You were a New York artist, Iowa-bred, with a narrow and idiosyncratic range of subjects. You painted bulldogs and cheerleaders, truck stops and mammoth-hunting cavemen. For two decades you inhabited a drowning world, which you nostalgized even as it vanished beneath a tidal swell of money. Its borders were 14th to Canal Street and Broadway to the East River; its capital was the Mars Bar. You were the first to help a friend and last to leave the party, and beloved by your fellow strivers. You were smart, funny, unfailingly courteous: the punk-rock pirate king of the art scene.
You loved your life. “But this is wonderful!” you would bellow when a work of art or meal delighted you. You had the best gigs: artist-in-residence at the Museum of Sex; interviewer at Whitehot Magazine; art handler for Manhattan’s galleries, bicycling up and down the island’s streets with a determined expression. But in your late forties you began to feel out of sorts: burdened, headache-y, doomed. Your friends and family worried. You made dates that you had difficulty keeping; often, you slurred words after a single beer. One night in July of 2015, during a visit to your younger sister in Boston, you collapsed with a seizure.
At Massachusetts General Hospital you were given a CAT scan, and spent a restless night, waking anxious and angry. The nurses wouldn’t let you step outside to smoke. “This is bullshit,” you said, and tried to leave. Your parents, also visiting Boston, begged you to stay for tests. Your technologist brother-in-law, who had been traveling, appeared and conferred outside your room with a doctor, whom he knew from his work. You heard the doctor ask, “I can see Joe is an unusual guy, but he hasn’t always been like this, has he?” The scans revealed what you most feared: an ominous cloud on the right hemisphere of your brain.
Jason Pontin (@jason_pontin) is an Ideas contributor for WIRED. He was formerly the editor in chief and publisher of MIT Technology Review; before that he was the editor of Red Herring. Now he is a senior partner at Flagship Pioneering, a firm in Boston that funds companies that solve problems in health, food, and sustainability. Pontin does not write about Flagship’s portfolio companies nor about their competitors.
Your doctor, a kind little man in a bowtie, said you must have surgery. You shaved off your long hair, and they wheeled you to an operating room. Afterward, the left side of your body was temporarily stunned, but you had a diagnosis: anaplastic astrocytoma, a brain cancer of the star-shaped glial cells called astrocytes. Your doctor said the good news was that such cancers don’t metastasize beyond the brain. “That’s the good news?” you replied. “Tell me the bad.” The surgeon had removed a ping-pong-ball-sized mass from your prefrontal cortex and parietal lobe, carefully removing necrotic flesh and skirting healthy tissue using a map generated by fMRI. But astrocytomas are diffuse, spreading their lacy filaments throughout the supporting and insulating tissues of the brain, and they grow back. Thirty percent of the tumor was still in your skull.
Humans are shy about mortality, and families adopt clinical language to talk about what they dread. What stage is this cancer? your family asked. “We don’t like to stage gliomas anymore,” your doctor reluctantly answered. “But this would be a stage 3 or 4 tumor.” There was no stage 5. He hastened to add, “Listen, Joe, no promises, but I think you’ve had this cancer for a while. You’ve not been yourself. Some of these tumors are slow-growing. We need to sequence the cancer before we make any plans.”
Your doctor, a distinguished Harvard Medical School professor of neurology, a PhD researcher as well as a clinician, explained that the gross morphology of cancers was misleading. Today, at teaching hospitals, doctors sequence the genes of cancerous cells and compare them to normal host cells, a technology called cancer genomics. When we know a cancer’s mutation, he said, it’s sometimes possible to customize treatment. Some of the drugs employed in precision medicine are remarkable, and if a patient has a specific mutation, they can (in combination with chemotherapy, radiation, or surgery) cure cancer, or at least make the disease a chronic illness like diabetes.
He rattled off examples. Small molecule drugs can target critical proteins within cancerous cells. For instance, Iressa inhibits the expression of a protein called epidermal growth factor receptor, whose mutation is implicated in lung and breast cancers. Lung-cancer patients with EGFR mutations who took the drug lived twice as long. Or, at great expense, we can genetically engineer a patient’s immune system to target a specific protein. Kymriah coaxes a very sick child’s own T-cells to attack a protein called CD19, expressed by the B-cell lymphomas. Nearly 80 percent of children with acute lymphoblastic leukemia, who had exhausted every other hope, were still alive 12 months after being administered the therapy.
A sample of the mass removed during your operation was sent to a lab. In a couple of weeks, you returned to MGH to hear what you thought would be your fate. You were told that a gene in your cancerous cells had mutated so that it no longer correctly expressed an enzyme named IDH1, important for cellular detoxification. For reasons scientists don’t fully understand, patients with this mutation live longer than those with a wild-type glioma, where mortality is often measured in weeks. In some cases, an astrocytoma is a secondary cancer from a glioma that has been lurking in the brain for years. Some patients with IDH1 mutant gliomas live for decades. Your doctor warned you, “There’s a small clinical trial of an IDH1 inhibitor. The cancer board will meet to discuss your case, but it’s likely we won’t agree on your treatment.”
It was true. Your doctor recommended proton radiotherapy, without chemotherapy. The surgeon wanted to do nothing at all: Leave it alone, he counseled, as if your cancer were an animal. You requested another opinion, and your doctor told you to see his colleague up the river at Dana Farber Cancer Center. He could guess what the colleague would say. At Dana Farber, the fiftysomething head of neuro-oncology pleaded with you: “I’ve been doing this for 30 years. Oncology is more of an art than a science, but I’ve never regretted throwing everything at an astrocytoma. You should do radiation and chemotherapy. And wear a special hat. An electrical hat will make the cancerous cells more chemo-sensitive.”
You had to laugh. At the next consultation, you asked your doctor, “This is the best hospital in the world. How can you guys know why I’m sick but not know how to treat me?” He frowned, embarrassed, and spread his hands. “Consensus on the best treatment varies by tumor,” the doctor explained. “For some tumors, there are protocols and optimal treatment plans. But with other cancers, like your astrocytoma, the available therapies have limited efficacy, which leaves room for debate, especially about how much toxicity to accept.”
Cancer is a lottery, your doctor said; precision medicine isn’t always possible. We don’t know whether we should accept the low efficacy and high toxicity of current treatments, or refer the patient to a clinical trial for an IDH1 inhibitor when there’s no way to know whether the newer medication will work at all. The blood-brain barrier makes brain cancers especially hard to drug. Worse, we have surprisingly little data. The first cancer was only sequenced in 2006.
You have the misfortune to get sick during a liminal age, where we know a little but can do less. We don’t know why you’re sick, he confessed—not really. We can sequence your cancer’s mutation, but that doesn’t explain why you have brain cancer. A person’s cancer might not have one cause or be a well-defined disease. We don’t know how your disease will progress; some of these tumors grow so slowly, you might die of something else.
“Right, but what do I do?” you asked. Your doctor said he couldn’t answer. There was no real standard of care for IDH1-mutant diffuse gliomas. You must decide for yourself. In the end, you chose your doctor’s plan, because you liked him best. Cost was no issue, because you had Medicaid. Through the fall, you endured proton therapy. Five times a week, over 30 sessions, you lay on your back with your head immobilized by a mask with clamps for your teeth, while charged particles irradiated your head. You began taking a medicine, called Keppra, to control your occasional seizures.
The Keppra made you testy. Other antiseizure drugs made you giddy or unable to focus. Eventually, you combined a lower dosage of Keppra and Clonazepam. You lived on the top floor of your sister’s house, and made art. You tried to paint but you were dissatisfied with the results, and in a burst of creativity that winter and spring, you created a series of absurd and painterly collages: a gray, dour Nixon, surrounded by blooming, pink garden roses; your doctor, dressed as Napoleon, riding a giant ocelot. You showed your collages at a gallery in Brooklyn. You worked cheerfully at your physical and occupational therapy. Cautiously, you allowed yourself to plan for the future: Maybe you’d go back to school; perhaps you’d return to your life in New York.
It wasn’t to be. In the spring of 2016, your seizures became a monthly ordeal. You found yourself neglecting the left side of the world unless your sister reminded you. In the summer, you visited England with your sister and brother-in-law, admired the Titians and Tintorettos in National Gallery, and walked around Stonehenge and the hills of the Lake District. It was very pleasant, but it was also increasingly tiring to walk. Your left hand was stiffening into a claw. You liked to hold your two-year-old niece, but your sister feared you’d drop the girl.
Back in Boston, your doctor ordered another MRI, and saw what might be new tumor growth. Unsure, he requested a needle biopsy, and then diagnosed a scarring common with radiation therapy, telling your family not to worry too much. In September, you traveled to the LA Art Book Fair, but became overwhelmed by the vast city and got lost. Your seizures were weekly now, and that winter you fell headlong down the stairs of your sister’s house, splitting open your eyebrow.
In the new year, you fell on the ice while walking your brother-in-law’s bulldog, and couldn’t figure how to get up. After more scans, your doctor put you on an anti-angiogenic drug, which would starve your cancer of blood: you said you were “blastin’ Avastin.” In May of 2017, you went to Rome for your brother-in-law’s 50th birthday, where you toured the Sistine Chapel and saw Michelangelo’s Last Judgement. You visited the Borghese Gallery and wondered how Bernini made marble resemble soft flesh. Afterward, you asked to stroll back to your lodgings across the dusty Borghese Gardens. It was dusk, and you were so happy, but suddenly your leg shook and your arm flexed, and this time the seizure wouldn’t stop even when you took three emergency doses of Clonazepam, and your brother-in-law had to help you to the rear seat of a taxi while the driver spluttered and protested.
Things moved more quickly. In Boston, your sister tearfully conceded she couldn’t take care of you anymore. In August of 2017, you moved back to Iowa to live with your parents. You wore a support on your left leg, then a sling for your arm, and then you carried a cane. You, who read every day, stopped reading. You, for whom art was life, stopped making art. In early March, you woke, unable to walk. You were hospitalized. Scans showed a tornado of tumor growth.
You were moved to a hospice. An oncologist said, “This tumor will take your life.” You were dependent on other people, but politely thanked everyone for small kindnesses. Your friends came from New York and all over the country, some bringing you art they had made. You remembered everything, and told funny stories. In April, you talked less, and seemed tired. You became quiet. On April 16, 2018, your family was with you, and you looked everyone in the eye, and smiled. Then you slept, and your breathing changed. You are dead.
Jason Pontin was the brother-in-law of the artist Joe Heaps Nelson, who died last April.