Annals of Clinical & Laboratory Science 34:355-356 (2004)
© 2004 Association of Clinical Scientists
The First Tumor Pathologist
Steven I. Hajdu
Address correspondence to Steven I. Hajdu, M.D., 1759 Drumcliff Court, Westlake Village, California 91361-1636; tel 805 496 0691; fax 805 496 0620.
Keywords: history of science, history of pathology, tumors, Johannes Müller
In the 18th century, tumors and cancers were described and defined in a medical dictionary as they appeared to the naked eye [1]. Nobody collected tissue samples for microscopic examination until Johannes Müller (1801–1858) (Fig. 1
) and his assistants began their studies in Berlin in 1833.
Müller was appointed as professor and chairman of the Department of Anatomy, Physiology and Pathology at the University of Berlin in 1833. He had a solid education in zoology, biology, embryology, comparative anatomy, physiology, chemistry, and pathology [2]. Among his laboratory staff were histologists– Theodor Schwann (1810–1882), Jacob Henle (1809–1885), Rudolph Kölliker (1817–1905), and Robert Remak (1815–1865), physiologists– Hermann Helmholtz (1821–1894), and Du Bois-Reymond (1818–1896), and a pathologist– Rudolph Virchow (1821–1902) [3].
Müller and his coterie of laboratory physicians were familiar with the work of botanists and plant physiologists such as Robert Brown (1773–1858), who in 1831 established the concept of nucleated cells, and Matthias Schleiden (1804–1881), who collaborated with Schwann to establish the cell theory in 1838 [3]. Müller’s laboratory had the latest achromatic compound microscopes, which permitted visualization of objects as small as one µm. Müller insisted that his assistants all become skilled microscopists. He, himself, before he focused on tumor pathology, was occupied with embryology and physiology [2]. He discovered the cellular nature of the notochord and achieved the chemical isolation of chondrin and gluten. He described the radial (Müller) fibers of the retina and gave an explanation of color vision; he confirmed by experimentation the Bell-Magendie concept of spinal nerve roots, and suggested that fever is a nervous reflex [3]. He discovered the paramesonephric duct (Müllerian duct) and deduced that this duct forms the uterine tubes and certain vestigial pelvic nests. This discovery led to the recognition of mixed mesodermal (Müllerian) tumors of the female pelvic organs [4]. While his handbook of Human Physiology [5] was in press, he turned to the microscopy of tumors.
In his monograph on cancer [6], published in Berlin in 1838, Müller provided a systematic analysis of the microscopic features of benign and malignant human neoplasms. An English translation was published in 1840 [7]. Müller attributed cancer to formation of new cells inside a diseased organ, with a potential to spread to other parts of the body through vessels (metastasis). He associated cancer with aging and believed in the regression of cancer by necrosis (apoptosis)[6,7]. He distinguished microscopically carcinoma simplex or fibrosum (scirrhous or squamous carcinoma), carcinoma reticulare, carcinoma alveolare (adenocarcinoma), carcinoma medullare, carcinoma fasciculatum (spindle cell carcinoma), and carcinoma melanodes (pigmented melanoma). As to connective tissue tumors, he described enchondroma, osteoma, myxoid and simple lipomas, cystosarcoma of the breast, tumor fibrosus (desmoid tumor), chondroscarcoma, and osteosarcoma [6,7]. In his book [6] there are 4 plates with over 100 drawings illustrating the microscopy of cancers, including breast carcinoma, melanoma, parotid tumor, chondroma, chondrosarcoma, and osteosarcoma (Figs. 2,3).
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Fig. 2. Mononucleated and binucleated cells from a very hard mammary carcinoma simplex (Plate 1, Fig. 14, of Müller’s book on cancer [6].
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Fig. 3. Tumor cells from a soft, cystic osteosarcoma of the mandible. (Plate II, Fig. 17, of Müller’s book on cancer [6].
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Although Müller observed that tumor tissues have their analogy in normal tissues, he erroneously concluded that cancer developed not from normal tissue but from germ cells that are scattered among normal tissue elements. Although he was able to distinguish many tumors by microscopic appearance, his limited experience in tumor microscopy is shown by his statement that carcinomas in their most intimate cellular features do not differ from the tissue elements of benign tumors. He added that microscopic and chemical studies are not definitive enough for the diagnosis of carcinoma and that one must depend on its clinical behavior to determine whether a tumor is benign or malignant [6,7].
Müller’s hobby was reading history. In 1848, while serving as rector of the University of Berlin, he sided with conservatives and was unsympathetic with the students’ revolutionary movement [4]. He suddenly resigned and went into retirement at age 47. After his resignation, several people had to be appointed to fill the positions he had held alone [2]. Although his former assistants retained lifelong loyalty to Müller, his bouts of depression became progressively more frequent and prolonged. He died alone at age 57, possibly from suicide [4].
During his lifetime, Müller received numerous awards and recognitions. He was a member of many prestigeous societies including the Philosophical Society of Philadelphia and the Academy of Arts and Sciences of Boston [3].
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References
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- Motherby G. A New Medical Dictionary or General Repository of Physic Containing an Explanation of the Terms. J. Johnson, London, 1791.
- Garrison FH. An Introduction to the History of Medicine. Saunders, Philadelphia, 1929.
- Robins V. The Story of Medicine. Tudor Co, New York, 1931.
- Castiglioni A. Histoire de la Médicine, Payot, Paris, 1931.
- Müller J. Handbuch der Physiologie des Menschen. Hölscher, Coblenz, 1833–1838.
- Müller J. Ueber den feinern Bau und die Formen der krankhaften Geschwülste, G. Reimer, Berlin, 1838.
- Müller J. On the Nature and Structural Characteristics of Cancer. (English translation by C West). Sherwood, Gilbert and Piper, London 1840.
This article has been cited by other articles:
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S. I. Hajdu
Samuel D. Gross of Philadelphia: Pathologist, Surgeon, and Medical Historian
Ann. Clin. Lab. Sci.,
January 1, 2007;
37(1):
102 - 104.
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