Are we ready for the new humans?
- February 17, 2023
- Kevin Davies
Siddhartha Mukherjee tells the story of cells, those fundamental units of life, mixing trademark reflections with historical vignettes and scientific lucidity.
The Song of the Cell: An Exploration of Medicine and the New Human. By Siddhartha Mukherjee, Scribner, 2022, 496pp, £25/$32.50
The human body contains about 30 trillion cells, give or take a few billion. Hundreds of billions of these cells, especially in the blood and gut lining, are replenished on a daily basis. As our cells continuously divide and replicate, mistakes inevitably creep into their DNA, which can disrupt the exquisite choreography of cellular division and differentiation. As the late writer John Diamond observed, by the time someone reaches the age of 40, most of their cells have divided a few thousand times: ‘How could it possibly not be that a few of them would band together in a state of cytological anarchy that leads to cancer and death.’
A little more than a decade ago, Siddhartha Mukherjee announced himself as a truly accomplished science author. Published in 2010, The Emperor of All Maladies was a mesmerising biography of cancer, exploring the molecular underpinnings of the disease and the ingenuity of scientists and physicians on a quest to devise more potent and precision-guided therapies. The book was adapted into a documentary series for American Public Television by the legendary Ken Burns and earned the author a Pulitzer Prize.
Mukherjee followed up that success with another bestseller – The Gene – which also received the Burns documentary benediction. What makes Mukherjee’s literary success all the more remarkable is that these are mere extracurricular projects. By day, Mukherjee is an oncologist, professor, and researcher at Columbia University in New York. Perhaps, like the Christian Bale character in The Prestige, he has a secret twin, or maybe he’s cloned himself? I don’t know how he finds the time.
In his latest book, The Song of the Cell, Mukherjee returns to his cellular biology roots with another heady mix of historical vignettes and lucid scientific explanations intermixed with candid personal stories and reflections, many featuring patients he has treated over the years. He effortlessly marries an assured medical authority with a uniquely poetic prose that lifts every chapter, although it might not suit every reader’s taste.
Mukherjee traces the genesis of The Song of the Cell to three articles he published between 2017-2021 in The New Yorker. One of those essays was a wake-up call to the scientific and medical communities to learn lessons from the COVID-19 pandemic. In the book, Mukherjee quotes the noted Yale University immunologist Akiko Iwasaki, who frames the central pathology caused by the SARS-CoV-2 virus as an ‘immunological misfiring.’ ‘I had not even heard the term before,’ Mukherjee writes, ‘but its immensity hit me: at its core, the pandemic, too, was a disease of cells … viruses are inert, lifeless without cells. Our cells had woken the plague and brought it to life.’
Even as Mukherjee wrestled, like everyone else, with the mental and physical hardships posed by the pandemic, COVID provided further impetus for a book that, in a way, he says, ‘demanded to be written.’
Mukherjee writes persuasively that our understanding of cellular biology and behaviour has and is transforming medicine. We use drugs and other stimuli — antibiotics, chemotherapy, electricity — to alter cellular properties. We transfer cells from person to person — blood transfusions and bone marrow transplantation. We use cells to engineer the production of drugs such as insulin and other recombinant proteins. And in one of the hottest areas of medicine, we use gene editing and other tools to rewrite their genetic architecture.
Although not intended to be a history of cell biology per se, Mukherjee spends considerable time recalling heroes of the field. Most of the big names are here, some more familiar than others — titans such as Robert Hooke, Antoine van Leeuwenhoek, Louis Pasteur, Rudolf Virchow (an early inspiration for the book) to more recent pioneers such as Paul Nurse, Lee Hartwell and Tim Hunt.
A recurring theme, as stated in the book’s subtitle, is that of the ‘new human.’ Mukherjee explains that he is not using the term in the sense of a sci-fi character or in the sense of transhumanism (humans endowed with additional genes or traits). Rather, he refers to humans ‘rebuilt anew with modified cells,’ who look and feel just like anyone else. I’m not convinced that the ‘new human’ thesis is fully justified — we simply don’t have too many examples to go on at present. One recent success story is Alyssa, an English teenager treated at Great Ormond Street Hospital in London with a modified version of CRISPR called base editing to combat her acute leukemia.
Mukherjee doesn’t care to speculate too much about the future of medical therapies using advanced technologies such as synthetic biology. (For that, readers might consider a book such as The Genesis Machine by Amy Webb and Andrew Hessel). Rather, it’s left to the reader to extrapolate from the selected examples offered in the book.
That said, Mukherjee envisions a future in which ‘we learn to manipulate [cells] into new forms, or perhaps even create synthetic versions of cells, and parts of humans.’ An inspiring example is Emily Whitehead (to whom the book is dedicated). In March 2012, six-year-old Emily became one of the first patients to receive an experimental new cellular therapy at Children’s Hospital of Philadelphia. Two years earlier, she was diagnosed with a drug-resistant form of acute lymphoblastic leukemia.
Doctors led by Carl June trialed an experimental CAR-T cell therapy, in which Emily’s T cells (a form of white blood cell) were extracted, genetically modified, and reinfused into her body. Three days later, however, Emily’s kidneys shut down and, on the verge of multi-organ failure, she was rushed to intensive care. ‘We thought she was going to die,’ June recalled, even drafting an email to the university provost to prepare for the worst. But after treatment to calm the cytokines raging in her body, Emily made a remarkable recovery — and has been in remission ever since. If Emily had not survived, the entire field of cellular therapy would have been dealt a devastating setback.
What sets Mukherjee apart is not just the assured expertise he brings to his subjects from his front-row seat as a physician. He also writes with a trademark elegance and elan that few authors can match (I’m frequently reminded of former New York Times science writer Natalie Angier). A few sections in the book in particular stood out for me. One is in his writing about blood, which should not come as a surprise as the author originally trained as a hematologist.
‘I spend most of my Mondays with blood,’ Mukherjee writes. ‘I arrive much earlier than my patients, when the morning light is still aslant across the black slate of the lab benches … I sit by the microscope in the darkened room, a notepad by my side, and whisper to myself as I go through the slides … I love looking at cells, in the way that a gardener loves looking at plants … Blood speaks to me — but only if I pay attention.’
Mukherjee devotes one of the six main sections of the book to blood, masterfully teasing out the functions of various blood cell types — the restless cell, the healing cell, the guardian cell, the defending cell, the discerning cell, and the tolerant cell. He returns to blood in closing the book with a belated reference to ‘the first molecular disease’ — sickle cell anaemia. Thanks to the advent of CRISPR and genome editing, dozens of patients have essentially been cured over the past few years in an ongoing clinical trial using the CRISPR ‘genetic scissors.’ This controlled act of DNA surgery ingeniously switches on expression of a gene that encodes one of the subunits of fetal hemoglobin, a perfect substitute for the globin chain containing the sickle cell mutation. Adult hemoglobin is thus transformed into a fetal facsimile – or as Mukherjee puts it, ‘old blood becomes young.’
Another standout section sees the author discuss his own mental health. In 2017, he writes, he was overcome by a wave of depression, probably not unrelated to his father’s death the previous year. In the book, he describes a productive conversation with his friend Paul Greengard, a renowned neuroscientist at Rockefeller University who died in 2019. Greengard told him that depression is not just a wiring problem but a cellular disorder, in which chemical signals malfunction and create a dysfunctional state in a neuron. Deep brain stimulation, or ‘cell circuit therapy’ is a promising approach for a variety of neuropsychiatric disorders.
As The Song of the Cell took shape during the height of the COVID pandemic, Mukherjee observes that the triumphalism surrounding the rapid development of RNA vaccines ‘fails in the face of more than 6 million deaths.’ It is a poignant reminder of the work ahead. As Mukherjee writes: ‘[The pandemic] exposed gaping fissures in our understanding … I cannot think of a scientific moment that has revealed such deep and fundamental shortcomings in our knowledge of the biology of a system that we had thought we knew. We have learned so much. We have so much left to learn.’