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

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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 Diseases: A Biography of Cancer(2010) and has since had a large popular following. In the “The Song of the Cell: An Exploration of Medicine and the New Man‘ he repeats an intriguing formula. He tells a living story – a dear friend’s fatal melanoma, a particular patient’s illness and successful treatment, his own experience of depression, a researcher’s valiant struggles past and present – and relates it to the wider science. Mukherjee writes clear sentences full of metaphors as pedagogical tools: the cell as “spaceship”; the cell nucleus as “command center”; the genome as “library”; Neutrophils, white blood cells critical to the immune response, as “teenage soldiers sent into battle”; and MHC class 1 molecules on the cell surface as “two open halves of a hot dog bun”.

The refrain of the book is that the cell “an independent being – a unit – forming a part of the whole.” Organisms, including humans, are no more or less than the sum of these parts. The author’s overall goal is to show “how the concept of the cell and our understanding of cell physiology, altered medicine, science, biology, social structure and culture” and what he believes the future of cell manipulation will hold – spare parts for “the new Human” of its subtitle.

Although Mukherjee’s cell saga is not strictly chronological, in the first part of the book he summarizes their early history, 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 discovered living beings, “animalcules”, under the magnifying glasses he made. The author addresses the debates that raged in the 18th and 19th centuries between mechanists, who understood nature as a machine reducible to its component parts (reductionism), and vitalists, who argued that this sum was insufficient to explain life. raged. Mukherjee takes the conventional view that vitalists have suggested a divine ingredient as the source of invigoration. Some did. However, members of the French Montpellier school did not propose a supernatural ingredient, but rather a functional, relational, dynamic biology that could not be reduced to its elements. In this “holistic” model, the sum is greater than its parts.

Although the reductionists won this debate, and “vitalism” is a word used with caution in science, a battle between reductionism and wholeness has been revived in 21st-century philosophy of science and systems biology. The authors of “Complex systems are more than the sum of their parts‘, a 2015 publication in Integrative and Comparative Biology, are not alone in arguing that as organisms become more complex, new properties emerge from their dynamic networks. From this perspective, dissecting a living thing into its component parts and reassembling it does not provide a complete understanding of the whole organism. This controversial subject is never mentioned in the book.

Mukherjee tells of the beginnings of the cell theory among 19th century European scientists and the growing consensus that the cell is the basic unit of life in plants and animals. He follows this story with more cellular tales of medical intervention, drawing back to historical scientific antecedents when necessary – antibiotics, in vitro fertilization, gene editing, monoclonal antibodies, vaccines, deep brain stimulation (an implanted device that has shown some success in Parkinson’s and depression patients), immunotherapies against cancer, bone marrow transplants and stem cell research.

Mukherjee speaks openly about medical failure, the heartbreak of treating patients who suffer and die, and the moral hazard that comes with innovation, and he acknowledges that much is still unknown in cell science. Echoing his pathologist hero, Rudolf Virchow (1821-1902), who viewed the cell as a citizen of a larger society, Mukherjee emphasizes the limitations of ‘atomism’ and the importance of ‘networking’. He “extends” Virchow’s cell biology: “Beyond the isolated understanding of cells, the decoding of the inner laws of cellular citizenship – tolerance, communication, specialization, diversity, boundary formation, cooperation, niches, ecological relationships – will result the birth of a new kind of cellular medicine.”

Metaphors are crucial to thinking in science. As a philosopher of science, Evelyn Fox Keller, has argued, metaphors can both open and close avenues of discovery. The figurative is easily confused with the literal. The notion of the genome as master molecule, commander, code and blueprint has often been confused with concrete reality, even though, as Mukherjee points out, citing the great geneticist Barbara McClintock, the genome is “a delicate 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 belonging to a person (a self) and invading microbes or other “foreigners” (a non-self). . Mukherjee explains that Frank Macfarlane Burnet codified the self/non-self framework for the immune system in the mid-20th century and provides many examples of cells that “recognize” and destroy antigens – substances that trigger an immune response. Although Mukherjee takes the distinction between self and other literally, it too is a metaphor, an enigmatic concept borrowed from psychology and philosophy and challenged in immunology. “Humans,” he writes, “do not have to worry about cells from other human bodies invading and colonizing our bodies and trying to impersonate themselves.” He describes the threat of interbreeding as “chimerism,” telling us that this “merging of physical selves is not a New Age fantasy but an ancient threat”.

Mukherjee fails to mention that human reproduction is a cooperative fusion of cellular selves — the fertilized cell, or zygote, is made by two humans — and the embryo-fetus is, in part, a genetic stranger to the pregnant person. But the maternal immune system doesn’t reject the embryo, which scientists have puzzled over for years. I’ve always wondered why pregnancy, during which the self/not-self paradigm is challenged, is rarely mentioned in the discussion. In addition, cell transfer across the placenta from fetus to mother and from mother to fetus, another amalgamation of the physical self known as microchimerism, has recently been recognized as part of normal pregnancy. Fetal cells can survive in the mother for decades, and researchers are working to understand the role these migrated cells play in immune rescue and disease. Mukherjee also disregards the fact that humans are hosts to a large number of “alien” microbes and viruses (the non-selfs of the human microbiome and virome) that 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 that Mukherjee takes for granted.

It is not uncommon to find entrenched orthodoxies in popular science books. What is odd is that Mukherjee’s emphasis on “connectedness,” “cooperation,” and “ecological relationships” in biological processes is on the verge 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 contaminated,” though the word is ubiquitous in systems biology, a field dedicated to science, according to Christopher Wanjek. Write for the National Institutes of Health, “to understand the big picture—be it at the organism, tissue, or cellular level—by putting its parts together. This is in stark contrast to decades of reductionist biology, which is all about picking the pieces apart.”

Despite the omission of important contemporary debates in biology that have roots in earlier centuries, The Song of the Cell is a vivid, personal, detailed, often moving account of the cell in medical history and its promise in the present. Time will tell 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 an Associate Professor of Psychiatry at Weill Cornell Medical College.

An exploration of medicine and the new man

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