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Letter from Joshua Lederberg to William Hayes

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b-3-l U, 1952 My dear Hayes: Your letter of the 8th has just now arrived. I judge that you will but recently have received mine of the 5th. This crossing of ideas as well as correspondence is coming to be a regular thing. I think my letter may have anticipated some of the points raised in yours (or vice versa). However, my note, upon a re-reading appears rather obscure, so that I will try to clarify it. I shall not be surprised to find that this tnessgge will again cross yours, but this kind of exchange of ideas is abso- lutely indispensable. First of all, I don't think a detailed comparison of experimental protocols is essential. There is no doubt we have all run into the same thing, both with respect to the differential fertility of F+ x F- as compared with F+ x Ff, and the effct of F-polarity on the segregation ratios. I noticed this about 3 months a$?~, but was rather puzzled that W-F- x TL-F+ was much more fertile than B&F+ x ‘IX-F+ or F- which are about the same. Kith some further comparisons using other 5: 2nd TL stocka, I've come to the conclusion that there is a gradi- ent of F+ potency. Of the stocks you have, the F- would be a zero grade, 5%161 -no-&i be +I, and TL-F+ +2.. The fertility of a combination would depend on the degree of separation of the parents (along the line of the Hartmann theory of relative eexuality in the algae). In addition, S tt cells generally can function (almost) [email protected] as relative F- . This would account for the very low yields of B&!-F+ S x TL-F+Sr on streptomgtcin agar, as compared with the cross x TL-FLSr (E-ll77), There is also an effect of segregation ratio of the Sr factor, but this is not enough to account for the differehce. As to the segregation ratios, the effect of F-polarity wau under our noses ZJJJ~SL three yews but ( as usual.?) we :Ilissed Lt unt.11 the compatibility story came to light. Filial TL- cultures extracted fromhheterozygotes were observed to give &k&s inverted segregations in cross

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