February 25, 1952 Dear Cavalli: Your letters and Hfr culture just received. The latter is working nicely against W-1177 and also W-1177F+, so that I find no surprise, as you antichpated. . Hayes eeems to have made a remarkable discovery; if you get this letter in time,I hope you will convey my respects to him. [May I tell you also that I was very much annoyed that he should have spoiled his contribution by his rash and unrestrained speculation about the role of lambda, and talking about "self-reproducing gametes"|. he may not know how much confusion this is going to cause, especially after our work on the Salmonella transduction is published. We have been taking great pains to Keep clear the delineation of the 3. coli and Saimonella work, and such premature speculations will not help at all. Probably Hayes, yourself, and I have been doing this experiment all at the same time. The result is coming through now. The paint igs to establish a connection between Hayes' finding and our ‘work on F. Ag we have all known for some time, BM~ F+ s° x TLE, - F- st (58-161 x W-1177) is moderately fertile even on streptomycin agar; whereas BM- F+ S x TLB,— F~ 3° is not. In my own observations, I had cagually assuned that this was due to the linkage relations which give a preppnderance cf 3* protrutrophs in the first cross, S° in ths secund, out I aow agree that Hayes is quite correct. I have just com pared these crosses with Bi F+ s" x TLB,- F+ 3° (+677 F+) and BM- F~ S" x TILB)- F+ S%. Both of the latter are fertile cn streptouycin ugar! F- therefore protects th fertility of S® in the presence of streptomycin if the othar parent is S™. I am setting up other combinations of a similar design. If they agree, it will be necessary to postulate a second sexual function G, of which most or all stocks are G+, but smmex which, in S® cells is subject to inhibition by sm. ‘share I think Hayes has gone overboard is ¢:ssigning detailed meanings to the mmmmmn second funcbiogj, aspecially this business of "aextruded- phag-stick-to-cells". Gsuaxcmekixgusixmmmaks The picture does suggest that cne parent must be F+, the other G+ for sexual reproduction to cccur, but to refer to either as a male or female gamete is going far beyond the evidence, I will admit that it is more likely that the cytoplasmic structures are inhibited by sm, which would give G- a male-Like character, but tosre is no evidence still that is inconsistent wita isoganous fusion. I see no point in maxing a fantasy of the story bayoad the necessities cf the evidence: at least in publication, Uccamts razor whould be applisd gonercusly. Sincs ay last letter, I have been thinking about the form of a publication. I am rather opposed to the idea of notes to Nature, and am very much in fevor of writing a joint paper, mather than coincident notes. I have hac. some experience with the latter, and all it does is require other peuple cither to give two references, or choose one. In view of the very gratifying sympathy of thought, objectiveg and experiment expressed in our correspondence, I would be very pleased at such an exposition of it. I am there- fore proposing that we write a full paper together, and submit it to Genetics. This jour- nal is now edited in this department, which makes many details such simpler. In parti- cular, minor revisions such as might otherwise be troublesome in o transé&lantig collabo- ration present no serious problem. ‘tf it will facilitate the proper clarification of our work in relation to Hayes} I would be amenable to a premonitery note in Nature, to accom- pany Hayes’ if he is also agreaable. In order to minimize priority cuestions, I propose that you assume senicr authorship for publication in an American journal, and the converse in a European. Mrs. Lederberg should, by rights, appear as a co-author in any full, (non-polemical!) exposition. By the time you receive this, I will have (T hope) reached a definite conclusion on the sm experiments; perhaps you will as well. I have not yet written on this subject; I would prefer to mention it as succinctly as possible, still giving Hayes his due, and with as little speculative discussion as possible. I am enclosing a draft that correspogids to my conception of the paper. As you can see, it is already of a respectable size, although no-one will accuse it of being padded. I send it only as a basis for discussion between us, and assuming that it will not hamper the free expression of your side of it. I will admit readily that this version is strongly biased by my own viewpoint, but I have had so-many experiences of a similar outlobk that I do not anticpate any difficulty. If we can put.together a manuscript within a short time, it need not be letter—perfect to be submitted to Genetics (and reserve 4 place). If we are reasonably prompt, we can still find a place in the September issue. *he editors have already expressed their interest. Entirely aside from any other pressures (reak or imaginary), the writing of the draft convinced me that the time was appropriate. The SM-experiments now ina progress were an afterthought, provoked by Hayes' paper in the Jan. 19 Nature which arrived a day or two ago, but do not seriously affect the structure of the paper, and should be described readily in half a page. ah tan ees tals te ive\, 111 getie “eespeges (A t the .mestupapid advyaude scien the, som ot eabs_t ew y ay have n prefer >