The Lister Institute of Preventive Medicine. Chairman of the Governing Body : Sie Henry H. DALE, O.M., G.B.E., M.D., F.R.C.P., F.R.S. CHELSEA BRIDGE ROAD, Hon. Treasurer : THe RT. Hon. ViscouNT WAVERLEY, P.C., G.C.B., LONDON, S.W.I. G.C.S.1., G.C.LE., F.R.s. Director : Telegrams : “‘ Bacteriology, Knights. London.” PROFESSOR A. A. MILES, C.B.E., M.D., F.R.C.P. Telephone : SLOaxg 2181, 4th.May 1955. Professor J.lederberg, Department of Genetics, University of Wisconsin, Madison, Wis, USA. Dear Josh, Many thanks for your letters of 11 and 20 April, for the "Genetics" abstracts, and for the draft. As to the létter, I have not yet given it adequate study, so I won't comment to any extent. As to publication, I am inclined to agree that our different ways of writing things up, together with such discrepancies as remain and the laboriousness of having to correspond rather than talk make a joint paper hardly practicable. I agrees twin papers as you suggest. From my point of view J.G.M. would be preferable, and as far as close contact with the editor, goes I am O.K. here. I saw Standfast yesterday, he says that average delay is now about usual, 1.6. something like 6 months from submission to appearance, and I think this is no worse than else-~ where e As to joint paper and abstract for Genetics Soc., I am agresable; it is hell to say anything on this subject in 250 — words, and I would prefer to let you do this. As I don't disagrees with anything you say, (but merely assert something further) T feel confident anything you might say will be 0.K. by me, whereas the veveraes case might not hold. I enclose the abstract (circulated, and will ultimately appear in Heredity) of my paper to Genetical Soc, here. This had to be 200 words only, which forced me to be less non-commital than I wanted to bee I hope the inverbed commas round "gene" etc. soften the effect a little. As to terminology, I shall now revise and shorten my draft, and see if it can be done without neolggisms; if not catenate and linear seem about equally good. On symbols, I rather fancy your Oneek notion. How about E for exceptional cell, defined in terms of more than (n) motile progeny, and “epsilan" for the (hypothetical) particle conferring the E property? And similarly ‘ G vert. hep. te bE t fhe he f Ae tol =? on M oe (perhaps with superscript number) for cell with less than (n) motile progeny and "mu" for the (hypothetical) meps ? No doubt both Greek letters have been used before, but not I think in bacteriology in any related sense. Could you sometime, let me have the full references which will go with your draft ? The papere I don't lnow are Jennings 1937 (o# 1927) , Kallio, Lansing 1948. Sonneborn 3955 ,1954, Barton 1950, Wangermann, 1954. I am much impressed by your general discussion and mean to spend some more time on it. One point on which I would like formation (and which might perhaps be included in your draft) is p.4 "10% had 2 or more, up to 100". Do you have any detailed distributions 2 Your 11:20 split does not worry me too much. My use of 10 as a discriminant is empirical, based on apparent bimodal distribution in SWB41. If it had occurred in SW541 I should fairly confidently diagnose the 20 one as an E and the other as a non-E. However, without an estimate of n, which involves making an estimate of the"efficiency of detection"of uni-catenate cells, one cannot tell whether this is plausible. You say you had not a notion of Q's work. I did in fact mention it in my letter of Srd. February (para 5), however, maybe you mean no notion before this. This work is going ahead. He hopes to extend to other genera in which 0 strains are available. If all goes well, he,or he and I, might do a short communication on this, 6g. letter to Nature, in due course. To revert to your letter of 11 April, I am glad to hear the Gal-duction story is out, and hope to read it in full soon. How do you explain the instability? I suppose by interpellation, ; forming a "re-duplication"., Its hard to see why the same does not occur in Salmonella. In your one on phase-variation you speak of correlation between antigenic state of donor. and competence of lysate; ado you mean by this state of donor as to phase expressed at time of lysis ? You may remember that I did not detect any obvious difference in competence of lysate of TM2 in phase 1 or phase 2 when tested for ability to transduce 1. I shall be interested to hear if you did finally demonstrate this effect. You say someone, it looks like Iino, isputting steam on again on phase variation. Wh is this? Only progress here is on double specificity of initials from SW545. Using my own sera, fully cross-absorbed, I am now convinced this is genuine, as tested by micro-manip. transfer into various sera indroplets. Only just started on this, so details later. I have belatedly started .uaihg 643 derivatives as donors, which makes yield much better; my thanks to you for this idea, -3 = One last point, raised by 2, on your draft Page 13, suggestion 3, I hypothesise that the mep is & particle which generates a flagellum 6. basal granule, not the extra-cellular flagellum itself; because our (incomplete ) acid-washing expériments indicate that treatment which destrovs flagella does not destroy the mcp. A minor point, but as you are being so complete it might be as well to include it. "i tt he ws0 As to "crucial pedigrees". fT sent these, in an admittedly mepn$ state, on quarto sheets, some months ago. They need re-drafting, with index numbers for particular cells, to fit draft, this is not done yet. Thats all about drafts, drat them, Not much news from here, We have just gob: over a Soc .Gen.Microbiol. meeting, at which Guy Meynell and I had a paper on use of mixtures of tagged variants of a pathogen, togee if LDs50 dose of, say, 1 represents the situation where the average probability p that an inoculated organism will multiply and infect is small, here 7 x 1078 s SO that for dose of 107, e “Ph & 0.5, where n is ID5q dose. This went off O.K., though Oo ur results are not as clear-cut as we hoped. Harriett Taylor 1s giving 5 lectures here next week, I hope to pump her on an eas way of getting up optimal conditions for Pn, transformation, the N.Y.U. method is too tricky I think. Its a pity Hotchkiss publishes so little details of his set-up. I would very much like to spend some time at Madison, and must thank you for your kind words and invitation. Unfortunately I can't very well leave thig place, for more than a holiday, for some time anyway. Why don't you and Esther Come over for a long stay, and do some work here? We have room enough really. (And incidentally if you ‘have anyone bright who wants to come and work in London for a while, let me know. There do not seem to be as many people here ag one might expect coming into this field, whiah is a pity when one has space and could probably raise money). TI think it is time you both visited this side of the Atlantic. cy Yours sincerely, Dyce PS Pont Fae bmegeivti Zen pb Pew = SL tbo EF SOECE bine | Doness Shiléo Geren 4 bss, “ Ch. 4 i - fits © Evhin ¢ 40” ~ 1 & fixe B.Stocker,. S< 2 bt ‘ . belie fy ‘ ° ‘4 . Omnvtonn., H