The Emperor of All Maladies is a fantastic book written by the oncologist Siddhartha Mukherjee which details the history of cancer and was published in 2010 and won the Pulitzer Prize. It is a truly great read, for it effectively communicates the biology of cancer, its relationship with humanity, and potential treatments.
The Emperor of All Maladies begins with a harrowing statistic by Siddhartha Mukherjee - in 2010, more than six hundred thousand Americans and more than 7 million Homo Sapiens in total will die of cancer. He then states that in the US, one in three women and one in two men will develop cancer in their life. Cancer is a leading cause of death in many developed countries, and this is due to all the forms cancer takes. Mukherjee writes that many diseases which are put under the category of cancer are deemed as such because they all involve abnormal cell growth. He then tells the audience that he used the experiences of some of his patients, leading him to change their names to protect their privacy. To begin his book, Mukherjee describes how one of his patients, a woman named Carla, was thirty-six when she was diagnosed with leukemia. One morning, she woke up with a numb headache, and she knew something was wrong because some time earlier bruises had suddenly appeared on her back. When she was admitted to the hospital, it was found that she had less than one third of her red blood cells - they have been replaced by blasts, malignant white cells. Mukherjee writes that leukemia is an especially deadly form of cancer, as it is “cancer of the white blood cells-cancer in one of its most explosive, violent incarnations … ‘even a paper cut is an emergency’” (3). When Mukherjee met Carla, he told her that chemotherapy will begin immediately after some more tests are conducted, and that she has a 30% chance of being cured. Mukherjee writes of the history of leukemia treatment, and states that leukemia earned its name from the Greek word leukos, which meant “white.” Leukemia involves the rapid multiplication of blasts/lymphoid cells which do nothing but take up space in blood vessels, for they never mature. Mukherjee details that while regular adults would have five thousand white blood cells per microliter of blood, Carla’s blood had ninety thousand, which was eighteen times the regular amount. When it comes to treating leukemia, aggressive chemotherapy has to be used to kill off the blasts, but this is also risky, for as of the current moment, chemotherapy doesn’t discriminate - it kills both regular and cancerous cells. As Mukherjee put it, “We would push her deeper into the abyss to try to rescue her. For Carla, the only way out would be the way through” (18).
Mukherjee writes of Sidney Farber, a doctor who was greatly involved in cancer treatment. Mukherjee then writes of the wonders that science could produce, as penicillin, just a few years after being invented, was mass-produced, making it greatly affordable to almost everyone. He states that in the twentieth century, as cancer received its spotlight, the general public lacked understanding of it, leading them to view it with terror (and rightfully so). The public demanded the US government to fund cancer research, but the mass outcry over cancer died out when WWII began, for there were more immediate concerns. Mukherjee writes that leukemia belongs to the field of hematology, for it impacts the blood. He writes of anemia, which is manifested in a deficiency of red blood cells. Farber tried to treat leukemia by administering folic acid to children. Instead of alleviating their symptoms, it greatly worsened them. Farber then hypothesized another possible treatment, believing that there was a decent chance that an antifolate could effectively deal with leukemia. He eventually tested his hypothesis on a child named Robert Sandler who was suffering from aggressive leukemia which caused him excruciating pain, lethargy, joint aches, a limp, and cancerous growths. It appeared that the antifolate had worked, for “The white cell count, which had been climbing astronomically-ten thousand in September, twenty thousand in November, and nearly seventy thousand in December-suddenly stopped rising and hovered at a plateau. Then, even more remarkably, the count actually started to drop, the leukemic blasts gradually flickering out in the blood and then all but disappearing” (33-4). Farber and his medical partner, Sandler, attempted to treat even more children with their method, and soon discovered that the antifolates could drastically decrease the number of leukemia cells in the short run. However, in the long run, the leukemia would return stronger than ever, seen in how they were largely resistant to the antifolates. Robert Sandler, for instance, died in 1948 when he relapsed. Fortunately, complete recoveries did happen, causing the treatment to become famous.
Mukherjee details that every age has its own disease. Tuberculosis, one of the most devastating diseases in human history, was a vital part of Victorian romanticism and the age, as people at the time viewed dying of tuberculosis as being a good way to perish. For instance, people like Lord Byron commonly “fantasized about dying of the disease to impress his mistresses. ‘Death and disease are often beautiful, like … the hectic glow of consumption’” (38). Cancer, fortunately, has not been romanticized as a disease, and it is an infamous disease due to how it is commonly viewed - cancer is not infectious (only known method of transmission is genetic, from parent to child), causing it to be viewed sometimes as a trial for the individual. Furthermore, sometimes the cancer cell itself was viewed as an individualist trying to create their own fate in their world, seen very well in how “metastasis” (the movement of malignant cancer cells to other parts of the body) is a combination of “meta” and “stasis,” translating to “beyond stillness” in Latin. Mukherjee writes that while tuberculosis drains the lungs of life (hence its name “consumption” - victims became gaunt, pale, listless; they had been consumed by the disease), cancer fills the body with large amounts of harmful cells, sometimes leading to physical deformations. He then describes that “A cancer cell is an astonishing perversion of the normal cell … it exploits the very features that make us successful as a species or as an organism” (38). Like regular cells, cancer cells multiply, though they never stop. Cancer cells are also deadly because they multiply rapidly, quickly inflating their numbers, which causes natural selection to some degree - even if treatments like chemotherapy are used, it is likely that some cancer cells would survive, and then multiply, creating cancer cells which are highly resistant to said treatment. Mukherjee describes that cancer has been with humanity for an extremely long time, as it begins with our biology, seen in potential issues with cell division. An Egyptian scroll which detailed treatments for various diseases gave various practical treatments and descriptions of diseases was found in 1862. While it excellently addressed many diseases, for breast cancer it noted in one sentence that there was no potential treatment. In the Histories of Herodotus, the story of Atossa, the queen of Persia, was briefly detailed. It is quite apparent that she is suffering from breast cancer, as she had a large tumor on her chest. When she realized that she was ill, she became angry and withdrew socially. She had her slave, Democedes, amputate the tumor. It is not known what happened to her afterwards, for she was never mentioned again.
Mukherjee describes that cancer has also been traced to the Egyptians - the tumors were discovered via mummies. He then describes that “Louis Leakey, the anthropologist who dug up some of the earliest known human skeletons, also discovered a jawbone dating from two million years ago from a nearby site that carried the signs of a peculiar form of lymphoma found endemically in southeastern Africa … If that finding does represent an ancient mark of malignancy, then cancer, far from being a ‘modern’ disease, is one of the oldest diseases ever seen in a human specimen-quite possibly the oldest” (43). Mukherjee then states that cancer, for much of humanity’s history, was an indiscreet disease, for the life expectancy was much lower in the past. The incidence of cancer has a positive correlation with age: since people didn't commonly live to old age in the past, they frequently died before even getting the chance to develop cancer. Mukherjee details that a thirty-year-old female has a 1 in 400 chance to get breast cancer, while a seventy-year-old female has a 1 in 9 chance. He provides a list for the audience, detailing that “In most ancient societies, people didn't live long enough to get cancer. Men and women were long consumed by tuberculosis, dropsy, cholera, smallpox, leprosy, plague, or pneumonia. If cancer existed, it remained submerged under the sea of other illnesses. Indeed, cancer’s emergence in the world is the product of a double negative: it becomes common only when all other killers themselves have been killed” (44). Mukherjee then states that civilization didn't create cancer; instead, it unveiled it. A large percentage of deaths today are related to cancer because, as stated before, other diseases have been greatly dealt with. Leprosy is extremely rare, there is treatment for plague, pneumonia, tuberculosis, dropsy, and cholera, and smallpox was virtually exterminated in an international health campaign. As those diseases weakened in strength, cancer took their place. This again shows the power of perspective: it is true that cancer has become more prevalent, but that was directly due to massive improvements in medical care made in the past few centuries.
Mukherjee writes that diseases are commonly named after their symptoms. For instance, “influenza” was derived from “influentia” because superstition decreed that the movement of the planets led to this disease. “Tuberculosis” was named after “tuber,” which derived swollen glands. “Cancer” was first named “karkinos,” which was Greek for “crab.” It was named as such because those who had cancer commonly reported that the physical pain caused by it were akin to being stabbed by a crab. Galen, a prominent doctor, misunderstood cancer, for he viewed disease as being due to an imbalance in the four humors, which was entirely untrue. After his death, a scientist named Vesalius dissected corpses to further his knowledge of the human body, which led to the discrediting of Galen’s theory. From 1846-1867, there were major improvements in the field of surgery, seen in the invention of anesthesia and antiseptics. Mukherjee then discusses William Stewart Halsted, who is infamous among modern doctors for his extreme approach towards cancer. Halsted, after graduating from Yale, discovered surgery roughly by accident, as he didn't want to be a merchant in his father’s company. He became interested in cancer treatment, and believed that when it came to breast cancer in women, a total mastectomy (the amputation of both breasts) would effectively cure them of their ailment (metastasis was not discovered at that point in time). While Halsted was able to do these extreme surgeries, they weren’t always effective, for malignant cancer cells could simply emerge somewhere else in the body. Furthermore, the women who would undergo these surgeries would be permanently mutilated, but things such as these were viewed as mandatory for recovery for previous doctors, for they believed that lacking the nerve to do radical operations would only spell disaster for the patient in the long run; sacrifices had to be made for long-term benefits.
Some time after Halsted, the X-ray was invented. Like cancer, the potential dangers of radiation found in X-rays were not fully known for years. By the time people understood the dangers of radiation poisoning, some people had already died from exposure, such as Marie Curie. Oncologists, upon realizing that X-rays could kill cells, thought that it could be an option for cancer treatment; since cancer was a systemic disease, then a systemic treatment could be a potential cure. This led to the concept of specificity, in which doctors tried to find a substance which would kill cancer cells while sparing regular ones. Some of the first substances to be used as potential treatments included dye, and during WW1, they were used as chemical weapons, a gross abuse and distortion of their original supposed use. When mustard gas was invented and used, it killed thousands of people while maiming thousands more. When survivors were examined, it was found that their bone marrow was depleted of blood-forming cells. Doctors then saw this as a potential treatment, and two doctors, Louis Gilman and Alfred Goodman, injected small doses of mustard into people. When Gustaf Lindskog, a forty-eight-year-old New Yorker suffering from lymphoma was treated, he underwent a remission. But like antifolates, remissions occurred. Regardless, doctors tried to synthetically create chemicals which would succeed at the task of specificity. Most of the results were unsatisfactory, for the remissions would only be brief, commonly lasting for only a few days. Farber eventually met a doctor named Koster, and they tried to make the public conscious of cancer by opening a hospital for children. They eventually hosted a child who had cancer, nicknamed “Jimmy,” on television. Jimmy, save for his cancer, was a regular, understandable, happy child, and, to the delight of the audience, his favorite baseball team visited him. The Jimmy Fund effectively made the public adamant against cancer, and they raised more money than was anticipated, showing the things that are capable when cooperation is reached.
Mukherjee then writes of Mary Lasker and Albert Lasker, who were socialites who focused on fighting against cancer. They eventually teamed with Farber, and Mary Lasker focused heavily on publicizing the campaign, writing urgently that hundreds of thousands of Americans (not mentioning those in other areas of the world) don’t have the luxury of time - they need innovative breakthroughs as soon as possible. After political lobbying, the Senate in 1954 gave the NCI (National Cancer Institute) the money to conduct research. Mukherjee writes that “Between 1954 and 1964, this unit would test 82,700 synthetic chemicals, 115,000 fermentation products, and 17,200 plant derivatives and treat nearly 1 million mice every year with various chemicals to find an ideal drug” (122). The NCI, while doing research, were extremely careful to not gain a negative reputation, for while treatments were desired ardently, they had to make sure to keep the patients alive. For instance, when they prescribed a two-drug regimen to deal with the cancer, they found that while it was hard to survive under such conditions, it gave better results. A doctor, MIn Chiu Li, later discovered that cancer treatment should continue long after physical symptoms have abated. While this may sound like common sense for most people today, at that point in time it was viewed as absurd, causing Li to be fired. Regardless, the lesson had been learned: a patient who many seem temporarily fine may not be in that same state in the future. As Mukherjee writes, “As Li had predicted, with several additional doses of methotrexate, the hormone level that he had so compulsively trailed did finally vanish to zero … While the patients who had stopped the drug early inevitably relapsed with cancer, the patients treated on Li’s protocol remained free of disease-even months after the methotrexate had been stopped … This strategy-which cost Min Chiu Li his job-resulted in the first chemotherapeutic cure of cancer in adults” (138). Upon this discovery, chemotherapy entered a new age: instead of radically treating patients through physical amputation, doctors would use punishing levels of drugs to kill off cancer cells. Two scientists who were colleagues, Freireich and Frei, developed a regimen to deal with cancer. The chemicals they used were vincristine, amethopterin, mercaptopurine, and prednisone, causing it to be known as the acronym VAMP.
VAMP was described by Mukherjee as life-threatening and targeting leukemia. When Frei and Freireich presented it to the scientific society, they gained negative reception, as many worried that few people would survive the routine. Freireich later recounted that “‘it was a terrible, catastrophic showdown. We were laughed at and then called insane, incompetent, and cruel.’” (144). The trial, though, was launched in 1961. When the children were first given VAMP, many of them slumped close to death, for it wiped out many of their cells. However, after three weeks, some of his patients recovered: “The bone marrow biopsies came back one after another-all without leukemia cells. Red blood cells and white blood cells and platelets sprouted up in an otherwise scorched field of bone marrow. But the leukemia did not return … This-after near-complete devastation-was a remission so deep that it exceeded the expectations of everyone at the NCI” (145). When another trial was used, the results also seemed to be successful. However, the success, like most of the efforts against cancer, was short-lived: while the leukemia had been largely killed off, they invaded the brain. Mukherjee writes that although VAMP was successful at destroying cancer cells in the body, the leukemia cells had simply colonized the nervous system, causing most of the children treated to die. Despite this, a few children remained perfectly fine, and lived cancer-free for the rest of their lives. Mukherjee then writes of Hodgkin’s disease, which frequently involves the inflammation of the glands of young men. One of Mukherjee’s patients found out he had Hodgkin’s disease when he was twenty four. Hodgkin’s disease, unlike many other cancers, spreads locally - it is much more predictable. Vincent DeVita, a doctor, invented MOMP (composed of methotrexate, vincristine/Oncovin, nitrogen mustard, and prednisone), a highly toxic combination (like VAMP) to deal with advanced Hodgkin’s disease. While VAMP was dangerous because it drastically decreased the white blood cell count of children, MOPP (a later version of MOMP) was terrifying in that it caused people to literally die from nausea. Mukherjee details, “The nausea that accompanied the therapy was devastating. It appeared suddenly, then abated just as suddenly, almost capable of snapping the mind shut with its intensity … Several young men and women, cured of Hodgkin’s disease, would relapse with a second cancer-typically an aggressive, drug-resistant leukemia-caused by the prior treatment with MOPP chemotherapy. As with radiation, cytotoxic chemotherapy would thus turn out to be a double-edged sword: cancer-curing on one hand, and cancer-causing on the other” (165).
While MOPP brought about traumatic and devastating experiences, it was effective in certain cases, causing swollen lymph nodes to go back to normal in mere weeks. That is, in one trial, in just half a year, thirty-five of the forty-three patients enrolled had been completely cured of Hodgkin’s disease. Another doctor, Donald Pinkel, a student of Farber, believed that VAMP didn't succeed because it wasn’t intensive enough. He coined the term “total treatment,” which involved combinations of combinations (up to eight chemicals could be administered to the patient at once); Mukherjee writes that when it comes to the treatment, it is tortuous, for “To start … the standard antileukemic drugs were given in rapid-fire succession. Then, at defined intervals, methotrexate was injected into the spinal canal using a spinal tap. The brain was irradiated with high doses of X-rays. Then, chemotherapy was bolstered even further with higher doses of drugs and alternating intervals, ‘in maximum tolerated doses.’ Antibiotics and transfusions were usually needed, often in succession, often for weeks on end. The treatment lasted up to two and a half years; it involved multiple exposures to radiation, scores of blood tests, dozens of spinal taps, and multiple intravenous drugs … Even at St. Jude’s, the regimen was considered so overwhelmingly toxic that … the senior researchers, knowing its risks, did not want to run it” (168). Mukherjee writes that oncologists called this strategy “total hell.” From 1968 to 1979, there were eight trials, and the results were overwhelmingly successful: out of the thirty one patients, twenty seven were completely free of cancer. Furthermore, “The median time to relapse … had stretched out to nearly five years-more than twenty times the longest remissions achieved by most of Farber’s first patients” (170). In that trial, one third of the patients who were cured never experienced a relapse. In total, over the years, there were 278 patients. Among those who had been cured, only a fifth relapsed, while the other eighty percent remained cured.
A major part of cancer is obviously the cause, hence the somatic mutation hypothesis of cancer. This theory states that carcinogens (things which increase the likelihood of getting cancer) are dangerous, and said carcinogens include soot, smoking, and tobacco. Viruses can also cause cancer, such as RSV, a virus that spread from cell to cell. Epstein-Barr virus (described with the acronym EBV) was also found to be a disease that can cause cancer. During the presidency of Richard Nixon, the National Cancer Act was passed after some struggle. The National Cancer Act allocated $400 million to cancer research in 1972, $500 million in 1973, and $600 million in 1974. While this was a major victory in the war against cancer, many scientists viewed such a stratagem as being premature, for they felt like they didn't know much about cancer itself. Faber, soon after the bill was passed, died on March 30, 1973 in his office from cardiac arrest. Mukherjee then describes that he eventually called Carla after her chemotherapy, for he had good news; there was no sign of leukemia in her marrow. Mukherjee remarks that Faber, in a sense, died at the right time, for in 1973 scientists began debating the very fundamentals and assumptions of cancer treatment. For instance, Halsted’s belief in the validity of radical surgery was largely discredited, and people began focusing more on the patient. Mukherjee then writes of the invention of Cisplatin (short for “cis-platinum”), which had the molecular structure of an atom with four branches. For many years, chemists saw it just as a beautiful atom due to its symmetry. This all changed when Barnett Rosenberg, a biophysicist at Michigan State University, found by accident in a laboratory that cisplatin could cause bacterial cells to multiply less rapidly. That is, “Cisplatin had chemically attacked DNA with its reactive molecular arms, cross-linking and damaging the molecule irreparably, forcing cells to arrest their division” (204). Cisplatin then became the next drug which was aggressively used to combat cancer, and, for some patients, it effectively cured them of their cancer; they didn't even relapse.
Cisplatin, on the other hand, also produced terrible physical symptoms: it filled the patient with nausea that would rarely abate, causing patients to vomit an average of twelve times a day. Despite that, it was viewed as being miraculous due to its remission rates. Oncologists were eventually viewed disfavorably as they experimented with various treatments, as various patients said that they felt like their doctors didn't care about them. This attitude and fear towards oncologists was present in many literary works, such as Wit by Edson. A new treatment was eventually invented to deal with prostate cancer. It should be noted, though, that most of the people with prostate cancer are old people, so they usually die with prostate cancer than because of it. It was later hypothesized that prostate cancer could be effectively dealt with by cutting off testosterone levels. When this was attempted, this also led to the feminization of male bodies. This hypothesis was soon extended to women, and an estrogen antagonist (a drug which decreases the amount of estrogen receptors available), ICI 46474, long believed to be a useless drug, was used to treat women who were dying of advanced, malignant breast cancer. To the amazement of all, it was effective for ten out of forty six patients, for it rapidly decreased the size of tumors and lung metastases, lessened bone pain, and sophened the lymph nodes. An oncologist, Gianni Bonadonna, did research on the relationship between relapsing and continuous treatment. She criticized the medical society as being hostile to mere experimentation, seen in their painful adherence to rigid dogmatism, clearly illustrating the importance of open-mindedness and intellectual flexibility. Or as Nietzsche would put it, “The snake which cannot cast its skin has to die. As well the minds which are prevented from changing their opinions; they cease to be mind.” Despite their resistance, Bonadonna did her research, and found that half of the women who were given no therapy after their initial treatment relapsed, while only a third of the women who received therapy relapsed. Mukherjee then writes of the importance of palliative care, as certain patients may not survive chemotherapy; those who are very unlikely to survive should be given the opportunity to leave life gracefully and in a way unfettered by agony and discomfort.
Mukherjee then gives some statistics regarding the amount of lives saved through cancer treatment. In the end, it was estimated that 35,000 to 40,000 lives were annually saved from dying of cancer. Put in the big picture, it could be calculated that “less than one in twenty patients diagnosed with cancer in America, and less than one in ten of the total number of patients who would die of cancer, had benefited from the advances in therapy and screening” (228). Regardless, progress was progress, but it was still disconcerting - while diseases like tuberculosis found efficient treatments, cancer refused to abate (though to be fair, tuberculosis remains one of the biggest killers of Homo Sapiens today, killing more than one million people a year). Mukherjee then writes that cancer treatment began to focus more on prevention over the years, as many of the causes of cancer are wholly preventable. For instance, a surgeon, Percivall Pott, found in 1775 that most of his patients who had scrotal cancer were chimney sweeps: “poor, indentured orphans apprenticed to sweeps and sent up into chimneys to clean the flues of ash, often nearly naked and swathed in oil” (237). Soot, of course, was a carcinogen, and in 1788, the Chimney Sweepers Act was passed, which stated that children under the age of eight are not to be employed as chimney sweeps. By 1875, using young children as chimney sweeps was entirely forbidden. Remarkably, “the man-made epidemic of scrotal cancer among sweeps vanished over several decades” (239). This clearly illustrates that many cancers could be prevented by informing the public and by passing safety legislation. Some doctors then began turning their attention to the cigarette, which was a global addiction. It was everywhere, for young people smoked it to show their defiance (today it takes the form of vapes), professionals smoked it to calm their nerves, and even political prisoners in labor camps such as the Gulags used it as currency. Although doctors tried to bring this pressing topic up repeatedly, they constantly faced setbacks, as the cigarette industry was extremely powerful: in the early 1960s, $5 billion worth of cigarettes were sold annually. Furthermore, cigarette companies pushed for misinformation campaigns and used political lobbying to work against reform.
Doctors eventually showed that cigarettes can cause cancer by using mice, and the tobacco industry responded by stating that mice were too unlike humans to draw any parallels. Despite the efforts of the tobacco industry, doctors were able to use surveys and medical data to show the truly detrimental effects of smoking. That is: “the increased risk of cancer was nearly five- or tenfold in smokers,” the effects of smoking were consistent across many demographics, “tobacco was linked to lung cancer-precisely the site where tobacco smoke enters the body,” “the longer one smoked, the greater the increase in risk,” “the more one smoked in quantity, the greater the risk for lung cancer,” and “smoking had been correlated … with lip, throat, tongue, and esophageal cancer” (255-6). Evarts Graham, who came up with much of the aforementioned data, quit smoking, but he still died from aggressive lung cancer at the age of seventy four. As he put it, while it was true that he had quit smoking for five years, he had made smoking a frequent habit for fifty years, which caused irreversible damage. When data like this came out, the tobacco industry had to respond by putting an FCLAA label which warned of the potential danger of cigarettes. Furthermore, the surgeon general clearly stated that tobacco could cause cancer, and public opinion worsened towards the industry. The public became quite enraged when they found out that the tobacco industry had clearly and consistently lied over the years of the potential danger of smoking by trying to make it seem safe. Furthermore, even when the tobacco industry was in clear trouble, they refused to stop their denial, seen in how they tried to compensate people who had developed a tobacco addiction as little money as possible, as well as engaging in an ad hominem assault on a doctor who had studied cancer in mice, seen in how they asked him why he wasn’t trying to save human beings (quite ironic, since they were the ones greatly responsible for killing them). The cigarette industry still remains a very powerful one, and people continue to die of completely preventable lung cancer. This is especially relevant with the relatively recent invention of vapes which primarily target young people, which is a despicable piece of marketing. Mukherjee tellingly writes that “despite the evident seriousness of this addiction and its long-term consequences, tobacco consumption continues relatively unfettered even today. Smoking rates, having plateaued for decades, have begun to rise again in certain demographic pockets … a nation where nearly every new drug is subjected to rigorous scrutiny as a potential carcinogen, and even the bare hint of a substance’s link to cancer ignites a firestorm of public hysteria and media anxiety-one of the most potent and common carcinogens known to humans can be freely bought and sold at every corner store for a few dollars” (275).
Mukherjee then writes that the mid and late 1980s saw the emergence of extreme cancer treatments; medicine, at that point in time, truly seemed to be capable of anything. Bone marrow transplants were used, and an extreme treatment was devised: chemotherapy would be used to annihilate as many cancer cells as possible, and the frozen marrow would be dethawed and given back to the patient to start their recovery. Mukherjee writes of the invention of the ABMT treatment, which made it possible to give previously unimaginable levels of drugs. The doctor Frei then invented STAMP (Solid Tumor Autologous Marrow Program), which, as its name suggested, was supposed to violently stamp cancer out in a patient. The first patient to undergo it was a thirty young old woman who had terminal cancer. To begin the treatment, bone marrow was needed, and disaster struck, almost ruining everything: the needle put into her skin broke. Fortunately, it was safely removed, though it was too close for comfort for the doctors involved. STAMP seemed to work, as it produced powerful remissions. While more cancer treatments were invented, not everyone could afford them, for they could cost anywhere from $50000-$400000. There was a case where a woman who had aggressive cancer died after she was denied insurance by her insurance company because the company alleged that the treatment was still “investigational,” clearly showing the ethical implications of medical care. Furthermore, scientists discovered that the war on cancer was at a stalemate, for the numbers weren’t going down. Mukherjee then discusses the biology of cancer. Cancer cells, unlike regular cells, are immortal, for they don’t respond to apoptosis, or orders to commit suicide from the body. Furthermore, the cancer cell proliferates of its own accord, ignoring the surrounding environment. Cancer cells are capable of doing harm because they could sometimes move to other areas, and they also make use of angiogenesis, forming blood vessels to provide them with the body’s blood. Cancer cells were discovered to be capable of occurring because of chromosomes/genes, seeing how some cancers are highly heritable. Furthermore, the reason cancer cells don’t die or listen to the body’s signals is that one of their receptors responsible for turning them off has been switched off by accident. As Mukherjee puts it, cancer cells begin when “positive” and “negative” genes cause a cell to become cancerous. That is, positive genes add behaviors to a cell that is cancerous: “In their mutant form, these genes are driven into perpetual hyperactivity, unleashing cell division beyond control … ‘a jammed accelerator,’” while negative genes like Rb, otherwise known as anti-oncogenes or tumor suppressor genes, serve as a safeguard against uncontrolled cellular reproduction. However, in cancerous cells, tumor suppressor genes have been shut off, which causes a cell to lose control.
Mukherjee writes that doctors have tried to isolate the genes responsible for causing cancer, and they were able to identify some. By the early 1990s, scientists have realized that cancer is an eerie parallel of regular biology, for cancer is entirely genetic: “Nothing is invented; nothing is extraneous. Cancer’s life is a recapitulation of the body’s life, its existence a pathological mirror of our own … down to their innate molecular core, cancer cells are hyperactive, survival-endowed, scrappy, fecund, inventive copies of ourselves” (388). Mukherjee provides an effective piece of narration to help the audience understand the development of cancer. In the narration, a forty-year-old fire-safety-equipment installer accidentally inhaled a sliver of asbestos from his equipment. When it enters his lungs, a positive mutation happens, causing a cell to multiply rapidly. A decade later, the tar of his cigarette coincidentally interacts with the rapidly-producing cells in his lungs, activating a second oncogene. Another decade later, those cells are screened via an X-ray, and the radiation creates another mutation. Next year, another accidental mutation deactivates the second tumor suppressor gene, thereby “creating a cell that possesses two activated oncogenes and an inactive tumor suppressor gene” (389). After that happens, the cancer begins to truly grow, using angiogenesis to support itself. It takes some time for the man to realize that he has a problem, and when chemotherapy is finally administered, the cancer has spread to his pelvis and ribs. When put on chemotherapy, many of the cancerous cells are killed, but the cells which survive the deadly toxins by natural selection become resistant, and “Seven months after his initial diagnosis, the tumor relapses all over the body-in the lungs, the bones, the liver. On the morning of October, 17, 2004, deeply narcotized on opiates in a hospital bed in Boston and surrounded by his wife and children, the man dies of metastatic lung cancer … I began this as a hypothetical story of cancer. The genes, carcinogens, and the sequence of mutations in this story are all certainly hypothetical. But the body at its center is real. This man was the first patient to die in my care during my fellowship in cancer medicine at Massachusetts General Hospital” (390).
Mukherjee then provides a helpful list of attributes which cancer cells possess. They are, to summarize: (1) rapid proliferation/pathological mitosis (caused by oncogenes like ras or myc), (2) inability to obey growth-inhibitory signals (due to inactivated tumor suppressor genes like retinoblastoma/Rb), (3) inability to obey apoptosis/programmed cell death (because they’re immortal), (4) “Limitless replicative potential: cancer cells activate specific gene pathways that render them immortal even after generations of growth,” (5) the ability to grow new blood vessels (angiogenesis), and (6) tendencies to migrate to other parts of the body (metastasis) (391). Mukherjee then writes of the future of cancer treatment. He states that even though cancer remains a deadly disease, massive improvements have been made. Jimmy, for instance, recovered from cancer, never relapsed, and led a normal life. He then writes of his own patients, detailing how Carla survived. The young man who went to him to be treated for Hodgkin's disease was cured, though he suffered scarring. Mukherjee writes that these patients weren’t miracle cases, but fairly regular ones: “They represent a routine spectrum of survivors-Hodgkin’s disease cured with multidrug chemotherapy; locally advanced lung cancer controlled with surgery, chemotherapy, and radiation; lymphoblastic leukemia in a prolonged remission after intensive chemotherapy” (400). Mukherjee then describes that many cancers have been given effective medication, and various medicines are awaiting approval and hold much promise. Social trends have also improved in some ways, for when social people quit smoking, those around them commonly did too. However, this should rally people against tobacco once and for all, for when vigilance is relaxed, cancer cases commonly return. Scientists have also begun to map a genome map to see which genes are closely correlated with cancer - those which are closely tied jut out from the map like mountains, while those which are mostly unrelated remain flat like a board. It was discovered that thirteen pathways were closely linked to cancer. While Mukherjee acknowledged that the creation of future cancer treatment would be a daunting task, like the development of past treatments, it could also be seen as a relief: thirteen, though significant, is not a very large number. Mukherjee then reminds the audience of current trends: as people live to older ages, more people will experience cancer. Cancer will therefore become the new normal, replacing previous diseases as a large killer.
Mukherjee then hypothesizes about the future of cancer treatment. He says that because cancer is intrinsically linked with our biology, and mutations would probably occur sometime or later, it is possible that it might never be completely stamped out, for it acts as a limit to our survival: “As our cells divide and our bodies age, and as mutations accumulate inexorably upon mutations, cancer might well be the final terminus in our development as organisms” (462). He then says that destroying cancer altogether is an extreme goal; instead, we should settle for a more realistic option by focusing on preventing people dying from cancer when they’re still young. He then discusses Atossa, and uses her to illustrate the evolution of cancer treatment, showing the audience how much technology has improved: in 2500 BC, she would be offered no treatment, in 500 BC, she would undergo a mastectomy, in the medieval period her black bile would be purged to no avail, in 1778 she would undergo localized surgery and “remote sympathy,” in 1890, surgeons following the lead of Halsted would give her a radical mastectomy, in the 1950s, she would be given a simple mastectomy or a lumpectomy and radiation, in the 1970s, she would be given chemotherapy, in 1986, the gene responsible for the cancer would be found, and in the mid-1990s, her cancer would be diagnosed at an early age and her daughters would be screened and subsequently treated for cancer. Mukherjee then writes that in 2050, Atossa might “arrive at her breast oncologist’s clinic with a thumb-size flash drive containing the entire sequence of her cancer’s genome, identifying every mutation in every gene. The mutations will be organized into key pathways. An algorithm might identify the pathways that are contributing to the growth and survival of her cancer. Therapies will be targeted against these pathways to prevent a relapse of the tumor after surgery” (465). Mukherjee then writes as a counterweight and reality check that the survival rates for some cancers have not improved by much. For instance, pancreatic cancer still kills people painfully very quickly. Regardless, it is impossible to predict progress, thereby making major discoveries and better treatments not only possible, but quite likely, so long as doctors continue their valiant and diligent efforts. Mukherjee then writes inspiringly that “onkos,” used by the Greeks to describe tumors, could be interpreted as “mass” or “burden.” However, “onkos” came from the word “nek.” “Nek” “means to carry, to move the burden from one place to the next, to bear something across a long distance and bring it to a new place. It is an image that captures not just the cancer cell’s capacity to travel-metastasis-but also Atossa’s journey, the long arc of scientific discovery-and embedded in that journey, the animus, so inextricably human, to outwit, to outlive and survive” (466-7).
Personal thoughts:
The Emperor of All Maladies by Siddhartha Mukherjee is a great book detailing the history of cancer and cancer treatment. It is effective due to Mukherjee’s explanation of the disease, his excellent description and narration of the treatments, and his use of personal anecdotes over his years as an oncologist. After reading this book, one will definitely be much more informed of cancer, and it is entirely worthwhile to be read. Indeed, while the subject matter is upsetting due to its relevance, it can also be seen as a tale of triumph; as Mukherjee noted many times, humanity has come a long way in the field of medicine and technology in just a few thousand years, which, geographically speaking, is nothing - the Earth, after all, has existed for 4.5 billion years. I highly recommend The Emperor of All Maladies to anyone interested in cancer, medicine, culture, poignant writing, and harrowing stories of survival and recovery.
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