The Cancer Chronicles Read online

  About a year after he showed me his lab in Princeton, Austin was invited to Davies’s domain at Arizona State University to give a talk called “Ten Crazy Ideas About Cancer.” In the end he came up with five, and one in particular has stuck in my mind. It was about mitochondria. I remembered my surprise when I learned years ago that the mitochondria, these tiny things inside our cells, might once have been bacteria—individual creatures that became trapped somehow. The mitochondria have their own DNA and can replicate independently within the cytoplasm. With their ability to burn glucose and power the Krebs cycle—the chemical dynamo that energizes the cell—these symbionts provided their hosts with an evolutionary advantage. They have also long been suspected of playing a part in cancer. Mutations to the mitochondrial DNA are found in many different tumors. That might just be collateral damage from the havoc of a cell careening toward malignancy. But there are reasons to think the mitochondria are more directly involved. For one thing they help initiate apoptosis, the cellular suicide routine. In his crazy ideas talk, Austin speculated that cancer might begin when the mitochondrial symbionts rebel. From the wear and tear of generating energy, they become damaged and spew out free radicals that eat at other parts of the cell, including the genome. The cell gets sicker and the only recourse is to destroy itself. But the mitochondria refuse to cooperate. They don’t want to die. More mutations follow and the cell becomes malignant.

  The picture Austin drew reminded me of A Wind in the Door, an allegorical novel by Madeleine L’Engle in which forces of good and evil contend over the universe. It is a sequel to A Wrinkle in Time, which I discovered as a boy in my junior high school library. It was in L’Engle’s fantasy that I first came across the idea of a tesseract—a four-dimensional cube. The idea blew my eighth grade mind. A Wind in the Door is even stranger. This time Charles Wallace, the precocious young protagonist, is suffering from a degenerative disease. His mitochondria are gravely wounded, and his microbiologist mother discovers the cause. There are symbionts within the symbionts—the fictional farandolae—and they are rebelling. They are egged on by the Echthroi, supernatural agents of entropy. Swooping through the universe, they destroy order by what they call Xing—unnaming things, eating information. Charles Wallace and his sister beat back the demons and after a trip inside a mitochondrion the boy is saved. But in the real world the Echthroi are always with us, stripping off labels, dedifferentiating cells, freeing them to make cancer.

  Early in the spring, a year after the Relay for Life and a year after the last of Nancy’s radiation, we traveled to Patagonia to celebrate. There was a lodge on a lake in the mountains, and for years it had been high on our list of places to see. We wouldn’t be roughing it. Each evening the guests were served fine dinners with good Chilean wines. Our room, through sheer luck, was the best in the house, with a view of both the lake and a waterfall. But the luxury wasn’t the main draw. Each morning we would depart with a group on hiking expeditions to glaciers, mountains, lakes, and rivers. Nancy looked so thin and frail to me, but she made it to the very end of every hike.

  One evening after dinner we walked out of the lodge and the stars were more brilliant than we had ever seen. Brilliant and strange. The constellations were unfamiliar, and a pair of dwarf galaxies stared down at us like two big eyes. It took a minute to realize that they were the Magellanic Clouds. Magellan had used them to navigate in the Southern Hemisphere, where the North Star is not visible. And it was within these starry nebulae that Leavitt discovered the Cepheids. Had she lived in this century, the statisticians tell us, her odds of getting stomach cancer would have been much lower. But it still probably would have killed her. With few symptoms at first, it is another of those cancers that is often not noticed until it has metastasized. Chemotherapy or radiation can only hold it in abeyance. For all our understanding of cellular science there is still so much progress to be made. But there are occasionally good surprises. Nancy’s odds hadn’t been good either, and soon she was thriving. Back in Santa Fe she bought a new bicycle and rode in the Santa Fe Century, covering fifty miles.

  Every few months she would go to the cancer center for a blood workup. They were keeping their eye on her level of CA-125, a protein that is used as a biomarker for the presence of endometrial and other cancers. Too much CA-125 doesn’t necessarily mean the cancer is back, and you can have cancer without elevated CA-125. It’s a blunt-edged tool, but in any case Nancy’s remained normal. She also had a PET scan twice a year, and every time she was clear.

  In the fifth year after cancer she bought a horse—something she had wanted to do since she was a girl—and then another horse, and in the sixth year A.C., as she called it, she had fallen in love with two and a half acres of land on the far side of town. It had barns and stables and bordered a square mile of open land. She was determined not to waste a day of a future she had almost lost. It wasn’t an expensive piece of property, and she had inherited a little money after her mother died of breast cancer. So we took out another mortgage and bought the land, and she rode her horses there whenever she could. We called it the ranch.

  I wasn’t a rider but I became obsessed with combating the weeds. There were hordes of the nastiest varieties. In the gardens at home I confronted an occasional kochia. Here they were everywhere. Even worse was a cousin of the weed—another invader from the Russian steppes—called Salsola tragus, or tumbleweed. Perversely embraced as an icon of the Old West, it first came to South Dakota in the late 1800s possibly from the Ukraine. I imagined it arriving as a seed stuck to an immigrant’s sock. Then it began spreading everywhere. Some farmers thought it was part of a conspiracy and gave it another name, Russian thistle. On the Nevada test range, after aboveground nuclear explosions were banned, salsola was the first life to come back.

  I tried everything but ionizing radiation to eradicate it. Early in the spring the plants began to appear as tiny bluish-green stars. I learned to recognize them immediately, surgically removing them with a hoe. When that task became overwhelming I burned them with a weed torch. And still they would appear and grow larger, developing ugly lizard-like purple-striped stems. The stems would grow into a tangle bristling with thousands of thorny seeds. A single tumbleweed could have a quarter million of them. I bought a book on weed science and picked the best chemo—an herbicide called 3,5,6-trichloro-2-pyridinyloxyacetic acid, or triclopyr. It was said to break down rapidly in the soil so the environmental impact was low, and it was selective, killing various kinds of weeds but not the native grasses we wanted to encourage. Spray it on a plant and it travels through the phloem and concentrates in the rapidly proliferating cells of the meristem. There it is believed to mimic plant growth hormones called auxins. Throwing this wrench into the machinery causes the new stems to grow stunted and gnarled, and the plant soon dies. It looks like it is writhing in agony. It was like chemo in reverse, inducing something like cancer. I was careful as I sprayed, in case the fine print was mistaken when it said triclopyr was not a human mutagen or otherwise known to be carcinogenic. It decomposed rapidly enough that it was not believed to hurt wildlife or to pollute the water table.

  For all that work Russian thistle continued to spring up by the dozens. When Nancy wasn’t working or caring for her horses and when I wasn’t writing, we would walk every square foot of the land pulling up the weeds by their roots. Every weekend we filled big plastic garbage bags with hundreds of them and I hauled them to the dump. The hope was to grab every one before it set seed—to break the longstanding cycle. In the spring dead skeletons of Russian thistle would tumble in from afar, but we hoped to reach an equilibrium, something we could control. It was a relief when winter came and everything stopped growing.

  Come spring we anxiously surveyed the land. It seemed clean at first, then patch by patch the evil little stars reappeared and the battle resumed. I began to notice that the seedlings hid from me beneath junipers, crouched almost invisible next to fence posts and rocks. And when I did spot them, just an inch or two high, s
ome of them were already producing seeds—stealthily reproducing before I could stop them. They seemed to be adapting to me, evolving before my eyes.

  There is an old thought experiment in physics involving Maxwell’s demon, an imaginary little creature who tries to overcome the universe’s inevitable march to disorder by catching wandering molecules and nimbly returning them to their proper location. Replacing each fallen grain in a slumping sand castle. Pulling every weed in a pasture. Repairing every mutation in a cell’s DNA. With effort entropy can be forestalled—life itself consists of vessels of order swimming against the entropic tide. With our tools and intelligence we can strike small victories and hold off death for a while. But it is the tide that will eventually prevail. Try as he might, Maxwell’s demon will ultimately be defeated. In the end, the Echthroi always win.

  Epilogue

  Joe’s Cancer

  A life-view by the living can only be provisional. Perspectives are altered by the fact of being drawn; description solidifies the past and creates a gravitational body that wasn’t there before. A background of dark matter—all that is not said— remains, buzzing.

  —JOHN UPDIKE, Self-Consciousness

  The next spring at the ranch, I’m told, the salsola was as bad as ever. I wasn’t there to see it. During that year our marriage ended, seventeen years after it had begun. For a long time our lives had been diverging. The cancer had brought us closer but now it was gone. Brushing so near death makes a person think about how she wants to spend what is left of life. Nancy had her reasons for deciding it was not with me.

  Around that time I received an e-mail from my youngest brother, Joe. He was on the road between his home in Dallas and Albuquerque, driving one of his daughters back to college. Somewhere in the expanse of eastern New Mexico he was chewing on a snack when suddenly he heard a loud crack and a searing pain ripped through his jaw. He continued on to Albuquerque and lay awake all night before flying home to see his doctor.

  Although he hadn’t talked much about it, Joe had been having trouble with his mouth for years. It had begun when a white area appeared on the gums of his lower left jaw. A biopsy found abnormal cells that were described as precancerous. Nothing to worry about—just to keep an eye on as you might a suspicious mole. The problem didn’t arise again until three years later when he felt a soreness. It was also in his lower left jaw. During the next few months, a dentist, an internist, and an oral surgeon each concluded that the best course was to wait and see. Which is what he did until the pain got worse and he was found to have an abscess where a wisdom tooth had been extracted. There was also bone resorption in the area and a couple of dying teeth. All of this was on the left side of his mouth. The skeletal erosion was shored up with bone grafts, the two teeth were extracted, and work began on placing artificial implants. Meanwhile the pain in his jaw continued and was soon accompanied by a ringing in his ears and a sore throat. An otolaryngologist prescribed an antibiotic mouthwash. He had another bone graft and then, not long after, came the incident on the highway.

  The next day in Dallas Joe was given a CT scan and told that he had dislocated his jaw—that all the dental work had caused him to chew in a way that had twisted the bone from its socket. It seemed like a plausible explanation. The doctor prescribed muscle relaxants and, as Joe put it, soft, squishy foods. The white area first noticed three years before was still there and had grown larger. A stabbing pain in his ear led to another CT scan and, for the first time, an MRI. An MRI, I later learned, may be more likely to see abnormalities in soft tissue. And there it was. Inside his mouth and beneath the skin, a tumor—about an inch long—was eating into my brother’s jawbone. A biopsy identified it as squamous cell carcinoma, the same cancer Percivall Pott found in the chimney sweeps and that Katsusaburo Yamagiwa induced by applying coal tar to rabbits’ ears. A PET scan showed that it hadn’t spread anywhere else in his body. Holding on to that fact, Joe sent my siblings and me an e-mail with the subject line: “Good News!” That is the kind of man he was.

  There was so much more information about this cancer than there had been for Nancy’s carcinoma. Squamous cells form the outer layers of the epidermis, the envelope of flesh that is exposed to the world. Beneath them are the basal cells. As skin cells die and slough off, it is the basal cells that divide and produce replacements. These push upward to form the outer skin. Carcinomas of the basal cells are the ones that are usually harmless. Years ago I’d had one removed from the side of my nose. Carcinoma in the squamous region is more aggressive, but it still has a relatively high survival rate, especially if caught early on. What was occupying Joe’s body is referred to specifically as squamous cell cancer of the head and neck, and the National Cancer Institute said that about 52,000 people would be diagnosed with it that year. Why he was one of them was another mystery. Other than being male and over the age of fifty, he had none of the risk factors. He drank alcohol sparingly and he had never smoked. He did not chew betel nuts, which is offered as an explanation for the high rate of the cancer in Southeast Asia. He was tested and found clear of HPV, another possible factor.

  Surgery lasted eight hours and was mostly a success. The tumor was now 2.5 inches long—more than twice the size measured a few weeks earlier in the MRI—and was found to be wrapped around a nerve. That accounted for the racking pain. The mass was successfully extracted along with the damaged part of his jaw. While that was happening a piece of bone was removed from his hip to fill the gap. In the end it couldn’t be used. That much of the surgery was a waste. The arteries in the transplant site had collapsed so that there wasn’t enough blood flow to support a graft. Later on there would have to be another operation. But for now the important thing was that the cancerous tissue was apparently gone. Of thirty-one lymph nodes that had been removed, only one was found to have been affected. Maybe it had done its job and kept the malignant cells from moving farther. Their next stop is usually the lungs.

  With a tracheotomy to help him breathe and a feeding tube temporarily threaded through his nose, Joe recovered for nine days in the hospital and then went home. Next would come six weeks of chemo (cisplatin and Erbitux, a monoclonal antibody) and radiation. He would also be given a medication meant to protect his saliva glands from burns, and a feeding tube would be installed in his stomach. He was taking this all with a humbling equanimity even when, just before treatment began, he noticed a swelling. A new tumor was growing, this one in his upper left jaw. Another was found near his Adam’s apple.

  “I always thought that hearing the words ‘you have cancer’ were the worst you could hear,” he told us, “but I was wrong. ‘We found more tumors’ is much worse.…I think I now realize just what a vile, evil sickness cancer is. The doctors keep chasing it around the body.”

  I thought again of Solzhenitsyn’s Cancer Ward, where one of the patients is speaking in awed resignation about his own malignancy: “A melanoblastoma is such a swine you only have to touch it with a knife and it produces secondaries. You see, it wants to live too, in its way.” The recurrences of Joe’s cancer were happening in spots that had been disturbed by the surgery, and the doctors thought the new tumors might have somehow been seeded during the operation. But there were other possibilities. I found a paper from 1953 describing a concept called field cancerization—multiple primaries springing up in the same location at about the same time. It was possible that malignant cells from the original tumor could spread to nearby locations. But studies suggested that, in cases like Joe’s, each tumor might have developed independently. That seemed like an incredible coincidence, but there were ways it might happen. Researchers had discovered that tissue lying between squamous cell tumors—tissue that otherwise appeared normal—had genetic abnormalities, including mutations to the tumor suppressor gene p53. The mouth and throat are steadily exposed to carcinogens. A cell damaged by a mutagen would give birth to progeny all with the same defect. One of those might sustain another hit and give rise to a family of doubly mutated cells. In time, as
the cells kept dividing, there would be a field of precancerous cells, all with multiple mutations and each awaiting the final push. Another possibility is that the cancer field was created early on during development, when a mutated mother cell gave rise to progeny that were all dispatched to form the lining of the mouth and throat. From the very beginning these cells would share the same abnormalities—a head start in becoming cancerous. However the field came to exist it would be lying there primed—“a ticking time bomb” one paper called it—for multiple cancers. Yet it still seemed strange that so many cells could acquire that final precipitous mutation—all at about the same time—especially in someone who wasn’t smoking or drinking or chewing betel nuts.

  After the initial shock, Joe accepted the news as another setback. It just meant expanding the target of the radiation and altering the chemo. He believed deeply in God and his doctors, and his wife and daughters kept him looking ahead. “I have a virtual army of people praying for my health and recovery—from all cultures, all denominations,” he wrote on a webpage his family maintained to keep people apprised of the news. “I have no doubt I will get rid of this cancer and will be back to normal—whatever it takes to do it. I am so blessed that I know in the depths of my soul that I will defeat this.” It would be good to believe in God. After two weeks of treatment his patience was rewarded. “Good news! End of week two and one of the tumors is GONE! Just a hole where it used to be. The others should soon follow.”

  His treatment was as rough as it gets. Twice he returned to the hospital with nausea and dehydration—the results of an infection. But he passed the halfway point—he told us he saw the light at the end of the tunnel—and then began the recovery from the cure. He felt better than he had in months and was happy how quickly he was able to work again from home. And then he got pneumonia, and at the hospital the doctors noticed a mass near his esophagus. It might just be mucous, they assured him. Of course it was a new tumor. As he prepared for six more weeks of radiation and chemo, another tumor appeared in his jaw. The doctors said that one too could be treated. “Great news!” Joe wrote again. “Longer time in treatment, but it can be beat!”