An Elegant Defense

by Matt Richtel

  Also, simply, lack of sleep often is caused by stress and leads to more stress.

  So you get stressed, don’t sleep, your sympathetic response kicks in, your immune system gets dampened, and the cycle, through more stress and less sleep, spirals. Alone this is key. But Dr. Irwin offers a fascinating nuance.

  He believes that only part of the immune system gets dampened by this cycle. Stress and lack of sleep, Dr. Irwin believes, make it tougher to fight viruses but easier, or at least less difficult, to fight bacteria.

  His theory makes perfect sense from historical and evolutionary standpoints. Picture your forebear facing an acute threat—say, an attack from a lion or bear or from a fellow human with a spear, or simply having injuries from a fall or scratches from a rock or bush. The immediate threat would come from a puncture wound or bite and the bacteria that might be transferred by that injury. So it stands to reason that the immune system would favor lending its limited resources to a bacterial response over a viral one.

  To be clear, the release of cortisol can dampen both types of immune responses—to allow us to remain alert during an acute threat—but Dr. Irwin sees the dampening as having a greater impact on a response to viruses.

  In either case, virus or bacteria, these primitive responses can wind up having a perverse effect in the modern world. After all, these primitive systems kick in all the time, as if the body were responding to an attack by a lion or bear, but the actual threats are much different today, and often much less dangerous.

  “Those same systems of alarm and threat can become activated in a social situation. You get into an interpersonal situation, an argument with your boss at work,” said Dr. Irwin. “The sympathetic nervous system gets hijacked. It’s just as if we were exposed to an acute threat in Neanderthal times and were hurt.”

  Often, Dr. Irwin said, the culture adds another layer, pushing us forward, rather than letting the system settle down through withdrawal or sleep. “It’s a badge of honor to see how little sleep you can get by on. If you can sleep less and maintain function at work, you’re a better professional. You’re a better human being. That crazy logic has led to a sleep-deprived society, and that is having huge health consequences.”

  As concerns autoimmunity, there hasn’t been a large study that has expressly tested the relationship among stress, sleep, and a hyperactive immune system, but Dr. Irwin says “there’s a good case to be made” for a link between sleeplessness and autoimmunity. At the very least, the indirect connection speaks for itself: Lack of sleep leads to stress and vice versa, creating a vicious cycle that disregulates the immune system.

  Dr. Lemon, the Denver physician who treated Merredith and believes strongly in the hygiene hypothesis, says she tells patients worried about their immune systems, “Your job isn’t to keep your house spotlessly clean. You should sleep until you’re not tired anymore. Sleep is the easiest medicine to regulate. A single night alters your immune system. It blows things out of whack in one night.”

  She says that she is by no means blaming people who get diseases like autoimmunity or cancer for their stress or sleeplessness.

  Sometimes disease just happens.

  It happened to Jason. He’s our last story, the most telling of all about this extraordinary moment in time when we’re putting to work nearly a century of understanding the balance of our immune system.

  Part V

  Jason

  36

  A Word About Cancer

  In late summer of 2010 Jason was diagnosed with Hodgkin’s lymphoma.

  It’s a cancer of the immune system. The word lymphoma refers to the lymphatic system, the network of nodes where the immune cells gather. In Hodgkin’s—named for the nineteenth-century English doctor who discovered it—B cells have mutated into malignancy.

  Cell mutations take place all the time inside the body. All of us get cancers. You might well have one now. Most of these mutations die off, simply because they are too mutant to survive or because the immune system identifies them as alien and destroys them. In the case of Hodgkin’s, the cancer takes advantage of the immune system, dupes it, and even uses it to thrive.

  The cancer cells “look like self in disguise,” said Dr. Alexander Lesokhin, an expert in blood cancers and a hematologic oncologist at New York’s Memorial Sloan Kettering, one of the leading research institutes in the world. Part of the way that Hodgkin’s and other cancers disguise themselves is by tricking the T cells that would ordinarily help kill off the mutation. What the cancer does is send a signal to the T cell to self-destruct.

  Why would the T cell do that? Why would it even have such a receptor on its surface capable of receiving a self-destruct signal?

  It’s because the immune system has many mechanisms that are aimed at slowing it down, shutting it off, keeping it from overheating. Cancers take advantage of these fail-safe mechanisms to survive.

  The self-destruct receptor on the T cell is called programmed death. For short, PD.

  On the cancer is a molecule called PDL-1, a programmed death ligand that binds to or connects to the PD receptor on the T cell.

  Inside Jason’s body, malignant B cells had grown and were using PDL-1 to put the brakes on the killing part of his immune system. At the same time, now that the immune system had received a message that the cancer was “self” and not alien, the immune system actually set out to protect and support the cancer.

  Dr. Lesokhin said it appears that “the tumor co-opts the immune system and says, ‘I’m okay. I just want you to help me grow.’”

  It’s tempting to anthropomorphize the cancer and think of it as cunning, or strategic, but, really, cancer is a product of the same evolutionary processes that lead to our own survival, or that of any other species or organisms. When a mutation occurs inside us, it thrives if it has developed the ability to evade our body’s defenses. Over the course of our lifetimes, we’re being thrown tons of twists by malignant cells, and it takes only a handful to turn on the immune system’s brake and start a cascade of malignancy.

  “It’s basically evolution at work in real time, a Darwinian survival system,” Dr. Lesokhin said.

  In the case of blood cancers, the exact mechanism is still being explored, but Dr. Lesokhin hypothesizes that the successful cancers result from an evolutionary process in which the surviving mutations are the ones that evolve a key adaptation that allows them to “use the immune system or avoid the immune system.”

  Jason had this growing inside him. A cancer had figured out how to turn down his defenses, mute them, while using the might of the immune system to build the infrastructure—the blood and tissue roadways and constructions—to help the cancer grow.

  In Jason’s immune system, there had been a coup. Left untreated, the malignant cells would’ve reproduced unchecked, voraciously eating up more territory, invading organs, causing normal bodily functions to slow or cease. Jason would’ve lasted only four months. Fortunately, there was a veritable nuclear bomb to deal with those rogue cells—or so it would have seemed.

  Chemotherapy is brutal. “When you have cancer, you spread napalm on it and burn everything to the ground,” Jason’s oncologist, Dr. Mark Brunvand, told me.

  Mostly through dumb luck, scientists had at least found an effective version of napalm for Hodgkin’s, the kind of cancer Jason had. It provides a 90 percent survival rate.

  The chemotherapy drugs target cells that are fast dividing, which is a marker of cancer. The malignant alien cells reproduce quickly, just like those healthy cells in a wound that are being fed by blood and protected by the immune system itself. The evil malignancies co-opt the system, and in an odd way, they get treated to the privilege of dividing quickly. There are other cells in the body that also divide quickly, including hair follicles and cells in the gut and mouth.

  A fire hose was spraying Jason’s Festival of Life with poison. That terrible toxic cocktail called ABVD was effective against all these cells, but its list of possible side effects reads lik
e a who’s who of extreme irritants and dangers: bruising, bleeding, tiredness, constipation, flulike symptoms, hair loss, mouth ulcers, sore eyes, dizziness, and on and on. On top of this is insomnia, which can be a byproduct less of the chemotherapy than of the use of steroids. These are used, as you know by now, to limit inflammation and cut down a massive immune system response. Why, you might ask, would you limit an immune response in a time of cancer?

  In this case, you want toxins in your body. Poison is your ally, and the more it can be allowed to flow freely, the greater the chance it will target these fast-dividing cells. But part of the way that steroids suppress the immune system is by activating the adrenal glands (remember that when stress and adrenaline get activated, they suppress the immune system).

  In short, there is nothing good about chemotherapy other than the fact that it can save your life. A trade-off, often, worth making.

  Chemotherapy, Jason discovered, is also expensive. The first clinic he visited told him that the terrible toxic cocktail known as ABVD entailed “twelve chemos at $8,500 a pop. They realized I had bogus insurance, and they cut me loose.”

  He was two days away from treatment and needed a safety net. He found it at Denver General Hospital, a catchall for the uninsured or poorly insured, the place where you end up when they find you on the street with a gunshot wound or an opioid overdose, or where you go when you’ve got cancer and no money to treat it. It was October 2010. Jason jumped in, sort of. During his first round of chemo, he had trouble getting to his appointments on time.

  He was “always on the road, always busy,” said Dr. Michael McLaughlin, his first oncologist. “I thought: This guy is on the run.”

  Jason’s chemo didn’t work. He was one of the unlucky 10 percent whose cancers manage to survive the toxins. Sometimes this happens because cells mutate in the face of the drug’s onslaught and become resistant to treatment. Relatedly, for the best chance of attaining good results, the treatment needs to be given in the proper doses at the right times. Jason thus didn’t do himself any favors by missing some appointments, potentially giving the cancer more time to adjust to the treatment. Whatever the reason for the chemo’s failing, and there can be no way of knowing for sure, the race to save Jason’s life had begun.

  37

  Laughter and Tears

  Jason could tell a yarn. He could hardly talk without telling a yarn; according to his zealous world view, every day was an adventure. He would relate his experiences like a combination of a bard, radio talk-show host, and bawdy comedian, punctuating his tales with occasional bursts of laughter, often directed at himself. His mother thought he’d missed his calling as a comedian—“the funniest person I know,” she told me with understandable maternal bias—but often Jason’s actions and audacity were the funniest part of the story.

  When I think about Jason’s cancer saga, I find myself thinking about a particular night of storytelling that took place by phone in late spring of 2011. It was a night when Jason and I began to reconnect in a much more real way, after having come to live very different lives.

  I lived in a light-brown stucco flat in an almost-suburban residential neighborhood in San Francisco, and Jason lived in Las Vegas and his van. The night he called, I’d helped put our toddlers to bed—Milo was two and his newborn sister just six months. They slept in a back bedroom; Meredith, my wife and their mom, read in the room next to theirs. In the front room of the house, I sat on a giant blue ball we used to bounce the kids on when they had trouble calming down or sleeping.

  Jason talked about his cancer. He discussed missing chemo appointments with the same self-effacing humor he’d employed when he talked about forgetting to study for a French test in eleventh grade. It was nothing to get worked up about, or even a badge of honor, especially when there were so many more adventurous things to do.

  He launched into a story about driving across the country to a sales conference. By this time, he had the Ford Windstar. During the trek, he’d wound up driving through Kansas, where he’d heard on the radio there was a good high school basketball tournament going on, and he’d decided to make a pass through and watch the games.

  “The motels were filled up,” he said. “I slept in the van. The van was full of trinket boxes, and it was so stuffed in there that I could barely make room on top of them. I could barely fucking breathe!” I feared his happy laughter would wake the children. I was right there with him, totally swept up in his journey.

  Then boom, he’d be off to the next topic. He told me off-color stories of past dating conquests and failures, and he also suggested those days might well be behind him. “Dude, have I told you about Beth? She’s awesome.”

  Beth Schwartz, his girlfriend, had angel written all over her. She was right in Jason’s wheelhouse. She loved football—she’d been sports editor of her high school paper in Houston; she was an athlete herself, a soccer player and track runner; and she loved to laugh and thought he was hilarious. He found her beautiful. He also might not have fully grasped just how wide the latitude of her ability to either ignore, or even appreciate, his flights and dreams.

  They met Labor Day weekend in 2006. She’d broken her leg in an in-line skating accident and was on crutches when she showed up at a West Virginia alumni club mixer to watch the Mountaineers play on the screens at Sierra Gold, a medium-size tavern-style joint. Beth was in a back room when she overheard someone say her name. It was some old-timer in the alumni club, who answered “Beth,” in response to Jason, who had asked him: “Who is that girl on crutches?”

  Jason was in the bar for work purposes. He was setting up a fantasy football terminal that he’d come up with. (Beth called it “a crazy stupid Boondoggle Sports Network.”)

  She told me: “I looked at him and thought: ‘Uh-oh, I’m in trouble.’”

  Why, Beth?

  “He just looked like trouble—somebody in Crocs and cargo pants and a T-shirt that looked like it hadn’t been washed in a few days.”

  Soon they were drinking at the bar. While Jason was trying to seal the deal, another man tried to hit on Beth. The guy had tried to make a joke about how Beth looked so young, and he wondered if her mother was at the bar too. It was awkward, and Jason smoothly retorted: “Let me give you some friendly advice. Never try to pick up a lady by asking about her mother.”

  “He had me. Right there,” Beth said.

  In addition to Beth’s other attributes, she had a job that played into Jason’s love of adventure. She was editor of a high-end luxury magazine in Vegas, which meant she got invited to every notable restaurant opening and concert. It was Las Vegas, on the house. “Being the Italian talker he was, he could sit there and hold court—if I could get him to dress properly,” Beth said.

  There were quiet times too. A typical date involved the pair of them going to a bookstore or a coffee shop to read. Jason devoured history books, and loved that Beth was also an avid reader. There were times when it could feel downright domestic.

  That night, on the phone, Jason had a question for me.

  “Rick,” he said (short for Richtel, and what he often called me), “do you think I should have a family?”

  I listened to his question. I couldn’t tell if he was serious or not.

  “You, Noel, Meier, everyone has settled down, and you guys seem really happy. I’ve been thinking about whether I’m running out of time.” He sounded mournful.

  “It’s great, Greenie. You’ll love going to bed at nine.” I was half joking, but also trying to soft-shoe the conversation to feel him out.

  “I’m serious. Should I?”

  “I’ll tell you one thing. It’s freeing as hell. I spend a lot more time thinking about stuff I love thinking about, writing and playing tennis and even playing music, rather than where my next date is coming from. And having kids and a wife you love—well, it’s impossible to describe how great it is until you’re in it.”

  “I don’t know, man . . .”

  He really did hate this subje
ct; that much I learned as time went by. He loved Beth, cherished her, but when I asked her if he wanted to put a ring on it, he’d shut down the conversation. It had nothing to do with Beth, I realized, and a lot more to do with commitment. Maybe because of the loss of his dad or his love of the open road—I could never be sure.

  It dawned on me that night, or shortly after, that my own relationship with Jason had transformed. We were genuine friends now, and a lot of that had to do with my own bout with illness. I told Jason what I’d been through.

  It happened when I was twenty-five.

  I can picture the moment, if not the day and precise year. I’ll put it around late 1991 or 1992. I was out for a jog in Palo Alto, where I worked at my first newspaper job. I felt light-headed. This had been happening off and on. I went to a doctor who’d been assigned to me by my medical insurer. He was a great guy, in his seventies or early eighties, I’d guess. I’d gone to him a few times to relate these symptoms, and he just gave me antibiotics and kindly sent me on my way.

  Even I knew it was not the right course of action. I was due for a self-reckoning.

  About three years prior, after I graduated from UC Berkeley, I went to Europe with friends. While in a youth hostel in Rome, I wrote a life-changing postcard. It was written midsummer, to the School of Journalism at Columbia University, which I’d applied to and which had put me on its waiting list. The postcard rhymed and explained that if they didn’t take me off the waiting list and admit me, I would spend all my tuition money on booze.

  I had little business being on the waiting list at the esteemed school in the first place. I’d never done any journalism, which tended to be a prerequisite. The reason I’d applied, in my final semester at Berkeley, was driven by a gut-level understanding that I liked to write and ask questions and explore ideas, that I had something of a heightened curiosity instinct. True story: Two days after I returned from Europe, I was back in Boulder, with no freaking clue about what I was going to do with my life, when the phone rang.