An Elegant Defense

by Matt Richtel

  With the industrialization of food, we packaged and processed and transported food and got more calories to more people, helping cut down sharply on malnutrition. But our industrial processes introduced junk food, and obesity has soared around the globe, doubling in seventy-three countries since 1980, and rising in most others. Diabetes is rampant. Poor diet is killing us by the millions.

  An atomic bomb ended a terrible war. The same technology leaves us in constant peril.

  With television, computers, and phones, communications have become the stuff of nineteenth-century science fiction. Texts from Everest! But we are increasingly drawn to the bells and whistles, the novelty, the rush of dopamine when we stare narcissistically into a selfie camera while we are driving.

  Industrial processes changed every facet of life, from clothing and housing to transportation and communications. But smokestacks led to a changing climate with apocalyptic dangers.

  And there is arguably no more powerful medicine on earth than antibiotics. They are vital for our survival. Full stop. But their widespread use also threatens now to cause the evolution of bugs that will make past plagues look like the common cold.

  These examples are not arguments against progress. This is not Luddite talk. But it is an argument for awareness. Sometimes we cannot control our world and hold it too tightly without squeezing some of the life from it.

  In the case of the immune system, we have tried to overengineer. It has cost us. We must learn sometimes to let nature lead.

  It’s what Merredith teaches us. She has learned the hard way.

  In December 2017, Merredith was taking a walk with her dogs, just six months after she and I had taken the walk I described at the beginning of the book, when she showed me how the sun inflamed her skin. One of the dogs, Bam-Bam, stopped suddenly. Merredith tripped over the dog and landed on a rock. Exquisite pain rocked her arm.

  As she walked to her car to go to the emergency room, she could see her arm hanging so loose it was as if it were flapping in the wind.

  The humerus was so shattered that it required forty-four pins and two plates. The surgeon told her that he suspected this was from all the medications she’d taken, weakening her bones.

  Merredith’s journey draws me back to the challenges of tinkering with the immune system. She came eventually to treat herself less with modern medicine and more so with primitive methods, the tools of our great-grandparents, herbs and rest and nutrition, vitamins, turmeric, tart cherry. These are not chosen at random, nor merely the stuff of folk wisdom. Some of these have decided scholarship backing up their anti-inflammatory properties. (She also swears by probiotics.)

  She knows her triggers: sun—“especially sun”—sugar, processed foods, whey.

  She has become her ship’s captain. “The clues were there and I could find them. I could listen to my body. I controlled for what I could and then researched other symptoms and causes, found papers and studies showing, for example, that autoimmune patients typically have massive deficiencies in vitamin D. So I added vitamin D. I already knew anecdotally from my own experience that B vitamins could be incredibly helpful in warding off fatigue. I began adding water-soluble liquid B vitamins (i.e., MiO) to my water. And so on, all trial and error, until I cobbled together a regime that seemed to work. It’s not perfect, but it’s important to note that I am not worse than when I was on medications.”

  Much of what I’ve written here is a celebration of science and of medicines born of it. In no way do I intend these takeaways to detract from human progress. The best example is the advent of antibiotics. It helped begin a journey that leaves us now with another incredible milestone, the drug that gave Jason another year of life. I wish for everyone, for my family, for myself, the development of treatments that will prolong and enrich a quality life.

  What Merredith’s story illuminates, though, is that these drugs—as the immune system teaches—must also be used with an eye toward the delicate balance that has led to the survival of our species. Even now, though, we are pulling back sharply on the use of antibiotics so that the element that saves us doesn’t lead to civilization-threatening pandemic.

  The takeaway here is to understand the risks and the motivations of companies selling the drugs that address diseases.

  “The pharmaceutical industry has made a business out of targeting them with specific drugs and antibodies. I can’t stand it any longer,” said Dr. Dinarello, who helped us understand fever and interleukins. “Psoriasis, arthritis, bowel disease. The industry is targeting different ways of treating them—all targeting cytokines.”

  But the risk is infection, even cancer. Why? Because, as you now know, you’re tinkering with a very sensitive system.

  “Take the patient. His immune system is pretty much under control. His physician says, ‘You can feel a little bit better if you add this antibody. You do have the risk of infection, but we can take care of that,’” Dr. Dinarello says. “Patients go for the risk.”

  Big money is at stake, he said, and added: “Just look at the ads on TV.”

  The profits are huge. Decent chance that use of these could help save your life or the lives of your children or grandchildren. Better chance it’ll come with side effects.

  Coincidentally (or maybe not), the very night after I interviewed Dr. Dinarello on this subject, I was watching the news, and on came an ad for a drug called Otezla, which is used to treat psoriasis. The ad noted a list of potential side effects, which in and of itself is little different from many ads for drugs. Some sounded quite typical, like nausea and diarrhea, but others stood out. “Some patients reported depression and suicidal thoughts.”

  Now that the connections between inflammation and mood were clearer to me, these potential side effects seemed to feel more real, not just “in the head.”

  I went to the company’s website, and that’s where I found additional disclosures. The FAQ on Otezla states:

  The exact way in which Otezla works in people with psoriasis or psoriatic arthritis is not completely understood. Based on laboratory studies, what is known is that Otezla blocks the activity of an enzyme inside the body called phosphodiesterase 4 (PDE4). PDE4 is found inside the inflammatory cells in the body and is thought to affect the process of inflammation. By blocking PDE4, Otezla is thought to indirectly affect the production of inflammatory molecules, helping to reduce inflammation inside the body.

  To Dr. Dinarello, the issue of the side effects of these medicines underscores a simple message: “It reveals how sensitive the immune system is to suppression.”

  Buyer beware. Be aware. Take care. You tinker with the immune system at your own risk.

  For those who seek a different path, like Merredith, there are things we can manage, things that science shows us are powerful. The best examples are those over which we have complete control: sleep, exercise, meditation, and nutrition.

  Sleep and exercise play such a key role in keeping the immune system in check, partly by keeping the adrenal system from firing too intensely; when it does become too intense, adrenaline—epinephrine and norepinephrine—can create the cycle in which cytokines are released, leading to inflammation, sending the system further out of balance, even leading to more sleeplessness and more adrenaline. Not only can inflammation increase, but other parts of the immune system can become compromised, less able to function. At the very same time, the festival becomes susceptible to overzealous immune cells and to pathogens that are not held in proper check, like herpes.

  The so-called type A lifestyle is a good way to let your immune system go wacky, and to no good end. Linda Segre can attest to that.

  With regard to nutrition, a simple conceit: The less toxic the things you put into your body, the less likely your body is to create, or need to create, an inflammatory response. When there is an alien presence—say, cigarette smoke—it leads to a disease cascade, including inflammation and then a need to rebuild damaged tissue. The more times there is such damage, the likelier the new ce
lls will be malignant ones, with the terrible combination that leads to successful cancer. When it comes to food, science identifies risks associated with unnatural substances you digest, additives and chemicals and factory inventions that are not actual food. They make it likelier that your immune system has little choice but to react.

  There is even more evidence supporting the value of lifelong exercise. One particular study, published in 2018, shows the importance of exercise to the immune system and longevity. The study looked at the immune systems of people aged fifty-five to seventy-nine, comparing more sedentary people with regular cyclists. The people who exercised showed several crucial differences in their elegant defenses: The cyclists produced more new T cells from the thymus, and they had fewer cytokines that cause the thymus to decay. The upshot of the research is that exercise slows the natural aging process of the immune system.

  These tips are well-worn, but perhaps at least you can now see the scientific basis for them and the way they connect to your immune system.

  Or you can take your cue from Dr. Ephraim Engleman, who was an immunology giant who by most standards lived forever. At one hundred and four, he got his driver’s license renewed. He still commuted to the office to study autoimmune disease. He died just shy of his hundred and fifth birthday. He was in his lab, at the University of California at San Francisco, where he pioneered research into causes and cures of rheumatoid arthritis. The year was 2015.

  An obituary published by the university listed his self-professed secrets for longevity: Avoid air travel, have lots of sex, keep breathing, and most appropriately, enjoy your work, whatever it is, or don’t do it.

  So there’s that.

  I tie these points together with my own observation drawn from the sum of my research. The more active you stay, body and brain, the more you signal your internal systems that you continue to play a vital role in your own survival and the survival of the species. This leads to a virtuous cycle in which key internal mechanisms continue to regenerate, allowing you to play a vital role and, when you do that, pushing the cycle on. By contrast, if you grow stagnant, physically and mentally, the system is signaled that you are calling it quits and it need not “waste” resources on your survival.

  Finally, among all these lessons is the one biggest surprise I took from writing this book. I’ll call it “The Meaning of Jason.”

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  The Meaning of Jason

  When I started reporting this story, just as Jason had risen from his deathbed, his cancer miraculously gone, I thought I might be writing a book about the quest for immortality. The journey of the immunologists was reaching a point at which we could resurrect people. As a species, led by an international cadre of brilliant scientists, we were discovering how to tinker with the immune system, such that we could prolong life for who knew how long.

  It was the first question I began asking: Are we looking at living a long, long time? How can I not wonder? Is this about immortality?

  It’s absolutely fair to say that the journey to extend life has been a defining characteristic of the human condition.

  If the quest has been immortality, we are miserable failures. Yes, we’re living longer, and better, but the best we’ve got to show for it is the occasional person who hits a hundred and ten. It’s a blip. Now I understand one of the key reasons. Our immune system is doing us in.

  You heard right. The defense network—so often upheld as the key to health, and it is that, certainly—plays a big part in the way Jason’s story ended, and in how all of our stories will end.

  The underlying reason for this particular meaning of life comes from several key aspects of the immune system—attributes that I’ve laid out over the course of this book.

  One has to do with the trade-offs that the immune system is constantly making to keep things balanced in the Festival of Life. Take, for example, wound healing. The immune system has to allow our cells to divide so that we can rebuild after injury. The immune system fosters new cell development, helps access blood and nutrients, lets the festival thrive. But this trade-off also allows for the strong possibility—even inevitability—that malignant cells will thrive.

  “Cancer happens in everyone,” Dr. Jacques Miller, who a lifetime ago discovered the role of the thymus, told me as we discussed the meaning of the immune system and life. The brain will fail, the organs will shut down, the lungs will flood. Some of these will owe to breakdown of our defenses, some to an overwhelming pathogen, but some, like cancer, will arise from a complicity of the immune system itself.

  The reason is that the immune system hasn’t evolved to defend us as individuals. It has evolved to defend our genetic material and the species as a whole. It does an extraordinary job of keeping us alive until we reproduce and then rear our offspring. After that, it does an even better job of moving us out of the way.

  “Evolution has decreed we cannot live forever,” Dr. Miller said. “Nature, evolution, has decreed you’ve got to make way for the next generation.”

  Ruslan Medzhitov, the Yale scholar whose pioneering work illuminated the innate immune system, echoed this thought and added a point that no medicinal fix we contrive will lead us to live forever. “There is no ultimate solution. There is no free lunch. If you cure cancer, you will have more cases of neurodegenerative disease. If you cure neurodegenerative disease, a major plague will come for people who are a hundred years old. There is no ultimate solution, nor should there be.”

  But this reality is blessed with light. “We have to distinguish between life-span and health-span,” Medzhitov said. “You don’t want to live forever, but you do want to be healthy when you’re old.”

  This is what all these inventions and innovations have provided us: a bit more life and a whole lot more comfort as we age. Less pain, anxiety, disabling disease. Less fragility.

  As a species, we have strived for immortality and attained only a distant second place. But third place sucked a lot, earlier death, agony.

  The Meaning of Jason holds two competing principles in exquisite balance: We must continue to strive, dream, and exercise all the passions that have gotten us this far, while also doing a much better job of accepting death. Death is not just inevitable, not just programmed into us and facilitated in ways by our immune system. It is essential for our survival.

  It is not an easy leap to at once be driven by terror of death and yet embrace it with humility and grace. Our continued health lies in creating this balance, as elegant as the balance struck by the immune system itself.

  On January 1, 2017, I was back in Colorado, loading the family into the car after a ski day, when my cell phone rang. I figured I’d let it go to voice mail. Big flakes floated down, and I was harried. But the caller was Guy Greenstein, Jason’s brother, and I just had this strange feeling.

  “Hey, Guy.”

  “Hey, Matt. I have some bad news. My mom died.”

  Guy had found their mother collapsed outside of her bathroom. It looked like it had been the heart, and fast.

  “The coroner, Mike, he said to me: Didn’t I just see you?”

  Rest in peace, Catherine Greenstein.

  Six months later, I lost my beloved grandmother, Anne Richtel, just a few days shy of her hundredth birthday.

  In October of 2017, Ron Glaser went into hospice in the memory care unit. He became confined to a wheelchair because of the risk of falling. He understood little.

  “I can put my face literally two inches from his, and he will look through me,” Jan Kiecolt-Glaser told me. In her particular spirit, she managed to find the glitter. “There are still golden moments when he recognizes me and smiles.”

  Two months later, almost a year to the day that Cathy died, Dr. Ben Barres, the guru of dementia and the immune system, passed away on December 27, 2017. He was sixty-three. He’d hoped, he told me, to have an immunotherapy reprieve like Jason. He did leave a monstrous legacy that may yet spare us some of dementia’s cruel ignominy. He embodied proof of the value of
diversity. Born a woman, he became a man and experienced the world through different eyes, perhaps allowing him to see what others could not.

  During this project, death came and went. This, as I say, is not the place I expected to end up. I thought I’d tell the story of Jason driving in the foul-smelling Windstar to Denver to get his injection, waking up one morning to hear his girlfriend say his tumors disappeared, and then going on to another adventure. I thought he’d populate the world with yarns and fumes, pausing only briefly to fuel up at 7-Eleven for more snacks. In that survival story, I imagined, would be hope for all of us.

  Not infrequently, after Jason’s death, and well before, I began to think of him in a new, and particular, light. I saw him as a son—the son who lost his father. This perspective is excruciating for me because my own son, Milo, is ten. Like Jason, he’s a jock—Prodigy 2 is what Jason called him. I’m Milo’s coach, just like Jason’s dad coached him. Like Jason and his dad, Milo and I are thick as thieves. Just like most fathers and sons. My daughter, Mirabel, is eight, a creative, funny, loving soul; a child of such magnificence, as is her brother. I dared not dream of having such offspring and somehow did. The prospective horror of leaving behind a son and daughter, a family, or losing one, has become palpable. Like so many, I count my blessings every day. Each day, I count with a little more gratitude. We have a finite time in this Festival of Life. It is beautiful. It hurts.

  Thanks to science and wisdom both, we possess more comfort as we age, and knowledge about how our bodies work so as to make better choices. When sickness hits, we will get another year, or two or ten. The Argonauts have given us the miracle of extra days, and when my time is nigh, I’ll thankfully gulp every extra minute.

  But I’ve also come to see a different reason for hope. The gifts given to us from human learning have come through extraordinary cooperation, through hard-earned and lucky experimentation—in labs, yes, but also in homes and statehouses, and in the “two steps forward, one step back” of cultural, political, social, and scientific advance. We won’t skirt inevitable death, not as individuals. However, when we pull back the lens, the Festival of Life can rage on if we find harmony as a species. Maybe, when it comes to it, I will have been able to give my son and daughter tools to carry with them and bring us all a molecule closer to peace.