Notwe cher Alain: (Deco) This letter is something of an act of contrition. Your christmas card has _. been resting in the "urgent" file of correspondence, as a constant reproach; the false urgency of hani-to-mouth business is all that has Bept us from answeekng. Actually, we have not been altogether remiss: last year as soon as you mntioned that you were interested in receiving the Scientific American, I started what proved to be involved negot&dtions with the publishers: the trouble was that I asked one of my colleagues here who already receives the magazine to put you down forna gift subscription, as this would save you the maghaficent sum of $1; unfor tunateky, their bookkeeping machinery seems to have broken down over this arrangegent, and it was many months before they acknowledged the order. They. finally did so not long ago, ani claim that you have been receiving the journal; I hope this is correct. (The annual subsoription is $6.50 under these conditions; you must still have some $$ to your credit: I hope you have a record of how mech, am I hope your future instructions will be more promptly emecuted. Have you had any further difficulty with the Soolety of American Immunologists?) Your colleagues! innumerable visits to the U.S. have given oppprtunities far. the exchange of cordialities, but I am very sorry we have not been able to see one another for so long. Jacques again teased us about "when we could come to Europe"; noone seems to believe us when we say it 1s a simple matter of finances, and that Europeans have a far easier tims finding subsidies for transatlantic visits than we so. But it is so. Jacques proved himself again the mst charming of egoists during this last trip (last November), but I am afraid that the momentar: ferfection of each transient scheme of enzyme synthesis evokes some impatience after a while: his account this time of the "y" system seemed to many to be glib, beautiful and unsatisfying. But we have to withhold judgment until the full experi- mental details are published so they can be critically reviewed. Jacques and we had an illuminating discussion about motivation in science; I wonder if you can tell m if this is typical of the French outlook. I hai remarked that there was no point getting excited about the scientific fads of each moment, except insofar as they gave an immediate persohal enjoyment. From a global, histori- cal perspective, lasting importance would attach not to the obvious progress of each moment, but to completely kew ways of looking at scientific problems that ipso facto will not be appreciated by contemporary thought; we would have no way of predicting what would be the real adwances of our science; at most the most brilliant among ua would constitute a footnote, not a chapter in the ultimate Bis- tory of science. Jacques’ answer was that he was interested only in absolute, ultimate 'truth', and that 1f he did not believe his work was in the forefront of historical advance, if he could not believe himself to be so~tspeak a Pasteur, he would abandon science. I am not sure how far this reflects his actual viewpoint, and how mich this was just taking the other standpoint for argument's sake. During the last year, not mich altogether new has happened in the lab, and as usual mich of our werk is in the progresdlon of earlier findings. I am sure our papers are a better way of telling you about it. Esther is still trying to trace the prophage through the Gal-lambda transduction system; Kalckar (at Bethesda) has lately been doing the enzymology of the Gal~ mtants. Curiously enough, the most common mutant has the same ehzymatic block as is found in the human genetic disease of galactosemha.More surprisingly, some of the mtants have blocks in different steps, and we are now trying to see &f the biochemical and genetic organiza- tion of the Gal~ mitants shows any coprespondence. Somewhat to my surprise, there arechints of a story similar to Demerec', but the work hasn't Bone far enough to warrant any conclusions. I myself have been occupied with writing up old work (e.g. a terrible job now in organizang collected pedigrees on the hereditary "chains" of motility in abortive transduction in Salmonella, tnx parallel with Bruce Stosker's work) and with conjugation processes involving various Hfr strains (a variety that Elie and Francois had discovered about the same time I had stumbled onto it). I am also trying some DNA-transduction experiments with bacterial protoplasts, so far with nof luck at all. Last November, we had to move out of our lab. so that it could be remodelled; we moved back only in April. We are now much more comfortably set up, though space is still not very large; except for occasional difficulties with storage, however, we are quite comfor&able and have room for 810 people doing our kind of micro- biological work. Part of our difficulty comes from having to ke self-contained as we are the only micrebiolggists on campus. You probably won't remember most of the group now here, zonctheybonakiogunexaiwm as the others have all gone else- where; I won't burden you with their present identities— there are three students, one US, one Australian, one Japanese, and all excellent, and three pos tdoctorals besides Esther and m. On of theae you might know, Newton Morton, who did his thesis with Jim Crow in statistical—human genetics. He is joining the medical faculty to initiate a program in genetics there, but wants some laboratory experience first. Next year will be quite a potpoumri: a Danish couple (grskov); a German Heumann) and a Finn (Saris) are comings it strikes m that relatively very few French students and postdoctorals have come to the stateats— is this anly because Paris already _ has so many opportunities in the fields I know about, or is this also true of your science courses at the universities? How about your own work? I know only that you had gotten interested in "acquired tolerance"— what about it? Of cours 8, this subject might have the most fascinating genetic implications, as the mechanism might involve the transduction of some hereditar entities (chromosomal, cytoplasmic?) from the graft to the host cells. What are your ideas as to its mechanism? I hope you are not neglecting any oppor tunity to use exact genetic differemces, specifically Snell's isogenic-resistant mouse strains, for this kind of work. An interesting angle on this subject, which I have been waiting to see for a long time, has appeared recently: a paper by Good of Minnesota (in an out-of- they way medical journal called "Journal-Lancet", June '55) describes experiments with agammaglobulinemic children. Thess children tolerated grafts of lymph nodes from normal individuals, and thereby became able to produce antibodies. An adequate me ans of suppressing the existing antibody-forming mechanism would immm seem to be the sine qua non for development of tolerance in adults. (I am sure you will also have seen the note in Nature recently by Ford et al on rat-mouse chimeras). However, I jus had a letter from Snell wherein Ye concludes that his enhancing factor system is based on the production of just enough antibody to suppress further sensitization of the host by the graf$; obviously, there has not been enough application of "classical" serological technique in the study of these phenomena; I assum that cirecukating antibody is not demonstrable in prehatally acquired tolerance. Is this so? I hope ourd atrocious performagce as correspondents does not discourage you, any more than it is a reflection of our hope of preserving a warm amitde. With the best from both of us, \ ~ ?