MBioS-ChE 574 Reeves Lecture 1 History of Biotechnology · • Bt corn – 3.5 billion pound yield...

MBioS/ChE 574

Class Notes:

http://molecular.biosciences.wsu.edu/academics/courses/mbios574.htm

Protein Biotechnology

http://www.biotechnology.wsu.edu/

http://molecular.biosciences.wsu.edu/biotech.html

Biotechnology Programs at WSU:

What is Biotechnology? What is Biotechnology?

Words We Hear …GMO’s Jeremy RifkinFrankenfoods (Franken-everything) Identity PreservationBiodiversity BioremediationCloning Regulatory GuidelinesDNA Testing USDA/APHIS/FDA/EPARecombinant DNA AllergensTransgenics Herbicide-Resistant WeedsGreenPeace Antibiotic GenesFriends of the Earth Terminator TechnologyToxic to Insects (everything) GenomicsTaco Bell Taco Chip Recall BioinformaticsMonarch Butterflies Stem CellsProteomics Nanotechnology

Words We Hear …GMO’s Jeremy RifkinFrankenfoods (Franken-everything) Identity PreservationBiodiversity BioremediationCloning Regulatory GuidelinesDNA Testing USDA/APHIS/FDA/EPARecombinant DNA AllergensTransgenics Herbicide-Resistant WeedsGreenPeace Antibiotic GenesFriends of the Earth Terminator TechnologyToxic to Insects (everything) GenomicsTaco Bell Taco Chip Recall BioinformaticsMonarch Butterflies Stem CellsProteomics Nanotechnology

BIOTECHNOLOGYA very broad field which encompasses

precise manipulations of living organisms themselves or the products that they make or the processes they carry out.

BIOTECHNOLOGYA very broad field which encompasses

precise manipulations of living organisms themselves or the products that they make or the processes they carry out.

Protein Biotechnology●Production of biologically or commercially

useful protein or peptide products employingthe use of recombinant DNA or molecularbiology techniques

●The foundation of many current biotechnology and pharmaceutical companies

How Old is Biotechnology? How Old is Biotechnology?

Beer, Bread, and Wine Making are Centuries Old.

Beer, Bread, and Wine Making are Centuries Old.

Ancient Egyptian drawing of a cylinder seal impression on a jar stopper bearing the name of Khasekhemwy, a Dynasty 2 pharoah. It shows a grapevine trained to run along a trellis or arbor. (around 2700 b.c.)

Throughout History Selective Breeding Has Led to Greater Diversity and Higher-Yielding Varieties of Plants and Animals.

Thomas Fairchild Fairchild’s mule

Traditional Breeding and Selection Methods Led to the Development Of Many Different Varieties of Plants and Animals

Fairchild’s mule gave birth to many of today’s hybrid flowers

Gregor Johann Mendel

●Discovered the Laws Governing theGenetic Inheritance of ‘Traits’ byScientific Experimentation

●Founded Modern Genetics

Maize Was Transformed into Modern Corn byMendalian Genetic Crosses and Selection

Teosinte Modern corn

How Old is “Modern Biotechnology”?

James D. Watson

Francis H.C. Crick

Herbert W. Boyer

Stanley N. Cohen

1953 Described the

DNA double-helix

1973Discovered

Gene Splicing and Gene Cloning

Science Vol. 222, Nov. 1983 Time Magazine, March 1997

1983 SCIENCE Cover – Transgenic Mice1997 TIME Cover - Dolly

Embryo development after successful somatic cell nucleartransfer to in vitro matured human germinal vesicle oocytes*

Hum. Reprod. Advance Access published online on May 18, 2007

B. Heindryckx1,3, P. De Sutter1, J. Gerris1, M. Dhont1 and J. Van der Elst2

Infertility Centre, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium 2 Centre for Reproductive Medicine,

Universitair Ziekenhuis Brussel, 1090 Brussels, Belgium

Somatic Cell Nuclear Transfer (SCNT)

Timeline of Modern Protein Biotechnology●1976: The tools of recombinant DNA are first applied to a human

inherited disorder. Molecular hybridization is used for the prenatal diagnosis of alpha thalassemia. Yeast genes arefirst expressed in E. coli.

●1978: Hutchinson, Edgell and Smith demonstrate that its is possible to introduce specific mutations at specific sitesin a DNA molecule and thus produce specifically modifiedrecombinant proteins.

●1978: Human insulin gene cloned into E. coli by Genentech scientists.Genentech licenses the insulin gene technology to Eli Lily.

●1982: Humulin, Genentech’s human insulin produced by Eli Lily,becomes the first FDA approved recombinant DNA drug.

Timeline of Modern Protein Biotechnology, cont.

●1985: Genentech becomes the first biotechnology company to launch its own biopharmaceutical product, ProTropin –growth hormone for children with growth hormone deficiency.

The rest, as they say, is (more recent) history!

Modern Biotechnology really refers to

Molecular BiologyMolecular Genetics

and Genetic Engineering

Modern Biotechnology really refers to

Molecular BiologyMolecular Genetics

and Genetic Engineering

KEY ELEMENT OF BIOTECHNOLOGY/

GENETIC ENGINEERING

Can Use Recombinant DNA Methods To Move A Gene From Any Organism To Any Other Organism

Desired gene

Traditional Genetic BreedingDNA is a strand of genes, much like a strand of pearls. Traditional genetic breeding combines many genes at once via crossesand selection.

Traditional donor Commercial variety New variety

Desired GeneX =

(crosses)

(many genes are transferred)

Modern BiotechnologyUsing modern biotechnology, a single gene may be added to a DNA strand.

Desired gene Commercial variety New variety

(transfers)

=

Desired gene

(only desired gene is transferred)

How Big is Biotechnology? How Big is Biotechnology?

Biotechnology Industrial Areas

Agriculture PharmaceuticalsHealth CareFoodEnergyEnvironmentBioremediation

Biotechnology Industrial Areas

Agriculture PharmaceuticalsHealth CareFoodEnergyEnvironmentBioremediation

• More than 325 million people worldwide have been helped by the more than 155 biotechnology drugs and vaccines approved by the U.S. Food and Drug Administration (FDA). Of the biotech medicines on the market, 70 percent were approved in the last six years.• There are more than 370 biotech drug products and vaccines currently in clinical trials targeting more than 200 diseases, including various cancers, Alzheimer's disease, heart disease, diabetes, multiple sclerosis, AIDS and arthritis.

Biotechnology Industry Statistics

•There are 1,457 biotechnology companies in the United States, of which 342 are publicly held.

• Market capitalization, the total value of publicly traded biotech companies at market prices, was $206 billion as of mid-April 2003.

• The biotechnology industry has mushroomed since 1992, with revenues increasing from $8 billion in 1992 to $34.8 billion in 2001.

• The U.S. biotechnology industry currently employs 191,000 people; that's more than all the people employed by the toy and sporting goods industries.

www.bio.org/er/statistics.asp

• More than 325 million people worldwide have been helped by the more than 155 biotechnology drugs and vaccines approved by the U.S. Food and Drug Administration (FDA). Of the biotech medicines on the market, 70 percent were approved in the last six years.• There are more than 370 biotech drug products and vaccines currently in clinical trials targeting more than 200 diseases, including various cancers, Alzheimer's disease, heart disease, diabetes, multiple sclerosis, AIDS and arthritis.

Biotechnology Healthcare/Pharmaceuticals Statistics

•More than 325 million people worldwide have been helped by the more than 155 biotechnology drugs and vaccines approved by the U.S. Food and Drug Administration (FDA).

• There are more than 370 biotech drug products and vaccines currently in clinical trials targeting more than 200 diseases, including various cancers, Alzheimer's disease, heart disease, diabetes, multiple sclerosis, AIDS and arthritis .

www.bio.org/er/statistics.asp

How are Transgenic Plants or ‘Genetically Modified

Organisms (GMOs)’ Produced?

How are Transgenic Plants or ‘Genetically Modified

Organisms (GMOs)’ Produced?

In General, Plant Biotechnology TechniquesFall Into Two Classes

• Identify a gene from another species which controlsa trait of interest

• Or modify an existing gene (create a new allele)

Gene Manipulation

• Introduces that gene into an organism• Technique called transformation• Forms transgenic organisms

Gene Introduction

Insect Resistant Plants Through Genetic EngineeringBacillus thuringiensis (Bt) Toxin

Bt Transgenic Plants are Insect Resistant

Lab Testing The Transgenics

Insect Resistance

Transgene=Bt-toxin protein

Bt+

Worldwide/year:

Source: National Center for Food and Agricultural Policy

• Bt corn – 3.5 billion pound yield increase and $125 million in additional income

• Bt cotton – 185 million pound yield increase and $102 million in additional income

• Biotech soybeans – $1 billion in additional income through production cost savings

ChrysanthemumGrapeTrefoilKiwiRose

Canola

Alfalfa

Sugar Beet

Tobacco

Mustard

Cotton

Soybean

Tomato

Potato

Maize

CabbageBarleyCucumberRice

SpruceStrawberryPetuniaChicory

CranberryEggplantMellonFlax

Plum TreeCarnationWheatCantaloupe

Sweet PotatoCarrotSugarcaneSunflower

AsparagusPepperWalnutBirch

WatermelonFescueRaspberryLettuce

PapayaServiceberrySweetgumRapeseed

Fodder RapeEucalyptusCauliflowerSquash

Oilseed RapePeanutApplePoplar

Modified Bt Plants in Field TrialsModified Bt Plants in Field Trials

More ExamplesSalt Tolerant

Transgene=Glyoxylase I

Mercury Resistance

Transgene=Mercuric ion reductaseCold Tolerance

Transgene=CBF transcription factors

Products in the pipeline

• Pest- and disease-resistant cassava

Agronomic benefits

Benefits of biotechnology – More food

• Disease-resistant bananas

• Disease-resistant sweet potatoes

• Oranges resistant to citrus canker

In the World in 2003…Global biotech crop acreage grew to more than 167 million acres in 2003 according to the International Service for the Acquisition of Agri-biotech Applications. Since 1996, when the first biotech crops were commercially grown, the global biotech crop area has increased 40-fold to a total of 7 million farmers in 18 countries. A total of 85 percent of growers using biotech crops are small farmers in developing countries, which representsnearly one-third of the global biotech crop area.

In the World in 2003…Global biotech crop acreage grew to more than 167 million acres in 2003 according to the International Service for the Acquisition of Agri-biotech Applications. Since 1996, when the first biotech crops were commercially grown, the global biotech crop area has increased 40-fold to a total of 7 million farmers in 18 countries. A total of 85 percent of growers using biotech crops are small farmers in developing countries, which representsnearly one-third of the global biotech crop area. In the USA in 2003…

90% of Soybeans are GMO’s80% of Cotton crop 50% of Corn crop

In the USA in 2003…90% of Soybeans are GMO’s80% of Cotton crop 50% of Corn crop

Conventional:Wide Hybridization introduces 100,000 potentially negative genes in order to obtain one desirable diseaseresistance gene.

Induced mutagenesis has been used for decades to creategenetic variants.

Genetic Engineering:Introduce one (or a few) foreign “good” genes into thebest accepted cultivar background.

Bt or Disease Resistance genes might enable reduction by80% of insecticide or fungicide chemical applications.

Conventional:Wide Hybridization introduces 100,000 potentially negative genes in order to obtain one desirable diseaseresistance gene.

Induced mutagenesis has been used for decades to creategenetic variants.

Genetic Engineering:Introduce one (or a few) foreign “good” genes into thebest accepted cultivar background.

Bt or Disease Resistance genes might enable reduction by80% of insecticide or fungicide chemical applications.

Is a GMO more dangerous than a conventionally derived cultivar?

“No conceptual distinction exists between genetic modification of plants and microorganisms by classical methods or by molecular techniques that modify DNA and transfer genes.”

— National Research Council

Government Regulation

46

USDA report says impact of Bt corn on butterflies is “negligible”

“The College supports the use of biotechnology to develop food crops that contribute to global food security and enhance the safety and nutritional value of the food supply.”

— American College of Nutrition Statement on Crop Biotechnology

“There is no reason to suppose that the process of food production through biotechnology leads to risks of a different nature than those ... created by conventional breeding.”

— Society of Toxicology Statement on the Safety of Foods Produced Through Biotechnology

“Biotechnology experts believe that the current regimen of tests has been adequate for ensuring that GM foods marketed to consumers are as safe as conventional foods.”

— General Accounting Office

“Indeed, the use of more precise technology and the greater regulatory scrutiny probably make them [biotech foods] even safer than conventional plants and foods.”

— European Commission research report

Some Early, Medically Important Recombinant ProteinsProduct Broad Approved Medical Use●Insulin Diabetes●Human growth hormone Growth deficiency●Interferon-α Cancer, viral infections●Anti-T-cell antibody Organ transplantation●Hepatitis B antibody Hepatitis B infection●Tissue plasminogen activator Cardovascular disease●α1-Antitrypsin Emphysema (some forms)●Interleukin-2 Cancer●GMCSF Immunological deficiencies●Coagulation factor VIII Haemophilia A●Interleukin-10 Prevention of thromobcytopenia●Epidermal growth factor Burns, cancer●Follicle-stimulating hormone Infertility●Glucagon Reversal of insulin-induced

hypoglycaemia

Biopharmaceutical

(i.e., specific disease symptoms)

http://www.alltech-bio.com/

For over 20 years, Alltech has researched, developed and manufactured natural ingredients for use in animal, alcohol and food production. Natural biotechnology and fermentation are the core technologies underlying Alltech's rapid development. With over 1,300 employees worldwide, offices in 44 countries and distribution to over 76 countries, the company is positioned to meet the changing needs of the global marketplace http://www.alltech-bio.com/

Alltech, Inc.3031 Catnip Hill PikeNicholasville KY 40356

1044 East Chestnut StreetLouisville, Kentucky 40204502.515.1492 (ph)520.832.2308 (fax)

http://www.sheltoweellc.com

Sheltowee is an innovative pharmaceutical company that develops, licenses and markets category-leading nutraceutical and medicinal health products.

Large Scale Biology Corporation is one of the world's leading companiesdedicated to the discovery, analysis,manufacture and commercialization ofproteins. LSBC's activities are builtaround an integrated suite of ultra-

sensitive, industrial-scale technologies created to realize the full commercial and pharmaceutical potential of biology.

The Company's headquarters and Genomics Division are situated in Vacaville, California. Its BioprocessingDivision is in Owensboro, Kentucky, and its Proteomics Division is located at Germantown, Maryland.

http://www.lsbc.com/

Equine Biodiagnostics Inc., is a laboratory specializing in diagnostic testing for the veterinary health care industry. Guided by a distinguished group of scientific advisors, EBI's highly qualified technical and professional staff is always ready to provide reliable and cost-efficient laboratory results in a timely manner. Our mission is to strive for excellence in all aspects of our services.

Coldstream Research Campus Lexington, KY 40511

www.ebiky.com/

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UGA Researchers Use Transgenic Trees To Help Clean Up Toxic Waste SiteCan genetically engineered cottonwood trees clean up a site contaminated with toxic mercury? A team of researchers from the University of Georgia - in the first such field test ever done with trees -is about to find out.The results could make clearer the future of phytoremediation –a technique of using trees, grasses and other plants to remove hazardous materials from the soil. UGA scientists and city officials in Danbury, Conn., planted on July 16 some 60 cottonwoods with aspecial gene at the site of a 19th-century hat factory in that northeastern city. "We hope to see a significant difference in the levels of mercury in the soil within 18 months, perhaps as much as a twofold reduction," said Richard Meagher, professor of genetics at UGA. The field test is a collaboration between UGA, Western Connecticut State University, Applied PhytoGenetics, Inc., of Athens and the City of Danbury.

http://www.sciencedaily.com/

Mice, men share 99 percent of genesBy Marsha WaltonCNN

(CNN) --When it comes to DNA, it turns out there's not that much difference between mice and men.Mice and humans each have about 30,000 genes, yet only 300 are unique to either organism. Both even have genes for a tail, even though it's not "switched on" in humans."About 99 percent of genes in humans have counterparts in the mouse," said Eric Lander, Director of the Whitehead Institute Center for Genomic Research in Cambridge, Massachusetts. "Eighty percent have identical, one-to-one counterparts."The mouse is the only mammal, after the human, whose genome has been sequenced. The rodent's genetic sequence was published in this week's edition of Nature Magazine

Scientists say mice and humans descended from a common ancestor about the size of a small rat.

www.cnn.com/tech/Science

Any Questions/ Discussion?Any Questions/ Discussion?