Self & Other

Epilogue

What Your Body Is Doing While You Read This

Let me put you back on the bicycle.

You are seven. The sidewalk has, very rudely, left a tiny crack. The front wheel jerks. You go down. Your knee meets the concrete. There is a moment of confusion, then pain, then the bead of blood. The ninety seconds we promised at the beginning of this book begin now.

Watch them again.

The skin at the edge of the wound has, in the first second after the impact, already begun to spill chemicals into the surrounding tissue. They are not generic chemicals. They are signals, with specific shapes and specific meanings, recognized by specific receptors on specific cells. The local capillaries widen, which is why the area starts to feel warm. Plasma leaks out into the tissue, carrying complement proteins among many others. Some of those complement proteins are already binding to the surfaces of the bacteria that the sidewalk introduced — latching on, calling for backup, in some cases drilling holes directly through the bacterial walls.

Macrophages, who lived in this small piece of tissue before any of this happened, who have been there your whole life patrolling and sampling and eating any debris they could find, are now responding to the cytokines the damaged skin cells are pouring into their environment. They wake up. They begin to work. They release cytokines of their own, signaling outward to anyone who will listen.

In the bloodstream a few millimeters away, neutrophils receive the message. They begin to stick to the walls of the local blood vessels, then squeeze through the gaps between vessel cells, then crawl into the tissue. Within minutes there will be hundreds of millions of them, then a billion. Most will die there. They will pour bleach onto the bacteria that crossed the sidewalk into your bloodstream. They will sometimes explode outward, casting nets of their own DNA to trap the things they could not catch any other way. By tomorrow, the yellowish liquid that may have collected at the surface of the cut will be mostly the bodies of these cells — the kindergarten class that ran toward the fire and did not come back.

A dendritic cell, somewhere in the tissue, has eaten a fragment of bacterium. It is now climbing, slowly, through the lymphatic vessels toward the nearest lymph node. In its hands, metaphorically, are pieces of evidence — small bacterial proteins it has chopped up and shoved into its MHC molecules and is carrying like flashcards. When it arrives at the lymph node, it will begin walking along rows of T cells and B cells, holding up its evidence, asking the question that started this book: does anyone here recognize this?

Most will not. Some will. The ones who do — maybe one in a hundred thousand, maybe rarer — will, in the next few hours, begin the slow careful process we spent Chapter 3 describing. They will divide. The first daughter cells will divide again. Within a few days, your body will contain millions of cells specifically tuned to recognize whatever the dendritic cell brought to them. Some of those cells will become factories, pouring antibodies into your bloodstream. Some will become killers, looking for any of your own cells that the bacteria have managed to infect. Some will, eventually, become memory cells, settling into your bone marrow or your lymph nodes and waiting, perhaps for the rest of your life, in case the same bacteria ever come back.

This is happening right now in the kid’s knee. None of it is being directed by a brain. None of it is being asked for. The kid is, mostly, just looking around for whoever is going to come help.

What Continues

In the days after, while the kid forgets all of this and goes on with their life, the work continues.

The macrophages will not stop. After the neutrophils have largely died and been cleaned up, the macrophages will keep eating. Now, mostly, they will be eating dead neutrophils — cleaning up the casualties of the fight, breaking them down to their components, recycling what can be recycled. Other macrophages will switch from their attack mode to a healing mode, releasing different signals: inflammation can stop now, blood vessels can come back to baseline, new tissue can be built where old tissue was lost. The active resolution we discussed in Chapter 8 begins.

The skin at the edge of the wound will begin to grow inward. Cells that were content yesterday to be skin cells will, today, divide and reach across the gap to find the skin on the other side. A scab will form on top of all of this, made of clotted blood and other proteins, protecting the work happening underneath. Within a week or two, the wound will be mostly closed. Within a month, the scar will have begun to fade.

In the bone marrow and lymph nodes, the memory cells will quietly take up their posts. They may sit there for the rest of the kid’s life. The kid will, on most days, never know they are there. If a similar bacterium ever crosses into their bloodstream again — from another fall on another sidewalk forty years from now — the memory cells will recognize it within hours, not days. The fight, the next time, will be over before it ever felt like a fight.

This is what an immune system, working as designed, does. The cost — to the kid — was a sock that needed washing, a few minutes of crying, and a scab to pick at over the next two weeks. The benefit was a small, irreversible upgrade to a defense system that was already, by the time of the fall, the result of a hundred million years of evolution and seven years of personal calibration.

The Other Bodies

The kid in this story is, statistically, going to be fine. The system will work. The fall will be one of thousands of small immune events the kid’s body handles over the course of a life, and almost none of them will be remembered.

But this book has not only been about the kid in this story.

In another body, somewhere, the same fall is happening to a child whose immune system was, from birth, missing some specific component. Their neutrophils don’t move quite right, or their B cells don’t activate properly, or their thymus never developed. The same fall, in their body, is more dangerous. They are also reading this book, or being read it. They deserve to be in this story too.

In another body, somewhere, the same kind of immune cells we just watched do their work are, at this moment, attacking some part of the body that does not deserve attacking. A pancreas. A joint. A stretch of myelin. The system is doing what it was designed to do, but at the wrong target, and the consequences will be a chronic disease that the person will live with for decades. They are also reading this book.

In another body, somewhere, a tumor that the immune system has been quietly catching for years has finally figured out how to escape. The cells we have been watching — the macrophages, the killer T cells, the dendritic cells — are no longer winning. The person whose body this is in will, in the next year, sit in a small room while a doctor explains what is happening. They are also reading this book.

The book has been for all of them. The book has tried, throughout, to honor that the same system runs in all of these bodies. The bacterium on the kid’s sidewalk and the autoimmune attack on someone’s pancreas and the tumor escaping someone’s surveillance — these are not different systems. They are the same system, calibrated differently, running into different challenges, sometimes succeeding and sometimes failing. The cells are the same cells. The chemistry is the same chemistry. The difference is in the dice.

The kid on the bicycle does not need to know any of this to be fine. The people in the other bodies, often, do need to know it, because knowing it is part of how they make sense of what their body is doing and what it is not. This book has been for them most of all.

Maya, One More Time

Somewhere in the same town, on the same Saturday, the teenager from Chapter 10 is also outside.

Maya is now seventeen. Her diagnosis was a year ago. She is at a swim practice. Her continuous glucose monitor is tucked under the strap of her swimsuit; her pump is in a small waterproof case, attached to a different strap. Her moms know where she is. The team coach knows what to look for. Maya, by now, knows her own body well enough that she rarely gets surprised.

While she swims, every cell in her body is, of course, doing the same things every cell in everyone else’s body is doing. The macrophages are patrolling. The dendritic cells are sampling. The B cells and T cells are waiting, in their lymph nodes, for whatever they will be needed for next. The MHC molecules on every one of her cells are holding up their flashcards.

In her pancreas, almost all of her insulin-producing cells are gone. The autoimmune attack of Chapter 10 is essentially complete. Her body has been getting the insulin it needs, instead, from a small clear plastic line that ends in a needle in her abdomen and a pump on her hip and an algorithm running on a phone in her gym bag. The system is, with care, working.

Most of her body is doing exactly what most of everyone’s body is doing. One small piece of her body, in one specific way, is not. That is what living with an autoimmune disease, for many people, is. It is not the whole story. It is one chapter of a longer book that, like the rest of the bodies in this epilogue, mostly takes care of itself.

Maya finishes the swim and gets out of the pool. The chlorine stings her eyes, the way it stings everybody’s eyes, for reasons that have nothing to do with diabetes. She is hungry. She enters the carbohydrates from the snack she is about to eat into her pump. The pump delivers a precise dose of insulin. She eats the snack. She is going to be fine.

This is the book.

Most of immunology, like most of biology, like most of medicine, is the slow, careful work of figuring out what is actually going on inside bodies. The work has produced, in the last hundred and fifty years, an understanding deeper than anything humans have ever had about themselves. The understanding is incomplete. It is also, at this point, vast. The vaccines that have prevented millions of deaths, the treatments that have transformed autoimmune disease in the last twenty years, the cancer immunotherapies that have rewritten the prognosis of certain diseases, the genetic and cellular therapies that have saved children who, fifty years ago, would not have lived a year — these all came out of the same work. They all came out of researchers doing what researchers have always done: noticing something strange, asking what it means, refusing to let go until the answer is clearer than it was.

The hope of this book is that you, the reader, now have a working picture of the system that has been keeping you alive your whole life. Not the supplement-aisle picture, which has nothing to do with how the system works. The actual picture: the cells, the molecules, the slow careful negotiation between self and other, the layered defenses, the inevitable mistakes, the long arc of medicine learning to help when the mistakes happen.

If you are well, this picture is a way of being grateful for what is happening inside you. You did not earn it. You did not build it. It is, in a real sense, an inheritance.

If you are unwell, or someone you love is, this picture is something different. It is a way of understanding that the disease is not a moral event. It is a particular calibration of an enormous system that has, in your case, run into trouble that medicine is increasingly able to help with. The disease is not your fault. The disease is not a failure of effort. The system that produced it is also, to a startling degree, the same system that we are getting better at fixing.

The kid on the bicycle is back on the bicycle. The scab on their knee is, by now, almost gone. The memory cells in their lymph nodes will outlive most of the things this book has discussed. The kid does not know any of this. The kid does not need to.

But you do, now. And the next time you watch a kid fall off a bicycle, or read a news article about a new biologic, or sit with someone you love through a diagnosis, what is happening will look different to you.

Not less amazing. More.

— The End —

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