This book is the story of the cell. It is a chronicle of the discovery that all organisms, including humans, are made of these “elementary particles.” It’s a story of how cooperative, organized accumulations of these autonomous living units – tissues, organs, and organ systems – enable profound forms of physiology: immunity, reproduction, sentience, cognition, repair, and rejuvenation. Conversely, it is the story of what happens when cells become dysfunctional, tipping our bodies from cellular physiology into cellular pathology-the malfunctioning of cells precipitating the malfunction of the body. And finally, it is a story about how our deepening understanding of cellular physiology and pathology has sparked a revolution in biology and medicine, leading to the birth of transformational medicines, and of human beings transformed by these medicines.
I confess, I’m a biology nerd. One off my most crammed-full bookshelves holds books on medicine, from a 1992 Merck Manual to everything Oliver Sacks, Berton Roueché, and Harold Klawans wrote to all the how-I-became-a-doctor books to terminal-illness memoirs to forensic pathologist tell-alls. Of the 40-odd science moocs I’ve taken, more than 30 were bio: biochem, anatomy, physiology, molecular biology, immunology, etc. etc. So this book was a dream come true: a review of nearly all of it, from the first microscopists discovering cells to the components of blood to how muscles contract to IVF and COVID and genetic engineering.
As with many general readership books about science – in the vein of Ed Yong’s An Immense World, which I read earlier this year – the book combines science information with stories about their discovery.
Mukherjee takes us briefly through the founding years of the discipline. How did these scientists figure out how cells work? The cell membrane was a puzzle: the cell has to communicate with the rest of the organism, but how? Thus were discovered pumps and channels and receptors: “Porosity, in short, represents an essential feature of life – but also an essential vulnerability of living.” Where did cells come from? One of the earliest tenets declared, “all cells come from cells,” and that led to embryology.
Mostly, scientists cooperated. Matthais Schleiden and Theodor Schwann added to François-Vincent Raspail’s tenets of cell theory (“each cell selects from its surrounding milieu, taking only what it needs”) and founded the field of cell biology. Rudolf Virchow added what is a central point of the book: all pathology is cellular pathology. But that isn’t to say there were conflicts, as in the story of the anatomy professor murdered in 1642, possibly over a credit-sharing dispute regarding the recently discovered pancreatic duct: “I cannot think of another murder incited by a duct,” writes Mukherjee.
One of the sections I found most interesting was on homeostasis, the body’s drive to keep things stable, predominantly via the kidneys, liver, pancreas, and brain. Mukherjee takes us through what happens when we have lunch, thus disturbing our balance of water, salt, and sugar:
The concept of homeostasis (the word is derived from the Greek words homeo and stasis, loosely meaning “related to stillness”) was first described by the French physiologist Claude Bernard in the 1870s and further developed by the Harvard University physiologist Walter Cannon in the 1930s.
For generations before Bernard and Cannon, physiologists had described animals as assemblages of machines, sums of dynamic parts. Muscles were motors; the lungs a pair of bellows, the heart a pump. Pulsing, swiveling, pumping; physiology’s emphasis was on movement, on actions, on work. Don’t just stand there, do something.
Bernard inverted that logic. “La fixité du milieu intérieur est la condition de la vie libre, indépendante“: the constancy of the interior environment is the condition of free and independent life, Bernard wrote in 1878. In shifting physiology’s focus from action to the maintenance of fixity, Bernard changed our conception of how an organism’s body works. A major point of physiological “activity,” paradoxically, was to enable stasis. Don’t just do something, stand there.
While the clear explanation is from his ability as a scientist and teacher, that reversal is the mark of a storyteller.
Our immune system is also explored in some depth. The book was partly written during the early part of the COVID epidemic, so it features prominently, but so does HIV and cancer, Mukherjee’s primary field of research. Some of his passages are highly emotional: his despair over the frequent failures of the first bone marrow transplants, his narratives of beloved colleagues he’s lost along the way.
He doesn’t veer away from the mistakes science has made along the way: a researcher who overstepped and used genetic modifications inappropriately (and went to jail for it), attitudes that are slowly being revised:
The paper by Edwards, Steptoe, and Bavister, “Early Stages of Fertilization in Vitro of Human Oocytes Matured in Vitro,” was published in the journal Nature in 1969. Unfortunately, Jean Purdy, who had performed the experiment, was not credited, consistent with the conventional practice of cutting women out of science. Later, both Edwards and Steptoe made several attempts to acknowledge her contributions, for IVF was born in Purdy’s hands. In the lab, she created the first human embryo produced through IVF; in the hospital, she would later cradle the first IVF baby. In 1985, she died of melanoma at just thirty-nine years of age, never able to fully garner the scientific recognition due to her.
The title of the book comes from two directions. In an interview at the Jaipur Literature Festival, Mukherjee uses the metaphor of an orchestra: just as two orchestras can play very different music though they have the same instruments played by the same musicians, so cells can serve different functions and have different structures though they have the same genome. It’s all a matter of the score and director, which in cellular terms, translates to the complex topic of gene regulation: biochemical signals that encourage production of one protein while discouraging another.
But it’s in the book itself that he reveals his key metaphor:
In his 2021 book on ecology and climate, The Nutmeg’s Curse: Parables for a Planet in Crisis, Amitav Ghosh recounts the story of an eminent professor of botany who accompanies a young man from a local village to guide him through a rain forest. The young man is able to identify each of the various plant species. His acumen stuns the professor, who compliments him on his knowledge. But the man is dejected. He “nods and replies with downcast eyes. ‘Yes, I’ve learned the names of all the bushes, but I’ve yet to learn the songs.'”
Many readers might read the word song as metaphorical. But in my reading, it’s far from a metaphor. What the young man laments is that he hasn’t learned the interconnectedness of the individual inhabitants of the rain forest – their ecology interdependence – how the forest acts and lives as a whole. A “song” can be both an internal message – a hum – and, equally, an external one: a message sent out from one being to another to signal interconnectedness and cooperativity (songs are often sung together, or to one another). We can name cells, and even systems of cells, but we are yet to learn the songs of cell biology.
This is Mukherjee’s fourth book. I overlooked his books on cancer (The Emperor of All Maladies) and genetics (The Gene: An Intimate History), and his lecture-turned-pamphlet The Laws of Medicine. I must correct these oversights.
A Just Recompense 