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 • 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
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.
Even Iowa Wants to Know What Is Going On http://www.extension.iastate.edu/agdm/articles/hof/HofJan09.html
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.
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.
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
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
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 *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 • 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
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?
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 10-9 meters 1 meter • 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
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
A B A,B O Out of 100 donors . . . . .
stopped Gene therapy • Delivery of therapeutic genes into the body to correct disease conditions created by faulty gene • How is it done? 1 2 4 3
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
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.
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)
Calgene’sFlavrSavr 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 • Calgeneset 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 • FlavrSavr tomatoes spoiled slower than wild tomatoes at room temperature • 1 lb weight and timer to measure firmness • Field test • FlavrSavr tomatoes ripened as fast as wild tomatoes, rotted slower • File Patents • Solicit FDA Approval • Demonstrate that FlavrSavr tomatoes do not pose a health risk