Cancer: A Historical Perspective By Lawrence Broxmeyer MD
Hodgkin’s cancer under attack
When Virginia Livingston was a student at Bellevue Medical College her pathology teacher mentioned, rather disparagingly, that there was a woman pathologist at Cornell who thought Hodgkin’s disease (a form of glandular cancer) was caused by avian tuberculosis [1]. This lady had published, but no one had confirmed her findings. Afterwards, Livingston compared slides of both. In Hodgkin’s, the large multinucleated giant cells were called Reed–Sternberg cells. They were similar to the giant cells of tuberculosis, which formed to engulf the tubercle bacilli. Livingston stored away in her memory that this lady pathologist was probably right but she would have a difficult time in gaining acceptance.
By 1931, Pathologist Elsie L’Esperance was seeing ‘acid fast’ tuberculosis-like bacteria riddling her Hodgkin’s cancer tissue samples. And that germ, once injected into guinea pigs, caused them to come down with Hodgkin’s too, fulfilling Koch’s postulates. L’Esperance brought her stained slides to former teacher and prominent Cornell cancer pathologist James Ewing. Ewing initially confirmed that her tissue slides were indeed Hodgkin’s. But when he found out that her slides came through guinea pig inoculation of the avian (fowl) tuberculosis she had found in humans with Hodgkin’s, Ewing, visibly upset, said that the slides then could not be cancer.
It betrayed his checkered history of high-placed medical politician. In 1907, you could have approached Dr. James Ewing about a cancer germ, and he would have embraced you over it. At that time, both for he and the rest of the nations medical authorities, it was not a question of whether cancer was caused by a germ, but which one. Was not it Ewing, at one time, who had proclaimed that tuberculosis followed Hodgkin’s cancer “like a shadow”?
But shortly after, James Ewing, “the Father of Oncology”, sent a sword thru the heart of an infectious cause of cancer with “Neoplastic Diseases” [2], becoming an ambitious zealot for radiation therapy with the directorship of what would one day be called Sloan–Kettering squarely on his mind. His entry lay in prominent philanthropist James Douglas. A vote for Ewing, Douglas knew, was a vote for continued radiation and James Douglas began sizeable uranium extraction operations from Colorado mines thru his company, Phelps Dodge, Inc.[34].
Soon Sloan became known as a radium hospital and went from an institution with a census of less than 15% cancer patients, separated by partition, lest their disease spread to others, to a veritable cancer center. But the very history of radiation revealed its flaws, and by the early 1900s nearly 100 cases of leukemia were documented in radium recipients and not long thereafter it was determined that approximately 100 radiologists had contracted that cancer in the same way [3].
Still, Ewing, by now an Honorary Member of the American Radium Society, persisted.
Elise L’Esperance was anything but alone in linking Hodgkin’s to a germ called Avium or fowl tuberculosis. Historically Sternberg himself, discoverer of Hodgkin’s trade-mark Reed–Sternberg cell, believed Hodgkin’s was caused by tuberculosis. Both Fraenkel and Much [35] held, as L’Esperance, that it was caused by a peculiar form of tuberculosis, such as Avium or Fowl tuberculosis, and of all the cancers, debate over the infectious cause of Hodgkin’s waxed the hottest.
Into this arena L’Esperance stepped in 1931, with few listening. She would publish Studies in Hodgkin’s Diseases [4] in an issue of Annals of Surgery. It proved to be the one legacy that no one, not even Ewing, who would soon die from a self-diagnosed cancer, could take away.
Dr. Virginia Livingston
”Our (cancer) cultures were scrutinized over and over again. Strains were sent to many laboratoriesfor identification. None could really classify them. They were something unknown. They had many forms but they always grew up again to be the same thing no matter how they were cultured. They resembled the mycobacteria more than anything else. The tubercle bacillus is a mycobacterium or fungoid bacillus.”–Virginia Livingston, 1972
Virginia Wuerthele-Caspe Livingston was born in Meadville, Pennsylvania and went on to obtain impeccable credentials. Graduating from Vassar, she received her M.D. from N.Y.U. The first female medical resident ever in New York City, with time Livingston became a Newark school physician where one day a staff nurse asked medical assistance.
Already diagnosed with Reynaud’s syndrome, the tips of this nurses fingers were ulcerated and bled intermittently. Livingston diagnosed Scleroderma. But upon further examination there was a hole in the nasal septa, something that Livingston had previous seen in the mycobacterial diseases TB and Leprosy.
So Livingston approached dermatologist Eva Brodkin and a pathologist for confirmation, all the while convinced that mycobacterial infection was causing the Scleroderma. She then preformed cultures from a sterile nasal swab – mycobacteria appeared, everywhere [1]. Injected into experimental chicks and guinea pigs, all but a couple died. Upon autopsy, the guinea pigs had indeed developed the hardened skin patches of Scleroderma. . . some of which were cancerous.
Momentum builds
Livingston, now possessed, solicited fresh sterile specimens of cancer from any operating room that would give them to her. All cancer tissues yielded the same acid-fast mycobacteria. New Jersey Pathologist Roy Allen confirmed her findings. Livingston and Allen then found that they could actually differentiate malignant from benign tissue by their mycobacterial content [5]. But still the explanation for why the cancer germ showed so many different forms was elusive.
Try as she might, part of Virginia Livingston’s problems in an American validation of her multi-shaped cancer germ lay firmly entrenched in the history of medicine, especially in the constantly changing field of microbiology. Louis Pasteur could handle being quickly rushed off a Paris Academy of Sciences podium to escape harsh reaction to his suggestion that children’s milk be boiled first, but he could not tolerate his rival Pierre Bechamp’s statement that a single bacteria could assume many, many forms. On his deathbed, Pasteur was said to have changed his mind when he said: “The terrain is everything”, meaning the culture or milieu that bacteria grew on or in could change their shape or characteristics. But it was too late and even today, most conventional microbiologists deny the existence of such form changing (or pleomorphic) germs.
Robert Koch, Father of Bacteriology and discoverer of tuberculosis, could have helped. When he first worked with the bacteria anthrax, he noticed that anthrax’s classical rod shape became thread-like inside the blood of laboratory mice. And then, after multiplying, they changed again, into the same assumed spore-like forms he later documented in tuberculosis as well.
Aware of what she faced, yet undismayed Livingston methodically went about proving cancers true cause. First in her line of attack were the long suspected and well-publicized tumor agents of Rous, Bittner and Shope. By photomicrographs, Livingston and her group demonstrated acid-fast mycobacterial forms in each of these so-called “viral” cancers. This included the famed Rous chicken sarcoma.
Early on, Virginia Livingston had decided that she needed help in validating her cancer germ and nobody knew the shapes and staining capacities of mycobacterial-related germs better than Dr. Eleanor Alexander-Jackson of Cornell. As far back as 1928, Eleanor Alexander-Jackson, bacteriologist, had discovered unusual and to that point unrecognized forms of the TB bacillus, including its filterable forms. By 1951, Alexander-Jackson was considered the expert TB microbiologist at Cornell.
In the same year, another American, H.C. Sweany proposed that both the granular and other forms of tuberculosis that passed thru a filter caused Hodgkin’s cancer [6]. This was subsequently supported by studies by Mellon, Beinhauser and Fisher [7,8]. Mellon prophetically warned that tuberculosis could assume both its characteristic red acid-fast forms as well as blue nonacid-fast forms indistinguishable from common germs such as Staphylococci, fungi and the Corynebacteria and that this would surely perplex modern microbiologists.
When organized medicine choose to ignore these studies, Jackson warned that a so-called cure for TB could be as short-lived as it took classical TB rods, for the moment gone underground as a nonacid-fast form, to resurface one day and spring back towards destruction. Although American medicine had no serious time for Alexander-Jackson or her discoveries, it would not disturb her for as long as she focused on tuberculosis and its cousin, leprosy. But when her focus shifted towards Livingston’s cancer germ, it would move to destroy her. She simply posed too great a threat.
Recognition
By December of 1950 Livingston, who would go on to write over 17 peer reviewed articles by the end of her career, wrote, together with Jackson and four other prominent researchers, what still stands as a milestone on the infectious nature of cancer [9].
At the AMA’s 1953 New York exhibit, participants interest was particularly riveted towards an exhibit of Livingston’s cancer germ, live. The press, muzzled by Sloan Kettering’s head, Cornelius Rhodes, was not allowed to interview or report on this exhibit. Above, the cancer germs seemed indestructible, surviving a five-day experience of intolerable heat from closed-circuit microscopy [1].
As Livingston and Jackson’s work on the cancer germ became more and more
