Historical Notes on Cancer Metastasis in Animals

WIB Onuigbo

Correspondence to
Professor WIB Onuigbo, Founder-Director, Medical Foundation and Clinic, 8 Nsukka Lane, Uwani, P. O. Box 1792, Enugu
E-mail: wilson.onuigbo@gmail.com


Abstract
The old literature on the transportation of cancer from the primary seat to the secondary sites mostly dealt with the human disease. Therefore, the present work notes the counterpart observations documented on animals by the old masters from 1846 to 1896.

Key words
Cancer, history, spread, human beings, animals.

In a review1 of the history of the bodily spread of cancer through the blood stream, I aimed at “recalling the old concepts, controversies, and conclusions, and noting, with the advantage of historical hindsight, points of particular interest to modern oncological research.” On reading it afresh, I was struck by its almost exclusive devotion to the human disease, there being but mere mention of the feasibility of animal experiments. In like manner, other reviewers2,3 paid little attention to tumor spreading in animals. Therefore, the present review aims at correcting this wide gap by documenting the observations duly made by the old masters in respect of cancer carriage in animals.

Animals interested no less an authority than John Marshall,4 when he was the President of the General Medical Council in 1891. Thus, he recalled how he dissected and examined a wild hare sent to his own master, Robert Liston. As he noted, it had “a well marked soft adenoid tumor of the mammary glands on the left side of the body.”

Body of knowledge was such that by 1846 Coote5 compared human and animal melanoma. In his experience, it was rapidly fatal in man but “not so fatal” in the horse. He cited a surgeon who knew of a horse whose tumor was excised and yet it lived and worked for ten years. He instanced, on the other hand, the observations of another surgeon:

I do not mean to assert that by excising a melanotic tumour (from the horse) we effectually prevent a similar morbid formation from ever appearing there; on the contrary, there is great chance of some of the neighbouring parts becoming affected in a like manner; for it is well known that an isolated melanotic tumour rarely appears in an animal without announcing a species of melanotic predisposition, under the influence of which the whole body becomes ‘farcied out’ with melanotic formations.

Formations of cancer were cited on her own part by Eva Field6 in 1894. She followed W. G. Spencer’s account of cancer in the mammary glands of a cat as was published in the Proceedings of the London Pathological Society. In that animal, extension took place by way of the lymphatics through the thoracic duct and right lymphatic duct, and thence to the lungs by way of the pulmonary circulation. She herself contributed personal cases. One cat brought to her by a fancier exhibited breast carcinoma. This tumour was well described as being situated in the left posterior mammary gland, lying to the anterior border of the nipple which was not involved. At autopsy, the peritoneum, gastric serosa, spleen and kidneys showed metastatic nodules. More importantly, these nodules were also found in the axillary, inguinal and mesenteric lymph nodes.

Nodes of the inguinal group were found to have been invaded in the research that Smith and Washbourn7 of Guy’s Hospital described as a series. In their experience, tumors on the genitalia of dogs had spread from animal to animal on the basis of coitus. The mucous membranes of the vagina and penis were attacked. It was in one case that a secondary lymph-nodal tumor was mentioned.

Mentioned by Livingood,8 a Fellow in Pathology at the Johns Hopkins University, was the advice given by no other authority than Welch. That master was heartily thanked “for his happy instigation, that a more minute study of a series of tumors found growing spontaneously in mice in captivity would prove an interesting problem.” In particular, interest centred on “the possible homology and analogy of these tumors to those found in humans.” One white mouse had a growth removed during life “under surgical precautions” from the neck and shoulders. It was examined and confirmed microscopically. The story ended thus:

Several months after removal of this tumor there was a recurrence at the seat of operation (Fig. 2), and associated with this, on the death of the mouse, was found a metastatic deposit in the lung.

Lung metastases occurred from a tumor growing from the inner side of the foreleg of another mouse. The microscopical appearances were figured well. As he discussed pointedly,
The elements making up the tumor and method of their growth differ in no way from those of growths occurring in human beings. Two of them give metastases which preserve the original type of structure and cells. One gives further evidence of its malignant nature by recurrence three months after removal . . . The rate of growth of none was noted, except the recurrence of tumor No. 2, which was very rapid.

Rapid or slow growth must have been of some interest. In fact, Birchmore,9 who was interested in the relationship between the diseases of man and domesticated animals, gave an account of numerous cases. Apparently, only one was frankly malignant in a hen whose rate of growth was described as follows:

The next time I noticed her, about midsummer, she was moving in so peculiar a manner that I caught her, made an examination, and found the left sole occupied by an elastic mass of about the size of a pigeon’s egg. The leg soon became useless, and the hen died marasmic. On postmortem, I found the lymphatic glands enlarged, containing multinucleated cells, the stroma proliferating pari passu. The extremity of the tarso-metatarsal bone was a mass of encephaloid disease.

Disease of the metastatic type so interested the above researcher that he ended his report with a pleasant plea. “Any persons,” he wrote, “knowing of similar cases will confer a favor by sending descriptions and either drawings or sections showing the microscopic anatomy.”

Anatomy of the microscopic type was of necessity hampered during the yester years. Thus, John Marshall,10 in the “Morton Lecture on Cancer and Cancerous Diseases” delivered in 1889, lamented thus:

If you study the older descriptions of this disease you will see that they are especially remarkable for the keen appreciation of the conditions of growth, their whereabouts, the progress they make, the general career, as it were, of these tumours; but the writers are specially ill informed as regards their structure.

Structure of the invaded tissue was necessarily a moot point. Nevertheless, early descriptions were, I believe, so clear as to be indicative of primary tumors growing in animals and metastasizing both locally and distantly just like how they were described contemporaneously in humans. As to the future, Mike Sharp11 of Edinburgh’s Moredun Research Institute pointed the way forward during the 14th November, 2002, Veterinary Symposium on “Pathogenesis of infectious disease: emerging aspects.” In part, his findings in respect of ovine pulmonary adenocarcinoma (OPA) were suggestive as follows:

OPA is a relatively well-differentiated tumor of alveolar type II and/or Clara cells that exhibits multifocal growth. It therefore exhibits similar pathological and epidemiological features to bronchioloalveolar carcinoma (BAC) in humans and is considered a useful model for the study of carcinogenesis.

Carcinogenesis, in conclusion, has long been the subject of research with animals. In this context, Kardinal,12 in his Outline of the History of Cancer, showed how Johannes Fibiger (1867-1928) started with work which grew out of the presence of a nematode worm found in a spontaneous gastric carcinoma in three wild rats. This eventually culminated in 1926 in the award of the first Nobel Prize for cancer research. Who knows? More may follow in this field!

Acknowledgments
I would like to acknowledge the opportunity which I had as a medical student at the University of Glasgow where Professor D F Cappell arranged for me to have “Open Access” to the Library by kind permission of the Librarian. Dr A T Sandison was very helpful also. As my interests grew, the Librarians of other British Universities and the Royal Colleges as well as the British Medical Association, the Liverpool Institution and the Wellcome Trust gave much assistance.

References

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