Who do I think I am, titling a chapter “The Meanings of Life”?
This is not a typo, either. I emphasize meanings, plural.
I’m not so audacious as to think I can distill it all into a single meaning of life.
But I can say with a straight face that I have a decent idea of several of life’s essential attributes, as seen through the lens of the immune system. This network is so central to our being, our survival, that its inner workings offer elegant lessons for living better, even living longer.
Each of these lessons comes from understanding what makes the immune system so effective. It is eons old, honed and polished by evolution, and so, by definition, very good at what it does.
First, everything is connected. Cancer, autoimmunity, HIV, the common cold, allergy. The immune system, our elegant defense, is the river that runs through every aspect of health and wellness. It tends to the festival of our lives, and it does so by seeking balance and harmony.
It seeks peace with its surrounding environment. This is a far different idea from the one I began with when I started to learn about the immune system and assumed—as I suspect many people do—that its chief jobs are to defend and attack. Defend, yes; attack, not necessarily. In fact, the immune system is constantly seeking to maintain harmony, not just by limiting its attacks to all but the most necessary ones, but also by cooperating with the organisms that surround and invade it. At its core, it tries to discern self from other, but having done so, it doesn’t just destroy what is alien.
It has made allies of the bacteria that thrive within it, and the bacteria have made an ally of the host. In fact, if our immune system had gone to war with each organism it deemed as different, the species would not have survived. For us to have a fully effective immune system, we need regular engagement with bacteria in our environment and in our gut.
This realization adds a profound level of nuance to the idea of what self is, and what other is. What is alien, what is foe, what is ally, what is partner?
This teaches us clearly that our survival, as individuals and a species, is best served by cooperation. This may sound obvious, but civilization, even of late, has been dominated by the push and pull of our competing instincts to cooperate and alienate, to see what people share in common or prey on what divides them. The lesson of the immune system is that the better able we are to find common ground, the more allies and weapons we have to contend with a greater, common foe.
This is a powerful argument too for diversity. The more diverse our genetic tool kit, the more options and ideas we have to enable our common survival. Bob Hoff was the ultimate outcast, a gay man in Des Moines. He is not someone to be castigated as different, though, but to be embraced as a genetic and cultural ally, a brother, an essential part of our common survival.
The scientists from other countries created the foundation of learning that became the medicines that forestalled Jason’s death, helped Linda, and that may yet come from Bob’s contributions. If we learn together and cooperate, we can tackle autoimmunity and cancer and Alzheimer’s, and who knows what other seemingly impossible foes.
Conflict has its inevitable place. Societies and people will collide, just as at times our immune system must play a vigorous defense. But the immune system cautions us to take the least destructive path possible to a livable balance. When we don’t cooperate, when we err too easily on the side of war—literal and proverbial, physical and verbal, armed and political—we emulate one of the most self-destructive of our traits: an overheated defense system. In fact, among the biggest misconceptions that I took into this book was that it is better to have a superpowered immune system. The advertisements are everywhere urging “Boost your immunity!”
Wrong.
Dr. Fauci, one of the leading scientific lights in the world, said that when he hears ads promising to boost your immune system, “it almost makes me chuckle. First of all, it is assuming your immune system needs boosting, which it very likely doesn’t. If you do successfully boost your immune system, you might boost it to do something bad. Even with the very dramatic positive results we’re getting from immune therapy with cancers, we’re looking at clinical trials with very, very toxic side effects. It doesn’t just suppress the cancer but puts in a bunch of things that put system out of whack.”
Some of the most devastating chronic deadly conditions in the festival that is our life arise when this system goes even a touch out of control. Fatigue, fever, stomach issues, rashes, organ failure, flooding of the lungs, and on and on. These effects are so devastating that it is difficult at some points to know the difference in the effects between pathogen and inflammation. Sometimes these effects are actual autoimmune disorders. Other times, they are episodes of overheating, the fatigue and acne and sores and leaky-gut-prompted stomach issues that kick in when our elegant defense turns into a police state.
The immune system teaches us to err on the side of cooperation and acceptance.
It is true too on the other side of the equation. If you suppress your immune system deliberately, through medication, it can mean trouble. Dr. Fauci has never treated Merredith Branscombe—the woman whose autoimmunity remains elusive—but I talked about her situation with him and he was sympathetic to her quandary. The mechanisms behind autoimmunity, for as much as we’ve learned, remain murky, even as the monoclonal antibody treatments have become more precise.
“Generally, you have to give broadly nonspecific suppressors of the immune system,” Dr. Fauci said. “It comes with absolutely inevitable toxicities.”
There’s a significant lesson here for society. In our quest to build a perfect and efficient world, we have overcorrected.
As I noted earlier, it’s hard to name a single profound innovation that hasn’t had extraordinary side effects. When cars hit the scene, we had much greater freedom of movement and incredible new efficiencies, and also crash-related deaths soared; driving is now the single most dangerous thing most people will do today.
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 cells 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.”