Cancerland

by David Scadden

  In modern times, the construction of Egypt’s Aswan High Dam flooded thousands of square miles and created vast new habitats for the snail. Rising rates of schistosomiasis brought death and suffering, which inspired Mahmoud’s work. In 1972, he published his first paper on the disease, which addressed the mechanism it triggered to cause anemia. Mahmoud then systematically attacked aspects of the disease ranging from its life cycle to its epidemiology. (The dam and the way of life in Egypt were key in this regard.) Mahmoud probed the worm for vulnerabilities in its various stages and development and places of residence. He conducted research on basic concerns, such as the best way to count the number of tiny worm eggs in a urine sample, to the mutation of the parasite in diabetic mice. Along the way, he became keenly interested in the fact that in some cases, the human immune system defeated the parasite, which suggested a pathway to a vaccine. A safe vaccine would, of course, engage the body’s immune system to defend against the parasite and make postinfection treatment, with its side effects and unpredictable results, unnecessary.

  Viewed from the distance of a few decades, I can see Mahmoud’s work demonstrated how a huge problem could be broken into pieces for research. He was, by the time we met, a master scientific navigator who turned the disease he studied into a world of its own, completely worthy of exploration. In our first encounter, I asked him some very basic questions about the immune system’s inability to reliably defeat schistosomiasis—how could it not recognize and destroy a worm?—and he wasn’t content to just talk. He invited me to join his lab and contribute to the search for answers.

  At the moment he made the offer, I wasn’t at all confident that I could develop the skills, including the habits of mind, that scientists possess. I thought that serious research was done by men and women who were so extraordinary that I shouldn’t even imagine joining them. But I accepted Mahmoud’s offer and took my place at a lab table amid the type of glassware that I had once clinked around with in my parents’ basement. If I didn’t yet have the scientific reflexes to be a real investigator, Mahmoud was willing to let me start developing them.

  My first assignment involved putting immune cell lymphocytes, the body’s defenders, together with the tiny schistosome worms. Once they had a chance to do battle, I used a microscope to do an assessment, counting the parasites that remained, as well as the immune cells. Ideally, this labor would be one step forward in the effort to discover what might be enabling the immune response, and in time, this knowledge might be the key to a vaccine.

  In the lab, I could see, in real time, that after first contact, the immune cells made good progress against the flukes. However, at some point, the tide turned. As Mahmoud told me, “The worm is capable of altering itself in a way that some survive.” As this response occurred, the immune cells also adapted. As the weeks passed, my fluke counts varied, with the invader prevailing at some points and the defenders succeeding at others. In this case, the metaphor that suggests the body is the arena where battles are waged seemed especially apt. This work was simple, but it wasn’t an academic exercise designed to produce a predictable result. Mahmoud saw no reason to engage medical students in busywork, so even though it required more from him, he assigned us real work. The work was quite thrilling to me, because I could see cell biology at work through the lens of the microscope. I never accomplished the goal of capturing that moment when the immune cells vanquished the parasite. Technology hadn’t advanced far enough to make this possible. But the work had value nevertheless, and it opened my eyes to the possibilities of medicine based on immunology. It also set me on the road to becoming a scientist. These positives took the sting out of being left off the list of authors when the study I contributed to was published. Like every young doctor or scientist, I craved that kind of recognition, but Mahmoud gave me so much more that I couldn’t imagine complaining about such a small disappointment.

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  The hope I felt doing science in Mahmoud’s lab helped to balance much of what I saw in my clinical education where we doctors in training encountered patients at every stage of care, from admission through treatment and then in recovery. Much of what I witnessed in the various university-affiliated hospitals (included were a public hospital and a Veterans Administration facility) shocked me. It wasn’t that the level of care was substandard. In fact, for the time, it was quite high. What was shocking was the trauma I saw inflicted on patients’ bodies despite all the medicines, advanced techniques, and precautions. Nowhere was this more evident than it was in the operating room.

  Modern surgery can be traced to the famous ether dome at Massachusetts General Hospital, where, in 1846, a dentist named William Morton used the gas to render unconscious a man named Edward Gilbert Abbott. (Earlier experiments with the gas had involved healthy volunteers who inhaled it and then stumbled around laughing. These demonstrations were dubbed “frolics” and were considered a form of amusement for participants and witnesses alike.)

  The ether dome, which still stands, is a space as austere as an old New England church. Observers gaze down from rows of wooden seats that rise steeply from the operating room floor and are separated from each other by curving wooden barriers, which are painted white. Abbott, who was strapped to a chair, was given enough gas to make him completely unresponsive. A Harvard Medical School professor named John Collins Warren then removed a tumor from Abbott’s neck. Warren’s assistants, who were accustomed to holding patients still as they were cut, probed, and stitched, watched in wonder.

  Dr. Warren, who was perhaps the most respected surgeon in the country, worked quickly and without saying a word. He knew that anesthesia was so revolutionary that skeptics might think it was a scam. Eager to quell the skeptics, Warren broke his silence as he finished the operation and declared, “Gentlemen, this is no humbug.” Abbott, upon awakening, said he felt that his neck had been scratched.

  When it worked, and it usually did, anesthesia made surgery a less painful and chaotic process, but it remained a gruesome affair, especially for the uninitiated. Except for truly minor procedures, surgery involves the kind of cutting, bloodletting, and (sometimes) breaking of bones that you might imagine occurs in a butcher shop. Although it is done with infinitely more care, surgery on human beings exposes us as animals quite similar to others, with our skin and layers of fat, muscle, and organs. Some of the odors that emanate from the body, like the metallic scent of blood or the smoky/meaty aroma from cauterization, are easy to imagine. Infected body parts and organs can be so putrid that the people in the OR sometimes put oil of wintergreen on their masks so they can continue to work. In my early training, I may have been most upset by amputations done on patients who had Buerger’s disease. Almost always caused by smoking, this illness blocks blood supply to the extremities, causing pain, and gangrene, which often leads to the loss of fingers, toes, hands, or feet. The journalist John McBeth wrote about his struggle with this disease and the amputation of his right leg in a book chapter he called “Year of the Leg.”

  Although generally less dramatic than leg amputations, cancer surgeries of the late 1970s were done without most of the less-invasive techniques used today. Big incisions were required to expose tumors, which varied greatly in size and appearance. Some small lung cancers, for example, look like tiny heads of broccoli sprouting hairlike microvilli. In a smoker with advanced disease, the lung itself may be blackened by tobacco tars and the cancer could be a diffuse white mass. Brain cancers are often shaped by the surrounding structures and wind up looking like little pyramids, dumbbells, plums, or kidney beans.

  The surgeries performed to remove malignancies were often quite complicated procedures. Great care was taken to remove as much cancerous tissue as possible without causing too much collateral damage. This was extremely difficult to do in this era before modern imaging technology and computer-assisted resection. Teams of physicians and nurses worked on patients who could be under general anesthesia for many hours. With less-reliable technology than we have toda
y, manual experience was critical for the members of these teams.

  The drama and stress of the operating room help explain why you find certain personality types beneath the surgical masks. As one study presented at a medical education conference in 2013 indicated, surgeons tend to be energetic, aggressive extroverts. They are less agreeable than other doctors, but more conscientious. These traits tend to become more pronounced over time. An old surgeon is likely to be among the most self-confident but also the most careful doctors in the hospital. He or she would also be, in professional terms, a direct descendant of William Stewart Halsted.

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  A clinician who was also a scientist, Halsted was the most influential American surgeon of the early twentieth century. He rose to fame after performing two emergency lifesaving procedures on family members. In the first, he removed his mother’s gallbladder in an operation done on her kitchen table. In the second, he used his own blood to transfuse his sister, who was hemorrhaging after giving birth. Halsted created the first formal training programs for surgeons, invented sterile rubber gloves for use in the operating room, and applied the scientific method to research into anesthetics. Here he met his match in the newly developed medicine called cocaine, which he tested on himself. A paper written under the grip of addiction was so garbled it almost ruined him. However, he recovered both his health and his standing in the medical community and saved countless lives with dramatic operations. None was more dramatic than the radical mastectomy surgery he devised for breast cancer patients.

  Halsted, who was an imposing figure with piercing blue eyes and a forceful personality, is widely regarded as the most important surgeon in U.S. history. His methods greatly reduced the risk, suffering, and mortality rates associated with most operations. This success made him a kind of demigod in American medicine, and he used his clout to influence practice across the country. In the case of his radical mastectomy, Halsted proselytized for his aggressive operation with messianic zeal. In his view, only the removal of the entire breast, as well as adjoining muscle and lymph nodes, could possibly save a patient with any trace of a malignancy. It became the standard and remained so even after a so-called modified radical mastectomy was devised in the 1940s.

  As late as 1972, Halsted’s radical mastectomy was still the surgeon’s treatment of choice, with the largest percentage of patients undergoing this kind of procedure. Many patients also favored it, believing that the most dramatic intervention gave them the best shot at long-term survival. But as data accumulated, including some generated by studies that enlisted courageous patients in comparison trials, doctors began to see that there was often no real advantage to the Halsted operation. Almost two-thirds of women who got a radical mastectomy died within five years, a result that had been unchanged since the 1930s. Press reports on these numbers often mentioned First Lady Betty Ford, who had undergone a radical mastectomy, as an example of someone who may not have required it. One book on this subject noted that most of the doctors who performed radical mastectomies were not actually cancer specialists and may not have kept up with the research. When I took care of women who’d had radical mastectomies, I saw why they might question the treatment. The operation was more than disfiguring. It was absolutely devastating to the bodies of women who were left with little more than heavily scarred skin stretched over their ribs. No wonder some of them had their doubts about the procedure and whether taking so much flesh was really necessary or worth the loss of a part of themselves so visible and emotionally freighted.

  Mrs. Ford’s candor about her experience with mastectomy, at a time when many people still hid the fact that they had breast cancer, helped move society toward more open conversations about diagnosis and treatment of a disease that caused thirty-three thousand deaths per year. Science was also yielding information at a quickening pace. In 1974, researchers at the M.D. Anderson Hospital in Houston published a study showing a genetic component in breast cancer risk, and in 1975 came news that an early-detection program was extremely effective at finding signs of the disease at a stage when it could be treated most effectively.

  By 1977, patients and activists were leading a growing effort to bring cancer treatment out of the shadows and to encourage more thoughtful treatments. Women were so willing to talk about breast cancer that twenty of them staged a protest inside the Saks Fifth Avenue department store in New York when managers refused to hire a woman who had recently had a mastectomy. The protesters, among them members of a postmastectomy support group, picketed the store and ceremoniously destroyed their Saks credit cards. Protesters like the ones at Saks and self-help support groups that advocated for patient autonomy irritated physicians who still clung to the doctor-as-God identity that had become common in the profession. To be fair, a great many patients wanted their doctors to be gods, because they found comfort in the idea that someone more knowledgeable was in charge. This is why Lewis Thomas described a physician’s confidence as a source of “faith and hope,” which my experience suggests has real value to patients and their families, who are reassured by the feeling that their shamans have a connection with some force beyond their own. At the same time, however, physicians know the limitations of medicine and that complications are common and so varied that even the simplest interventions can backfire. Even the simplest of “good” medicines, like penicillin, can have a lethal side in the wrong or, in penicillin’s case, allergic person.

  As a doctor in training, I occasionally thought about the Wizard of Oz pulling levers behind a curtain as I sought to be a source of assurance for patients. Sometimes I was simply borrowing the confidence of senior doctors, who had seen so many similar cases that I had confidence in their judgments. Nevertheless, the fear that I was a fraud persisted, and many of my medical school classmates harbored similar feelings.

  My fears about being an impostor ebbed a bit as I was mentored by the top clinicians, including Richard Graham, who always seemed to strike the right balance, reassuring patients without promising miracles. Unlike other senior doctors, Graham adapted well to challenges that came with patients who had begun to read media articles about their illnesses and came armed with both questions and opinions. More and more people wanted to have a greater say in their care. For women dealing with breast cancer, the issue was also linked to the larger issue of gender equality. A great many felt that the largely male medical profession had too much say over their bodies, and they were eager for more of a voice in how they were treated.

  Patients who did their own research often discovered options for care that they had never known existed. In the case of breast cancer, a surgeon at Cleveland Clinic, which was affiliated with Case, began performing an operation called a lumpectomy in the late 1960s. This technique involved removing the tumor and just a bit of nearby tissue, while leaving most of the muscles intact. The surgeon, George Crile Jr., was from a royal family of medicine.

  His father, George Washington Crile, who is credited with pioneering blood transfusion in the United States, became famous as a field surgeon in the First World War. He was so respected in military circles that a World War II Liberty ship was named for him.

  Heir to a great name in medicine, the junior Crile was so prominent that he could command a hearing for his ideas, but even he took a risk as he stood against Halsted orthodoxy. His critics said his success came because his patients were cherry-picked in a way that guaranteed Crile success. At one American Cancer Society meeting, a surgeon angrily complained that “women are coming in waving the articles [about lumpectomy] in their hands.” This was precisely the point, in Crile’s mind. He considered many radical surgeries unnecessary and thought women should have more options.

  Some cancer surgeries were followed by radiation therapy, which aimed to kill additional tumor cells by damaging their DNA. Radiation was first used to destroy cancer cells in 1896, a year after Wilhelm Röntgen discovered x-rays. In the 1930s, the famous radium watch dial painters’ case showed that radiation also caused cancer.
Medicine is full of such paradoxes, so the radiation-cancer dynamic wasn’t shocking to physicians. However, it did complicate the public perception of a treatment that was the only option for certain brain cancers and commonly used against leukemias and lymphomas.

  As I saw in the hospitals affiliated with Case, radiation therapy came with side effects, including exhaustion, nausea, and sometimes pain. However, these were generally not as severe as the side effects caused by chemotherapy, which was also given to people suffering from a whole range of cancers. Developed and tested in the decades after the Second World War, chemotherapy drugs were basically poisons. They were medicines if they killed more cancer cells than normal cells, but they always caused lots of collateral damage. Their effectiveness had been shown first in children with leukemia. Success was later seen in testicular cancer and lymphoma, offering drug-induced cures when previously only surgery (“A chance to cut is a chance to cure”) was able to claim curative effects. That led to a heady optimism and application of drugs singly and in combination against a range of cancers. Many—like lung, liver, and pancreatic cancer—were largely insensitive, but advances were made in colon and breast. Inevitably, these cell toxins acted blindly, killing healthy cells along with cancerous ones and damaging vital organs as well as tumors. Cells that divided rapidly, like those in bone marrow, the mouth, and the gut, were generally more vulnerable.

  The focus of early chemotherapy drugs was to poison rapidly dividing cells, since that seemed a hallmark of a malignancy (a presumption since shown to often be incorrect). The result was to halt production of the normal cells that rapidly turn over in the body. Cells for virtually every tissue barrier against the outside world—such as hair, nails, and the tissues of the skin, mouth and airway, and intestines—are replenished at very high rates every minute of every day. When a poison is introduced that stops cell division, the consequences are predictable: mouth ulcers, hair loss, diarrhea, and infections. Low-level infections occur almost uniformly as the intestinal barrier is compromised and there is limited surveillance from immune cells to clear the invading bacteria. That causes the general misery of fatigue, fever, and loss of appetite we associate with infections. Further, the poisons affect sensory cells and often lead to severe nausea for which there was little potent antidote until the late 1980s. In my days as a resident, I saw hundreds of people suffering from these symptoms. Nurses and doctors tried to make them comfortable, but there was little we could do. The struggle could be heartbreaking to watch. Often lying still, except when they had to vomit, people knew they were somewhere near the precipice of death from the drugs that were supposed to help them. In rare cases, chemo would kill by damaging the heart, lungs, or kidneys, or making it impossible for the body to fight a serious infection.