Biotechnology: Past, Present, And Future

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