[written in Lederberg's handwriting, EDWARD M. JOHNSON]
[stamped, THE ROCKEFELLER UNIVERSITY OFFICE OF THE PRESIDENT MAY 27 1988]
Dear Dr. Lederberg,
Thank you for your recent note and the reference on the tungsten microprojectiles. Also, thank you again for agreeing to submit
our article (Appel et al.; "Asbestos Fibers Mediate . . . ) to PNAS. I want to answer a few of your queries.
We have thought of patenting an asbestos transfection process, but when we brought it up with a couple of companies, none
seemed interested. Also, one potential problem might be that we published an abstract on this at the FASEB meeting more than
a year ago.
There are a scattering of other papers in the literature regarding use of abrasives or minerals to assist in transfection.
You recall the Fraenkel-Conrat papers using carborundum on tobacco leaves. There was also a paper by Singer and Fraenkel-Conrat
using Bentonite (Virology 14, 59-65; 1961). I think Bentonite is high in aluminum silicate. George Dubes
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published a paper, referred to in our article, on the use of various mineral silicates to enhance uptake of viral RNA into
cells. I believe Dubes was actually the first to transfect using calcium phosphate, as well.
There are several ways to explain the synergism with smoking, but nothing very easily testable. The explanation we favor is
that different oncogenes (or sets of oncogenes) might be activated by either asbestos or smoking. Each separately must await
some additional event(s) to be oncogenic, but together they are sufficient or more nearly so. The precedent is cooperation
between myc and ras oncogenes. Of course this is total speculation, but not outrageous. One might expect that mutation by
chemical carcinogens through smoking would affect different DNA sequences than mutation by DNA integration following transfection.
Tom Fasy (who is a pathologist here and the actual asbestos expert -- my work being primarily on DNA replication; Tom was
also at Rockefeller) intends to follow up this work with animal asbestos inhalation experiments using myc and ras oncogenes
bound to chrysotile. That would directly demonstrate that transfection with asbestos could cause cancer. As an alternative
to inhalation, he is also thinking of intraperitoneal injection since
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that would affect the mesothelium.
We have now received the comments of reviewer number 1 (thank you for conveying them), and we eagerly await those of the second
reviewer. I realize that you are busy, and we are sincerely grateful for the time you have devoted.