In author Siddhartha Mukherjee's new book The Song of the Cell, cell biology becomes a rich journey – part historical saga, part detective story – and also leans into futurism.Deborah Feingold/Supplied
Vincent Lam is a physician and the Scotiabank Giller Prize-winning author of Bloodletting & Miraculous Cures whose forthcoming novel, On the Ravine, will be published in February.
- Title: The Song of the Cell
- Author: Siddhartha Mukherjee
- Genre: Non-fiction
- Publisher: Simon & Schuster
- Pages: 496
To contemplate the living cell is to consider the stuff humans are made of, for cells are the essential building block of life. In The Song of the Cell, Siddharta Mukherjee tells the story of their continuing discovery. He explores the significance, now that our knowledge allows us to alter cells within our own bodies. The implications for humanity are that we are close to what Mukherjee explains is “a new kind of medicine – cellular therapies – based on our deciphering the physiology of cells.” If we soon possess the ability to repair pre-existing vulnerabilities in our genetic code, or grow replacement organs to repair our fragile biology, will we be a new kind of human? Mukherjee brings the reader to the brink upon which we stand, where these possibilities are tantalizingly close.
To wonder at the lives and deaths of cells is to enter a world both Lilliputian in scale and awe-inspiring in complexity and revelation. Mukherjee employs the literary equivalent of a massive zoom lens, both tracing the history of physicians and scientists who parsed living beings into ever-smaller constituents – organs, cells, sub-cellular structures, DNA – and then zooming out to the paradigm shifts in our understanding of ourselves that this knowledge required. Through cell biology we know our species’ ancient links to all other life on this Earth and can marvel at our personal trajectory from a single-cell embryo to our present consciousness. Within complex multicellular beings like ourselves, context, relationships and interactions define the function and meaning of each cell. These interactions are the evolving area of the science where Mukherjee envisions The Song of the Cell will be sung.
In our current era we assume tap water can be made safe, forgetting John Snow, who through epidemiological detective work in the 19th century arrived at the then-radical proposal that, as Mukherjee writes, the “morbid matter of cholera [was] … most likely that of a cell” and the mysterious source of an outbreak was a contaminated well.
We take it for granted that a blood transfusion may save a life following a traumatic injury, not considering that it was only about a century ago that Karl Landsteiner characterized blood groups – making it possible to safely transfuse blood cells. We scarcely remember that type 1 diabetes was a death sentence until Frederick Banting, a Toronto doctor, and his colleagues identified and purified insulin. This hinged upon an understanding of pancreatic cells.
Mukherjee recounts the history of these once world-changing discoveries that are now woven into our assumptions. The implication is that ideas and technologies that currently feel like science fiction may soon be similarly commonplace. The cautionary tale of He Jiankui, who performed genetic manipulation on two human embryos with little ethical justification and was subsequently sentenced to prison, makes the point that it is one thing to acquire technical abilities – another to use them wisely.
The conceptual shifts required for past advances to be accepted were immense, taking humanity on a long arc from the Greek concept of vitalism to our current state of experimental, evidence-based inquiry. From the ancient concept of “humours,” we moved to a mechanistic sense of our bodies as if they were some gigantic clockwork. We are now progressing to a deeper awareness of that clockwork being dynamic, its cells subject to alteration by their environment and experiences.
Today, the understanding that most disease states – from cancer to heart attacks to dementia – have a cellular basis brings with it an ambitious question: Can we alter the course of disease by repairing cellular components that are dysfunctional? Can conditions that are now at best treatable become curable? In some cases, the answer is already “yes.” Mukherjee introduces us to patients like Emily Whitehead and Timothy Ray Brown, who respectively have had refractory acute lymphoblastic leukemia and HIV cured by experimental cell therapies. They may be the first glimmer of the future of medicine.
Supplied
The possibilities to alleviate human suffering are tantalizing: Could it become possible to take a person’s own cell from their skin or blood, and create an induced pluripotent stem cell (a cell that could grow any other kind of cell), and from this create any cell that a person needs for repair – for instance cartilage or neurons, which our bodies do not naturally replace? What would this mean for the treatment of arthritis or brain injury? Currently, we read, researchers are developing a cellular “artificial pancreas,” hoping to implant this into type 1 diabetics, building a bioartificial liver out of liver cells, and attempting to build a bioartificial heart out of cardiac cells derived from stem cells.
Nonetheless, the reality that human beings remain fragile, and our knowledge incomplete, is underscored when Mukherjee outlines the subterfuges of the SARS-CoV-2 virus. In some infected persons, it has a particular ability to evade early immune responses and yet set the stage for a later overwhelming and sometimes fatal immune response. Despite our huge advances in cell biology, a virus has upended human life on this planet for three years through its manipulation of cellular mechanisms. Like all science, each new piece of knowledge begets questions, and Mukherjee lists the major outstanding mysteries around SARS-CoV-2 in a frustrated litany, concluding, “The monotony of answers is humbling, maddening. We don’t know. We don’t know. We don’t know.”
I was surprised that Mukherjee did not delve further into the current science of the impact of the environment upon cellular mechanisms, for example the proposed effects of trauma upon telomere length, which is thought to be a marker of age-related diseases. I would have expected such a compelling writer and scientist to linger further upon this most poetic discovery: that the largest forces in our world – how we treat one another – affect each of our health via our tiniest constituents, our cells.
Also absent is a discussion of the economic and social implications of new treatments. High development and manufacturing costs, coupled with the treatment of some conditions that are rare, have meant that gene therapies have thus far landed on the market with six- and seven-figure price tags per treatment, making them inaccessible for many. It would be fascinating to know what Mukherjee, who is both a doctor caring for patients and a scientist involved in developing cutting-edge CAR-T cell therapy, thinks about these thorny issues.
Mukherjee’s deep engagement with cell biology and cellular medicine animates The Song of the Cell. Cell biology becomes a rich journey – part historical saga, part detective story – and also leans into futurism. The great achievement of The Song of the Cell is to transcend the gap between the technical knowledge and the human drama of this field of science. Mukherjee shows us that cell biology already deeply informs our present lives, but so much shimmers in the near-horizon, at once microscopic in detail, and massive in its implications for humanity.
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