July 1, 1966 Dear David: This is in reply to your letter of June 22, 1966. I wholeheartedly agree that a determined effort must soon be mounted to get at the sequence of both MS-2 and QB. I was happy to learn that you had spent the time in Sanger's lab to familiarize yourself with his method. In accordance with this intent, I would appreciate it if you would list with as much detail as possible all of the necessary software and hardware you think we should have available. In this connection I should like to note that we have learned how to split the QB molecule into a 1/3 and 2/3 piece, so that we can separate the two ends. This should provide a fairly easy way of determining a number of things, including the direction of replication. It might be advisable if you would send along the sample of your Z1k/1 RNA phage, so we can compare it with QB. There is a corrected piece of information, which I should pass on to you. Although we failed to find methionine in the complete hydrolysate of the QB coat protein, we persistently found some evidence for trace amounts amounting to less than one residue per 20,000 daltons. However, we have since found a peptide fragment containing methionine, so there must be at least one residue of this amino acid in it. I look forward to hearing from you with the details necessary to order the required equipment. With kindest regards, Sincerely yours, S. Spiegelman