disease (CJD).

Jessie Gelsingers deah in a human gene-herapy experimenriggers increased scruiny o he echnology.

ALSO IN THE 1990s

A deecive DNA repair gene is discovered and linked o he-rediary colon cancer.

A recombinan rabies vaccine is esed in raccoons.

A bioechnology-based biopesicide is approved or sale in heUnied Saes.

Te rs European paen on a ransgenic animal is issued or aransgenic mouse sensiive o carcinogens.

2000

A rough dra o he human genome sequence is announced.

Te rs complee map o a plan genome is developed:Arabidopsis thaliana.

Bioech crops are grown on 108.9 million acres in 13 counries.

Developers o ransgenic rice enhanced wih bea caroeneGolden iceannounce hey will make he echnologyavailable o developing counries in hopes o improving hehealh o undernourished people and prevening some ormso blindness.

Kenya eld ess is rs bioech crop: virus-resisan swee poao.

2001

esearchers wih Chinas Naional Hybrid ice esearch Cen-er repor developing a super rice ha could produce doublehe yield o normal rice.

Genome sequences are compleed o he agriculurally impor-

an baceria Sinorhizobium meliloti, a nirogen-xing species,and Agrobacterium tumeaciens, a plan pes.

A single gene rom Arabidopsis is insered ino omao plans ocreae he rs crop able o grow in saly waer and soil.

Te worlds rs biorenery opens in Blair, Neb., o conversugars rom eld corn ino polylacic acid (PLA)a compos-ie biopolymer ha can be used o produce packaging maeri-als, clohing and bedding producs.

Te FDA approves an gene-argeed drug called Gleevec(imainib) o rea paiens wih chronic myeloid leukemia.I is hailed as he rs o wha is hoped will be a series o new

cancer drugs based direcly on geneic discoveries.

2002

A dra sequence o he rice genome is compleed, marking hers genome sequence o a major ood crop.

Te rs dra o a uncional map o he yeas proeome, anenire nework o proein complexes and heir ineracions, iscompleed.



Inernaional consoriums sequence he genomes o heparasie ha causes malaria and he species o mosquio haransmis he parasie.

Te dra version o he complee map o he human genome ispublished.

Scieniss are orced o rehink heir view o NA when heydiscover how imporan small pieces o NA are in conrollingmany cell uncions.

Scieniss make grea progress in elucidaing he acors ha

conrol he diereniaion o sem cells, ideniying more han200 genes ha are involved in he process.

esearchers announce successul resuls or a vaccine againscervical cancer, he rs demonsraion o a prevenaive vac-cine or a ype o cancer.

Scieniss complee he dra sequence o he mos imporanpahogen o rice, a ungus ha desroys enough rice o eed 60million people annually.

Te Japanese puersh genome is sequenced. Te puershsequence is he smalles known genome o any verebrae.

Scieniss a Sony Brook Universiy in New York assemble asynheic virus, polio, using genome sequence inormaion.

2003

Brazil and he Philippines grow bioech crops or he rs ime.

Te U.S. Environmenal Proecion Agency approves he rsransgenic rooworm-resisan corn, which may save armers$1 billion annually in crop losses and pesicide use.

An endangered species (he baneng) is cloned or he rsime. 2003 also brough several oher cloning rss, includingmules, horses and deer.

Dolly, he cloned sheep ha made headlines in 1997, is euha-nized aer developing progressive lung disease.

Japanese researchers develop a bioech coee bean ha is nau-rally decaeinaed.

China grans he worlds rs regulaory approval o a geneherapy produc. Gendicine, developed by Shenzhen SiBionoGenech, delivers he p53 gene as a herapy or squamous cellhead and neck cancer.

McKinsey & Co. projecs indusrial bioechnology could reach$160 billion in value by 2010.

FDA approves he rs nasal-mis inuenza vaccine, FluMis.

2004

Te FDA approves he rs ani-angiogenic drug or cancer,Avasin (bevacizumab).

Te FDA clears a DNA microarray es sysem, he Am-pliChip Cyochrome P450 Genoyping es, o aid in selec-ing medicaions or a wide variey o common condiions.

An NA-inererence (NAi) produc or age-relaed wemacular degeneraion becomes he rs NAi produc o ener

a clinical rial.

GloFish, he rs bioech pe, his he Norh American marke.

Te Unied Naions Food and Agriculure Organizaionendorses bioech crops.

Te Naional Academy o Sciences Insiue o Medicine(IOM) nds bioech crops pose no more healh risks han docrops creaed by oher echniques. Te IOM recommends bas-ing ood-saey evaluaions on he resuling ood produc, nohe echnique used o creae i.

FDA nds a ype o bioech whea sae aer a ood saey review.

Te chicken genome is sequenced by he Chicken GenomeSequencing Consorium.

Te rs cloned pe, a kiten, is delivered o is owner.

Te laboraory-ra genome is sequenced.

esearchers complee he sequence o he chimpanzeehu-maniys closes primae relaive.

Te Canadian bioech company Iogen achieves he rs com-mercial producion and delivery o bioehanol, producing heuel wih bioech enzymes and whea sraw.

2005

esearchers a he Universiy o Georgia successully producea cow cloned rom he cells o a carcass.

FDA or he rs ime approves a drug or a specic race. Tedrug, BiDil, reas congesive hear ailure in sel-idenied blackpaiens.

Te Energy Policy Ac is passed and signed ino law, auhoriz-ing numerous incenives or bioehanol developmen.



Te Naional Insiues o Healh launches a pilo projec odeermine he easibiliy o Te Cancer Genome Alas. Te ul-

imae goal would be a complee map o he genomic changesinvolved in all ypes o human cancer.

Scieniss a he Ceners or Disease Conrol & Prevenionparially synhesize he u virus ha killed a leas 20 millionpeople worldwide in 19181919.

Scieniss a Harvard Universiy repor success in converingskin cells ino embryonic sem cells hrough usion wih exis-ing embryonic sem cells.

On May 7, he one billionh acre o bioech seed is planed.

he World Healh Organizaion (WHO) issues Modern

Food Biotechnology, Human Health and Development, whichconcludes bioech oods can enhance human healh andeconomic developmen.

Te Briish research rm PG Economics Ld. nds ha heglobal use o bioech crops has added $27 billion o armincome and reduced agriculures environmenal impac.

A consorium o scieniss led by he Naional Human Ge-nome esearch Insiue publishes he dog genome. I belongso a 12-year-old boxer.

Te rs enzymes or low-energy (cold) ehanol producion

are commercialized as corn-derived ehanol producion his 4billion gallons per year.

2006

Te American Dieeic Associaion publishes a rearmed sae-men o suppor or agriculural and ood bioechnology.

Dow AgroSciences wins he rs regulaory approval or a plan-made vaccine. Te vaccine proecs poulry rom Newcasledisease.

enessen LLC receives approval o begin selling animal eedmade rom high-lysine bioech corn. Lysine is essenial in

animal dies, especially hose o swine and poulry.

esearchers develop bioech pigs ha produce high levels oomega-3 aty acids wih he help o a gene rom he roundwormC. elegans.

FDA approves he recombinan vaccine Gardasil, he rsvaccine developed agains human papillomavirus (HPV), aninecion implicaed in cervical and hroa cancers.

2007

esearchers a he Universiy o Wisconsin, Madison, and Kyoo

Universiy in Japan announce successul reprogramming o hu-man skin cells o creae cells indisinguishable rom embryonicsem cells.

esearchers a Childrens Hospial Boson and he HarvardSem Cell Insiue deermine ha discredied Korean scienisHwang Woo-Suk creaed he worlds rs embryonic sem cellline derived rom parhenogenesis.

Te FDA approves he H5N1 vaccine, he rs vaccine ap-proved or avian u.

Universiy o Bualo researchers describe he cenral mecha-

nism o acion or enzymes.aiwanese researchers develop a bioech eucalypus ree haingess up o hree imes more carbon dioxide han conven-ional varieies. Te bioech eucalypus also produces lesslignin and more cellulose.

Korean researchers unveil he rs-ever poodle clone.

U.S. researchers announce he producion o bioech catleha canno develop prion proeins. Prions have been implica-ed in he degeneraive neurological disease bovine spongiormencephalopahy.

2008

Te dra corn genome sequence is compleed. I is only hehird plan genome o be compleed, aer Arabidopsis and rice.

Sources:Access ExcellenceBiotech 90: Into the Next Decade,

G. Seven Burrill wih he Erns & Young Highechnology Group

Bioechnology Indusry OrganizaionGenenech, Inc.

Genetic Engineering NewsInernaional Food Inormaion CouncilISB News ReportInernaional Service or he Acquisiion

o Agri-Bioech Applicaionsexas Sociey or Biomedical esearchScienceScience NewsTe Scientist



Biotechnolog Polic Milestones

1902

Te Biologics Conrol Ac passes o ensure puriy and saey oserums, vaccines and similar producs.

1906

Te Food and Drugs Ac is signed ino law, prohibiing iner-sae commerce in misbranded and aduleraed ood, drinksand drugs. (Noe: For a deailed FDA imeline, visi htp://www.da.gov/opacom/backgrounders/miles.hml.)

1930

Te Naional Insiue o Healh is creaed (laer o becomehe Naional Insiues o Healh as new research insiues inspecic disease or research areas are added).

1938

Congress passes Te Federal Food, Drug, and Cosmeic(FDC) Ac o 1938, one o a handul o core laws governinghe FDA. Among oher provisions, he FDC Ac requiresnew drugs o be shown sae beore markeing. Tus begins anew sysem o drug regulaion.

1946

ecognizing he hrea posed by loss o geneic diversiy, heU.S. Congress provides unds or sysemaic and exensiveplan collecion, preservaion and inroducion.

1962

Talidomide, a new sleeping pill, is ound o have caused birhdeecs in housands o babies born in Wesern Europe. TeKeauver-Harris Drug Amendmens are passed o require drugmakers o demonsrae ecacy and greaer drug saey. Tebigges change is ha, or he rs ime, drug manuacurers are re-quired o prove o FDA he eeciveness o heir producs beore

markeing hem.

1965

Presiden Johnson signs H.. 6675 o esablish Medicarehealh insurance or he elderly (coverage or he disabledwas added in 1972) and Medicaid or he indigen. AlhoughMedicare covers drugs used in clinics and hospials, i omisoupaien prescripionsa gap ha will grow in signicanceas pharmaceuicals, including many bioech drugs, become amore imporan componen o care. (See he Kaiser Family

Foundaions complee Medicare imeline a htp://www.k.org/medicare/imeline/p_enire.hm or more deails.)

1971

Presiden Nixon calls or a War on Cancer and signs he Na-ional Cancer Ac ino law, simulaing new research.

1974

Leading biologiss call or a volunary moraorium on recom-binan DNA experimens while saey sandards are se.

1975

Some 150 scieniss, atorneys, governmen ocials andjournaliss mee a he Asilomar Conerence Cener nearMonerey, Cali., o discuss recombinan DNA research anddevelop sric saey proocols.

1976

Te NIH adops guidelines or ederally unded recombinanDNA research, wih oversigh provided by he ecombinanDNA Advisory Commitee.

1980

Te Supreme Cour decides in Diamond vs. Chakrabarty haanyhing under he sun ha is made by he hand o man,including bioechnology-modied organisms, is paenable.Te decision helps open he oodgaes o a wave o invesmenha includes he rs bioech IPOs.

Te Paen and rademark Ac Amendmens o 1980com-monly known as he Bayh-Dole Aclay he ground rulesor echnology ranser rom academia o indusry. Te accreaes a uniorm paen policy among ederal agencies ha



und research and species ha ederal gran recipienssuchas universiies and small businessesown ederally unded

invenions.

1983

Te Orphan Drug Ac is signed ino law, creaing new incen-ives o conduc &D on herapies or rare diseases. Morehan 250 orphan drugs have reached he U.S. marke in heyears since.

Congress creaes he Small Business Innovaion esearch(SBI) gran program, a boon o cuting-edge bioech researcha small companies.

1986Te U.S. governmen publishes he Coordinated Framework orRegulation o Biotechnology, esablishing more sringen regula-ions or rDNA organisms used in agriculure han or hoseproduced wih radiional geneic modicaion echniques.Te ramework claries he agriculural bioech responsibili-ies o he Food & Drug Adminisraion, he U.S. Deparmeno Agriculure and he Environmenal Proecion Agency.

1988

he U.S. Paen and rademark O ice grans Har vard Uni-versiy a paen or a mouse used or cancer research (he

OncoMouse).

Te Unied Saes launches he Human Genome Projec whenCongress appropriaes unds or he Deparmen o Energyand he Naional Insiues o Healh o suppor research odeermine he srucure o complex genomes. Te projec isully underway by 1990.

1992

Te FDA clears he way or agriculural bioechnology prod-ucs wih a saey assessmen and guidance o indusry.

Te Prescripion Drug User Fee Ac (PDUFA) is signed ino

law, insiuing drug and biologic applicaion review ees haprovide he FDA wih resources o review producs aser. Tesuccessul program is reauhorized in 1997, 2002 and 2007.

1993

Te Bioechnology Indusry Organizaion (BIO) is cre-aed ou o he merger o wo predecessor organizaions, heIndusrial Bioechnology Associaion and he Associaion oBioechnology Companies. (A hisory o BIO is posed onBIO.org in he Abou BIO secion.)

1997

Te Food and Drug Adminisraion Modernizaion Ac

(FDAMA) is signed ino law, codiying adminisraive changesbegun in 1995 and inroducing new reorms. Provisionsinclude crieria or as-rack drug developmen, easier paienaccess o experimenal drugs and medical devices, and anonline daabase o clinical rials.

1998

Congress underakes a doubling o he Naional Insiues oHealh budge in ve years, raising i o $27 billion by 2003.Since hen he agencys budge has sagnaed.

1999

Presiden Clinon signs an execuive order o promoe devel-opmen o biobased producs and bioenergy.

2000

Te Biomass esearch and Developmen Ac is signed inolaw o promoe conversion o biomass ino biobased indusrialproducs.

2001

Presiden Bush announces ha ederal unding will be madeavailable o suppor research using embryonic sem cell lines

creaed as o Aug. 9, 2001.

2002

Te Farm Securiy and ural Invesmen Ac includes bioechmeasures such as signicanly increased unding or researchand risk assessmen and new programs or promoing bioech-nology in developing counries. Te legislaion also supporsindusrial bioechnology wih a new requiremen or ederalagencies o buy biobased producs, such as plan-made plasicsand biouels, whenever easible.

2003

Te Medicare Modernizaion Ac becomes law, providingprescripion drug coverage or senior ciizens and he disabledbeginning Jan. 1, 2006.

2004

Te FDA publishes a whie paper oulining he Criical PahIniiaive, which seeks o expedie drug developmen by promo-ing he use o echnologies such as compuer-based predicivemodels, biomarkers, imaging echnologies and improved clinicalrial design.



Te Projec BioShield Ac is signed ino law, providing $5.6billion over 10 years or he ederal governmen o procurediagnosics, herapies and vaccines o proec Americans romchemical, nuclear and biological warare agens.

Caliornia voers pass Proposiion 71, which suppors embry-onic sem cell research wih $3 billion in unding over 10 years.

2005Te Energy Policy Ac o 2005 passes, auhorizing $3.6 billionin unding or bioenergy and biobased producs.

Pandemic legislaion signed ino law provides $3.8 billionor preparedness, including $3 billion or medical couner-measures. Te legislaion also includes liabiliy proecion ormanuacurers o hese producs.

2006

Te World rade Organizaion issues a condenial nalruling on he U.S./Canada/Argenine challenge agains heEuropean Union (EU) on approval o new bioech crops.

According o news repors, he ruling concludes ha he EUbreached is rade commimens wih respec o 21 agricul-ural bioechnology producsincluding ypes o oi lseed,rape, maize and coton.

In his Sae o he Union address, U.S. Presiden George W.Bush expresses suppor or bioehanol made rom agriculuralwases and swichgrass.

2007

Congress passes Te Food and Drug Adminisraion Amend-

mens Ac (FDAAA), which provides FDA wih subsanialresources or enhancing and modernizing he FDA DrugSaey Sysem. Legislaion o reauhorize he PrescripionDrug User Fee Ac also passes in conjuncion wih FDAAA.FDAAA is widely considered he mos sweeping FDA over-haul in decades. Previous landmark FDA legislaion ocusedon premarke esing o saey (he FDC Ac) and ecacy (heKeauver-Harris amendmens); his legislaion ocuses on post-marketsaey. Among is many provisions, FDAAA requiresgreaer collaboraion beween he FDA and drug manuacur-ers o develop risk-evaluaion and miigaion sraegies prioro approval, gives he FDA new labeling auhoriy, and calls or

an enhanced clinical rials regisry and a resuls daabank.

Te U.S. Deparmen o Energy (DOE) invess more han $1billion in biorenery projecs and bioenergy research cenersin 2007.

Te Energy Independence and Securiy Ac o 2007 becomeslaw, esablishing a new enewable Fuel Sandard ha callsor naionwide use o 36 billion gallons o biouels by 2022,including 21 billion gallons o advanced biouels and cellulosicehanol.

2008

Te FDA publishes a avorable risk assessmen or ood de-rived rom cloned animals and heir ospring. Te assessmenreecs FDAs review o more han 700 scienic research sud-ies, conduced over he pas 30 years. Te agency concludesha oods rom animal clones and heir ospring are equiva-len o oods rom oher livesock.

A press ime, he House and Senae had boh passed heGeneic Inormaion Nondiscriminaion Ac, and PresidenBush was expeced o sign i ino law. Te law will proecagains job or healh insurance discriminaion based ongeneic esing resuls.

A press ime, Congress is considering sweeping paen reorm.Visi he Inellecual Propery secion o BIO.org or inormaion.



Here is an overview o he major echnologies and ools used inbioech.

Bioprocessing Technolog

Te oldes o he bioechnologies, bioprocessing, uses living cellsor he molecular componens o cells manuacuring machineryo produce desired producs. Te living cells mos commonlyused are one-celled microorganisms, such as yeas and baceria;he biomolecular componens used include DNA (which en-codes he cells geneic inormaion) and enzymes (proeins hacaalyze biochemical reacions).

A orm o bioprocessing, microbial ermentation, has been usedor housands o years o brew beer, make wine, leaven bread andpickle oods. In he mid-1800s, when we discovered microorgan-isms and realized hey were responsible or hese useul producs,we grealy expanded our use o microbial ermenaion. We nowrely on he remarkably diverse manuacuring capabiliy o nau-rally occurring microorganisms o provide us wih producs suchas anibioics, birh conrol pills, vaccines, amino acids, viamins,indusrial solvens, pigmens, pesicides, biodegradable plasics,laundry-deergen enzymes and ood-processing aids.

CELL CULTURE

Cell-culure echnology is he growing o cells ouside o livingorganisms (ex vivo).

PLANT CELL CULTURE

An essenial sep in creaing ransgenic crops, plan cellculure also provides us wih an environmenally sound andeconomically easible opion or obaining naurally occur-ring producs wih herapeuic value, such as he chemohera-peuic agen pacliaxel, a compound ound in yew rees andmarkeed under he name axol. Plan cell culure is alsounder sudy as a manuacuring ool or herapeuic proeins,and is an imporan source o compounds used as lavors,

colors and aromas by he ood-processing indusry.

INSECT CELL CULTURE

Insec cell culure can broaden our use o biological-conrolagens ha kill insec pess wihou harming benecial ones orhaving pesicides accumulae in he environmen. Even houghwe have recognized he environmenal advanages o biologicalconrol or decades, he manuacure o such producs in marke-able amouns has been impossible. Insec cell culure removeshese manuacuring consrains.

Like plan cell culure, insec cell culure is being invesigaed as aproducion mehod o herapeuic proeins. Insec cell culure is also

being invesigaed or he producion o VLP (virus-like paricle)vaccines agains inecious diseases such as SAS and inuenza,which could lower coss and eliminae he saey concerns associ-aed wih he radiional egg-based process. A paien-specic cancervaccine, Provenge, ha uilizes insec cell culure is up or FDAapproval, along wih a second vaccine or Human Papilloma Virus(HPV), Cervarix.

MAMMALIAN CELL CULTURE

Livesock breeding has used mammalian cell culure or decades.Eggs and sperm, aken rom geneically superior cows and bulls,are unied in he lab, and he resuling embryos are grown in

culure beore being implaned. A similar orm o mammaliancell culure has also been an essenial componen o he humanin vitro erilizaion process.

Our use o mammalian cell culure now exends well beyond hebrie mainenance o cells in culure or reproducive purposes.Mammalian cell culure can supplemenand may one dayreplaceanimal esing o medicines. As wih plan cell culureand insec cell culure, we are relying on mammalian cells osynhesize herapeuic compounds, in paricular, cerain mam-malian proeins oo complex o be manuacured by geneicallymodied microorganisms. For example, monoclonal anibodies

are produced hrough mammalian cell culure.Scieniss are also invesigaing he use o mammalian cellculure as a producion echnology or inuenza vaccines. In2006, he Deparmen o Healh and Human Services awardedconracs oaling approximaely $1 billion o several vac-cine manuacurers o develop new cell-culure echnologiesor manuacuring inuenza vaccine. Cell-culure echnologyhas been used or oher vaccines, bu each vaccine process isunique and inuenza vaccine manuacuring has radiionallybeen perormed using large quaniies o eggs. New manuac-uring echnologies are an essenial par o pandemic inuenzapreparedness and require exensive research and developmen.

Cell-culure echniques could enhance he manuacuringcapabiliies and capaciy.

Recombinant DNA Technolog

ecombinan DNA is he oundaion o modern bioechnology. Teerm recombinantDNA lierally means he joiningor recombin-ingo wo pieces o DNA rom dieren sources, such as rom wodieren organisms.

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Monoclonal anibodies can be creaed in mouse cells, bu oenhe human paien mouns an immune response o mouse ani-

bodies. Tis immune response no only eliminaes he herapeu-ic MAb adminisered, bu is also dangerous or paiens and maycause lasing damage. o reduce his problem scieniss creaechimeric, or humanized, anibodies in which some pars o mouseorigin are replaced wih pars o human origin. Such anibodiesare less likely o rigger an unwaned immune response.

Cloning

Cloning echnology allows us o generae a populaion o genei-cally idenical molecules, cells, plans or animals. Is applicaions

are exraordinarily broad and exend ino many research andproduc areas. Any legislaive or regulaory acion direced acloning mus ake grea care in dening he erm precisely soha he inended aciviies and producs are covered while oh-ers are no inadverenly capured.

MOLECULAR OR GENE CLONING

Molecular or gene cloning, he process o creaing genei-cally idenical DNA molecules, provides he oundaion ohe molecular biology revoluion and is a undamenal ool obioechnology. Virually all applicaions in bioechnology, romdrug discovery and developmen o he producion o ransgenic

crops, depend on gene cloning.

Te research ndings made possible hrough molecular cloninginclude ideniying, localizing and characerizing genes; creainggeneic maps and sequencing enire genomes; associaing geneswih rais and deermining he molecular basis o hese rais.For a ull discussion, see page 25.

ANIMAL CLONING

Animal cloning has been rapidly improving livesock herdsor more han wo decades and has been an imporan ool orscienic researchers since he 1950s. Alhough he 1997 debu

o Dolly he cloned sheep was a worldwide media even, animalcloning was no alogeher new. Dolly was considered a scien-ic breakhrough notbecause she was a clone, bu because hesource o he geneic maerial used o produce Dolly was anadul cell, no an embryonic one.

Tere are, in ac, wo ways o make an exac geneic copy o anorganism such as a sheep or a laboraory mouse:

Embryo Spliting is he old-ashioned way o clone. Embryospliting mimics he naural process o creaing idenical wins,only in a Peri dish raher han he mohers womb. esearch-

ers manually separae a very early embryo ino wo pars andhen allow each par o divide and develop on is own. Te

resuling embryos are placed ino a surrogae moher, wherehey are carried o erm and delivered. Since all he embryoscome rom he same zygoe, hey are geneically idenical.

Somaic cell nuclear ranser (SCN) sars wih he isola-ion o a somaic (body) cell, which is any cell oher han hoseused or reproducion (sperm and egg, known as he germcells). In mammals, every somaic cell has wo complee ses ochromosomes, whereas he germ cells have only one compleese. o make Dolly, scieniss ranserred he nucleus o a so-maic cell aken rom an adul emale sheep o an egg cell romwhich he nucleus had been removed. Aer some chemicalmanipulaion, he egg cell, wih he new nucleus, behaved likea reshly erilized zygoe. I developed ino an embryo, whichwas implaned ino a surrogae moher and carried o erm.

Animal cloning provides many benes. Te echnology canhelp armers produce animals wih superior characerisics, andi provides a ool or zoo researchers o save endangered spe-cies. Also, in conjuncion wih recombinan DNA echnologies,cloning can provide excellen animal models or sudying geneicdiseases and oher condiions such as aging and cancer. In he u-ure, hese echnologies will help us discover drugs and evaluaeoher orms o herapy, such as gene and cell herapy.

Protein Engineering

Proein engineering echnology is used, oen in conjuncionwih recombinan DNA echniques, o improve exising proeins(e.g., enzymes, anibodies and cell recepors) and creae proeinsno ound in naure. Tese proeins may be used in drug develop-men, ood processing and indusrial manuacuring.

Proein engineering has mos commonly been used o aler hecaalyic properies o enzymes o develop ecologically susain-able indusrial processes. Enzymes are environmenally superioro mos oher caalyss used in indusrial manuacuring because,as biocaalyss, hey dissolve in waer and work bes a neuralpH and comparaively low emperaures. In addiion, becausebiocaalyss are more specic han chemical caalyss, hey alsoproduce ewer unwaned byproducs. Makers o chemicals, ex-iles, pharmaceuicals, pulp and paper, ood and eed, and energyare all beneing rom cleaner, more energy-ecien producionmade possible wih biocaalyss.

Te characerisics ha make biocaalyss environmenallyadvanageous may, however, limi heir useulness in cerainindusrial processes. For example, mos enzymes all apar a



high emperaures. Scieniss are circumvening hese limiaionsby using proein engineering o increase enzyme sabiliy under

harsh manuacuring condiions.

In addiion o indusrial applicaions, medical researchers haveused proein engineering o design novel proeins ha can bindo and deacivae viruses and umor-causing genes; creae espe-cially eecive vaccines; and sudy he membrane recepor pro-eins ha are so oen he arges o pharmaceuical compounds.Food scieniss are using proein engineering o improve heuncionaliy o plan sorage proeins and develop new proeinsas gelling agens.

In addiion, researchers are developing new proeins o respondo chemical and biological atacks. For example, hydrolases

deoxiy a variey o nerve agens as well as commonly usedpesicides. Enzymes are sae o produce, sore and use, makinghem an eecive and susainable approach o oxic maerialsdeconaminaion.

Biosensors

Biosensor echnology couples our knowledge o biology wihadvances in microelecronics. A biosensor is composed oa biological componen, such as a cell, enzyme or anibody,linked o a iny ransducera device powered by one sys-

em ha hen supplies power (usually in anoher orm) o asecond sysem. Biosensors are deecing devices ha rely onhe speciciy o cells and molecules o ideniy and measuresubsances a exremely low concenraions.

When he subsance o ineres binds wih he biological com-ponen, he ransducer produces an elecrical or opical signalproporional o he concenraion o he subsance. Biosensorscan, or example:

measure he nuriional value, reshness and saey o ood.

provide emergency room physicians wih bedside measures ovial blood componens.

locae and measure environmenal polluans.

deec and quaniy explosives, oxins and biowarare agens.

Nanobiotechnolog

Nanoechnology is he nex sop in he miniaurizaion pahha gave us microelecronics, microchips and microcircuis. Teword nanotechnology derives rom nanometer, which is one-hou-

sandh o a micromeer (micron), or he approximae size o asingle molecule. Nanoechnologyhe sudy, manipulaion and

manuacure o ulra-small srucures and machines made o asew as one moleculewas made possible by he developmen omicroscopic ools or imaging and manipulaing single moleculesand measuring he elecromagneic orces beween hem.

Nanobioechnology joins he breakhroughs in nanoechnol-ogy o hose in molecular biology. Molecular biologiss helpnanoechnologiss undersand and access he nanosrucuresand nanomachines designed by 4 billion years o evoluionaryengineeringcell machinery and biological molecules. Exploi-ing he exraordinary properies o biological molecules and cellprocesses, nanoechnologiss can accomplish many goals ha aredicul or impossible o achieve by oher means.

For example, raher han build silicon scaolding or nanosruc-ures, DNAs ladder srucure provides nanoechnologiss wih anaural ramework or assembling nanosrucures. Tas becauseDNA is a nanosrucure; is highly specic bonding properiesbring aoms ogeher in a predicable patern on a nano scale.

Nanoechnologiss also rely on he sel-assembling properies obiological molecules o creae nanosrucures, such as lipids hasponaneously orm liquid crysals.

Most appropriatel, DNA, the inormation storage

molecule, ma serve as the basis o the nextgeneration o computers.

DNA has been used no only o build nanosrucures bu also asan essenial componen o nanomachines. Mos appropriaely,DNAhe inormaion sorage moleculemay serve as he ba-sis o he nex generaion o compuers. As microprocessors andmicrocircuis shrink o nanoprocessors and nanocircuis, DNAmolecules mouned ono silicon chips may replace microchipswih elecron ow-channels eched in silicon. Such biochips areDNA-based processors ha use DNAs exraordinary inorma-ion sorage capaciy. (Concepually, hey are very dieren romhe DNA microarray chips discussed below.) Biochips exploihe properies o DNA o solve compuaional problems; inessence, hey use DNA o do mah. Scieniss have shown ha1,000 DNA molecules can solve in our monhs compuaionalproblems ha would require a cenury or a compuer o solve.

Oher biological molecules are assising in our coninual queso sore and ransmi more inormaion in smaller places. Forexample, some researchers are using ligh-absorbing molecules,such as hose ound in our reinas, o increase he sorage capac-iy o CDs a housand-old.



Some applicaions o nanobioechnology include:

increasing he speed and power o disease diagnosics.

creaing bio-nanosrucures or geting uncional moleculesino cells.

improving he speciciy and iming o drug delivery.

miniaurizing biosensors by inegraing he biological andelecronic componens ino a single, minue componen.

encouraging he developmen o green manuacuring pracices.

Microarras

Microarray echnology is ransorming laboraory researchbecause i allows us o analyze ens o housands o daa poinssimulaneously.

Tousands o DNA or proein molecules, or issue samples, canbe analyzed on a single chipa small glass surace ha carriesan array o microscopic poins ha indicae each molecule orsample ha is being sudied.

DNA MICROARRAyS

DNA microarrays can be used o analyze an enire genome on

one chip. Tis provides a whole picure o geneic uncion or acell or organism, raher han a gene-by-gene approach.

Scieniss can use DNA microarrays o:

deec muaions in disease-relaed genes.

monior gene expression.

diagnose inecious diseases and ideniy he bes anibioicreamen.

ideniy genes imporan o crop produciviy.

improve screening or microbes used in environmenal cleanup.

DNA-based arrays are essenial or using he raw geneic daaprovided by he Human Genome Projec and oher genomeprojecs o creae useul producs. However, gene sequence andmapping daa mean litle unil we deermine wha hose genesdowhich is where proein microarrays can help.

PROTEIN MICROARRAyS

Te srucures and uncions o proeins are oen much morecomplicaed han hose o DNA, and proeins are less sable hanDNA. Each cell ype conains housands o dieren proeins,

some o which are unique o ha cells job. In addiion, a cellsproein proleis proeomevaries wih is healh, age, andcurren and pas environmenal condiions.

Proein microarrays may be used o:

discover proein biomarkers ha indicae disease sages.

assess poenial ecacy and oxiciy o drugs beore clinicalrials.

measure dierenial proein producion across cell ypes and

developmenal sages, and in boh healhy and diseased saes.sudy he relaionship beween proein ineracions and uncion.

evaluae binding ineracions beween proeins and ohermolecules.

Te availabiliy o microarray echnology has enabled researcherso creae many ypes o microarrays o answer scienic ques-ions and discover new producs.

TISSUE MICROARRAyS

issue microarrays, which allow he analysis o housands o is-

sue samples on a single slide, are being used o deec molecularproles in healhy and diseased issues and validae poenialdrug arges. For example, brain issue samples arrayed on slidesconneced o elecrodes allow researchers o measure he elecri-cal aciviy o nerve cells exposed o cerain drugs.

WHOLE-CELL MICROARRAyS

Whole-cell microarrays alleviae he problem o proein insabil-iy in microarrays and permi a more accurae analysis o proeinineracions wihin a cell.



Boh academic and indusrial scieniss have come o dependon various bioechnologies o sudy he workings o biologi-cal sysems in remarkably precise deail. Tese bioech researchools have allowed hem o answer long-sanding scienicquesions and have changed he quesions hey ask, he problemshey ackle and he mehods hey use o ge answers.

Research Applications oBiotechnolog

esearchers use bioechnology o gain insigh ino he precise deailso cell processes: he specic asks assigned o various cell ypes; hemechanics o cell division; he ow o maerials in and ou o cells;he pah by which an undiereniaed cell becomes specialized; andhe mehods cells use o communicae wih each oher, coordinaeheir aciviies and respond o environmenal changes.

Once hey have eased apar deails o a process, researchers mushen reassemble he pieces in a way ha provides insigh ino heinner workings o cells and, ulimaely, o whole organisms.

UNDERSTANDING CELL PROCESSES

esearchers have made remendous progress oward charinghe pah o a cell rom a single, erilized egg o a whole organism.Te developmen o a mulicelled organism rom a single cell

involves cell prolieraion and cell diferentiationgroups o cellsbecoming specialized, or diereniaed, o perorm specic asks.Cell diereniaion is he process o urning o cerain geneswihin a group o cells while urning on ohers. Scieniss areopimisic abou elucidaing he many seps in he diereniaionpahway and ideniying he exernal and inernal acors regula-ing he process. wo imporan breakhroughs have ueled hisopimism: he developmen o a proocol or mainaining humansem cells in culure and he birh o he cloned sheep Dolly.

A delicate balance exists between actors that

stimulate cell division and those that inhibit it. An

disruption o this balance leads to uncontrolledcell prolierationcanceror cell death.

We have known or decades he basic requiremens or keepingsmall numbers o plan and animal cells in culure. We main-ained hese culures primarily o collec producs ha cellsproduce naurally. For example, plan-cell culure gives us avors,colors, hickeners and emulsiers or ood processing.

esearchers now are keeping cells in culure o invesigae hemolecular basis o many cell processes, especially cell growh,

prolieraion, diereniaion and deah.

All cells progress hrough essenially he same cycle: Tey in-crease in size up o a cerain poin, he geneic maerial replicaes,and he cell divides in wo. Undersanding wha conrols the cellcycle is essenial o undersanding he cause o many human andanimal diseases, he basis o increasing crop plan yields, and ameans or quickly increasing he cells used o manuacure prod-ucs as diverse as ermened oods and medicines.

Improvemens in cell-culure echnology have allowed us obeter undersand he molecular basis o he cell cycle. Te rig-orously conrolled sequence o seps in he cell cycle depends

on boh geneic and nuriional acors. A delicae balance ex-iss beween acors ha simulae cell division and hose hainhibi i. Any disrupion o his balance leads o unconrolledcell prolieraioncanceror cell deah.

Sudying cells in culure has led o a radical revision o our viewo cell deah. We once hough cells died in an unorganized,passive way, as cell pars and processes gradually deerioraed.Bu we now know ha much cell deah is a highly organized,well-planned sequence o evens programmed ino he genome.Prolonged cell sress and oher acors rigger programmedcell deah, or apoptosis, in which he cell dismanles isel in anorderly way, breaks down is genome and sends a signal o heimmune sysem o dispach whie blood cells ha will remove i.

Programmed cell deah eliminaes cells wih damaged DNA,removes immune sysem cells ha atack healhy cells and shapesissue ormaion during developmen. A beter undersanding ocell deah can also help us gure ou why only some cells wihenvironmenally damaged DNA urn cancerous; wha breaksdown in auoimmune diseases; and how o creae beter issuesor replacemen herapies.

STEM CELL TECHNOLOGy

Aer animal cells diereniae ino issues and organs, some

issues reain a group o undiereniaed cells o replace haissues damaged cells or replenish is supply o cerain cells,such as red and whie blood cells. When needed, hese adultstem cells (ASCs) divide in wo. One cell diereniaes ino hecell ype he issue needs or replenishmen or replacemen,and he oher remains undiereniaed.

Embryonic stem cells (ESCs) have much greaer plasiciy hanASCs because hey can diereniae ino any cell ype. Mouseembryonic sem cells were discovered and culured in he lae1950s. Te ESCs came rom 12-day-old mouse embryo cells

from biotechnology to biology:Using Biotech Tools to Understand Life



ha were desined o become egg or sperm (germ cells) whenhe mouse maured. In 1981, researchers ound anoher source

o mouse ESCs wih oal developmenal plasiciycells akenrom a 4-day-old mouse embryo.

In he lae 1990s researchers ound ha human ESCs could bederived rom he same wo sources in humans: primordial germcells and he inner cell mass o 5-day-old embryos. Tese humanembryonic sem cells were ound o have he same pluripoenproperies. Consequenly, scieniss believe ESCs have enormouspoenial o lead o reamens and cures or a variey o diseases.

Scieniss also have been able o isolae sem cells rom humanplacenas donaed ollowing normal, ull-erm pregnancies. Un-der cerain culure condiions, hese cells were ransormed ino

carilage-like and a-like issue.

Mainaining culures o ESCs and ASCs can provide answers o crii-cal quesions abou cell diereniaion: Wha acors deermine heulimae ae o unspecialized sem cells? How plasic are adul semcells? Could we conver an ASC ino an ESC wih he righ combi-naion o acors? Why do sem cells reain he poenial o replicaeindeniely? Is he acor ha allows coninual prolieraion o ESCshe same acor ha causes unconrolled prolieraion o cancercells? I so, will ransplaned ESCs cause cancer?

Te answers o hese and many oher quesions will deerminehe limis o he herapeuic poenial o ESCs and ASCs. Only

when hey undersand he precise mix o acors conrolling pro-lieraion and developmen will scieniss be able o reprogramcells or herapeuic purposes.

Using sem cell culures, researchers have begun o elaborae he in-ricae and unique combinaion o environmenal acors, molecularsignals and inernal geneic programming ha decides a cells ae. Is-raeli scieniss direced ESCs down specic developmenal pahwaysby providing dieren growh acors. Ohers discovered ha nervesem cells require a dose o viamin A o rigger diereniaion inoone specic ype o nerve cell, bu no anoher.

What actors wipe out a dierentiated cells identit

and take it back to its embronic state o complete

plasticit? Beore Dolls birth, we did not know we

could ask that question, much less answer it.

Anoher ype o ASC, mesenchymal stem cells, can diereniaeino a leas hree dieren cell ypes (a cells, bone cells andcarilage cells) depending in par on he mix o nuriens andgrowh acors. Teir desiny also depends on heir physicalproximiy o one anoher. I mesenchymal sem cells are ouch-ing each oher, hey may become a cells; i he cell densiy is

oo high, hey will no diereniae ino bone cells even whenprovided he appropriae nuriens and chemical signals.

esearchers have recenly demonsraed ha some ypes omesenchymal sem cells migh have even more developmenalexibiliyin vivo. When injeced ino mouse embryos, hesecells diereniae ino mos o he cell ypes ound in mice. In2005, researchers a Johns Hopkins Universiy began wha wasbelieved o be he rs clinical rial in he Unied Saes o adulmesenchymal sem cells o repair muscle damaged by hearatack. esuls o he rial, which used an Osiris Terapeuicsexperimenal echnology, were promising, even hough i wasonly a Phase I sudy or saey. Fory-wo percen o paiens whoreceived he herapy experienced improvemen in heir condi-ion a six monhs, versus only 11 percen o placebo paiens.

Anoher approach o developing herapies based on cells akes adieren ack. aher han deermining he molecular evens haurn a sem cell ino a specic cell ype, scieniss are sudyinghe de-diereniaion process.

THE LESSON OF CLONING:

DE-DIFFERENTIATION IS POSSIBLE

Scieniss had assumed a specialized animal cell could norever o he unspecialized saus o an embryonic sem cell.(Ineresingly, specialized plan cells reain he poenial ode-specialize.) Tey assumed a gene urned o during he di-

ereniaion process could no be acivaed. Te birh o Dollyproved ha assumpion was incorrec. In a procedure knownas somatic cell nuclear transer (SCN), a nucleus rom a ullydiereniaed body (somaic) cell was placed in an egg, andis ideniyadul sheep mammary gland cell nucleuswaserased. Ta egg developed ino Dolly.

Te birh o Dolly via SCN showed ha he geneic program-ming o a nucleus rom a specialized somaic cell can be erasedand reprogrammed, in vitro, by placing i in an egg cell. Te eggdevelops ino a 5- or 6-day-old embryo ha is geneically ideni-cal o he animal ha provided he nucleus, and cells aken romhe embryo can develop ino any cell y pe ound in he animal.

Aer SCN showed we could generae ESCs conaining undi-ereniaed geneic maerial rom adul cells or some animals,i seemed likely we could develop similar echniques or usinghuman paiens own geneic maerial o develop replacemencells and issues or herapeuic purposes. Tis idea is calledtherapeutic cloning.

Oher possibiliies are now emerging or cellular de-diereni-aion and re-diereniaion. For example, diereniaed bloodcells, when sarved, rever o a sem cell-like condiion. Wih



he proper coaxing, scieniss have convered hose cells inonerve and liver cells and even ino blood vessels, which consis

o wo cell ypes wih very dieren uncions: muscle cells orconracion and cells lining he inner surace or movemen osubsances ino and ou o he blood. In addiion, scieniss haveesablished condiions or de-diereniaing a highly specializedype o nerve cell ino a ype o neural sem cell. Te neural semcells were hen reprogrammed ino many oher ypes o cellsound in he nervous sysem.

In 2005, Harvard Universiy scieniss succeeded in creaing cellssimilar o ESCs by using a human skin cell wih an ESC. Te re-suling hybrid cell was de-diereniaed and ESC-like. wo yearslaer, researchers a he Universiy o Wisconsin, Madison, andJapans Kyoo Universiy succeeded in reprogramming skin cellsino cells indisinguishable rom embryonic sem cellswihouusing egg cells or ESCs as saring maerial. Insead, hey useddieren combinaions o genes o rigger de-diereniaion.

Te researchers noed ha work wih embryonic sem cells remainscriical. I is simply oo early in his young scienic eld o knowwhich echniques will prove mos eecive in medical applicaions.

UNDERSTANDING GENE FUNCTION

Te cell processes described abovegrowh, prolieraion,diereniaion, apoposisand many more are carried ou andconrolled by proeins. Proeins are he molecular players ha

regulae and drive each minue sep o he overall process.

Undersanding he deails o cell processes in healh and diseasemeans undersanding proeins. Because genes conain heinormaion or making proeins, undersanding proeins meansundersanding gene uncion. Te ools o bioechnology givescieniss myriad opporuniies o sudy gene uncion. Hereare only a ew o he ways bioechnology allows invesigaors oprobe he geneic basis o cell uncions.

Molecular Cloning

I scientists voted or the most essentialbiotechnolog research tool, molecular cloning

would likel win.

I scieniss voed or he mos essenial bioechnology researchool, molecular cloning would likely win. Eiher direcly orindirecly, molecular cloning has been he primary drivingorce o he bioechnology revoluion and has made remark-able discoveries rouine. Te research ndings made possiblehrough molecular cloning include ideniying, localizing andcharacerizing genes; creaing geneic maps and sequencing

enire genomes; associaing genes wih rais and deermininghe molecular basis o he rai.

Molecular cloning involves insering a new piece o DNA inoa cell in such a way ha i can be mainained, repl icaed andsudied. o mainain he new DNA ragmen, scieniss inseri ino a circular piece o DNA called a plasmid ha proecshe new ragmen rom he DNA-degrading enzymes ound inall cells. Because a piece o DNA is insered, or recombinedwih, plasmid DNA, molecular cloning is a ype o recombi-nan DNA echnolog y.

Te new DNA, now par o a recombinan molecule, replicaesevery ime he cell divides. In molecular cloning, he word clonecan reer o he new piece o DNA, he plasmid conaining henew DNA and he collecion o cells or organisms, such as bac-eria, conaining he new piece o DNA. Because cell divisionincreases, or amplies, he amoun o available DNA, molecu-lar cloning provides researchers wih an unlimied amoun o aspecic piece o geneic maerial o manipulae and sudy.

In addiion o generaing many copies o idenical bis o geneicmaerial, molecular cloning also enables scieniss o dividegenomes ino manageable sizes. Even he simples genome

he oal geneic maerial in an organismis oo cumbersomeor invesigaions o single genes. o creae packages o geneicmaerial o sizes ha are more amenable o sudies such as genesequencing and mapping, scieniss divide genomes ino hou-sands o pieces and inser each piece ino dieren cells. Tis col-lecion o cells conaining an organisms enire genome is knownas a DNA library. Because ideniying and mapping genes relieson DNA libraries creaed wih molecular cloning, o clone canalso mean o ideniy and map a gene.


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veloped mehods o knocking ou specic genes and learned howo mainain culures o embryonic sem cells. Using his suie o

echnologies, researchers have creaed animal disease models orAlzheimers disease, aging, cancer, diabees, obesiy, cardiovascu-lar disease and auoimmune diseases. Using nuclear ranser andembryonic sem cell culure, scieniss should be able o developanimal disease models or many more species.

Putting the Pieces Together:Omics and Related Tools

Bioechs powerul research ools have se a as pace or basicscienic discovery. Tey have enabled researchers o easeapar cellular and geneic processes so horoughly ha weare beginning o undersand biological sysems a heir mosundamenal levelhe molecular level. Bu biological organ-isms do no operae as molecular bis and pieces. Te only wayo ruly undersand organisms is o reassemble hese bis andpieces ino sysems and neworks ha inerac wih each oher.

Tis need o assemble separae ndings ino a complee picurehas given birh o a rash o omics: genomics, proteomics,metabolomics, immunomics and transcriptomics. Tese researchavenues atemp o inegrae inormaion ino whole sysemsraher han ocus on he individual componens in isolaion

rom each oher. Te bioechnologies are imporan ools inhese endeavors, bu inormaion echnologies are also essen-ial or inegraing molecular daa ino a coheren whole.

Te elds o research described below bridge scienic discov-eries in cellular and molecular biology wih heir commercialapplicaions.

GENOMICS

Genomics is he scienic sudy o he genome and he rolegenes play, individually and collecively, in deerminingsrucure, direcing growh and developmen, and conrollingbiological uncions. I consiss o wo branches: srucuralgenomics and uncional genomics.

Structural GenomicsTe eld o srucural genomics includes he consrucion andcomparison o various ypes o genome maps and large-scaleDNA sequencing. Te Huma

Documents

Guide To Biotechnology