In The song of the cell, physician-scientist Siddhartha Mukherjee takes us through a guided tour (de force) of the most basic unit of life itself—the cell. As one would expect from a book written by Mukherjee, whose earlier works include The emperor of all maladies: A biography of cancer and The gene: An intimate history, this exploration is an enthusiastic and intellectually satisfying one. As an explainer of events and processes in medicine, Mukherjee is now the equivalent of Carl Sagan for space sciences.
This book is a non-linear history and narrative of the cell—its microscopic anatomy, biochemical processes, pathology—in 24 chapters. We travel from the past (from 1665, when the first cells were seen and the word “cell” itself was created by the polymath-scientist, Robert Hooke who was struck by the regularly arranged “boxes” in a thin slice of cork when he studied it under a microscope and perceived a resemblance to the living quarters of monks) into the present day, and take a peek into the near future. Hooke’s discovery was followed by that of Antonie van Leeuwenhoek, a Dutch draper and amateur scientist who explored rainwater, seawater, and his semen with the aid of a microscope and discovered fascinating tiny organisms which he labelled “animalcules”.
Although the botanist Matthias Schleiden and the zoologist Theodor Schwann had proposed that the cell was the basic unit of life as early as in the 1830s, there was a lack of clarity about where those cells originated from. The French radical (in every sense of the word) scientist, François-Vincent Raspail, posited that cells arose from other cells. This was underscored by the genius German pathologist Rudolf Virchow who added that disease resulted when these cells went awry. In hindsight, a most obvious concept but clearly not obvious enough to generations of thinkers.
There are a staggering amount of specialised cells in the human body; and each of these is staggering in its simultaneous simplicity and complexity of structure and function. Mukherjee takes you, like in the 1966 science-fiction film Fantastic Voyage, on a swim through the cell, where you meet and learn more about the various components (“organelles”) such as mitochondria, endoplasmic reticulum and the nucleus. Chapters that elaborate on the various functions of the cell, such as cell division, cell development, defence mechanisms, and so on, follow. The author enlightens us about the biologic processes, intersperses it with history and often leads on to the latest medical application of our knowledge of the process.
Consequently, the explanation of cell division leads to the story of the first test-tube baby. It is precisely because of this approach that he can educate us about the thalidomide tragedy in the chapter on cell development. In the late 1950s and early 1960s, thousands of pregnant women who took a thalidomide pill to prevent morning sickness delivered babies with malformed (“seal limbs”) or absent limbs or with cardiac and other organ defects. Cell development had gone astray because the drug had interfered with the proteins that play a role in normal development of the heart, limbs and organs.
The rest of the book has essays on individual specialised cells such as platelets and lymphocytes in that marvellous fluid tissue, blood, as well as cardiac muscle cells and cells in the brain such as neurons (the “contemplating cell”), as also the ignored-until-now glial cells. In all this, do recall that cells in the body do not live in isolation; rather, they constantly communicate with each other and listen to each other’s signals—or their “songs”.
All great scientists, I suppose, have to be mavericks, in order to question dogma. Quixotism repeatedly surfaces as scientists challenge cherished beliefs and propose and prove new theories about our very own bodies. For instance, we have believed for long that cells differentiate, that is, they progress from an uncommitted “stem” cell to a final, mature, committed cell at which stage they stop and change no further. Yet, in 2006, Japanese scientists achieved the seemingly impossible when they experimentally reconverted mature fibroblasts into stem cells by introducing appropriate genes into their nuclei. This is akin to finding the fountain of youth.
Other examples include the preposterous idea of researchers in 1975 to fuse a cancerous plasma cell with a B-lymphocyte (both being types of blood cells). This resulted in a unique cell which secreted specific proteins called “monoclonal antibodies”, undoubtedly, the most significant advance in laboratory diagnostics and in treatment in the past half-century. This finding was so revolutionary that the National Research Development Corporation in the United Kingdom could not think of an obvious practical use for this finding and chose not to patent it, resulting in the loss of billions of dollars to them. Because, almost immediately, medicine changed, and today medicine without monoclonal antibodies is pretty much like medicine without anaesthesia or antibiotics.
The quirkiness in their scientific thinking suffuses into scientists’ normal lives as well. Albert Szyent-Györgyi, tired of serving in the First World War, shot himself in the arm, claimed that it had happened in battle and got himself discharged from the army—all so that he could return to science.
It is an indicator of how rapid the progress in cell biology has been, when one realises that many of the audacious discoveries (of which numerous have resulted in Nobel prizes) that startled us just a few years ago now seem almost quotidian. In the past decade alone, we have had two such ideas—gene editing (Clustered Regularly Interspaced Short Palindromic Repeats or CRISPR) and CAR-T (chimeric antigen receptor T cells).
In CRISPR, highly specific and directed editing of genes can be performed so as to transmogrify cells. Mukherjee explains that this mechanism is so effective that it is the equivalent of locating and deleting one word in one book of a library that contains 80,000 books.
It goes without saying that gene editing in humans opens a minefield of ethical quandaries. In 2017, He Jiankui, a Chinese researcher, decided to go ahead anyway and created gene-edited babies. The result? Babies with altered genes but of uncertain, dubious and potentially harmful outcomes. Jiankui was jailed for three years for flouting the most basic of principles of medical ethics and for experimenting when no experiment was needed.
Consider the CAR-T phenomenon, the latest bullet in our armamentarium against cancer. We know that cancer cells escape being attacked by the soldiers of the immune system by adopting different approaches. One manner of achieving this is by ensuring that the soldier cells do not perceive the cancer as foreign. It turns out that a family of soldiers, the T lymphocytes, have a safety switch (a “checkpoint”) on so as not to attack the body’s own cells. Now, CAR-T cells have this blocking mechanism itself blocked by drugs (“checkpoint inhibitors”) and can now attack the tumour by recognising it as alien.
Is it possible to write a book on medicine in 2022 and leave out COVID-19? Obviously not, more so because the disease is the result of floundering of the immune system. After all, it is the host cell, which, when taken over by the virus, fails to secrete Type I interferon, which is one of the defence mechanisms. The song of the cell is thus a history of medicine in the 20th and 21st century, with a decided slant towards cell biology.
Mukherjee’s vivid descriptions are not restricted to the cell. Nobel Prize winner Sidney Brenner has eyebrows like “twin caterpillars”, another Nobel Prize winner Paul Nurse reminds him of an “elderly wizened Bilbo Baggins”, and a colleague, Chuck Chan, looks like “a punk rocker”. Hindu mythology crops up on more than one occasion. As in his earlier books, the author seamlessly interweaves present-day life into the events that created our current concepts of cell biology. The reader is privy to Mukherjee’s enthralling research, his interactions with family, colleagues, patients and mentors.
The new human
What of the future? Here is where the subtitle of the book—the new human—comes in. Mukherjee proposes that the very concept of medicine is artificial. Assisted reproduction, blood transfusion, and bone marrow transplants (topics examined in the book) are commonplace now. Ideas such as editing genes to reduce cholesterol levels and thus reduce the chances of a heart attack, permanently replacing adult-type haemoglobin with foetal-type haemoglobin in the red blood cells of adult patients with sickle cell anaemia (because the disease only affects adult haemoglobin, not foetal haemoglobin), placing electrodes in the brain so as to cure depression—these ideas seem revolutionary today, but may perhaps not be in the future.
This may sound like science fiction, but is not. All of this is being researched and experimentally performed or on the anvil at the moment. Human beings in the future may well be the sum of many vastly different parts, some original, some replaced or edited later from their own or others’ bodies.
“We are all made of star-stuff,” Carl Sagan famously said, indicating that, at a molecular level, all the particles in our bodies had been created from the death of stars. Mukherjee reminds us we should be equally fascinated by the fact that biologically we are all made up of numerous extraordinary building blocks—the cell.
Sanjay A. Pai is a Bangalore-based surgical pathologist and amateur medical historian.