The discovery that tumors consisted of cells required the proof of cytology. Mainly German and
French scientists were involved in this research. No doubt that Paris was arguably the world center of
medicine in the first half of the nineteenth century. The new way of thinking, the "philosophy of
observation" became apparent with the storm of the French revolution in 1789. Francois Xavier Bichat
(1771-1802), the founder of the science of tissue, did not yet use the microscope. When Oliver Wendell
Holmes (1809-1894), later professor at Harvard, was a young physician working in Paris in 1833/34, he
came to know all the celebrities of the Paris Medical College of the period, yet could not discern any
microscope, "individuals had begun to use the instrument, but I never heard it alluded to by either
professors or students". In France, only outsiders began to use the microscope on plant and animal
tissue: Rene-Joachim H. Dutrochet (1776-1874) and Francois Vincent Raspail (1794-1878). In 1824,
Dutrochet published his observations: "Recherces anatomiques et physiologiques sur le structure intime des animaux et des vegetaux et sur la
motilite (Anatomical and physiological research on the internal structure of animals and plants
and on the mobility). He was convinced that not only plants but also the animal tissue consisted of
cells "cellules globuleuses" (globular cells).
Fifteen years later, in 1839, Theodor Sc(1810-1882) published his book "Microskopische Untersuchungen uber die Ubereinstimmung in der Struktur und dem Wachstume
der Tiere und Pflanzen" (Microscopical examinations on the accordance with structure and growth in
animals and plants) in Berlin. Histology and cytology gained a new basis by this epochal work. Schwann
was a student of Johannes Muller (1801-1858), the Berlin anatomist and physiologist. We owe to him the
first work on microscopy of tumors: "Uber den feineren Bau und die Formen der
krankhaften Geschwulste" (On the fine structure and the forms of morbid tumors) (Berlin, 1938).
What was Muller's purpose? He wrote: "Der Zweck einer microskopischen und
chemischen Analuse musste sein zu wissen, ob es innere, wesentliche Unterschiede der Geschwulste nach
ihrer Organisation und chemischen Zusammensetzung gibt, und wenn es solche gibt, sie
festuzustellen" (The purpose of the microscopical and chemical analysis should be to know whether
there are internal, essential differences of tumors according to their organization and chemical
composition, and if there are any, to come to know them). This purpose is still valid today. At the
time of Johannes Muller, however, microscopy was still in its infancy. There was only a speculation on
the origin of cells, e.g., arising from a liquid blastema.
Robert Remak (1815-1865), another Berlin student of Johannes Muller, proved in 1852-1854 that both
embryonic tissue and "krebshafte Geschwulste" (cancerous tumors) grew by
cell division. Soon after that, in 1855, Rudolf Virchow (1821-1902 coined the famous phrase "Omnis cellula a cellula" in Wurzburg.
It was known, of course, that there were benign and malignant tumors. At that time (1854), Virchow
also doubted whether the tumors could be exactly differentiated microscopically. The physician, of
course, yearned to differentiate between benign and malignant tumors in order to prognosticate for the
patient. Scientifically such a classification was thought to be just as little justifiable as the
differentiation between useful and toxic plants in botany.
The doctrine of Hermann Lebert (1813-1878) on the specificity of cancer cells dominated the
discussion on microscopic diagnosis of cancer in Paris. IN 1845, Lebert emphasized the variability of
cell and nuclear forms, the number and size of nuleoles in cancer cells defining: "Nous croyons pouvoir affirmer que le globule concereux a des characters tranches que le
distinguent de toutes autres especes de productions morbides" (We think being able to confirm that
the cancerous cell has definite characteristics distinguishing it from all other morbid conditions).
In 1851, Virchow opposed Lebert's opinion. He recognized that the structure of cancer cells,
especially the size of their nucleus and nuclear bodies, very frequently gave the best diagnostic clue.
But he had also seen such elements of tumors that could not be recognized as cancer. The famous Parisian
surgeon Alfred Armand Velpeau (1795-1867), for whom Lebert examined breast tumors, was also critical of
the morphologic specificity of cancer cells: "Au fit, le microscope et la cellule
cancereuse n'ont donc encore rien donne d'assez incontestable pur servir die base a la determination du
cirugien quand il s'agit d'exsterper ou de respecter les tumeurs de la mamelle" (1854) (in fact
the microscope and the cancer cell are still doubted and not useful to the surgeon whether to remove or
to leave the breast tumors).
Nevertheless Lebert's specific cancer cell was definitely supported by others. One of them was Paul
B Broca (1824-1880) in Paris, with his work "Traite des tumeurs" (1886)
(Treatment of tumors). In Edinburgh there was John Hughes Bennett (1812-1875) in his book " On cancerous
and cancroid growths" (1849) and, in the USA, Francis Donaldson (1823-1921) with his effusive paper:
"The practical application of the microscope to the diagnosis of cancer" (1853).
From September 1854 to January 1855, at the Academie de Medecine, Paris there was a continuing
discussion on the usefulness of the microscope in tumor diagnostics and on the curability of cancer.
Cancroids, differentiated from "genuine" cancer by Lebert, were discussed also. With a German-French
cooperation between pathologist and surgeon – very uncommon at that time – R. Virchow and A. Velpeau
published together on this topic" "Trois observations des tumeurs epitheliales
generalisees" (1855) (Three observations on epithelial generalized tumors). The term "cancroid"
used for many different tumor forms and hardly defined, caused more confusion than clarity. The surgeon
Velpeau, however, had no doubts: "Ansi, pas d'illusion de cancroide est un
cancer" (Consequently, no illusion, the cancroid is a cancer).
H. Lebert, since 1853, Professor at the medical Clinic in Zurich, and Rudolf Virchow remained friends
in spite of their opposite opinion of the microscopic specificity of cancer cells. Lebert's works from
Paris were well recognized by Virchow and published in his Archives. About 30 years later, in 1888,
Virchow again referred to this dispute with the "Paris Micrograph School" and said that the specific
cancer cell of Lebert had slowly been buried for decades, the history of the microscopic tumor diagnostic
remained a history of errors, not least by Virchow himself. To date, that history and the continuing
role of the microscope have not lost their importance.
