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5 December 2022

What cells tell us about life

Siddharta Mukherjee’s new study of how cells work reveals the complexities of the human body – and the science that could improve it.

By Henry Marsh

Ever since I was a medical student 50 years ago, I have understood that I am 37.2 trillion cells, with an even larger number of bacterial cells in my intestine, upon which I depend. It is an extraordinary thought, and it is difficult to find the language to describe this unimaginably large collection of profoundly cooperative minute biochemical factories that somehow combine to make me feel like a coherent individual. And, even more remarkably, all the cells are the progeny of a single cell, with each cell containing all the DNA instructions for assembling the entire organism.

In his latest book, The Song of the Cell, Siddhartha Mukherjee uses a variety of words and phrases – ecologies, sociologies, cellular citizenship – in trying to convey the staggering complexity of the way in which our cells work and relate to each other. Mukherjee is a practising oncologist as well as a gifted writer – his first book, about cancer, The Emperor of All Maladies, won a Pulitzer Prize. Cancer provides a backdrop to this new book: in Mukherjee’s words, cancer, along with the so-called autoimmune diseases, represents a “violation of the social compacts between cells”.

The story starts in the distant past when single cells started to combine together to form colonies and then increasingly complex organisms with specialised cells. It is apparent from the evolutionary record, Mukherjee tells us, that this happened many times in many different organisms. There are clearly major advantages to being multicellular, and laboratory experiments with single-cell yeasts that clump together to form “snowflakes” have confirmed this, although we can only speculate as to what these advantages might be.

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The word “cell” was first used by the polymath Robert Hooke in 1665 to describe the microscopic structure of cork viewed down his compound microscope. This was simply a description of what he saw and there was no suggestion that these “cells” (named after monks’ cells in monasteries) might be the basic units of life. At the same time in Holland, the pioneering microscopist Antonie van Leeuwenhoek was reporting on seeing “animalcules”, microscopic living creatures never seen before. But there was little understanding for the next 200 years as to the significance of their observations. From then on, however, there has been unstoppable progress, leading to the manipulation of cells and organisms by gene editing in the past decade.

Mukherjee, however, strives to point out just how little we still comprehend. It is thought, for instance, that human cells contain up to 10,000 different proteins, each with specialised functions, many of them involved in networking with other cells. Only a few hundred of these are properly understood.

The book begins with a meeting in 1837 between two German scientists: Theodor Schwann, a zoologist who was examining tadpoles, and Matthias Schleiden, a botanist who was investigating plants. They realised that animals and plants had something in common – they were both formed of cells. There was a fundamental unity underlying all living things.

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After an account of the basic mechanics of how cells divide and replicate, and of their metabolism, Mukherjee devotes a chapter to each of the major cellular systems and organs – such as the blood, the heart, the pancreas, the immune system and the brain – and describes some of the historic research that led to our current understanding of how they work.

The narrative is enlivened by pen portraits of the scientists involved – somewhat de rigueur in a book like this, but Mukherjee has a happy turn of phrase. One of his teachers was “a balding octogenarian in polished wing tips with a patrician air” and the Nobel Prize-winning geneticist Sydney Brenner had “fabulously bushy eyebrows, like caterpillars, lifting and waving with joy every time we told him of a new experimental result”.

Mukherjee also includes moving vignettes about some of his oncological patients, and describes his own deep joy at looking at blood cells – he specialises in haematological oncology – down a microscope. He moves seamlessly, to great effect, between the personal and the scientific.

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The book has a grand subtitle: “An Exploration of Medicine and the New Human”. Our ever-increasing understanding of cellular physiology and genetics means, says Mukherjee, that we will soon be re-engineering ourselves. Plans for an artificial pancreas and an implantable liver are already well under way. He discusses how the American philosopher Michael Sandel has argued against human enhancement on the grounds that it will damage human morality. Our ethical world-view, Sandel believes, is partly based on accepting that what we are born with is a gift, which we must make the most of, rather than something that can be altered with technology (a process that would disproportionately benefit the wealthy).

Mukherjee used to agree with Sandel, but now he thinks that the distinction between emancipation from disease and augmentation of the healthy is so blurred that “augmentation has become the new emancipation”. I am not sure if I agree – legal distinctions could surely be made between correcting diseases and pure augmentation, although I don’t dispute it would be difficult. There are rigorous attempts to ban doping in sport, for instance. But Mukherjee is right to point out in the next few paragraphs how genetic engineering will probably soon cure the tremendous suffering caused by diseases such as sickle cell anaemia. “We’ve thrown open the black box of the cell,” he tells us. “To snap the lid shut now might be to foreclose the possibility of a magnificent future.”

The title, The Song of the Cell, is explained by reference to the story of a professor of botany being guided through a rainforest by a local young man, who knows the names of all the plants but is saddened that he “has yet to learn their songs”. Mukherjee says we are still stuck with a similar, atomistic view of cells. He believes that the word “holism” has become “defiled” in the reductionist laboratories of modern science. We need, he tells us, to hold two ideas in our head at the same time: that cells and genes are both individuals and parts of a whole. He suggests that experience with non-Western philosophies might help here.

Be that as it may, the book is a remarkable achievement – a fascinating and highly readable crash course on the complexities of cellular physiology and of life itself. I wish it had been available 50 years ago when I was struggling through the dull, dry lectures of my pre-clinical studies at medical school.

Henry Marsh is an author and former neurosurgeon. His most recent book is “And Finally: Matters of Life and Death” (Jonathan Cape)

The Song of the Cell
Siddhartha Mukherjee
Bodley Head, 496pp, £25

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This article appears in the 30 Nov 2022 issue of the New Statesman, World Prince