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7/27/2019 Bacteriophage [Compatibility Mode] (2)
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20:20:20:20: BacteriophageBacteriophageBacteriophageBacteriophage
STSC123: Darwins Legacy Lecture 20
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20: Outline
Bacteriophage
20.1 Viruses
20.2 Delbrck and
Phage group
20.3 Community and the Rise
of Molecular Biology.
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20.1 Viruses
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Cash Crop in Danger Tobacco was cash crop and also legal tender
throughout the world
Heavily cultivated in monoculture fields
Tobacco Mosaic Disease first described inAmerica in Virginia area in late 19th century.
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Tobacco Mosaic Disease
1879 A. Mayer names this Tobacco Mosaic
Disease
1892 D. Ivanowski demonstrates that TMD
cannot
1898 M.W. Beijerinck TMD is neither bacteria
or corpuscular body but something else henames a contagium vivum fluidum
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Tobacco Mosaic Virus Abundantly produced in the
infected plant
Not transmitted by other vectors
Infected lants have visible
malformations
First virus to be purified and
crystallized(1935), detected in
analytical ultracentrifuge (1936),
and to be visualized in an
electron microscope (1939)
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Bacteriophage
Doctors in India notice cholera bacilli
destroyed by something in the Ganges
First theorized in 1915 by Frederick Twort
ept. , x e re e namesbacteriophage- bacteria eater- and recounts a
story of the dramatic recovery of a man with
dysentery cured by bacteriophage. Parasites versus chemical catalysts
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Two Directions
1. Clinical Applications
- University Systems and Government
- Pasteur Institute
- medical schools
2. Basic scientific experimentation
- Rockefeller Foundation- California Institute of Technology
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Rockefeller Foundation Science of Man funding program
eugenics pre WWII/molecular biology postWWII
Warren Weaver funnels money
into biology that is interdisciplinary-chemistry/physics/biology
Post 1953, the Nobel Prize was given to 18
scholars for molecular biology research; 17funded by Rockefeller Foundation underWeaver
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Emory Ellis
- Emory Ellis, a chemist, uses
phage to investigate tumorgrowth.
-
replicates itself.
- Follower of de Hrelle
- works with virus that infectse.coli
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From the beginning, our interest was in
growth processes, and not in classifying
different races of phage, or in findingmedical uses for them. It was fortunate that
the phage isolated was one which dHerelle
Model System
wou ave ca e v ru ent. Its a sorpt on tobacteria in young dense cultures was rapid,
making it possible to start growth of a parent
phage population with reasonable
simultaneity, so that their progeny might
graduate from the infected bacterial cells
also with a reasonable degree of simultaneity.
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Model System
Standardized organisms
Prototypes within which keybiological questions are askedand resolved
Technologies that study them
Self reinforcing qualityThe more people study them,
the more they are used, theeasier they are to use in studies
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20.2 Max Delbruck and the phage
group
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Max Delbruck- Born in Berlin-
1906
- Studied Physics
in Gttingen
-
- 1930-post
doctoral work
with Max Bornin Copenhagen
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Complementarity
-Multiple ways of
seeing a problem-Experimentation
natural occurrence
- paradoxes lead to
new avenues of
thinking
How can you apply this to Biology?
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Early Biology Work
-1932- back to Berlin to work withOtto Hahn and Lise Mietner
-Joins biology discussion group with
Russian Drosophila geneticist N.Timofeeff-Ressovsky and physicist
K.G. Zimmer
-Physical nature of the gene andeffects of radiation upon it
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On the whole, the successful theories of biology
always have been and are still today simple and
concrete. Presumably this is not accidental, but isbound up with the fact that every biological
henomenon is essentiall an historical one one
A Physicists Want Ad
unique situation in the infinite total complex oflife.
Such a situation from the outset diminishes the
hope of understanding any one living thing by
itself and the hope of discovering universal laws,
the pride and ambition of physicists.
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Take for instance, ordinary classical genetics of
some higher organism. We find that heredity is
controlled by genes linearly arranged in
chromosomes, and it might seem that the
Continued
pro em o repro uct on as een re uce tothat of the reproduction of the genes, but this is
not true because no gene has been observed to
reproduce except within the intact functionalcell. We have every reason to believe that this
dependence on the intactness of each cell is an
essential one.
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The fact that there are many different genesin each cell, and that we have learned to
combine different sets of enes in
Continued
hybridization experiments, teaches us thatthe thing that is reproduced is a complex
thing, but does not teach us how to break
down the problem into simpler problems.
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Move to CalTech- Accepted as a post-doctoral fellow for
Rockefeller Program- Welcomed into Morgans fly lab
-
Did he want to work on flies orwas he already leaning towardphage?
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Ellis and Delbrck- One Step Growth
Curve 1939
- Confirms de Herelles theories of virusreplication process
- mathematicall anal zes that rocess
- Helps Delbruck decide that the latent period
of the virus life cycle is worth further study.
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Salvador Luria- Born in Turin, Italy in 1912
- Studied Medicine atUniversity of Turin
- Fled Fascist Ital in 1938
and with help of EnricoFermi, was awarded a
Rockefeller Fellowship at
Columbia University
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Luria-Delbrck Experiment (1943)- Fluctuation Test
- Last Bastion ofLamarckism
- mutations in absence of
se ec on pressures
(bacteriophages)
-Constant rate of random
mutations in bacteria
populations
-Darwins natural selection
applies to bacteria
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Delbrck-Luria-Anderson (1943)-T.F. Anderson working
with RCA electron
microscope-Luria and Delbrck
become interested in
taking micrographs ofphage
-Public first micrographs
of phage-Raise questions- tails?
Mobility? Living or dead?
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Alfred D. Hershey-Born in Owosso,
Michigan
-Ph.D. in bacteriology
Michigan State University
-
Washington University inSaint Louis
-moved to Cold Spring
Harbor in 1950-Carnegie Institute
director 1962
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Hershey- Delbrck Phage
Recombination (1946) Working independently, they discovered that
introducing multiple strains of virus to bacteriacaused these viruses to recombine with eachother.
genetic recombination in T2when cells wereinfected simultaneously with several h andseveral r mutant particles, they produced not
only those two types but wild-type and hr doublemutants as well.
Beginning of phage genetics. Hershey and RaquelRothman man T2 phage genome (1948-49)
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Hershey Laboratory-Did not love
technology.
-Man of few words in
laboratory
- a on y one ot erworker in lab during
early years at Cold
Spring Harbor:Martha Chase
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Chase-Hershey Blender Experiment (1952)
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Blender Experiment continued Used radioactive sulfur isotopes to label protein
coat of virus; Used radioactive phosphorousisotopes to label DNA of virus. (two separate
cultures; two separate experimental steps)
Allows phage to infect bacteria Puts this into blender until bacteria and virus
proteins separate
Sulfur found in supernatant, phosphorous foundwith bacteria cells- can be isolated to create more
infective phage stock.
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20.3 Community and the Rise of
Molecular Biology
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Rise of Molecular Biology Unity of life common to all organisms
Employed simple biological systems-primarilybacteria and viruses- as model systems applicable
Generally looked for mechanisms of upward
causation
Borrowed methods from physics, mathematics,and chemistry as well as genetics, embryology,
physiolo0gy, immunology and microbiology
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Molecular biology continued Based on protein paradigm- salient features of
life can be explained by the structures andfunctions of protein molecules
Could only be investigated with sophisticatedand complex apparatus
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Tools of the Trade Microscopes
Petri dishes Autoclaves
Electron microscopes
Ultracentrifuges Electrophoresis
X-ray diffraction
Isotopes
Scintillation counters
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Social structure of research Interdisciplinary nature of problems
Interdisciplinary nature of people Cost of equipment
Led to a prizing of cooperation and a
heightened sense of scientific problems as groupproblems
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Social Structure In the early days I had not ultimate goal in research
except to see how life processes work. Once started
with bacteriophages, I continued research on thembecause it seemed that here one could do moreinteresting experiments than with any other material.
,
these viruses was highly compatible; among ourselveswe saw , and still see, very little competitive secrecyand back biting: we were all interested in cooperatingwith each other to promote the work as a whole.
-Thomas F. Anderson
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Cold Spring Harbor-Phage Courses begin in ColdSpring Harbor in 1945-Runs for 26 years
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California Institute of Technology
Max Delbrck
returns in 1947 The Vatican
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"The Phage Church, as we were sometimes
called, was led by the Trinity of Delbrck,Luria, and Hershey. Delbrck's status as
him the pope, of course, and Luria was thehard-working, socially sensitive priest-
confessor. And Al (Hershey) was the saint."
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