Pandora's DNA: Tracing the Breast Cancer Genes Through History, Science, and One Family Tree

by Lizzie Stark

  Halsted made his mark on the medical profession in part because he appeared at just the right time. Advances such as antisepsis had been discovered in Europe but had not spread to, for example, the hospital where Halsted began his career. As Mukherjee writes, he “entered surgery at a transitional moment in its history. Bloodletting, cupping, leaching, and purging were common procedures.” In 1877 Halsted left for a two-year tour of Europe, where he met and studied with the continent’s best surgeons and pathologists—including Virchow’s students. And he brought some of their practices—including antisepsis—home with him.

  Halsted pioneered many important medical techniques, and he must have had nerves of steel. In 1882 he removed his own mother’s gallbladder on her kitchen table, one of the first such operations; he was also the first surgeon to successfully transfuse blood—into his own sister, who was bleeding after childbirth. An early adopter of antiseptic techniques, he built his own facilities in a tent outside Bellevue because he found the hospital’s operating theater filthy. When one of his nurses suffered raw hands from sterilizing them in carbolic acid before operations, Halsted asked the Goodyear Rubber Company to manufacture a rubber glove, and he introduced them into the operating room. In the mid-1880s during the height of his surgical career in New York, Halsted and his colleagues experimented with cocaine in order to prove its use as a local anesthetic, injecting themselves along the major nerves. Ignorant of the drug’s addictive powers at first, Halsted ended up a cocaine fiend. A trip to a sanatorium in Rhode Island cured him of his dependency by hooking him on morphine. He’d fight the addiction to both drugs for the rest of his life while still maintaining an extraordinary practice.

  Halsted moved with his wife from New York to Baltimore in 1889, where he joined the brand-new Johns Hopkins Hospital as the surgeon-in-chief, but he retired from social life and became a recluse. His perfectionism and desire for control manifested themselves again. He self-administered morphine on a strict schedule and in tightly controlled doses and raised purebred dachshunds and thoroughbred horses. He bought enough French shirts that he could send them back to Paris to be laundered because Americans couldn’t starch a shirt to his requirements. With the same precision and fanaticism, he devoted himself to curing breast cancer.

  Now that anesthesia had made long operations possible and antisepsis had made surgery less lethal, surgeons could perform successful mastectomies more frequently. But patients regularly relapsed months or years after surgery, often around the margins of the original operation, as if shards of cancer had been left behind. English surgeon Charles Moore noticed this pattern in the 1860s and solved the problem by taking more tissue; to spare women by removing less of their bodies was a “mistaken kindness,” he suggested. German surgeon Richard von Volkmann removed a minor pectoral muscle along with the breasts and experienced a recurrence rate of “only” 60 percent. Halsted thought he could do better. So he pioneered a more extensive mastectomy that would become the gold standard for breast cancer patients for the next two generations.

  New York surgeon Willy Meyer and Halsted independently arrived at the same conclusion in the 1890s—the pectoralis major as well as the minor should be removed. Halsted dubbed the procedure a “radical mastectomy,” meaning “radical” in its original Latin sense of “root”—he intended to carve out the roots of breast cancer. But soon, the phrase would also come to mean “extreme.” Removing the breast and pectoral muscles wasn’t enough for Halsted. He knew cancer was a cellular disease and worried that surgeons who cut into the breast or used their hands to remove tissue might spread cancer cells elsewhere in the chest cavity. By the turn of the century, Halsted advocated an operation that removed breast, pectoral muscles, and lymph nodes in the armpit in a single block.

  The brutal procedure caved in women’s shoulders and harmed their arm mobility. Removing lymph nodes could cause patients’ arms to swell painfully with accumulated fluid, a condition known as lymphedema. But the practice also saved lives. And in advanced cancer patients, the operation was palliative—delivering them from tumors that might otherwise burst through their skin—preventing them from rotting to death. Halsted presented a stunning paper on his patients at the 1898 American Surgical Association meeting in New Orleans. Of 133 patients, 76 were more than three years out from surgery, and 52 percent of them had not relapsed—a significant 8 percent improvement over Volkmann’s less radical procedure. In the coming years, Halsted performed hundreds of mastectomies, gathering data that allowed him to assign stages to tumors and helped with prognosis. He figured out that cancer that had spread to lymph nodes had a poorer prognosis than cancer confined to the breast, and he concluded that earlier surgery, ideally performed before cancer spread to the lymph nodes, worked better. As Mukherjee points out, Halsted’s success kicked off a “macabre marathon” to see who could carve out the most tissue. Surgeons cut through the collarbone and further into the chest to excise the lymph nodes stationed there.

  The surgery undoubtedly saved lives, but it relied on a faulty one-size-fits-all approach to cancer and on a misconception of cancer as a local disease that spreads slowly outward from the site of origin. As we now know, some cancers grow slowly, and others grow quickly, or simply aggressively, hitching a ride to other tissues even when the original tumor is small. Mukherjee makes the point that a radical mastectomy cannot cure a woman with metastatic cancer, cancer that has spread to other sites in the body, because “her cancer is no longer a local problem.” In contrast, a Halsted mastectomy might cure a woman with a small local tumor, “but for her, a far less aggressive procedure, a local mastectomy, would have done just as well.”

  In 1957, thirty-five years after Halsted died, my great-aunt El had his eponymous mastectomy on one of her breasts. She had barely reclaimed her thirty-four-year-old body from giving birth to Lisa, her youngest, in January, and by September the dreaded diagnosis arrived. In a letter to her mother, El wrote that she would have the mastectomy because she needed to continue living—she had Ralph and the kids to think of—and that she wasn’t going to be like Trudy. The procedure removed her breast and pectoral muscles, along with the lymph nodes in her armpits and under her collarbone, and the nodes deep in her chest that were positive for cancer. The doctors also biopsied her collarbone and rib bones.

  The surgery wasn’t the only treatment that disfigured her. By the time El developed breast cancer, scientists had discovered more of the weapons in the modern cancer-fighting arsenal. Since she worked as a nurse at a teaching hospital, she had many friends—doctors and surgeons—conducting research. Kathy, her oldest daughter, says she received the most up-to-date medical treatment, including the newer cancer-fighting weapons of radiation and chemotherapy. Radiation had been around for a few decades, but chemotherapy was in its infancy at the time. Kathy believes that her mother was part of a study on chemotherapy, but unfortunately, the details of El’s treatment have moved into the opaque past—her medical records are long gone.

  Radiation therapy and chemotherapy, like so many medical advances, intersect with the legacy of war. In the case of radiation, the intersection is indirect, but personal. The phenomenon of radiation had been discovered in the last years of the nineteenth century. The strange invisible rays could penetrate skin, revealing a person’s inner skeletal structure, and they could also harm humans. Marie Curie’s hands blackened and peeled after she refined a tiny quantity of radium, for example, while a vial of the element in her husband Pierre’s waistcoat pocket scarred his hip. The burns went deeper than just the skin—as scientists later figured out, radiation had the power to damage cellular DNA, which either made cells die or stopped them from dividing. The first use of radiation in cancer treatment occurred in Chicago in 1896, one year after the discovery of X-rays. Medical student Emil Grubbe figured that radiation might kill rapidly dividing cells—cancer—so he rigged up an X-ray tube, and each day for eighteen days he bombarded an elderly woman with advanced breast cancer that had recurred after her
mastectomy. Although her breast tumor shrank, her cancer had already metastasized to other parts of the body, and she died a few months later. Still, the treatment was promising. Once the Curies discovered radium—which produces beams of energy more intense than X-rays—oncologists had a more powerful weapon against tumors. Unfortunately, no one understood that the power of radiation was truly awesome. Marie Curie succumbed to leukemia in 1934, brought on by her unshielded handling of radioactive materials. And in 1960 Emil Grubbe died of multiple forms of cancer after enduring many operations to amputate his fingers, left hand, and part of his face due to radiation damage. Radiation could shrink tumors, but too much of it caused cancer and death. Figuring out the right dosage to shrink tumors without causing enduring harm took decades.

  Radiation turned doctors into Goldilocks, searching for the dosage that was “just right.” Too much radiation had nasty side effects and could kill healthy organs and normal tissue. Too little radiation failed to shrink tumors. Geoffrey Keynes, the younger brother of the influential economist John Maynard Keynes, played an instrumental role in promoting radiation as a form of cancer therapy. After a stint as a medic during World War I, Keynes decided he’d seen enough dismembered body parts for several lifetimes, so surgical solutions to cancer—and the Halsted mastectomy in particular—repelled him. He turned to radium as a possible therapy for breast cancer. At first, he tried placing radium pellets into large inoperable breast tumors and found that this shrank the cancers. Next he began to wonder whether radiation, used in combination with conservative breast surgery—lumpectomies, which removed only the tumor and a little surrounding tissue, or simple mastectomies that did not take chest muscles—might cure women with less advanced cancers. In 1935 he compared the survival rates for patients treated with surgery and radiation at his hospital—St. Bartholomew’s in London—to patients treated with radical mastectomy; it was nearly identical at five, ten, and fifteen years out. Forty-two percent of both sets of patients were alive a decade and a half after treatment. Conservative surgery plus radiation worked just as well as Halsted mastectomies. Although Keynes’s startling discovery in England should have shaken the medical establishment, America ignored his research until the mid-1950s. The influence of Halsted’s surgical radicalism held such sway that lumpectomy plus radiation didn’t gain mainstream acceptance until a study published more than forty-five years later, in 1981, the year of my birth, reaffirmed that lumpectomy plus radiation was just as effective as radical mastectomy.

  Early radiation therapy often took the form of embeddable pellets, but by the mid-twentieth century, radiation beams had become part of treatment. High-intensity beams allowed doctors to treat tumors deeper beneath the skin, where weak beams could not penetrate without lasting exposure that severely damaged skin. Delivering a single tumoricidal dose of radiation also killed too much normal tissue, so doctors spread radiation out over several days or weeks. My great-aunt El and my grandma Meg received their radiation during a time when doctors were still figuring out methods and dosages. Meg received radium crystals for at least one of her two episodes of breast cancer, and her treatment burned a hole in her breast plate that only surfaced several decades later, masquerading, for a terrifying week, as a recurrence. The beams of radiation my great-aunt El received permanently scarred the skin of her chest.

  The carnage of war inspired Geoffrey Keynes to pioneer less gruesome treatments involving radiation, but chemotherapy is an even more direct legacy of battle; it’s a derivative of the mustard gas that wreaked such havoc during World War I. When studying mustard gas survivors and autopsies of gas victims, scientists on both sides of the Atlantic noticed dried-up bone marrow, damaged lymph nodes, and ulcerated gastrointestinal tracts. This fact—that mustard gas destroys cells that replicate quickly—should have interested cancer scientists, but it lost distinction among WWI’s long catalog of recorded horrors. During World War II, however, scientists had another chance to make the leap, after a tragedy near the port of Bari, Italy, in 1943, where German planes attacked a fleet of Allied ships, including one transporting a top-secret shipment unknown to even its own crew: seventy tons of mustard gas. The ship caught fire, pouring its lethal load into the air and water. More than one thousand American soldiers and several thousand Italian civilians died in the catastrophe. Colonel Stewart F. Alexander, who was assigned to investigate the incident, noticed the destroyed lymphatic tissue and bone marrow in the victims and wondered whether mustard gas could do the same thing for someone with leukemia or lympho-sarcoma. He sent his results to Yale University researchers Louis Goodman and Alfred Gilman, who had been studying the effects of the gas in animals. In 1942, they convinced a surgeon to inject one of his lymphoma patients with it. His tumors shrank promisingly but ultimately recurred. After receiving the Bari data, the pair began dosing other lymphoma patients with the drug.

  Over the next decade, scientists refined scads of unpronounceable toxic chemicals, from busulfan to triethylenethiophosphoramide, chemicals that kill rapidly dividing cells like cancer. Unfortunately, they massacre other fast-growing tissues, not merely the ones trying to kill the patient, including hair follicles, bone marrow, and the digestive tract, which can cause side effects such as hair loss, nausea, and reduced immune function.

  Before the cancer, my aunt El was striking—tall, thin, with determined ice-blue eyes and dark brown locks. After the cancer, she looked different. Her Liz Taylor-thick hair fell out during the chemotherapy. It grew in thin, never regaining its original lushness, and she had to wear it short from then on. The radiation to her entire chest cavity singed the fat around her heart and damaged the surrounding arteries, as well as scarring the skin on her chest. For the rest of her too-short life, she would have stooped shoulders, caved in by the Halsted mastectomies—two years after her original diagnosis, she chose to have her other breast removed prophylactically, an unusual move for the time. Kathy remembers how pleased her mother was when her father purchased a dryer for the family. Thanks to the Halsteds, which had weakened her arms and reduced their mobility, El found it difficult to hang clothes out to dry on the lines. She had lymphedema in both arms, which was painful in the summer, though she never complained.

  El responded to the ravages of cancer, in part, with fashion. She’d always been into clothing and enjoyed looking nicely turned out. She bought beautiful custom-made outfits from a couture boutique in Rockford, clothing that looked “very French” to daughter Kathy. But the clothes also served a necessary purpose: due to the physical damage from radiation and mastectomy, they needed to cover her to the collarbone. In particular, El required custom-made swimsuits, and when they went to the pool in the summer other little girls would tease Kathy about her mother’s odd concealing swimwear. Because El had grown up with two sisters, Kathy says, “She was very comfortable changing clothes while she would talk to me, or I would run into the bathroom and talk to her while she was in the shower. But this was a lifelong dramatic change. And it was not talked about.” Her mother’s disfigurement affected Kathy’s development during adolescence. “She was the only adult woman I’d seen nude,” she says. And because her mother didn’t have breasts—not even fat or muscle under the surgical site, “I didn’t know if I would have big ones or little ones or what they would look like. There was all this confusion about what they would look like.” In contrast, while I was growing up, my mother was very private about her body—I don’t think I’ve ever seen her topless in a changing room. When I asked her about it once, she told me that at the time of her cancer the doctors recommended that women who had mastectomies not appear naked in front of their daughters for fear of frightening them. Years after El’s breast cancer, when she was gravely ill with ovarian cancer, El would tell Kathy that the breast cancer hadn’t diminished her, that her husband had always made her feel beautiful. He took her dancing. He bought her jewelry. He treated her as just as beautiful and feminine as she’d been before the surgery. Kathy notes that her mother was a product of
a time before women’s lib, when femininity and attractiveness didn’t come from within but rather from how men responded to you. As Kathy puts it, “She always talked about her sense of attractiveness in terms of how my father treated her and responded to her.” And he treated her like a woman.

  True to the social conventions of the time, El never referred to her cancer as such, but rather as “my surgery.” Kathy remembers sitting at the kitchen table with her mother and her mother’s friend when she was about twelve—around seven years after El’s ordeal. They’d just eaten a meal together. As Kathy tells me, “One of them made a reference to cancer, to my mom having cancer, and I remember it being devastating because no one ever used the word. And I looked at her and said, ‘Oh my God, you had cancer.’ And she got angry and said, ‘Of course I did.’ It was a forbidden thing to talk about.” Many years later, when Kathy began working at a medical center in Chicago, Illinois, as a psychologist, she would still have to ask the physician’s permission to use the word “cancer” with patients she was treating. Some people died without ever hearing the word used to describe their condition—it was thought it might upset patients so much that it would interfere with the regimen of care.

  After El’s treatment for breast cancer in 1957, my family enjoyed a respite from cancer for the next decade, until a fateful day in 1968. El and Ralph and their younger daughter Lisa were gathered in the kitchen at the end of the day after work. For Lisa, who was ten at the time, the moment exists in horrific, replayable slow motion, each action etched forever in her memory. El opened a letter from my grandma Meg—her sister—and her hand began to shake. Then Lisa’s even-keeled, unemotional mother put a hand on the kitchen counter to steady herself and started sobbing. My grandmother Meg had developed breast cancer at only thirty-nine years old. It was the beginning of a very bad decade for the two surviving Muehleisen sisters.