Book review of The Song of the Cell: An Exploration of Medicine and the New Human by Siddhartha Mukherjee

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Siddhartha Mukherjee, an oncologist and professor of medicine at Columbia University, won the Pulitzer Prize for his first book, “The Emperor of All Maladies: A Biography of Cancer” (2010), and has had a large popular following ever since. In “The Song of the Cell: An Exploration of Medicine and the New Human,” he repeats an engaging formula. He tells a vivid story — the fatal melanoma of a dear friend, a particular patient’s illness and successful treatment, his own experience of depression, the valiant struggles of a researcher in the past and present — and relates it to the broader science. Mukherjee writes lucid sentences dense with metaphors as pedagogical tools: the cell as “spacecraft”; the cell’s nucleus as “command center”; the genome as “library”; neutrophils, white blood cells crucial to immune response, as “teenage soldiers deployed to battle”; and MHC class 1 molecules on a cell’s surface as “two open halves of a hotdog bun.”

The book’s refrain is that the cell is “an independent living being — a unit — that forms a part of the whole.” Organisms, including human beings, are no more or less than the sum of those parts. The author’s sweeping ambition is to show “how the concept of the cell and our comprehension of cellular physiology, altered medicine, science, biology, social structure, and culture” and what he believes the future of cellular manipulation will bring — replacement parts for “the new human” of his subtitle.

Although Mukherjee’s cell saga is not strictly chronological, he summarizes its early history in the first part of the book, including the invention of the microscope in the late 16th century and its most famous users: Robert Hooke, the author of “Micrographia” (1665), who gave the cell its name, and Antonie van Leeuwenhoek, who spotted living creatures, “animalcules,” under the magnifying lenses he had made. The author covers the debates that raged in the 18th and 19th centuries between mechanists, who understood nature as a machine reducible to its discrete parts (reductionism), and vitalists who argued that this sum did not suffice to explain life. Mukherjee advances the conventional view that vitalists proposed a divine ingredient as the source of animation. Some did. Members of the French Montpellier school, however, proposed no supernatural ingredient but rather a functional, relational, dynamic biology that could not be reduced to its elements. In this “holistic” model, the sum is more than its parts.

Although the reductionists won this debate and “vitalism” is a word used in science only with caution, a struggle between reductionism and holism has been revived in the 21st-century philosophy of science and in systems biology. The authors of “Complex Systems are More Than the Sum of their Parts,” a 2015 paper in Integrative and Comparative Biology, are not alone in arguing that as organisms get more complex, new properties emerge from their dynamic networks. From this perspective, breaking a creature down into its discrete parts and putting them back together again will not give a full understanding of the whole organism. This contested issue is never mentioned in the book.

Mukherjee recounts the beginnings of cell theory among 19th-century European scientists and the growing consensus that the cell is the fundamental unit of life in plants and animals. He follows this history with more cellular tales related to medical interventions and retreats to historical scientific progenitors as needed — antibiotics, in vitro fertilization, gene editing, monoclonal antibodies, vaccines, deep brain stimulation (an implanted device that has shown some success with Parkinson’s and depression patients), immunotherapies for cancer, bone marrow transplants and stem cell research.

Mukherjee is candid about medical failures, the heartbreak of treating patients who suffer and die, and the moral risks that come with innovation, and he admits that much remains unknown in cell science. Borrowing from his pathologist hero, Rudolf Virchow (1821-1902), who viewed the cell as a citizen in a larger society, Mukherjee stresses the limits of “atomism” and the importance of “interconnectedness.” He “expands” Virchow’s cell biology: “Beyond understanding cells in isolation, deciphering the internal laws of cellular citizenship — tolerance, communication, specialization, diversity, boundary formation, cooperation, niches, ecological relationships — will result in the birth of a new kind of cellular medicine.”

Metaphors are crucial to thought in science. As one philosopher of science, Evelyn Fox Keller, has argued, metaphors may both open avenues of discovery and shut them down. The figurative is easily confused with the literal. The idea of the genome as master molecule, commander, code and blueprint has often been mistaken for concrete reality, even though, as Mukherjee points out, quoting the great geneticist Barbara McClintock, the genome is “a sensitive organ of the cell.” It is inert without its cellular environment.

Throughout the book, Mukherjee uses a common metaphor for the immune system as a battleground between “us” and “them” — the cells that belong to a person (a self) and invading microbial or other “foreigners” (a non-self). Mukherjee explains that Frank Macfarlane Burnet codified the self/non-self framework for the immune system in the middle of the 20th century and provides many examples of cells that “recognize” and destroy antigens — substances that trigger immune response. Although Mukherjee takes the self/other distinction literally, it too is a metaphor, a riddled concept borrowed from psychology and philosophy, which is being challenged in immunology. “Human beings,” he writes, “don’t have to worry about cells from other human bodies invading and colonizing our bodies and trying to pass themselves as selves.” He describes the menace of mingling as “chimerism” and tells us that this “fusion of physical selves — is not a new age fantasy but an age old threat.”

Mukherjee does not mention that human reproduction is a cooperative fusion of cellular selves — the fertilized cell or zygote is made from two people — and the embryo-fetus is partly a genetic foreigner to the pregnant person. But the maternal immune system does not reject the embryo, something scientists have puzzled over for years. I have always wondered why pregnancy, during which the self/non-self paradigm is rendered moot, is rarely brought up in the discussion. Further, cell transfer via the placenta from fetus to mother and mother to fetus, another fusion of physical selves known as microchimerism, has recently been acknowledged as part of normal pregnancy. Fetal cells can endure for decades in the mother, and researchers are working to understand the role these migrated cells play in immune rescue and disease. Mukherjee also leaves out the fact that humans are hosts to vast numbers of “alien” microbes and viruses (the non-selves of the human microbiome and virome), which are not only tolerated but necessary for our survival. Philosophers of biology, including John Dupré, Polly Matzinger, Thomas Pradeu and Alfred Tauber, have challenged the self-other assumption Mukherjee takes for granted.

There is nothing odd about finding entrenched orthodoxies repeated in popular science books. What is odd is that Mukherjee, with his emphasis on “interconnectedness,” “cooperation” and “ecological relationships” in biological processes, hovers on the brink of countering his own reductionist argument that the whole is the sum of its parts. He flirts with a form of holism, an idea he calls “scientifically defiled,” though the word is ubiquitous in systems biology, a field dedicated, according to Christopher Wanjek, writing for the National Institutes of Health, “to understanding the larger picture — be it at the level of the organism, tissue, or cell — by putting its pieces together. It’s in stark contrast to decades of reductionist biology, which involves taking the pieces apart.”

Despite its omission of important current disputes in biology, which have roots in earlier centuries, “The Song of the Cell” is a lively, personal, detailed, often moving account of the cell in medical history and its promise in the present. Time will decide if Mukherjee’s new human, “a new sum of new parts,” belongs to our future.

Siri Hustvedt is the author of 13 books, most recently “Mothers, Fathers, and Others.” She is a lecturer in psychiatry at Weill Cornell Medical College.

An Exploration of Medicine and the New Human

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