Biotechnology: Past, Present, And Future Donna C. Sullivan, PhD
Division of Infectious Diseases Univ. Mississippi Medical
Center
Slide 2
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
Slide 3
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
Slide 4
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
Slide 5
GASOHOL: Are We Starving Children to Drive Our Hummers?
Slide 6
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.
Slide 7
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.
Slide 8
Does It Have To Be That Way?
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Even Iowa Wants to Know What Is Going On
http://www.extension.iastate.edu/agdm/articles/hof/HofJan09.html
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Historical Trend Ethanol And Flex Vehicles In Brazil
Slide 12
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
Slide 13
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.
Slide 14
Even if you dont, you can have your car converted. Several
companies provide kits to convert gasoline powered vehicles to
FFVs.
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!!
Slide 17
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.
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And Its Not Just Someplace Else.
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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
Slide 20
Columbus, Mississippi
Slide 21
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
Slide 22
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
Slide 23
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
Slide 24
Personalized Medicine
Slide 25
People Have Been Making Decisions Based on Biotechnology for
Years: Testing for Downs Syndrome and sex Karyotyping
Slide 26
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
Slide 27
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
Slide 28
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
Slide 29
Identifying sets of disease genes by microarrays
Slide 30
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?
Slide 31
Microarray for Leukemia screening
Slide 32
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
Slide 33
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
Slide 34
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
Slide 35
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
Slide 36
Monoclonal antibodies
Slide 37
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
Slide 38
Pharmacogenomics
Slide 39
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
Slide 40
Cloned Biopharmaceuticals PRODUCTAPPROVED USE InsulinDiabetes
Human growth hormoneGrowth deficiency Interferon Cancer, viral
infections Hepatitis B VaccineHBV prevention Tissue Plasminogen
activatorCardiovascular disease ErythropoietinAnemia
Interleukin-2Cancer
Slide 41
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
Slide 42
Pigs genetically engineered to lack a sugar-producing gene that
causes human bodies to reject pig organs
Slide 43
Slide 44
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.
Slide 45
More Than One Kind of Cloning
Slide 46
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
Slide 47
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)
Slide 48
At The Table
Slide 49
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
Slide 50
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
Slide 51
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
Slide 52
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
Slide 53
Labeling Laws?
Slide 54
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.
Slide 55
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.
Slide 56
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
Slide 57
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)
Slide 58
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
Slide 59
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
Slide 60
US Crops of Genetically Modified Organisms
http://www.ers.usda.gov/Data/BiotechCrops/
HT=herbicide-tolerant
Slide 61
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.
Slide 62
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.
Slide 63
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.
Slide 64
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
Slide 65
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)
Slide 66
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.
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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: