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Rudolf Virchow's Medical School Dissertation on Rheumatism And SPECIAL ARTICLE Rudolf Virchow’s Medical School Dissertation on Rheumatism and the Cornea: Overlooked Tribute to the Cornea in Biomedical Research Curtis E. Margo, MD, MPH,*† and Lynn E. Harman, MD* theory to scientific-based concepts dealing with the cell.1,2 Purpose: ’ To critique Rudolf Virchow s medical school dissertation The event that usually marks this transition was a series on rheumatism and the cornea and to determine whether it might of biweekly lectures delivered at the Pathological Institute have anticipated his remarkable career in medicine. of the University of Berlin. From February through 3 Methods: Review of the English translation of Rudolf Virchow’s April 1858, Virchow introduced his doctrine of cellular de Rheumate Praesertim Corneae written in 1843. pathology, casting aside generations of conjecture about the nature of illness with the observation that the true Results: The dissertation was more than 7000 words long. Virchow nexus of disease resides in the chemical and physical considered rheumatism as an irritant disorder not induced by acid as activities of cells. Virchow used transcripts of these traditionally thought but by albumin. He concluded that inflamma- lectures to write his landmark text Cellular Pathology, tion was secondary to a primary irritant and that the “seat” of published later that year. The thesis of Cellular Pathology rheumatism was “gelatinous” (connective) tissues, which included was expressed so clearly and forcefully that popular the cornea. He divided kerato-rheumatism into different varieties. theories such as vitalism and humoral pathology were The prognosis of keratitis was variable, and would eventually lapse doomed to irrelevance. into “scrofulosis, syphilis, or arthritis of the cornea.” Although he was just 37 years old when he wrote Cellular Pathology, Virchow had become the leading voice Conclusions: ’ Virchow s dissertation characterizes rheumatism in in European medicine (Fig. 1). His ascent to chair the terms of chemical and tissue interactions that make little sense in the prestigious Pathology Institute and to become the editor ’ context of today s knowledge of rheumatic disease and keratitis. editor of Archives of Pathological Anatomy, Physiology, Ironically, many of these concepts were made obsolete by the cellular and Clinical Medicine was due to his skills as a microscopic model of disease that Virchow championed. Virchow decided to pathologist and his ability to synthesize biomedical obser- pursue the study of rheumatism through the cornea because he thought vations into theories and testable hypotheses. Fifteen years that the cornea was an ideal tissue to study disease. This discernment earlier, Virchow had written (in Latin) his medical school was passed on to his students whose seminal contributions to general dissertation on rheumatism and the cornea. With no more pathology were based on research with the cornea. It is debatable background than a single ward experience at the Charité ’ whether Virchow s insight into the importance of the cornea in Hospital, he completed his dissertation on October 21, biomedical research at such an early stage of his career could have 1843, the day he graduated from Friedrich Wilhelm predicted his monumental contributions to medicine. University. Cost of privately printing the document was Key Words: rheumatic keratitis, Ruldolf Virchow, ophthalmic paid by his father, who gave the work to his friends. We history reviewed Virchow’sdissertationde Rheumate Praesertim Corneae to determine whether this inaugural work could (Cornea 2015;34:235–238) have anticipated the prodigious accomplishments that were to lie in his future. udolf Virchow (1821–1902) was arguably the single Rmost influential physician in modern medicine, having MATERIALS AND METHODS steered the profession away from centuries of metaphysical Rudolf Virchow’s dissertation de Rheumate Praesertim Corneae was translated from Latin by Leland J. Rather and is found in an appendix to a volume of letters Virchow wrote to Received for publication October 14, 2014; revision received October 29, his parents from 1839 through 1864.4 Literally translated “On 2014; accepted October 30, 2014. Published online ahead of print ” December 18, 2014. Rheumatism, Especially of the Cornea, the dissertation will From the Departments of *Ophthalmology, and †Pathology and Cell Biology, be referred to as rheumatism and the cornea. The text is Morsani College of Medicine, University of South Florida, Tampa, FL. approximately 7200 words and has no illustrations. After the The authors have no funding or conflicts of interest to disclose. preface, it is organized into 28 sections, many of which are Reprints: Curtis E. Margo, MD, MPH, Department of Ophthalmology, Morsani College of Medicine, University of South Florida, MDC 21, 12901 Bruce just a single paragraph. The translation is accompanied by B. Downs Blvd, Tampa, FL 33612 (e-mail: [email protected]). a 3-page forward by L. J. Rather, Emeritus Professor of Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved. Pathology at Stanford University. Cornea Volume 34, Number 2, February 2015 www.corneajrnl.com | 235 Margo and Harman Cornea Volume 34, Number 2, February 2015 currently accepted theory of pathogenesis, explicitly that a “morbid substance mixed in the blood is carried to various organs and excites in them an irritation that resembles inflammation.”4(p161) Traditional teaching had implicated acid as the irritating substance, but Virchow cited more recent research in medical chemistry by Justin Liebig (1803–1873) that incriminated albumin as the putative substance. He dismissed the importance of other causes of rheumatism such as aberrant electricity by not discussing them. Nearly half way through the dissertation, Virchow reviewed the anatomy of the cornea. Citing the work of others, he described the stroma as consisting of bundles of extremely delicate fibrils “that run everywhere in conjoined networks, leaving hollow areas of free spaces.”4(p167) The horizontal fibrils were covered by an epithelium. The fibrils are transparent and gathered together by lattices running in vertical and oblique directions. He described a “humor” within the cornea but stated that its origin was controversial. Nothing in the anatomic description of the cornea appeared to correspond to Descemet membrane or the endothelium. Virchow stated that the healthy cornea did not contain blood vessels, and later concluded that vascularization was patho- gnomonic of inflammation. The middle part of the dissertation was devoted to a discussion on rheumatism and the cornea. Virchow divides corneal involvement into 3 varieties: (1) simple, (2) kerato- rheumatism, and (3) torpid. In the simple variety, fever is rare and the cornea becomes cloudy, or whitish or bluish. He credits Jüngken with observing that the surface of the cornea is eroded, depressed, or elevated (the latter suggested to Virchow the possibility of phlyctenule). As the disease progressed, nerves are affected resulting in photophobia, miosis, pain, and tearing. In kerato-rheumatism, the substance that triggers the disorder enters the cornea and then provokes inflammation. Corneal vascularization characterizes the early stages of this variety, which explained why other clinicians have referred to it as rheumatic vascular keratitis. Virchow cited Jüngken who described the “corona of vessels” that surrounds the margin of the cornea as characteristic. As inflammation intensifies, these vessels can become confluent appearing as a “bloody fillet.” In the final stages of the disorder, the entire cornea is ’ FIGURE 1. obscured by vessels visible to the naked eye. To Virchow s Limestone monument honoring Rudolf Virchow in knowledge, no early stage of kerato-rheumatism had been Karlplatz, Berlin. The sculpture that caps the monument has provoked a variety of interpretations (personal collection of studied pathologically. the author). The third variety of corneal rheumatism was torpid, but which Jüngken called scrofulous keratitis. Virchow believed that this type of keratitis represented a chronic form of either RESULTS of the 2 previous varieties, but did not elaborate further on Virchow began his dissertation by providing background pathogenesis. on how he became interested in the subject of rheumatism and The remaining portion of the text described the chronic the eye through his medical school mentor Johann Christian nature of rheumatic keratitis, regardless of variety. Incomplete Jüngken (1794–1875). A surgeon at Charité Hospital, Jüngken, healing and abscess formation were 2 undesirable outcomes. cared for a number of persons having eye disease. Virchow Virchow drew on the similarities of rheumatic phlyctenae of the justified his study by explaining that “the rubric of ophthalmia” cornea and miliary rheumatism, arguing that phlyctenae of the for which ocular inflammations were collectively referred, was cornea are a form of rheumatic exanthema. It is unclear whether too broad a category for meaningful. He hoped to shed light on Virchow added any newly created information to the literature rheumatism of the cornea by separating it from other or simply reviewed and discussed what was already known. ophthalmias for specific analysis. After acknowledging that Virchow ended his dissertation abruptly with 2 rheumatism affects others parts of the body, he described the thoughts: First that “incomplete healing with metastases of 236 | www.corneajrnl.com Copyright Ó 2014 Wolters Kluwer Health, Inc. All rights
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