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Medical Subject Headings (MeSH):
Simian virus 40
Restriction Enzymes and the "New Genetics," 1970-1980
29 September 1976
I have finally arrived back in Ann Arbor after a very stimulating year. Unfortunately, the politics of recombinant DNA have
put me in a holding pattern. As you recall, just before the Boston meeting, I wrote to you to tell you that we had put the
SV40 into the left operator region of lambda. We prepared the DNA and were ready to do the translation experiments with the
help of the reagents you sent over. However, during the Boston meeting which Noreen attended, the discussion of the vector
that I had helped her prepare led her to feel uncertain in its use. As you may recall, the vector we had prepared had an amber
mutation in the W gene, and another amber in the S gene. In addition, the lambda had deletions of att, red, immunity, and
nin. They had been grown in m- and r- hosts. The only difference between our vector and the Enquist vector was that it had
one more amber mutation (E) in the left arm. However, it did not have the cI deletion. For this reason, Noreen felt it was
only right to start all over again and make the vector with the 3 amber mutations. To do that we had to start with a host
that did not have the suppressor fragment in it and cross in an Fe mutation. After this was done, we did another in vitro
recombination to put a suppressor fragment in the lambda as I have drawn below.
Although time was short, I then used the purified ev 117 and got another SV40-lambda recombinant. However, all of this was
at the very end of my time in Edinburgh, and this left no time for testing out the new recombinant, and no time for doing
At present I am waiting to hear from Noreen to make sure that the new recombinant tests out, and that she has confidence that
the new vector is correct. At the time that I did this work she was in Switzerland and I did not get a chance to talk to her
before I left. So, after frantic work I just about got back to where I was when I wrote to you in June. This still leaves
us without the chance to check translation.
I'm writing you just to catch you up on the news and not because I am clear on what do next. My own inclination is to
wait until Noreen gets in touch with me and is ready to send me the recombinant molecule that I made. I then imagine it will
be necessary to clear the vector with the NIH advisory panel. If it clears, and I see no reason why it shouldn't clear,
I think that you and I could discuss the best way to perform the translation experiments rapidly.
At the present time all of this is disappointing and I hope everything can be straightened out. I will get in touch with you
as soon as I find out about my recombinant molecule and the state of the vector.
Again, thank you for your help, and I certainly hope that things will work out.
Roy D. Schmickel, M.D.
Professor of Pediatric and Comm. Diseases
[HANDWRITTEN RESPONSE: I may not have made it clear but the problem Noreen has is to show the E- mutation is in the final
vector because Sup F fragment suppresses the amber mutations. What's more, it is a double Sup II mutation. Which goes
to say that the more complicated a vector is, the more unsafe it is because of the difficulty in testing it safely.