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Address correspondence to Steven I. Hajdu, M.D., 1759Drumcliff Court, Westlake Village, CA 91361-1636, USA; tel

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A Note from History:The First Cellular Pathologists

Steven I. Hajdu

Keywords: History of pathology, history of cytology, Hermann Lebert, Julius Vogel

Fig. 1. Plate VIII from Vogel’s Pathological Anatomy of theHuman Body [2] (For descriptions of the figures, see the text.)

By all rights, Julius Vogel (1814-1880) and HermannLebert (1813-1878) should be household names topathologists, cytologists, and all who are interestedin the history of science and medicine. But, due togross neglect by historians, Vogel’s and Lebert’s majorcontributions to laboratory science and medicinehave remained largely unappreciated for 150 years.Readers of the Annals may find it disappointing, asI did, to observe that Morton’s monumental MedicalBibliography does not include either Vogel or Lebertamong the >7000 entries [1].

Julius Vogel, a disciple of Johannes Müller, wasprofessor of pathology at Göttingen in Germany.He was a skillful microscopist and was expert in basicsciences as well as anatomic and clinical pathology.He was one of the first to attempt grafting tumorsin animals. Within 5 years after Theodor Schwann(1810-1882) and Matthias Schleiden (1804-1881)announced the cell theory and Johannes Müller(1801-1858) finished his monograph on cancer,Julius Vogel’s pioneering book on PathologicalAnatomy was published in Berlin. Vogel’s text wasrapidly translated from German into English andwas published in London and Philadelphia in 1847[2]. George E. Day, the translator, wrote that thelaborious translation had been undertaken becauseof the lack of any book in English that embracedthe recent discoveries in chemistry and pathology.

Vogel’s Pathological Anatomy [2] was the earliestcomprehensive pathology text that contained macroscopic, histopathologic, and cytopathologic

illustrations. The book consists of 482 pages of text,10 plates of illustrations with >100 figures; and 42pages of legends for the figures. In addition to adozen illustrations of surgical specimens, histologic

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sections, concretions, and crystals, the bulk of thefigures show benign and malignant cells. Among thefigures are cells from tuberculous granuloma,cirrhotic and fatty liver, granulation tissue, gangreneof the foot, blood and blood clot, hyperplastic lymphnodes, nasal polyp, parotid tumor, enchondroma,papillary tumor of the bladder, polypoid tumor ofthe uterus, lipoma, and carcinomas of the breast,lung, uterus, and testis. Vogel also included cells fromsputum in cases of pneumonia, bronchitis, andtracheitis and cells from pleural and pericardialeffusions.

The 11 figures on Plate VIII (Fig. 1) are printedwith 9 pages of detailed microscopic descriptions.Vogel’s legends state that Figs. 1-3 show carcinomaof the testis (malignant germ cell tumor). The cellsare variable in size and form, with round (a), oval(b), candate (f ), and entirely irregular forms. In somenuclei, big nucleoli are visible (c, h). Fig. 2 showsfibers that remained after sections were treated withacetic acid. Figs. 3 (a) and (b) show tumor cells insidea capsule (seminoma?). Figs 4 and 5 are from a 14-pound carcinoma of the liver (hepatoma?). Figs. 6and 7 illustrate a soft cancer of the knee joint of ayoung man (giant cell tumor?). Fig. 8 shows cancercells from a scirrhus carcinoma of the breast(infiltrating duct carcinoma) and Fig. 9 shows tumorcells from retroperitoneal and pulmonary metastasesof the testicular primary tumor illustrated in Figs.1-3. Vogel gives credit to Johannes Müller for Fig.10, which shows the reticular stroma of a breastcarcinoma, and Fig. 11, which shows an alveolarcarcinoma (adenocarcinoma) of the stomach.

The other forgotten pathologist is HermannLebert. He was born in Germany but did most ofhis clinical work, writing, and teaching while he wasProfessor of Pathology in Paris and later in Zurich.Lebert lectured and wrote in French. His threelandmark books were published in Paris from 1845to 1857 [3-5].

Lebert’s Physiologie Pathologique [3] contains>1000 pages and an atlas with 249 figures (somehand colored) on 22 page-size plates. The legendsfor the figures are very detailed and occupy 33 pages.The text and figures are almost equally devoted toinflammatory changes, infectious lesions, benigntumors, and cancers, as seen with the naked eye and

under the microscope. The most notable illustrationsin the atlas are brain abscess, tuberculous granulomain the brain, tuberculous lymphadenitis, sebaceouscysts, cholesteatoma, melanosis coli, echinococcusin the liver (with hooklets and all), and ciliated andnon-ciliated (metaplastic) cells in sputum. Thefigures of tumors include cells from squamouspapilloma and condyloma, pulmonary chondroidlesions (chondroid hamartoma?), fibroadenoma andphyllodes tumor of the breast, chondromatosis ofthe fingers, dermoid cyst of the ovary, meningioma,fibroma of the skin (dermatofibrosarcoma), tumorof the knee joint (villonodular synovitis), post-amputation tumor (amputation neuroma), cancerof the uterine cervix (squamous carcinoma), cancerof the colon (adenocarcinoma), cancers of themaxilla, lung, and buccal mucosa, metastatic gastric

Fig. 2. Plate XIX from Lebert’s Physiologie Pathologique [3](For descriptions of figures, see the text.)

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cancer in the liver, sarcoma of the uterus, and spindlecell sarcoma of soft tissues.

Fig. 2 of this commentary (Plate XIX fromLebert’s Physiologie Pathologique [3]) shows acombination of histologic sections and isolated cellsin 11 drawings that are identified as Figs. 1 to 11.In the plate, Figs. 1 and 3 to 6 show histologicsections and cells of breast cancer. Fig. 2 showscrystals from a breast cancer. The legend callsattention, in Fig. 6, to enlarged nuclei (b), macro-nucleoli (c), and cancer cells infiltrating fat (e andf ). Figs. 7-11 show histologic sections and cells ofan encephaloid tumor (germ cell tumor) of the testis.Giant cells are shown in Figs. 10 and 11.

For their microscopic examinations, Vogel andLebert sliced fresh tissues with a razor-like knife andprepared cell samples (smears) by scraping, washing,or by squeezing the tissue slices. Samples from fluidswere placed on glass slides without preservatives.Most microscopic preparations were unstained, butoccasionally a drop of iodine was applied as a stain.

In his text on cancer (1851), Lebert [4] gaveconcise summaries and organ specific descriptionsof all forms of tumors. The book consists of 885

pages and discusses the dietary, surgical, and medicaltreatment of cancer. In 1857, Lebert [5] publisheda comprehensive pathology text in two volumes thatcovered everything that was known at that timeabout anatomic pathology, as well as discussions onclinical pathology.

It is fitting to emphasize the crucial importanceof Vogel’s and Lebert’s roles in developing theconcepts of cellular pathology. Vogel and Lebertestablished the solid basis on which RudolphVirchow, in the 1860s, built his general theory aboutcells.

References

1. Norman JM. Morton’s Medical Bibliography. UniversityPress, Cambridge, 1991.

2. Vogel J. The Pathological Anatomy of the Human Body.(Translated from German by George E. Day.) Lea andBlanchard, Philadelphia, 1847.

3. Lebert H. Physiologie Pathologique ou Récherches Clinique,Experimentales et Microscopiques. Bailliére, Paris, 1845.

4. Lebert H. Traité Pratique des Maladies Cancéreuses et desAffections Curables Confondues aver le Cancer. Bailliére,Paris, 1851.

5. Lebert H. Traité d´Anatomie Pathologique Générale etSpéciale. Bailliére, Paris, 1857.

The first cellular pathologists: Hermann Lebert and Julius Vogel

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