Cancer: An Introduction

There are only a handful of historical documents that mention diseases even remotely comparable to cancer. Imhotep, the most celebrated of ancient Egyptian medical men, identified a “bulging mass in the breast” of one patient, and even with all of the most powerful pseudoscientific cures at his disposal, that for cancer was expressed in minimal form: “There is none”. A millennium and a half later, the Greeks gave it a name, cancer, derived from the similarity in appearance of one of its forms to Mediterranean crabs. Galen, progenitor of much of Western medical practise straight through to the seventeenth century, linked it to an excess of black bile in the body, yet stated that surgical removal of cancerous tumours could resolve nothing, as black bile was an inextricable component of a body. Balance, not elimination, was his goal.

Though there are certainly exceptions, such as childhood leukaemia, cancer is generally a disease of old age. As the median mortality of even affluent cultures was typically well under the age of 50 prior to the twentieth century, cancer had not yet become as prevalent in society as it is today. Present, yes, but not widely acknowledged; an incurable stigma. Although medicine had certainly improved from its foundations, and took on a rapid pace during the Enlightenment years, nineteenth century doctors still relied on a troubling combination of myth and science for much of their daily work. It took the emergence of anaesthetics and other drugs, as well as powerful new surgical tools, to make the exacting surgeries of cancer removal a possibility.

The most influential of the late-nineteenth century cancer surgeons, Dr William Stewart Halsted, decided that the best approach to breast cancer was not to excise only the obvious lumps, but to perform the complete removal of the infected breast, along with much of the surrounding tissue. The prevailing hypothesis at the time, Halsted’s own “centrifugal theory”, held that cancer started at one point on the body, and expanded from there like the shards from an exploding missile. By removing cancerous and proximal tissue, the expansion might be halted. Muscles, including those the patient needed to operate her arm, were often a target in Halsted’s extreme approach to cancer removal. His own patients, and many of the other women who underwent radical mastectomy in the ensuing decades, were permanently disfigured. Were his theory correct, his efforts were easily justifiable, and in the 1890’s, no one had the tools to really put it to the test.

There were few in the surgical community able to challenge the idea that such extreme surgeries were ineffective. For nearly sixty years, the vast majority of surgeons held strong to Halsted even as radiation therapy entered the field. The first challenger was Dr Geoffrey Keynes, who demonstrated in the 1920’s that localized surgeries combined with radium exposure could at least match the cancer recurrence rate of radical mastectomy patients. His was a small voice, and largely ignored until 1953, when another surgeon, Dr George Barney Crile, attended a lecture on the history of breast cancer and learned of Keynes’ experiments. That work, combined with Crile’s own experience with his patients and known rates of remission, led to his quick departure from the practise of radical mastectomy. He had come to the realization that cancers that had yet to metastasize could be removed locally, without the need for catastrophic excision, whereas cancers that had already metastasized would be unaffected by even the extreme measures on which Halsted and his cohort relied. In a roundabout kind of way, Galen’s idea that cancer was systemic and thus rendered surgical techniques ineffective was vindicated. The dogma of “centrifugal theory” had begun to lose its grip, and new ideas about the spread of cancer were now germinating.

Cancer, along with other devastating health disorders, is an extremely sensitive issue for great swaths of the public. Far less than the Six Degrees of Bacon are needed to find a person in your network who has suffered from cancer. We all want that miracle cure promised long ago, at the beginning of the War on Cancer. But we are most unwilling to allow researchers to perform even the most basic of trials; catch a whiff of a promising new drug or procedure, and many people would drop everything to save themselves or their mothers, who might (just possibly) be saved in that first test cohort. Survival is the goal for patients, as it is for their doctors and surgeons. Evidence of a new drug’s efficacy is a distant concern for people in dire need, and few have the patience or time to truly determine if that new drug is in any way better (or worse) than placebo.

The search for a cancer cure throughout the twentieth century generally began from the invention of a drug, surgery or other procedure, with theories about why it worked developed essentially as afterthought. Within a year of Roentgen’s 1895 discovery of X-Ray radiation, med student Emil Grubbe tried to treat a breast cancer patient with a protective tinfoil covering and radium exposure. There was some slight remission in her localized cancer, but it had already metastasized and she survived only a few months after the first experiment. Still, this was a definite response, which gave Grubbe the impetus to continue his experiments with new patients. Radiation quickly became a possible “miracle cure”, but proper dosages were not yet understood, nor its potential for triggering new cancers. Radiation therapy, it turned out, is also antagonistic to healthy cells, but those that divide slowly are much less vulnerable than cancerous ones to destructive mutations.

In 1919, Edward and Helen Krumbhaar, American pathologists studying mustard gas survivors, noted a curious commonality among them. Most people were already well aware of the immediate complications of mustard gas – burnt skin, blisters, blindness, breathing problems – but the long term difficulties had as yet gone unremarked. Soldiers who had survived the worst attacks had somehow lost the ability to generate white blood cells. Their bone marrow was so horribly damaged that some patients required monthly transfusions. Here, for the first time, was a poison that could selectively attack a specific cell type, but in the chaos of the post-war period, the Krumbharrs’ paper was published and quickly forgotten. Chemotherapy, the dream of curing cancer through drug intervention, would take a few more decades to really take off.

Childhood leukaemia was first identified in the mid-nineteenth century as a “suppuration [conversion into pus] of the blood”. White blood cells would suddenly swamp the veins of a child, their survival reduced to five years, at best. Like any cancer, leukaemia was a horror, but there is something particularly cruel about the disease when it hits the young. What made it a primary candidate for chemotherapy tests was that it was a simple matter to determine the extent of the cancer, and the strength of each new concoction designed to alleviate and nullify the disorder. By withdrawing the blood through a needle, and counting the different types of cells, basic statistics could divine the quality of cancer remission.

Nitrogen mustard, a close relative of the poisons used in World War I, was among the first candidates for chemotherapy. The penumbra between “poison” and “medicine” was never so fine as during the nascent days of this bold, new therapy. Patients could be taken right to the edge of the abyss before dosages would be reduced and blood production recover. Doctors toyed with the dosages needed of each new chemical, each new regimen of administration. The early years of chemotherapy studies were truly manic, defined by the euphoria of success, only to be followed by defiant recurrences less than a year later. As some patients did, indeed, recover fully, never to battle cancer again, doctors had to ask themselves whether they had simply not been radical enough with the poisons/medicines given to their relapsed patients. It was a tricky question, with no answer forthcoming.

For a full century, even as doctors were desperately searching for a cure, there was no consensus on what cancer itself actually was. Galen knew it as an imbalance of the humours, nothing more. Halsted’s centrifugal theory concerned only its spread. The somatic mutation hypothesis of cancer, sparked by investigations into the high incidence of cancer patients in particular professions, was, in Halsted’s era, still a popular notion that held that environmental carcinogens could permanently alter the structure of the cell. But this hypothesis was thrown into disarray when Peyton Rous discovered in 1909 that chicken sarcoma (a cancer of the connective tissues in chickens) was spread by a viral infection. A discovery in the 1970s linked at least one human cancer to the viral agent hepatitis B. Later that same decade, a bacterial origin for stomach cancer was identified. The true genetic origin of cancer was not properly understood until the 1980s.

DNA uses a very simple language to communicate incredibly complex ideas. It is the cookbook from which everything we are is written down. It defines not only the ingredients themselves, the proteins of which we are made, but the timing for when they are to be used in a cell’s life. This is the key to understanding cancer. Cell division is controlled by proteins called kinases, some of which order a cell to start dividing, and others which tell it to stop. In general, there are two stop kinases to each start, and all three must mutate in order for a cell to divide unrelentingly. So long as they don’t exist, the stop kinases aren’t around to cease division; the start kinase need only remain on.

Here is cancer, simply stated, but still a monster to resolve. It is not a single disease, however much we might insist on lumping its various classes together. Any cell can become cancerous, after all, and each type of cell has its own characteristics, its strengths as well as its vulnerabilities. So, too, can cancerous cells mutate even further, which is what allows them to so often return with a vengeance on their victims.

The genetic understanding of cancer’s origins is valuable knowledge, but not one that we currently know how to act on. Cancerous cells aren’t foreign bodies susceptible to the modes of attack used on other forms of disease. You can’t vaccinate against cancer. We can dream of creating retroviruses that latch on exclusively to cancerous cells and reassert the proper commands, but that is not yet science fact. We will, however, continue to use and refine the tools we have, and work towards the day when we can put the ugly days of cancer behind us forever.

RESOURCE

Mukherjee, Siddhartha. The Emperor of All Maladies: A Biography of Cancer. Simon & Schuster, 2010.

 

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