Begin at the beginning, inside a cell. That’s where the mystery starts. Float around in the protoplasm for a while, inspecting the nucleus, looking for broken cogs, rusty machinery. Squeeze through the membrane pores and inspect the surface proteins there. Cells tell stories if you look closely enough. If you know how to read them.
“Cells speak to me, especially blood cells,” says Siddhartha Mukherjee, ’93, the Pulitzer Prize–winning physician-author. He’s seated at a microscope in his Columbia University oncology lab on a snowy winter morning, peering inside white blood cells—immune cells designed to fight off infections—in a smear of bone marrow on a glass slide. Cancer can hijack these cells, destroying the body’s ability to fight infection. He describes these mornings in his latest book, The Song of the Cell.
“On Monday, I arrive much earlier than my patients, when the morning light is still aslant across the black slate of the lab benches. I close the shutters and peer through the microscope at blood smears,” he writes. “The slides are like previews of books, or movie trailers. The cells will begin to reveal the stories of the patients even before I see them in person.”
Mukherjee, both a hematologist and an oncologist, transforms the stories hidden within our cells into massive, bestselling books that explore what it means to be human in a world where cells define all life. His three best-known titles journey first through the history of cancer, then genes, and finally cells, building metaphors and asking weighty questions about the foundations of science and where it is headed. Then he takes what he learns from his explorations in writing and returns to the laboratory with new ideas for treating patients. Those explorations, in turn, feed his work with four biotech start-ups he co-founded—three in the United States and one in India—that are developing therapies for leukemias and other blood cancers.
“Sid thinks big and sees big,” says Atul Gawande, ’87, himself the author of four bestselling books on medicine, a surgeon, and a friend of Mukherjee’s. “He’s able to see the entire landscape of cancer, the gene, and then the cell, and then on and on. He’s driven by understanding at the molecular level what our lives are like as an organism, and even at the societal level. That’s how he makes sense of the world.”
‘Sid thinks big and sees big. He’s able to see the entire landscape of cancer, the gene, and then the cell, and then on and on.’
From the microscope room, Mukherjee walks down a hall, past the lab’s work benches, into his office. The phone rings. It’s his wife, the sculptor Sarah Sze, calling from across town, where she’s installing an exhibit at the Guggenheim Museum, to remind him to pick up one of their daughters after school—they have two, ages 13 and 18. (In 2016, Vogue magazine ran a photo of Mukherjee and Sze in her New York studio under the headline “Meet the Most Brilliant Couple in Town.”) The pair were recruited together to Columbia in 2009, where Mukherjee is an assistant professor of medicine and Sze is a professor of visual arts.
Mukherjee apologizes for his messy office, but it’s not messy, really, just a reflection of the many different directions his mind spins. Leaning back in his chair, he surveys the books and papers scattered across his desk, which is next to an overfilled bookshelf. History, medicine, science, literature—he quotes from across disciplines not only in his writing but also in his daily conversations. He has a particular fondness for the playwright Anton Chekhov, who, he likes to point out, was also a physician. “I read all the time,” he says. He reads in bed, at the kitchen table, in his lab, on planes. That’s how he writes, as well—whenever he gets a free moment. He nods toward what he calls “his famous red writing bed.” It’s a cot, now faded orange, covered with an old quilt.
Mukherjee’s books, beginning with The Emperor of All Maladies, which tells a history of cancer and won the 2011 Pulitzer Prize for general nonfiction, are talked about in the scientific community “with some kind of awe,” says Irving Weissman, a Stanford professor of pathology and of developmental biology who is renowned for his stem cell research. The Gene, Mukherjee’s 2016 bestseller, charts the discovery of the basic unit of heredity, from Gregor Mendel’s wrinkled peas to the genetic engineering tool CRISPR. And The Song of the Cell, published in 2022, is a 496-page crash course in cellular biology—one that helps readers understand the significance of medicine’s cellular therapies and the promise they hold for treating anything, or maybe everything, that ails us.
What’s special about Mukherjee, Weissman says, is that he thinks deeply about the world of science and medicine and can translate that to the public. “Being creative in two fields and having the desire to try to help people with your creativity—well, I think that encapsulates Sid.”
Life’s Work
Mukherjee was fascinated with cells early on. But then he was interested in so many things. Born in Delhi in 1970, he trained as a singer of Indian classical music, learned languages easily, and explored everything from science to poetry to art to philosophy. He remembers a biology teacher who talked about the big unanswered questions in the field, like how do your cells take on different functions, since they all contain the same DNA? How do they form an organism?
As an undergraduate at Stanford, he worked in the lab of Nobel laureate Paul Berg, famous for his recombinant DNA research that led to gene splicing and helped launch the biotech industry. He liked how Berg’s career brokered the worlds inside and outside the lab. “Paul was one of the global leaders in what is now the field of the ethics of genetics,” Mukherjee says. “I was very interested in ethics.” After graduating, he moved to England to attend Oxford University on a Rhodes scholarship, where he lived the life of a scientist, immersed in the world of immune cells, T-cells, and cell surface proteins. His PhD in immunology provided some of the keys to unlocking future therapies. To truly understand medical science, though, he believed he needed to learn from patients as well, so he moved to Boston, where he enrolled in medical school at Harvard.
During an oncology fellowship at the Dana-Farber Cancer Institute in Boston, Mukherjee faced daily life-or-death decisions about patient treatments. That’s when he started keeping a journal, trying to make sense of so much suffering. The Emperor of All Maladies draws from those experiences—“an epic story that he seems compelled to tell, the way a passionate young priest might attempt a biography of Satan,” wrote Jonathan Weiner in a New York Times review of the book.
“[As] I emerged from the strange desolation of those two fellowship years, the questions about the larger story of cancer emerged with urgency,” Mukherjee wrote in the book’s prologue. “How old is cancer? What are the roots of our battle against this disease? Or, as patients often asked me: Where are we in the ‘war’ on cancer? How did we get here? Is there an end? Can this war even be won?” Mukherjee spent five years reading scientific papers and history books, and interviewing physicians, scientists, and patients. Among his chapters are the stories of Atossa, the Persian queen whose Greek slave cut off her cancerous breast, and the primitive radiation and chemotherapy treatments of the early 20th century.
“I was thinking, ‘Who is going to read 600 pages on cancer?’ ” Sze recalls. “ ‘It sounds like a real downer.’ ” She admits now that she couldn’t have been more wrong.
The book begins on May 21, 2004, just after Mukherjee’s patient Carla Reed was admitted to the cancer ward on the 14th floor of Massachusetts General Hospital. The 30-year-old kindergarten teacher and mother of three from Ipswich, Mass., was diagnosed as having acute lymphoblastic leukemia (ALL). ALL grows out of the bone marrow, where it produces white blood cells that don’t look normal under a microscope. Reed’s were broken cells, unable to fight off infections. And they would multiply quickly, crowding out the healthy blood-forming cells needed for life. “Leukemia is cancer of the white blood cells—cancer in one of its most explosive, violent incarnations,” Mukherjee wrote. “Its pace, its acuity, its breathtaking, inexorable arc of growth forces rapid, often drastic decisions; it is terrifying to experience, terrifying to observe, and terrifying to treat.”
That first day in the hospital, Mukherjee told Reed her chances of survival were 30 percent and that chemotherapy would begin immediately. He would infuse toxic chemicals into her body repeatedly over the coming months. She slept poorly, her hair fell out, she couldn’t eat. Treatment after treatment, lying on a table, she told Mukherjee she often wondered whether she would ever wake up.
“Walking across the hospital in the morning to draw yet another bone marrow biopsy, with the wintry light crosshatching the rooms, I felt a certain dread descend on me,” Mukherjee wrote, “a heaviness that bordered on sympathy but never quite achieved it.” It wasn’t the first time he’d realized the need to create space for himself, separate from his patients. In 2002, he’d attended an exhibition at the Museum of Fine Arts, Boston, where he met the artist. They fell in love, and after their wedding in 2004, Sze remembers her new husband being overcome by worry for his patients. But she also remembers how, even then, he continued to think on a grand scale. Late one night, she joined him for dinner at the hospital cafeteria.
“Everyone was in scrubs, looking worn out,” Sze remembers. “We were having something like mac and cheese, I don’t know, it was all looking very grim. He told me: ‘There are two things I want to do. I either want to write a book about cancer or start a hospital in India.’ I thought, ‘Great, sweetheart, there goes your beeper.’ ”
Reed would fully recover, rejoining the life of her family. For Mukherjee, watching such transformations were among the most “sublime moments of my clinical life.” He set out to recapture that feeling again and again.
Family Stories
The Gene elevated public discussion about genetic research, just as The Emperor had done for cancer. “First the idea of the gene had to be invented. Then the physical entity, present in each cell of our bodies, in every living thing, had to be discovered,” wrote James Gleick in a New York Times review. “The story of this invention and this discovery has been told, piecemeal, in different ways, but never before with the scope and grandeur that Siddhartha Mukherjee brings to his new history.”
In the story, Mukherjee writes of family distress and mental illness as he explores the intersections of biological inheritance and historical trauma, of genetics versus the environment. “Madness has been among the Mukherjees for generations,” he writes. In Delhi, he and his older sister grew up in a home that included their paternal grandmother and an uncle, her adult son, who had schizophrenia. Another of his uncles had bipolar disorder. Mental illness was seen as a family affliction. In the book, he recalls his grandmother, Priyabala, with reverence. “She weathered the buffets of heredity with something more than resilience: a grace that we, as her descendants, can only hope to emulate.” He dedicated The Gene to his grandmother and to Carrie Buck, a young woman forcibly sterilized in 1927 under Virginia’s eugenics law.
A few years later, Mukherjee turned his writerly attentions from the gene to the cell. It happened during the COVID-19 pandemic, when he was immersed in broken cells and surrounded by sickness, the ambulance sirens a constant wail outside his New York office window. He was desperate for a world of cohesion and symmetry, so he wrote about the need for balance within cells. He probed how human health depends on cellular connection, much like it does on human connection. And that brought to mind how much he had missed his family during his first year at Stanford, a story he tells in The Song of the Cell.
Through exchanging letters with his dad, he learned more about the migration journey he’d taken. Sibeswar, known as Shibu, had fled his home in East Bengal (now Bangladesh) with his mother and four brothers just before the partition of India in 1947. The upheaval was one of the most violent in world history. “Partition was the big story [that] loomed on our lives for a long time,” Mukherjee says. “It was such a traumatic event.” Through the letters, Mukherjee began to understand how hard his father had worked to build a new sense of belonging in Delhi. In the winter of Mukherjee’s frosh year, Shibu sent him a plane ticket home to India, knowing his son would need comforting. “My father was there, as he would be year after year, when I returned, with a white shawl draped around himself, and an extra one to wrap around me,” Mukherjee writes. “Coming back. Belonging.”
The Song of the Cell follows the history of scientific inquiry that eventually discovered life was built out of the microscopic units we call cells. Mukherjee’s narration keeps readers swimming through protoplasm, the living part of a cell, with its nucleus, cytoplasm, and organelles. Mukherjee discusses the ethical debates that have surrounded novel technologies such as in vitro fertilization, stem cell transplants, and gene cloning. And he explores the concerns surrounding modern-day advances in genetic manipulation, urging caution in the new world of CRISPR, a powerful gene-editing technique that he and other scientists use in their labs but that also could be used in the creation of designer babies.
“He’s very artful in telling stories that make you feel the humanity behind the science stories,” says Tyler Johnson, a Stanford clinical assistant professor of medicine in oncology and a science writer. “He’s able to demystify the inner workings of DNA and cellular metabolism in a way that is faithful to the science but comprehensible to people who are not scientists.”
Making Therapies
Mukherjee, dressed in a blue plaid suit and a black collarless shirt, with a gold ring on each hand, gets up out of his chair and strides through his office door, headed down the hall to the heart of his lab, the benchwork rooms with beakers and centrifuges and jeans-clad scientists growing cancer cells and creating therapies.
Mukherjee’s lab studies the biology of blood development in premalignant and malignant diseases such as myelodysplasia, which often advances to acute myelogenous leukemia (AML), a cancer characterized by an overproduction of immature blood cells that take over the bone marrow and pour into the bloodstream. About half a dozen projects in the lab aim to fight these diseases by using new gene-editing approaches such as base editing, which helps scientists more precisely target small, cancer-linked mutations. Most of the projects are focused on improving treatments for AML, the deadliest form of leukemia.
Abdullah Mahmood Ali, an assistant professor of medical sciences at Columbia who collaborates with Mukherjee, updates him on the progress of an experimental therapy to treat AML—a variation on bone marrow transplants that protects healthy cells from the toxicity of treatments that can kill not only cancerous cells but also healthy ones. Using CRISPR, the scientists took blood stem cells from a bone marrow donor and tweaked the cell surface proteins, which communicate with other cells, to make them “invisible” to targeted immunotherapy. Think of it as an invisibility cloak, Ali explains. The therapy is undergoing human testing at Vor Bio in Boston, a biotech start-up that Mukherjee founded.
‘My primary interest is human therapy. I like to make medicines. It’s the most exciting thing you could ever do.’
“My primary interest is human therapy,” Mukherjee says. “I like to make medicines. It’s the most exciting thing you could ever do.” When he’s in the clinic, Mukherjee treats the “sickest of the sick”—patients who have undergone chemotherapy and bone marrow transplants and still relapsed, says Azra Raza, a physician-scientist who researches blood cancers at Columbia. He then brings his motivation to cure them into the lab. “Someone like Sid comes around once in a generation,” Raza says. “He has an incredible mass of information in his head. He thinks quantum leaps ahead of other people.”
Returning Home
It’s late afternoon, and the light in Mukherjee’s office begins to fade. But Mukherjee is still thinking and talking and making plans. He talks about the art scene in New York City, visiting museums on weekends. He admits, a bit sheepishly, that he also has artistic talents. In fact, some of his obsessive doodling of molecules appears in his books. He grins. Sure, he’s obsessive about his work, but he loves his life outside the office. He and Sze throw elaborate dinner parties in their Manhattan apartment, for which he cooks. Sze describes how, when her husband likes a dish at a restaurant, he dissects it, smelling it, tasting it, talking to the chef if he can’t figure out how it was made—and then re-creates it at home. “It’s a good metaphor for how he looks at life,” Sze says. “He’s always kind of sniffing out good ideas. Always on the prowl for things to be cracked open and solved.”
The family travels every year to New Delhi. Mukherjee’s father and grandmother have passed, but his mother still lives in the home where he grew up. He also makes regular trips to Bengaluru, where his start-up Immuneel Therapeutics treats leukemia patients who have relapsed with chimeric antigen receptor T-cell (CAR-T) therapy, an approach that uses the body’s own immune system to ambush cancer cells. CAR-T therapies have been available in the United States for about a decade, treating certain blood cancers—though not AML—at a cost of around $400,000 per patient, but weren’t available in India. The first clinical trial at Immuneel plans to include up to 24 pediatric and adult patients.
“This is the first child that we treated,” Mukherjee says. He’s looking at a photo of a 9-year-old boy in India attached to an IV bag. “This is me opening his therapy line,” Mukherjee says proudly. “He was very, very sick, close to dying.” One year out from his CAR-T therapy, his cancer was in remission.
Again, Mukherjee’s cell phone starts ringing. When he hangs up, he’s strangely still. The constantly moving fingers, combing through his hair, twiddling pens, touching items on his desk, riffling papers, doodling, suddenly cease moving.
“I just heard about a friend who is dying,” he says. (Author and historian Patrick French died the next day in London.) Slouching low in his chair, Mukherjee discards his shoes, and rests his stockinged feet on the quilt-covered writing bed. He’s a great compartmentalizer, he says. That’s how he does so many things. But sometimes worlds collide, like this moment in this lab where he makes medicines and learns about a friend he can’t save. He looks at his feet resting on the cot, then touches the quilt, lovingly.
“It’s hand-blocked,” he says. “It’s special, from India, a work of art.”
Tracie White is a senior writer at Stanford. Email her at traciew@stanford.edu.
