Siddhartha Mukherjee on New Book “Song of the Cell”

CHRISTIANE AMANPOUR, HOST: Now, the integrity of democracy is not the only issue, an institution that needs protection. Our next guest is keen to highlight another. The Pulitzer prize-winning author, Dr. Siddhartha Mukherjee believes we are living in an anti-science moment. That’s despite new medical breakthroughs, helping ill patients defy the odds. He details some of these stories in his new book, “The Song of The Cell”. And here he is with Walter Isaacson.

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WALTER ISAACSON, HOST: Thank you, Christiane. And Siddhartha Mukherjee.

SIDDHARTHA MUKHERJEE, AUTHOR, “THE SONG OF THE CELL”: Thank you for having me.

ISAACSON: This great new book, “The Song of The Cell”, is really the third in the series after your “Emperor of All Maladies” about cancer, and then “The Gene”, a very personal book about how the genes determine everything from our health to our mental health. Tell me why you did this book now on the cell?

MUKHERJEE: This book is a follow-up from “The Gene”, because while I was writing “The Gene”, I realized that a gene is an incredibly important unit of information that codes for all of the things that happened in life. But a gene itself is lifeless without a cell. It’s a molecule. It’s a chemical. Ironically, “The Gene” encoded in the DNA, the double helix, has become the iron of life. You know, when you see a portrait of life, you always see the double helix. But in fact, it is the cell that enlivens the gene. And finally, we’re beginning to enter the century of the cell, which we’re beginning to enter a time when we can manipulate cells using genes, using gene therapies, using medical therapies, et cetera. It is one of the most exciting times for the biology of cells and learning the biology of cell. And so, I thought that this book was very timely to convey the excitement and also the potential of what we can do as we learn more and more about cells.

ISAACSON: You have called this book, “The Song of The Cell”. And it seems to me there’s a metaphor there, because a cell is like a single note. But when they come together, the song is different. It is greater than just the individual notes.

MUKHERJEE: Absolutely. And there are two metaphors there. One is the one you just described, which is that multicellular organisms develop songs. They develop songs in the sense that they can communicate with each other, they mix with each other, and they can create properties, emergent properties, that could not be present in a single cell alone. So, there is a song there. The second metaphor is the one that we had started off with which is that genes are like a musical score. But a score is not music. It needs a musician to play it. And it’s the cell that plays out that music. It plays out the genome. It plays the — as it were, the score or the orchestra of the genome until it becomes a song.

ISAACSON: You know, when I was reading your book, it seems like the metaphor is there with the book itself. Because unlike some of your other books, it’s not just a pure narrative. There’s lots of little cells. It’s like a collection of cells, your book is, and then they come together. Was that intentional to use the cellular formation as a metaphor for the book?

MUKHERJEE: When you write a book, it’s — you know, like, “The Song of The Cell” explaining the history and the future and the excitement of cell biology, you have to think about structure. And usually often, you know, you form — you follow historical narrative. You follow time. The problem with following time, in this case, is that multiple discoveries in cell biology were happening at the same time. And it would be impossible — you would have to flip from one cell type to another cell type, to another cell type, to another cell type, another cell type. It’s not like DNA or the gene where you’re, sort of, essentially carrying out a chronological series of discoveries until you find your ultimate understanding of gene. In this case, there are multiple things that are happening at the same time, and cells are extremely diverse. And so, the only way this book could be written, so that it would not become a complete confusion, was to really imagine it as a series of almost short stories. Each one with his own chronology. So, you have a chronology of the immune system. You have a chronology of the formation of bone. You have the chronology of stem cells. You have a chronology of, you know, blood. So, each chapter, really, is a mini history. And put together, it sort of becomes the — what I call “The Song of The Cell”. So, it’s organizational structure is both a challenge, but also, I think, somewhat interesting and, I would say, to me at least, fun to write because I could write about each of these separately, like, little mini chronologies or mini short stories that then come together to form a larger picture.

ISAACSON: Like all of your books, this one is very personal and has very personal stories in it. Including Sam, the sportswriter who gets cancer. Tell me about him and how the story of his cancer helped you understand the cell.

MUKHERJEE: Well, just — the book opened with two very contrasting stories. Both of which involved cancer. So, the Sam, the sportswriter, and Emily Whitehead, the young lady, young woman with leukemia. In both cases, we used two different forms of immunotherapy. So, let’s focus on Sam. In Sam’s case, we used — doctors, a friend of mine, and doctors used a kind of immunotherapy that uncloaks the cancer cells that have cloaked themselves and made themselves invisible to the immune system. There are new medicines, many of us are familiar with them. There are new medicines that enable us to uncloak a cancer cell because cancer cells builds, sort of, invisibility around them to survive the — an immune attack. These medicines uncloak that and make the cancer revisable or visible to the immune system. The trouble was that when you uncloak a cancer cell and make it visible to the immune system, you also uncloak the normal cells in your body and make them visible to the immune system and you get, as a side effect of these medicines, you get autoimmune diseases. And in Sam’s case, he got autoimmune hepatitis — autoimmune disease of the liver. So, every time he would increase the dose of these uncloaking medicines, taking away the invisibility cloaks of cancer, we would also, though, unfortunately, spur or spark the autoimmune disease in the liver. And there was no place that we could find in Sam’s case, sadly, where there was the exact right level of medicine that would make the immune system attack his cancer, but not attack his liver. And unfortunately, he died because we could never find that right spot, the sweet spot where we could just attack his cancer without simultaneously killing off his liver cells.

ISAACSON: Throughout this book, you talked, not only about the historical figures, but you go back to poets and to philosophers. In fact, you go all the way back to Aristotle in the middle of the book. How does that help us understand?

MUKHERJEE: Well, I think it is important to understand the idea — for people to understand the idea that science is a continuous conversation that, you know, goes all the way back to (INAUDIBLE). It’s not like, you know, pathology or our desire to solve illness, suddenly, sort of, sprung (ph) about in the 18th century, or our desire to understand the human body sprung about in the 19th century. People like Aristotle — philosophers like Aristotle and others in various cultures have for, really centuries, been trying to understand the body. Been trying to understand inheritance, trying to understand what makes someone sick. Is it a divine phenomenon? Is it, you know, is it a mental problem? Et cetera, et cetera. So, I wanted to show that there is a lineage of conversations that extends way back into philosophers such as Aristotle. In fact, for the longest time in history, they — you know, scientists were called natural philosophers. There were term natural philosophers because they — there was really no distinction made in them and philosophy. And so, it’s really important to understand that that lineage is a continuous lineage and is very important for our contemporary understanding of science and how we do science. And, you know, we’re living in an age where it’s very — it’s — we’re living in a very anti-science moment, politically. People have distrust science. People think that, you know, scientists are egg heads who are out to make the world worst. And it’s very important to remember that that is really not the case. Scientists are trying to find out how the world works, how nature works, and have been doing so, not just yesterday or the day before yesterday. They have been doing so for generations, going all the way back to very revered figures such as Aristotle.

ISAACSON: In your book, and in your book “The Gene”, you talk about the mental illness that affects your family. Madness, you say, runs in the Mukherjee family. Tell me about that personal experience and as you deal with it in this book and in “The Gene” how that drives your thinking.

MUKHERJEE: Well, the idea of mental illness is very important because it drives a particular way of thinking of, you know, about suffering. In this book and in “The Gene”, I make a very important distinction between disease and desire. Suffering — diseases is suffering. Disease has fundamentally to do with suffering. Desire, on the other hand, has to do with augmentation, making ourselves better, and trying to be taller, stronger, live longer, et cetera. Medicine has made a very strong distinction between suffering and augmentation, or enhancement. Mental illness is an incredible arena where we can really explore, I think, our understanding of suffering, and I explored it in my own family and myself, and distinguish it from other forms of illness because mental illness — one of the problems with mental illness is that that it’s very – – it’s abstract. You don’t have a lump in your body. You don’t have a tumor growing somewhere. It is the state of your brain. And therefore, I think, for many years it was neglected. Depression was a neglected disease. Schizophrenia is a poorly understood disease partly because they are so abstract. But they are very much low side of suffering. And so, I wanted to be — I wanted to show or demonstrate the idea that can be suffering and suffering that maybe — that has to do with genes or with cells, that may be more protean and more abstract than, as I said, a lump growing in your body or an autoimmune disease where you have manifestations on — in your skin. And I wanted to show or demonstrate that that suffering is as real for me, my family, and for all the people who suffer from mental illness, as any other physical manifestation of illness. And that’s why it sort of comes a little — comes up in the book, in book “Gene” and in “The Cell”.

ISAACSON: To what extent are you driven by your own personal biography?

MUKHERJEE: Well, the idea of a personal biography in a book is very important to me. Because, again, it’s very easy to write a book as, you know, you’re an abstract off the object. You’re, sort of, you’re the narrator but you keep a distance from all of this. For me, that book is less personal. It’s not — it’s less readable, it’s less relatable. I want people to understand that who — I want people to understand who is writing this book and from what viewpoint and why. What is the drive behind the book? What drives me? Who am I? And why, you know, why have I chosen to write this book? What is driving me in this particular book? So, I find the personal memoir aspects of it, again, enliven the book as me — for me as a writer and hopefully, enliven the book for the reader as well because they can understand who I am, where I am coming from, and what drives the — what the drives and passions of the book are.

ISAACSON: The subtitle of your book refers to the new human. Tell me what your vision of what the new human could be.

MUKHERJEE: Well, the new human is a provocative subtitle. And it’s provocative because, you know, I think for a long time, we’ve been thinking about the so-called new human as a kind of prosthetic sci-fi version, infrared equipped and, what I call, Keanu Reeves in a black moon from the “Matrix”. For me, the new human is not that. The new human for me, the capacity of cellular engineering, rebuilding bodies to cells. The capacity of cell engineering and genetic engineering of our body before gene engineering has really cellular therapy or cell engineering. You put the gene in the wrong cell, you don’t get any genetic immune (ph). That capacity, the capacity to transplant cells, to move cells between bodies, to rebuild of the human from our acomistic (ph) blocks, from you know, cell by cell, as it were stem cells that rejuvenate entire blood systems. The capacity for us to be able to put electrodes in our brains and stimulate cells so that we can battle diseases like, you know, really treatment resistant depression. All of these are, to me, new humans. These are not augmented humans. These are humans in whom we’re using cells to rebuild degenerating or dysfunctional organs and organ systems and cellular systems, such that they can be relieved from dysfunction disease.

ISAACSON: You are a great cancer researcher. Tell me what cellular biology is going to do next in our fight against cancer.

MUKHERJEE: So, I would say two things. First of all, cellular biology will help us understand the cancer cell in a deeper way. So far, a lot of cancer biology has been focused appropriately on cancer genetics, which is important. Cancer is a disease of mutated genes. But the cellular biology of cancer still remains quite unknown. So, for instance, how do cancers form homes for themselves? How do they blow out of blood vessels? I mean, these are questions that have, you know, permeated the field for a long time, but we’re finally getting answers to them. How do cancers become invisible to the immune system? Why, and this is a very important question, why do cancers metastasize to certain organs such as the liver, but don’t metastasize to an adjacent organ, the spleen? That doesn’t have to do — you can read the genome of a cancer cell, or a genome of a normal cell. The genome will not give you the answer to those questions. It’s only cell biology that will give you the answer to the question. Cancer cell biology. And the second is that now we can potentially use our understanding of cell biology, especially the immune system, to direct new medicines against cancer. And it’s not just the immune system. There are other systems, understanding the homes that cancers build around themselves. Understanding how they metastasize at a cellular level will hopefully create a whole new vision of medicines that we will be able to use against cancer. So, both, I would say, understanding cancer and directing therapies against cancer depend on our understanding of cell biology and the cell biology of cancer.

ISAACSON: Siddhartha Mukherjee, thank you so much for joining us.

MUKHERJEE: Thank you, Walter.