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The Joshua Lederberg Papers

Letter from Joshua Lederberg to Edward L. Tatum Annotation pdf (205,895 Bytes) ocr (2,332 Bytes)
Letter from Joshua Lederberg to Edward L. Tatum
An important early piece of correspondence between the two scientists on what would eventually be the basis for their Nobel Prize-winning research, i.e., sexual recombination in bacteria. The letter embodies Lederberg's proposal to Tatum to search for such genetic recombination. The letter was written by Lederberg from Columbia College of Physicians and Surgeons where he was a medical student in the last months of the Navy V-12 program, the war (World War II) having ended only weeks before.
Item is a photocopy.
Number of Image Pages:
2 (205,895 Bytes)
1945-09-19 (September 19, 1945)
Lederberg, Joshua
Tatum, Edward L.
This item is in the public domain. It may be used without permission.
Medical Subject Headings (MeSH):
Cell Culture Techniques
Escherichia coli
Genetics, Microbial
Exhibit Category:
The Development of Bacterial Genetics
Lederberg Grouping: Correspondence A
Box Number: 8
Folder Number: 83
Unique Identifier:
Accession Number:
Document Type:
Letters (correspondence)
Physical Condition:
Series: Correspondence, 1935-2002
SubSeries: 1947-1953
Folder: Tatum, E. L.
Metadata Last Modified Date:
Linked Data:
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Annotation by Joshua Lederberg:
Keywords:  E. coli; genetic recombination; Salmonella; Yale;
   Ryan; P-269

This letter embodies my proposal to Tatum to search for genetic
recombination in bacteria.  Ryan had smoothed the path.  I applied
to work in his lab; and he responded by offering me a fellowship
contrived by the Jane Coffin Childs Fund.

This is derived from my carbon copy.  Letter was written from
Columbia P&S where I was a medical student in last months of the
Navy V-12 program, the war having ended only weeks before.

jl  7/4/98

Transcript: 19 September  1945 letter to Ed Tatum [P-269
                              19 September 1945

Dr. E. L. Tatum
Dept. of Botany
Yale University
New Haven, Conn.

Dear Sir:

     Your recent paper, 'X-Ray Induced Mutant Strains of Escherichia
Coli' has just come to my attention, and has proven very fascinating.
I should be very much obliged to you for reprints of this paper
and your preliminary one last summer.  I shall take the liberty of
writing to you at this length in support of a request that I hope
you will entertain.

     After doing some work on adaptation (part of which is nearly
ready for publication) in Neurospora mutants, it occurred to me
that no adequate investigation of a genetic nature had been made 
to demonstrate the existence or absence of sexual recombination in
bacteria.  Such things as the distribution of somatic and flagellar
antigens in the Salmonella group very strongly suggest that such
a process may occur, but no very successful attempt seems to have
been made to determine the recombination of bacterial characters.
The nutritional mutants described by yourself and Roepke et al.
would seem to fill the bill.  We did not have any of those organisms
in this laboratory, but in a strain of E. coli (6522) I had been
able to select out a methionineless strain by serial passage through
basal medium plus sulfanilamide and methionine as Kohn and Harris
described (J. Bact '41) and a prolineless strain was obtained quite
fortuitously (so far as I know) on a plating of the parent wild type.
It was interesting that you also obtained a 'prolineless' as a
spontaneous mutant.)  No thorough investigation of the biochemical
behaviour of either strain has been made, but it appears that the
proline requirement of the latter is very much reduced or spared
by small amounts of tryptophane, and possible other amino acids.  
Unfortunately I do not yet have not pursued this further.  If you
would like to have a culture of this strain for comparison with
your other prolineless, I should be delighted to send it to you.

     I have not yet gone very far in the genetic tests I mentioned
(explicitly) on these strains: the methionineless is quite rough
therefore possible not so satisfactory.  I had planned to do
essentially what you have accomplished: prepare a double mutant by
subjecting the prolineless to the same selective procedure used
obtaining methionineless, but that seems unnecessary now for a
demonstration that independent (X-ray mutable) genes exist.  It
has seemed to me, however, that despite the apparent stability of
the types I now have, and what is I hope adequate technique to 
eliminate contamination that it would be highly desirable to have
genetically marked strains before any attempt was made to perform
the experiment.  I should therefore be very much obliged to you
for cultures of your biotin double mutant series for the purposes
of this investigation.  To diminish the possibility of contamination
I would like to ask only for those double mutants in which the
biotinless gene is associated with another very stable gene.  In that
case a simple biotinless will never have been in this laboratory
(to the extent of our knowledge.)  It should, furthermore, be
advantageous to use stocks of heterogeneous origin in the event
that there exist mating types, sterility factors, etc.  I would
propose to inoculate into the same tube (under varying conditions)
two different mutants, and select for wild types (50 or 100%
of which should be marked with biotin) by inoculating into minimal
from that mixed culture.  Experiments already performed show that
there is in some cases little or no rapid symbiotic growth
comparable to the Neurospora heterocaryons.

     If an investigation of this sort has already occurred to you,
please let me know, as I am sure that you can do a much better job
and have better facilities for it than I; on the other hand, if 
your plans do not include work such as this I should appreciate
very much the service I ask of you.

     One further point: the fact that a variety of mutants can be
obtained suggests very strongly that the bacteria are (at least
during some phase) haploid.  It is possible on the other hand
however that diploid mutant heterozygotes could, if a sexual process
exists, have a homozygous segregant in a later generation.  Have
you any information on this point?  I note that (according to your
paper) your cultures were incubated 4 hours after irradiation.
Have you any suggestions as to the number of generations traversed
in this time by your strain?

                                Very sincerely yours,

                                Joshua Lederberg, A.S.V-12 USNR.

jl 6/7/03