Siddharta Mukherjee (New Delhi, India, 52 years old) is an oncologist at Columbia University (United States) and is considered one of the best living writers on cancer, having won the Pulitzer Prize in 2011 for The emperor of all evil. The revolution in cancer treatments in the last decade has led him to work intensively on an update of this work, which he announces for 2024 and advances some of the topics that he will address: “The most important thing is how we are understanding the connections between inflammation, obesity and cancer,” says Mukherjee, who explains his new scientific project to bring CAR-T cell therapies to India, in collaboration with Spanish researchers.
In his latest book, the harmony of cells (Debate), takes a tour of the exciting history of the discovery of the cell and the amazing development of new therapies based on them, such as CAR-T, which have managed to cure blood tumors that a few years ago were a death sentence. In this videoconference interview, he reflects on how the next advances in medicine will reach us, which aspire to win crucial battles in the fight against cancer, Parkinson’s or Alzheimer’s; warns of the need for human co-pilots to use artificial intelligence in medicine and calls for more connected research between three types of scientists (discoverers, connectors and implementers) so that we don’t miss the opportunity to make some of the great medical breakthroughs expected in the coming decades a reality.
Ask. What led you to choose cancer as an object of study?
Answer. Cancer has been, and continues to be, one of the greatest mysteries in medicine. It is a very deep mystery, not only in regards to cell biology, but of the whole body; of physiology and genetics. Somehow, it is also a mystery of personal identity and survival. Cancer encompasses multiple stories: scientific, personal, medical, psychological. It’s the biggest mystery anyone can solve. Every year new ideas and approaches emerge. Trends come and go, but the mystery remains unsolved; and you have to get it resolved.
Q. Since you wrote your cancer biography there has been a therapeutic revolution with immunotherapy and CAR-T. Do you think enough progress has been made?
R. I am writing an update of The emperor of all evil. It will probably come out early next year and will have more details on immunotherapy and CAR-Ts. I myself have launched two efforts in those two fields and they are very exciting. One of them is a collaboration with Spain, with the Hospital Clínic of Barcelona.
In general, I think that for some types of cancer we have 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 is still a little early for these advances. But for some cancers like leukemia, myeloma, and lymphoma, we’ve made incredible progress with CAR-T therapy and immunotherapy. With immunotherapy I had made a personal guess in my life: I believed that I would never see long-term survivors with metastatic lung cancer. But thanks to these treatments there are already. They are not many, 20% of the patients, but still it is really amazing. The last thing I would say is that finally, after many years, we are beginning to make extremely important advances in the prevention and early detection of cancer.
Q. What improvements are there in that aspect?
R. Most important is how we are understanding the connections between inflammation, obesity and cancer. It’s a whole new way of thinking about prevention. Until now this had focused on finding carcinogens. And, of course, we have 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 are also realizing that another part 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 his book he talks about new humans to refer to people like Emily Whitehead, cured of blood cancer thanks to CAR-T cell transplants…
R. We always think of this idea of new human beings as something robotic or prosthetic or bionic, and we forget that in fact the type of personality or the type of human that we are creating with 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 have quietly assumed that they are part of human beings. And I wanted to make a provocative idea that these chimeras that we are creating are actually a new form of human beings. I think there are going to be steps towards the creation of a new human being, or a new form of humanity. And that raises a lot of important questions about who that person is and how we should think of them.
Q. Do you think there will be more children like Lulu and Nana, the first gene-edited babies in the crazy experiments of He Jiankui, who has been released from prison and back into science?
R. We will see some more, yes. There will be some drive to create, or at least to push the boundaries in this arena. But I don’t think they will be very successful. 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 it seems to create taller and stronger children.
We use diet in combination with anticancer drugs, almost turning diet into one more drug
Q. Before you mentioned your current scientific projects. What exactly do they consist of?
R. We have created the first integrated CAR-T therapy hospital in India. It was a huge effort. People said it was impossible. But in collaboration with the Hospital Clínic de Barcelona, and supported by our research, we have 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. And those trials are also showing very interesting positive data. They are precision diets and have to do with how cancer cells absorb nutrients. They are based on high-quality science, on studies that have been published in the last 10 years. We are developing it 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 that serve as nutrients for tumor cells.
Q. What results are you seeing in patients?
R. There are incredible stories. I have seen children of seven and eight years old, who would not have had access to any other therapy in India, receive CAR-T and some of them are still in good health almost a year later. I have also seen a woman treated with dietary therapy in combination with cancer drugs who had an incredible response. She had endometrial cancer.
Q. Could advances in knowledge of cell biology be applied to better understand and treat mental and neurological diseases?
R. I think we are entering a new era in neuroscience. We begin to understand how something that is material, 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. And I think once we start to understand that, 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, raising 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 his book he also talks about how, at various times in history, fundamental discoveries have been made that have then been ignored for years, even decades. Does that still happen today?
R. 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 they come together, they can achieve very powerful things. And one of the things I regret at science conferences is that these three groups generally don’t get together.
Q. Do you see cause for concern in the increasing use of artificial intelligence (AI) in medicine?
R. There is a very obvious cause for concern: can we protect the autonomy and private data of patients against these AIs that can enter the databases? Also, as there is more and more AI in medicine, we lose that incredibly important quality that is the human presence. When you get to talk to a chatbot instead of a human, how does it make you feel? Even if that robot behaves like a human. Third, the quality of the information that is being generated by AI is very varied. Sometimes it’s very good, sometimes not so much. So 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 as co-pilots with each other. And the 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 disease instead of well. We become different in our anticipation of what happens next. There is fear, there is a kind of resignation and also the idea that there is always someone watching behind you. And I think we underestimated how those changes could change who we are and what we do.
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