He is described as part of a select group of doctor-writers (such as Oliver Sacks and Atul Gawande) who have "transformed the public discourse on human health",[8] and allowed a generation of readers a rare and intimate glimpse into the life of science and medicine.

As a biology major at Stanford University, he worked in Nobel Laureate Paul Berg's laboratory, defining cellular genes that change the behaviours of cancer cells.

[15][16] In 2009, Mukherjee joined the faculty of the Department of Medicine in the Division of Hematology/Oncology at the Columbia University Medical Center as an assistant professor.

[20] In January 2025, Mukherjee launched Manas AI, an AI-enabled drug discovery startup, together with Reid Hoffman, with about $25 million in venture capital funding.

[34][35] Mukherjee's lab has also identified novel genetic mutations in myelodysplasia and acute myelogenous leukaemia and has played a leading role in finding therapies for these diseases.

[40][41] Mukherjee's team have shown that OCR cells can be transplanted into animals, and they can regenerate cartilage and bone after fractures.

They showed that ketogenic diet suppressed insulin production in the body, and this in turn enhances pharmaceutical inhibition of PIK3CA, a gene which is mutated and commonly overactive in cancers.

[44] Mukherjee's lab, with the help of PureTech Health plc, has been investigating chimeric antigen receptor redirected T cells (CAR-T) therapy in a joint venture called Vor BioPharma since 2016.

[49] On 18 April 2011, the book won the annual Pulitzer Prize for General Nonfiction; the citation called it "an elegant inquiry, at once clinical and personal, into the long history of an insidious disease that, despite treatment breakthroughs, still bedevils medical science.

[54] Based on the book, Ken Burns made a PBS Television documentary film Cancer: The Emperor of All Maladies in 2015,[55] which was nominated for an Emmy Award.

[61] Suzanne O'Sullivan, reviewing in The Guardian, explains the book as a tool for "the reader to imagine they are an astronaut investigating the cell as if it is an unknown spacecraft".

In his 2016 article "Same but different" in The New Yorker, Mukherjee attributed the most important genetic functions to epigenetic factors (such as histone modification and DNA methylation).

Jean-Baptiste Lamarck, in the early nineteenth century, had supposed that when an antelope strained its neck to reach a tree its efforts were somehow passed down and its progeny evolved into giraffes.

But, if epigenetic information can be transmitted through sperm and eggs, an organism would seem to have a direct conduit to the heritable features of its progeny.

Such a system would act as a wormhole for evolution—a shortcut through the glum cycles of mutation and natural selection... Lamarck is being rehabilitated into the new Darwin.

"[63] The article was critiqued by geneticists such as Mark Ptashne, at the Memorial Sloan Kettering Cancer Center, and John Greally, at the Albert Einstein College of Medicine, because of overemphasis on histone modification and DNA methylation.

Steven Henikoff, at the Fred Hutchinson Cancer Research Center, opined that, "Mukherjee seemed not to realize that transcription factors occupy the top of the hierarchy of epigenetic information," and said, "histone modifications at most act as cogs in the machinery.

"[67] Omission of transcription factors was viewed as an "overarching" mistake,[68] as Richard Mann at the Columbia University Medical Center remarked: "Only a talmudic-like reading can reveal a hint that something other than histone modifications are at play.

"[73] Phillip Ball, British science writer and editor of the journal Nature, also agreed that Mukherjee certainly "got some things wrong".

"[73] According to Ute Deichmann of the Ben-Gurion University of the Negev, even if there are evidences of variation by epigenetic inheritance, they would not be counted as Lamarckian as they are not acquired or adaptive.

Reviewing the book in The Spectator, Stuart Ritchie, a psychologist at the University of Edinburgh, remarked that Gardner's theory is "debunked" and that "general intelligence is probably the most well-replicated phenomenon in all of psychological science.