The Death of the Humoral Theory of Disease

When last we left the humoral theory of disease, it had survived the debunking efforts of Vesalius and Baillie. Black bile might not exist, but investigators found other body fluids besides blood, phlegm, and yellow bile to take its place. In the seventeenth century, an Italian physician named Gaspare Aselli discovered the small lymphatic channels, the conduits through which the extracellular fluid called lymph flows and eventually returns via the thoracic duct to the circulation of the blood. Aselli proposed that abnormalities of lymph might account for cancer; after all, tumors often appeared within the bead-like structures arrayed along the lymphatics that we know as lymph nodes. Such was the staying power of this paradigm of human disease that the humoral theory hung around until the middle of the nineteenth century when the development of cell theory finally put it down for good.

The independent but complementary observations of Theodor Schwann and Mattias Schleiden in animal and plant tissues led the two friends in 1838 to propose the fundamental axioms of cell theory: all living organisms are composed of cells, and cells are the basic units of life. A few decades later, the renowned Prussian pathologist Rudolf Virchow added the third axiom that all cells come from pre-existing cells. Virchow was also the first to suggest that cancer cells arise from previously normal cells, although his ideas about how this might occur proved erroneous. By the end of the 19th century, the combined observations of Robert Koch, Louis Pasteur, and Robert Lister established the germ theory of disease, and the obituary of the humoral theory of disease was written.

But what of cancer? Could the germ theory account for this disease? An infectious cause for cancer was not immediately apparent, although researcher Peyton Rous discovered the first recognized carcinogenic (cancer-inducing) virus in the 1910s. This virus transmitted sarcoma, a type of cancer affecting muscles, bone, and similar tissues, in chickens. Subsequent work has implicated several other viruses in human cancers: Epstein-Barr virus in a particularly aggressive type of lymphoma named for its describer, Dennis Burkett; human papilloma virus, linked to many cancers of the cervix, anus, and head and neck region; hepatitis B and C virus and primary liver cancers; and one of the herpesviruses and an unusual skin cancer called Kaposi sarcoma. But I am now well ahead of myself in my pursuit of explanations for cancer.

Medical observers had determined that cancers often developed in persons exposed to various environmental or industrial substances. Percivall Pott gets the credit for being the first to make the link after observing the plight of young chimney sweeps, chronically covered in soot that often accumulated in the folds of undergarments, susceptible to skin cancers involving the genitals. Several of the early researchers who worked with radioactive substances, such as Pierre and Marie Curie, succumbed to cancers if they did not first die of radiation poisoning. And burgeoning industrialization in the west brought new health perils to workers, including cancers induced by long-term exposure to various chemicals.

That cancer has several different causes became increasingly clear. What remained elusive was an explanation. How do we get from cause to effect? What is the nature of cancer? If not the effect of “evil” humors, if not excessive lymph accumulation, if not (mostly) germs, what? To this we turn next.