Featured in the
Time 100 list of most influential people, Mukherjee writes for The New Yorker and is a columnist in The New York Times. 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.[9] His research concerns the physiology of cancer cells, immunological therapy for blood cancers, and the discovery of bone- and cartilage-forming stem cells in the vertebrate skeleton.[10]
Siddhartha Mukherjee was born to a
Bengali Brahmin family in New Delhi, India. His father, Sibeswar Mukherjee, was an executive with
Mitsubishi, and his mother Chandana Mukherjee, was a former school teacher from Calcutta (now
Kolkata). He attended
St. Columba's School in Delhi, where he won the school's highest award, the 'Sword of Honour', in 1989. 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. He earned membership in
Phi Beta Kappa[12] in 1992, and completed his Bachelor of Science (B.S.) degree in 1993.[1]
Mukherjee is a trained
haematologist and oncologist whose research focuses on the links between normal
stem cells and cancer cells. Through his findings, he had shown the roles of cells in cancer therapy.[21] He has been investigating the microenvironment ("
niche") of stem cells, particularly on
blood-forming (haematopoietic) stem cells. Blood-forming stem cells are present in the
bone marrow in very specific microenvironments.
Osteoblasts, cells that form bone, are one of the principal components in this environment. These cells regulate the process of blood cell formation and development by providing them with signals to divide, remain quiescent, or maintain their stem cell properties.[22] Distortion in the development of these cells results in severe blood cancers, such as myelodysplastic syndrome and leukemia.[23] Mukherjee's research has been recognised through many grants from the
National Institutes of Health and from private foundations.[10][24][25]
Mukherjee and his co-workers have identified several genes and chemicals that can alter the
microenvironment, or niche, and thereby alter the behavior of normal stem cells, as well as cancer cells.[26][27][28][29][30][31] Two such chemicals – proteasome inhibitors[26] and activin inhibitors[32] – are under clinical trials.[33][34] 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.[35][36]
Bone formation
Mukherjee's team is also known for defining and characterizing skeletal stem/progenitor cells (also called osteochondroreticular or OCR cells). In 2015, they prospectively identified these progenitor cells from bone, and showed, using lineage tracing, that these cells can give rise to bone, cartilage, and
reticular cells (hence the term "OCR" cells). They established that these cells form a part of the adult skeleton in vertebrates, and that they maintain and repair the skeleton.[37]
OCR cells are among the newest progenitor cells to be defined in vertebrates.[38] The work generated wide interest and was described in journals as a major breakthrough for understanding biology and for understanding diseases such as
osteoporosis and
osteoarthritis.[39][40] Mukherjee's team have shown that OCR cells can be transplanted into animals, and they can regenerate cartilage and bone after fractures.[37] With Daniel L. Worthley's team at the University of Adelaide and South Australian Health and Medical Research Institute they have been working on the
translational cell-based research on osteoarthritis and cancer.[37][41]
Metabolic therapies for cancer
Mukherjee's lab has also been investigating the interaction between cancer genetics and the microenvironment, including the metabolic environment. It has been well established that metabolism in cancer is fundamentally altered,[42] Mukherjee's team has found the role of a high-fat, adequate-protein, low-carbohydrate diet (
ketogenic diet) in cancer therapy. 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.[43]
Immune therapies for acute leukemia
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.[44] They have combined CAR-T therapies with genetically modified hematopoietic stem cells to specifically target malignant hematopoietic lineages, while transplanted stem cells replenish the lineage but remain antigenically concealed. This technology has been developed so that, in addition to B cell malignancies, other lineage specific cancers could be targeted.[45] This provides an important new approach to managing acute myeloid leukemia.[46]
Books
In 2010,
Simon & Schuster published his book The Emperor of All Maladies: A Biography of Cancer[47] detailing the evolution of diagnosis and treatment of human cancers from ancient Egypt to the latest developments in
chemotherapy and
targeted therapy.[48] On 18 April 2011, the book won the annual
Pulitzer Prize for General Non-Fiction; 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."[49] It was listed in the "All-Time 100 Nonfiction Books" (the 100 most influential books of the last century)[4] and the "Top 10 Nonfiction Books of 2010" by Time in 2011.[50] It was also listed in "The 10 Best Books of 2010" by The New York Times[51] and "Top 10 Books of 2010" by O, The Oprah Magazine.[52] In 2011, it was nominated as a
National Book Critics Circle Award finalist.[53]
Mukherjee's 2016 book The Gene: An Intimate History provides a history of genetic research, but also delves into the personal genetic history of the author's family, including mental illness. The book discusses the power of genetics in determining people's health and attributes, but it also has a cautionary tone to not let genetic predispositions define fate, a mentality that led to the rise of
eugenics in history and something he thinks lacks the nuance required to understand something as complex as human beings.
Harriet Hall describes Cancer and The Gene as "the story of science itself".[56]The Gene was shortlisted for the
Royal Society Insight Investment Science Book Prize 2016, "the Nobel Prize of science writing".[57] The book was also the recipient of the 2017
Phi Beta Kappa Society Book Award in Science.[58]
Ken Burns made a two-part PBS Television documentary film The Gene: An Intimate History in 2020.[59]
In his book The Song of the Cell, published in 2022, Mukherjee describes the history and medical mystery from the discovery of cell. Narrated in metaphors, many of which he created, such as "gunslinging sheriff" for antibody and "gumshoe detective" to
T cell, he tells the development of cell biology and how it became vital to modern medicine, from genetic engineering to immunotherapies.[60]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".[61]
Chance events—injuries, infections, infatuations; the haunting trill of that particular nocturne—impinge on one twin and not on the other. Genes are turned on and off in response to these events, as epigenetic marks are gradually layered above genes, etching the genome with its own scars, calluses, and freckles.[62]
Mukherjee also claimed that understanding of epigenetics "would overturn fundamental principles of biology, including our understanding of evolution," as he said:
Conceptually, a key element of
classical Darwinian evolution is that genes do not retain an organism's experiences in a permanently heritable manner.
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.
Darwin discredited that
model. Giraffes, he proposed, arose through heritable variation and
natural selection—a tall-necked specimen appears in an ancestral tree-grazing animal, and, perhaps during a period of famine, this mutant survives and is naturally selected. 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.[62]
The article, an excerpt from the chapter "The First Derivative of Identity" of his book The Gene: An Intimate History,[63] "unleashed a torrent of criticism" from geneticists, as The Guardian book review wrote.[64] As David Hornby of the University of Sheffield put it: "all (scientific) hell broke loose! It seemed to some that the slumbering giant of Lamarck was about to gain a new audience."[65] Mukherjee foresaw the reaction, as he noted: "These fantasies should invite skepticism."[62]
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. They commented that these two processes have only minor influences in overall gene function.
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."[66] Omission of transcription factors was viewed as an "overarching" mistake,[67] 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."[66]
It is now generally believed that histone modification and DNA methylations are major factors of epigenetic functions, aging and certain diseases,[68] and with an ability to influence
transcription factors.[69] However, they contribute little to development.[70][71] In response, Mukherjee did admit that omission of transcription factors "was an error" on his part.[66] However, The New Yorker defended the article that: "None of it negates the fundamental importance of transcription factors."[67]
Jerry Coyne of the University of Chicago remarked: "Until there is evidence for this kind of evolutionary transformation—ANY evidence, people should stop yammering about this kind of 'Lamarckian' evolution."[72] Phillip Ball, British science writer and editor of the journal Nature, also agreed that Mukherjee certainly "got some things wrong". Writing in the
Prospect, he said, "Such claims [that some epigenetic changes can be inherited] are controversial—but even if they prove to be true, it seems highly unlikely that the effect will persist for many generations of will have long-term consequences for human evolution."[72] 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.[73]
Mukherjee did not say that epigenetic processes have established Lamarckism, as he noted in his article that "epigenetic scratch marks are rarely, if ever, carried forward across generations."[62] In an interview on
NPR, he said, "[Lamarckian inheritance is] very rarely true and I would say almost never true".[74]
Mukherjee also criticises the
IQ test as a measure of intelligence, and endorses the
theory of multiple intelligences (introduced by
Howard Gardner) over
general intelligence. He argues that the results of IQ tests for determining general intelligence do not represent intelligence in the real world. 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."[75]
2017: Phi Beta Kappa Society Book Award in Science for The Gene.[58]
2017: Wellcome Book Prize (shortlisted) for The Gene.[86]
2018: Honorary doctorate degrees in medicine from the Royal College of Surgeons of Ireland,[87] and from the University of Southern California.[88]
2023: The Song of the Cell: An Exploration of Medicine and the New Human. Notable Book, American Library Association. Reference and User Services Association.[89]
Mukherjee lives in New York and is married to artist
Sarah Sze, winner of a
MacArthur "Genius" grant and representative of the United States to the 2013
Venice Biennale. They have two daughters, Leela and Aria.[92]
^
abNew York Times Sunday Book Review Editorial Staff (24 November 2010).
"100 Notable Books of 2010". New York Times Magazine. Retrieved 28 September 2014.
^Dimopoulos, Meletios A; Goldschmidt, Hartmut; Niesvizky, Ruben; Joshua, Douglas; Chng, Wee-Joo; Oriol, Albert; Orlowski, Robert Z; Ludwig, Heinz; et al. (2017). "Carfilzomib or bortezomib in relapsed or refractory multiple myeloma (ENDEAVOR): an interim overall survival analysis of an open-label, randomised, phase 3 trial". The Lancet Oncology. 18 (10): 1327–1337.
doi:
10.1016/S1470-2045(17)30578-8.
PMID28843768.
^Komrokji, Rami; Garcia-Manero, Guillermo; Ades, Lionel; Prebet, Thomas; Steensma, David P; Jurcic, Joseph G; Sekeres, Mikkael A; Berdeja, Jesus; et al. (2018). "Sotatercept with long-term extension for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes: a phase 2, dose-ranging trial". The Lancet Haematology. 5 (2): e63–e72.
doi:
10.1016/S2352-3026(18)30002-4.
PMID29331635.
^McGonagle, Dennis; Jones, Elena A. (2015). "A new in vivo stem cell model for regenerative rheumatology". Nature Reviews Rheumatology. 11 (4): 200–201.
doi:
10.1038/nrrheum.2015.21.
PMID25734973.
S2CID29933567.
^López, V.; Fernández, A.F.; Fraga, M.F. (2017). "The role of 5-hydroxymethylcytosine in development, aging and age-related diseases". Ageing Research Reviews. 37: 28–38.
doi:
10.1016/j.arr.2017.05.002.
PMID28499883.
S2CID3748806.
^"Padma Awards Announced". Press Information Bureau, Ministry of Home Affairs, Government of India. 25 January 2014. Archived from
the original on 22 February 2014. Retrieved 26 January 2014.