How Cells’ Complex Choreography Sustains—and Ends

Whenever I walk along the streets of London, I never cease to be amazed by a city where millions of people can work, travel, and socialize so seamlessly. A complex infrastructure, and hundreds of thousands of people, all work in concert to make it possible: the London Underground and buses to move us around the city; the post office and courier services to deliver the mail and goods; the supermarkets that supply us with food; the power companies that generate and distribute electricity; and the sanitation services that keep the city clean and remove the enormous quantities of waste we produce. As we go about our business, it is easy to take for granted this incredible feat of coordination that we call a civilized society.

The cell, our most basic form of life, has a similarly complex choreography. As the cell forms, it builds elaborate structures like the parts of a city. Thousands of synchronized processes are required to keep it functioning. It brings in nutrients and exports waste. Transporter molecules carry cargo from where they are made to distant parts of the cell where they are needed.

Just as cities cannot exist in isolation but must exchange goods, services, and people with surrounding areas, the cells of a tissue need to communicate and cooperate with neighboring cells. Unlike cities, whose growth is not always constrained, the cell needs to know when to grow and divide but also when to stop doing so.

Cities and entire societies, empires, and civilizations grow and die just as cells do.

Throughout history, cities were imagined by their inhabitants to be permanent. We don’t go about our lives thinking that the city we live in will one day cease to exist. Yet cities and entire societies, empires, and civilizations grow and die just as cells do. When we talk about death, we aren’t usually thinking about these other kinds of death; we mean as it occurs to each one of us as individuals. But it turns out to be tricky even to define an individual, let alone what we mean by its birth or death.

At the moment of our death, what exactly is it that dies? At this point, most of the cells in our body are still alive. We can donate entire organs, and they work just fine in someone else if transplanted quickly enough. The trillions of bacteria, which outnumber the human cells in our body, continue to thrive. Sometimes the reverse is also true: suppose we were to lose a limb in an accident. The limb would certainly die, but we don’t think of ourselves as dying as a result.

What we really mean when we say we die is that we stop functioning as a coherent whole. The collection of cells that forms our tissues and organs all communicate with one another to make us the sentient individuals we are. When they no longer work together as a unit, we die.

Death, in the inevitable sense we are considering in this book, is the result of aging. The simplest way to think of aging is that it is the accumulation of chemical damage to our molecules and cells over time. This damage diminishes our physical and mental capacity until we are unable to function coherently as an individual being—and then we die. I am reminded of the quote from Hemingway’s The Sun Also Rises, in which a character is asked how he went bankrupt, and he replies, “Two ways. Gradually, then suddenly.” Gradually, the slow decline of aging; suddenly, death. The process of aging can be thought of as starting gradually with small defects in the complex system that is our body; these lead to medium-sized ones that manifest as the morbidities of old age, leading eventually to the system-wide failure that is death.

Even then, it is hard to define exactly when this happens. Death used to mean when someone’s heart stopped beating, but today cardiac arrest can often be reversed by CPR. The loss of brain function is now taken as a more direct sign of death, but there are hints that even that can sometimes be reversed. Differences in the precise legal definition of death can have very real consequences.

Harvesting organs for donation from two persons in two different US states could be perfectly legal in one and murder in the other, even if they were both considered dead using identical criteria. A girl who was declared brain dead in Oakland, California, was considered alive by the standards of New Jersey, where her family lived. Her family petitioned and eventually had her body transported with its life support equipment to New Jersey, where she died a few years later.

If the precise moment of our death is ill-defined, so too is the moment of our birth. We exist before we emerge from the womb and take our first breath. Many religions consider conception to be the beginning of life, but conception too is a fuzzy term. Rather, there is a window of time after a sperm has made contact with the surface of an egg during which a series of events has to take place before the genetic program of the fertilized egg is set into motion.

After that, there is a multi-day window during which the fertilized egg undergoes a few divisions, and the embryo—now called a blastocyst—has to implant itself in the lining of the womb. Still later, the beginning of a heart develops, and only long after that, with the development of a nervous system and its brain, can the growing fetus sense pain.

The question of when life begins is as much a social and cultural question as it is a scientific one, as can be seen by the continuing debate over abortion. Even in many countries where abortion is legal, including the United States and the United Kingdom, it is a crime to grow embryos for research beyond fourteen days, which corresponds roughly to the time when a groove called the primitive streak appears in the embryo and defines the left and right halves. After this stage, the embryo can no longer split and develop into identical twins. Although we think of birth and death as instantaneous events—in one instant we come into existence and in another we cease to exist—the boundaries of life are blurry. The same is true of larger organizational units. It is hard to pinpoint the exact time when a city came into existence or when it crumbled.

What we really mean when we say we die is that we stop functioning as a coherent whole.

Death can occur at every scale, from molecules to nations, but there are common features of the growth, aging, and demise of these very different entities. In every case, there is a critical moment when the component parts no longer allow the organic whole to function. Molecules in our cells work in a coordinated way to allow the cell to function, but they themselves can suffer chemical damage and eventually break down. If the molecules are involved in vital processes, their cells will themselves begin to age and die.

Moving up the scale hierarchy, the trillions of cells in a human being carry out their specialized duties and communicate with one another to allow an individual to function. Cells in our body die all the time, with no adverse effects. In fact, during the growth of an embryo, many cells are programmed to die at precise points of development—a phenomenon called apoptosis. But when enough essential cells die, whether in the heart or the brain or some equally critical organ, then the individual can no longer function and dies.

We human beings are not so different from our cells. We carry out roles in groups: companies, cities, societies. The departure of one employee will not normally affect the functioning of a large company, and even less that of a city or a country, just as the death of a single tree says nothing at all about the viability of a forest. But if key employees, such as the entire senior management, were to leave suddenly, the health and future of the company would be in doubt.

It is also interesting to see that longevity increases with the size of the entity. Most of the cells in our body have died and been replaced many times before we ourselves die, while companies tend to have much shorter life spans than the cities in which they operate. The principle of safety in numbers has driven the evolution of both life and societies. Life probably began with self-replicating molecules, which then organized in closed compartments that we know as cells. Some of those cells then banded together to form individual animals. Then animals themselves organized into herds—or, in our case, communities, cities, and nations. Each level of organization brought greater safety and a more interdependent world. Today hardly any of us could survive on our own.

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