The discovery of captopril: reply.

Abstract

I wish to draw your attention to an editorial published in the May 2003 FASEB Journal (17, 788–789) by Smith and Vane, because I disagree with the concept expressed and the description of some events that I witnessed. The article deals with the discovery of captopril, the first angiotensin I converting enzyme (ACE) inhibitor active after oral administration. The authors state “We know of no government money that went into any part of the discovery and development of this drug. We are very unhappy to have people with no direct knowledge of the history of captopril pontificating on the use of government money.” The history of the development of ACE inhibitors contradicts this statement. For example, in the fifties Leonard T. Skeggs, Jr., who discovered the conversion of angiotensin I to the active form, angiotensin II, by ACE in horse plasma, was an employee of the Veterans Administration Hospital in Cleveland during all of his professional career. ACE inhibitors not only block angiotensin I conversion, but also the inactivation of bradykinin by the removal of two carboxyl-terminal amino acids. Many beneficial effects of the therapeutic application of ACE inhibitors are attributed to enhancing bradykinin activity, hence, ACE is also called kininase II. Dr. H.Y.T. Yang and I discovered an enzyme in kidney and human plasma and named it kininase II independently. Subsequently, we characterized kininase II as being identical with ACE. I was supported then and have been ever since, almost entirely by the National Heart, Lung, and Blood Institute of NIH. The clinical studies on the application of ACE inhibitors in the U.S. of John Laragh, Haralambos Gavras and others also depended on NIH support. All of the above contradicts the statement that no government money went into the development or any part of the discovery. In addition, the article neglected to mention Arnold D. Welch, who as the President of Squibb and Sons Institute for Research and Development, was responsible for getting his old friend John Vane as consultant to initiate research on ACE inhibitors. It was also Dr. Welch who hired Smith and appointed me as consultant to Squibb at that time. Concerning the clinical testing of an ACE inhibitor, on behalf of Squibb Company and Arnold Welch, I got John Laragh interested first in the subject during a lunch at Columbia University where he worked. Since Arnold Welch, a much admired, outstanding and successful scientist, scholar and administrator, passed away last year, I wish to point out his key role in the development of ACE inhibitors that was omitted from the article. Ervin G. Erdos Department of Pharmacology University of Illinois College of Medicine at Chicago