‘The Cell Is a Bigger Picture of What Life Is,’ says Siddhartha Mukherjee

Over the last 12 years, Siddhartha Mukherjee has devoted his research and writing to exploring what it means to be human. The Indian-American cancer physician and associate professor of medicine at Columbia University, New York, has written the Pulitzer Prize-winning The Emperor of All Maladies: A Biography of Cancer (2010) and The Gene: An Intimate History (2016). Given that he writes on science, with the flair of a poet, Mukherjee is now ensconced in a unique niche; in 2016, Vogue ran an article about him and his sculptor wife Sarah Sze, with the headline, ‘Meet the Most Brilliant Couple in Town’.

The 52-year-old author is now out with The Song of the Cell: An Exploration of Medi­cine and the New Human (Allen Lane; 576 pages; ₹799). In his new book, he paints an epic portrait of the cell, from its discovery (in the late 1600s) to its rebirth; and takes readers on a journey to understand life in terms of its simplest unit—the cell. The “new human”, he writes, will not be a science fiction version of The Matrix, with “Keanu Reeves in a black muumuu”, but instead, “rebuilt anew with modified cells, who looks and feels (mostly) like you and me”. Here, he talks about, among other things, how scientists have created new treatments and new humans through their exploration of cells.

Whether it is Emperor of all Maladies or The Song of the Cell, it seems memoir, history and science are the three prongs of your books. Can we talk about these three genres?

When I started reading literature about medicine, writings about medicine, I often found them siloed in categories, it would either be historical, or memoir, or very restricted in their own ways and I was very puzzled by that because medicine is a very human profession. Doctors are human beings treating human beings. And I found this separation of identities very destabilising because I wanted to invoke who was writing the book. What were they feeling like, as they wrote the book, what were their impulses? What were their challenges? Who was this person? And so even from my first book, even in the Emperor, I made what I think was then a relatively off-the-beat decision, which is that I would combine all these genres and make no distinction between them. I wouldn’t be apologetic about revealing my own vulner­abilities, my own feelings about the writing, about the book in general. And so, I began to write, in a way that moves between all three genres. Is it a memoir? Is it a his­torical document? Is it a personal story? Is it a journey? I like that ambiguity. I think that’s very important. Most importantly, it reveals who the writer is and gives the reader a relationship with the writer, that’s not the om­nipotent, omniscient doctor, which I am not and which doctors are not. But instead reveals the person writing the book and that’s why I’ve mixed these genres right from the beginning.

You said you do this unapologetically and I think that hints at how you’ve had to push back against the norm. What have been some of the challenges of that?

Well, the challenges are that people don’t know where to put me, put the books. Do you shelve the Cell under memoir? Under history, under medicine, under science? And to some extent the challenge has been precisely that and also moving between them. How do you make a book come alive in a personal way? That has always been an important question for me. That involves reveal­ing something very intimate. I want to keep the intimacy of these books. But on the background of the intimacy is this massive epic nonfiction painting of history—the discovery of extraordinarily fundamental things about the world.

What people often forget is that in writing these books, the most important things in a book are invisible. They’re the tendons and the ligaments that join the various pieces of any of my books together and they have to be invisible. They have to be brushed so finely that they become ineffable, invisible, even unavailable, so that when you’re moving from one genre to the other, you don’t feel as if you have a sense of whiplash against one.

You write, “The skin hadn’t begun to sag, the brain had.” The Emperor came out in 2010. A decade later, do you think your writing has changed with age?

It’s a difficult question. I think that as a more experienced writer, as I’ve written more, there’s a lot of paring back that I do now. Even though my brain is sagging, I’m more comfortable in my skin as a writer. I have fewer doubts about what I’m doing, as I’m going ahead and doing these things. On the other hand, of course, there’s always this tension between memoir and science writing and his­tory. But I think navigating that has become easier. Once again, there’s a big question that always overhangs these books, which is structure. So much about these books is finding a structure to reveal a story. And a lot of work, what I would call invisible work, goes into precisely finding a structure to tell a story, and this book takes a very unusual structure. It starts off chronologically, as you know, but then it becomes a kind of series of linked short stories as well, because each chapter takes on a cell and describes the micro history of that cell and that fits that micro history with medicine. And then puts it into the kind of broader glimpse that we have of how we live and what life is. It begins with cell division, moves on to the development of more complex systems, like the immune system and then finally moves on to organs themselves like the heart and the pancreas, etc. So, each chapter is a micro history, but the real thrust of this book is to convey the incredible excitement that our knowledge of cells and cellular therapy and cellular en­gineering is bringing to the world. And also, the perils, the moral perils and medical perils, that any such revolution in the making inevitably precipitates.

I read how a vast majority of people in the UK who know their child will be born with Down’s syndrome have an abor­tion. And a mother, whose child has Down’s, has made this documentary about how in future there might be no one who looks like her child. As a man of medicine, how do you respond to that?

I think the important thing is to leave choices. I make a very important distinction between disease and desire. So, we under­stand disease as obviously linked to human suffering and desire as a mechanism to augment or enhance who we are and how we imagine ourselves. But it’s important to realise that they are dif­ferent things, obviously, and there’s been a bright-line distinction between them for a long time. We’ve generally known what disease is, and we’ve generally known where desire begins, but one of the perils as we explore this new universe of cellular and genetic engi­neering—and I should remind people that genetic engineering is

cellular engineering—is that if you put the gene in the wrong cell at the wrong time in the wrong place, you won’t get anything. Genes are lifeless by them­selves. Genes need to come alive and only cells can bring them alive. A gene is like a musical score without the mu­sic, and the cell is what brings that song alive. Hence, “the song of the cell”.

But to go back to your question, there was a bright-line distinction between disease and desire. Those bright-line distinctions are now beginning to become challenged. They are still there and you can still make out when those bright-line distinctions have been crossed. I talk about the case of the Chinese researcher He Jiankui [who changed a gene in twin girls, which eventually sent him to jail].

But there are certainly cases where those bright-line distinc­tions become much, much more blurred. Examples of that as you just gave are children with Down syndrome who are actually now living longer and longer because of various medical therapies and have lives that are certainly challenged but nonetheless, some parents may choose not to have screening for Down syndrome. Throughout my lifetime, I’ve seen several patients with Down syndrome because they have an increased risk of blood disorders, including leukaemia. It’s absolutely true that there is an increased risk of suffering, but also, when you meet a child with Down syn­drome and you see their relationships with their families, those are beautiful relationships.

Cases like Down syndrome, and there are several others, lie in the blurry lines. There is certainly medical suffering involved with many of these children. In those cases, the decision is usu­ally best left to the individuals and a sense of autonomy for their parents helps because otherwise if we rob them of that autonomy, then we commit the worst of the two crimes, which is to forcibly define things as diseases, when they actually lie in a more blurry line between. This is just to emphasise that there is a very humane quality about judging or understanding where suffering begins and what point of time that suffering tips over into disease. The important thing is to leave that autonomy with individuals who choose to screen or not screen their foetuses for Down syndrome. That’s an individual choice.

You mentioned augmentation. And it takes me to a line which I had highlighted in your book—“augmentation has become the new emancipation,” which I found very interesting.

Imagine a day in which we use cellular genetic engineering to make ourselves taller, more robust, potentially more long-lived, etc. Of course, it is a human desire and it has to do with our de­sire to augment ourselves, augment our bodies. The line refers to the fact that we feel as if that is now sort of manifest destiny. It’s something that we can claim for humans, as we move forward. One problem with that line of thinking is that it ignores equity. Only some peo­ple can afford this manifest destiny. The second problem is, of course, the notion of manifest destiny in the first place. Are we really emancipating our­selves? Are we really alleviating some­thing that then allows us to have this new kind of life? But more and more, this idea that we could augment our­selves is becoming sort of the new way human beings seem to think of eman­cipating themselves from the troubles of the world. I give the example of com­panies that have been set up to infuse young human plasma into old people.

People are dreaming of times when they can use cellular engineering to renew, rejuvenate themselves. This kind of idea is becoming progressively linked with eman­cipation, which is, you know, the relief from the troubles of the human body and of ageing, and all the troubles that come with it. The blurring of those lines creates a whole series of moral dilem­mas, which I tackle in the book and the only way to solve those moral dilemmas is to have a public conversation about them as the book hopes to initiate.

What do you think will be some of the most compelling ques­tions when it comes to cell therapies in our immediate future?

The first obvious question is—safety and efficacy. To what extent are we being safe and effective? Cell therapies are challenging in many ways. They are expensive, they are labour intensive. They could be toxic and they can often not work. So, we need to set standards and create mechanisms by which we understand cell therapies and understand where we’re going with cell therapies so that as we move forward, we can fully appreciate these chal­lenges in their fullness. It’s still a young field. This book is not only about cell therapy, it’s also about understanding the biology of cells. So, I think that the challenges are all of those things. And we have seen those challenges manifest themselves.

You saw what happened. Emily Whitehead [a teenager who has “altered the history of cellular therapy”] almost died. In the first bone-marrow transplantations, hundreds of people died in that process. But now it’s become a life-saving procedure, so you have to go through a very ordered channel, making sure that these regulatory channels are not violated. That there is no secrecy, that we appropriately judge benefit versus risk versus harm. Also, be­cause these are laborious and expensive, we need to intrinsically maintain some sense of equality or equity as we move forward with these life-changing, life-altering kinds of therapies.

It is interesting how at one point in the book you mention that we don’t know the song of the cell.

We know some of the songs of the cell! The cell sings out—not to be too metaphorical about it—but the cell deciphers multiple codes and sends out multiple signals at the same time. So, on one the hand, the cell is an integrating machine. It integrates messages from the genome, from genes and then achieves its function. It’s an incredibly obvious, but also incredibly important, idea that ev­erything that you and I are doing now, our conversation, while we metabolise, our respiration that’s going on that allows us to live, is all dependent on cellular activity. If cellular activity was to cease, we would immediately stop working. I think we’re beginning to decipher how a cell could take this genome that we have, all the genes that we have, integrate them so that the cell can have its own unique function. A neuron in your brain looks and behaves and does things that are completely different from a liver cell in your liver. Yet they are reading out parts of the same genetic code. They have the same genes inside them, it’s just that they’re reading out or expressing subsets of genes that allow them to perform their unique functions, so I think that that piece of the deciphering, the integration, is half known and half unknown.

The more complex piece, which is even less known, I think, is how cells behave together as a system to create an organism and to really make an organism survive. That’s a second song, as it were. So this is an intracellular set of signals. And I think we are in the early phase of deciphering how these intercellular signals enable really complex physiology. And even in the systems that we have studied the best, such as the immune system or the heart, we’re beginning to understand these communications at a level that we hadn’t understood before. And finally, we are arriving at a more integrated and holistic picture of human physiology, which I think will motivate new kinds of medicines and a whole new kind of understanding of both biology and medicine.

You write how the pandemic punctured our collective hubris, leaving us with “We don’t know, we don’t know”. Do you feel that in less than two years the lessons of the pandemic have been forgotten?

I think so. I think every time we don’t know, it motivates some people to want to know. Scientists want to know, scientists want to understand. There is a narrative, which is very posi­tive, about science and the pandemic. We made vaccines in record time. We now have antiviral drugs and real strat­egies to help patients with severe Covid.

During the time I wrote the book, almost a year ago, there was so much uncertainty. And I think that, in a later edition, some of those ‘we don’t knows’ will go away and be replaced with ‘what we do know’.

As you mention, the Covid vaccine has been a true achievement of science. How do you explain the vaccine resistance in the US?

It is a very poisonous form of anti-science that spread through America in the last, I would say, four to six years. It’s linked to conspiracy theories, of course, that have been proliferating in the US. There’s been a deep politicisation of science and not only in America, I think, but also in India.

With the benefit of hindsight, what do you think India could have done better during the pandemic?

The first thing that comes to mind was a total collapse of in­frastructure and public health. The amount of spending that a country of 1.3 billion people does on public health in India is re­ally staggeringly small. Our hospitals are underequipped. Many, many lives could have potentially been saved if our public health networks were strengthened, and if our hospital system was strengthened. Even something simple like a safety-net hospital system for people in severe distress would have helped, and that was absolutely lacking. Second, there were major supply-chain issues. How one thing gets to another place. Ironically, I heard from close friends that there’s enough oxygen in India to supply all the necessary ventilators and oxygen chambers for patients dying of pneumonias; it’s just made in a different place and what was necessary was to transport it from one place to another. It’s just simple things like transporting it or moving it around.

In retrospect, the strengthening of public health networks and this solving of supply-chain issues would have been the first stabs at solving Covid. Second, I think the lockdowns were very badly mismanaged. Basically stranding people—people who had homes, could go into homes. But migrant workers, and those dependent on daily wages for their income, were totally stranded. They probably got more exposed from their forced migration than they would have been otherwise, and so I think for a long time there was com­plete chaos, and it was only once things started to settle down that these mass migrations and the displacement and excess deaths that came from all of this was finally managed and we were able to get on top of it. But it was heart-breaking to see it happen in real time.

I was intrigued when I read that the favourite part of the workday is when you sit and stare down the microscope.

Well, it allows me to glimpse a world inside a world. And it allows me to be quiet with my thoughts. The hospital is such a loud place—bells ringing and alarms going off and being dragged from one place to another. There’s a kind of meditative quality to sitting down and just looking and discover­ing the world within the world. So I think that’s the reason—the medita­tive qualities are very appealing in the midst of all the chaos that surrounds the delivery of medical care.

authorbookscell therapydoctorhuman cellSiddhartha Mukherjee