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

by Lizzie Stark

  Paleopathologist Arthur Aufderheide, a distant cousin of my father, performed autopsies on mummies. In 1990, while on an archaeological dig in the Peruvian Andes, he sliced open a woman about my age, in her mid-thirties, but a thousand years dead and mummified by the environment. Beneath papery dried skin on her upper left arm, he found a knob of bone cancer. He wasn’t the only paleopathologist to find this sort of thing in mummies—cancerous abdominal tissue discovered in mummies in Dakhleh, Egypt, dates to 400 BCE, for example. Sometimes, archaeologists don’t find actual cancerous tissue but rather the signs that cancer has traveled there before, such as the tiny holes bored in bone by advanced strains of skin or breast cancer. Anthropologist Louis Leakey found a two-million-year-old jawbone that contained signs of a rare type of lymphoma, although pathology never confirmed the diagnosis.

  The oldest written record of cancer—the Smith Papyrus—describes forty-eight types of malady with scholarly detachment, everything from broken hands and crushed vertebrae to skin abscesses, and includes both palliative and curative treatments. Although written in the seventeenth century BCE, it’s believed to contain teachings from a thousand years earlier from the Egyptian doctor Imhotep. Case forty-five involves “swellings on the breast, large, spreading, and hard; touching them is like touching a ball of wrappings, or they may be compared to the unripe hemat fruit, which is cool and hard to the touch.” In his book The Emperor of All Maladies, oncologist and cancer historian Siddhartha Mukherjee recognizes the words. There could “hardly be a more vivid description of breast cancer,” he writes. Yet Imhotep prescribes no poultices or balms for this case. The section under “therapy” reads, “There is none.”

  The semi-mythical Greek physician Hippocrates named this inexorable illness karkinos, meaning “crab,” around 400 BCE. It’s unclear exactly how Hippocrates meant this crab metaphor—tumors can be hard, like a crab’s shell, or perhaps cancer spreads like a crab on the move, or causes pain like a crab pinch. Later Roman doctors adopted the name cancer, the Latin word for crab, and extended the metaphor. Surrounded by filaments—probably blood vessels—some tumors resembled crabs, their legs reaching into the surrounding tissue.

  When cancer goes untreated, tumors become painful, burst through the skin, and exude smelly dark liquid. Because breast cancer is one of the most common cancers—in our disease-prone day and age it will afflict one in eight women—and one of the most visible cancers, occurring in a part of the body where it may be felt, and sometimes seen, rather than in a more hidden internal organ, historical records have no shortage of women who have suffered and died from the disease. Atossa, a queen of ancient Persia and wife of the ruler Darius, let a slave cut into her breast to lance her tumor, her survival probably proving that it was not cancer, but a benign breast disease. Louis XIV’s wife, Anne of Austria, had been a fastidious woman in life, but as she died the servants who changed her bandages covered their noses with perfumed handkerchiefs to escape the putrid stench of her weeping tumors. It must have been humiliating.

  Before he became a monster, Adolf Hitler was a momma’s boy. His mother, Klara, developed a breast lump in 1905 but did not mention it to her doctor until several years later, when the chest pains began keeping her up at night. A mastectomy was not enough to save her, and Hitler went begging to the family’s Jewish doctor, Eduard Bloch, for something—anything—that might prolong her life. With the usual options exhausted, Bloch offered an experimental and primitive chemotherapy treatment. He reopened Klara’s mastectomy scars and applied an iodine-based medicine that burned its way into the tissues. Each treatment left Klara screaming and in pain for hours afterward, and as a side effect, paralyzed her throat. For forty-six days she weathered the ordeal while her son watched and cared for her. Though Klara died, Hitler felt so grateful to Bloch that he paid the doctor in full and sent him yearly Christmas cards for a time afterward. Thirty years later, Bloch used his connection with the family to save himself, secretly contacting the Führer’s younger sister to speak on Bloch’s behalf. Within weeks he had all the paperwork he needed to emigrate to the United States, as well as an exemption from wearing the J on his clothing. As breast cancer historian James Stuart Olson put it, “It was a curious irony: while Hitler contemplated the liquidation of millions of Jews, he made sure one escaped.”

  Where cancer goes and medicine fails, fear follows. My family knows this fear; in some ways we’ve made it our friend, used it to spur us on to medical treatments that other people—mostly those who don’t understand the history of cancer in our family—find a bit extreme. Our suffering begins with Gertrude Frida Muehleisen, my great-aunt Trudy, whose ring I wear. Her story, passed down through generations clouded with their own anxieties about cancer, reads vaguely like a Rorschach inkblot for the unifying experience of cancer: fear.

  Though she has a very German name, Trudy was born in China on April 23, 1921, to my newly wed great-grandparents, missionaries for a denomination that would later become the United Church of Christ. Though my grandmother’s loopy cursive leaves so much out, it notes Trudy’s baptism, presumably at the hand of her father, thirteen days after her birth. A younger sister, Elfrieda Katherine, followed in 1922. At the time, kids of missionaries usually got packed off to boarding school. My great-grandmother, whose parents had been missionaries in India, had hated being separated from them as a child and wanted a different experience for her own children, so when Trudy was two and Elfrieda—El—was one, the family packed up and moved to the United States, eventually settling near Milwaukee. Five years later, in 1928, my grandma Margaret—Meg—became their first and only child born in the United States.

  They arrived just in time for the Great Depression, a tough time for most Americans and tougher still for pastors like my great-grandpa, who relied on his congregation’s donations to survive. Perhaps this explains why so many of my grandmother’s childhood stories revolved around food—barrels of sauerkraut her mother cured on the porch, memories of parishioners buying two heads of cabbage and donating the wormy one to her family, her prodigious love of hard-boiled eggs, and occasions when she was dolled up for her father’s visits to congregants during which she maneuvered for treats with backhanded suggestions like, “If someone offered me a cookie, I wouldn’t say no.”

  By all accounts, my great-grandmother was a difficult, critical woman who did not bear the family’s new poverty well. She also suffered from short-term depression and psychosis, if the genealogy notes my grandmother left behind are correct, and this affected her three daughters. And something about the era, with its paucity of resources, or her personality, seemed to make her daughters competitive with one another. If you ask El’s family, they’ll say my grandmother Meg was the favorite child, the youngest, the baby, the daddy’s girl. If you ask my family, they’ll say that Elfrieda, the great beauty, the brainiac, was the favorite. Trudy has no family to speak for her, so her position remains a mystery.

  One thing is clear, though: El and Trudy couldn’t wait to leave. Both obtained nursing degrees in their mid-teens, moved out, and began working. Trudy fled far, to Newfoundland, Canada, and followed the family’s humanitarian bent, nursing the indigent poor at the Grenfell Mission, one of the region’s first permanent medical facilities. For a few years, my grandfather says, she did everything from milking cows to delivering babies. She met, fell in love with, and became engaged to a young man—no one remembers his name—who met a tragic end. He took a boat out into the ocean, and the boat came back without him. My grandmother believed that her eldest sister never got over this loss, that it explained part of what happened afterward. My grandpa thought it contributed to Trudy’s somber nature—she was less vivacious and feisty than her two younger sisters. Eventually, Trudy moved back to Milwaukee and worked for the county as a nurse, paying house calls on locals.

  It’s not easy to talk about cancer in the best circumstances, but in the 1940s and 1950s, social norms made it even harder. As my grandfather puts it, “First of all, talkin
g about breasts was pretty much off limits, and talking about breasts and having a problem with them was even more secretive. You’d tell someone you had a broken leg, but you didn’t want to tell them you had stomach cancer, liver cancer, breast cancer, cancer of the brain. Those were always way out of the limits of public conversation.” The titillation of breasts, the secrecy that shrouded cancer, and the intense emotions illness evokes muddle the narrative. Perhaps this explains why three different stories have come down to me.

  My mother, my aunt Cris, and I all inherited the same version: Trudy knew she had cancer and chose to do nothing about it because the only treatment available—a radical mastectomy—terrified her. The story carries the intimation that she struggled with the loss of her fiancé and saw no reason to live. As Cris puts it to me, “She sort of existed as this tragic romantic character in the background.” The tragedy and romance appealed to me as a young woman too—in college I’d write my first real short story about Trudy. For me, the moral of this story is that Trudy was smart enough to be terrified of the treatment but not brave enough to make the brutal decision to take off her breasts.

  El’s eldest child, Kathy, inherited an altered version of the tale. Trudy first felt the lump in her breast at age twenty-seven or twenty-eight, but as a nurse she either assumed she was too young to get cancer or she didn’t want to undergo a disfiguring operation because she was single and despaired of getting a husband. So she watched the lump. By the time she did opt for a mastectomy—contrary to my family’s version—the cancer had spread. For Kathy, the moral of the story is “Do not delay.”

  My grandpa provides yet another account. After Trudy’s mastectomy, he says, she did better before taking a sharp turn for the worse. He and my grandmother took her in because she was single, and later my great-grandparents moved in as well. As Trudy sickened, the family became more desperate, eventually pinning their hopes on the Lincoln cure, which involved injecting, sniffing, or topically applying bacteria that had been destroyed with viruses. The so-called cure, invented by Massachusetts physician Robert E. Lincoln, who eventually lost his license, was used to treat everything from sinus trouble to cancer. Although my grandfather thought it was a scam, he drove Trudy down to the clinic for her treatment at least once. Even if Trudy was strong enough to bear up to the mastectomy, in this version she falls victim to chicanery.

  No matter whether she succumbed to fear, delays, vanity, or false hope, Trudy’s story is cautionary. All versions end the same way: Trudy died of breast cancer in 1953 in my grandparents’ home in Wisconsin at age thirty-one, leaving behind bereft parents, bereft sisters, and five small nieces and nephews—my aunt Cris and my mother Gretchen, and their three cousins. Everyone mourned her rotten luck and lost life, of course, but at the time it seemed like an isolated incident.

  If Trudy’s tale is cautionary, then El’s is historical, encapsulating many developments in modern medicine. Like Trudy, El fled home in her mid-teens to become a nurse. After receiving her nursing degree she wanted to go to university, so she cut a deal with Beloit College in Wisconsin: she’d be the nurse in exchange for tuition, room, and board. While she was there she cared for a soldier who had contracted malaria in the Philippines during World War II and who had returned to Beloit to finish his degree. Ralph’s medical release required him to seek regular care from a local medical practitioner. The army probably meant only for a few months, but he did the army one better and married her, not knowing that, by the end, he’d be the one caring for her. They moved to Rockford, Illinois, where he sold large factory apparatus and she defied traditional expectations by pursuing her own career outside the home, becoming a teacher at a local nursing hospital. She had four children, two boys and two girls in quick, alternating succession, giving birth to her youngest, a daughter, in January of 1957, just four years after Trudy’s death. That September, she found a lump in her breast and was diagnosed with breast cancer. She was only thirty-four.

  Luckily for El, in between Imhotep’s dire pronouncement about cancer treatment and her own diagnosis, science had come a long way. For millennia, the concept of humors had dominated Western medicine. Hippocrates—the eponymous source of the oath to do no harm that doctors still take today—believed that the four ancient elements of air, fire, water, and earth had analogues in the human body in the form of blood, yellow bile, phlegm, and black bile. His theory held that healthy humans maintain a balance of the four fluids, but when they get out of whack, illness results. The writer and Roman physician Galen, who practiced around 180 CE, applied humoral theory directly to particular illnesses: cancer, for example, resulted from an excess of black bile.

  Galenic theory treated illness as a systemic problem that required a systemic, not a local, solution. By that reasoning, the surgical removal of a tumor might bring immediate relief but failed to address the underlying cause because it did nothing to restore the correct balance of humors. Due to Galen’s influence, doctors largely abandoned the idea of surgery as a cure for cancer in favor of systemic bleedings and purgings. The anatomists who mapped the human body from the 1500s to the late 1700s—often dissecting corpses nabbed from graves or the thieves’ gallows—upended Galenic theory. Their failure to find any trace of black bile in the normal human body laid the groundwork for surgical extraction of tumors. If illness wasn’t due to humoral imbalances, then perhaps cancer wasn’t a systemic disease, as Galen would have it. Perhaps it was local and could be cured through the knife.

  Until the late 1890s, surgery was a gruesome, life-threatening procedure, often performed without the mid-century development of anesthesia and the later spread of antisepsis. Surgeons executed their jobs in coats spattered with festering body fluids from earlier operations—stained jackets meant a doctor had a lot of experience hacking patients open; stains were badges of honor. In an era before doctors understood germs as the vectors for disease, many patients died of postoperative infection.

  The development of anesthesia, cellular pathology, and germ theory in the mid-1800s revolutionized the medical landscape and made complex surgery—including surgery for breast cancer—possible and survivable. In 1847, Hungarian-born obstetrician Ignaz Semmelweis unearthed the startling solution to the problem of infant mortality at the University of Vienna. The university hospital had two maternity wards, each of which delivered about thirty-five hundred babies annually. Doctors and medical students staffed one of the wards, while midwives staffed the other. In the doctors’ ward, about 20 percent of the mothers—around seven hundred women per year—died. Meanwhile, the midwives’ ward sustained a maternal mortality rate of only 1.7 percent, or about sixty women. Semmelweis decided to investigate that striking difference. He noticed that the doctors did something the midwives didn’t—they often performed autopsies in one section of the hospital and then hustled over to the maternity ward to deliver babies. Perhaps, Semmelweis mused, the doctors were transferring some invisible illness from the corpses to the mothers. He began washing his hands with chlorine solution and got the other doctors to do the same. One month later, the maternal death rate in the doctors’ ward had dropped to 1 percent. Scottish surgeon Joseph Lister’s research confirmed Semmelweis’s observations. Inspired by Louis Pasteur’s recent discovery of microbes, Lister began sterilizing his hands, bandages, and his patients’ surgical sites with carbolic acid, dropping infection rates drastically. He published his results in 1869 in the Lancet, and antisepsis was born.

  In addition to contending with post-op infections, surgeons back in the day had to operate really fast. No matter how drunk you get someone, they will still wake up and thrash around if you saw off their leg, and it’s pretty hard to do delicate, complex work under those circumstances. As scientists in Europe developed antiseptic techniques, surgeons in America discovered the wonders of anesthesia. After months of dosing cats and dogs with ether, dentist William Thomas Green Morton moved up to humans who needed teeth extracted. On October 16, 1846, at Massachusetts General Hospital in Boston, h
e knocked out a patient for half an hour while physician John C. Warren removed a facial tumor.

  Though the twin discoveries of anesthesia and antisepsis spread slowly, they gradually made surgery less painful as well as more survivable. At the same time, advances in cellular theory laid the groundwork for modern methods of cancer diagnosis. In the late 1830s, German botanist Matthias Schleiden and physiologist Theodor Schwann discovered that all living things are made out of cells. German pathologist Rudolf Virchow built on this idea, theorizing that cells only came out of other cells. This had direct implications for cancer medicine. If true, it meant that living things grew either when their cells got bigger or when their cells multiplied, and Virchow extended these observations to every human tissue. By examining cancers of bone and connective tissue under a microscope, he figured out that cancer was a disease of unchecked cell growth. Virchow found that the nuclei of normal cells looked different from their cancerous brethren. By the time he died in 1902, medicine understood that, at core, all cancer arises from excessive cell growth and that malignant lesions and benign ones look different under a microscope.

  Enter the epic surgeon William Halsted, a man of outsized importance and big ego whose name would be forever attached to the radical surgery that mutilated and saved both El and my grandma Meg, and scores of other women over the two generations that his influence lasted.

  Born in 1852 to a wealthy family, William Halsted was a flawed, complex man. Known as a party boy and athlete in his youth, he graduated from both Andover and Yale before hunkering down as a medical student at the College of Physicians and Surgeons in New York City in 1874. Here, his nervous, obsessive personality manifested through his devotion to anatomy; he devoured the textbooks. By the time he became a surgical resident at Bellevue Hospital in New York City, he’d already had his first nervous breakdown.