‘The Song of the Cell’ review: Understanding life in terms of its simplest unit

How does a unicellular zygote become a complex human being? How does it develop into specialized organs, such as the heart, liver, brain and kidneys? Why do some cells get corrupted? Why do organs malfunction? How do human diseases occur? How do fractures heal? How does the liver regenerate? Can we re-engineer the human body?

It is a “virtuoso act, an elaborate, multipart symphony perfected by millions of years of evolution,” writes Siddhartha Mukherjee, oncologist, haematologist, storyteller par excellence, in his latest work, The Song of the Cell: An Exploration of Medicine And The New Human.

Diligent scientists, daring explorers

Mukherjee is the biology teacher you wish you had in school. He tells fascinating tales about diligent scientists, daring explorers, and eccentrics, each of whom was obsessed with some question about the tiniest unit of the body. Cells are not just small structures that link together to make a complex organism. In the book, they come alive, like members of a family, some quirky, some sedate, some angry, some cooperative, some downright recalcitrant. They eat, sleep, think, reproduce and perform various physiological functions. And they die and are reborn.

Mukherjee’s book builds on his earlier works. The Emperor of All Maladies, which won him a Pulitzer Prize, he says, was “an overarching quest to find cures for cancer or to prevent it”. In his second book, The Gene, he attempts to decipher the code of life. In The Song of the Cell, Mukherjee takes us on another journey: “to understand life in terms of its simplest unit – the cell.” Its anatomy, physiology and interactions with other cells make up its music.

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Way back in 1665, an English scientist and man of letters Robert Hooke peered at a thin slice of cork using a hand-held microscope to see “a great many little boxes” (they were actually cell walls). He called the polygonal structures cells, from the Latin word cella, or “small room”.  A decade later, a cloth merchant Antoine van Leeuwenhoek used the microscope to examine cloth to grade it. He soon became compulsive with the microscope, examining everything around him. One day, he examined a drop of water from the roof and saw dozens of tiny organisms swimming in it (he called them animalcules). But Leeuwenhoek was not a scholar and was secretive, relying only on letters from people who swore that they had seen the things he had seen.

The discovery of microbes

Hooke and Leeuwenhoek were able to establish that both plants and animals were agglomerations of tiny cells. More than 100 years later, other microscopists established that cells came together to form tissues and organs. Soon, they began to focus on the physiology of the cell. They found that cells have different proportions of water, carbon and bases which enter and exit the cells. And where do the cells themselves come from? In 1830, German scientist Robert Remak saw a chicken blood cell split in two. A few decades later, German scientist Rudolf Virchow established that “omnis cellula e cellula” or “from cells come cells”. That led him to ask whether cell dysfunctions were responsible for malfunctions in the body. His hypothesis shook the world of medicine. If a tissue or organ was diseased, argued Virchow, the pathological changes could be traced back to the unit that composed the tissue – in other words, the cell. That, in turn, led to the discovery of microbes and the diseases they cause, and the life-saving work of Louis Pasteur and Robert Koch.

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As we deepen our understanding of the cell, writes Mukherjee, “we find ourselves able to pry open these black boxes and alter the fundamental properties of living units…. Can we build a cell with a different kind of interior milieu, different substructures and therefore different properties?” The early 1900s were a period of rapid evolution of biochemistry, with the discovery of DNA and RNA. The cell was no longer just a little box. It brimmed with substructures, each with a life of its own. By the 1950s, medicine and surgery witnessed an explosion of organ-directed therapies: rerouting blood vessels in a heart to bypass a blockage, or replacing a diseased kidney with a transplanted one. It soon gave way to functional cellular anatomy and physiology, the loci for disease and therapeutic intervention. In the last 20 years, scientists have altered cells to bring about new therapies. In May 2021, Chinese scientists began trials of gene therapy to halt the progressive loss of vision in patients.

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Cell reengineering

Mukherjee’s writing is vivid and rich in metaphors: red blood cells look like pillows that have been punched in the middle; an antibody is a gun-slinging sheriff itching for a showdown with a gang of molecular criminals in the centre of town; T-cells are gumshoe detectives going door-to-door looking for criminals. The author asks you to imagine swimming through a cell’s cytoplasm, discovering various organelles. Or walking through a library of 80,000 books and being able to zero in on the one book with a particular misprinted word in one sentence of one page of one book, and fixing the error.

Would scientists one day be able to take, say, a skin cell and re-engineer it to produce a zygote? And from that extract a stem cell that can repair any organ? Like a snail that leaves a slimy trail of its cells and yet regenerates the tissue to prevent itself from rubbing itself into oblivion, will the human body be able to regenerate itself? Some of it is already happening in laboratories. Scientists are making bio-artificial livers and hearts, or pumping stem cells into knees to prevent the cartilage from wearing out. Cell regeneration could help a very short person be taller, or help someone to overcome a muscle-wasting disease. But what if we wanted to use the technology to enhance ourselves, say, to look taller or have bigger muscles? Would that be ethical? A commercial enterprise in California already harvests plasma from young people and injects them into the shrivelling bodies of aging billionaires.

Gene therapy, gene editing and genetic selection have occupied ethicists, doctors and philosophers for decades. “But genes are lifeless without cells,” Mukherjee writes. “The real ‘raw material’ of the human body is not information, but the way that information is enlivened, decoded, transformed and integrated – i.e., by cells.” He quotes philosopher Michel Sandel as saying the genomic revolution induced a kind of moral vertigo. “But it is the cellular revolution,” Sandel predicts, “that will actualize this moral vertigo.”