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~' THE ROCKEFELLER UNIVERSITY . m NEW YORK 10021-63QV ~ 1230 YORK AVENUE • NEW YORK March 21, 1985 - Dr. Roy E. Morse Vice President Research and Development R. J. Reynolds Industries, Inc. Winston-Salem, North Carolina 27102 Dear Roy: I had the pleasure of spending a good portion of Saturday, March 16th with Dr. Stanley Prusiner in San Francisco. We went over his latest work, vouch of which is about to be published, and were thoroughly impressed with the remarkable progress he has been able to make in recent months, partly through the cooperation he has developed with colleagues at the California Institute of Technolog•y and the Swiss Institute of Technology in Zurich. Prusiner's perceptions and initiatives are, of course, behind all of this, but it is interesting to note that his work is catching on sufficiently well that outstanding groups are now so anxiOus to cooperate in cooperative ways. As the refinements of experimentation advance, it becomes even more clear that there is very little, if indeed any, nucleic acid in the scrapie prion._ It now seems almost certain that it is a pure protein as Prusiner felt so strongly was probably the case two and three years ago. Moreover, it is clear that the prion is very closely related to a protein, which Prusiner terms the homologue, that appears as a constituent produced normally in many cells. It remains to be seen if one can determine precisely what the difference between the two is. Actually that difference may be relatively subtle as we know from other examples. In any case, the prion, in addition to behaving quite differently in the presence of degrading agents, has the well-known destructive infectious effect, whereas the homologue is a normal, useful protein which might be termed benign. The ref inements of the work from this point onward ought to be much more direct: than they were in the past since so much about the structure is known. Among other thing s this makes it possible to synthesize portions and, indeed, a:l of the constituents involv.d with the use of modern techniques. While nothing is aom letely straightforward in these matters, the whole problem ~a now far more uanagcable than it was ssveral years ago but will,. at the same timo, • uontinu. .to be very . exciting. : . : . . 4... . • ... . . • , . s

Dr. Roy E. Morse March 21,, .1985 Page 2.*"- .. .196 0 Prusiner has several crucial experiments underway after having completed a complete write-up for publication of the most important discoveries made•this far. It now seems to be essentially certain that Creutzfeld-Jacob disease, to which humans are susceptible, is a very close rela- tive of scrapie. The:re still does not seem to be any close link with Alzheimer's disease however. Sincerely, Frederick eitz F P

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