biotechnology: past, present, and future donna c. sullivan, phd division of infectious diseases...

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 6000 BC: Sumarian and Babylonian beer 4000 BC: Egyptian leavened bread, cheese, mushroom cultivation 4000 BC: Egyptian leavened bread, cheese, mushroom cultivation At time Genesis was written: wine At time Genesis was written: wine 1857-1876: Pasteur demonstrated fermentation by microorganisms 1857-1876: Pasteur demonstrated fermentation by microorganisms

The Brave New World We are at the beginning of the biotech century We are at the beginning of the biotech century Biotech is expanding Biotech is expanding Industrial & environmental applicationsIndustrial & environmental applications Medical applicationsMedical applications Food and agricultural applicationsFood and agricultural applications

Bio Mass Biomass already supplies 14% of the worlds primary energy consumption. Biomass already supplies 14% of the worlds primary energy consumption. On average, biomass produces 38% of the primary energy in developing countries. On average, biomass produces 38% of the primary energy in developing countries. USA: 4% of total energy from biomass, around 9000 MegaWatts 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. 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. 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 Dont 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

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. MYTH: More energy goes into producing ethanol than it delivers as a fuel. FACT: In terms of fossil FACT: In terms of fossil energy, each gallon of energy, each gallon of ethanol produced from ethanol produced from corn today delivers one corn today delivers one third or more energy third or more energy than is used to produce it. than is used to produce it. Raw MaterialEnergy output/ Energy input Wheat1.2 Corn1.2-1.5 Sugar beet1.9 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. 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. FACT: Ethanol blends in use today have little impact on fuel economy or vehicle performance.

Even if you dont, you can have your car converted. Several companies provide kits to convert gasoline powered vehicles to FFVs.

The U.S. has Abundant Cellulose Sources Corn Stover Corn Stover Rice Straw Rice Straw Wheat Straw Wheat Straw Barley Straw Barley Straw Sugar Beet Tops Sugar Beet Tops Alfalfa Alfalfa Switch Grass Switch Grass Saw Dust Saw Dust Sugar cane waste Sugar cane waste

Biomass: And It Doesnt Have To Be Just Plants. Bio Mass from cattle manure, agricultural waste, forest residue and municipal waste. Bio Mass from cattle manure, agricultural waste, forest residue and municipal waste. Anaerobic digestion of livestock wastes to give bio gas Anaerobic digestion of livestock wastes to give bio gas Fertilizers as by product. Fertilizers as by product. Average electricity generation of 5.5kWh per cow per day!! 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 Its 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. 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 "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 Multi-feed stock ColumbusColumbus GreenvilleGreenville Soy Soy NatchezNatchez Make your own Make your own Arkansas company sells kitArkansas company sells kit

BIOTECHNOLOGY AND MEDICINE Pharmaceuticals Pharmaceuticals Antibiotics-most come from microbesAntibiotics-most come from microbes Biopharmaceuticals Biopharmaceuticals Monoclonal antibodiesMonoclonal antibodies VaccinesVaccines Gene therapyGene therapy Diagnostics Diagnostics

Biotechnology has Revolutionized Drug Development Injected insulin directly supplements an insufficiency in diabetics Injected insulin directly supplements an insufficiency in diabetics Prior to 1982, insulin was primarily extracted from pig pancreas Prior to 1982, insulin was primarily extracted from pig pancreas 50 pigs sacrificed to produce sufficient insulin for one person for one year50 pigs sacrificed to produce sufficient insulin for one person for one year Risk of disease transmission, shortages, immune system rejectionRisk of disease transmission, shortages, immune system rejection Use gene splicing to insert human insulin gene into bacteria Use gene splicing to insert human insulin gene into bacteria Plentiful supplyPlentiful supply No risk of animal disease transmissionNo risk of animal disease transmission Reduced risk of immune system rejectionReduced risk of immune system rejection Traditional pharmaceutical methods involve chemical synthesis and biological extracts and pharmaceuticals are often indirect effectors 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 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 Downs Syndrome and sex Karyotyping

Screening For Genetic Abnormalities Fluorescent in situ hybridization (FISH) used to detect: Fluorescent in situ hybridization (FISH) used to detect: Extra chromosomesExtra chromosomes Missing parts of chromosomesMissing parts of chromosomes DNA swapping across different chromosomesDNA swapping across different chromosomes Chronic myelogenous leukemia Chronic myelogenous leukemia DNA exchange between chromosome 9 and 22DNA exchange between chromosome 9 and 22 ACCATG GTATAC * TGGTAC * CATATG Fluorescent DNA probes

Allele Specific Oligonucleotide Analysis (ASO) Analyze DNA from cells of 8- 32-cell-stage- old embryo created by in vitro fertilization Analyze DNA from cells of 8- 32-cell-stage- old embryo created by in vitro fertilization Allows individuals to select healthy embryos before implantation 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 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. 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. 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 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? 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 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? 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? How do we ensure privacy and confidentiality?

Microarray for Leukemia screening

Drug delivery Getting drug to target organs and tissue Getting drug to target organs and tissue Oral drug to treat arthritis in knee is not very efficientOral drug to treat arthritis in knee is not very efficient Drug solubility may be an issueDrug solubility may be an issue Microspheres Microspheres Insulin delivered as a powder through an inhaler

Nanomedicine Nanometer is one billionth of a meter Nanometer is one billionth of a meter May be used for delivery of small sensors to target sites in bodyMay be used for delivery of small sensors to target sites in body Unclogging arteriesUnclogging arteries Detect and destroy cancer cellsDetect and destroy cancer cells 1 meter 10 -9 meters

Artificial blood Cell-free solutions containing molecules that can bind and transport oxygen like hemoglobin Cell-free solutions containing molecules that can bind and transport oxygen like hemoglobin Benefits Benefits Disease-free alternative to real bloodDisease-free alternative to real blood Constant supplyConstant supply Universal donor typeUniversal donor type Disadvantages Disadvantages Cannot perform all the functions of a red blood cell-only oxygen deliveryCannot perform all the functions of a red blood cell-only oxygen delivery Source of iron Source of iron Carbon dioxide removal 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+ Everyone A-A+ A- AB+ AB-A- O- O-EveryoneO- 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 Delivery of therapeutic genes into the body to correct disease conditions created by faulty gene How is it done? How is it done? 1 2 3 4 stopped

Pharmacogenomics

Epogen Biotechs First Blockbuster Erythropoietin (EPO) is a hormone that increases red blood cell proliferation Erythropoietin (EPO) is a hormone that increases red blood cell proliferation Used to treat anemiaUsed to treat anemia Reduces need for blood transfusionsReduces need for blood transfusions Development timeline Development timeline Initially purified from 2,500 quarts of human urine in 1976Initially purified from 2,500 quarts of human urine in 1976 Patents filed in 1984Patents filed in 1984 Efficacy demonstrated in 1986Efficacy demonstrated in 1986 Approved for HIV patients in 1990 14 years after first purification!Approved for HIV patients in 1990 14 years after first purification! Expanded approvals thereafterExpanded approvals thereafter Developed by Amgen Developed by Amgen CEO is a former US Navy nuclear-submarine chief engineerCEO is a former US Navy nuclear-submarine chief engineer Prior science training: High-school biology, college chemistryPrior science training: High-school biology, college chemistry

Cloned Biopharmaceuticals PRODUCTAPPROVED USE InsulinDiabetes Human growth hormoneGrowth deficiency Interferon Cancer, viral infections Hepatitis B VaccineHBV prevention Tissue Plasminogen activatorCardiovascular disease ErythropoietinAnemia Interleukin-2Cancer

Xenotransplantation Transplanting organs from one species into another Transplanting organs from one species into another May someday become an alternative to human-to-human transplantation May someday become an alternative to human-to-human transplantation 1984 baboon heart transplanted into a 12- year-old human girl1984 baboon heart transplanted into a 12- year-old human girl Girl died after 3 weeks as a result of organ rejection Girl died after 3 weeks as a result of organ rejection Can be avoided by matching immune system of donor and acceptorCan be avoided by matching immune system of donor and acceptor Major histocompatibility complex Major histocompatibility complex Human leucocyte antigen (HLA) present on all of our cellsHuman 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. 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 Waste water and sewage treatment Safe drinking waterSafe drinking water Acceptable sewage disposalAcceptable sewage disposal Landfill technologies Landfill technologies Composting Composting Bioremediation Bioremediation Bioleaching Bioleaching

Bioleaching To Solubilize Elements Bioleaching costs 33-50% less than direct smelting Bioleaching costs 33-50% less than direct smelting Commercially important metals Commercially important metals Copper (10% of total production in US)Copper (10% of total production in US) UraniumUranium (4000 tons/year in US) (4000 tons/year in US) OthersOthers (zinc, cobalt, lead) (zinc, cobalt, lead)

At The Table

Calgenes Flavr Savr Tomato Most tomatoes are gas-ripened Most tomatoes are gas-ripened Picked while green to prevent damage during shippingPicked while green to prevent damage during shipping Sprayed with ethylene to ripen prior to saleSprayed with ethylene to ripen prior to sale Result is bright red but tasteless tomatoesResult is bright red but tasteless tomatoes Vine-ripened tomatoes sell for a premium Vine-ripened tomatoes sell for a premium Tastier than gas-ripened tomatoesTastier than gas-ripened tomatoes Cost more to deliver to market, have shorter shelf-livesCost more to deliver to market, have shorter shelf-lives Polygluconase enzyme was associated with ripening in 1984 Polygluconase enzyme was associated with ripening in 1984 Highly expressed in red tomatoes, absent in green tomatoesHighly expressed in red tomatoes, absent in green tomatoes Calgene set out to reduce expression of polygluconase to delay ripeningCalgene 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 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 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 Isolate PG gene and generate antisense tomatoes Develop assay for ripening Develop assay for ripening Flavr Savr tomatoes spoiled slower than wild tomatoes at room temperatureFlavr Savr tomatoes spoiled slower than wild tomatoes at room temperature 1 lb weight and timer to measure firmness1 lb weight and timer to measure firmness Field test Field test Flavr Savr tomatoes ripened as fast as wild tomatoes, rotted slowerFlavr Savr tomatoes ripened as fast as wild tomatoes, rotted slower File Patents File Patents Solicit FDA Approval Solicit FDA Approval Demonstrate that Flavr Savr tomatoes do not pose a health riskDemonstrate that Flavr Savr tomatoes do not pose a health risk

Market Launch Taste of Flavr Savr tomatoes not as good as competing premiums Taste of Flavr Savr tomatoes not as good as competing premiums Flavr Savr gene was not introduced into premium tomato varietiesFlavr Savr gene was not introduced into premium tomato varieties Flavr Savr tomatoes could not withstand shipping Flavr Savr tomatoes could not withstand shipping Firmer than vine-ripened, but not as durable as green tomatoesFirmer than vine-ripened, but not as durable as green tomatoes General lack of expertise in the fresh- tomato business General lack of expertise in the fresh- tomato business Product pulled from marketProduct pulled from market Flavr Savr tomatoes had marginal added value; could not be sold at a profit 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. FDA safety standards are consistent for all foods. A label disclosure would be required if.. A label disclosure would be required if.. Allergens were present in the foodAllergens were present in the food Levels of naturally occurring toxins had increased.Levels of naturally occurring toxins had increased. Nutrient composition or profile had been changed from its traditional counterpartNutrient 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 Tomatoes enriched with flavonols Soybean and canola oils with higher levels of vitamin E Soybean and canola oils with higher levels of vitamin E Vitamin-enriched rice Vitamin-enriched rice Decaffeinated coffee Decaffeinated coffee Bananas to deliver a hepatitis vaccine Bananas to deliver a hepatitis vaccine Oranges resistant to citrus canker Oranges resistant to citrus canker Disease-resistant sweet potatoes Disease-resistant sweet potatoes Pest- and disease- resistant cassava Pest- and disease- resistant cassava Disease-resistant bananas Disease-resistant bananas Potatoes to protect against cholera, E. coli and Norwalk virus Potatoes to protect against cholera, E. coli and Norwalk virus Apples to protect against RSV 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 Canola Corn Corn Cotton Cotton Papaya Papaya Potato Potato Soybeans Soybeans Squash Squash Sugar beets Sugar beets Sweet corn Sweet corn Tomato 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. 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. 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. 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 Sheep alpha1 anti trypsin deficiency leads to emphysemaalpha1 anti trypsin deficiency leads to emphysema CFTR treatment of cystic fibrosisCFTR treatment of cystic fibrosis tissue plasminogen activator - treatment of thrombosistissue plasminogen activator - treatment of thrombosis factor VIII, IX -treatment of hemophiliafactor VIII, IX -treatment of hemophilia Fibrinogen -treatment of wound healingFibrinogen -treatment of wound healing Pig Pig tissue plasminogen activator - treatment of thrombosis tissue plasminogen activator - treatment of thrombosis factor VIII, IX -treatment of hemophilia 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 mouses 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:

biotechnology: past, present, and future donna c. sullivan, phd division of infectious diseases...

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