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Clin. Cardiol. 23, 550–552 (2000)
This section edited by J. Willis Hurst, M.D., and W. Bruce Fye, M.D., M.A.
Hector O. Ventura, M.D.
Section of Cardiology, Department of Medicine, Tulane University Hospital and Clinic, New Orleans, Louisiana, USA
Fig. 1 Rudolph Ludwig Carl Virchow, 1821–1902.
Source: Photograph reproduced from Ref. No. 2 (public domain).
In the mid-nineteenth century, the fundamental role of the "sick cell" as the essence of all diseases was not known. This concept had to await introduction until the renowned German physician and pathologist Rudolph Virchow1 published his masterpiece Cellular Pathology as Based upon Physiological and Pathological Histology. He wrote that the cell is "the ultimate irreducible form of every living element, and . . . from it emanate all the activities of life both in health and in sickness." He was to become one of the most important physicians of his time. His influence in medicine was to be felt for many years. Utilizing data from the multiple dissections he performed throughout the years, Virchow derived a general theory of the disease processes and subsequently fought for its acceptance.
Rudolph Ludwig Carl Virchow (Fig. 1) was born on October 13, 1821, in Schivelbein, Pomerania. In 1838 he won a scholarship to study medicine at the Friedrich-Wilhelms Institute in Berlin and received his medical degree in 1843.1 During medical school, Virchow was inspired by the work of Johannes Peter Müller, whose researches in physiology were leading to important new advances in studies of microscopic and pathologic anatomy.
After graduation, Virchow became an intern at Berlin's Charité Hospital, a very important institution in medicine at the time. It was there that Virchow began his lifelong career in pathology. He served as a prosector of pathology, performing dissections for anatomical demonstrations, and in 1847 he became a privadozent, which allowed him to become a teacher. His scientific endeavors enabled him to study the inflammatory theory of atherosclerosis, to describe that pus was made up of white blood cells, and to define leukemia as a disease.1 Perhaps a more important contribution was the introduction of new methods of research, namely, experimental pathology. With his friend Bruno Reinhardt, he also created a new journal, Archiv für pathologische Anatomie und Physiologie, und für klinische Medizin, today known as Virchow's Archives. By no means was he detached from the social unrest characteristic of the 1840s. Virchow published a weekly paper, Die Medizinische Reform, that had a markedly political orientation, and his editorial comments as well as his articles annoyed the German authorities. He became politically engaged after investigating a typhus epidemic in Upper Silesia, which was the home to an oppressed Polish minority in Prussia. As part of a commission formed by the government following an exposé in the press, Virchow traveled to the region, reported that the essential basis for the epidemic was social, and prescribed "democracy, education, freedom, and prosperity."2 For his harsh antiroyalist views and his political stance, his salary was cut off and therefore he was effectively removed from the Charité. He left Berlin to occupy the new chair of pathologic anatomy at Würzburg. There, he spent seven years building a reputation as a teacher and researcher. He not only was the author of many papers on pathologic anatomy but also had begun the publication of his monumental Handbuch der speziellen Pathologie und Therapie. In addition, during his tenure at Würzburg, he had begun to formulate his now famous theory of cellular pathology. Virchow's importance at Würzburg also can be measured by the increase in attendance at the school and by the students whom he taught. Names such as Friedreich, Haeckel, Rindfleisch, Gegenbaur, and Kussmaul later became prominent physicians.3
In 1856, Virchow was recalled to Berlin to become Professor Ordinarius of Pathology, and he dedicated within the great Charité the first institutional building ever solely devoted to study and research in this branch of medicine. Virchow had not been long in Berlin before he established the capital's medical statistics, particularly those related to housing and death rate, infant mortality, and causes of death. The limits of medicine were not enough for this man of tremendous energy and variety; therefore he became a member of the municipal council in 1861 and in 1862 he was elected to the Lower House with "Kulturkampf" as a slogan. In addition to his medical duties at the Charité he gave personal attention to army sanitation from 1866 to 1870 previous to the Franco-Prussian war. In 1870, he took the first hospital train to France and back home; during the remainder of the conflict he fought epidemics among soldiers in the field and prevented other epidemics in the barracks. After the war Virchow played a leading role in the construction of Moabit, Friedrichsheim, and urban city hospitals. In the same year, 1871, he designed the model sanitary system for Berlin. His gradually widening interests led him as far as ancient Troy in 1879, and to Spain and Portugal in 1880 in pursuit of his studies in anthropology and archeology. In 1880, at the age of 60 years, he entered the Reichstag, arraying himself immediately among Bismarck's bitterest opponents. All these activities and more occurred while he was paving the way to the foundation of modern medicine. Small in stature, he has been described as "an elastic, professional figure, with snappy black eyes, quick in mind and body, with a touch of Slav, something of a martinet in the morgue or lecture room, often transfixing inattention or incompetence with a flash of sarcasm."4 His working technique was also very impressive. No detail was too insignificant for his personal attention; he possessed a meticulous sense of order and did not know confusion or hurry; indeed, there was practically no time when a humblest research worker, after failing to secure an assistant to look through his microscope, found him inaccessible. His professional activities continued until his eightieth birthday. He was in full possession of all his faculties, able to appreciate and enjoy a national holiday in his honor, commendations from governments or scientific societies around the world, and the great gold medal of science from the Kaiser himself. Three years before his death he dedicated the celebrated pathologic museum to which he had donated his own personally assembled collection of more than 23,000 specimens. His productive life came to an end on September 5, 1902, at age 81. While attempting to board a streetcar in Berlin, he slipped, fell, and fractured his femur. He subsequently died of complications following this accident. The funeral ceremonies were held in the Berlin Rathaus.3
Virchow's contributions to medicine were numerous. He published an incredible number of studies from 1843 to 1901. These were assembled by Schwalbe immediately after Virchow's death. Virchow's bibliography required 118 pages and the total number of publications was 2,124. Among the more outstanding of his major contributions to scientific literature, some that molded medical thought for all times must be mentioned: Archiv, 1847; Virchow's Jahresbericht, 1851; Handbuch der speziellen Pathologie und Therapie, 1854; Die Cellularpathologie, 1858; Die Krankhaften Geschwuelste, 1863, 1865, and 1867; and Sectionstechnik, 1876. "Experiment" he wrote, "is the ultimate court of the science of pathologic physiology."5 He established the study of normal structures as key to understanding pathologic ones. He was the first to develop a necropsy technique that disturbed structural relations to the minimal degree and favored diagnosis to the maximum. Early on in his career, he demonstrated the importance of fibrin in the blood coagulation process and he coined the terms embolism and thrombosis. It was early in the 1850s that he developed the cell doctrine and the fundamental principles of cellular pathology. With the appearance of Cellular Pathology as Based upon Physiological and Pathological Histology, modern clinical medicine was founded. "What Virchow accomplished in Cellular Pathology," writes physician and author Sherwin Nuland,5 "was nothing less than to enunciate the principles upon which medical research would be based for the next hundred years and more." Inspired by Theodore Schwann's cellular theory, Virchow corrected and extended it. He called the cell the fundamental unit of life and hypothesized on the existence of cell division to account for reproduction. He demonstrated that muscle and bone are composed of cells, that connective tissue was mixed with nerve cells in the spinal cord and brain, and he developed a basic classification of cellular tissue. In summary, Virchow formulated what came to be known as the cell doctrine: Ommis cellula e cellula (every cell arises from another cell). He wrote, "Development cannot cease to be continuous, because no particular generation can start a fresh series of developments. We must reduce all tissues to a single simple element, the cell" . . . "the ultimate irreducible form of every living element, and . . . from it emanate all the activities of life both in health and in sickness."2
In the field of cardiology, Virchow made a seminal contribution to the understanding of atherosclerosis.6 Until Virchow's, several theories on the pathogenesis of atherosclerosis had been proposed. The most popular at the time was the thrombogenic theory, championed by Rokitansky in 1841. He proposed that the deposits observed in the inner layer of the arterial wall derived primarily from fibrin and other blood elements rather than being the result of a purulent process. Subsequently, the atheroma resulted from the degeneration of the fibrin and other blood proteins as a result of a preexisting crasis of the blood, and finally these deposits were modified toward a pulpy mass containing cholesterol crystals and fatty globules. This theory came under attack by Virchow with the presentation of his inflammatory theory a few years later. His description of the pathogenesis of atherosclerosis was an in-depth study of the histologic characteristics of the atherosclerotic lesion in all its stages. First and foremost, he recognized that the atherosclerotic lesion was situated within or underneath the intimal layer of the vasculature and that the primary deposit occurred by imbibition of certain blood elements. Accordingly, the next stage was due to a softening of the connective tissue matrix at the site of deposition followed by an active proliferation within the intima. A fatty metamorphosis of the connective tissue cells followed, which ultimately led to intimal thickening. In attempting to explain the nature of the process, Virchow utilized the name of "endarteritis deformans." By this he meant that the atheroma was a product of an inflammatory process within the intima and that the fibrous thickening evolved as a consequence of a reactive fibrosis induced by proliferating connective tissue cells within the intima. He maintained that mechanical forces initiated the irritative stimulus and that the endarteritis was part of a repair mechanism. His theory has elements that are acceptable to current thinking, but it also has features that have been invalidated. However, suffice it to say that Virchow's concept of local intima injury as the initiating "irritative" stimulus is still accepted and it has been extended to include other factors besides mechanical factors. In 1864, two years after his pupil Von Recklinghausen described the association of numerous rhabdomyomas of the heart and sclerotic changes in the brain, Virchow reported the case of a child with brain tuberous sclerosis and rhabdomyoma of the heart whose sister died of a cerebral tumor. This was the first hint of the familial nature of the disease.7
Another very important contribution to medicine was the instruction of many famous physicians who have carried forward the torch of the master. These names include pathologists such as Von Recklinghausen, Klebs, Cohnheim, Ponfick, Orth, and Grawitz, and chemists such as Hoppe-Seyler and Salkowski. Virchow's conclusions transmitted by his associates and followers were to make every student around the world cell-minded.3 Here in the United States, the influence of Dr. Welch and Dr. Osler has been paramount in pathology and medicine for many decades. Welch also drew inspiration from Cohnheim, who himself was part of the small group taught by Virchow. Osler was inspired by Virchow when he spent three months at the Charité observing clinics and Virchow himself. He writes in a letter " . . . But it is the master mind of Virchow, and the splendid Pathological Institute which rises like a branch hospital in the grounds of the Charité, that specially attracts foreign students to Berlin."8a
Rudolph Virchow created the basis for experimental pathology and made observations in medicine that have stood the passing of time. His life was dedicated not only to the study of medicine but also to patients, since he believed that physicians "ought to be the attorneys for the poor." His contributions to human knowledge went beyond medicine and encompassed other branches of the humanities. In an address about Virchow's life, on the occasion of the celebration of Virchow's seventieth birthday, William Osler wrote about his personal association with " . . . the father of modern pathology." Regarding the importance of Virchow's work, he wrote " . . . The influence of his work has been deep and far reaching, and in one way or another has been felt by each one of us."8b Perhaps his life can be best summarized by his biographer at the time of his death, "Germany would complain of having lost four great men at once: her leading pathologist, her leading anthropologist, her leading sanitarian, and her leading liberal."2
Address for reprints:
Hector O. Ventura, M.D.
Tulane University Hospital and Clinic
1415 Tulane Avenue, HC-19
New Orleans, LA 70112, USA
Received: July 23, 1999
Accepted: July 26, 1999