Siddharta Mukherjee, oncologist: ‘Cancer is the greatest mystery that someone could solve’

Siddharta Mukherjee, 52, is an oncologist at Columbia University. The American doctor is considered to be one of the greatest living writers on the subject of cancer. His bestselling book, The Emperor of All Maladies, won the 2011 Pulitzer Prize for Non-Fiction. The revolution in cancer treatments in the last decade has led him to work intensely on an update of this work, forthcoming in 2024. “The most important thing happening in the field is how we’re understanding the connections between inflammation, obesity and cancer,” Mukherjee opines. His latest scientific project involves bringing CAR-T cell therapies to India — where he was born — in collaboration with Spanish researchers.

In his latest book, The Song of the Cell (2022), he teaches readers the history of how the cell was discovered, while addressing the amazing development of new therapies based on them (such as CAR-T), which have managed to cure blood tumors that, just a few years ago, were a death sentence.

During a video interview with EL PAÍS, Mukherjee reflects on how the next medical advances will reach us. He hopes that they will help win crucial battles in the fight against cancer, Parkinson’s or Alzheimer’s. The writer warns about the need for human co-pilots for artificial intelligence (AI) in healthcare, while calling for more connected research between three types of scientists — discoverers, connectors and implementers — so that we don’t miss out on the great medical advances, which are expected to come true in the coming decades.

Question. What led you to choose cancer as a field of study?

Answer. Cancer has been, and continues to be, one of the greatest mysteries in medicine. It’s a very deep mystery, not only [regarding] cell biology. It’s a mystery of the whole body, in physiology and genetics. And it’s also a mystery of personal identity and survival. Cancer encompasses multiple stories: scientific, personal, medical and psychological ones. It’s the biggest mystery that someone could solve. Every year, new ideas and approaches emerge. Trends come and go, but the mystery remains. It needs to be solved.

Q. Since you wrote your biography of cancer, there has been a therapeutic revolution with immunotherapy and CAR-T (engineering immune cells to treat cancer). Do you think enough progress has been made?

A. I’m writing an update to The Emperor of All Maladies. It will probably come out early next year, and it will have more details on immunotherapy and CAR-Ts. I myself have launched two efforts in these two fields. One of them is in collaboration with Spain, with the Hospital Clínic of Barcelona.

Generally, I think that — for some types of cancer — we’ve made tremendous progress. Immunotherapy has greatly changed the prognosis of some types of cancer. We’ve also just seen amazing vaccine data for melanoma and pancreatic cancer. I would say that it’s still a little early [to celebrate]. But for some cancers, like leukemia, myeloma and lymphoma, we’ve made incredible progress with CAR-T therapy and immunotherapy.

With immunotherapy, I once made a personal guess that, in my lifetime, I would never see long-term survivors with metastatic lung cancer. But thanks to these treatments, there are now [long-term survivors]. Not many — only 20% of the patients — but still, it’s really amazing. The last thing I would say is that finally, after many years, we’re beginning to make extremely important advances in the prevention and early detection of cancer.

Q. What other major improvements have been made in the prevention and detection of cancer?

A. The most important thing is how we’re understanding the connections between inflammation, obesity and cancer. It’s a whole new way of thinking about prevention. Until now, [researchers] focused on finding carcinogens. And, of course, we found some extremely important ones, such as smoking. But many people who don’t smoke get lung cancer, bladder cancer, or esophageal cancer. And they wonder why. Obviously, some of it has to do with genetics, with the misfortune of random mutations that occur in cells. But we’re also realizing that another part [of these cancers] has to do with inflammation. Detecting that inflammation — and knowing exactly how the body becomes inflamed — will be crucial in figuring out what to do and how to manage these complex cancers.

Q. In your book, you talk about “new humans,” in reference to people like Emily Whitehead, who was cured of blood cancer thanks to CAR-T cell transplants...

A. We always think of this idea of “new human beings” as something robotic or prosthetic or bionic. We forget that, in fact, the type of human that we’re creating via cell transplants is also bionic. When the first blood transfusions were given, many people thought that their psyche would change, because their blood was changing. And of course, that’s not true. But the idea was that, by transplanting cells, we would become chimeras — part of other human beings. These technologies have emerged so quickly that we’ve quietly assumed that they’re part of being human. And I wanted to raise the provocative idea that these chimeras that we’re creating are actually a new kind of humanity.

Q. Do you think there will be more children like Lulu and Nana? These were the first babies created through gene-editing experiments by Chinese geneticist He Jiankui. After being sentenced to prison for three years, he has since returned to science.

A. We will see some more, yes. There will be some drive to create [genetically-modified beings] or, at least, to push the boundaries in this arena. But I don’t think that [there will be much success]. People think that this dystopia is very close. But the idea of casually making a baby stronger or taller is a fantasy. The reality is that the more we understand biology, genetics, and the cell, the more complicated [the endeavor] seems.

Q. You mentioned your current scientific project. What exactly does it consist of?

A. We’ve created the first integrated CAR-T therapy hospital in India. This was a huge effort, people said it was impossible. But, in collaboration with the Hospital Clínic de Barcelona — and supported by our research — we’ve started and almost completed a clinical trial with very positive results.

Another project I’m working on is using diet to radically change the behavior of cancer cells. We use diet in combination with medication, almost turning diet into just another medication. Our trials are also showing very interesting, positive data. These precision diets have to do with how cancer cells absorb nutrients — they’re based on high-quality science, on studies that have been published in the last 10 years. We’re developing [the treatment] through a company, Faeth. One approach is to use diet to lower insulin levels. The other is to remove two amino acids from the blood, both of which serve as nutrients for tumor cells.

Q. What results are you seeing in patients?

A. There are incredible stories. I’ve seen seven and eight-year-old children — who wouldn’t have had access to any other therapy in India — receive CAR-T [cell therapy] and some of them are still in good health almost a year later. I’ve also seen a woman treated with dietary therapy in combination with cancer drugs who had an incredible response. She had endometrial cancer (which affects the lining of the uterus).

Q. Could advances in knowledge of cell biology be applied to better understand and treat mental and neurological diseases?

A. I think we’re entering a new era in neuroscience. We’re beginning to understand how a set of cells with connections between them can give rise to amazing properties. And this has to do with the way the wiring works and how the connections communicate, if the cells communicate with each other. Once we start to understand [these connections], we’ll also start to understand the pathology.

Many diseases of the brain are related to cell biology, like the dysfunctional cells in Alzheimer’s or Parkinson’s. These are pathologies of cellular origin. A person with Alzheimer’s disease experiences profound memory loss, [which raises] the question of what memory is, where it resides in the brain, and how memories are formed and preserved. These two lines of research — the pathological and the more metaphysical — must finally converge if we really want to cure these diseases.

Q. In your books, you also talk about how at various times in history fundamental discoveries have been made that have subsequently been ignored for years, even decades. Does that still happen today?

A. Yes, we always miss an opportunity to speed up some ideas. Some scientists are “discoverers.” That’s what they do: they discover things. Another group of scientists are “connectors”: they establish connections between different ideas. And then, there’s a third group that I would call “implementers.” They turn inventions into reality. When [these three types of scientists] come together, they can achieve very powerful things. Unfortunately, they don’t tend to meet.

Q. Do you see cause for concern in the increasing use of AI in medicine?

A. There’s a very obvious cause for concern: can we protect the autonomy and privacy of patients against these powerful AI engines that can enter the databases? Also, as there’s more and more AI in medicine, we lose that incredibly important quality that is the human touch. When you talk to a chatbot instead of a human, how does it make you feel? Even if that robot behaves like a human.

The quality of the information that’s being generated by AI is very varied. Sometimes, it’s very good. Sometimes, not so much. I think we still need a human being to act as a filter. I call it a co-pilot model. You need the AI and humans [to work together]. And then, there’s a final question. I think it’s the most interesting one, from a philosophical point of view: are we going to create a kind of total surveillance around us, constantly scanning ourselves for diseases? This shadow of AI has the ability to fundamentally change our culture, because now we always live on the threshold of [becoming] ill, instead of being well. There’s the fear — [and] there’s a kind of resignation — about someone always watching you. I think we’ve underestimated how this can change who we are and what we do.

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