February 11, 1974 Dear Dr. Berg, I have a great many reservations about the experiment you propose and a great deal of thought should be given to possible hazardous consequences. That's not to say that there are such consequences but very frankly, cutting up HSV DNA and randomly inserting it into a [lambda] phage DNA may well generate something quite nasty as well as what you want. If one could manage to isolate just the tk or a small piece of DNA containing the tk, the insertion of that piece of DNA into a phage or plasmid carrier would certainly be preferable. I don't know Bernie Rotman's cell culture set up and therefore can't commment on the adequacy of the containment features for E. coli; they may very well be adequate but I suspect that large scale growth or phage will ultimately be the goal and that's where I have serious reservations about containment. My own prejudice (and it is only a prejudice at present) is to call a moratorium on such experiments pending a conference I expect to call (very likely next Fall or early Winter) to explore the ramifications and possible dangers (if any) to such experiments. But most important such a conference can consider whether any kind of controls are necessary or possible to prevent an unwanted director. I can't expect that my prejudice is enforceable but you did ask my opinion. And that is, I would not do that experiment now! Of course, if there is such a Conference, you and Bernie would be invited to participate. With best regards to Alvin and Bernie, Sincerely,