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What Is Biotechnology?
Using scientific methods with organisms to
produce new products or new forms of organisms
Any technique
that uses living organisms or substances from those organisms to make or modify a product, to improve plants or animals, or to develop microorganisms for specific uses
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Beer is an ancient foodstuff
Ancient beer was not
just drink, but food
Thick drink with high caloric value
as well as alcohol
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Yeast cells
Both beer and bread were developed around
the same time in the middle east
Early bread was
flat, but when wild yeast contaminated the dough, a fluffier, sweeter bread was created
Beer arose out of the liquid soaked bread
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Cheese & yogurt also came about due to
microbial contamination
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Classical Biotechnology
Refinement of fermentation techniques during 18th and
19th C.
During 20th C. fermentation expanded to the production
of:
Glycerol
Acetone
Butanol
Lactic acid
Citric acid
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Herbal plants have been used since ancient times
Even
today, 25% of our common medicines contain at least
some compounds obtained from plants
Why do plants create these compounds?
Protection from herbivory and predation
Allelopathy - plants secrete toxins from their roots that prevent the germination of other plants in their root zone
Biopharmaceuticals
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Alkaloids: Over 5,000 alkaloids have been identified in
numerous plant families, most in the angiosperms
Contain nitrogen
Alkaline
Bitter
Physiological effect on animals, often on nervous system
Names of most alkaloids end in "...ine"
http://www.life.umd.edu/classroom/bsci124/lec29.html
http://www.uky.edu/~dhild/biochem/26/quinoline.gif
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Common Medicinal Alkaloids & their Sources:
Morphine Poppies
Caffeine Coffee/Tea
Nicotine Tabacco
Emetine Ipecac
Atropine Belladonna
Quinine Cinchona Tree
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During 19th C. quinine was critical to British
colonial expansion
Extracted from the bark of the cinchona
plant
Not enough could be extracted, another source was needed
http://www2.unil.ch/lpc/images/docu04/0_doc/quinine.gif
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Bayer discovered way to synthesize acetylsalicylic acid
Known under
its trade name, Aspirin
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Penicillium mold
In 1928 Alexander Fleming noticed something odd
about a petri dish contaminated with mold
The mold seemed
to kill the bacteria
Fleming was unable to isolate the bactericidal action
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In 1940 Norman Heatley finally showed that
penicillin could stop infection
Mice were infected with streptococcus
bacteria
Half were given penicillin.
Those receiving penicillin survived, those that didn’t died.
No penicillin penicillin
24 hrs. later
No penicillin penicillin
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1st human patient was a policeman with
staphylococcal & streptococcal infections which had already taken part
of his face and an eye
He began to recover, but later died
2nd patient was a 15 yr. old boy septic from a hip operation
Two days after receiving penicillin his temperature dropped back to normal after being at 100° for 2 wks
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By D-Day the U.S. was making millions
of doses.
Unfortunately, neither Heatley nor his boss patented
the discovery. This was done by U.S. firms.
Thus for 25 yrs. England had to pay royalties on its own discovery.
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Genetics - historical perspective
Practical genetics 7,000 yeas ago
corn breeding - Central America
rice breeding - China
horse pedigree
- Babylon
Genetics - science - Mendel
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A domesticated animal is one which has been
bred in captivity
Thru artifical selection they are modified from
their ancestors for use by humans
Before After
http://www.doganswers.com/method.htm
http://www.billybear4kids.com/animal/whose-toes/toes-61a-wolf.html
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Wolf/Dog domestication lead to:
Alteration in body size
Reduction in
skull & tooth size
Shortening of the jaw bones
Affection for
humans
Variation in coat color
Tendency towards barking
By 6000BC dog skeletons are found along side human remains
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http://nemp.otago.ac.nz/read_speak/2004/read_comprehension/shrek.htm
Modern sheep have been bred not to lose
their wool
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Most domesticated species arose in SW Asia
or China
Of the ~150 species of terrestrial non-carnivores >100
lbs, only 14 have been domesticated
13 are of Eurasian origin, one from mesoamerica
None derive from Australia or sub-Saharan Africa
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Desirable Characteristics for Domestication of an Animal Species
Value to humans as food, draft, fiber, or hunting
Large
herbivores offer energy use advantages
Rapidly reach their desired size
Must be able to breed in captivity
Good disposition & social structure
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The switch from hunter-gatherer to farmer took place
between 10 000 & 5 000 years ago
Both Eurasia
& the Americas developed large numbers of domesticated crops
The development of agriculture required changes in wild plants such that they were amendable to cultivation
Many of these changes were either brought about by humans or were capitalized by them
Plant Domestication
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Example
Wheat is a grass spread seeds called grains
Mutants
developed that did not lose seed
This made it easier
for humans to collect
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Hybridization played a role in the evolution of
modern grains
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Changes in corn size from 5000 BCE to
1500CE
The evolution of modern corn took several thousand years
Selection
for larger ears by mesoamericans created modern corn by the time Europeans had reached the Americas
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Mutation responsible for this change has been identified
It
is not a change in a gene itself, rather
it is a decrease in the expression of the gene tb1
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Later Concepts
1900 - Not until 34 years after
its publication did Mendel’s work receive additional attention, with
publications in 1900 by three Botanists: Hugo de Vries, Carl Correns, and Erich von Tsernak;
1902 - Walter Sutton first integrated the concepts of chromosomes with Mendel’s laws, in studies of grasshopper reproduction and cell division and concluded that Mendel’s heritable factors must be on the chromosomes.
1907 – T.H. Morgan began his work with fruit flies, ultimately mapping gene locations.
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First Structure
By 1910 actual components known (nucleotides)
Phoebus Levene
proposed a tetranucleotide structure for DNA
Tetranucleotide repeat of
ATCG
Own data showed nucleotides not in 1:1:1:1 ratio
Differences “probably experimental error…”
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So…
If DNA was a single covalently bonded tetranucleotide
structure then it couldn’t easily encode information
Proteins, on the
other hand, had 20 different amino acids and could have lots of variation
Most geneticists focused on “transmission genetics” and passively accepted proteins as being the likely genetic material
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T. H. Morgan’s Fruit Flies 1907-1930s
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Frederick Griffith, 1928
Transformation of Bacteria
Transforming factor ?
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Avery, McCarty and MacLeod
After 10 yrs of effort
published work using Griffith’s approach to assay for the
genetic material
Used
Cell-free extract of S cells
From 75 liters of cell culture obtained 10-25 mg of “active factor
Proteases, RNases, DNases, etc.
Transforming factor is DNA
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Erwin Chargaff
1949-1953
Digested many DNAs and subjected products to
chromatographic separation
Results
A = T, C = G
A + G
= C + T (purine = pyrimidine)
A + T does not equal C + G
Members of a species similar but different species vary in AT/CG ratio
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X-ray Crystallography of DNA
Franklin and Wilkins
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Watson and Crick
1953 propose double helix model
Right-handed double
helix
Collaborated at Cambridge, England.
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Impact
Article in Nature
“It has not escaped our notice
that the specific pairing we have postulated immediately suggests
a possible copy mechanism for the genetic material”
Second paper 2 months later describes semiconservative replication and that mutations must change bases in DNA (information encoded in the bases and their order)
DNA became the genetic material…