“Cell therapies change the definition of human”

“Cell therapies change the definition of human”

In India, it was very difficult to buy books when Siddhartha Mukherjee (New Delhi, 1970) was a child. At that time, in order for the book lover to overcome this huge obstacle, he made a pact with his father: every Christmas, as a gift, he would receive as many books as he had years ago. He claims this saved him. Educated at Stanford, Oxford and Harvard universities, Mukherjee is a professor of medicine, oncologist and researcher at Columbia University (USA), and one of the most prominent figures in science communication today. He is the author of four books in which he explores biomedical issues, but also delves into history, the history of humanity and his own, and reflects, ultimately, on the human condition.

The researcher recently visited Barcelona to present his latest book, Cell harmony (debate) at the Institute of Bioengineering of Catalonia (IBEC), where he also spoke about advanced therapeutics, early disease detection and personalized medicine with Catalan researchers.

After writing about cancer and then about genes, he has now moved on to cells. because?

– It is part of a quartet that I am preparing, because life for me is like a quartet. After finishing a book about the deepest diseases of life, such as cancer, and then understanding the fabric of life, genes and DNA, I thought I needed to write about the basic units of what we define as life cells, because we are only now beginning to understand them. You also agree that there’s a revolution happening in medicine, cell therapies, and I wanted to talk about that as well, because a lot of our understanding of medicine today is based specifically on understanding cell therapy. In fact, the idea for this final book came at the end of the bookEmperor of all evilWhich I ended with a question: If cancer is the definition of abnormal, then what is normal? How do we define normal physiology? These questions are the basis of the new work.

Were you able to find the answers there?

– I started to respond to it from different points of view. There is a paradox that in physiology we mean by normality a set of standards of life and a certain definition of living organisms. But all this is evolving and in the book I try to go further to explain what life is.

To do this, talk about Songs Cells and how they must coordinate within the orchestra, which is the tissue, the organism, to play the tune of life.

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– That’s right, and it’s an important limitation to investigate, because we don’t understand how physiology fits. We are only beginning to understand parts of it and realize that the whole process is much more complex, because without understanding how each cell fits together, how the orchestra fits together, we cannot understand life. To do this, we now take a more ecological perspective to think about the cell in the context of other cells. This is very new and very exciting, and has actually led to a lot of the treatments that we’ve developed.

Can you give an example?

We discovered that when you take a certain drug that is designed to kill cancer cells, healthy cells in the body, which also receive it, react by essentially nullifying the mechanism by which that drug can prevent the cell from tumorigenesis and becoming resistant to the treatment. Therefore, if we want to understand the effects of the drugs we develop, we cannot continue to study what happens in the cancer cell in isolation, but must take into account the context of healthy cells in the body.

He claims there are “new humans”, people treated with cellular therapies, and compares them to cybernetic beings.

– Most of us are electronics in some way, or it would be more accurate to say cellular electronics, made up of cells. Consider a blood transfusion: a person accepts living fluids from another person, so that the donor’s red cells become part of another individual’s body. Although we don’t think of blood donation recipients as complex, they really are. As we delve deeper and deeper into the world of cells, we will learn how to handle them more and use them better. For example, we already stimulate neurons artificially; We artificially create new life forms, altering genes within cells to create new genes within the body that do not exist outside of that organism. So I think the idea of ​​what a human being is and what it is is changing because of the use of these cell therapies.

It’s very provocative.

– Yes, but also important.

Should we be afraid of him?

– Obviously there are reasons to do this, because there is a very fine line between what is and what is healing from to improve. Treatment is the attempt to rid someone of a disease, while improvement is the desire to make a person have superior characteristics. This idea of ​​improvement involves a series of very deep and critical ethical questions that need to be answered, such as who is this new human being; What are its characteristics? Improvement is only within the reach of the rich?, among others. In the context of gene therapy, we’ve thought a lot about this, and there is no gene therapy without cell therapy, because cells are the way genes are expressed.

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There are already proposals to improve animal species at risk of extinction due to climate change and make them more resistant to new conditions. Can humans be made more resistant to cancer?

– Attempts are already underway to do this, but so far from a pharmaceutical standpoint. For example, there is an ongoing trial that seeks to reduce the risk of certain types of obesity-related cancer by treating the metabolic disease. In these cases, a hormone is injected into the patient to attack obesity and the patient is followed for years to see if this reduces his chance of developing a tumor. In doing so, we create a new dimension of human beings. Are we really underestimating your chance of developing a tumor? We don’t know yet, but just wanting to know the answer is very provocative.

He confirms that in the not-too-distant future, we will treat diseases, even psychological ones, with cells, not medications.

– Yes, and in fact we already do this with some diseases, such as blood. Very soon, sickle cell anemia, beta thalassemia, and others will be treated with genetically modified cells. or diabetes; Now we can make cells that secrete insulin. Doesn’t this sound really amazing?

naturally. And neurological diseases?

– We are already able to make neurons in the laboratory, but we do not know whether they will work in the brain or not; This will require a complex experiment in many ways. But we can stimulate neurons in the brain and create states of consciousness that are different from normal and affect mood, movement, or symptoms of other disorders. This is also a cell therapy.

What other cell therapy projects are you working on?

-We are looking into how to create new types of hybrid immune cells to treat some types of cancer. The body’s defense system consists of two wings. On the one hand, B and T cells, and on the other hand, the first line of cells that are the first to react when an attack occurs.

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The first is more accurate, the second is faster.

– Well, we created cells that are different from the two, but they have the ability to reach cancer cells more efficiently. It is a hybrid between the two parts of the immune system, and has the ability to see and kill cancer cells. Unlike B and T lymphocytes, these hybrid cells are actually able to penetrate the tumor, which is one of the main barriers that exist today, because immune system cells cannot enter it. What we do is completely new cells, which never existed before, which we genetically engineer and manufacture. At the moment, we are already conducting a clinical trial on breast cancer and the results we are getting are very hopeful.

From the clinic to Bangalore

Siddhartha Muhirki took advantage of the visit to IBEC to go to the Hospital Clínic de Barcelona, ​​a center that has a project underway in India, his home country, to implement general CAR-T cell therapies in that Asian’s hospitals. nation. “We have already been able to treat 25 patients, most of whom are currently in remission,” explains this oncologist.

In 2021, the first CAR-T cell therapy was approved in Spain for use against acute lymphoblastic leukemia, the most common type of cancer in children. Called CAR-T ARI-0001, it was developed entirely by Hospital Clínic de Barcelona and was the first drug to be 100% approved globally. This was an unprecedented achievement, because it allowed us to produce this strategy, which represented a real revolution in oncology for the treatment of previously untreated cancers and leukemias, significantly reducing costs.

When Mujerki found out about the clinic’s development, he contacted them and in 2020 they signed an agreement to bring the same technology to India. Thus, they have implemented a unit at the Oncology Hospital in Bangalore, modeled after the one in Barcelona, ​​where they manufacture these immunopharmaceuticals using the same technology. They have already given it to patients in a clinical trial and hope the results will allow it to be approved and marketed at an affordable price. “We also hope that we can return to Barcelona in the near future with the new knowledge we are developing in India,” he says.

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