At the biology-level, what is “the self”? | The Song of The Cell Book Review

Wow. This is a book you have to read for yourself.

Once again, Dr. Siddhartha Mukherjee has managed to leave me speechless. He is one of the best writers I have ever come across – and I do not say that lightly. In his latest 377-pg book The Song of the Cell: An Exploration of Medicine and the New Human, he somehow manages to make advanced cell biology feel like poetry. Seriously.

As an example of the beautiful, elegant writing, here is an excerpt that describes blood’s functionality:

“Blood? It is a conglomerate of organs, a system of systems. It has built training camps for its armies (lymph nodes), highways and alleys to move its cells (blood vessels). It has citadels and walls that are constantly being surveyed and repaired by its residents (neutrophils and platelets). It has invented a system of identification cards to recognize its citizens and eject intruders (T cells) and an army to guard itself from invaders (B cells). It has evolved language, organization, memory, architecture, subcultures, and self-recognition. A new metaphor comes to mind. Perhaps we might think of it as a cellular civilization” (p242).

I’ve read three of his four books and it’s always a love-hate relationship when the end is near. On one hand, I’m excited to pronounce myself finished, to have, at least at one time, known all the knowledge it contains. On the other hand, I never want his books to end; they’re deep, insightful, beautifully-written, and, above all, they actually make me think. It’s very clear that they’re written by someone who loves to write (as opposed to the many who write to build credibility or to claim the title “author”). As I finished this book, I sat thinking, there’s only one book of his left to read. I don’t want it to be all over. He better be working on another…

Curious to learn more about this incredible author, I googled him halfway through this book. I came across an interesting article that walked through his typical week. I found out he goes to the bookstore most Sundays with his family. They all pick out a book, then go home and spend the afternoon reading it. I wasn’t surprised. It suddenly made more sense how he could interweave quotes from Aristotle and Shakespeare into the complex history of medicine.

Plus, he is not just the writer, the chronicler of history; he is also the doer, the cutting-edge scientist, doctor, researcher. At the end of the book, he tells the behind-the-scenes story of extremely innovative and game-changing research that he is personally working on… a radically new hypothesis about osteoarthritis, “It isn’t merely a degeneration of cartilage cells, caused by grind and tear. It is, first, an imbalance caused by the death of Gremlin-marked cartilage progenitor cells that cannot generate adequate bone and cartilage to keep up with the demands of the joint. And so we have a theory to answer the age-old mystery: Why doesn’t cartilage in joints get repaired, just as a bone fracture does, in adults? Because the repairing cells die during the journey.”

With new understanding comes new treatments – it’s amazing to have a front-row seat and an engaging narrative to learn about the latest research. I’ve personally seen my mom struggle a lot with arthritis and am very interested in diving deeper into the latest research to see what solutions might be available.

While I love his books, and this one especially, they always take me time to read. You read a little, let it digest, then return for more. It took me ~5 months to read this book. It might not be a quick read but it is a quality read… and with that, I could pretend to come up with some key takeaways but the reality is that the “key takeaways” of this book are too nuanced, too beautifully explained, too intricately woven into the stories that shaped modern medicine to just pluck them out and let them stand alone. Instead, here are some quotes that try to capture the main ideas.

1. On the Beautiful Complexity of Cells:

“A cell is not a blob of chemicals; it has distinct structures that allow it to function independently. The subunits are designed to supply energy, discard waste, store nutrients, sequester toxic products, and maintain the internal milieu of a cell” (p74).

2. On the Evolution From Single Cell to Multicellular Organisms & the Concept of “Self”

“Under the right evolutionary pressure, single cells can become multicellular aggregates over a mere few generations. We can only generate theories about why single cells are so singularly drawn to form multicellular clusters. But the reigning theories suggest that specialization and cooperativity conserve energy and resources while allowing new, synergistic functions to develop. What we do know is that the evolution of multicellularity was not an accident, but purposeful and directional” (p134).

“What is the self? An organism, as I suggested before, is a cooperative union of units; a parliament of cells. But where does the union begin and end? What if a foreign cell tried to join the union? What passport must it carry that enables it to pass? As the Caterpillar in Alice in Wonderland asked Alice, ‘Who are you?’” (p 226).

“The self is defined, in part, by what is forbidden to attack it. Biologically speaking, the self is demarcated not by what is asserted but by what is invisible: it is what the immune system [which attacks invaders] cannot see” (p233).

3. On the Cell’s Journey To “Identity”

“The growth of an embryo is a process, a cascade. At each stage, preexisting cells release proteins and chemicals that tell the newly emerging and newly migrating cells where to go and what to become” (p142).

“The process of switching genes on and off is vital, giving the cell its identity. The set of on/off genes instructs a neuron to be a neuron, and a white cell to be a white cell. During the development of an organism, genes – or rather proteins encoded by genes – tell cells about their relative positions and command their future fates” (p89).

“The sequence of DNA in all the cells (i.e., the genome) is identical in nearly all our cells; it is the subset of genes that is turned ‘on’ and ‘off’ in a heart cell, or a skin cell, that determines its identity. What if we could change that pattern–turn stem cell genes ‘on’ and ‘off’ in a skin cell? Would the skin cell now turn into a stem cell–capable of making not just skin, but bone, cartilage, heart, muscle, and brain cells–i.e., every cell in the body?” (p333).

Shinya Yamanaka made a stem cell out of a fibroblast – a transition thought to be impossible in biology; these were termed induced pluripotent stem cells, or iPS cells (p334).

“In principle, you could repeat the process infinitely… every degenerated organ, or tissue could be regenerated, and regenerated again, ad infinitum (to be fair, no has tried this yet). I sometimes think of the Greek story of the Delphic boat. The boat is built of many planks. Bit by bit, the planks decay and are replaced by new ones, until all of them are new. But has the boat changed? Is it even the same boat? These musings may seem metaphysical today. But they may soon become physical. ” (p335).

4. On Cells’ Relation to Disease:

“Medicine isn’t a doctor with a black bag. It’s a complex web of systems and processes” (p260).

‘“The body is a cell state in which every cell is a citizen… Disease is merely the conflict of the citizens of the state brought about by the action of external forces”’ (p48, quote from Rudolf Virchow).

‘“Life is, in general, cell activity… Every disease depends on an alteration of a larger or smaller number of cellular units in the living body, every pathological disturbance, every therapeutic effect, finds its ultimate explanation only when it’s possible to designate the specific living cellular elements involved”’ (p52, quote from Rudolf Virchow).

5. On the Remarkable Nature of Blood & the Heart

“Blood speaks to everyone and everything: it is the central mechanism of long-distance communication, of transmission, in humans. Be it hormones, nutrients, oxygen, or waste products, blood delivers and connects – talks – to every organ and from one organ to the next” (p154).

“Contemplate the heartbeat: this phenomenon that many of us might consider the epitome of the everyday–the heart will beat more than two billion times over an average person’s life–is, in fact, a miraculously complex feat of cell biology. The heart is a model of cellular cooperation, citizenship, and belonging” (p262).

6. On the Nature of Hormones, Our Long-Distance Messengers

“There must be a means for one part of the body to ‘meet’ a distant part of a body. We call these signals ‘hormones,’ from the Greek hormon–to impel, or to set some action into motion. In a sense, they impel the body to act as a whole” (p298).

“The pancreatic beta cells control metabolic homeostasis through the hormone insulin. The kidneys’ nephrons control salt and water, maintaining a constant level of salinity in the blood. The liver, among many of its functions, prevents us from being soused in toxic products, including ethanol [alcohol]. The brain coordinates this activity by sensing levels, sending out hormones, and acting as a master orchestrator of balance-restoration” (p312).

7. On the Future of Cell & Genetic Engineering

“Whether by embryo selection or by gene editing, the genetic manipulation of the human embryo to arrest diseases (or, perhaps, to enhance human abilities) seems, every day, to become an inevitable destination for medicine” (p130).

“As the combined forces of genetics and cell engineering extend their reach to touch new depths of the human body and personhood, the ‘moral landscape’ has changed radically: the borderlands between the emancipation from the ravages of disease (extreme short stature, or the muscle-wasting cachexia) and the augmentation of human features (increasing height or bulking up muscle) are blurring” (p373).

“A start-up called Ambrosia is offering transfusions of matched young blood plasma ‘harvested from youths between sixteen and twenty-five years old’ to supposedly rejuvenate the creaking, but very wealthy, shriveling bodies of aging billionaires. Rather than draining old blood from the dead, you infuse young blood into the aged–embalming in reverse (I am tempted to draw an analogy to vampirism, but perhaps we will find a new euphemism for this chilling kind of attempted cellular rejuvenation…” (p374). As an interesting aside, one liter of “young blood” costs $8,000.

As always, Dr. Mukherjee leaves me in awe of human civilization and our ability to figure out the complexities of the world we live in. An example many people today are probably less aware of: diabetes, which we understand and can treat reasonably well today, was once a “mystifying disease” (p302); just like the pancreas was once thought of as a “glorified pillow” to protect the stomach from crushing blood vessels against the spine (p298).?

Yet, even with all we’ve learned, there is still, as Dr. Mukherjee puts it, “another layer of organization left to learn: the ecosystem of cells. It is the music that drives the complexity of cellular physiology–and, conversely, the playlist of malignant pathology–that remains one of the unsolved puzzles of cell biology” (p314).

I started with this and I’ll end with it: This is a book you have to read for yourself. It is engaging but it is also humbling. At the end of the day, as David Matthews famously sings, “We are all just a collection of cells overrating ourselves.”