The Song of the Cell

Title: The Song of the Cell – An Exploration of Medicine and the New Human

Author: Siddhartha Mukherjee

Publisher: Penguin Random House, 2022 (First)

ISBN: 9780670092727

Pages: 473

 

Efforts to understand the fundamental building blocks that make up the complex whole of living organisms was an exercise eagerly taken up by intellectuals in all civilizations of the world. Many intelligent guesses were put forward which could not be evaluated until the physical infrastructure for observing what is happening at the smallest levels could be developed. The invention of telescopes revolutionized astronomy and its counterpart – microscopes – opened up an unknown world before the incredulous researchers. For the first time, they began to discern an underlying uniformity in the composition of various organs within an organism and even across organisms. Following many leads found by experimenters, it was established that cells form the building blocks of life. This book is a chronicle of the discovery that all organisms, including humans, are composed of the basic units called cells and how these cooperative and organized accumulations enable aggregate traits like immunity, sentience, reproduction and cognition. It is also the story of what happens due to dysfunction leading to death and the transformative medicines that are being developed. Siddhartha Mukherjee's other books – the masterpiece ‘The Emperor of All Maladies’ and ‘The Gene’ – were reviewed earlier here.

 

Mukherjee begins by a brief survey of the ancient theories that tried to explain how life functioned. One such was vitalism which postulated a vital force that was present in all living beings as essential for birth of life. Another related idea was preformation. This speculated that microscopic shapes of adult animals reside in sperms. After fertilization with an egg, this is then expanded in size like a balloon surface does. However, cell theory demolished both these by the 1850s. Mankind woke up to a new idea which proved that cells are the basic building blocks of life. All our organs are made of cells that share many similarities like a membrane wall, metabolism, waste processing, nucleus and portals for entry and exit of chemicals. The instructions for creating new cells and for synthesizing proteins are contained in the DNA stored inside the nucleus. Even though the same genome is encoded in each cell, only parts of it are enabled in each organ. The physiology of an organism is the result of chemical reactions happening inside the cells. Likewise, the pathology of an organism is the outcome of another set of reactions which do not contribute to the well-being of the cell and the organism. This cellular targeting is the cause of why medicines succeed in curing the individual. Every potent antibiotic recognizes some molecular component of human cells that is different from a bacterial cell. Penicillin killed the bacterial enzymes that synthesized its cell wall, resulting in bacteria with ‘bullet holes’ in their cell membranes. This helped only because the human cell wall was different from a bacteria’s. But cancer cells share most of the features of normal cells and that’s why destroying them is so difficult and normal tissue is also affected as collateral damage in chemotherapy.

 

Technology has been able to probe deep into outer space and watch the formation and death of star systems in distant galaxies where light itself takes several years to reach. Considering the depth of information – at least, many viable hypotheses – on astronomy, it is astonishing as well as slightly embarrassing that we know very little about cells, on which our body and very life is totally dependent. The author gives a summary of how they originated. The origin of eukaryotic cells – those with a nucleus, like all animal cells – took place around two billion years ago. This is said to be ‘a strange, inexplicable turn for evolution’ (p.71) and also ‘an evolutionary mystery’. It has left only the scarcest of fingerprints of its ancestry or lineage. This is thought to be a black hole at the heart of biology. The growth of cells, by a process called cell division, is also a complex and mysterious operation. It includes a least understood phase called G2, where the division temporarily halts and checks for major errors in DNA duplication that may lead to catastrophic mutations. In such a case, it aborts the process but allows small mutations; otherwise there won’t be any mechanism available for evolution to operate. ‘Black hole’, ‘mysterious’, ‘least understood’, ‘inexplicable’ are all terms that make the opponents of evolution exuberant with joy. But wait, the working of the cell is so complex that they are not even wrong! A serious and fruitful study on cells developed only by mid-twentieth century and the field is still open for revolutionary discoveries.

 

As we read more and more of this book’s contents, we get more and more astonished at the ingenious inner working of the cell. Such is the organization and direction going on at the microscopic level! Frankly speaking, if somebody is led to think that this entire set up must be the creation of a superior intelligence of creator, they can’t be blamed outright. But as you delve deeper, chinks begin to appear and what is most evident is behind the veil is imperfection at every stage of the cellular process. Otherwise, we won’t die, won’t age or even get sick. Perhaps, we may not even be born! The process of blood clotting after a wound illustrates this in detail. Clotting is orchestrated by a special protein called von Willebrand factor (vWf) which circulates in blood as well as located under the cells that line blood vessels. Injury to the vessel caused by the wound exposes the vWf protein. This prompts the other vWf to gather around the injury. A cascade of changes is then launched which leads to the synthesis of another protein called fibrin. This forms a mesh on which the platelets are trapped which forms the clot and stops blood flowing out. So much is perfect design, but the incompetence manifests itself later. As a person ages, cholesterol-rich plaques are formed inside the blood vessels which hang on to the walls of arteries and stick to heart’s valves. When such a plaque accidentally ruptures or breaks, it is unfortunately sensed as a wound. The cascade to heal wounds is then activated. Platelets rush to the site to heal the wound and results in blockade and heart attack. This leads to the conclusion that if life is thought to be the handiwork of a creator, he is certainly intelligent, but not perfect. And this violates the first principle of religion about omnipotence.

 

This book examines each functional subunit of the human body and explains how it functions at the cellular level. The heart, brain, kidney, liver, blood, spleen, pancreas and neurons are handled in sufficient detail. I’m afraid some of it may be a little too thick for readers uninitiated into serious biology like me. However, these chapters are treasure chests of a lot of information and learning. Most developments in cell biology are surprisingly modern. The physiology of T-cells, an essential part of immunity, was identified only half a century ago. The thymus gland which produced it was till then thought to be a vestigial detritus of evolution with no useful function. How the immune system distinguishes between the body’s own cells and foreign invaders is a miraculous process. Mukherjee emphasizes this as it is highly relevant in cancer treatment which is his specialization. The present state of cancer therapy is handicapped by the immune system’s inability to distinguish cancer cells as something hostile to the body’s well-being.

 

The subtitle of the book mentions ‘new human’ whose potentialities are at once exciting and a bit terrifying. This involves genetic manipulation to alter the destiny of humans before birth or when afflicted with disease. Early experiments are now on to search for specific disease-causing genes at the embryo stage and alter them to benign versions before implanting the embryo into the uterus. Needless to say, this is still in its infancy and there’s lot of scope for regulatory supervision. In some cases of cancer in grown up persons, modifying the genome of specific immune cells or therapeutic agents to zero in on the cancer cells and sparing healthy cells is technically feasible. Another aspect of the new-human paradigm is the full scale development of stem cells which is a special kind of cell which can be used to create any type of cell. Normally, a skin cell produces another skin cell and a muscle cell creates a muscle cell. However, a stem cell can be programmed to create any of these. The book records a recent experiment in which a normal cell could be converted to a stem cell. This will greatly assist in developing organs outside the body that can then be used to replace defective ones inside. Mukherjee also stresses on the dynamic equilibrium which pervades at the level of cells which is called homeostasis. Cells die continuously and new ones take their place. Death is a relative balance between forces of decay and rejuvenation. If you tip the balance in one direction, you fall off the edge. Or in other words, the moment you stop growing, you start dying.

 

The book is divided into many parts dealing with fundamental aspects of cells like origin, reproduction, anatomy and metabolism and then goes on to explain each in some detail. Lot of footnotes is included which the author urges us to read carefully. Mukherjee, himself of Indian ethnicity, freely uses Indian philosophical, metaphysical and even mythological symbols to illustrate abstract concepts happening at the level of cells. This is a welcome innovation in books of this genre. This book introduces many advanced ideas which must be well understood by the readers in order to follow the argument intelligently. It must be confessed that this is a bit tedious and there are some pages on which it feels like a text book than a volume of popular science. Still, it must not be missed in one’s reading career. It is also suffused throughout with sublime wonder at the intrinsic functioning of the cell which the readers readily share. However, the illustrations are not at all attractive as many of them are reproduced from the original papers which were intended for a scholarly audience. This should be simplified and made arresting with good graphics in future editions. The author and publisher must seriously consider this suggestion.

 

The book is highly recommended.

 

Rating: 4 Star