Nobel laureate Venkatraman Ramakrishnan examines ageing and death from a chemist’s perspective

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 socialise 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 civilised 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 synchronised 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 neighbouring 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.

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 civilisations 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 form 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 ageing. The simplest way to think of ageing 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 ageing; suddenly, death. The process of ageing 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.

Death can occur at every scale, from molecules to nations, but there are common features of the growth, ageing, 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 specialised 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 organised in closed compartments that we know as cells. Some of those cells then banded together to form individual animals. Then animals themselves organised into herds – or, in our case, communities, cities, and nations. Each level of organisation brought greater safety and a more interdependent world. Today, hardly any of us could survive on our own.

‘The Immortal Gene and the Disposable Body’ by Venkatraman Ramakrishnan in A Touch of Genius: The Wisdom of India’s Nobel Laureates, edited by Rudrangshu Mukherjee, Aleph Book Company.