The first cytopathologist

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The 1830s were the formative years in biology, physiology, and cytology. Researchers in the experimental and anatomic pathology laboratories disabused fallacious hypotheses of the 1700s that internal organs of the body were chiefly composed of fibers, nerves, and vessels; were the ultimate building blocks of life; and functioned independently in disease and health. Technical improvements in microscopes in the early 1800s paved the way to the accumulation of knowledge of submicroscopic structures first in plants and later in animal tissues. Johannes Muller (1801-1858), a German physician, had a solid education in zoology, biology, embryology, physiology, and macroscopic pathology. He was a protean laboratory investigator but his forte was microscopy. He was appointed as professor and chair of the Department of Anatomy, Physiology, and Pathology at the University of Berlin in 1833 (Fig. l). Muller 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 advanced the concept of nucleated cells, and Matthias Schleiden (18041881), who collaborated with Muller’s assistant, Theodor Schwann (1810-1882), to establish the cell theory in 1838. Muller was an adroit microscopist. He delineated, among other things, the cellular nature of the notochord, the radial (Muller) fibers of the retina and the paramesonephric duct (Mullerian duct). His inquisitive mind and curiosity led him to themicroscopyof tumors. In his compendious treatise on tumors and cancers, published in 1838, Muller provided a systematic analysis of the microscopic features of benign and malignant