The Cancer Chronicles Page 10
While too little sonic hedgehog signaling can cause birth defects, too much can drive the formation of malignancies both in children and adults: a brain tumor called medulloblastoma, for example, and basal cell carcinoma, the most common (and usually innocuous) form of human cancer. These skin growths tend to arise slowly and are easily excised in a dermatologist’s office. But in people with Gorlin syndrome, hyperactive hedgehog behavior can cause hundreds of the carcinomas to appear. One study found that a cream containing cyclopamine beat back the growths, and a treatment involving another hedgehog inhibitor has been approved by the Food and Drug Administration.
The morning talks left me feeling frazzled (that is also the name of a gene, and sizzled is too), and I decided to take a quiet stroll through the poster session. In what has become a tradition at scientific meetings, row upon row of corkboards were arranged so scientists—usually graduate students and freshly minted PhDs—could pin up large placards describing in pictures and words some of their experimental achievements. Years ago when I was haunting neuroscience conferences, grazing the posters helped me acquire a lay of the land. Again I found myself becoming immersed in exciting, sometimes bewildering new territory. On this particular afternoon there were 148 posters on developmental biology, and many of the researchers were standing ready to run through the details.
Heading down one of the aisles, trying to avoid being buttonholed, I lingered for a moment at a seemingly unmanned presentation titled “Novel Transcription Factor Involved in Neurogenesis.”
“Would you like me to explain my poster?” A young woman had suddenly appeared. I saw on her name tag that she was Emma Farley from Imperial College in London. I usually preferred to struggle through the posters in solitude but her enthusiasm was hard to resist. Starting at the upper left-hand corner, she explained how a molecule, Dmrt5, equipped with a molecular digit called a zinc finger, might help control the genetic switches during the maturation of the brain. The experiments were with mice and chickens. I followed as best I could as she periodically glanced at my face for signs of comprehension. At what level should she calibrate her explanation?
“What animal do you work on?” she finally asked. Drosophila, Xenopus, C. elegans…so many possibilities. I told her I was a science writer. She ratcheted down the level a couple of notches until I got the gist. Grateful for her patience, I walked to the lobby, sat down with my laptop, and googled “zinc fingers,” “Dmrt5,” and “Emma Farley,” seeing that she had received a prize for an earlier version of her poster. Piece by piece I was putting together a map.
Once you stumble upon a strange new word, your brain seems to sprout receptors for it. As I walked by more posters, terms that only hours ago were unfamiliar leapt at me again and again. We won’t understand cancer without understanding development, and it was astonishing how, in the year that had passed since the previous meeting, so many new scraps of information had accumulated, the titles laden with that curious terminology: “Fat-Hippo Signaling Regulates the Proliferation and Differentiation of Drosophila Optic Neuroepithelia.” (During development Hippo genes help determine the size of organs and have been implicated in certain cancers.) “Fox1 and Fox4 Regulate Muscle-Specific Splicing in Zebrafish and are Required for Cardiac and Skeletal Muscle Functions.” (When mutated, they too can propel the growth of malignant tumors.) To draw attention to the findings, a poster would occasionally take a whimsical turn. “1 + 1 = 3” explored the synergistic relationship between two hormones in plant growth. “Where’d my tail go?” was about the Araucana chicken, bred with a mutation that affects its lower vertebrae.
Of all the presentations I saw that day, one lodged deepest in my mind. Weaving through another aisle of posters, titles to my left, titles to my right, I was stopped in my tracks by six little words: “How heart cells embrace their fate.” I knew by now that “cell fate” is a technical term and not a philosophical one, that it refers to a fully differentiated cell—one in which the proper pattern of genes has been activated to make a skin cell, a muscle cell, a brain cell. And the subject of this particular study was not the human heart but that of a lowly sea squirt. Still the words rang like poetry.
Just about a mile uptown from the biology meeting was University Hospital, where, not so long ago, Nancy and I had reported for her surgery. Cancer cells are those that rebel against their fate—they hope for so much more—and it made it harder for her knowing that her cancer was in her womb. The ticking biological clock had become a ticking time bomb—anti-life.
The day had begun inauspiciously. The receptionist was brusque, unaware or uncaring that the polite, quiet woman she was talking to was carrying a cancer that could kill her. The admissions clerk was friendly but apologetic. There were no beds available. Like an airline the hospital engaged in deliberate overbooking. Maybe that is inevitable in a major medical complex that also serves as the principal trauma center for the state. In any case Nancy would be entered into the information system as a “floater”—unassigned until, sometime after her surgery, a bed opened up on one of the wards. A floater. The clerk probably didn’t know that is police slang for a corpse found facedown in a lake.
The next time I saw Nancy that morning she was lying on a gurney, being prepared for surgery. How bravely she was taking this. As a supervisor stood by, a student nurse stabbed at one of Nancy’s veins to draw blood. She missed by a mile and pierced a nerve, causing damage that would persist long after the surgical scars healed. That morning it seemed like a small thing. The anesthesiologist arrived and then the surgeon, offering reassuring words. The double doors opened and my wife was wheeled away.
It was 11:30 a.m., the first Friday in November. We were told it would be a long operation. I found a chair in a quiet corner of the large waiting area, and when I got tired of sitting I would walk the hallways and then find another place to sit. Two hours passed, then three. I didn’t want to stray far and miss the surgeon or an assistant emerging with a report. I prayed—if that is what it means to repeat, obsessively, beseeching words in your head. My only god was Einstein’s—the laws that govern mass and energy unfolding in the warp of space and time. As my own time slowed, I thought about the strange beauty of science’s own creation story. How, long ago on earth, atoms had clasped with atoms to form a multitude of molecules of all different shapes and sizes. How these tiny bits of matter had glommed onto one another in countless configurations, until somewhere along the way one emerged that could duplicate itself. How stray atoms would stick to its nooks and crannies, and what peeled from the mold was another tiny structure identical to the first. And so the process was repeated, matter begetting matter again and again—until somewhere in earth’s blue waters the self-perpetuating machinery became caught in a tiny membranous bubble. The ancestral cell was born. It divided and divided, copying itself into child cells that were copied again. All the while molecules inside the cells were subtly changing, mutating spontaneously or from the radioactive background of the earth. But of the new cells that emerged, some were better able to prosper. They could move more quickly toward food or away from danger. Something resembling cancer cells must have appeared in the primordial soup—savage, satanic, proliferating at the expense of the rest. But it would be the cells that could congregate and cooperate that would go on to form multicellular creatures, giving rise to the flora and fauna, the creatures of the earth—these exquisite assemblages in which occasionally a cell, like one inside Nancy, would revert to the wild.
Reverie by reverie afternoon became evening, and still there was no word. I must have covered every linear foot of every hallway on every unlocked floor. I was surprised how easy it was to roam at random without a hospital ID. I walked outside, where orderlies and other staff stood smoking cigarettes. I walked by the emergency room, where victims of knives, automobiles, and guns arrived in ambulances. I walked back up the steps to the surgical floor and sat again. I took out my laptop and tried to work on a book I was writing. It was about Henrietta Leavitt, the w
oman who in the early 1900s discovered the blinking stars astronomers use as beacons to measure the emptiness of the universe. She died, childless, of stomach cancer. Before long Nancy’s brother arrived. The earth had continued to rotate and it was dark outside. The cafeteria closed, and the lights were turned off. We were shooed into a hallway where a family—the only other visitors still on the floor—waited for the outcome of someone else’s long surgery.
Finally at 7:30 p.m., eight hours after Nancy had been taken to the operating room, her surgeon emerged, as they do, with his mask hanging loose around his neck. In what is called a modified radical hysterectomy, he had removed her ovaries, fallopian tubes, and uterus, where a tumor—the one that had started this whole thing—had eaten 3 millimeters deep into the endometrial lining and begun spreading into the upper end of her cervix. From there the cancer had maneuvered down one of the round ligaments, which help hold the uterus in place, occupying surrounding tissue as it headed for the right groin—the place where that swollen lymph node had appeared. There it invaded the skin and jumped through the lymph system to nodes in her left groin. Enlarged lymph nodes had also appeared in the pelvic region, two of them angling dangerously close to a vein, but it wasn’t yet clear whether these were also cancerous. All of the diseased and suspect tissue had been removed and samples sent for biopsy.
For all of that there was plenty of good news. There was no sign that the cancer had reached any of the organs that sit so close to the uterus: the bladder, the rectum. The cancer had not learned how to form tendrils into the blood system. The operation had gone cleanly and there was no need for a transfusion. Nancy had lost only 300 cubic centimeters of blood, a little over a cup. In his notes for the report that would be typed up a few days later, the surgeon wrote, “Complications: None.”
He led us to the recovery room where she lay, just barely awake. She smiled when she saw us and then lapsed back, safe for the night, into unconsciousness. Remembering all this now I am washed over by the sadness my wife had felt about not having children in our lives—a sadness she had tried so many times to explain to me, to get me to feel in my own heart. Now childbearing was no longer an option—with me or with anyone. Instead of an embryo, a cancer was growing inside her, one that like all cancers had borrowed some of the mechanisms of embryogenesis.
Chapter 7
Where Cancer Really Comes From
In the 1890s William T. Love, foreseeing an economic boom along the banks of the Niagara River, began excavating a canal. It would skirt past Niagara Falls, allowing boats to travel between Lake Erie and Lake Ontario. More important, the diverted water would be used to generate hydroelectric power. Drawn by a seemingly inexhaustible supply of energy, new industries would spring up. Workers would commute to modern factories from a showcase urban development he would call Model City.
Love’s plan depended, in large part, on the need for power-hungry customers to come to the electricity, which in those days was generated in a form pioneered by Thomas Edison called direct current. Direct current could not be carried very far before it faded. The lightbulbs of customers at the end of the electrical lines would be dimmer than those closer to the generating plant. But Niagara’s advantage was short-lived. Around the time Love’s canal had broken ground, the Serbian inventor Nikola Tesla and his employer, George Westinghouse, introduced alternating current generators and transformers. Before long, electricity, produced at Niagara and elsewhere, could be stepped up to high voltages and transported across the country. That and the great economic panic of 1893 put an end to the Love Canal project, leaving an unfinished ditch about 3,000 feet long and 100 feet wide that residents of Niagara Falls, New York, adopted for swimming and ice skating.
Though Love’s project was a failure, other industries, including chemical manufacturers, grew up along the river, and in the years around World War II, the Hooker Electrochemical Company acquired the abandoned canal for use as a dump. Over the next decade, the company disposed of some 22,000 tons of toxic waste, including carcinogens like benzene and dioxin. In 1953 the site, now closed and covered with dirt, was given for a token payment of one dollar to the local school board with the understanding that it was filled with chemical waste. An elementary school was built there anyway and the city envisioned turning part of the old dump site into a park.
During the next two decades land bordering the canal was sold and developed, and in the late 1970s, after a couple of years of unusually high precipitation, residents began to complain of a sickening smell. When an official from the Environmental Protection Agency came to inspect in 1977, he saw rusting barrels of waste that had found their way to the surface. Potholes were oozing waste into several backyards, and it had seeped into the basement of one home. “The odors penetrate your clothing and adhere to your footwear,” the official reported. Three days later his sweater still stank. The neighborhood was evacuated, a national emergency declared, and the investigations began.
Whole books have been written attempting to apportion blame among Hooker, the school board, the real estate developers, and the city of Niagara Falls for what everyone agrees was an environmental disaster. (Joyce Carol Oates incorporated the saga into a novel.) Just as difficult has been determining the damages caused by the dump to public health. Early in the crisis, the EPA estimated that people living along Love Canal stood a 1 in 10 chance of getting cancer during their lives just from breathing the polluted air. But several days later the agency admitted to a mathematical error: the increased risk was actually 1 in 100 and far less for people just a few blocks away. Another EPA report found that some of the thirty-six residents who volunteered for tests showed signs of chromosomal damage—more than considered normal. But it was dismissed by a panel of medical experts led by Lewis Thomas, chancellor of Memorial Sloan-Kettering Cancer Center, as “inadequate” and so poorly executed that it “damaged the credibility of science.” A later study for the Centers for Disease Control found no excess of chromosomal aberrations.
Cancer can take decades to develop, and those who continued to follow the case awaited the results of a thirty-year retrospective by the New York State Department of Health. With so many variables to juxtapose, studies like this are fraught with uncertainty. Age, sex, and proximity to the canal had to be taken into account. Almost half of the 6,026 residents who were surveyed worked in jobs where occupational exposure might be a risk, and about two-thirds of them had been smokers. About the same proportion drank alcoholic beverages.
When the study was complete, the epidemiologists reported that the birth defect rate for children born to parents who had lived near the canal was double that of Niagara County and also higher than for the rest of the state. Compared with the population at large, slightly more girls had been born than boys—another hint that Love Canal chemicals may have had genetic influences. Despite the hints of teratogenic effects, the study found no convincing evidence that life by the canal had given people cancer. A few types of cancer were slightly more prevalent than expected but the numbers were so small that they were considered within the range of chance. The overall cancer rate was actually a little lower than for the general population.
Birth defects and cancer can both arise from mutations, so why would there be signs of one without the other? It seems plausible that the dividing cells of a developing embryo would be more sensitive to disruptive influences than cells in a fully formed person. And while a single mutation might be enough to derail a developmental pathway, several of these hits would usually be required for a cell in an organ to break away and become cancerous. But even after three decades, the seeming head start provided by Love Canal hadn’t been enough to produce an obvious excess of malignancies.
For many of us who grew up during the exuberant beginnings of the environmental movement of the 1970s and 1980s, that outcome was almost beyond belief. We were influenced by Silent Spring, Rachel Carson’s elegant warning about pesticides and the environment, and scathing polemics like Samuel Epstein’s The Po
litics of Cancer. We worried about saccharine and Red Dye No. 2, and later about Alar on apples. We were told of a modern epidemic of cancer—“the plague of the twentieth century”—that was being imposed on the public by irresponsible corporations and their effluents. Food additives, pesticides and herbicides, household cleaners—all of these were said to be corrupting our DNA. We were pawns in “a grim game of chemical roulette,” Russell Train, the administrator of the EPA, warned in a story that was picked up by newspapers across the country. “Strange new creatures of our own making are all around us, in our air, our water, our food and in the things we touch. When they hit us, we don’t feel a thing. Their ill effects may not show up until decades later, in the form of cancer or even generations later in the form of mutated genes.” We were in the midst of what the historian Robert Proctor called “the Great Cancer Wars.”
Ninety percent of cancer is environmental—we heard that again and again. There was a conspiratorial bent to some of the warnings: the same companies that produced the carcinogenic chemicals also made the drugs used for the chemotherapeutic cures. They were profiting from cancer on both ends. Rhetoric like that was extreme, but the overall message seemed so plausible. Many manufactured chemicals are considered carcinogenic. They can be found among the known and suspected agents listed in the National Toxicology Program’s 499-page Report on Carcinogens. Depending on the degree of exposure, workers in industries that use or produce these substances take on an increased health risk. As the chemicals diffused through the atmosphere, severe effects on the public were bound to become evident—beginning in the present and escalating year by year with the accumulation of broken genes.