Joshua Leder­berg and the "Cel­lu­lar­ity" of Bac­te­ria

by Elio

Joshua Leder­berg died re­cently. His is a revered name among our older read­ers, and we as­sume that many younger ones also know of him. But just in case, let us men­tion some of what made him a gi­ant in mod­ern bi­ol­ogy. He is best known for find­ing that bac­te­ria have sex, that is that they can un­dergo cell-to-cell con­ju­ga­tion. He then dis­cov­ered (with Nor­ton Zin­der, a grad­u­ate stu­dent) that genes can also be ex­changed via phages: trans­duc­tion. Thus Leder­berg dis­cov­ered two of the three ma­jor mech­a­nisms for gene trans­fer in bac­te­ria. The third, trans­for­ma­tion by naked DNA, had al­ready been dis­cov­ered, or else – who knows? – he might have found that one, too. He then en­tered the fray re­lated to the ori­gin of mu­ta­tions. For this pur­pose, he in­vented, to­gether with his wife Es­ther, the replica plat­ing tech­nique, which al­lowed him to demon­strate that mu­ta­tions were spon­ta­neous and ran­dom, not in­duced by some­thing in the en­vi­ron­ment. He did this by com­par­ing a mu­tant colony iden­ti­fied on a replica plate with the cor­re­spond­ing colony on the mas­ter plate, and show­ing that they both had the same prop­er­ties. That ended the ar­gu­ment, at least for the time.

Joshua Leder­berg (1925 – 2008). Source

These ac­com­plish­ments place Leder­berg among the great bi­ol­o­gists of all times. How­ever, Leder­berg did much more.

Af­ter be­com­ing one of the youngest no­belists in his­tory, he went on to ded­i­cate him­self to mat­ters such as exo­bi­ol­ogy (a term he coined), pub­lic pol­icy about in­fec­tious dis­eases, and bioter­ror­ism.

Let me ex­pand on why his con­tri­bu­tion tran­scends the phe­nom­ena he dis­cov­ered. By the mid– 1940's, it was be­com­ing ev­i­dent that bac­te­ria were cells. But were they cells like all other cells, or were they some­thing dif­fer­ent? Many bi­ol­o­gists were still re­luc­tant to ad­mit bac­te­ria into the realm of "reg­u­lar" cel­lu­lar be­ings. Leder­berg be­lieved that sort­ing this out was of cen­tral impor­tance. This is re­vealed by the in­ter­est he took in bac­te­r­ial cy­tol­ogy, in­clud­ing his find­ing that peni­cillin in­duces the for­ma­tion of spher­o­plasts. But it was his dis­cov­ery that bac­te­ria could mate that swept away the re­main­ing hes­i­tan­cies. Sud­denly, the door was opened for bac­te­ria to take their place as cells like all oth­ers – no longer some bi­o­log­i­cal odd­ity. Lederberg's dis­cov­ery was most de­ci­sive in bring­ing about this new aware­ness.

I would also like to share with you this re­sponse re­ceived from Robert Mur­ray, one of the founders of bac­te­r­ial cy­tol­ogy.

You are right in say­ing that Leder­berg re­ally had in mind that bac­te­ria were real cells. I know this be­cause both C. F. Robi­now and I spent time with him be­fore and while he was at Wis­con­sin; he was very much in­ter­ested in the cel­lu­lar­ness of bac­teria. I am pretty sure that a good part of the stim­u­lus came, as it did for me, from read­ing Rene Du­bos' book, The Bac­te­r­ial Cell, and think­ing about the mi­cro­graphs in the ad­den­dum in that book by Robi­now. Leder­berg im­plies that in­debt­ed­ness in the fore­word he wrote for a com­pendium of clas­sic pa­pers, Mi­cro­bi­ol­ogy: a Cent­enary Per­spec­tive, (un­for­tu­nately not all I would have put in) edited by Jok­lik et al. and put out by ASM Press in 1999. Look at his sec­ond page where he states:"A ma­jor con­cep­tual turn­ing point was the pub­li­ca­tion of Rene Du­bos' The Bac­te­r­ial Cell in 1945 just in the midst of the wave of dis­cov­ery of spon­ta­neous mu­ta­tion, of ge­netic trans­for­ma­tion, of (con­ju­gal) ge­netic re­com­bi­na­tion – i.e., sex – in bac­te­ria, and soon af­ter virus-me­di­ated trans­duc­tion." My, that was dis­cov­ery plus some­thing spe­cial that came to a mind pre­pared to think hard about ex­per­i­ments that told one some­thing. I sup­pose one could add the in­flu­ence of Cold Spring Har­bor and a few other good minds of the time. No­body seems to re­ally re­mem­ber Bea­dle and Tatum, who got Josh on his way.

Leder­berg did some­thing for plas­mids, too, and I re­mem­ber him set­ting me straight on bac­te­ri­ocins. He mat­tered to me. I talked to the grad­u­ate stu­dents this morn­ing about him as the pre­lim­i­nary to a weekly sem­i­nar – so also thank you for stim­u­lat­ing that bit of teach­ing. The three vi­rol­o­gists (or­ga­niz­ers of the event and the speaker) had not heard of Leder­berg. So your blog is worth­while. The stu­dents wanted a date or two as a way of or­ga­niz­ing their his­tor­i­cal thoughts. I asked the class who had "al­ready dis­cov­ered" trans­for­ma­tion by naked DNA and no­body, in­clud­ing fac­ulty present, could an­swer! The years 1945 to 1953 put a lot of the ba­sis of mod­ern bi­ol­ogy into fo­cus.