Part one of the Siddhartha Mukherjee interview: “Even mental diseases have an impact on cellular behaviour”

One of the remarkable things you do in the book is to help link widely different ideas. After telling us about the Indian idea of “tat twam asi” and the question of “Self”, you quote Harold Varmus, the Nobel-winning cancer biologist, who called cancer a “distorted version of our normal selves.” And you mention “horror autotoxicus” – when the body poisons itself. From baldness via alopecia areata to Raynaud’s disease to Lupus – it seems the world of the body attacking itself (“its self”) is not just a puzzle but also a mystery. You write: “It’s like a fire feeding on itself: once the barrier to the self has been broken, everything that is Self can be under attack.” What does “Self” mean at a cellular level? Can there be a meaning about what Self means, as is popularly understood, at a cellular level, or is that a fallacy of composition of some sort?
I think that’s not a fallacy. The Self is obviously an extraordinarily complex thing. There’s a distinction that I make between the functional Self—the Self with agency—and the Self that has sentience and consciousness. Now, no one would say that T-cells have consciousness or sentience. They have a certain degree of agency, and they have a certain degree of autonomy. They have a certain degree of function. And so on that level, on the level of agency and function, T-cells are made and the immune system is made to distinguish Self from non-Self.

That is not to imply that they have anything beyond that, any sort of conscious function beyond that. But it is to imply that they do have properties that have to do with that agency and function. And that we need to understand those properties if we want to understand the biology of the Self.

A deeply evocative phrase in the book is “cellular civilisation”. You write about how covid was Vamana and humanity was like Mahabali – a microscopic virus that grows to swallow the world. While reading that phrase, what I realised about your writing is how you borrow metaphors wherever they come from in order to help convey a story. In one of the footnotes you mention: “I have tried to avoid an enormous amount of immunological jargon here.” Where does this facility for metaphors and images come from?
I mean, people have always talked about metaphorical language in my writing. I don’t think of them as metaphors. I think of them as stories – often minor stories. I mean, if you think about my books, they have a particular structure. There are a series of linked stories. And in a kind of almost a fractal way. If you go into the stories, there are stories within those stories. And so I don’t think of myself as a kind of explicitly metaphorical writer. I think of myself really as a storyteller. And those stories then become.

I mean if you want to call them metaphorical, yes they can be metaphorical. But those stories become parts of a much larger story and they can link together. They come back, they haunt you and I think that facility really comes from listening to stories as a child. I mean, if there’s one thing that among the many things that India is, India is a land of stories. There’s constant storytelling. And I think that that’s what motivates this kind of writing – people call it metaphorical, but as I said, it’s not really metaphorical. It is trying to tie together, as I said before, it’s trying to tie together a series of stories which I tell, which are linked but also ultimately parts of a whole.

One of the interesting learnings from your three books that I have gathered is that human knowledge operates between two vast unknowns. At the highest level, the biggest question we have is “what is life” – and this, as you write, remains a “metaphysical conundrum”. And then, at the most microscopic level, genetic modification of cells is fraught with unknown risks because we are yet to fully understand the correlations across genes. Reading you, my sense is that even as we solve the answers at the microscopic end, the question of “What is Life” will continue to be elusive. Is it an answerable question?
I mean, the question of “What is Life” is not an unanswerable question. And I do think it’s a question that doesn’t have a single answer. There are questions that are unanswerable because they have no answer. The question of what is life has a multiplicity of answers. And that’s because the criteria for life are a multiplicity of criteria. So I think that is the only way that will ever be solved. The multiplicity of criteria is by understanding that.

Life is, as I said, a kind of a menu. And I think it’s an answerable menu. You can look at a collection of cells or a collection of whatever it might be and say – well, this is living and this is not living. We have criteria. It’s not a free-for-all. But I think those criteria aren’t pinned to one single idea or one single criterion, but in fact are spread through multiple criteria, and only if a being fulfils all those criteria do we call it living.

You have been writing for a general reading population for nearly a decade. These topics are often stunningly opaque to most of us, and yet are intimately connected to our welfare and ideas of self. To write well and communicate widely is difficult. What sustains your continued interest to communicate to the wider public? Why do you do it? It is so much hard work.
I do it because I think that these ideas need explanation. They need to breathe. And in our particular popular culture today these ideas can be removed from the life of public discourse and a lot of my effort is to reinsert them in public discourse. And to emphasise how important it is.

It’s incredibly important to understand genes and genetics if we want to understand – just to give you one example – what to do about understanding disease. A disease like schizophrenia, for instance, where there is so much taboo attached to that disease. It’s very important to think about cells because we are inventing new forms of cellular therapy. Thousands of men and women will go through, for instance, IVF. And not for a moment think about the idea that was sort of bred and born as cellular therapy.

So a lot of what I do, the urge to write, is to bring people into my world. You can almost call it a kind of selfish urge because I find that this world is incredible. It’s the same reason I think that cosmologists write about the cosmos. I mean, you could say, well who particularly cares about Alpha Centauri, or some galaxy that we’ll never, ever go to and you can’t even see at night. But there’s a kind of thrill and excitement about bringing people into this world, which is very important to communicate.

During covid, I saw you write, tweet, try to educate people – as if to awaken people from a kind of stupor. What did the covid experience teach you personally about being a doctor and thinker on medicine that you didn’t know before?
Well, I mean some of it was outside medicine but it’s very relevant to medicine. We think about medicine as a doctor with a black bag. But of course, an entire system perpetuates and moves behind the scenes to enable medicine to work. There are issues about the supply chain. There are issues about who stocks the room where the masks are kept. Who ensures that appropriate equipment is available in one part of the country and not in others.

One of the shocking things about India when the worst of covid hit, there was enough oxygen in the country to go around. It’s just that it was in the wrong place, and there was no mechanism to get it to the right place. So part of the stupor was to remind people, patients and doctors alike, that we imagined medicine as a particular system of practices.

But it’s much, much more beyond that. There are components of gossip in medicine. There’s components of how doctors communicate, for instance, through Twitter. And if you don’t understand those components, you will not understand how and why medicine works. You imagine it again as a doctor with a black bag. And that would be a terrible misconception, because that’s not what medicine is.

The way sciences are taught in Indian schools is almost indistinguishable from tedium, rote memorisation, and often misses the big picture. As a professor and teacher, have you thought about how science education can be improved right from schools to university? Like, what can people do? Or is it too large a problem? And it has only smaller bespoke solutions.
I think the answer is going to be a mixture of what’s bespoke and what’s not bespoke. I think the answer is going to be, for science and scientists in general, very broad. And they start from very early on in life. Again, science is not a textbook. Science and medicine, generally. Similarly, I mean, this is the one conception that I think I really want to remove.

There is a sense in India that science is a textbook or a series of questions that you can master in an exam. And when I first came to the United States to work with science and scientists, I realised that all of that knowledge is just the basis or the beginning. You need to have it. But it just forms the foundation for real knowledge and real knowledge I think is exploratory knowledge.

And so one fundamental thing to communicate to people is that learning a textbook, learning biology, and figuring out sort of where organs sit and how they communicate and who makes insulin and etc etc is just a foundation. The really interesting thing about science is not the foundation. It’s the creative aspect of science, which it actually shares with other creative disciplines, like the arts. Where you ask a question that’s not been asked before and wonder why it’s not been asked before what the answer could be to that question.

That’s where things get really interesting. That’s where things gets very interesting. And that’s where we all suddenly discover that there is a completely new way of thinking about science. That has nothing to do with the way we’ve thought about it before.

One way I have been thinking about your books is as a trilogy about the bodily existence of humans, You have been trying to educate the rest of us from the cutting edges of scientific inquiry on what an average Indian would think of as phenomena related to srishti, sthithi, and samhara. The Gene as srishti or creation, Cancer as samhara or destruction, and now Cells as sthithi or the state of preservation. This is a physicalist description, a model in my head. How do you think about your three books? How do they talk to one another? Do they stand alone? Are they in conversation with each other?
You’ve got it; and you hit the nail on the head in some ways because I think the actual right way to read these books is to start with Gene, go to Cell, and then end, at least for now, with Emperor [the book on cancer]. Because the gene is the fundamental unit of information. The cell is the enlivening of that information and the construction of being, and the dysfunction of cells is what causes cancer.

I mean, you can certainly read these chronologically as they came out. And that would also tell you a different story. It would tell you the story about cellular dysfunction; and then go deeper and deeper. As it were, you could do a telescopic or a microscopic reading. The microscopic reading would be going from Cancer to Cell to Gene. The telescopic reading would be to go from Gene to Cell to Cancer . So there are many ways you could come to the book. But I think in some ways, I like your typology, because that is the typology that’s in the book. It’s about three fundamental ways of being that ultimately end up with three fundamental ways of thinking about the biological universe.

One of the most rewarding aspects of your books is that there are so many wonderful sentences, brimming over with a poetic sensibility, memorable phrases tucked away here and there. What I get is that science is important but writing well matters to you as well. Your book is peppered with lines or quotes from other writers – from Salman Rushdie to Wallace Stevens and others. Who are the people whom you read, or go back to read, from the “literary” world? Who has influenced how you think about your own writing?
If I think about it, I don’t make any distinctions. I’m a very catholic reader. I read books that I like to read. I find them fascinating and interesting. And then I stop reading when I think that the books are not of interest to me. So, I think that capacity allows me to be very broad and I happen to like poetry a lot. So I read a lot of poetry.

People often ask me, “do you go back and find these quotes”. And I say, absolutely not. These quotes are often things that come to me while I’m writing a chapter. So, sometimes they’ll be scientific. Sometimes there’ll be – I’m just opening the book and looking. There’s a quote from Robert Burns: “when a body meets a body” [“Comin’ Thro’ the Rye”, 1782] which of course is the quote from which [JD] Salinger’s novel Catcher in The Rye comes from. But of course, when you think about the word “antibody”, you suddenly realise it is when a body meets a body. And that’s why that quote comes about. It’s because I read Salinger as a child and was always fascinated by the idea of when a body meets a body.

So I don’t make that distinction. In fact, I try to be as broad and wide as I possibly can in my thinking about any and all of this. And so that’s how these books get written. They get written because they form a corpus, as it were, of writing which has to do with so many different aspects of the written word and of how writing is done.

We are used to scientists, we are used to thinkers. There is a line that I had noted down from somewhere: “A great thinker is ultimately a mystic, a great scientist is a detective of sorts.” This dichotomy may be spurious, but as somebody who engages with the unknown on a regular basis, as someone who has seen many people die painful deaths-, do you end up thinking about what we could call “spiritual” questions? Or do you just set them aside?
I think “spiritual” questions can be answered by different people in different ways. In some ways, the fundamental practice of science for me has a component to it – I wouldn’t describe it as spiritual – but I would certainly describe it as a component that has very much to do with learning a new language.

“Spiritual” is a word that I don’t fully understand. And I don’t claim to understand either. But I do think that there’s a quality which I’d love to preserve in my books where the thinking transcends just sort of your day to day, matter of fact kind of attention. Because I think that does a kind of disservice to the depths of knowledge that science can bring you to, that medicine can bring you to, and medicine especially because you’re encountering a kind of lived science.

You’re encountering a science which has to do very much with how we live, what we do as we live, how we encounter death. And so medicine has a particular capacity, I think, to raise these questions and hopefully to answer them. But to certainly raise them.

This is the last question. You are probably running out of time. And I have to run to work. You wear many hats. You’re a professor. You’re a doctor, father, husband, essayist, writer of books and even singer – I heard you in Brooklyn a few years ago where you sang some Malkauns. How do you manage your time? How do you go about doing so many things and fulfilling so many responsibilities, while preserving the time to write?
I would say that I’m the master of bad time management. [Laughs.] I do things as they come along and try not to make distinctions between them – I do pride myself in meeting deadlines. I almost always meet deadlines, though barely. I sort of move through at least my own life based on what the demands are at the moment, at those moments. And I try very much not to get caught up or hung up on demands that I think are extraneous. I try to remove them. And that might mean, as I said, changing my behaviour around the daily activities of life.

I don’t have very much, whether fortunately or unfortunately [laughs], I don’t have very much balance in work and life. My wife, who is a very prominent artist, also doesn’t have any such balance either [laughs]. We work to live. And so I think that’s the best way I can answer that question. I just sort of do what I can, as it were. In doing so, I have managed over the years to find a way to continue. I’m not sure I can answer that question.

Courtesy: Mathrubhumi.

Keerthik Sasidharan is the author of The Dharma Forest (Volume 1 of The Dharma Cycle), which was long listed for the JCB Prize for Literature. Volume 2 will appear in late 2023. He can be found here on Twitter.