A life in many cells
A fascinating history of modern medicine, this book takes the reader on a guided tour of the most basic unit of life—the cell.
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 polymathscientist 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 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. There are a staggering number 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 because of this approach that he can educate us about the thalidomide tragedy in the chapter on cell development.
THALIDOMIDE TRAGEDY
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 awry 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 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.
QUIRKY THINKERS
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.
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 that secreted specific proteins called “monoclonal antibodies”— 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.
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 principle 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 the 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.
Mukherjee’s vivid descriptions are not restricted to the cell. Nobel Prize-winner Sidney Brenner has eyebrows like “twin caterpillars”, he writes; 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 presentday 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.
Many of the audacious scientific discoveries that startled us just a few years ago—such as gene editing and CAR-T—NOW seem almost quotidian.
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 the chances of a heart attack; permanently replacing adult-type haemoglobin with foetaltype 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 seem revolutionary today, but may perhaps not be so in the future.
“We are all made of star-stuff,” Carl Sagan famously said, indicating that, at a molecular level, all the particles in our bodies were created from the death of stars. Mukherjee reminds us that we should be equally fascinated by the fact that biologically we are all made up of an extraordinary building block—the cell. m Sanjay A. Pai is a Bangalore-based surgical pathologist and amateur medical historian.