Transcript History of Discoveries in Molecular Biology

“ IF THE ULTIMATE AIM OF SCIENCE IS TO
CLARIFY MANKIND’S RELATIONSHIP TO
THE UNIVERSE , THEN BIOLOGY MUST BE
GIVEN A CENTRAL POSITION”
Jacques Manod ,Nobel prize
(allosteric transitions)
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Scientific
discovery
in
molecular
biology
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MOLECULAR
BIOLOGY
BIOCHEMISTRY
CELL BIOLOGY
GENETICS
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1600s 1800s 1850s 1900s 1950s 2000s
1632-1723
 Antony van Leeuwenhoek –
shopkeeper, Dutch
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1635-1703
 Robert Hooke – physicist, London
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Micrographia, published in 1665
. . . I could exceedingly plainly perceive it to be all perforated and porous, much
like a Honey-comb, but that the pores of it were not regular. . . . these pores, or
cells, . . . were indeed the first microscopical pores I ever saw, and perhaps, that
were ever seen, for I had not met with any Writer or Person, that had made any
mention of them before this. . .
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1600s 1800s 1850s 1900s 1950s 2000s
1800-1882
 Friedrich Wöhler German chemist
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synthesized a natural
product - urea (1828)
Bridge between
living/non-living
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Urea Cycle
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Urea - nitrogenous waste of mammals.
Comes from the breakdown of amino acids
Ammonia - extremely toxic base and its
accumulation in the body would quickly be
fatal.
The liver contains a system of carrier
molecules and enzymes which converts the
ammonia (and carbon dioxide) into urea.
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Urea
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Industrial use - the manufacture of plastics
(specifically, urea-formaldehyde resin), a
component of many fertilizers, providing a
nitrogen source that is necessary for
plants.
Laboratory use - a powerful protein
denaturant.
Medical significance - high levels of urea in
the blood indicate a problem with the
removal, or more rarely with the overproduction, of urea in the body.
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1600s 1800s 1850s 1900s 1950s 2000s
1773 – 1858
 Robert Brown-Scottish botanist
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Found nucleus (1825)
Brownian Movement
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1804-1881
 Matthias Schleiden -German botanist
1810-1882
 Theodor Schwann - German cytologist ,
physiologist
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Developed the cell theory in 1839, which identified cells
as the fundamental particles of plants and animals
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1821-1902
 Rudolf Virchow - German pathologist
"Omnis cellula e cellula" (where a cell arises, there a
cell must previously have existed). (1858)
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1822-1895
 Louis Pasteur –French
chemist
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Solved the mysteries of rabies, anthrax, chicken
cholera, and silkworm diseases, and contributed to
the development of the first vaccines
Reason for fermentation (yeast)
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1823-1884
 Gregor Mendel – Czech monk
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Fundamental laws of genetics (1865)
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1844-1895
 Friedrich Miescher - Swiss physician
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isolated nucleic acid
became known as nucleic acid after 1874, when
Miescher separated it into a protein and an acid
molecule.
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1843-1905
 Walter Flemming - German scientist
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1870 Discovered chromosomes
1871 Discovered mitosis
Linked mitosis to Mendel’s observations
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1600s 1800s 1850s 1900s 1950s 2000s
1860-1917
 Eduard & Hans Buchners– German
brothers
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Eduard Buchner Winner of the 1907 Nobel
Prize in Chemistry
1897 - Discovery of cell-free fermentation
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1862 - 1915
 Theodor Boveri – German biologist
1877-1916
 Walter Sutton - graduate student in the
Department of Zoology
(1902) chromosome theory of Heredity
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1920
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Nucleic Acids major component of
chromosomes
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1881 – 1955
 Sir Alexander Fleming
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Nobel Prize in 1945.
"One sometimes finds what one is not looking
for."
He published a report on penicillin 1929,but it
raised little interest
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1927
 James Sumner – American
biochemist
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Purified and crystallized the first
protein enzyme (urease from
bean)
1946 - Nobel Prize for
Chemistry
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1881 - 1941
Frederick
Griffith -an English army medical
officer
 in 1928 Discovered “Genetic
Transformation”
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Frederick Griffith’s 1920s
Experiment
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1600s 1800s 1850s 1900s 1950s 2000s
1877-1955
 Oswald Avery –
American bacteriologist
S
R
DNA
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1943 – proved that DNA carries genes
S
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Discovery of DNA
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the extracts of heat-killed S bacteria cells
contained
protein, RNA and DNA
which of these substances were essential for
transformation?
How did they figure out which substance was
essential for transformation?
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Discovery of DNA
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They decided to use the process of
elimination
Extracts were treated with either
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Proteases (to destroy protein)
RNase (to destroy RNA)
DNase (to destroy DNA)
Transformation was due exclusively to
DNA
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Alfred Hershy and Martha Chase
1952
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used bacteriophage to prove that
DNA was the hereditary material
the bacteriophage was the ideal organism
for
settling the debate between protein and
DNA.
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What are viruses?
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Viruses are organized
associations of
macromolecules:nucleic acid
contained within a
protective shell of
protein units .
A virus is NOT alive.
A virus is NOT made out
of a cell.
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DNA discovery Hersy-Chase 1952
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DNA discovery Hersy-Chase
1952
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1929-1992
 Erwin Chargaff – Austrian
American biochemist
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(1950) Discovered the
base-pairing regularities or
"complementarity
relationships" of nucleic
acids that provided one of
the key steps in developing
a structural model for DNA.
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1920 – 1958
 Rosalind Franklin- English
Chemist
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the most beautiful X-ray
photographs of any substance
ever taken
(1952) crucial contributions to
the solution of the structure of
DNA
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1953
 James Watson – American ornithologist
 Francis Crick – British Physicist
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1955
Fred Sanger- British Biochemist
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The Nobel Prize in Chemistry 1958
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First complete sequence of the protein
(insulin)
The Nobel Prize in Chemistry 1980
"for their contributions concerning the
determination of base sequences in nucleic
acids"
 Principle of the Chain-terminating (dideoxy
Method for Sequencing DNA
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Marshall W. Nirenberg
Heinrich Mathieu
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protein synthesis poly-U
experiments and the first clue
to the genetic code
1968 - Nobel Laureate in
Medicine
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1980
 Paul Berg, Walter Gilbert, Frederick Sanger
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The Nobel Prize in Chemistry 1980
"for their contributions concerning the
determination of base sequences in nucleic
acids"
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1978
 David Botstein - California
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Discovery of Restriction Enzymes
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1977
 Bill Rutter and Howard Goodman
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Isolated the gene for rat insulin
1978
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Harvard researchers used genetic engineering
techniques to produce rat insulin
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Kary B. Mullis
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1980
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1980 - Kary B. Mullis
 Cetus Corporation in Berkeley, California,
invented a technique for multiplying DNA
sequences in vitro by, the polymerase
chain reaction - PCR. PCR has been called
the most revolutionary new technique in
molecular biology in the 1980s. Cetus
patented the process, and in the summer
of 1991 sold the patent to Hoffman-La
Roche, Inc. for $300 million
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The idea was not the product of a painstaking laboratory
discipline, but was conceived while cruising in a Honda
Civic on Highway 128 from San Francisco to Mendocino.
"I do my best thinking while driving," the scientist with
the tanned face and bleached hair once explained. For
this brilliant idea born at the speed of 50 m.p.h., he
received a $10,000 bonus from Cetus, with whom he
eventually parted ways. (Cetus later sold the technolgy to
LaRoche for $300,000,000.) He now lives in a small
apartment across from Windansea Beach, a surfing spot
made famous by Tom Wolfe's novel, "The Pump House
Gang." A man interested in many things in life besides
molecular biology and surfing, he has refused to team up
with the biotechnology industry or academia. Currently,
he consults and lectures around the world about
biotechnology or the development of the scientific
method, its successes and its failures.
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1983
 Jay Levy's lab at University of California
San Francisco and Pasteur Institute in Paris
and at the NIH isolated the AIDS virus
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1986
 A regiment of scientists and technicians at
Caltech and Applied Biosystems, Inc.,
invented the automated DNA fluorescence
sequencer
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1990
 Mary Claire King,
epidemiologist at UCBerkeley
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reported the discovery of
the gene linked to breast
cancer in families with a
high degree of incidence
before age 45.
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1997
 Researchers at Scotland's Roslin Institute
report that they have cloned a sheep-named Dolly - from the cell of an adult ewe.
Polly the first sheep cloned by nuclear
transfer technology bearing a human gene
appears later.
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1999
 “Celera genomics” – Rockville, Maryland
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Drosophila genome
http://www.fruitfly.org/
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2000
 Complete Human Genome Project
http://www.genome.gov/
2002
 Mouse Genome Project
http://www.informatics.jax.org/
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Physicists developed the most powerful
techniques used by biochemists:
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Electron microscopy
X-ray diffraction
Nuclear Magnetic Resonance
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FUTURE PROGRESS
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DEVELOPMENT AND DIFFERENTIATION
BRAIN FUNCTION
MOLECULAR BASES FOR ALL DISEASES
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NOBEL
http://www.nobel.se/