10 Autoimmunity was an emerging and exciting frontier. The concept of Burnet that autoreactive cells could escape into the peripheral circulation as “forbidden clones”11-13 heralded an era of disease discovery and understanding, and autoimmune hepatitis was a product of this surge. Autoimmunity, however, was still a vague pathogenic mechanism; it was not an etiologic agent like a virus or a drug; and it
could not be measured in the clinic. The evolving requisites for autoimmunity, especially the requirement for the transfer of disease by antibodies or lymphocytes, were restrictive,14,15 and “autoimmune” vied with “idiopathic” as an apt descriptor for the EGFR inhibition fledgling condition. The wobbly legs of autoimmune hepatitis would persist for at least 2 decades. Systemic lupus erythematosus almost swallowed it16 and drug-induced17 and virus-related18,19 conditions repeatedly threatened its SB203580 legitimacy. The goals of this review are to illustrate the dynamics of successful clinical investigation in liver disease and to underscore the vital role of the clinician nonscientist in starting and completing the circle of care from bedside-to-bench-to-bedside. Autoimmune hepatitis will be the “illustrative model” by which to accomplish these goals, and I will be the typical “clinician nonscientist.” The script can be applied broadly and accommodate any
substitute model or actor. The principal components of this tutorial are indicated below, and they rely heavily of good fortune, good mentoring, appropriate goal identification, adherence to protocol, compulsive record keeping, personal resilience, and strong collaborations. CALD, chronic active liver disease; HBsAg, hepatitis B surface antigen; HLA, human leukocyte antigen; IAIHG, International Autoimmune Hepatitis medchemexpress Group; MELD, Model for End-Stage Liver Disease. From 1969 to 1972, I had the good fortune to interact with academic clinicians who had a keen interest in
the study of liver disease (Table 1). At the Philadelphia General Hospital, Geobel Marin advocated the principles of controlled clinical trial and “double-blinded” investigation as the bases for new knowledge in clinical medicine, and my first article comparing peritoneoscopy with unguided needle biopsy of the liver illustrated some of these principles.20 At the University of Pennsylvania, Roger Soloway had just returned from a fellowship at the Mayo Clinic, and he presented wonderful data derived from a now classic controlled clinical trial that described the natural history and treatment of “chronic active liver disease”.21 My commitment to the study of liver disease was established through these contacts in Philadelphia as was my desire to train at the Mayo Clinic. Fortunately, Bill Summerskill agreed to accommodate this desire. The military draft interrupted my transition to Mayo, but my assignment to the U.S.