THE JOHNS HOPKINS UNIVERSITY BALTIMORE, MARYLAND 21218 DEPARTMENT OF BIOLOGY 23 February 1989 Dr. Bernard D. Davis National Institutes of Health Bld. 16 Room 207 Department of Health and Human Services Bethesda, MD 20892 Dear Bernie: Thank you for your letter of February 13 regarding the current situation in Congress and, indeed, throughout the public nationally. Most scientists doing research take for granted that errors in interpretation and judgment are almost always picked up by the work of others later on and that such errors are, in a sense, automatically corrected. I share with you the worry about the "mad scientists" image that so many people are beginning to accept. In connection with your request for "my biggest error in research," I do indeed have one rather amusing example from my own scientific background. I enclose a photocopy of the paper published back in 1955, and it seems ideal for your purposes since it contains as authors the names of individuals such as Linderstrdm-Lang, Schellman,Harrington, etc., generally considered to be moderately honest folk. This paper purports to demonstrate that the activity of ribonuclease is essentially independent of hydrogen bonds since the enzyme digested both RNA and a synthetic substrate at the same rate in the presence or absence of urea. The summarizing statement at the end of this short note gives our interpretation at the time. A few years later while Michael Sela was visiting my laboratory at the NIH, we found that the three-dimensional structure of ribonuclease, although enormously disorganized by 8 mol urea, was snapped back into essentially native shape by the addition of certain polyanions and, certainly, by RNA itself. Thus the stabilization of the three-dimensional structure by hydrogen bonds was restored in the presence of the substrate and other polyanionic materials, and the original conclusion was therefore entirely incorrect. One could term the earlier conclusions "misinterpretation" or even "professional naivete"; however the name of Kai Linderstrdm-Lang in the author list would safely rule out such appraisal. The same would, I think, apply to the term, "fraudulence." Mistakes are made all the time Dr. Bernard B. Davis National Institutes of Health Page Two 23 February 1989 but most of them seem to be corrected eventually. As far as a paragraph for your collection, I would think that the second page of this small reprint beginning with, "All the data" and ending with the list of authors might be enough to serve Barbara Culliton's purposes. Best regards. Hope to see you soon. Sincerely, Chris&??Anfinsen CBA:djh Enclosure