The Cancer Chronicles (13 page)

In one session after another in Albuquerque, sonic hedgehog was there. It sets in motion a complex molecular cascade—what biologists call the
shh signaling pathway—that also involves patched, smoothened, and other genes. In mammals, sonic hedgehog helps establish the left-right symmetry of the body and brain and guides the patterning of the skeleton and nervous system, linking bones with muscle and clothing them with
skin. A dose of
cyclopamine is not the only way to gum up the works. In the developing embryo, mutations can suppress sonic hedgehog, giving rise to a human
deformity called
holoprosencephaly. As with the lambs, the baby’s brain doesn’t properly bisect into hemispheres. There may be a nose with a single nostril or a mouth with one instead of two front teeth and, in the most severe cases, a cyclopean eye centered like a headlamp in the face. So many things have to go right during the formation of a child—the proper chemical signals produced, transmitted, and received at the proper locations, in the proper concentrations, at the proper times. More often than we realize, something goes wrong. It has been estimated that as many as
one of every 250 early embryos is holoprosencephalic. These pregnancies usually end in a
miscarriage, so the defect appears in only about 1 in 16,000 live births. Most of these babies die, but those with milder symptoms can live for years.

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 woman 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.

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.