September 23, 1953 Dear Bruce: This is in answer (I have to admit) to your letter of the 19th marked "urgent— re reprints", but I have been waiting for an opportunity to write you anyhow, about nothing in particular. I am surprised to realize that my last letter dates from about the first of June-- not entirely a matter of conscience, but also the appreciation of how many months have gone by without any particular happenings worth talking about. This time was consumed partly in summer indolence:: it was one h' of a hot summer here, and partly in frustration on such matte tting our space remodelled. It has not been, and we are ed as ever. However, we did make a trip to San Francisco, unfortunateky’ 4nd by car. There was some compensathon in visiting Tatum and van ine riends; much less in the S.A.B. meetings and connected businesg which obliged us fo come. ie thought often of your remark that there were stretthes of 200 no sight worth seeing, and did our best (p 3 not succe ly) to deny it to ourselves. ‘ie also thought how entartaintog tad én to have you in the back seat reading pig-Greek letters out 6f the B hile we drdve, as in times past. if \ } \ : | ia One reason we did not insist writing s her was our confusion about your moving and travel plans. ong you sperid in Europe, and when are you going over to Lister? I suppose we a e scheme of a circular letter to our multifarious friends abroad, ght hear from us more often, but I am not sure I wholeheartedly approve o AEYaARpQMMANt arrangement. » as you probably know. But among her souvenirs was a good case of stolytica, as the doctors here finally diagnosed it. Sha will, I tru over it fairly soon. By way of other news, Aleck Bernstein ‘arrived a week > and is already well started in some recombina-— tional essays witi\Py coli 9-55 and 0-111. “sther had previousl y gotten some en- couraging results es with K-12; the only serious point that can now be foreseen is the separability of the O and K antigens. But after this introduction, I expect he will be working on some of the Salmonella problems already started and mentioned in earlier |letters. Dave Skaar just completed his term here and has taken a job at Cold Spring Harbor in Brgson's lab; neither of us knows just what for. Larry iorse just completed his certification (1.e., most of his courses) and is slugging along admirably in the E. coli (Gal) transduction. “he matter is too detailed just now to be summarized briefly; the most interesting apa aspects are the correlation of transduction with lysogenization, and a special system in which nearly every phage particle is effective (sic). However, the transduction continues to be limited to a cluster of closely linked "pseudo—alleles" concerned with galac- tose fermentation. Also in E, coli, Tom Nelson (whom I do not think you met) has been accumulating more data along lines previously discussed icross-over hemi- zygotes for the Mal/S segment in diploids] which quite conclusively require a post— zygotic elimination from a complete diploid heterozygote. This does not directly rule out the Watson-Hayes proposal for a prezygotic elimination as well (4.6. defi- cient gametes) but makes it superfluous. There were several other features of this proposal that could not meet all the facts, e.g., aberrancies &n the segregationg ratios of markers from diploids already heterozygous for them, and to leave the diploid story, the expectation that the two complementary cross-over classes for any "unselected" chromosome has not been mat in any studied case. I have had some encouragement in cytological studies with Hfr x F- and am beginning to spend the larger part of my time in this work. This covers most of our staff; Esther will neaethirr ha wudétnn an sAAtedannl TAattawn nf hen awn QSuann Rawantdmwa hoa revit Helen Byers was abro school, cut her long yellow hair, and is engaged to be married to an ex—Marine, art-student, once-divorced man rather older than herself. [I recall her tender concern about your nutrition! ]. We were pleased to have a visit from Hayes about two weeks ago, just after we had settled to a new house (still rentef@) not far from where Jim Crow lives. He was as affable a chap as everyone had told us, and I think we were soon agreed that there were more terminological than substantial differences in our discussions of E. coli recombination. There are two major differences, however: 1) whether defects in the zygotes stem from already deficient F+ gametes, or subsequent to mating ~=mbombucttem and meiosis, and 2).whether there is an F+ agent, sepzzable from the bacterium,which has at once the properties of converting an F- recipient and accagionally of transducing a substantial (if in fact not the whole) part of the genotype of the F+ to the F— cell. I already men d some of the evidence that inclines us to our particular views with reSp As to 2), all of the t we ha Ne far been able to known properties of the "F+ agent" correspond to identify only with the entire cell, and there hag §o far been\no shred of evidence for a sub-cellular agent with the two crucial properties (or, ‘ig fact with either). Until the agent has been separated from the celldy I doubt that 2) has any real substance, and I am pleased that Hayes intends to devote considerable more attention to this so far unrewarded task. When (and-It) su Separation is made, it will be possible to test the putative, ole of t g\agent 3 in shabiaear aha itself. aantaxeattanen ~ PP ] ae ér too mugh/time on S. abortus-egui, and g y particular advances of under— ally did work as well as the previous he trick is to use a recently motilized “— As to Salmonella, I spent < on the java H,> H, 12 Guplicatig standing. 3S. gab}inarum --x —x IX XII a:— to bring out culture of H-901. Edwards fA 5 the gm transduced from gall déntical with that of S. entéritidis; that S. pullorym (Edwards #/i)\+ occasional swarms) but have not-yét found any evidences of H transduction. In some few othe eriments on miscellaneeus phages, k (determinative in S. typhi for Vi type K) andy ._Ytyping phage for S. paraf(B) are both reasonably wompetent in transda¢tion, but with rather restricted host-ranges, so they are not much use, except ifor trials of S. typhi~—x.... J am not at all happy about any rationale for tha host range of PLT22 (as well as BAOR) in view of occasional plaques on group C tures. These have not been accompanied by any transductions, and I have still to verify that some other phage is not responsible. You may have heard some odds and ends (e.g. from Kauffmann) concerning the coincidental transduction of I and V somatic antigens. We have run across these too, but I don't trast them as true bills. In similar experiments, we have also seen losses of the same antigens, and neither event has seemed to be correlated with the presence or absence of the corresponding antigen in the transducing source. I would (tentatively) conclude that the somatic antigens may play a secondary role in the dynamics of selection on semisolii agar, and that they are involved only in spontaneous variation. eq a7 the 4s > 3 Ls SS SAS SX SNS ee e Mes er ok (8 gk RRS a eh A” \ rubs yf The £ lapped Y (carriage included) As to reprints, I think we can afford to pay up to $120 for our share. I suggest you order any number (up to 1000) that can be covered by our joint contributions, It would help then to have 100 shipped directly to Norton, and the residue here. If you are able to share evenly in the costs, naturally so much the better, but a proration (with this Department also covering Nortpn's share) would be equally acceptable. If the JGM follows the practise of most other jcurnals, the unit cost should be substantially less on an order of 1000 than the price quoted for 100. If possible (and not prohibitively expensive) I would suggest shipment by post rather than ocean freight, from the angle of saving both time and customs formalities. Quite likely the reptbints will be large enough to qualify as "books" for which the rates are fairly reasonable. If the b shipment is to be made by freight, can you arrange to have a sample (say [2 orc50) 4¥"post? Please let me know just what order is placed so I can pr : range payment. i I would indeed like to accept your offe stracts of the Rome meetings. However, to avoid having to send these back, W .be possible to purchase them from or through you? I have a credit at the Of Bushey Heath (Spicer) to the amount ca. L.3:-~ available for sith a purpose.».°>Do you know anything of abstracts of the Bellagio meetigé? remitted $10 far advange registra- tion in hopes of receiving these’ststracts: jdid any appear? Various people have told us t youp’position at Lister is quite a prize. The very best wishes to you! Our doly’regret is the diminished likelihood that you might ever be p d to\aBbandon England in favor af a post closer to our own hand. i” i 7 ‘| Yours, - \\ i} ATED, to ‘ SN '/ Joshua Lederberg ee 2 anks for th¢\various cultures received over the summer (The Ti's and the \typhi and p Waa 6-farms). Have you made up a comprehensive chart of the \aktility infefactions? I may have mentioned some other miscellaneous past letters, but I will communicate directly with a ese. I have not heard from Spicer about SW-684 (the possible Gal vy). Could you simply return the culture (or a sub from it) without checking? If I haven't mentioned it before, the paper with Edwards has been accepted by Journal of Immunology, and is scheduled for October or November 1953, if you want to correct the reference. In re Q. yours of 6/30: I never have seen a swarm initiatang from a trail, but I doubt if it would be visible: the microcolénies of the trail would probably be scarcely larger than those of the inmingra ting motile cells. Une would have to judge from an apparent extra-marginal center of a swarm and this is dubious. So there is not necessarily any contradiction pif of the manipulation with the agar experiments. For all we know, the trails might represent a phenotypic lag in the effects of a Fla’ factor transduced to a cell which later segregated Fla+ but inviable (possibly lysed) and viable Fla~ karyonides. To account for the failure of branching, we would have to suppose that the phenotypic effect was localized and not proliferative, viz. a flagellar bundle, or andlage thereof. This picture might account for the production of nonmotile, temporary motile and stable motile individuals in a single clone.