On May 7 of this year, I received a Facebook message from a woman named Stephanie Lee:Hey Mark, I found that I have colon cancer today. I go for surgery Thursday morning. Please keep me in your prayers.
At the time, Stephanie was thirty-six and lived on the Gulf Coast of Mississippi, in the town of Ocean Springs. I had met her eight years before, when I worked with Tom Junod on a story for Esquire ("Mississippi Goddamn," November 2005) about how Hurricane Katrina had affected military families already enduring the calamities of the war in Iraq—the families whose suffering had been doubled by the wind and the rain and the floods. Junod and I met Stephanie at her grandmother's house in Lucedale, Mississippi, where she told her story. She was a small woman who worked as a pipe fitter at the Northrop Grumman shipyard, a fine-boned beauty with an intimidating reserve of tensile strength, a single mother whose face settled easily into stoicism and whose eyes lit up with challenge and dare. She'd spent most of her life bedeviled by inconstant men until she met Terrance Lee where she worked. He was a welder. He was younger than Stephanie, and quiet, but she thought he was like her in that he had a plan for making something of himself. Like her, he'd joined the Mississippi National Guard. They married and she e-mailed with him every night after he was called to Iraq in January 2005. She was seven months pregnant when his Humvee went over an IED. She was nine months pregnant when Katrina ravaged the Gulf Coast, and she got in her truck with her husband's .45 and drove nearly eight hours on snarled roads to Shreveport to find a generator so that her baby—Terrance's baby—wouldn't have to be born in darkness. Three days later, she gave birth to Marchelle, who never stopped reminding Stephanie both of her life with Terrance and of the impossibility of life without him.
A few years after her story ran in the magazine, I was surprised to receive a Facebook message from Stephanie that read, Remember me? Over a couple years we swapped the casual and fitful messages typical of Facebook. Then came her message of May 7.
A week later came another. I am well. The surgery went great, just waiting for the biopsy to find out if the cancer spread to my lymphoid. I'm sore and tired and feel so helpless right now, but I know it will get better.
A week after that: I have to have chemo, Mark. Keep me in your prayers.
"Am I gonna die?" Stephanie asked.
Stephanie was not alone. She had her seventeen-year-old daughter, Kamri, a student at the local high school, and she had Marchelle. She had friends and an aunt with whom she was close. Thanks to Terrance, she also had health insurance. Thanks to Terrance, she was able to walk into the Keesler Air Force Base Medical Center in Biloxi and receive treatment for a cost no greater than the utterance of a number. It was the last four digits of Terrance's Social Security number, and now it was her number, for her war. She had stage-three colon cancer. Following the surgery to remove the tumor from her colon, her oncologist wanted to treat her as aggressively as possible—six months of a combination of toxic chemicals known as FOLFOX6, administered every two weeks through a port installed between her left breast and her collarbone. The port was implanted under her skin on June 10, a week before her chemotherapy was set to start. It was supposed to be minor surgery, but two days later Stephanie woke up in such agony that there was fear that perhaps the surgeon who had installed the port had accidentally perforated her chest wall. He hadn't, but the news was even worse. She went to Keesler for a CT scan, and after she was done, she was waiting in the ER and an attending physician walked into the room. She said, "You know it's in your liver, right?"
Just like that.
The doctor held her, and together they wept. But a part of her just wanted someone—her own doctor—to tell her what it meant, so she would know what she had to do. The next Monday, June 17, her oncologist, Major Owen Roberts, entered the treatment room where she was waiting to begin her chemotherapy. Kneeling beside her, he apologized for the way she found out that her cancer had metastasized. He assumed, he said, that the surgeon, having been the first to review the CT scan, had told her.
"Am I gonna die?" Stephanie asked.
"I can't answer that," Dr. Roberts said. He then proceeded to tell Stephanie that she no longer had stage-three colon cancer. She had stage four. She might have twenty-eight months to live if she could tolerate the chemotherapy, six months if she couldn't. She was terminal.
So she was alone, after all.
Mark, the cancer has spread to my liver.
"Am I gonna die?" Stephanie asked.
"I can't answer that," Dr. Roberts said. He then proceeded to tell Stephanie that she no longer had stage-three colon cancer. She had stage four. She was terminal.I had begun talking with Stephanie regularly, and I was on the phone with her the day she was told she was going to die. I could hear her smacking her palm on the countertop in her kitchen in Mississippi. "I will go back to school, I will finish my degree in supply-chain management," she said, her voice raised and defiant. "I will get a job and become a success in my profession—I am good, Mark!—I will remarry, I will see my girls grow to become women, I will be a grandmother to my grandbabies!"
And then she came to tears. "It's not fair! Marchelle can't lose both parents before she's ten. It's not fair! My God!"
Though he insists on change, Eric Schadt never changes. No matter the season, he still shows up at both work and most social functions in a uniform of white polo shirt and hiking shorts. He still drives fast enough to terrify his colleagues, though instead of going to work in California on a motorcycle at a hundred miles per hour, he now runs two miles to catch a train to New York City, where he then runs another mile and a half to his office. He is still squat and powerful, his imposingly lumpy brow a phrenologist's dream and his nose the size of a crab apple. He still smiles all the time and sounds like a self-amused surfer. He still writes almost as fast as he breathes and speaks in torrents of scientific jargon that bear only an approximate relation to the English language. He still has a unique capacity for both collaboration and pissing people off. He still gets into public arguments with men of settled eminence—two years ago, he took on James Watson—by telling them they're clinging to failed paradigms that he is trying to displace. When he's asked the difference between what they do and what he does, he still says, "the difference between medieval alchemy and chemistry."
"That's exactly the kind of patient we take," Schadt said upon first hearing of Stephanie. "But it's a real long shot. I'd say one in a thousand.
What has changed—what he has changed—is his situation and his surroundings. When he was profiled in Esquire two years ago ("Adventures in Extreme Science," April 2011), he was an outsider enduring a kind of prestigious exile. It suited him. He had grown up in a small town in Michigan. He was the child of Christian fundamentalists and for much of his life a fundamentalist himself who still believes, more or less, in intelligent design. When he graduated high school, he joined the Air Force with the idea of subjecting himself to the rigors of Special Forces training. Instead, he blew out his shoulder on a climb, and the Air Force tried to salvage its investment by putting him through a battery of tests. He took them; when the scores came back, he was asked by stunned superiors if math had always come easily to him. Then he was sent to college and undertook the task of complete intellectual self-transformation. He received an undergraduate degree in applied mathematics and computer science at Cal Poly and his master's in pure mathematics at UC Davis. Pure math was, to him, the Special Forces of the mind—he took it because it was so hard, and he wanted to find out just how smart he was. He was pretty smart, as it turned out, but he despaired of working on problems that existed on the level of pure abstraction and had no bearing on the problems of the world. It seemed like, well, a sin. He went to UCLA to get a Ph.D. in the emerging field of biomathematics. The one problem was that the degree required a Ph.D.-level mastery of molecular biology, and the last biology course he'd taken was in high school. So he taught himself by reading textbooks. It wasn't hard. Pure math was hard. Molecular biology, after pure math, struck him as ridiculously easy.
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Schadt got a job at the pharmaceutical giant Merck and, availing himself of the Merck supercomputer, became one of the leading exponents of the medical use of what became known as Big Data. He also had amazing success coming up with new drugs for Merck, to the extent that at one point half the drugs in development started in Schadt's lab. Then he told Merck that they wouldn't work. What data had taught him was that the underlying faith of molecular biology—of all biology, since Watson and Crick had elucidated the structure of the DNA molecule—was false. Untold billions had been spent in the hope that we could understand disease one gene at a time, or one genetic pathway at a time; by targeting the gene or the pathway "for" Alzheimer's disease, say, we could target Alzheimer's disease itself. Schadt told Merck that this was a strategy doomed to fail, because disease arose not from single genes or pathways but rather out of vast networks of genes and pathways whose interactions could be understood only by supercomputers guided by abstruse algorithms. Evangelical still, though now evangelical on behalf of irreducible complexity, he asked Merck to remake itself in the image of the network model he was determined to pioneer. Merck declined and Schadt headed to Silicon Valley, to the land of data.
He wound up at a company that made advanced gene sequencers, Pacific Biosciences. There he tested his network model by resolving to become the "hub" of networks of collaborators. He did his supercomputing with Amazon; he put forth an idea of mapping pathogens in public places that attracted the attention of Google; he worked with researchers at Harvard to identify the strain of cholera ravaging Haiti and traced it to South Asian relief workers. But he still wanted what he wanted at Merck: the resources to prove he was either right or wrong. He thought he was going to get enough venture-capital money to start his own lab at UC San Francisco, but the problem with venture capitalists is that they don't want to give money—they want to make it. Schadt didn't want to make that kind of bet. He wanted someone to bet on him.
In the spring of 2011, he finally heard from a gambler. Well, not really—he heard from Mount Sinai, a century-and-a-half-old hospital and medical school on the East Side of Manhattan. He had always thought that he would stay on the West Coast, where, he says, "people are really good at making things." He had always looked askance at New York, where "they're only good at making money." But now, in hearing from Sinai, he was hearing from money itself. He was hearing, in particular, from a man who had done nothing but make money for the better part of his life, Carl Icahn. Sinai was an institution seeking to remake itself; Icahn was a man looking to put his name on a vision of the future. Schadt wound up meeting Icahn and afterward wrote in an e-mail, I think he liked that I had a rougher life growing up, where I guess he did as well. In July 2011, Schadt drove his family from Palo Alto to New York. In September, Mount Sinai announced that he would be head of the newly created Institute for Genomics and Multiscale Biology. A little more than a year later, Sinai announced that Schadt's operation would be renamed the Icahn Institute, just as the entire medical school would be renamed the Icahn School of Medicine at Mount Sinai. For the privilege, Carl Icahn had given Eric Schadt $150 million to claim the future of biology.
In some ways, everything had changed, for Schadt now had four hundred people working for him, along with nine gene sequencers at his disposal and a supercomputer named Minerva in the basement. In other ways, however, he remained a guy in shorts, a guy whose face was always agleam in the light of his laptop, a guy whose office walls were decorated with a palimpsest of indecipherable equations. Most important, he remained a guy who never said no—who never rejected anything as impossible—and when he learned that a woman from Mississippi whom Esquire had written about eight years earlier had been told she had terminal colon cancer, Schadt looked up and said:
"That's exactly the kind of patient we take."
It was, in the end, the reason he had come to New York. He probably didn't really need nine gene sequencers. He probably didn't even really need Minerva, because he could do supercomputing with Google and Amazon. But as both a lapsed molecular biologist and a lapsed Christian looking to establish a new faith, he needed something he had never had before. He needed patients. He needed someone like Stephanie Lee.
It was June 29, and Stephanie weighed ninety-nine pounds. She was not down to ninety-nine pounds, because she had not even really started losing weight yet. I had flown to Mississippi to be with her as she underwent her second round of chemotherapy (the first of three trips I would make over the summer), and in the two days before the chemo, we had eaten eight meals, trying in vain to get her to a hundred pounds. Cancer reduces people, but Stephanie Lee had always struck me as irreducible.
In the spring before Kamri was born, Stephanie had been too pregnant to make it to senior prom. But to make the evening special all the same, her boyfriend, the father of her baby, agreed that they would just go have a nice dinner and maybe see a movie. But when prom night came, her boyfriend didn't show. She waited and called and waited some more, and didn't sleep that night. The next morning, she tracked him to where he was, where Stephanie discovered that he had decided to take another girl to prom instead. She knew this because the girl was still there. Shattered by the betrayal, she nonetheless put up with it, because she and her boyfriend had talked so much about raising their daughter together. But then it happened again with another girl, and Stephanie knew she couldn't live like that. She found him at his house, the girl still there, and confronted him.
"I'm sorry," he said. "I did bad."
"Tell me that you don't love me," she answered.
"What? No!" he said.
"Tell me you don't love me. Now!" she demanded. "I have to get on with my life."
"Stephanie, I'm not gonna tell you something that's not true."
"And I am not leaving here until you tell me you don't love me."
"All right. Okay…" he finally said, resigned. "I don't love you."
With that, Stephanie turned and walked out of his life for good.
She learned early on that groveling got you precisely nothing. Or nothing that is worth the dignity you surrender. She learned early on that betrayal and abandonment were facts of life. I got to be a tough girl. And so when she chooses to make herself vulnerable to someone, the love is that much deeper. And so is the loss, too. She has had people in her life whom she can count on. But the two most important of these people aren't here anymore.
She called her grandmother "Muh," short for Mother Dear. Muh raised Stephanie, because my mother wasn't very mothering. For comfort sometimes, even as an adult, Stephanie would climb into her grandmother's bed with her. Everybody in the family knew that of all the grandkids, Stephanie was Muh's favorite. Her grandmother's house in Lucedale was the one place where she felt at peace, at home, like I belonged and was safe.
The year before Terrance was killed in Iraq, on a Sunday after church, Muh and Stephanie's grandfather, whom she called "Daddy," were hit head-on by a driver high on methadone on the road home from Mobile. When the call came, Stephanie refused to believe that her grandmother was dead, just as she would refuse to believe that Terrance was dead until she saw his body, just as she would refuse to believe that cancer was inside her because no one—at least at first—would show it to her. Stephanie Lee will not believe in something—apart from the good Lord—that she cannot see.
Now, the people she loves most appear to her in vivid dreams. Two years ago, her grandmother came to her. In the dream, Stephanie was broken down on the side of the road, and as she waited there for help, her grandmother and grandfather pulled up. Muh got out of the car and walked right up to Stephanie and squeezed her tight. "I love you, my girl, and you're going to be all right," she said. They were the same words her grandmother had spoken to her that morning before the crash, which struck Stephanie as bizarre, then and now, because in her family people don't say "I love you"—they either show it or they don't.
From the moment of her diagnosis, the most pressing thought in her mind had been Is this disease genetic? Will my daughters be vulnerable to this?Sitting on the couch in her living room, she told me she saw Terrance at night all the time. A year ago, he came to her with what felt like a special message. She was at a party and he was one of the guests. He was wearing a black Ecko shirt that he always wore, and she understood that he was dead, but in the dream it was as if the living and the dead weren't separated by much, and the sweetness and warmth of the reunion was so real that she could smell him and taste him. But then they settled into a sofa to talk, and as the party swirled around them, Terrance turned to her and said, "Stephanie, you have to let me go."
She shook her head at him. "I don't want to," she said. "I don't want to let you go. Nobody else is going to love me like you did."
"You have to listen to me," he said. "I love you, and I know you love me, but you have to let me go…."
Then Terrance got up and walked away. Stephanie followed after him, first speaking then screaming his name. And it was his name she was screaming when she woke up in her bed, alone. After the dream, she went through the house and took down most of the pictures of Terrance, leaving one by her bed and a small framed portrait on the wall in Marchelle's room, of the father she'll never know.
Even as she wondered now how different this cancer ordeal would be if Muh and Terrance were here with her, she was enough of a realist to tell herself that she was alone in the world. She sometimes believed that God meant it to be this way, for some reason that was not hers to divine. Of course, there were people on whom she could rely. There was her Aunt Cathy, whom everybody calls Spanky. It was Aunt Spanky who offered to be Stephanie's caregiver, carrying her to chemotherapy and seeing after her needs. And there was her stepfather, whom her girls call Rabbit and whose ribs are the only ribs her girls will eat. But Stephanie and her mother never have enjoyed much that you could call intimacy, she said.
And Stephanie's father? Well, she has had passing acquaintances who've been more important to her than her father. But we are always willing to set ourselves up for disappointment, aren't we? So in early June, she got his number from her Aunt Marvaline and called him. "I'm sick," she told him. "I have cancer."
Her father responded emphatically. "I need to see you," he said.
Before the call, Stephanie hadn't spoken to or seen her father in two years. And before that, there'd been silence for years more. Roger Nettles is his name, and he lives in Mobile, about an hour by car from Ocean Springs. To split the difference, they decided to meet in Lucedale, where he had once lived and where she grew up.
Roger Nettles is small and fine-boned, like Stephanie. In fact, as much as Stephanie was touched by her father's desire to see her, she was excited to see him for another reason: She needed to know from him how the people in his family die. From the moment of her diagnosis, the most pressing thought in her mind had been Is this disease genetic? Will my daughters be vulnerable to this? She knew that her father's mother died from drink, but that was all she knew. On the phone, she told him this, and her father said that yes, they would go through all the family history, as much as had been passed down. There was much to talk about.
On Saturday, June 8, Stephanie took Marchelle to stay with Terrance's grandmother and then drove the forty miles up to Lucedale to meet her father.
He didn't show up.
She hasn't heard from him since.
When Stephanie went to the Internet to find out about colon cancer, she said, she was surprised at what she discovered—she had a cancer often described as an "old man's disease." She was not an old man. Why did she have a cancer that in many cases develops slowly over time, from an accumulation of cellular insults? She not only had to wonder why she had cancer; she had to wonder why she had this kind of cancer. The question of whether she inherited a predisposition for colon cancer made her realize how little control she had over her future. It was one of the reasons she was so driven to find out what was happening to her. She had to know. Knowledge might not save her, but it could save her daughters, who would be able to get tested and, possibly, treated preemptively. It would be her gift to them.
It was her need for knowledge that allowed Stephanie to endure a distressing suspicion that the combination of her youth and her disease made her "interesting" to her doctors. "I think they want to keep me around as a lab rat," she said of her doctors at Keesler. She was not far off, though the same could be said of every member of the biomedical community she came into contact with, including Eric Schadt.
On June 22, two days after he'd found out about her diagnosis, Schadt called her in Mississippi and told her about a research study he was conducting at the Icahn Institute—a study that he called, with anodyne flourish, "Personalized Cancer Therapy Study." He put her in touch with Claire Davis, who works as his genetic counselor and handles patient enrollment. She told Stephanie about the risks involved and about the consent forms she would have to sign; she answered Stephanie's most persistent question by assuring her that yes, she would find out if her susceptibility to colon cancer was an inheritance she could have passed on to her daughters. On June 26, Schadt sent her a note informing her that she'd been accepted into the study, and she sent me a text: I'm shaking I'm so happy! And she wasn't just happy—she was proud. She was empowered by the promise of "personalized" cancer therapy being devised in a city she'd never visited by a scientist who wanted nothing less than to reinvent his science. Indeed, when she visited Keesler and told her oncologist that the eminent Eric Schadt was interested in her case, she mischievously and defiantly noted her doctor's surprise. Who would have thought, she wrote me later, that there'd be such a fuss about little ol' me?
She was so excited about being accepted into the study that she didn't register a crucial thing about it: It meant, by definition, that her situation was dire. It served as an acknowledgment that the "standard of care"—the accepted treatment for colon cancer that Keesler was providing—was not going to save her life. She wouldn't have been in the study otherwise. Indeed, she wasn't a patient at all. She was a subject. She wouldn't become a patient unless Schadt and those in his employ found something about her cancer that was novel and therefore vulnerable to novel forms of treatment. And even then, there was no guarantee she'd be able to get it. There was no guarantee of anything. Far from being a form of deliverance, her enrollment in the study—which was actually titled "Cancer Sequencing As a Tool for Characterizing Tumor Molecular Structures"—set her on another course of navigating the longest possible odds. She was out if her doctor at Keesler decided not to cooperate. She was out if the pathology lab at Keesler didn't send samples of blood and tissue, or if the samples were of a quality insufficient for genetic analysis. She was out if there was too much tumor in her tissue, or too little. She was out if the tissue had begun to die. She was out for any number of things, and even if she stayed in, Schadt might find no basis for alternative treatment. Or the drug companies might refuse to provide the medicine. Stephanie was just the twentieth person enrolled in the study; of these, Schadt had found reason to treat four. One had died. One benefited from what Schadt called a "home run"—her tumor was found to have "a novel driver" and so was responding to a novel treatment. That's one of twenty. When asked for Stephanie's odds, Schadt said they were far worse than even that: "One in a thousand." But even one in a thousand wasn't terminal. As Schadt said, "I'm not hopeful. But I'm optimistic because I'm an optimistic person. When the Powerball reaches $200 million, I buy a ticket."
On June 28, three days before Stephanie began her second round of traditional chemotherapy at Keesler, she signed consent forms authorizing the release of her blood and her tissues to the Icahn Institute for Genomics and Multiscale Biology.
Keesler Air Force Base in Biloxi is named after an aerial gunner from Mississippi who was shot down over France during World War I. His plane was in a dogfight, and Lieutenant Samuel Keesler kept shooting at the swarming enemy planes even as his own flaming plane plummeted to the ground. For his bravery in the face of futility, this fifteen hundred acres of south Mississippi bears his name.
Every other Monday, Stephanie leaves her apartment at 6:30 in the morning and makes the twenty-minute drive west on the coastal highway to the base's main entrance. "I hate this place, Mark,"she said as we arrived at the medical center during one of my visits last summer. "But I am so thankful for it, too." She stepped into the outpatient entrance and had her blood drawn, which might be the part of the whole miserable process that she dreaded the most, as the needle was so big and her arm was so small, and if they missed the vein the first time, they had to keep sticking her until they found it. Then into chemotherapy she went, the long and dismal treatment room bathed in fluorescent light, with a row of blue recliners lined up along the wall for a half dozen chemo patients at a time, most of whom were twice Stephanie's age.
The staff in the base oncology department is made up of both military personnel and civilians, but Stephanie was principally under the care of Major Roberts, the staff oncologist. At any given time, Dr. Roberts has roughly five hundred patients whose cases he follows, thirty or forty of those being patients at some stage of a chemo regimen and half of those being patients with a terminal diagnosis.
This ever-present degree of mortality gave the treatment room at Keesler an air of determined cheer. The nurses were attentive, smart, kind, and funny. They sat and talked with the patients, asked perfect questions, and knew the chemotherapy protocols and drug interactions as well as the doctors. The pharmacist was tall and blond and had comprehensive knowledge of everything that the FOLFOX cancer treatment can do to you and a mastery of her arsenal. She would sit and talk with Stephanie, listening intently, ready to dispense drugs for constipation, drugs for diarrhea, drugs for rashes, drugs for nausea, drugs for sleeplessness, drugs for the numbness in her hands and feet, and THC pills to stimulate appetite, although she readily admitted that cannabis works much better, but this is Mississippi and that will never be allowed. She explained the cell cycle and how chemotherapy works. "Cancer cells are always most vulnerable when they're growing, so we try to attack them then." And no, she said, there's nothing to be done about Stephanie's inability to taste anything anymore or about her extreme fatigue or about her hands and feet getting darker or about the extreme sensitivity to cold that made it impossible to touch things and made swallowing water feel like swallowing razor blades. But you should have seen the look in her eyes when she said this. The atmosphere in the treatment room at Keesler Medical Center was, in a word, loving.
And there is camaraderie among patients, old and young. On one treatment day, a woman spent a long time telling her story of diagnosis and metastasis and chemo. She was fifty but looked seventy, was bald and bloated from steroids, her eyes were bloodshot and her nose ran incessantly. But from this body being consumed by both cancer and by her cancer treatment came the most buoyant and youthful voice. She turned to Stephanie. "I have Jesus, so I'm fine, whatever happens. And you got Jesus, too, girl!"
Stephanie smiled and nodded, and groggily headed to the door to get home and to her bed. The drive back to Ocean Springs took her past the casino hotels that she makes a practice of staying away from. "Noooo, thank ya. I spend my money on things I can see."
She's choosy. She had been a pipe fitter at the shipyard and Terrance had been a welder, and he would think of reasons to show up over where she'd be working. He'd walk by and smile his gold-tooth smile, she said, and she would say, "Noooo, thank ya. Get rid of them gold teeth and we'll talk." And he did change for her. "He courted me, for six months, before we had sex. He courted me. Do you know how rare that is? He took a while just to hold my hand. Terrance got to know me in a way that no one else has."
We pulled into the parking lot at her apartment complex, into the special spot reserved for her by her landlord, marked by a sign that reads GOLD STAR WIFE. Before she got sick, she had been in the best shape of her life, but now the single flight of stairs up to her door felt like Everest. The strap of her bag bisected a tattoo that runs along her left shoulder: NO PAIN LASTS FOREVER. She dropped her bag inside the door and walked unsteadily to her bedroom, fell into bed, and disappeared under the comforter. Sometimes she would relax in front of a movie, but today she couldn't lift her head.
Soon Kamri and Marchelle came home, and they found her in a deep sleep. Kamri quietly closed her door. The place was nicely put together and spotless—kitchen was perfect, all the beds were made, and there wasn't a book or paper out of place. Kamri saw to that. She's become the boss of the house, like my mother, Stephanie had written in an e-mail.Since Stephanie got sick, Kamri rides herd over both her mother and her little sister. She would be starting her junior year at Ocean Springs High, but planned on taking extra courses so that she could graduate a year early, because she wanted her mother to be here to see her walk across the stage and get her diploma. She knows I am very sick, but she doesn't know the terminal part. Even so, she has an intuition that I'm going to die.
Marchelle knew her mother was sick, and she knew that the family routine had suddenly been upended, but she didn't know much more than that. She suspected that something was terribly wrong, though, and she was scared and needed attention more than ever.
"Mama, is the devil chasing you?" she had asked her mother.
"No!" Stephanie said. "Who told you that?"
"Grandma…" Marchelle said.
"Ain't no devil chasing me, Marchelle," Stephanie said. "I don't have the energy for this right now."
Stephanie had noticed that lately Marchelle had taken to talking in a higher voice, like a baby. "Don't talk like a baby, Marchelle!" she would tell her.
Earlier in the summer, Stephanie's Aunt Spanky had taken it upon herself to tell Stephanie's mother about her prognosis. She hadn't known. Stephanie's mom called from her job at Walmart to ask if it was true. Spanky then told Stephanie that her girls had to know, too, and that if Stephanie wouldn't tell them, then she would.
Stephanie was furious.
"That's not your business to do!" she had told her aunt. "Don't you dare! What is an eight-year-old child supposed to do with that information? And anyway, I don't know what's going to happen. Because I don't plan on dying. I'm gonna beat this thing! What I'm supposed to tell them, that I don't know if I'm gonna die?"
Aunt Spanky had backed down and apologized for causing Stephanie more stress.
A weak voice came from the bedroom. "Kamri, get that food away from me, it stink." But there was no food, just an olfactory trick of the chemo.
"Is there a pool at your hotel?" Marchelle asked me. "Can you take me swimming?"
"Is he in heaven?" she asked.
The pool at the Holiday Inn in Ocean Springs was just about big enough to hold a few rambunctious girls, and Marchelle quickly made friends with a couple of freckle-faced redheads about her age. She was having a blast, and an hour turned into three hours, and just like that the sun was setting and her new friends were getting dried off to go home. Marchelle was disappointed, didn't want for the fun to end, and protested every step to the car. When she got in and buckled her seat belt, she started to cry.
"I never get to go anywhere!" she said, between sobs. "This is the worst summer ever! Mama's always in bed and I have to stay…in…my…room!"
She was crying so hard, her shirt was wet. A dozen times she repeated that her mother was always in bed and that it was the worst summer ever. And then she screamed. "I don't have a family!" she said. "Not like other people!"
"Marchelle, you have a big family who loves you," I told her. "Your mother and your sister love you, your grandparents love you, you have aunts and uncles too many to count…."
"Where's my daddy!" she screamed. "Why isn't my daddy here! I want to see him. Please, I want to see him!"
We drove on in the dark, past the McDonald's and the post office and the hospital.
"Daddy! Daddy! Daddy! Daddy! Where's my daddy!"
"Marchelle!" I said. "Your daddy loves you very much, too."
Marchelle fell silent.
"Yes, baby. He's in heaven."
Early on the morning of July 20, I received a text that read simply: Mark.
Stephanie had been suffering through her third round of chemo, was weak and in crisis. Along with her chemotherapy that week, Dr. Roberts had started her on an additional powerful drug called Avastin, which is designed to starve the cancer of its blood supply and intensify the effects of the chemo. But Avastin also packs a wallop, with many serious side effects, including internal bleeding. Stephanie and her doctors didn't know it, but the timing couldn't have been worse for the new drug. The day before, she had gotten her period, and by that morning she was bleeding profusely. She sent another text: It's gushing out of me, like water.
I called her. She couldn't stand, couldn't dress herself, couldn't move. A good friend whom she had arranged to drive her to the hospital was at church and out of reach. "I'll drive myself," she said. But she knew that she couldn't do that. "I'll pass out and crash my truck, hurt somebody." And she couldn't even stand up—how was she going to drive? Kamri could drive her, but then Marchelle would have to go to the hospital, too, and "I don't want my baby seeing me go through this. I don't think this is going to end well."
She began to weep there on her bed. She doesn't allow herself such emotion easily—when she was first diagnosed, she was reluctant to tell many of her friends, because she didn't want to be surrounded by pity—but now she was letting go. She wailed, a deep and bitter cry, and then apologized for it. "I'm so sorry. I'm so sorry. But why is this happening? Where's my husband? Oh, my girls…"
When Terrance and Muh were killed, "I didn't want to be here anymore," she said. "I mean, I know my children need me, so I would never take my life, but I just felt like I wasn't supposed to be here." And now, as the chemo became debilitating, she began to understand for the first time the impulse to give up.
Kamri dressed her in silence, gently lifting her limp arms and legs. In times of stress, Kamri gets very quiet and moves very fast. Stephanie reached her friend, who rushed from church to drive her, so that Marchelle wouldn't have to go to the hospital and see her mother this way.
To get down the stairs, her friend cradled Stephanie in her arms like a baby. By now, she weighed just eighty-five pounds. At Keesler, she was found to be severely dehydrated and in need of a transfusion; she'd lost more than a liter of blood.
She hadn't known what Avastin would do to her. No one had asked about the timing of her menstrual cycle. And she still hadn't seen her cancer, hadn't seen a CT scan of her liver, and was growing increasingly frustrated at being left in the dark. No one's giving me any hope. I feel like my doctor doesn't care about me. If he can't do anything for me, then he should let me go, and I'll find somebody who can.
Dr. Roberts is tall, with a kind face and weary eyes. He often looks away from you when he talks. In late summer, when I was in Mississippi visiting Stephanie again, I talked with him in a conference room down the hall from his office, and he had traded his scrubs for his dress blues. He described for me the terrible dilemma of balancing hope with a terminal diagnosis.
"It's very difficult," he said. "Certainly with solid tumors, stage-four disease ultimately is probably going to be fatal. In stage-four colon cancer—and this would apply to stage four in most solid tumors, things like breast cancer and lung cancer and almost anything in the metastatic setting—the therapy is no longer in general, for most people, curative at that point. It's what we refer to as palliative. And, you know, part of that is the extension of life, okay? That's part of that goal; it's part of that palliation. But hopefully we are giving those folks an improved quality of life for the time, whatever time that is, that they have left.
"The thing I try to do with most patients—I feel that I owe it to them, you know?—I'm not going to try to squash their hope, but I have to be as realistic as possible based on my knowledge," he said.
Is Stephanie a candidate for surgery?
"Possibly," Roberts said. "That's for a surgeon to determine. But you have to ask yourself, what is the risk of having a fatal complication during the surgery? Where you're talking about going from twenty-eight months in terms of life span to dying on the operating table or dying shortly after due to liver failure, because of a complication. That's a significant thing to consider."
The chemotherapy regimen that Roberts had Stephanie on might be effective in attacking the cancer and shrinking her tumors, but in this palliative course of care, with this prognosis, Roberts also spoke in terms of "when the cancer begins to grow again."
Mishelle Morris-Magee, Stephanie's oncology case manager, spoke in much the same way, talking about the many cases she had seen in which, after initial success with chemotherapy, the cancer in its madness "breaks through," and sometimes comes back with what seems like a vengeance. "We have to watch Stephanie for that," she said. Because with a diagnosis such as hers, "You know it's coming, you just don't know when."
"Can you please tell them my life is at stake?" she said.
"Can you please tell them my life is at stake?" she said.
Like the staff in the treatment room, Morris-Magee is of extraordinary good cheer. "We will fight along with our patients as long as they want to fight," she said. "We will arrange for them to get second, third, and thirty-fifth opinions if that's what they want. We won't give up until they are ready to give up."
In that vein, Morris-Magee had been coordinating the exchange of tissue with her counterpart at Eric Schadt's lab at Mount Sinai. But it was now August 23, nearly a month since the original request for the vital samples, and despite Morris-Magee's best efforts, the Keesler pathology department hadn't yet responded.
In an attempt to speed things up, one day in the treatment room I asked Morris-Magee if it might be possible for me to speak to the pathology department. She answered that it would be problematic, and that the matter was going to be addressed that afternoon in a staff meeting, and as we talked Stephanie interrupted us both.
"Can you please tell them my life is at stake?" she said.
The healthy cells were as pink as a little girl's room. They were derived from thin slices of tissue—of Stephanie's and of Stephanie's tumor—embedded in wax, and the thin slices of tissue weren't pretty. They were gray and they were beige and they looked exactly like what they were: preserved pieces of meat. But Dr. Michael Donovan, the Mount Sinai pathologist now associated with Eric Schadt, had stained them so that he could see them, and now, under the microscope, they looked brand-new. They were the smooth-muscle cells lining Stephanie's gut, and magnified four hundred times, they looked almost fetal, as if, in all that bursting color, lay the germ of life itself.
They were not cancer.
Donovan made an adjustment and the pink cells on the slide gave way to cells that looked like packaged eggs. Also sliced out of Stephanie's gut, these were epithelial cells—something like skin cells. And just as the muscle cells were pictures of youth, the epithelial cells were the very images of order. They consisted of two rows of spherical structures, arranged by size, in descending order. They were pale purple instead of pink. They looked both fragile and worth keeping.
They weren't cancer, either.
Donovan shifted the microscope's focus by microns. He said, "This all will change as I move down, and it will change dramatically. The cells will get longer and more crowded. Everything will become more chaotic." But he didn't even have to say it. The change was atmospheric as much as it was visible. A good neighborhood had given way to a bad one; a bucolic past had yielded to a dystopian future. A riot had gone on. The eggs of the epithelium had been stepped on, by pitiless boots; the bright colors of the smooth-muscle cells now swirled in toxic pools, the sheen of industrial aftermath. Stained indigo, the machinery at the very heart of the cells—the mitotic spindles that are the signature of cell division—were apparent, but they were also everywhere, like popcorn boxes after a matinee, part of the cellular debris, the litter of cells dividing so fast they die.
"Cancer," the pathologist said.
It was September 10. Donovan had received the tissue samples from Stephanie's tumor the week before—or about five weeks after he had first requested them from the pathology lab at Keesler. The samples were not the flash-frozen tissue he always requests, because from flash-frozen tissue he can extract not just DNA but also RNA, and obtain more data. They were strictly standard of care, which is the "minimum daily requirement" of American medicine. But they were not necrotic—not dead—and they showed the 50-50 balance between healthy cells and cancer cells that Donovan required. He could use them. And now he was peering through a microscope at something Stephanie Lee had never been permitted to see in any form—her cancer. Donovan stood at the beginning of what Schadt called "the pipeline" at the Icahn Institute, and so, finally, did Stephanie's precious and precarious DNA. It was Donovan's job to extract it from her cells. Then it would go to another lab equipped with the gene sequencers that Carl Icahn had bought. Then the genetic data would go to two more labs for analysis.
The first thing that needs to be understood about Stephanie's data is that there would be a lot of it. From the samples of Stephanie's blood, the gene sequencers would generate the data about the genes in her "germline"—the genes (and the gene mutations) that she inherited from her parents and that existed in every cell of her body. From the samples sliced from her colon, the sequencers would generate data about her cancer and the mutations that produced it. But the data would be raw. It would contain millions of bits of genetic information, each one a sentence in the horror story that Stephanie's cancer was telling—and all those sentences, at least initially, adding up to a bewildering Babel. The data would exist right on the edge of incoherence; then Schadt and his scientists would strive both to make sense of it and complicate it. That's their trademark, and why they need a supercomputer. The genes that Stephanie was born with would be compared with the genes that were driving Stephanie's cancer. The genes that were driving Stephanie's cancer would be compared with the vast libraries of reference data-bases that already exist on all kinds of cancers. Then they would be plotted against the "network models" that the Icahn Institute is constructing, the millions of individual data points mined for their billions and even trillions of connections.
The result would not be dissimilar to the network model portrayed on the screen of Schadt's office on the afternoon of September 10—a blue sphere of genetic entanglement that resembled nothing less than the universe itself, with each gene a blue star and with some blue stars off by themselves and some clustered into galaxies of cellular activity. The model on the screen happened to be a model of the genes involved in aging, but the model of the genes involved in colon cancer wouldn't look very different. There would be a globe of blue stars. Somewhere on the blue globe would be plotted the mutant particularities of Stephanie's cancer, in red; and though the red stars would cohere into a malign galaxy the relative size of Andromeda, they would be the target of the scientists gathered that afternoon in Schadt's office.
Schadt's scientists—his biologists and his mathematicians—were from all over the world. Many had followed Schadt from the West Coast, but before they came to America, they lived in China and India and Russia. Now they had access to near infinities of information; indeed, they would soon have access to the near infinity of information generated by the DNA of a woman in Mississippi who had been given no information at all, except the information that she was going to die. It was a point lost on no one, least of all Schadt.
"Look, it's cool that we can do this," he said. "But the chances that we can help her are slim." Her chances might have been less slim, he added, if she'd had different care in the first place. Schadt had not grown up wealthy. He had grown up in rural isolation, and he knew, intimately, that life and death were a matter of access. He had no quarrel with the treatment that Stephanie's doctor was giving her in Mississippi; what rankled Schadt was the failure to find Stephanie other treatments at a time when such treatments abounded—"when clinical trials are springing up everywhere." And when he found out that Stephanie had never been shown her CT scan, well, "I honestly believe that's one of the darkest parts of human nature," he said.
"That's the Latin Bible."
Eric Schadt in an e-mail, September 13: We got DNA today! Stephanie's stuff will start then today or tomorrow, so hopefully we have something by end of week.
Schadt, September 18: Stephanie's samples will be off the sequencer by tomorrow morning. I thought we had the DNA in hand when I wrote last, but we actually didn't get it until later Monday. I will press on the analysis team to get through it asap.
Schadt, September 25: We learned after the weekend (Monday morning) that we did not get enough coverage of Stephanie's cancer genome to successfully complete the analysis. So we had to go back on the sequencer Monday and the new data came off later yesterday afternoon. The analysis then was just launched last night….
Schadt, September 27: The data now look sufficient to complete the analysis.
Schadt, September 30: The data for Stephanie look really good…I will meet with the group later today after the manual review and see if there is anything eye-popping.
The question that Stephanie had always asked—Did I get this from my family?—had been answered.
By "eye-popping," Schadt meant unexpected. He meant new. More than three months after Stephanie was told she might have just six months to live, she remained what she was at the start: a young woman with an old man's disease. She remained "interesting." What Schadt was searching for in her genetic data was the presence of something that really stood out—a network no one had seen before, a "hard-hitting mutation" that might not only reveal colon cancer at its source but also turn out to be vulnerable to a drug no one ever thought of before.
At 11:01 P.M. on October 1, Schadt e-mailed again. The preliminary analysis was complete, he wrote, and the data we generated on Stephanie are quite informative regarding the nature of her tumor.
The question that Stephanie had always asked—Did I get this from my family?—had been answered. Yes. Her cancer was part of her inheritance. She hadn't been born with it but rather with a predisposition for it. An inherited mutation in a gene that suppresses tumors, TP53, had turned the gene off. Another inherited mutation in the APC gene had predisposed Stephanie's colon to grow thick with polyps. The two inherited mutations had probably worked in tandem to turn a polyp into a tumor, and then the tumor had done the rest. It had done what tumors do, evolving by the addition of genetic mutations that now numbered about seventy. Whatever the tumor was when it started out—when it first bolted the body's natural restraints and turned to cancer—it no longer was now.
The mutations, however, were not novel. There are some scientifically very interesting things happening in her tumor, Schadt wrote. But after first pass we are not seeing any alternative treatment paths, given that the mutations she has are somewhat common and so already well matched to best treatments…. There is still some network modeling happening as well, so there could still be something that pops out. But wanted to let you know that at least with the mutation information there is not something that points to an unexpected driver mutation that suggests obvious alternative treatment (so no easy home run).
For four months, nobody knew anything about Stephanie Lee's tumor except that it had started in her colon, spread to her liver, and was killing her. Now Schadt and his team knew nearly everything it was possible to know. They also knew that, at least as of the first day of October, there was nothing they could do.
Marchelle has Terrance's hair—not coarse, soft as cotton," Stephanie said. "When he would grow his hair out he'd have the softest curls. I loved to have my hands in his hair." Stephanie finally believed her husband was dead, she told me this summer, when she saw his body at Marshall Funeral Home in Biloxi, ten days after he was killed. The first thing she did was touch his face, which didn't look like him for all the makeup, and touch his hair. She found the top of his head coated in a black wax that covered a wound. Oh, Terrance, what did they do to your head? She finally believed.
It had been four months since Stephanie had had the initial surgery to remove the tumor from her colon, three months since she had been told she was going to die, and still she hadn't seen her cancer. In fact, even as she had over the months gotten more and more chemo-sick, she hadn't for a moment felt sick from her cancer. In mid-September, she had a new CT scan to measure the chemotherapy's progress. In aggregate, her tumors had been reduced by 40 percent. And yet she was growing more frustrated than ever, because no one would explain to her what it meant. She had asked Dr. Roberts to see the scan, but he demurred. Could they do it another day? His office was messy.
In frustration, she arranged for an appointment to see another doctor to get a second opinion. And on September 19, in the office of Dr. Charles Conway at Ochsner Hospital in New Orleans, she saw her cancer at last. Pointing at her CT scan, Dr. Conway narrated Stephanie's insides: "Here's your heart, here's your lungs, here's your liver. And here are your tumors." Two
small tumors on the left lobe, three larger tumors on the right lobe, situated very close to major blood vessels.
No one had ever been more elated to see cancerous lesions. And Stephanie finally believed.
Conway is a surgical oncologist, and he told her that the Ochsner oncology board would meet to decide whether they could recommend a treatment approach different from that being offered at Keesler.
Including surgery on her liver, which in any case would carry great risk.
I'm so happy! she wrote to me, heedless of any danger. Stephanie didn't care. She had seen her tumors and she had met a man who might be able to cut them out of her. He gave me HOPE!!!
Schadt was not a doctor. He had a talent for recognizing patterns, coming up with ideas, and crunching numbers, not for treating patients. He'd never known what it was like to lose a patient because he'd had no patients to lose. Now he had subjects like Stephanie. They generated data whether they lived or they died. But he had moved to New York to live up to some inner directive to help people, a feeling of obligation oddly congenial to his restlessness and impatience—what he called, not altogether accurately, his ADD. "For me it's the exact right stressor," he said. "Why were we somewhat successful at Merck? Well, Merck was saying, 'All this network biology is cool, but if you don't get to drugs that get to market, you're fired.' That's a good driver. It's altruistic here, but it's the right stress point to drive you. You're not in it to get a cool paper. You're here to intervene and change the outcome for the patient. It can be depressing. But it makes you push that much harder and you see it in the group, too. You make choices you wouldn't make if you were not as motivated."
The choice that Schadt made after analyzing Stephanie's data was to admit that he was "not a cancer expert" and to seek out those at Sinai who were. There was some urgency. For one thing, time had never been on Stephanie's side. For another, her surgery was now scheduled for October 25. Schadt wanted to find the "right person"—the right oncologist—to consider her case before the decisive intercession of the scalpel. He found one in Dr. Randy Holcombe, the Mount Sinai oncologist with the most expertise in colon cancer. Was it possible for Stephanie to fly up to New York from Mississippi? Schadt wanted her to meet with Holcombe. He wanted her to hear what "the tumor board" at Mount Sinai had to say after it reviewed her case. Holcombe had agreed with Schadt's initial "nonexpert" interpretation of Stephanie's data; "there was not any alternative treatment for any drug currently on the market for cancer." There was, however, the possibility of finding drugs "coming through clinical trials but not yet approved."
"Why a fly? You can do this in a fly. You can capture the complexities of the tumor."
There was also the possibility of finding combinations of drug therapies devised by a Sinai researcher who had already begun transplanting Stephanie's mutated genes into the body of a fruit fly.
His name was Ross Cagan. He did not work for Schadt; he worked as a professor at Sinai. But they met every week, and after Schadt called on October 1 to tell Cagan about Stephanie Lee, he listened to Cagan's idea for her. A month earlier, Cagan had started doing something that he said "had never been done before." He started creating "personalized flies" for cancer patients. He took the mutations that scientists like Schadt had revealed and loaded them into flies, essentially giving the flies the same cancer that the patient had. Then he treated them. "Why a fly? You can do this in a fly. You can capture the complexities of the tumor."
A day after Cagan spoke with Schadt, Stephanie became the fifth person in the world to have a fly built in her image—or, rather, in the image of her cancer. In an ideal world, Cagan would have created as complex a creature as possible, burdening the fly with at least ten mutations. He gave Stephanie's fly three, because "Stephanie is on the shorter course. We're making the fly as complex as possible given her time." By October 11, however, Cagan already had "one possible drug suggestion for her"—or one possible combination of drugs, since he always tests at least two at a time. "In this center, the FDA will not allow us to put a novel drug in patient. To get a novel drug into a patient, we have to do a novel combination of [known] drugs. We have to use novel drug combinations that people have never seen before."
On October 9, Stephanie booked a flight to New York City and scheduled a consultation with Randy Holcombe and Ross Cagan, with the Icahn Institute paying for the consultation. On the next day, she drove to Ochsner Medical Center and signed the consent forms permitting Dr. Conway to resect her liver.
Back in June, Stephanie had delighted in telling her doctor at Keesler that "little ol'" Stephanie Lee from Ocean Springs had drawn the interest of an eminent scientist in New York. Three and a half months later, she had elicited his advocacy and had a chance to benefit from the most advanced oncology in the world. And yet she also had a very good chance of dying, and soon. At the start, she'd had nothing but faith. Now she had everything—knowledge and the benefit of incalculable resources marshaled on her behalf, both intellectual and monetary—but she had to decide whether to put her faith in something as elemental as a surgeon's knife or as impossible to believe as a fly glowing green with the cancer of little ol' Stephanie Lee.
It was a brilliant early morning—Friday, October 18—when I walked with Stephanie into Mount Sinai Hospital in New York. She exited the elevator on the third floor and told the woman behind the desk the name of the person she was meeting. The woman said, "Ms. Lee? Welcome to Mount Sinai."
"Oh, my God, Mark," she whispered to me. "Do they know me here?"
They knew her extraordinarily well; knew her down to the cellular and even the molecular level. And the fact that these thinkers were thinking about her inspired in Stephanie a combination of awe and relief. Stephanie had not only been resentful about being treated "like a number" at Keesler; she was terrified, because being treated like a number is a terrifying thing. It's primally terrifying, because you begin losing your identity even before you begin to die. At Sinai, she was Stephanie Lee. She had cancer. They were cancer specialists. They were pleased to meet her.
Stephanie was scheduled to meet with four oncologists, but with her surgery just a week away, she was most anxious to talk to one. Dr. Daniel Labow is in his mid-forties, with close-cropped salt-and-pepper hair and smiling eyes. He is the chief of surgical oncology at the hospital and is renowned for pioneering minimally invasive procedures.
"The good news is that your chemotherapy has been working," Dr. Labow told her. "So yes, I see an opportunity for surgery here." He cued up her most recent CT scan on the computer, and suddenly we were looking at a cross-section of Stephanie's body, from the top looking down. With each click of the mouse, Labow manipulated the images down through her body, her spinal column being the one constant landmark, until he came to her liver, and there, located disparately—some near the surface, some embedded more deeply in the organ—were her five lesions. They had all been shrunk considerably by the chemotherapy. But if chemotherapy were all there was for Stephanie, they would come back. Cancer wants to live, too. The time for surgery was now. "The goal here is to remove the disease while leaving as much healthy tissue as possible," he said. He recommended a combination of ablation—a technique that uses heat or cold or microwaves or radio frequencies to destroy tumors—and surgical resection.
Dr. Labow said he would call Dr. Conway in New Orleans to discuss the surgery.
"When I was diagnosed," Stephanie said to him, "I was told I had no options…."
"And now you have options," Labow said.
She saw Randy Holcombe next. One of the top colorectal doctors in the world, Holcombe had been consulting with Schadt on Stephanie's case. He understood the profound promise of the new genetic analysis going on in Schadt's lab. Several times as he spoke to Stephanie, he described the extraordinary picture of her cancer—its source and its behaviors—that the lab had created. "We now have more data about your cancer than you can imagine," he told her. But Holcombe is also an oncologist who is rooted in the more traditional methods of treatment, and in his view if those methods—chemotherapy, surgery—showed any promise at all, then they must be exhausted before any treatments suggested by Schadt's work, which most oncologists still regard as experimental, could be deployed. In their way, Dr. Labow and Dr. Holcombe had more in common with Dr. Roberts in Mississippi than with Eric Schadt just down the street.
The Icahn Institute for Genomics and Multiscale Biology, a few blocks away, is as starkly different from the rest of Mount Sinai as it can be. As you enter, you see whiteboard walls covered with dense computational scrawl. "Oh, Lord," Stephanie said, turning in a circle to look at the room. "Does someone understand all this?" Schadt introduced himself to Stephanie and showed us back to his office, where she asked him to see her fly. He clacked away at his keyboard and up came the image of what the people in his lab had taken to calling the "Stephanie Fly," its visible tumor glowing green with a fluorescent protein so that it might be more easily observed.
"I cannot believe that my tumor is in a fly!" she said. "A fly!"
Just that morning, Schadt told us, Ross Cagan had called him to say that they no longer had to search for a combination of drugs. After further study of Stephanie's mutations, Cagan had found a single drug, already approved (though not for colorectal cancer), that killed the tumor in the fly and "looks like it will knock Stephanie's cancer out."
Stephanie's eyes grew wide. "But if that's true," I asked Schadt, "then why would Stephanie have surgery and go in for more chemo? Why not follow this course of action instead?"
"Because," he said, "even brilliant oncologists don't go around shooting from the hip."
"But you don't mind shooting from the hip, right?" I asked.
"Oh, that's all we do," Schadt said.
We walked out of his office and around the corner, through double doors marked SCIENTIFIC COMPUTING, into a section of the lab crowded with garish lime-green cubicles, rows of them, populated by a United Nations of math nerds. And even though it was a Friday afternoon, every screen in every cubicle was filled with data, and the place was a hive of high-end analysis. "Come over here," he said, "I want to introduce you to the guys who did the deep analysis on Stephanie's data."
Walking up to two Russian bioinformatics scientists who work for him, Yevgeniy Antipin and Andrew Uzilov, Schadt gestured toward Stephanie. "Hey, guys, meet Stephanie Lee."
Antipin reached out to shake her hand, and Uzilov slowly rose from his chair, his face suddenly filled with emotion. He reached out both hands to her. "You're the person…." he said softly, with an expression of pure wonder.
The seventy-three mutations that he and Antipin had detected from complex data had just walked into the room. As Antipin explained to Stephanie that much of the computing at this level is automated but that jobs as critical as this one required manual analysis, Uzilov held on to Stephanie's hand, his eyes glistening.
Leaving the lab, we walked up Madison Avenue for a while in silence. Stephanie had her hands deep in the pockets of her peacoat against the early autumn chill. It had been a long, dizzying day. After a few minutes, I said, "So, what do you think?"
She stopped walking, looked over at me, and said, "I think I'm going to live."
Schadt and Cagan had never wanted to be cancer guys, but they were afraid they were going to become cancer guys, because now they were specializing in cancer. They weren't just conducting experiments with flies and data; they had a patient. They had Stephanie Lee. They wanted to save her life. In order to save her life, they'd had to learn as much as possible about the treatment of cancer, but they couldn't become cancer guys. Cancer guys are the guys who treat cancer every day and who learn that in the end very few lives are saved. Schadt and Cagan talked about that, after they finally met Stephanie on October 18. They asked themselves how many patients do you have to see die and how many treatments do you have to see fail before you inure yourself against the devastation of false hopes…before you not only assume but insist that everyone dies…before you become a cancer guy.
Now, on the morning of October 22, two days after Stephanie Lee got on a plane and flew back to Mississippi, Schadt and Cagan had to face the cancer guys. They were going to a meeting of the tumor board at Mount Sinai, a consortium of oncologists called in to decide a course of action in Stephanie's case. Schadt and Cagan were going to the meeting with good news—Cagan had stopped the spread of metastatic cancer in the Stephanie Fly. After creating a fly with three of Stephanie's active mutations, he had spoken to Schadt, and Schadt had told him that the network model of Stephanie's cancer showed activity in an unmutated pathway…that the pathway was behaving as if it had been flipped on by a mutated gene. So Cagan had activated that pathway and created a "four-hit" tumor in the Stephanie Fly…and he had found a drug that stopped its cells from spreading. A drug, as he had told Stephanie, that knocked the tumor out.
And yet Schadt and Cagan were tense, because the tumor-board meeting was full of cancer guys. And they knew what cancer guys do—they push the standard of care. They have the experience, and they have the statistics, and they knew that the standard of care, applied in this kind of case, might extend life by weeks or even months—and who were Schadt and Cagan to come in and say that weeks or months weren't important? Who were they to say that the standard of care should be abandoned because they had found a compound that knocked the tumor out in a fly? Schadt and Cagan were tense, all right, because of the inherent tension between clinicians who defined success in terms of time and scientists who defined success in terms of cure, between the standard of care and care that was nonstandard, by definition—that was as unique as Stephanie herself.
The tumor-board meeting was held at a clinician's hour—7:00 A.M.—and Schadt and Cagan were surprised from the start. They had expected six or seven doctors in attendance. Almost thirty showed up. These meetings usually went fast, with a consideration of a dozen cases in the course of an hour. But on this day, the whole tumor-board meeting was devoted to consideration of the tumor of Stephanie Lee. And Schadt and Cagan learned things from the cancer guys. Indeed, they saw for the first time Stephanie's five metastatic tumors, blown up on a CT scan. They listened to the surgeons go back and forth on the question of whether surgery was advisable, and then agree that it—surgery, along with the FOLFOX standard of care—might give her a 40 percent chance at five-year survival.
A 40 percent chance to survive five years? Both Schadt and Cagan had been operating on the assumption that she had months, perhaps weeks, to live. But now they were in a room with the cancer guys, and the cancer guys were "cautiously optimistic." The cancer guys were saying that they had—that science had—time. Of course, the standard of care would eventually fail; it always does. Of course, after three or four years, the patient would die; they always do. Of course, the cancer guys would exhaust the possibilities of chemotherapy, and the cancer guys know what happens after that. Schadt and Cagan didn't care…the moment in which cautious optimism had started to slide into cynicism was their cue. Schadt stood up and showed his own vision of Stephanie's tumor—the network model; the blue universe of data riddled with galaxies of malevolent activity. It looked to Cagan like a hair ball, and he could only imagine what it looked like to the cancer guys. But then he stood up and said that he'd taken the genes that Schadt had implicated in the galactic disturbances of Stephanie's tumor and implanted them in the guts of a fly. He said that he'd found a compound that shut them down, that knocked them out.
Schadt and Cagan knew they'd issued a challenge of some kind, but now came the final surprise. The cancer guys wanted to hear it. "They were like, 'Listen, you guys are saying that we don't have to do standard of care—we can do this?' " Cagan said. They were so used to the inevitability of losing hope in hopeless cases like Stephanie's. They were so used to having to watch people die. Now they quickly came up with a course of treatment for Stephanie. On the morning of October 25, she would get her surgery with Dr. Conway at Ochsner, a difficult and risky procedure in itself. Then if all went well, she would continue her standard of care with Dr. Roberts at Keesler. She wouldn't be cured, but with a little luck she would get time, and so would Schadt and Cagan. And they would also get more tissue, this time from the tumors in Stephanie's liver. The process would start over; Schadt's lab would sequence the genes from the tumorous tissue and then build a network model. Cagan would then implant the tumor into a mouse; he would then use the mouse to test the compounds he would screen in a ten-hit fly. And when the standard of care failed, they would be ready to attack her cancer with their own compound—and even to try to break down the tumor permanently with vaccines they hoped to create to respond to specific proteins in Stephanie's cancer that Schadt's lab identified. With the standard of care, Stephanie was looking at less than a coin-flip's chance of living to age forty-one. With Schadt and Cagan, she was looking at the possibility of life.
It was just over four months after Stephanie wept with an ER doctor who'd told her that she was dying. It was three months after she almost bled to death. It was two months after she begged Keesler to send her tissue samples to New York—"tell them my life is at stake." It was a month after the sequencers paid for by Carl Icahn told her that yes, she had been born predisposed to cancer. Now the oncologists at Mount Sinai were asking Schadt and Cagan if there was something they could do in their own intractable cases. And Dr. Holcombe was asking what studies had to be done to incorporate personalized therapy into the standard of care…a standard of care derived in part from none other than little ol' Stephanie Lee. There had been the imposition of obstacles at every step of the way, and the odds against her remaining on what Schadt called "a path to fight on" had beggared even his mathematical imagination. And yet here she was. Her tumor had become, in Ross Cagan's words, "at this point in time, the most fussed-over tumor that I'm aware of." Her cancer had become the sole subject of an hourlong and possibly historic meeting of the Mount Sinai tumor board, a meeting the significance of which Eric Schadt felt compelled to mark with a simple title:
"The Stephanie Event."
On October 22, the same day as the Stephanie Event in New York, Stephanie had a preoperative conference with the surgical team at Ochsner. She'd also found out that her mother had decided to take off from work in order to be with Stephanie before and after her surgery. "That's my daughter," her mother said. "I don't have but one child." She wasn't the only one—friends and family were coming from all over to be with her, and Stephanie was glad they were. She was starting to get scared. She was pleased when she heard that the scientists and doctors in New York had used her case to advance cancer care into the future. But she had her own Stephanie Event coming up: her surgery. They would be putting her out in three days, on Friday. And then, in a ritual almost as old as human civilization, they would be cutting into her, deep into her very vitals. And so she'd begun thinking of Terrance, as she always did when she was afraid. She talked to him, saying, Oh, how I wish you were here to hold me, before that surgery. How I wish you'd be there to see me, when I wake up. But Terrance wasn't there, except in her memories and her dreams. Cancer was. Even after all she'd been through, she hadn't put it behind her. No, it was still ahead of her, like her life, like the road to the surgical suite in New Orleans, and all unimaginable places that lay beyond.
UPDATE: Stephanie tragically died on the morning of February 4, 2015. She is survived by two daughters and leaves behind a legacy of hope and resilience. Read more about here life below, and please consider donating to the fund established in her memory here.
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Tom Junod is a writer at large at Esquire. He is the recipient of two National Magazine Awards from the American Society of Magazine Editors, the most prestigious award in magazine writing.
An Update:
AND STEPHANIE'S FUND: PLEASE DONATE HERE
Mark Warren is executive editor of Esquire magazine, where he has worked since 1988, directing much of the magazine's feature writing.
