June 1, 1956

cd

Dr, Philip E, Hartman

Department of Cenctics
Carnegie Institution of Washingto
Cold Spring Harbor

Long Island, New York

Dear Dr, Ilartman:

Thank you for your letter of May 23, I will be very happy to have an oppore
tunity to discuss these matters with you at Baltimore, However I hope you will
not take it amiss if I offer a comnent about the writing of review articles, I
know from ny own experience that it is vcry tempting to. try to keep up with the
very latest work at thc time of writing, However I have had enough sad experi-
ences of my own to want to warn you against overdoing this, Material in pub-
lished form is on the record for everyone to sec and for you to make your own
interpretations and there can be no later question about it. The responsibility
is clear, Suite the opposite is true of attributions based on hitherto unpub-
lished work, personal communications, etc. It would be difficult, for example,
for me to give you at this time a sufficiently complete account of the work on
abortive transduction of motility for it to be possible to write a completely re-
sponsible account of it. I would therefore urge that you not consider my remarks
as being on the record and that you confine any attributions in your own account
to work that has been published, There are, as you know, a few minor references
to these studies in the Oak Ridge Symposium article and in an abstract in Genetics
and perhaps a few other places, Right now both Stocker and I are busily engaged
in writing up this material in definitive form but it is somewhat more complicated
than your summary in the letter and it has been a rather difficult job to collect
this material for proper publication. Off the record, Stocker's view would postue
late two levels of unilinear inheritance, At the first level a particle is transe

mitted passively from generation to generation which confers motility on the cell

which bears it. We call this simply a motility-conferring particle and the most
plausible interpretation of it is that it is a single flagellum or flagellar
Anlage. However a single act of transduction can apparently result in the forma=
tion of a large number of motility-conferring particles and the complexity arises
from attempts to define the source of these many single particles, Dr. Stocker
suggests that at transduction a particle which may be considered a non-reproducing
gene is transmitted, we call this an E particle, that the E particle is also in-
herited in unilinear fashion and that the E particle has the property of manu-
facturing motility-conferring particles. Then at cell-division a sib to the

cell which carrics the F particle will contain a number of motility-conferring
particles, The latter are then sorted out until there is one per cell and we

then find unilinear inheritance of motility. Stocker and I differ only in our
view in the intensity of the proof for the unilinear inheritance of an E particle.
In my own experiments I have had some results which sugeest that the proverty of
producing many motility-conferring particles is not inherited in quite so
straightforward a fush'on as would be postulated on Dr. Stocker's interpretation.
However neither efx is sup,orted by entirely critical evidence and Dr, Stocker's
picture must be considered as a rather plausible if not critically proven hypothesis.
The question that I would raise is {a) whether unilincar inheritance really must
imply the transmission of a single particle inasmuch as we know so little about ‘
the basic morphology of cell-division and the rules governing the transmission of
Page 2 -~ Letter to P, E, Hartman June 1, 1956

cellular components. After all, "particle" simply means a rule of cell=division
and the fact that in certain countries the inheritance of land is entailed does
not mean that an acre is a particle, My second question is whether, given that
E and MCP are particles, we have critical evidence to identify them respectively
with a transduced gene and with the flagellum respectively. As I said before
these are plausible viewpoints but they hzeve not yet been subjected to really
critical analysis, Rather than being a gene for example the I particle might
simply be some organized product of the gene action, In that case we do not
have to postulate the occurrence of "ste nes" but merely that once a gene
has been in a cell it may leave behind residues of its action even if it itself
should fail to be incorporated into the chromosomes, It would be difficult to
design experinents that would distinguish between the inheritance of the trans-
duced gene and that of some of its residual products, As I indicated before,
these remarks are for your .own information and I hope you will not quote them
as comminications for your review although of course you may make whatever use
of them you wish in constructing your own interpretations, Anot er point on
which Dr, Stocker and I differ is the notion that only cells carrying several
MCP's are capable of swimming in semi-solid medium, The fraction of cells in
a clone which form trails in agar depends so mch on the precise concentration
of the agar that I doubt if any qualitative distinctions can be made on this
basis. The nonebranching of trails is probably a consequence of the use of
rather hard agar in which only a small fraction of (col lls can swim and also to

the fact that there ere chemotactic orientations en he agar away from the site |
of inoculation. When the experiments are done differently highly branched treils
can be found, As to your question whether nonemotile strains have been subjected
to recombination, I think that there is an explicit answer on this point in the
paper by Stocker, Zinder and myself in the Jour. of Gen, Microbiology. Trails
have been found in every combination where one also found the occurrence of
stable transductions of motility. As you probably know there has been only one
example of recurrence of identical Fla“ mutations and this pair of seeningly
allelic mutants, which were recovered from natural sources, may in fact have

had a common origin, The Fla~ mutants appear to occur in two groups, One of
them is a cluster closely linked to the H of one locus but we have been unable

to get definite evidence of their linkage to one another by any direct paths.

The other Fla" mitants may or may not be linked to one another but are @6hb06068
not linked to any common marker as far as we know.

With best regards,

Yours sincerely,

Joshua Lederberg

Professor of Genetics
JL /av

PS. I don't want to start a terminological squabble either here or at Baltimore
nor do I intend to prescribe your own choice of definitions, However if
you intend to use the term transduction in its narrower sense of phage
mediated transduction I hope you will not make the error which has appeared
in the literature of attributing tht definition to me. As I think should
be perfectly clear from the occasion of the first use of the term in this

context, which was in a review article in Physiological Reviews, transduction

was intended to name a hypothesis,namely the possibility of transmission of

q
 

Page 3 «= Letter to P, E, Hartman June 1, 1955

hereditary fragments from one cell to another, At the time the word was
first used in this laboratory we had no notion that phage played a mate
erial role in the Salmonella example of transduction and it seems to me
rather important to emphasize the genetic unity which has been demon~
strated many times between transduction as we see it in Salmonella where
phage is the vector and transduction by DNA which is exemplified in the
pneumococcus transformation, I would also object to an error that I
have made myself in referring to "a transduced cell", This may seem
like grammatical purism but I think that one would be likely to lose
sight of the process that we are trying to follow if we are careless in
the use of these terms and I am very sorry that I was not more careful
syself in this particular regard, I think that one must confine trans-
duced to that which is transduced, namely the fragment, and refer if you
like to transformed cells or transduction clones for what have you,

J. i.