A Talisman of Pathology

Sincemy appointment as the incoming 2016 Editor-in-Chief was announced last summer, I have received a number of perspectives on The FASEB Journal from contributors and readers, all positive. Some of the reviews also came from individuals who were prompted to look at the journal anew, with no editorial contributions to the journal or little familiarity with the publication; these comments also were encouraging. However, one of the comments in particular stood out and has been onmymind: “I am impressed by the breadth but, that said, there is a lot of inflammation.” I of course quickly realized that this meant the degree of topical coverage and not uncontrolled, reckless passion in certain articles. Here I briefly reply to this observation. My contention is that inflammation is not as much a distinct quantumlike discipline to which a particular journal might feel some obligatory allegiance but rather it is the underpinning of such a vast array of physiologic and clinical phenomena that essentially it is a disciplinary codex. Inflammation was discovered and rediscovered as many times as anything in the history of medicine. The standard story attributes the definitive case record to the Roman physician, Aulus Cornelius Celsus (25 BCE to 50 CE), who described a patient with a fulminating infection in the pleural cavity. His observation of “red and swelling, with heat andpain” (Fig. 1) (1, 2)became the iconic, tetrapartite signature of inflammation handed down to students of medicine for centuries. It is ironic that his patient was apparently anatypical case study in that swellingcan indeedbe a signature of inflammation but, of course, not always the accumulation of the pus seen by Celsus. Although I did not study medicine, I was a vaguely aware of key milestones during my postdoctoral and early career at the Worcester Foundation for Experimental Biology (Shrewsbury, MA, USA). Many of my colleagues were distinguished investigators in thefieldsof steroidchemistryand biology, and from them Iwas privileged to learn someof the milestones in the field of inflammation, in terms of both discoveries and the individuals involved. In those years, I also had thegood fortune tobecomevery close friendswith John B. Hench, an American historian at the American Antiquarian Society in Worcester, whose father had shared the 1950 Nobel Prize in Physiology or Medicine with his Mayo Clinic colleague, Edward Kendall, for the discovery of the therapeutic efficacy of cortisone for rheumatoid arthritis. This was one of the fastest awards of a Nobel Prize and was the incentive forMerck&Co. to enter, andwin, the race for the commercial production of cortisone. The second chapter in my journey toward a broader comprehension of inflammationwasmy good fortune in the 1970s and subsequently to become acquainted with Guido Majno, then Chair of Pathology at the nearby University of Massachusetts Medical School (Worcester, MA, USA). He had been trained in the internationally renowned mecca of pathology inMilan, Italy, followed by subsequent experience at other elite centers of pathology. As we began to see each othermoreoften,his charmandvast eruditionwere themost evident attributes, but another began to rise in crescendo, his belief I should say with almost religious fervor that inflammation underlies a far wider array of disease than previously recognized.As I continued tobe sobowledover inour conversations by his knowledge of the history of medicine, I would admiringly mention this to others. One day, a colleague said: “Don’t youknowabout thebook?” I replied that I didn’t. I was told (and I can remember the exact words as if it were yesterday): “Go to the library and look at The Healing Hand.” Upon finding the book (oversize, like the ancient monographs), I dove in and was stunned by its breadth and vast sweep of erudition. Although its title and subtitle conveyed a focus on the pathology and treatment of wounds, it is a work ofmagisterial command on the history ofmedicine. I soon acquired my own copy, which is the most treasured resource of any on my shelves. I shall not expound on it any furtherherebutwill always consider itmy stepping stone fora non–M.D.’s learning curve. More pertinent to my theme in this editorial, it wasmy colleague, Guido, and his remarkable book that preparedme to watch the continuing evolution of the inflammation field over the subsequent four decades sincewefirstmeteachother.Allduring that time,onalmost a weekly basis, I would learn of yet another vivid exemplification of Guido’s doctrine and would fondly remember his elegant Italian accent as he had said to me in those earlier days: “Thoru, whenever you have disease, there will almost always be inflammation if you have an open mind and look precisely enough.” Thus, in response to the reader’s observation: yes, we do publish a considerable portfolio of papers on inflammation. I am pondering that we should publish even more. Little did I think that I would ever be in a position of editorial leadership to say that when I first learned about the steroid era, Hench and Kendall, and met with Guido Majno.