What is Neoplasia?
The Cancer J. 4:4:228,1991

A little booklet "The story of an Idea" by A. Besredka (1) unveils a fascinating chapter of medical history. It describes the controversy between Elie Metchnikoff and contemporary pathologists led by Rudolf Virchow, on the role of macrophages in inflammation. It is illuminating to follow the confrontation between outstanding minds on an issue that today seems to be understood. Yet the lesson to be learned is relevant also to modern controversies.

Cohnheim and Samuel maintained that inflammation started from a molecular lesion of the vascular wall, followed by passive diapedesis of cells, and manifested clinically by "rubor". Metchnikoff realized that not all factors in inflammation are equally significant and divided them into essential and accessory. Some organisms, e.g., Echinoderms, in which the vascular system is open respond to infection by mobilizing "ameboid mesodermal cells" and this inflammatory process is unaccompanied by reddening. He maintained that cell mobilization ought therefore be regarded as primary factor of inflammation and vascular response, as secondary. Leading scientists like Rindfleisch, Waldeyer and Klebs, believed that immunity was a humoral function, and "there was nothing better than leukocytes to support the growth of microbes". When Virchow heard Metchnikoff's interpretation on the role of white blood cells in immunity he answered:" We pathologists think and teach the exact opposite: The microbes are well off within white blood cells and use them as means of transport for their dissemination throughout the host."

Both opponents agreed that after entering the body, anthrax bacilli penetrate white blood cells. As the disease progresses, more and more leukocytes become infested with rods, until the animal dies. Yet they differed in their interpretation of leukocyte infestation. Virchow maintained that the rods thrive, while Metchnikoff said that they succumb. The end of the story is known. This is why it is instructive to apply similar reasoning to unresolved controversies, like the meaning of neoplasia. First describe what is observed, group the factors into primary and secondary, and evaluate different interpretations.

Neoplasia starts as a cell clump that grows and multiplies. As disease progresses, more and more colonies spread throughout the body until the patient dies. There exists hardly any controversy on the interpretation of neoplasia. It is regarded as parasite destined to kill its host. In order to explore its possible benefits, we shall apply Metchnikoff's reasoning and group neoplastic manifestations into primary and secondary. Pre-clinical neoplasia will be regarded as primary factor, while clinical manifestations of neoplasia, as secondary. As long as neoplasia and micrometastasis remain undetected they do not cause any apparent damage to the organism otherwise they would be detected clinically and grouped as secondary manifestations.

Virchow regarded inflammation as dangerous since it was associated with a threat to the patient's life. Yet inflammation itself does not pose any threat, only its secondary manifestations, e.g., an abscess. Unless an intra-cranial abscess is drained the patient is doomed to die, in spite of the fact that inflammation is protective. By the same token, primary neoplasia might be essentially protective, while secondary factors, e.g., intracranial tumor, pose the real threat. It is striking that pain, the ubiquitous alarm mechanism of our body, is triggered only by secondary neoplastic manifestations, otherwise cancer screening would be much easier.

Could neoplasia be essentially protective while only its secondary manifestations endanger the patient? Perhaps somewhere in the ocean there exists a creature that lacks secondary neoplastic factors and thrives on primary neoplasia, waiting to be unveiled by a Metchnikoff.


1 Besredka A. The story of an idea. Translated from French by Riverson A, and Oestereicher R. Monographs of Pasteur Institute Masson & Co Editors, 1921.

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