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The Cold Spring Harbor Phage Course (1945-1970): A 50th Anniversary Remembrance

Authors:
Copyright
Q
1995
by
the Genetics Society
of
America
Perspectives
Anecdotal, Historical
And
Critical Commentaries
on
Genetics
Edited
by
James
F.
Crow
and William
F.
Dove
The
Cold
Spring
Harbor Phage Course (1945-1970):
A
50th Anniversary Remembrance
Millard
Susman
Laboratoq
of
Genetics, Medical School and College
of
Agricultural and Life Sciences,
University
of
Wisconsin, Madison, Wisconsin
53
706
T
HIS year marks the 50th anniversary of the birth
of the Cold Spring Harbor Phage Course and the
25th anniversary of its demise. The course was first
taught in 1945 by
MAX
DELBRUCK (with the assistance
of
A.
H. DOERMANN and
J.
REYNOLDS)
and last taught
in 1970 by WILLIAM F. DOVE and
RENB
THOMAS.
In
its 25-year lifespan, the Phage Course was remarkably
productive. Graduates included
MARK
ADms,
MARTHA
BAYLOR, SEYMOUR
BENZER,
ROBERT EDGAR,
HERMAN
KALCKAR,
AARON
NOVICK,
FRANK
STAHL, GUNTHER
STENT,
LEO
SZILARD,
NORTON
ZINDER,
and dozens of
others whose names evoke pleasant and reverent mem-
ories of the infancy of molecular biology. The lifetime
of the Phage Course coincided with a time when new
ideas emerged almost as abundantly as new details,
when students could be more or less familiar with the
entire literature, and when field representatives from
NIH frequently visited university campuses looking for
ways to invest federal research funds.
The Phage Course was started by
DELBR~CK,
whose
missionary devotion to bacteriophage biology led to an
explosion in the population of phage workers between
1940 and 1965
(LURIA
1966). The course was essential
training for more than a generation of phage biologists.
For some of us, it was truly an introductory course in
which
we
learned the arts of sterile technique, serial
dilution, soft agar plating, and plaque counting. For
others, already skilled in basic microbiological meth-
ods, the Phage Course was a rite of passage through
which ordinary microbiologists could become members
of
the Phage Group, a rather exclusive circle with DEL
BROCK
at
its
center.
For DELBRUCK, the only biology was “quantitative bi-
ology.’’ It was not surprising, therefore, that his course
for new phage workers was founded at the Cold Spring
Harbor Laboratory of Quantitative Biology. Nor was it
surprising that DELBRUCK, who was trained as a physi-
cist, looked
to
physics as a source of prospective quanti-
tative biologists. He believed that the complexities of
Genetics
139
1101-1106 (March, 1995)
biological systems might conceal new principles of phys-
ics and that the researchers most likely to discover these
new principles were physicists. He actively sought con-
verts, and among the most distinguished students
of
the Phage Course were a number of physicists, coaxed
by DELBRUCK to take a little taste of biology and discover
how delicious
it
could be.
I
took the Phage Course in 1957 at Caltech, which is
about as far from the Long Island home of the Course
as you can get in the contiguous United States. The
precedent for teaching the Cold Spring Harbor Phage
Course at remote sites was established early in
its
his-
tory. In 1949, for example,
DELBRUCK
himself offered
a cloned Phage Course at Caltech for a very small class,
consisting of
JEAN
WEICLE and OLE
MAALBE
(MAALOE
1966). When
I
took the course, it was taught by
RENB
COHEN, a French nuclear physicist recently turned
phage geneticist, and FRANK STAHL, a postdoc in the
phage group. COHEN was a teacher in the
DELBRUCK
tradition, bringing to the course a convert’s devotion
and a physicist’s rigor.
I
retain just
two
vivid recollec-
tions of discussions with
COHEN:
in one, he explained
his aversion to the “sandveetch,” which was a barbarism
because it had to be eaten with the fingers; in the other,
he explained why it would be impossible to manufac-
ture an optical device that could scan a petri dish and
count phage plaques. The other instructor, FRANK
STAHL, was working with
MESELSON
on ways to test the
idea that DNA synthesis was semiconservative.
My
clear-
est memory of STAHL’S teaching is a chalk-talk he gave
on “mating theory,” a mathematical analysis of recom-
bination in phage. The theory had appeared first in a
very difficult paper by VISCONTI and DELBRUCK
(1953) -a paper Stahl considered “one of the worst
ever written”-and, together
with
CHARLEY STEINBERG,
STAHL had reworked the old problem and produced a
comparatively clear and lucid theory (STEINBERG and
STAHL 1958). Standing at the blackboard and ex-
plaining the mathematics, STAHL did an imitation
of
1102
M.
Susman
DELBRUCK. I do not know if the imitation was calculated
or
unconscious, but the likeness was certainly evident
to anyone who had seen DELBRUCK lecture. The exposi-
tion moved slowly, interrupted by long pauses (eyes
shut tight to show intense concentration), mumbled
soliloquies, and sighs of satisfaction when the pieces
finally fell into place. I have always loved the STEINBERG
STAHL solution to “mating theory,” partly because
STAHL gave it to us that day in
1957
as
if
it were a
gift he had received directly from the gods. DELBRUCK
himself took little part in the course-he had turned
his attention by that time to phototaxis in Phyco-
myces-but his office was just across the hall from the
teaching lab, and he dropped in from time to time to
offer encouragement.
The students in this class were, I believe,
DENNIS
BAR-
RETT,
JOHN
CAIRNS, LEA SEKELY, ILGA LIELAUSIS,
ANN
ROLLER, EDWARD SIMON, BARBARA
SUSMAN,
and me.
There is some dispute about
ED
SIMON’S exact role in
the course.
LEA
SEKELY says he was her lab partner at
the beginning of the course, but that he dropped out
soon after the course began. DENNIS
BARRETT, BARBARA,
and I also believe that SIMON was a member of the class,
but SIMON himself says he did not take the course and
suggests that he was simply a “groupie.” We worked in
pairs.
My
lab partner was ILGA LIELAUSIS, who at the
time was the lead worker in the phage kitchen. She
was a gifted lab worker who eventually became ROBERT
EDGAR’S
co-author on a series of papers describing tem-
perature-sensitive mutants of phage T4. Our experi-
ments in the Phage Course always worked because ILGA
did all the pipetting.
My
wife,
BARBARA,
who at the time
was
WTTHEW
MESELSON’S
technician, was paired with
DENNIS BARRETT, a biochemistry graduate student who
is now an Associate Professor of Biology at the Univer-
sity of Denver. DENNIS loved folk songs and group danc-
ing and instigated much of the social life of Caltech
graduate students.
I
feel that I must record here an act
of heroism for which DENNIS deserves to be remem-
bered. A large group of us graduate students organized
a picnic one summer on the beach at Playa del Rey,
and DENNIS volunteered to shop for the food. Everyone
but DENNIS showed up on time. We spent a long, hungry
afternoon watching the planes from
LAX
take
off
over
our heads and wondering why
DENNIS
and the hot dogs
had not arrived. DENNIS finally appeared, laden with
grocery bags and wrapped in bandages. He had pur-
chased our provisions and then, bags in hand, had
walked through a plate glass window of the grocery
store, After visiting the Emergency Room and enduring
over 100 stitches, conscientious
DENNIS
retrieved the
bags
of
food from the grocery store and joined the
picnic.
EDWARD
SIMON is now a Professor of Biology at
Purdue. He was one of several students in our class who
decided to confirm the MESELSON-STAHL experiment
in organisms other than bacteria; ED showed with BrdU
labeling that DNA synthesis was semiconservative in
HeLa cells. LEA SEKELY is now Program Director in the
Chemical and Physical Carcinogenesis Program at NCI;
her specific area of interest
is
hormonal carcinogenesis.
ILGA LIELAUSIS retired from Caltech a few years ago.
Unfortunately,
I
have not been able to trace
ANN
ROLLER.
Certainly the most sophisticated member of the class
was
JOHN
CAIRNS.
CAIRNS
was already a well-known ani-
mal virologist. He had come to Caltech from Canberra
for a four-month visit to learn from
RENATO
DULBECCO
how to grow animal viruses in tissue culture. On dis-
covering that the famous Cold Spring Harbor Phage
Course was to be offered during that four months,
CAIRNS
decided to become a member of the class. He
was good-looking, self-assured, spoke with an accent
that was British rather than Australian, and had an inno-
vative flair. He was admirably modest, generous and
collegial, but he certainly stood out in our class. It was
rather as if SIR
LANCELOT
had decided to attend the
senior prom.JOHN and his partner,
ANN
ROLLER, did all
the experiments with such ease that they could always
manage to do something extra. It was
ANN
who shared
the news with the class.
“JOHN
and
I
tried
two
higher
multiplicities of infection to see
if
that affected the la-
tent period.”
‘~OHN
and I think we found a few new
plaque morphology mutants.” Even within the confines
of a scripted laboratory course,
CAIRNS
found ways to
be original.
Graduation parties were part of the tradition of the
Phage Course, probably because DELBRUCK liked par-
ties and looked for opportunities to arrange them (Fig-
ure
1).
BARBARA
and I missed the party celebrating our
graduation from the Phage Course because she was
pregnant and felt queasy that night. The party was at
the Prufrock House-so called because it was discreetly
listed in the Pasadena telephone directory under
‘7.
A.
PRUFROCK.” The house was occupied by
WTT
MESEL-
SON,
HOWARD TEMIN,
JAN
DRAKE, CHARLEY STEINBERG,
JOHN
CAIRNS
during his visit, and perhaps others whom
I have forgotten. The next day,
MESELSON,
obviously
shaken by the experience, told me about the party. The
celebration began with organized silliness; for example,
ILGA, blindfolded, had to use her toes to determine the
agar content of the medium in several petri dishes, and
ANN
and
JOHN
had to step into a closet and recombine
five of their “phenotypes” (articles of clothing) (Figure
2).
The party ended with a water fight that drenched
everything in the Prufrock House. The recipe for a
Phage Course graduation celebration generally in-
cluded generous quantities of agar, vodka, and water.
In
1960,
I
myself had a chance to teach the Phage
Course at Cold Spring Harbor. ROBERT
EDGAR
was an
Assistant Professor at Caltech at the time. CSH Director
ARTHUR
CHOVNICK invited EDGAR to teach the Phage
Perspectives
1103
Course, and EDGAR offered me the opportunity to serve
as his assistant.
I
decided this was a wonderful chance
to get some teaching experience and accepted the invi-
tation.
For
about five weeks that summer,
I
ate and slept
in Blackford Hall at the Cold Spring Harbor Lab and
spent most of every day with EDGAR, who was the most
meticulous and conscientious
of
teachers. We pretested
every experiment and did not give up until we could
be almost certain that the experiment would work. In
class, EDGAR was loud, eager, and vigilant. His pre-lab
lectures were pep talks-simple, clear, well organized,
and illustrated by poorly drawn diagrams with fre-
quently misspelled labels. (The class skit featured ED-
GAR
giving a spirited talk on the use of a spoon, which
looked in the drawing
like
a butternut squash and was
labeled “spone.”) He ran a group experiment as if he
were a coach training a football team. He shouted out
the time in kinetics experiments, strictly and noisily
enforced the rules of sterile technique, endlessly circled
the room to check that the surfaces of the soft-agar
plates were smooth as glass.
I
did learn a lot about
teaching that summer and, to the extent that my more
timid personality allows it,
I
continue to imitate EDGAR
when
I
teach students how to do a one-step growth
experiment.
EDGAR taught the portion of the lab course that dealt
with virulent phages, and ED LENNOX covered the tem-
perate phages.
I
believe LENNOX arrived at the Lab only
a few days before his section of the course began.
I
remember looking forward to meeting the ingenious
fellow who had used the power
of
phage biology to
demonstrate that individual antibody-producing cells
could produce one, and only one, antibody. Since LEN-
NOX
was on the scene,
I
find
it
surprising that
I
was the
FIGURE 1.-The Board of Examin-
ers at the Phage Course final examina-
tion and commencement exercises,
held at the Prufrock House, Caltech,
1957.
From the left: HARRY
RUBIN,
MAX
DELRRCJCK,
REN~
COIIEN,
MAT-
THEW
MESEISOK,
and FRANK STAlll..
The person with his back
to
the cam-
era may be
HARRIS
BERNSTEIN. (Photo-
graph courtesy
of
DENNIS
BARRETT,
University
of
Denver.)
one who lectured on the kinetics of phage neutraliza-
tion by antibodies. However,
I
remember vividly that
I
did give that lecture, since it was done impromptu dur-
ing a class break, when EDGAR suddenly, and without
prior notice, asked me
if
I
could explain the mathemat-
ics of “one-hit’’ phage inactivation. Fortunately, he
chose a topic that my Caltech training had prepared
me to discuss. We were at the time deeply immersed in
inactivation kinetics.
The able archivist at Cold Spring Harbor, CLARE
BUNCE, has found the lists
of
instructors, students, and
seminar speakers for every one of the Phage Courses
from
1945
to
1970.
The
only
records that have eluded
the archivist’s investigatory skills are the ones for the
summer of
1960,
when
I
assisted EDGAR and LENNOX.
My
memories of that summer at Cold Spring Harbor
have faded. We had roughly 20 students, and
I
spent a
lot of time with them, but the only ones
I
can name
with confidence are
NOBORU
SUEOKA,
ULF
HENNING,
IRWIN
RUBENSTEIN,
and FRED FRANKEL.
SUEOKA
is mem-
orable because he was such a gifted experimentalist and
had such a sharp eye.
For
example, he could always
spot the 0.2-ml pipette in the can of 0.1-ml pipettes
or
the pin-point colony on a supposedly sterile petri dish,
and he let us know gently that we had to prepare materi-
als more carefully if
we
wanted the experiments to work.
Other members of the class have become indistinguish-
able in my mind from the dozens of people with whom
I
talked and ate and swam, summer after summer, at
the annual Cold Spring Harbor Phage Meetings.
I
recall
two
notable scientific discussions that
I
had
with
BOB
EDGAR that summer. The first sticks in my
mind because it turned out to have damaging relevance
to my own work. When we first arrived at Cold Spring
1104
r
M.
Susman
I
L
‘,
I
-1
1
1
L,‘
I
FI(;t’KI.:
2.-The Kecoml,in;ltion Test,
in
\vhich
ASS
Rol.l.l<K
(lelt
panel)
NXS
rrquircrl
IO
csch;unge
live
phcnotvpcs (articles
of
clothing)
with
JolIs
<::\IKss.
When they emerged from the recomlination closet (right panel),
(AIRSS
(left)
was
dressed
as
ROILER,
and
ROI.I.ER
(right, with culture apparatus over hcr head)
was
dressed as
CAIKSS.
The gentleman in the derby hat in
the left wanel
is
DEI.RK~(:K:
the gentleman
in
the beret and muffler in the right panel
is
RLUIN.
(Photographs courtesy
of
DENNIS
BARRETI‘,
University
of
Denver.)
.
<>
Harbor that summer, EDCAR met with GEORGE STREI-
SINGER
and discussed several experiments on which they
might collaborate. One
of
these, EDGAR told me, was
a
mapping experiment
to
test for circularity of the link-
age map of phage T4. This, EDGAR believed, was
a
long
shot, but if
I::
coli
could have
a
circular linkage map,
why not T4? Their decision
to
test this unlikely hypothe-
sis codd not have come at
a
worse time for me.
My
thesis research at Caltech was aimed at determining the
size of the mating group in T4
(it.,
how many phage
chromosomes could participate in
a
single crossover
event). The experiment was based on the STEINBERG
STAHL mating theory, which in turn was based on the
assumption that phage chromosomes were linear.
While
I
was writing my Ph.D. thesis, STREISINCER, ED-
GAR, and GETTA HARMR-DENHARDT (1964) were doing
experiments that demonstrated the circularity of the
T4 linkage map and simultaneously demolished the the-
oretical underpinnings
of
my thesis. The discovery that
the map was circular was exciting in itself and led, over
the next
few
years, to marvelous revelations about the
complex life cycle
of
phage T4 (see, for example,
MOSIC
1983). For me,
a
graduate student working on the last
draft of my Ph.D. thesis, the news that T4 had
a
circular
map was worrisome. The Fates had arranged for me
to
defend my thesis dressed in the Emperor’s new clothes!
Fortunately,
MAX
was willing
to
let me get
a
degree on
the basis of my suddenly obsolete work because he
found my thesis interesting, and his sole test for an
acceptable Ph.D. thesis was that
it
be “either interesting
or
original-not necessarily both.”
Reality
was not on
his
list
of criteria. After
all,
MAX
never really believed
any experimental demonstration
of
anything.
The second discussion
I
had with BOB EDGAR took
place on the beach overlooking the outer harbor.
I
was
sunning with Bo13 and his wife, LOIS GLASS EDGAR, when
he told me that he had been thinking about changing
directions in his research when
we
got back to
Pasa-
dena. He might give up studying the mechanisms of
recombination in phage and start looking
for
a
new
class of mutants, mutants that were unable
to
grow at
elevated temperatures. HOROM’ITZ
AND
LEUPOLD
(1951)
Perspectives
1105
had done experiments like that with
Neurospora
and
E.
coli
and had shown that such mutations occurred in
exactly the same genes that had already been identified
by looking for other, more gene-specific phenotypes.
The advantage
of
“temperature” mutations was that
they were lethal only if the temperature was elevated.
Why not try to isolate mutants like that in
T4?
BOB
asked me to keep his plan
a
secret and, in particular,
not to tell CHARLEY STEINBERG about it, because he was
certain that CHARLEY would consider it ridiculous and
would think of
so
many excellent reasons
not
to do
the experiment that the project would be abandoned
before the first plate was poured. Of course,
BOB
did
do the mutant hunt when we got back to Caltech-in
a
locked room, safely out of CHARLEY STEINBERG’S
ken-and the
ts
mutants became
a
treasure that
BOB
shared freely with the phage world (EDGAR and LIE-
LAUSIS
1964).
The Phage Course of 1960 ended with the traditional
commencement ceremony. The featured speaker for
the Class of 1960 was the bombastic “DR. PLOTCHKISS,”
played, of course, by ROLLIN
D.
HOTCHKISS, who himself
had been
a
member of the very first phage class.
DR.
PLOTCHKISS wore, I believe,
a
mortar board over an
abundant and unruly mass of hair. He carried an enor-
mous, accordion-folded scroll of paper on which his
“speech” was written. He delivered 10 or 15 minutes
of loud, scholarly nonsense, and,
as
he spoke, his aca-
demic gown somehow fell open to reveal an impressive,
spherical belly on which was painted
a
huge red target.
JOHN
CAIRNS, who had been my classmate in the 1957
Phage Course, became the Director of the Cold Spring
Harbor
Lab
and invited me to be the Instructor for
the summer course in 1966. He asked me to suggest
candidates for the second Instructor position, and
I
immediately named FRANCES WOMACK, who was at
Vanderbilt University. I had never met FRANCES, but I
was greatly impressed by her published work on the
role of phage heterozygotes in recombination in phage
T4. She had done single-burst experiments using
so
many closely linked markers that her resolution of re-
combination events seemed almost the equivalent of
molecular sequencing (WOMACK 1963). Since DNA se-
quencing was not possible in 1966, FRANCES’ work
seemed wonderful to me-a combination of brute
strength and brilliant analysis.
I
figured that anyone
with the patience and energy to do crosses involving
nine markers or more could be counted on to carry
more than
a
fair share of the work that needed to be
done in teaching the Phage Course. I was right. FRANCES
was
a
perfect partner for the job. She was smart, full of
fun, and happy to take on big jobs. She was, however,
hard to get started in the morning, and her son and
daughter, who were up with the birds, would arouse
FRANCES
by
serving her
a
breakfast of Coca Cola in bed.
FRANCES seemed to be fueled by Coca Cola and almost
always had
a
bottle of it in her hand.
BARBARA
and I and our
two
sons, then
4
and
8
years
old, stayed in the Firehouse, which once housed the
Cold Spring Harbor fire department. In 1930, it
was
moved by barge across the harbor to the grounds of
the Biology Lab [and it has moved once more since we
stayed in it (WATSON 1991)l. When
RIC
DAVERN,
who
was associate director of the Lab, showed
us
to our
quarters, he seemed
a
bit apologetic, but we were com-
fortable in the small apartment, and the location was
perfect. Right next door was Davenport Laboratory,
where the Phage Course was taught; I could commute
from home to work in
two
minutes, and
so
could my
sons, who frequently came running into the lab while
an experiment was in progress to announce exciting
news of one sort or another. The class skit that summer
made much of my older son’s appearance one day with
a
huge horseshoe crab that he had captured while it
was spawning. The boys loved Cold Spring Harbor and
seemed extraordinarily energized by the sea, the enor-
mous grounds, the numerous places to climb and to
hide. I have often thought that
BOB
HASELKORN and
his family, who lived beneath us in the Firehouse, must
have had mixed feelings about their accommodation
that summer. They could hardly have failed to notice
the stomping of the
two
little boys upstairs.
Here are the students in the class that FRANCES and
I
taught in 1966. I cannot resist offering this
list
because,
like all teachers, I take pride in the accomplishments
of my students. (The degrees and institutions shown on
this list are copied from the original course roster.)
ANDREW
J.
BECKER,
Ph.D., Albert Einstein College of
Medicine; FLORENCE CAHN, B.A., MIT;
JOHN
H.
CASTER,
B.S.,
St. Louis University School of Medicine;
ANANDA
M.
CHAKRABARTY, Ph.D., University of Illinois-Urbana;
STANLEY
N.
COHEN,
M.D.,
Albert Einstein College of
Medicine;
DAVID
B.
FANKHAUSER, B.A., Johns Hopkins
University;
MARIA
C. GANOZA, Ph.D., NIH;
MAX
E. GOT-
TESMAN,
Ph.D., The Rockefeller University; THEODORE
GURNEY,
JR.,
Ph.D., MIT;
JOST
KEMPER,
Ph.D., Cold
Spring Harbor Laboratory of Quantitative Biology;
STANLEY P. LIEBO, Ph.D., Oak Ridge National Labora-
tory;
DANIEL
H.
LEVIN, Ph.D., Lab of Biophysics, Beth
Israel Medical Center; LEON
J.
LEWANDOWSKI, B.S.,
Wistar Institute;
CARL
R.
MERRIL.,
M.D.,
NIH; WIM
J.
MOLLER,
Ph.D., Johns Hopkins University School of
Medicine; HAROLD C. NEU,
M.D.,
Columbia University
College of Physicians and Surgeons;
JOHN
W.
QUIGL.EY,
M.S., Rutgers University; WOOLLCOTT
K.
SMITH, M.S.,
Johns Hopkins University; HIROKO WATANABE,
M.D.,
Royal Victoria Hospital, Montreal;
ROBERT
YUAN,
B.S.,
Albert Einstein College of Medicine.
Readers will, of course, recognize many names on
this
list.
It was, like all the other Phage Course classes,
a
collection
of
gifted people. Yet many of them had
1106
M.
Susman
never flamed a pipette, isolated a bacterial colony, or
seen a phage plaque.
A
few members of the class were
unfamiliar with semi-log graph paper, and we had to
explain to them how and why such paper is used. FRAN-
CES
taught them to recognize plaques arising from
phage HETs (single phage particles that give rise to a
mixed progeny of rand
r+
phages). She explained how
to do spot tests for complementation and recombina-
tion of rllmutants; she herself had done zillions of such
tests. We did a big single-burst experiment, another
of
FRANCES’ specialties.
I
prepared the class for experi-
ments that required mathematics-serum inactivation,
UV
inactivation, nitrous acid induction of mutations,
and mapping. The math was essentially the same for
most of the labs; only the notation changed. In addi-
tion,
I
tried, probably unsuccessfully, to get the class
excited about the STEINBERGSTAHI, mating theory.
And, following the
DELBRUCK
tradition, I derived the
Poisson distribution for the class. One cannot do phage
biology without the Poisson distribution. Like
W,
I
mischievously used a tank of tiny fish to illustrate the
derivation, thus creating an uncertainty in the minds
of my listeners concerning the origin of the “poisson”
in the name of the distribution.
I
will mention here only
two
of the students in this
engaging and brilliant class. STAN COHEN stood out be-
cause he was
so
busily involved in a research project
that was in progress at Einstein. He made
two
or three
phone calls a day from the wall phone on the South
wall of the Davenport Lab. He scribbled numbers on
his note pad, gave urgent instructions for the next ex-
periment, and always set up the time for the next con-
tact. FRANCES and
I
wondered why he had come to Cold
Spring Harbor when he was
so
intensely concerned
about work that was going on elsewhere. He was, how-
ever, an apt student and seemed genuinely interested
in the work he was doing in our course.
I
remember
ANANDA
CHAKRABARTY because he seemed
so
interested
in working on exotic organisms that grew on odd sub-
strates and smelled bad. Why would you want to work
on organisms that ate asphalt when you had access to
well-behaved organisms that ate carbohydrates?
Students participating in the Phage Course carried
home a great deal more than a handful
of
useful tech-
niques. They felt that they had been initiated into the
community of biologists. The course featured seminars
by leaders in the field, and the students could sit and
drink beer with them on the porch at Blackford Hall
or chat with them on the beach. When FRANCES and
I
taught the course, the seminar series included talks
by
C. A.
THOMAS, F. FRANKEL,
D.
J.
MCCORQUODALE,
R.
HASELKORN,
A.
SKALKA,
C.
RADDING,
E.
KELLEN-
BERGER,
E.
GOLDBERG,
J.
KARAM,
G.
MOSIG,
and
R.
S.
EDGAR. It was worth a student’s trip to Cold Spring
Harbor just to meet the scientists who worked year
round in the labs there; that included
BARBARA
MCCLINTOCK and
AL
HERSHEY.
I
remember with spe-
cial fondness PAUL
MARGOLIN,
who showed me the
elaborate model train layout that he constructed dur-
ing the winter months, when the social life at Cold
Spring Harbor went into hibernation. In the summer,
students could spend their evenings talking molecular
biology with
JIM
WATSON, GEORGE STREISINGER,
MAU-
RICE
FOX,
and a host of other visitors who were drawn
to the place year after year.
The pleasures of Cold Spring Harbor come not only
from the science, which is wonderful, but also from the
place, which is enchanting. The rhythm of the Phage
Course often fell into harmony with the rhythm of the
sea. We would schedule labs in the very early morning
in order to be able to dig clams in the afternoon. On
a hot day, when the beach was especially inviting, we
would delay an experiment until late afternoon and
head for the outer harbor.
I
remember one night when
BOB
EDGAR hunted me down and took me to the water’s
edge.
A
school of bioluminescent ctenophores sur-
rounded the boat dock in the inner harbor.
I
scooped
one of them into my palm. That simple blob
of
a crea-
ture has stuck in my memory; it was one of the most
beautiful things
I
have ever seen. That is what the Phage
Course and Cold Spring Harbor are all about-the
wonder and the elegance of life.
LITERATURE
CITED
EDGAR,
R.
S.,
and
1.
I,IF.IACJSIS,
1964 Temperature-sensitive mutants
of bacteriophage
T4
their isolation and genetic characterization.
Genetics
49:
649-662.
HOROWITZ, N. H., and
U.
LEUPWD, 1951 Some recent studies bear-
ing
on
the one gene-one enzyme hypothesis. Cold Spring Harbor
Symp. Quant. Biol. 16: 65-72.
LURIA,
S.
E., 1966 Mutations of bacteria and
of
bacteriophage, pp.
173-179 in
Phuge
and
the
Origins
of
Molecular
Biology,
edited by
J.
CAIRNS, G.
S.
STENT and
J.
D. WATSON. Cold Spring Harbor
Laboratory
of
Quantitative Biology, Long Island, NY.
MAAI.BE,
O.,
1966 The relation between nuclear and cellular divi-
sion in
E.scherichia
coli,
pp. 265-272 in
Phage and
the
Origzns
of
Molecular
Biology,
edited by
J.
CAIRNS,
G.
S.
STENI‘
and
J.
D. WAT-
SON.
Cold Spring Harbor Laboratory of Quantitative Biology,
Long Island,
NY.
Mos~c,,
G.,
1983 Relationship
of
T4
DNA replication and recombi-
nation, pp. 120-130 in
Bacta’qphuge T4,
edited by C.
K.
MA-
THEWS,
E.
M. KUTTER,
G.
MOSIG and P.
B.
BERGET. American
Society for Microbiology, Washington, DC.
STEINBERG, C., and
F.
STAHL, 1958 The theory
of
formal phage
genetics. Cold Spring Harbor Symp. Quant. Biol. 23: 42-46.
STREISINGEK,
G.,
R.
S.
EDGAR
and
G.
HARRAR-DENHMI’,
1964 Chro-
mosome structure in phage T4:
I.
Circularity of the linkage map.
Proc. Natl. Acad. Sci. USA 51: 775-779.
VISCONTI,
N.,
and
M.
DELBRUCK, 1953 The mechanism of genetic
recombination in phage. Genetics
38:
5-33.
WATSON,
E.
L., 1991
Houses
for
Science:
A
Picturial
Histoly
of
Cold
Spring
Harbor
1,uboratoly.
Cold Spring Harbor Laboratory Press, Cold
Spring Harbor, NY.
WOMACK,
F.
C., 1963 An analysis
of
single-burst progeny
of
bacteria
singly infected with a bacteriophage heterozygote. Virology 21:
232-241.
... In this context, scientific conferences and short courses are particularly important since scientists in general, and especially students, have the chance to meet potential collaborators and catch up with hot topics in their fields. In this sense, highlevel courses focused on training students and young scientists have been extremely prolific, as widely reported in the literature (Susman 1995;Stewart 2000;Patel et al. 2005;Svanevik and Lunestad 2015). ...
Article
Science is international by nature. Scientific exchange and international mobility are essential for training young scientists in general and international collaboration has been directly linked to high-quality science and innovation. In this article, we present evidence showing that international mobility has a direct and beneficial impact on scientific discovery, career development, and cultural maturity, especially for students and young scientists.
... Then, in 1999 my laboratory joined with those of the British cancer biologist Chris Potten and the American mammalian biologist Jeff Gordon to initiate a hands-on course in the genetics and biology of the laboratory mouse at The Jackson Laboratory. Years later, I find satisfaction in seeing the emergence of leaders who came to know one another as neophytes in a hands-on course (Susman 1995). After 1970, under the directorship of Jim Watson, the Phage Course at CSHL gave way to the Yeast Genetics Course. ...
Article
The Perspectives column was initiated in 1987 when Jan Drake, Editor-in-Chief of GENETICS, invited Jim Crow and William Dove to serve as coeditors of "Anecdotal, Historical, and Critical Commentaries." As the series evolved over 21 years, under the guidance of Crow and Dove, the input of stories told by geneticists from many countries created a panorama of 20th-century genetics. Three recurrent themes are visible: how geneticists have created the science (as solitary investigators, in pairs, or in cooperative groups); how geneticists work hard, but find ways to have fun; and how public and private institutions have sustained the science of genetics, particularly in the United States. This article ends by considering how the Perspectives series and other communication formats can carry forward the core science of genetics from the 20th into the 21st century.
Article
Full-text available
Until a dangerous bacterial infection left her husband near death 3 years ago, scientist Steffanie Strathdee had never heard of bacteriophage therapy. After it ultimately saved his life, however, she not only has become a staunch advocate of the therapy, but also now serves as co-director of the newly established Center for Innovative Phage Applications and Therapeutics (IPATH) at the University of California San Diego (UCSD) ( Figure 1 ).
Chapter
This article highlights Stahl's role as a leading expert on the central biological process of ‘genetic recombination’ (Stahl, 1987, 1988) during the last six decades as his main research interest, as well as his collaborations in deoxyribonucleic acid (DNA) replication, mutagenesis and genetic mapping. Starting with Stahl's PhD thesis (Stahl, 1956) on the genetic recombination of phage T4, and continuing with Stahl's seminal collaboration on the ‘Meselson–Stahl experiment’ which established how DNA replicates, a discovery for which both Meselson and Stahl remain best known, the article grounds Stahl's various contributions to molecular biology in his institutional legacies at the University of Rochester (PhD 1955), Caltech in the mid- and late 1950s and the University of Oregon at Eugene since 1959. The article further highlights Stahl's role as a foundation member of its Institute of Molecular Biology, his long-term collaboration with his late spouse Mary Morgan Stahl (1934–1996), his mentorship of two generations of students and his current collaboration, as a professor emeritus, with his former PhD student and partner Henriette (Jette) Foss. Stahl's contributions to the history of molecular biology, as both author and editor, are also mentioned.
Chapter
The article highlights Meselson's unique position in science and society as an innovative scientist involved in several ‘crucial experiments’ in molecular biology; a policy analyst in the domain of biological and chemical weapons for US administrations in the 1960s and 1970s; and a public intellectual shaping the public opinion against the use of such weapons in both war and peace times. Meselson's role in the ‘Meselson–Stahl experiment’ (hereafter the ‘M–S experiment’) which established the semiconservative mode of deoxyribonucleic acid (DNA) replication for which both Meselson and Stahl remain best known, is highlighted.
Article
This book explains the role of simple biological model systems in the growth of molecular biology. Essentially, the whole history of molecular biology is presented here, tracing the work in bacteriophages in E. coli, the role of other prokaryotic systems, and also the protozoan and algal models - Paramecium and Chlamydomonas, primarily - and the move into eukaryotes with the fungal systems Neurospora, Aspergillus, and yeast. Each model was selected for its appropriateness for asking a given class of questions, and each spawned its own community of investigators. Some individuals made the transition to a new model over time, and remnant communities of investigators continue to pursue questions in all these models, as the cutting edge of molecular biological research flows onward from model to model, and onward into higher organisms and, ultimately, mouse and man.
Article
près un rappel historique, et l’exposé de quelques notions concernant le bactériophage, faire le point des connaissances modernes sur son utilisation dans une perspective thérapeutique (phagothérapie).
Article
The segregation of nine genetic markers among the phages produced by individual, HET-infected bacteria has been examined. In the majority of cases, markers located near the end of the terminating strand in the heterozygous region appeared infrequently among the progeny.In five of these bacterial bursts, heterozygosity among the progeny phages was investigated. The majority of heterozygous progeny produced in HET-infected bacteria do not segregate markers in the polarized manner observed in the parent HETs. Progeny heterozygotes segregate both alleles for markers that were centrally located in the parental heterozygous region more frequently than for terminal markers. The average frequency of heterozygosity for a marker is not strikingly different among the progeny of a HET infection from that among progeny of a mixed infection.The data are consistent with a persisting overlap HET model, in which the overlap is not reproduced as such in the progeny.
Mutations of bacteria and of bacteriophage, pp. 173-179 in Phuge and the Origins o f Molecular Biology
  • S E Luria
LURIA, S. E., 1966 Mutations of bacteria and of bacteriophage, pp. 173-179 in Phuge and the Origins o f Molecular Biology, edited by J. CAIRNS, G. S. STENT and J. D. WATSON. Cold Spring Harbor Laboratory of Quantitative Biology, Long Island, NY
The relation between nuclear and cellular division in E.scherichia coli, pp. 265-272 in Phage and the Origzns of
  • Maai Be
MAAI.BE, O., 1966 The relation between nuclear and cellular division in E.scherichia coli, pp. 265-272 in Phage and the Origzns of Molecular Biology, edited by J. CAIRNS, G. S. STENI' and J. D. WAT- SON. Cold Spring Harbor Laboratory of Quantitative Biology, Long Island, NY.