Song of the Cell by Siddhartha Mukherjee review – the little lives within us
Cells build organisms from the ground up, and therefore to choose to write about them is to give oneself permission to explore almost any aspect of the living world. They are “a life within a life” as Siddhartha Mukherjee puts it in his latest book, which takes advantage of that licence to offer a comprehensive account of basic biology, alongside a history of the many great minds that have helped us to see beyond widespread misconceptions to scientific truth.
This is not just about clear-cut successes: alongside the stories of diligent scientists, there are intriguing tales of the many eccentrics whose contributions were vital to the transformation of medicine. As such, this is a book filled with missteps, arguments and prejudices. It almost made me feel sorry for my scientific colleagues, painstakingly working away in labs, trusting that systematic hard work is all that is required to achieve a big breakthrough.
Among the many colourful characters is the English polymath Robert Hooke. More than 350 years ago, he put a sliver of cork under a microscope and discovered it was made up of “a great many little boxes”. He called them cells, taken from cella, the Latin for “small room”. Hooke did not make the leap to the realisation that animals are made up of similar basic subunits. Perhaps he was distracted by his time spent rebuilding London with Christopher Wren after the great fire, or by his claim that he had described gravity before Newton.
A decade later, the Dutch cloth merchant Antonie van Leeuwenhoek put a drop of rainwater under a homemade microscope and saw tiny organisms that he called animalcules. Neither educated nor a gentleman, Leeuwenhoek struggled to be believed. He didn’t help himself by refusing to allow his equipment to be examined, instead relying on the very unscientific method of asking a ragtag collection of amateur citizens to testify that they had also seen what he had.
In the 1830s, German scientist Robert Remak, gazing at chicken blood under a microscope, saw a cell split in two. He had discovered that new cells were created by the division of preexisting ones, but was largely ignored and was not permitted professorship because he was Jewish.
Mukherjee uses sometimes salutary and always engaging stories such as these to teach the fundamentals of cell biology, but also to illustrate that no one individual is ever responsible for any advancement in science. Rather, progress is made in a series of often unwitting collaborations. A story told by a milkmaid about her clear skin might be the reason we have vaccines: the protection offered by cowpox infection against smallpox led Edward Jenner to perform the first inoculation on his guileless gardener’s son.
If you are not already in awe of biology, The Song of the Cell might get you there. It is a masterclass in how cells function and malfunction. Consider a virus replicating inside a cell, invisible to the body’s immune system and therefore able to multiply unchecked. How is it possible that the body’s defences, living as they do entirely outside the cell, can detect the alien presence within? The explanation comes in the form of a specialised molecule called MHC class 1. It is perfectly shaped to pick up fragments of internal cell protein so that it can draw them to the surface. There it presents its payload to the body’s surveillance system. As Mukherjee puts it, it is as though the immune system is being offered an amuse-bouche of the cell’s insides. Thus a foreign body is detected and the infected cell is destroyed. This system was not fully understood until the late 1980s, and I found it chilling to be reminded how many advances vital to modern medicine took place in my lifetime. The MHC class 1 pathway is targeted by Sars-CoV-2, which goes some way to explain why Covid has been so deadly.
Of course, none of this is anything compared with the elegant march that turns a single fertilised cell into a fully formed, brand new human being. It was once believed that we all appeared in the womb as miniaturised versions of ourselves and all we had to do was grow. Aristotle broke away from that idea and suggested we were sculpted from menstrual blood. The truth is more marvellous. One cell divides and the division continues until there are billions. And, although each of those new cells started out apparently so similar, they all have their own destiny. How do they know where to go and what to become? In Mukherjee’s words, it is “a virtuoso act, an elaborate, multipart symphony perfected by millions of years of evolution”.
The complexity is such that it’s almost surprising that everything works so well and that so few mistakes are made. But of course things
do go wrong. Cancer cells defy the processes that are supposed to keep them in check. Like viruses, they find ways to evade our defences so that they can multiply out of control. Mukherjee uses seminal medical cases and others from his personal and working life to illustrate how we have learned to harness the natural talents of the immune system to fight rogue cells. In 1975, scientists came up with a method of fusing an antibody-producing plasma cell with a cancer cell. The immortality of a cancer cell was thus gifted to the plasma cell, allowing the potentially limitless production of antibodies. In the 1990s, WH, a doctor slowly dying from lymphoma, was one of the first to benefit. Infused with cancer-fighting monoclonal antibodies, her tumour melted away and she survived.
Cell systems are intricate and this book imparts a lot of information. Catering for every level of reader, Mukherjee sometimes uses visual metaphor to simplify matters. He asks the reader to imagine they are an astronaut investigating the cell as if it is an unknown spacecraft. At times, these images were too simplistic for my taste. But that is a small criticism, because his overall achievement is to have created a guide with personality that can be understood whether or not you have prior knowledge of the subject. There is also plenty of entertainment to be had in following the careers of Nobel prize winners and those physicians who were almost right, but not quite. Science is logical and systematic but that is not always the case for scientific discovery.
Mukherjee talks of “the body as a cellular citizenship”, in which every cell somehow knows its place (even outside the heart a cardiac cell knows to keep pulsing). They are fired-up little engines, both self-contained and communicating with the larger machine. “Should all the billions of gently burning little fires cease to burn,” the physical chemist Eugene Rabinowitch wrote, “no heart could beat, no plant could grow upward defying gravity, no amoeba could swim, no sensation could speed along a nerve, no thought could flash in the human brain.” In so far as it is possible, Mukherjee has captured the wonder of that in one book.
• Suzanne O’Sullivan is the author of The Sleeping Beauties: And Other Stories of Mystery Illness. Song of the Cell: An Exploration of Medicine
and the New Human by Siddhartha Mukherjee is published by The Bodley Head (£25). To support the Guardian and the Observer buy a copy at guardianbookshop.com. Delivery charges may apply.
It is as though the immune system is being offered an amuse-bouche of the cells’ insides