dr. Siddhartha Mukherjee still remembers the first cell he grew: it was a mouse immune cell, and he grew it in a petri dish. As he examined it through the microscope, the cell moved, and Mukherjee was fascinated.
“I could feel the pulse of life moving through it,” he says. “Suddenly you realize that you’re looking at the basic, fundamental unit of life, and that this blob you see under the microscope—this glittering, glowing blob of a cell—is the basic unit that connects us and plants and bacteria and archaea and all those other genera and taxa throughout the animal and plant kingdoms.”
As an oncologist, cell biologist and hematologist, Mukherjee treats cancer patients and conducts research in cell engineering. In his new book, Song of the cellhe writes about the emerging field of cell therapy and how cell science may one day lead to breakthroughs in the treatment of cancer, HIV, type 1 diabetes, and sickle cell anemia.
Mukherjee is particularly interested in T cells — a type of white blood cell and part of the immune system that is activated to fight disease. He has treated patients in India who have certain types of cancer with genetically modified T-cell variants, and the results have been astonishing: “One day the cancer is there. The next day the cancer is practically gone, eaten away by these T cells,” he says.
Genetically modified T cells, known as CARs [chimeric antigen receptor ] T cells, they have become the main product in the treatment of certain types of leukemia, lymphoma and blood cancer. But, Mukherjee says, the cells have not yet been shown to be effective against solid tumors, such as those associated with lung and prostate cancer. He hopes further research could change that.
“It’s hard for me to convey the excitement that spreads throughout the entire field of cell biology…the kind of giddy, giddy, frenzy, psychic power that comes over you once you enter the field,” says Mukherjee.
Highlights of the interview
On using CAR-T cell therapy to treat Emily, a child with leukemia
[The treatment is] we extract T cells from the patient’s body. And then we use gene therapy to basically weaponize them, to activate them and weaponize them against cancer. We grow T-cells in flasks in a very, very sterile chamber. And then finally, when the cells grow and are activated, we reintroduce them into the patient’s body. So it’s a kind of gene therapy plus cell therapy – that goes back to the patient.
In Emily’s case, she was about 7 years old, I think, when she was first treated. She had a complete answer. She also had a very scary course. When the T-cells are activated, they release an incredible inflammatory cascade, kind of like, as I say in the book, it’s kind of like a raging soldier. And you can get such a rampage of cancer-killing T cells that the body goes crazy, it can’t handle this kind of attack. Now Emily, fortunately, was treated with medication to alleviate that attack so she ended up surviving. She is the first child treated with this therapy to survive and serves as an icon for this type of therapy. … She is still alive today and applying to colleges, I hear.
On how engineered cells target cancer cells
One angle is basically to find something on the surface of the cell, a flag, as it were, that will tell the immune system that it is not part of the normal repertoire of cells. So, for example, if I transplanted a piece of skin from one human being to another, that piece of skin would be rejected. And that’s because skin cells have flags on their surface, specific molecules on their surface, that T-cells recognize. And the T-cells come in and say, “Wait a minute, you don’t belong in this person” – and they’ll reject them. And that is why transplanted skin is rejected. So, one mechanism by which you can specifically direct the immune system against any type of cell is to find such a flag that is in the [the targeted] cell … and essentially engineering, using various methods of genetic engineering, engineering T cell or make antibodies against that flag, that molecule, that protein that is on the surface of the cell … and make the immune system reject that type of cell.
About how his experience with depression helped him empathize with his seriously ill patients
I could feel a sense of doom and also a sense of uncertainty. Uncertainty itself causes anxiety, which is actually one of the most prominent symptoms of depression. A lot of times people will come to you and say, “I’m very anxious,” but really, what’s happening with them is that there’s a depressive component behind it. Anxiety is a manifestation of this. It is a manifestation of a mood disorder, not some kind of special panic running through their brains. And I think illness causes one of the deepest forms of anxiety we know. Therefore, I strongly encourage, especially cancer patients, to seek psychiatric help, talk therapy, medication, if needed. And any kind of therapy that will help them because my own experience with my mood and my mood disorder has allowed me to really understand what patients are going through.
Deborah Feingold/Simon & Schuster
On anti-science sentiment during the pandemic in the US
[During the] the very uncertain time we had around the pandemic, things seemed to change and there was this big anti-scientific sentiment that said, “Scientists are egg-headed idiots because they keep changing their minds.” But we keep changing our minds because we retain the luxury or prerogative to change our minds when the facts change. And in the pandemic, the facts kept changing. …
There is a difference between uncertainty and authority. Uncertainty is not knowing something. … False authority claims something, even when you don’t know it. And I think those are two different things. Part of the anti-science sentiment that gripped the United States during the pandemic was due to the confusion between uncertainty and false authority or authority. There were many uncertainties and they were changing. And that’s part of the reason the CDC changed, the FDA changed. We had to adapt multiple times to multiple changes. I’m not saying they were always right. They could evolve. Sometimes they were wrong. Sometimes they were right. But what I am saying is that… the scientific process had to be maintained and was maintained throughout the pandemic.
Sam Briger and Thea Chaloner produced and edited this interview for broadcast. Bridget Bentz, Molly Seavy-Nesper and Deborah Franklin adapted it for the web.