From the Suitcase: Peyton Rous (1910 & 1911).

Peyton Rous had just joined the Rockefeller Institute (forerunner to Rockefeller University) in 1909, when he was visited by a farmer with a sick bird. A chicken’s illness would set Rous on the road to one of oncology’s most important discoveries, the realization that viruses can cause cancer- a finding so controversial that it would take the Nobel committee 50 years to recognize it.

Below are excerpts from Rous’ seminal 1910 and 1911 JEM papers (The Journal of Experimental Medicine’s online archives go back to 1896, and all papers older than 6 months are open access).

“The tumor here reported was found in a barred Plymouth Rock hen of light color and pure blood. It had existed for some two months before the fowl was brought to the laboratory”.

chicken

The patient (from Rous, 1910).

Transmissible, or infectious tumors had been noted before:

“(…) there have since been discovered a number of transmissible new growths of unusual behavior, among them a sarcoma of the dog, transmissible at coitus (Sticker, Ewing), an endemic carcinoma of fishes (Plehn, Pick, Gaylord), and a new growth of hares (yon Dungern and Coca), transplantable to animals of another species.”

In his 1910 paper, Rous created a reliable tumor transplantation system- in the process facing the complex problems of transplantation immunity:

“This was accomplished by the use of fowls of pure blood from the small, intimately related stock in which the growth occurred. Market-bought fowls of similar variety have shown themselves insusceptible, as have fowls of mixed breed, pigeons and guinea-pigs.”

The real leap, however, came in 1911, when Rous showed that an infectious agent was transmitting the cancer:

“A transmissible sarcoma of the chicken has been under observation in this laboratory for the past fourteen months,  and it has assumed of late a special interest because of its extreme malignancy and a tendency to wide-spread metastasis In a careful study of the growth, tests have been made to determine whether it can be transmitted by a filtrate free of the tumor cells. Attempts to so transmit rat, mouse, and dog tumors have never succeeded; and it was supposed that the sarcoma of the fowl would not differ from them in this regard, since it is a typical neoplasm. On the contrary, small quantities of a cell-free filtrate have sufficed to transmit the growth to susceptible fowls.”

The 1911 JEM paper’s method section is essentially a list of filtering and purity verification protocols to exclude bacterial contamination, leading up to Rous’ conclusion that something smaller, an “ultramicroscopic organism” was responsible*:

“The first tendency will be to regard the self-perpetuating agent active in this sarcoma of the fowl as a minute parasitic organism. Analogy with several infectious diseases of man and the lower animals, caused by ultramicroscopic organisms, gives support to this view of the findings, and at present work is being directed to its experimental verification. But an agency of another sort is not out of the question. It is conceivable that a chemical stimulant, elaborated by the neoplastic cells, might cause the tumor in another host and bring about in consequence a further production of the same stimulant. For the moment we have not adopted either hypothesis.”

You can read more on the history of viruses and cancer in Robin Weiss and Peter Vogt, “100 years of Rous sarcoma virus”.

*‘Virus’ had been around since 1892, when Dimitri Ivanovsky coined it to describe the agent causing tobacco mosaic disease, but the term was not yet in wide usage.

Bibliography.

Rous, P. 1910. A transmissible avian neoplasm (sarcoma of the common fowl). J. Exp. Med. 12:696705

Rous, P. 1911. A sarcoma of the fowl transmissible by an agent separable from the tumor cells. J. Exp. Med. 13:397411.

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