Walther Flemming on histology in medicine 1878: a newly discovered letter to his father.

Histology is a child of the 19th century, and its status in medicine was long in doubt. Was "microscopic anatomy" to be viewed as a refinement of the traditional discipline or as a technically complex subject of doubtful practical value? This was one of the questions that faced the commission charged with reforming examinations in German medical schools in 1878. One of its members, Carl Friedrich Flemming [1799-1880], was able to refer this matter to an acknowledged expert, his son Walther Flemming, who was Professor of Anatomy and Histology at the University of Kiel. Walther's views are contained in a letter that was recently discovered among Carl Friedrich's papers held in the State Library of Mecklenburg-Vorpommern in Schwerin. To the best of our knowledge, this letter is the only surviving piece of personal correspondence from the hand of Walther Flemming, one of the most distinguished biologists of his time. The original text, together with an annotated English translation, is published here for the first time. The letter throws new light on Flemming's attitudes to medical education, and also illuminates his relationship with his father, himself a figure of considerable stature in psychiatric medicine in 19th-century Germany. The younger Flemming [1843-1905], an acknowledged master of microscopy, made his most distinguished contributions to the field we now call cell biology. In addition to the terms chromatin and mitosis, we owe to him the first comprehensive account of the latter, as well as the fundamental insight that meiosis involves two successive divisions.

Reappraisal of the Hansemann-Boveri hypothesis on the origin of tumors.

Cancer is now known to be a genetic disease. In tumor development, cell nuclei undergo mutations, which can result in cytologically visible chromosome aberrations. The aneuploid errors may involve amplification or deletion of whole chromosomes or segments thereof. David Hansemann [1858-1920] and Theodor Boveri [1862-1915] were major contributors to early debates on the relationship between chromosomal defects, tumorigenesis and malignancies. In 1890, Hansemann observed asymmetrical nuclear divisions in human epithelial cancers. In these abnormal, but bipolar, divisions, a fraction of the chromosomes fails to segregate properly. Hansemann carefully documented the occurrence of asymmetric divisions in a wide variety of tumors. However, he remained a lifelong skeptic with regard to whether such events could be considered the underlying cause of tumors. Almost a quarter of a century after Hansemann's initial observations, Boveri considered the origin of tumors based on his earlier recognition of the functional specificity of each chromosome. He also explicitly drew on Hansemann's observations in proposing a model for tumorigenesis. Its central tenet was that a tumor typically originates from a single cell that has inherited a defined, but incorrectly combined, set of chromosomes. The rare occurrence of a pluripolar spindle represented Boveri's paradigm for a type of abnormal mitosis that can produce a host of random chromosomal combinations. He suggested that some of these combinations will induce tumorous transformation, and will inevitably arise occasionally. Since pluripolar and unbalanced bipolar divisions fail to distribute the hereditary chromatic material correctly, both of these mechanisms can give rise to tumor progenitors.