COLORADO GERALD B. UNIVERSITY OF COLORADO MEDICAL CENTER 4200 EAST NINTH AVENUE DENVER 20, COLORADO FOUNDATION FOR RESEARCH IN TUBERCULOSIS WEBB MEMORIAL BUILDING November 3, 1955 Dr. Joshua Lederberg Department of Genetics University of Wisconsin Madison 6, Wisconsin Dear Joshua: As you can imagine, I am delighted that Larry has decided to join us. Dr. Waring is still away and hasn't heard the good news, but I am sure he shares my enthusiasme The "proposal for a proposal" has been polished up and is in the process of being typed for distribution. Perhaps it will be done soon enough to be enclosed in this letter. I appreciate your help in prepar ing ite Do try to make the St. Louis meeting. As I told you, I think we would all benefit from your unbiased approach to some of our pet pro- blems.e I nave heard, unofficially, that the grant request which we sent to the American Trudeau Society on the subject of the metabolism of ison- jazid has been approvede Two of our people are working on techniques and are about ready to start working on animal and human sera. I enjoyed your remarks in the letter to the editor. There is much too little dissemination of this kind of information amongst the profession, to sav noting of the public. I have been laboring through Harris's book. I have scanned it completely once, but I am now reading it more thoroughly. I will have to admit there is a very great deal of new information on medical genetics that I had no inkling of vrior to your arousing my interest in it. I have corresponded with Herndon at Bowman Gray and Neel at Michigan to add to our file of information on Departments of Genetics in iedical Schools, They were not able to add anything illuminating, but their inter- est and enthusiasm in the subject should bear some weight. I have just been reading Jensen's article, "Some Remarks Concerm- ing Attenuated Isoniazid-Resistant Strains of Tubercle Bacilli," in the January, 1955, issue of Acta. Path. Micr. Scand. Jensen obviously is not aware of Gardner's work on the catalase activity of various strains Dr. Joshue Lederberg ~2= November 3, 1955 of mycobacteria. As you will remember, the sensitive wild strains were catalase positive. There were various types of isoniazid resistant mutants ranging from slightly reduced catalase activity to complete absence there- of. There appears to be a good correlation between catalase activity of these isoniazid resistant mutants and the!"pathogene& jy not only for experimental animals including the guinea pig, but also man. In other words, there are plenty of isoniazid resistant mutants capable of milti- plying in guinea pigs at the normal rate, namely those that are catalase positive. Jensen, also, does not seem to be aware that the BCG organism is catalase positive, and interestingly enough can be made isoniazid resistant, and as I understand it, with comparable reduction in catalase activity. Unfortunately I have not checked the above with Gardner, since he is out of town at the moment. With my very best to you and Esther, I am Sincerely, aE ose RSM: wm