1. Meet the Measles Is there anything more consequential than a child''s breath? In some ways, it is the most routine thing in the world. Tens of thousands in a day--over and over and over--but some breaths are more consequential than others. First breaths can be particularly fraught. My daughter was born when I was a pediatric resident, at the same hospital where I worked. Most mornings, I entered the building in an emotional state that lived somewhere on the spectrum between interest in what I might learn and dread at the mammoth list of tasks that I would have to complete before I could leave again. When my wife Shari and I walked in together, headed for the labor floor, I had a different kind of anticipation-a combination of excitement at the upcoming new chapter of our lives and abject terror at everything that could go wrong. I attended many deliveries as a resident, most of which were joyous, some of which were both tragic and, especially at that moment, easy to remember.

Despite efforts both conscious and unconscious, you retain what you see as a physician, and as is true with a duckling imprinting on its parent, sometimes what you encounter earliest in training has greater clarity, more staying power. Uterine ruptures, stillbirths, amniotic fluid embolisms-I had seen enough go wrong in delivery rooms that I was more frightened than was reasonable or logical. Samantha was born with her umbilical cord looped once around her neck-just once, not tightly, not a dangerous situation. She was blue when she first emerged, and I remember waiting for her first breath, repeating quietly the phrase I used when I was the one bringing a newborn patient to the warmer for assessment-equal parts greeting and prayer, "good baby, good baby, good baby." Sam''s breath came soon, and with it a pinking of her skin, a fidgeting of her limbs, and the beginning of a life. As any parent who has watched over a child knows, breaths can be filled with meaning. Our bodies take breathing pretty seriously, but the mechanics of the system are surprisingly straightforward. The oblong muscle of the diaphragm-a crosswise border at the bottom of the rib cage-contracts and descends, increasing the space available to the organs of the thorax (the heart, the lungs).

More space in the lungs means a drop in pressure, which causes air to flow in through a system of tubes-starting at the nose and the mouth, branching repeatedly along the way, and ending deep within the lungs. The inner portion of those tubes-where the liquid would be if they were straws-is the lumen, a path containing the air that we have just inhaled. Prior to the breath, that air had been most definitively outside of us, but now it inhabits a liminal space, both outside and in. The diaphragm relaxes back up, and the pressure difference is reversed-the air leaving our lungs, back out the way it came. Over and over, every single day. Our bodies have to maintain this cycle if we are to survive. Our airways, branch by branch by branch, represent a deep and ever-present connection between our human selves and that which surrounds us but is separate from us. This arrangement, with branching tubes inside of us containing the air that we inspire, implies that there are locations where inside and outside meet.

There must be a luminal border, a place where the last point made of human cells abuts the first point of the outside world. That border prevents some things from crossing into the tissues beneath-the protected, sterile parts of our lungs-and allows other things through. We don''t move air in and out all day every day for no reason. In the lungs, oxygen crosses the border into our blood, destined to be bound by the hemoglobin packed in our red blood cells and delivered throughout the body; carbon dioxide travels the opposite path, across the border and back into the airways, ready to be exhaled. It is a system set up for constant, regulated exchange. We have cells maintaining that important boundary between inside and outside. The epithelial cells that form the border crowd together tightly, making it difficult for anything that is not supposed to get through to do so. And other cells act as defenders of that barrier as well.

Macrophages reside in the air spaces, where they ingest and destroy debris or microbes, or alternatively process what they have found and present it to other immune cells, which gather in nearby lymph nodes. Dendritic cells live in the tissues below the border, but they extend tiny projections into the lumen-fingers in a grab bag-sampling its contents, evaluating potential threats. It''s a pretty impressive defense system, multilayered with built-in redundancy. Much of the non-air matter that we inhale is filtered out high up in the airways-trapped by mucus, ejected by the never-ending beating of whiplike cilia projecting from cells, pushing things up and out. What makes it into the lower airways is evaluated by these sentries-the macrophages, the dendritic cells-which can deal with threats or call in additional immune cells to help. It is striking, then, how effectively measles virus subverts this system. Like a first one, other breaths can be important events in the life of a child, even if their significance is easy to miss at the time. The first contact between a child and the measles virus isn''t usually dramatic or even noticeable.

Measles virions (viral particles), suspended in airborne droplets of saliva, mucus, and cells, enter silently, riding a breath. Some of those droplets follow the path of the tubes deep into the lungs, where they encounter the epithelial barrier and its protectors. There, the measles virus commits its first act of deception against its human host, but certainly not its last. The outer surface of a virion is speckled with proteins and sugars that can fit snugly into receptors on a host cell-a key sliding into a lock. Once that connection is made, the cell itself may pull the virus inside, unaware of the coming havoc. These receptors often play a role in normal cellular functions like acquiring nutrients or gathering information about the cells'' surroundings. Diabolically, viruses repurpose the machinery of ordinary business to enter the inner part of the cell, an essential first step toward turning that cell into a mass producer of new virions. H protein, located on the surface of a measles virion, binds specifically to a human protein called SLAM.

This interaction triggers a subtle rearrangement of other viral proteins, allowing the virion''s membrane to fuse seamlessly with that of the human cell. In a moment, virus and host become one. Microscopic interactions like this one mean everything for a virus and determine how it manifests in our macroscopic world. That lock-and-key requirement for specific receptors can determine viral host restriction (Does a particular virus infect animal, plant, or bacterial cells? What kind of animal? A primate? All primates or just humans?) and cell tropism (All human cells or just human lung cells?). Viruses can have strict host restriction, meaning that they infect only a single species or a small set of closely related species, or they can be more promiscuous. Influenza wouldn''t be the ever-changing worldwide threat that it is without its ability to infect multiple species-its receptor binding more foot in sock than key in lock. The life cycle of the influenza virus, which includes generation of genetic diversity during infection of birds and pigs, coupled with a prodigious ability to infect humans by targeting cells in both the nose and the lungs, make it a perennial and at times existential threat. Like influenza, the SARS-CoV-2 virus that causes COVID-19 can infect multiple host species.

It most likely first emerged in bats but was able to jump (or "spill over") to humans because our cells happen to have a protein similar to the receptor that the virus uses to get into bat cells. This factor is absolutely crucial. We have endured a multiyear global pandemic on the basis of these particular proteins fitting together. And it''s not just the fit-the location of receptors matters. Because that human receptor to which SARS-CoV-2 binds happens to be expressed in our airways, the virus can enter and cause damage there, allowing it to spread through our coughs and to infect a new host when they inhale. Likewise, human immunodeficiency virus (HIV), with a host range restricted to humans, targets specific cells of the immune system with the surface receptors that it needs for entry. The resulting immunodeficiency that accounts for HIV''s lethality is a by-product of its propensity to use receptors on immune cells. The disease is in the details.

Under normal conditions, SLAM-the measles virus receptor-helps immune system cells interact and exchange information. Macrophages and dendritic cells have lots of SLAM on their surface, but the epithelial border cells do not, so measles virions infect the airway sentries, a counterintuitive yet ultimately brilliant plan. Membranes fuse, and the infected cells ferry the virus past the border and into the nearby lymph nodes, where many more SLAM-expressing immune cells live-a feast for those viruses that just Trojan-horsed their way in. In the coming days, newly infected cells will emerge from the lymph nodes, allowing the virus access to the bloodstream-a flurry of invisible activity. From the outside, though, not even a sniffle. About ten days later, the prodromal phase, with its mild symptoms-a runny nose, a cough, fever, a little redness in the eyes-begins, worsening over the subsequent few days. These symptoms could easily be ascribed to any one of a million other things-a seasonal cold, the flu, even allergies if the fever isn''t too prominent. The child might still be well enough to be in school.

One.