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Biotechnology: Past, Present, And Future. Donna C. Sullivan, PhD Division of Infectious Diseases Univ. Mississippi Medical Center. History Of Biotechnology: Food And Beverages. 6000 BC: Sumarian and Babylonian beer 4000 BC: Egyptian leavened bread, cheese, mushroom cultivation - PowerPoint PPT Presentation
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Biotechnology:Past, Present, And Future
Donna C. Sullivan, PhDDivision of Infectious Diseases
Univ. Mississippi Medical Center
History Of Biotechnology: Food And Beverages
6000 BC: Sumarian and Babylonian beer
4000 BC: Egyptian leavened bread, cheese, mushroom cultivation
At time Genesis was written: wine
1857-1876: Pasteur demonstrated fermentation by microorganisms
The Brave New World We are at the
beginning of the biotech century
Biotech is expanding• Industrial &
environmental applications
• Medical applications• Food and agricultural
applications
Bio Mass Biomass already
supplies 14% of the world’s primary energy consumption.
On average, biomass produces 38% of the primary energy in developing countries.
USA: 4% of total energy from biomass, around 9000 MegaWatts
GASOHOL: Are We Starving Children to Drive Our Hummers?
US Dept. of Energy Web Page: FAQ Looks at Myths
MYTH: Ethanol cannot be produced from corn in large enough quantities to make a real difference without disrupting food and feed supplies.
FACT: Corn is only one source of ethanol. As we develop new, cost-effective methods for producing biofuels, a significant amount of ethanol will be made from more abundant cellulosic biomass sources.
Sugar Sources: Why Don’t We Use Them?
1/ Based on 2003-05 U.S. average raw sugar recovery rate of 12.26% per ton of cane and sucrose recovery from cane molasses at 41.6 pounds per ton of sugarcane.2/ Based on 2003-05 U.S. average refined sugar recovery rate of 15.5% per ton of beets and sucrose recovery from beet molasses at 40.0 pounds per ton of sugar beets.3/ Based on an average sucrose recovery of 49.2% per gallon of cane molasses.
Does It Have To Be That Way?
Even Iowa Wants to Know What Is Going On
http://www.extension.iastate.edu/agdm/articles/hof/HofJan09.html
http://www.extension.iastate.edu/agdm/articles/hof/HofJan09.html
Historical Trend Ethanol And Flex Vehicles In Brazil
US Dept. of Energy Web Page: FAQ Looks at Myths
MYTH: More energy goes into producing ethanol than it delivers as a fuel.
FACT: In terms of fossil energy, each gallon of ethanol produced from corn today delivers one third or more energy than is used to produce it.
Raw Material Energy output/Energy input
Wheat 1.2
Corn 1.2-1.5
Sugar beet 1.9
Sugar cane(Brazil)
8.3
US Dept. of Energy Web Page: FAQ Looks at Myths
MYTH: Ethanol-gasoline blends can lower fuel economy and may harm your engine.
FACT: Ethanol blends in use today have little impact on fuel economy or vehicle performance.
Even if you don’t, you can have your car converted. Several companies provide kits to convert gasoline powered vehicles to FFVs.
The U.S. has AbundantCellulose Sources
Corn Stover Rice Straw Wheat Straw Barley Straw Sugar Beet Tops Alfalfa Switch Grass Saw Dust Sugar cane waste
Biomass: And It Doesn’t Have To Be Just Plants….
Bio Mass from cattle manure, agricultural waste, forest residue and municipal waste.
Anaerobic digestion of livestock wastes to give bio gas
Fertilizers as by product. Average electricity generation of
5.5kWh per cow per day!!
Algae Tested As Fuel For Arizona Power Plant
The algae, which grow in racks of plastic bags, feed on the carbon dioxide in the exhaust of the power plant.
The system not only reduces the greenhouse gases coming from the power plant by 40% but can also produce biodiesel and animal feedstock as a byproduct without competing with the global food supply.
And It’s Not Just “Someplace Else”….
Notice the MICROBIOLOGIST!! University of Georgia researchers
have developed a new technology that promises to dramatically increase the yield of ethanol from readily available non-food crops, such as Bermuda grass, switch grass, Napier grass-and even yard waste.
"Producing ethanol from renewable biomass sources such as grasses is desirable because they are potentially available in large quantities," said Joy Peterson, PROFESSOR OF MICROBIOLOGY
Columbus, Mississippi
Biodiesel in Mississippi Multi-feed stock
• Columbus• Greenville
Soy• Natchez
Make your own• Arkansas company
sells kit
BIOTECHNOLOGY AND MEDICINE
Pharmaceuticals • Antibiotics-most come from microbes
Biopharmaceuticals• Monoclonal antibodies• Vaccines• Gene therapy
Diagnostics
Biotechnology has Revolutionized Drug Development
Injected insulin directly supplements an insufficiency in diabetics
Prior to 1982, insulin was primarily extracted from pig pancreas • 50 pigs sacrificed to produce sufficient insulin for one person for one
year• Risk of disease transmission, shortages, immune system rejection
Use gene splicing to insert human insulin gene into bacteria• Plentiful supply• No risk of animal disease transmission• Reduced risk of immune system rejection
Traditional pharmaceutical methods involve chemical synthesis and biological extracts and pharmaceuticals are often indirect effectors
Biotechnology uses biological synthesis and biologics are often direct effectors
BUILDING BIOTECHNOLOGY pp. 10-11, 36
Personalized Medicine
People Have Been Making Decisions Based on Biotechnology for Years: Testing for Down’s
Syndrome and sex
“Karyotyping”
Screening For Genetic Abnormalities Fluorescent in situ
hybridization (FISH) used to detect:• Extra
chromosomes• Missing parts of
chromosomes• DNA swapping
across different chromosomes
Chronic myelogenous leukemia
• DNA exchange between chromosome 9 and 22
ACCATG GTATAC*TGGTAC
*CATATGFluorescent DNA probes
Allele Specific Oligonucleotide Analysis (ASO)
Analyze DNA from cells of 8-32-cell-stage-old embryo created by in vitro fertilization
Allows individuals to select healthy embryos before implantation
SNPs are abundant Estimated that 1 SNP occurs every 1000-
3000 bp along the DNA of every chromosome
Over 1.4 million SNPS identified to date on human chromosome.
When SNPs occur in a gene that codes for a body function, a disease can result.
Pharmaceutical companies are cataloguing the chromosomal locations of SNPs
Identifying sets of disease genes by
microarrays
Testing Issues Should we test people for genetic
conditions for which no cure exists? What are the accepted consequences if a
parent learns their unborn child has a genetic defect?
What are the psychological consequences of a false results that indicates that a healthy person has a disease gene or a gene defect?
How do we ensure privacy and confidentiality?
Microarray for Leukemia screening
Drug delivery Getting drug to target organs and tissue
• Oral drug to treat arthritis in knee is not very efficient
• Drug solubility may be an issue Microspheres
Insulin delivered as a powder through an inhaler
Nanomedicine Nanometer is one
billionth of a meter• May be used for
delivery of small sensors to target sites in body
• Unclogging arteries• Detect and destroy
cancer cells
1 meter
10-9 meters
Artificial blood Cell-free solutions containing molecules
that can bind and transport oxygen like hemoglobin
Benefits• Disease-free alternative to real blood• Constant supply• Universal donor type
Disadvantages• Cannot perform all the functions of a red blood
cell-only oxygen delivery Source of iron Carbon dioxide removal
Type You Can Give Blood To
You Can Receive Blood From
A+ A+ AB+ A+ A- O+ O-
O+ O+ A+ B+ AB+ O+ O-
B+ B+ AB+ B+ B- O+ O-
AB+ AB+ Everyone
A- A+ A- AB+ AB- A- O-
O- Everyone O-
B- B+ B- AB+ AB- B- O-
AB- AB+ AB- AB- A- B- O-
Out of 100 donors . . . . .
84 donors are RH+
16 donors are RH-
38 are O+ 7 are O-
34 are A+ 6 are A- 9 are B+ 2 are B-
3 are AB+ 1 is AB-
A B A,B O
Monoclonal antibodies
Gene therapy Delivery of therapeutic genes into the body
to correct disease conditions created by faulty gene
How is it done?
1
23
4
stopped
Pharmacogenomics
Epogen – Biotech’s First Blockbuster
Erythropoietin (EPO) is a hormone that increases red blood cell proliferation • Used to treat anemia• Reduces need for blood transfusions
Development timeline• Initially purified from 2,500 quarts of human urine in 1976• Patents filed in 1984• Efficacy demonstrated in 1986• Approved for HIV patients in 1990 – 14 years after first
purification!• Expanded approvals thereafter
Developed by Amgen• CEO is a former US Navy nuclear-submarine chief engineer• Prior science training: High-school biology, college chemistry
Cloned Biopharmaceuticals
PRODUCT APPROVED USEInsulin DiabetesHuman growth hormone Growth deficiency Interferon Cancer, viral infectionsHepatitis B Vaccine HBV preventionTissue Plasminogen activator Cardiovascular disease
Erythropoietin AnemiaInterleukin-2 Cancer
Xenotransplantation Transplanting organs from one species into
another May someday become an alternative to
human-to-human transplantation• 1984 baboon heart transplanted into a 12-year-
old human girl Girl died after 3 weeks as a result of organ rejection
• Can be avoided by matching immune system of donor and acceptor
Major histocompatibility complex• Human leucocyte antigen (HLA) present on all of our
cells
Pigs genetically engineered to lack a sugar-producing gene that causes human bodies to reject pig organs
Tracy, a transgenic sheep, 1999
Her milk produced a human protein called alpha antitrypsin, a potential treatment for the disease cystic fibrosis.
More Than One Kind of Cloning
Environmental Biotechnology Waste water and
sewage treatment• Safe drinking water• Acceptable sewage
disposal Landfill technologies Composting Bioremediation Bioleaching
Bioleaching To Solubilize Elements
Bioleaching costs 33-50% less than direct smelting
Commercially important metals• Copper (10% of total production in US)• Uranium (4000 tons/year in US)• Others (zinc, cobalt, lead)
At The Table
Calgene’s Flavr Savr Tomato Most tomatoes are gas-ripened
• Picked while green to prevent damage during shipping
• Sprayed with ethylene to ‘ripen’ prior to sale• Result is bright red but tasteless tomatoes
Vine-ripened tomatoes sell for a premium• Tastier than gas-ripened tomatoes• Cost more to deliver to market, have shorter
shelf-lives Polygluconase enzyme was associated
with ripening in 1984• Highly expressed in red tomatoes, absent in
green tomatoes• Calgene set out to reduce expression of
polygluconase to delay ripening Produce tomatoes that can be transported
like gas-ripened tomatoes but are worthy of vine-ripened prices
Can compete with vine-ripened tomatoes because of greater durability and longer shelf-life
BUILDING BIOTECHNOLOGY p. 326
Path to Development
Isolate PG gene and generate antisense tomatoes
Develop assay for ripening • Flavr Savr tomatoes spoiled slower than wild
tomatoes at room temperature• 1 lb weight and timer to measure firmness
Field test • Flavr Savr tomatoes ripened as fast as wild tomatoes,
rotted slower File Patents Solicit FDA Approval
• Demonstrate that Flavr Savr tomatoes do not pose a health risk
Market Launch
Taste of Flavr Savr tomatoes not as good as competing premiums • Flavr Savr gene was not introduced into
premium tomato varieties Flavr Savr tomatoes could not withstand
shipping• Firmer than vine-ripened, but not as
durable as green tomatoes General lack of expertise in the fresh-
tomato business• Product pulled from market
Flavr Savr tomatoes had marginal added value; could not be sold at a profit
U.S. Labeling Policy for Food Biotechnology
FDA safety standards are consistent for all foods.
A label disclosure would be required if .. • Allergens were present in
the food• Levels of naturally
occurring toxins had increased.
• Nutrient composition or profile had been changed from its traditional counterpart
Labeling Laws?
Roundup Ready® Soybean First Crop Plant Produced By Monsanto Today, over 90% of
the soybean crop in the USA consists of Roundup Ready® plants.
Two thirds of the cotton and a quarter of the corn crop are Roundup Ready® plants.
Roundup Ready Corn 2 Roundup agricultural
herbicides have been on the market for 30 years.
Glyphosate is the active ingredient in Roundup, chances of weed resistance less likely than other chemistries.
After nine years of commercial use in the US, only two weeds have been confirmed resistant to glyphosate in Roundup Ready cropping areas.
The List Keeps Growing Insect resistant cotton
– Bt toxin kills the cotton boll worm
Insect resistant corn – Bt toxin kills the European corn borer
Herbicide resistant crops • Soybean, corn, canola,
sugarbeet, lettuce, strawberry, alfalfa, potato, wheat
Next Generation of Ag Biotech Products
Golden Rice – increased Vitamin A content (but not without controversy)
Turfgrass – herbicide resistance; slower growing (=reduced mowing)
Bio Steel – spider silk expressed in goats; used to make soft-body bullet proof vests (Nexia)
Products In The Pipeline Tomatoes enriched with
flavonols Soybean and canola oils
with higher levels of vitamin E
Vitamin-enriched rice Decaffeinated coffee Bananas to deliver a
hepatitis vaccine
Oranges resistant to citrus canker
Disease-resistant sweet potatoes
Pest- and disease-resistant cassava
Disease-resistant bananas
Potatoes to protect against cholera, E. coli and Norwalk virus
Apples to protect against RSV
Benefits of biotechnology – Better food
More Than 50 Biotech Food Products Have Been Approved For
Commercial Use In The US
Canola
Corn Cotto
n Papay
a Potato
Soybeans Squash Sugar
beets Sweet corn Tomato
Products on the market
US Crops of Genetically Modified Organisms
http://www.ers.usda.gov/Data/BiotechCrops/ HT=herbicide-tolerant
Genetically Modified Animals Genetically
modified sheep grow bigger and faster, produce double the amount of milk, can grow more wool, but require more care.
Tracy (1990-1997): Transgenic Ewe
Genetically modified so that her milk produced a human protein called alpha antitrypsin, a potential treatment for the disease cystic fibrosis.
GTC Biotherapeutics Pharmaceutical
product derived from transgenic goats modified to produce therapeutic proteins in their milk.
The product, ATryn (an antithrombrin) received regulatory approval in the EU in 2006 and in the U.S. in 2008.
Domesticated Farm Animals Are Being Used To Produce Pharmaceutical Products
Sheep• alpha1 anti trypsin
deficiency leads to emphysema
• CFTR treatment of cystic fibrosis
• tissue plasminogen activator -treatment of thrombosis
• factor VIII, IX -treatment of hemophilia
• Fibrinogen -treatment of wound healing
Pig tissue plasminogen activator -
treatment of thrombosis factor VIII, IX -treatment of
hemophilia
• Goat human protein C -treatment of
thrombosis antithrombin 3 -treatment of thrombosis glutamic acid decarboxylase-treatment
of type 1 diabetes Pro542 -treatment of HIV
• Cow alpha-lactalbumin-anti-infection factor VIII-treatment of hemophilia Fibrinogen-wound healing collagen I, collagen II-tissue repair,
treatment of rheumatoid arthritis Lactoferrin-treatment of GI tract
infection, treatment of infectious arthritis
human serum albumin-maintains blood volume
The SCID-hu Mouse Animal model for
the study of HIV/AIDS
Destroy the mouse’s normal immune system
Reconstitute with human immune cells (essentially a bone marrow transplant)
Transgenic Animals Transgenic Atlantic
salmon (bottom) overexpressing a growth hormone (GH) gene display rapidly accelerated rates of growth compared to wild strains and nontransgenic domestic strains (top).
GH salmon weigh an average of nearly 10 times more than nontransgenic strains.
By 2025, there will be another 2 billion
mouths to feed— United Nations
Population Fund
Benefits of biotechnology – More food
Developed world (EU, U.S., Japan) – Population: 1 billion– Income: $5,000+
Developing world (Asia, Latin America)– Population: 4.2 billion – Income: $400 - $5,000
Impoverished areas (Africa) – Population: 800 million– Income: <$400
More food will be needed to feed a growing
global middle class
— Consultative Group on International Agricultural Research
Benefits of biotechnology – More food
WORLD PRODUCTIVITYForests and woodlands 44.3%Grassland 9.7%Cultivated land 5.9%Desert and semi-desert 1.5%Freshwater 3.2%Oceans 35.4%
Farmers will need to at least double production over the next 25 years to meet increased demand.
Without an increase in farm productivity, an additional 4 billion acres of arable land will need to come under the plow by 2050.
— C.S. Prakash, founder and president of the nonprofit AgBioWorld Foundation
And In Case You Think Green Technology Is Only For Tree
Huggers In Oregon or Arizona…..
TVA’s First Solar Power Array In Mississippi
Located on the campus of the University of Mississippi in Oxford.
The solar photovoltaic (PV) system is built right next to the concession stand at Blackburn-McMurray Outdoor Intramural Sports Complex.
The entire system can produce about 51,500 kilowatt-hours of electricity a year; that’s equal to 343 blocks of electricity for Green Power Switch customers.
TVA’s Second Solar Power Array In Mississippi
Located on the campus of Mississippi State University in Starkville.
Built as a canopy to cover a sidewalk between the new Landscape Architecture Building and the Ammerman-Hearnsberger Pilot Food Processing Lab.
System can produce about 26,300 kilowatt-hours of electricity
Thank You.
Questions?
Comments?
Four crops accounted for nearly all of the global biotech crop area in 2002
Source: International Service for the Acquisition of Agri-biotech Applications
5%
12%
21%
62%
Canola
Cotton
Corn
Soybeans
Products on the market
Four countries accounted for 99 percent* of the global biotech crop area
in 2002
4%
6%
23%
66%
China
Canada
Argentina
United States
*Australia, Bulgaria, Colombia, Germany, Honduras, India, Indonesia, Mexico, Romania, South Africa, Spain and Uruguay accounted for the remaining 1 percent of biotech crop acres.
Source: International Service for the Acquisition of Agri-biotech Applications
Products on the market
WORLD PRIMARY PRODUCTIVITY
Net Productivity
Forests and woodlands 44.3%Grassland 9.7%Cultivated land 5.9%Desert and semi-desert 1.5%Freshwater 3.2%Oceans 35.4%
Using corn derived dextrose feedstock
Co-located near Cargill’s corn wet mill
Can produce over 140,000 tons per year of polylactide (PLA) polymers for fibers and plastic packaging
$300 Million Capital Investment19 months from ground breaking to prime product10 years to develop technology, know-how, and receptive market
Cargill-Dow: Blair, Nebraska
Pharmaceuticals from Plants
COMPOUND USE Vinblastin/vicristine Leukemia Ajmalicine Circulatory Digitalis Cardiovascular Quinine Malaria Codeine Sedative Pyrethrins Insecticides
Economically Important Therapeutic Agents
COMPOUND ORGANISM ACTIVITY Bactracin Bacillus sp. AntibacterialCephalosporin Cephalosporium sp. AntibacterialChloramphenicol Acremonium sp. AntibacterialPenicillin G Penicillium sp. AntibacterialStreptomycin Streptomyces sp. AntibacterialTetracycline Streptomyces sp. AntibacterialFumagillin Aspergillus sp. AmoebicidallNatamycin Streptomyces sp Food preservativeNisin Streptococcus sp Food preservative
Monoclonal Antibodies Cancer diagnosis and therapy Diagnosis of pregnancy Diagnosis of infectious diseases Prevention of immune rejection of
organs implants Purification of industrial products Detection of trace molecules,
organisms
DEFINE THE PROBLEM, DESIGN A CURE