Scientists, physicians, and patients use metaphors to understand the complex condition called cancer. These metaphors direct the process of research and treatment. It is sometimes useful to make explicit existing metaphors and their problems and to suggest new metaphors that might overcome them. Thinking of cancer in evolutionary rather than military terms offers new possibilities in connection both with research and treatment.
Cancer as a Metaphor:
“Illness is the night-side of life, a more onerous citizenship. Everyone who is born holds dual citizenship, in the kingdom of the well and in the kingdom of the sick. Although we all to use only the good passport, sooner or later each of us is obliged, at least for a spell, to identify ourselves as citizens of that other place,” (Sontag, 3).
In this way, Susan Sontag begins her essay, Illness as a Metaphor, where she explores the analogies, euphemisms, and symbols that western medicine has used to characterize both cancer and tuberculosis. She compares the 19th century conception of tuberculosis to the 20th century perception of cancer. Her investigation includes past and present cultural interpretations of the diseases. Sontag’s work is a wonderful analysis of how society understands and medical and scientific knowledge. I would like to use Susan Sontag as a starting point for discussing metaphors employed to describe cancer more generally.
It is possible to extend Sontag’s metaphor to include the role that doctors and researchers play. Doctors are anthropologists observing the inhabitants of the kingdom of the sick. Illness is the culture that these anthropologists are studying. The understandings that the doctor’s develop are incorporated into the theoretical work of researchers and social scientists. In turn, these syntheses are communicated to the anthropologists in the field. The anthropologists then try to translate this information into the language of the locals. The anthropologists equate scientific theories with ideas more familiar to the locals; they make metaphors.
To explore a particular concept, people employ analogies in the form of metaphors and similes. For example, metaphor is a type of figurative language in which two unlike concepts or things are made equivalent. A known and concrete quantity, the vehicle “carries” over onto the tenor, the unknown and abstract quantity. The tenor is cancer. Scientists use metaphors to translate their theoretical research for the doctors who are treating cancer. Doctors also exploit metaphors to transform medical interpretations of an illness to the patients experiencing it. Metaphors are shared between researchers, doctors, and patients.
The choice of the vehicle used in characterizing cancer determines how both patients and professionals understand this illness. The metaphor that scientists embrace summarizes their past research and provides directions for their future research. If scientists recognize cancer as an invasive force, then they will attempt to create weapons to repel, expel, or kill the invaders. This is the traditional line of thinking behind chemotherapy, radiation, and surgery. These treatments are the use of cytotoxic chemicals, radiation to kill cancer cells, or excision of the tumor mass. The ultimate goal is to cure a patient of cancer, by killing every last cancer cell in the body. Therefore, researchers are perpetually looking for affordable, efficient, nontoxic methods of destroying cancerous tumors.
The metaphors that doctors rely on will help them determine what is the best possible treatment for individual patients. Oncologists and hematologists must sort through an enormous amount of information in the form of clinical trials and pharmacological profiles. Their treatment goals influence their choice of strategy significantly. For example, a doctor might choose an aggressive treatment with chemotherapy and monoclonal antibodies for a middle aged patient with stage III lymphoma. The aim of this treatment would be to cure the patient of their cancer, to completely kill off the population of cancer cells in their body. However, the recommended treatment for an elderly patient with stage III lymphoma might differ significantly. The doctor might recommend only a monoclonal antibody, because it has significantly less side effects than traditional chemotherapy. It is unlikely that this treatment would cure the patient, however, it should extend their life span more than no treatment at all. The risk of adverse events in patients with multiple co-morbid conditions is that the treatment might shorten the patient’s life span. This is the logic of palliative care, lowering the tumor load and increasing survival without curative intent.
“Yet it is hardly possible to take up … residence in the kingdom of the ill unprejudiced by the lurid metaphors with which it has been landscaped,” (Sontag 4). Metaphors inform a patient’s expectation for their treatment, course of disease, and remainder of their lives. Historically, patients have had limited information about cancer, their own internal experience and anecdotes shared by family and friends. Therefore, they are reliant on their doctors for general facts about prognosis and treatment options. With the development of websites and online publications patients are gaining access to primary medical and scientific literature. The metaphor that is used to explain the cancer to the patient will influence how they live the rest of their lives. Older vehicles include cancer being a death sentence and suggested a hopeless state of affairs to the patient. More recently cancer is understood to be a body at war with itself, and the treatment is adding the non-cancerous cells to win the war. This more empowering metaphor encourages the patient to be brave, strong, a fierce fighter, and persistent. To loose the war to cancer represents a failure on the part of the patient and the treatment. It is condemning of both physicians and patients.
I would like to explore several common metaphors for cancer to see what elements of the illness they express. Cancer was once considered an unmentionable condition; it was not to be named. Cancer was “treated as an evil, invincible predator, not just a disease, most people with cancer will be demoralized by learning what disease they have,” (Sontag 7). The patients were prey animals, creatures of high fear and stress. Their predator was omnipotent and so impossible to defeat. This was the metaphor that physicians adopted for explaining cancer to their patients. The patients in turn transmitted this model to other people in their lives. Therefore, diagnoses were kept secrets, from employers, friends, family, and even the patient themselves. The reason for such secrecy was the perceived horrors of the disease. Cancer was not only a death sentence; it was a gruesome excruciating execution. The decay of the body was disgusting; there was disruption of bodily functions, vomiting, diarrhea, constipation, bleeding, swelling.
Cancer has commonly been referred to as a death sentence by researchers, doctors, and patients. The process of disease spread and patient death is considered certain in this case. The meaning of this metaphor is that the patient is being executed. The patient has been tried, found guilty of a crime, and punished by loss of their life. The important implication of this metaphor is the shame it places on the patient by raising the question of what crime they committed. Otherwise stated, what did the person do to make them deserve to die of cancer? This accusative position invokes questions about the patient’s moral status. Cancer carries the weight of moral and psychological implications. In more recent times, there has been a rebellion against the conception of cancer as a death sentence. The new research goals are to find ways of turning cancer into a chronic condition, an illness that might require long-term management but is not itself fatal. Researchers are hoping to convert cancer into diabetes, a disease that is successfully managed with medications and changes in life-style.
In America, politicians even have a metaphor for cancer. In 1971, President Nixon announced the War on Cancer and signed the National Cancer Act into law, (Begley 1). What constitutes winning the war is open to interpretation: elimination of cancer caused deaths, early detection, or prevention are all admissible interpretations. However, losing the war is simple to define: the absence of progress in treating cancer. Unfortunately, most data shows that we are losing the war, (Kolata). Significant improvements in breast, colon, and prostate cancer treatment have occurred. Death rates from bile-duct, liver, lung, melanoma, and pancreatic cancer have all increased since the War on Cancer was declared, (Begley 1) This data is particularly pathetic in comparison with the significant progress made in lowering the mortality die to heart disease. It raises questions about the effectiveness of current research and treatment strategies for cancer. The metaphor of war and enemy armies has not proven useful.
Although Sontag begins her essay with a metaphor for illness, she argues against the use of physical symptoms as the vehicle carrying over people’s psychological states. There is no such thing as a “cancer-prone character- someone unemotional, inhibited, repressed,” (Sontag 39). The somatic manifestations of disease are not representations of an abstract emotions or feelings. Disease is a material rather than mystical experience. Sontag’s thesis is that the associations or properties metaphors imbue cancer with are neither elucidating nor edifying; they are not useful. “It is toward an elucidation of those metaphors, and a liberation from them, that dedicate this inquiry,” (Sontag 4). She calls into question the necessity of using metaphors to understand cancer.
Cancer as ___________ Process:
The purpose of using metaphors to explain cancer is to summarize an overwhelming number of observations into a manageable amount. Cancer is a constellation of complex diseases. There is a considerable amount of information about cancer from causes to diagnoses and treatment. Currently research is conducted across many fields, including but not limited to: biological, organic, and inorganic chemistry, genetics, cell, and microbiology, histology, and immunology, hematology, and oncology. Communication between these different fields is often fractured; transdisciplinary work is not appropriately rewarded. The result of imperfect communication is specific limited knowledge of cancer is possessed by various researchers. There is a divorce between the practical understanding of physicians, the more theoretical concerns of academics, and the profit motivated work of pharmaceuticals.
There are many different ways to understand the cluster of diseases that doctors and scientists refer to as cancer. “All cancers are characterized by a loss of cellular growth control and genetic instability,” (Greif 186). This definition is readily applicable to the research problems and theories of scientists studying cancer. However, it is less germane to the physicians and patients concerned with the implications of the above-described biology. Transforming underlying biochemical processes into the symptoms of disease is where metaphors are important. They facilitate the connection between molecules and humans.
Over time, doctors’ and scientists’ understanding of cancer has become increasingly sophisticated. It has been recognized that different cancers kill in different ways. Some solid tumors, like pancreatic cancer, destroy the function of the organ in which they originate. Others, like breast cancer, metastasize to other organs such as the “liver, lungs, bones, and brain,” (Greif 188). It is not the primary tumor, located in the breast that is deadly, rather the metastases disrupting the function of vital organs. “Metaphorically, cancer is not so much a disease of time as a disease or pathology of space. Its principle metaphors refer to topography (cancer ‘spreads’ or ‘proliferates’ or is ‘diffused’; tumors are surgically ‘excised’), and its most dreaded consequence, short of death is the mutilation or amputation of part of the body,” (Sontag 14-15).
The recent cancer awareness campaigns are glamorizing cancer in the same manner that the Romantics of the 19th century made tuberculosis attractive. Healthy individuals are commended for contentious behavior in obtaining all the appropriate early detection tests. This list includes, but is not limited to, breast self-exams, mammograms, pap smears, colonoscopy, and PSA. Cancer survivors are valorized for winning their battle with illness. They are praised as tough soldiers and brave fighters. The ideal survivor is one who shows no evidence of the battle; they have rebuilt the war-torn country of their body. This trend is exemplified in the number of women opting to have reconstructive surgery after mastectomy, removal of their breast, (von Minckwitz). (A common component of the breast cancer treatment program.)
Cancer as an Evolutionary Process:
I would like to propose a new metaphor for understanding cancer; bacteria are cancerous cells. This formulation highlights the foreign and invasive nature of cancerous cells. They do not cooperate with other cells in the body and are not concerned with the survival of their host organism. However, both bacteria and cancer cells make use of their host’s environment for their own purposes. The biochemical machinery and macromolecules, which constitute the host’s body, are an environment. Modifications to the environment require the bacteria or cancer cells to evolve. The potential for cancer cells, like bacteria to evolve is not an entirely novel idea, however, its implications have not been fully considered.
The most important element of the similarity between cancer cells and bacteria is that both are capable of evolving resistance to the treatments doctors use to kill them. Their ability to rapidly develop resistance to treatment creates a “red queen dilemma” for doctors and researchers. Medicine and science are racing as quickly as they can just to keep up with the evolution of drug resistance in bacteria and cancer. Doctors and scientists are creating novel drugs and combinations of drugs to keep human bodies ahead of bacteria and cancer. “The main aim of these combinations is to obtain a synergistic or additive affect and to prevent or delay the appearance of resistant cancer cells,” (Awada, 56).
Unfortunately, those single celled runners will end up winning the race. It takes bacteria and cancer less time to evolve resistance to treatment, than it takes researchers time to develop new drugs or drug combinations. Improving current medications is also important; enhancing the bioactivity or lowering the toxicity of old drugs. The therapeutic index of a drug is the ratio of biological activity to toxicity. The process of drug development includes, natural product screening, a synthetic strategy for obtaining the desired chemical in large quantity, studies of its bioactivity, clinical trials, and approval by government for use as an antibiotic or chemical therapy.
The current metaphor for creating anticancer treatments is a search for anything: biological, chemical, radiation, or surgical that can kill cancer cells. One method of imagining new medicines are augmenting the bioactivity of proven medications by creating and testing synthetic analogs. “New therapeutic strategies exploit a critical function or genetic abnormality of a tumor,” (Awada, 53). Another is targeting the specific biochemical pathways related to cell growth. Important targets include: cell proliferation, differentiation, and function, invasion, angiogenesis. Molecular-targeted therapies- tyrosine kinase-dependent pathways including EGFR and VEGFR, Ras/Raf/rho signal transduction pathway, phosphoinositol 3-kinase cell survival pathway (regulates growth), molecules that interfere with the activity of Bcl-2 (protein involved in apoptosis), proteasome inhibitor causes the degradation of membrane receptor and apoptosis involved proteins, interference with the cell cycle- manipulating cyclins and cyclin dependent kinases. These targeted or biological therapies have a greater therapeutic index, but are not a cure for cancer, (Awada). They still face the same problems of treatment resistance and recurrence that older methods do.
The difference between cancer of humans, mammals, and plants highlights important evolutionary-development components of the disease. Cancer is a developmental process gone awry. Developmental processes diverged through the evolution of different species. Humans, horses, mice, and other mammals share cancers so similar that they respond to the same medications, (Giovanella, Meyer). Humans and horses are treated for lymphoma with identical regimens, (Meyer). However, plants a species that is significantly more evolutionarily distant from humans, don’t even get cancer. Plants do have benign tumors, or unnecessary growths. The absence of a circulatory system in plants prevents the potential for metastases. Plant growth follows a different pattern than mammalian growth. The cells of a plant are totipotent; they are capable of differentiating into any kind of cell. This is meristematic growth. When plant cell divide, the daughter cells simply become whatever the plant needs. This explains why it is possible to take a cutting of a shoot and grow a complete plant. Extra plants cells are not problematic to the organism. This is the fundamental difference between plant and mammalian cell growth.
The reason that I desire to equate bacteria and cancer cells is to foreground the role of evolution. The primary mechanism of evolution is natural selection; the process in which genetic mutations that confer reproductive and survival benefits become more common in a population over the course of generations. There are three conditions that must obtain in order for natural selection to occur. First, the evolving population must have variation. One of the defining features of tumors is the genetic instability and variety of their cells. This variation is heritable; when cancer cells divide and replicate the daughter cells share the same mutations. Heritability of variation is the second condition for natural selection. Third, the variation must enhance the fitness or survival and reproduction of the cancer cells. Since all three conditions are met, natural selection does occur in cancerous tumors.
Cancers begin when multiple genetic mutations increase a single cell’s survival and reproduction. One type of mutations activates oncogenes, genes that cause cell proliferation. Mutations that de-activate genes that inhibit cell replication, tumor suppressor genes. Another kind of mutations, results in a loss of function of DNA repair genes, so that the above mutations cannot be fixed. The descendents of this cell form a cancerous tumor. The cells are genetically unstable, which leads to diversity in the tumor population. Better-adapted cells produce a greater number of daughter cells and other descendents. As the tumor size increases, the cancer cells must acclimatize to different local environments. Cells at the center of the tumor have less access than cells at the perimeter to oxygen and nutrients. Therefore, the centrally located cells must become accustomed to scarce resources. A more dramatic example of cancer cell evolution is the formation of metastases, where cells depart from the primary tumor and settle in a new organ. The cells must rapidly adapt to their new environment. Cancer development and metastasis is dependent upon the process of evolution.
The evolution of cancer cells has important implications for future research and treatment. Evolution is driven by adaptation of the organism to its environment. In the case of cancer cells, their environment is the human body. Therefore, manipulating the human body applies selection pressure to the cancer cells. Introduction of chemicals that are toxic to most cancer cells does not kill the population; it selects for individuals with a genetic mutation that makes them immune to the effects of the chemotherapy.
An alternative to killing the tumor cells is to select for less aggressive or dangerous cancer cells, using drugs to increase their relative fitness. Essentially, the treatment would turn a malignant or invasive tumor into a benign tumor. The menace of metastases would be removed. The result of such treatment might not be a cancer free body, rather a body that can function despite its tumors. A more desirous and difficult goal of the treatment would be to evolve a cancer that could participate in a symbiotic relationship with their human host. Such interaction might be of mutual benefit to both organisms. Examples of naturally occurring mutualism are the presence of cellulase producing bacteria in cows. These bacteria provide an enzyme necessary for digestion to their host cows. Commensalism is another potential type of relationship, where one species benefits and the other species are not affected. The cancer cells might benefit from the environment of the human body, but not reduce the fitness of the human host. This symbiosis already occurs naturally with plants and their tumors.
Maley and his colleagues suggest another possibility. They propose selecting for cancer cells that are responsive or can be killed by chemotherapy. After achieving a genetically uniform population of these cells, chemotherapy would be used. The intended result is that all the cancer cells would be chemo-sensitive and killed. In order for this technique to work, literally all of the cancer cells would have to be chemo-sensitive. Otherwise, the treatment would not simply operate as efficient chemotherapy. It would not kill all the cancer cells, it would select for those cells that are resistant to the treatment. The primary problem with any single treatment for cancer is the genetic instability of the cancer cells. They are constantly evolving. The genetic composition of a particular tumor may vary at any given time. It may not be possible to achieve and maintain a population of chemo-sensitive cells.
A logical strategy for treating an illness capable evolution is to develop a medication that is able to co-evolve. Instead of utilizing chemicals to kill cancer cells, other living organisms with the faculty to evolve could be exploited. The organisms would have to meet two criteria. Firstly, they would have to toxic to the cancer cells and not normal cells in the human body. The specificity to distinguish between normal and abnormal cells is essential to minimalizing harmful side effects of the treatment. Secondly, the organisms must be competent to co-evolve with the cancer cells. If they are not capable of co-evolving with the cancer until the last cell is dead, then they present the same problem as current chemical therapies, resistance. One option is engineering viruses. Under ideal conditions an oncolytic virus would infect all the tumor cells and then die because of the absence of acceptable host cells.
Another possibility is deploying anoxic bacteria to act as competitors or predators of the cancer cells. The bacteria must be well adapted to the tumor environment; they need a significant survival advantage over the cancer cells. Anoxic bacteria are preferable to ordinary bacteria because they are capable of functioning in an oxygen poor environment such as the interior of a tumor. For the same reason, anoxic bacteria might not be able to out-compete the cancer cells at the perimeter of the tumor.
There are several general concerns that apply to both anoxic bacteria and oncolytic viruses. The evolution of living things is not predictable; therefore, it is uncertain how they might change over time. The risk that the bacteria or oncolytic viruses will evolve in such a way that they are no longer contained with in the tumor is a serious concern. They could become acclimatized to the human body and prove a new source of illness. This is a particularly serious problem in already compromised patients.
The examples above indicate the new lines of inquiry that arise from conceiving of cancer as bacteria and chemo-resistance as antibiotic resistance. This is certainly beneficial to scientists and researchers because it inspires novel approaches to the disease. Physicians, who already have some understanding of antibiotic resistance, may find it a simple parallel. Both scientists and physicians have the requisite knowledge of genetics and evolution. However, patients may lack such information. Without the necessary prerequisites, the metaphor may not be meaningful to patients. The vehicle, antibiotic resistance is not a simple or well-characterized concept. Therefore, the vehicle might be just as mysterious as the tenor. The metaphor might not convey anything to the patient. This is a grave concern and an important reason for further inquiry.
The metaphor of cancer as an evolutionary process provides a new summary of the observations about the illness. It offers a fresh perspective for researchers, physicians, and patients. The fruitfulness of this characterization can only be judged in the future. The novel research and treatments that it helps inspire will be the evidence.
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