Columbia University Medical Center

In New Book, Siddhartha Mukherjee Details the History of the Gene

Following his Pulitzer Prize-winning book about cancer, “The Emperor of All Maladies,” Columbia oncologist and scientist Siddhartha Mukherjee, MD, DPhil, turned his attention to the impact of genes on our lives and our very identity in his new book, “The Gene: An Intimate History.” The CUMC Newsroom sat down with him recently to discuss how the book came about and what he hopes it will accomplish.

CUMC Newsroom: You were prompted to write your book, “The Emperor of All Maladies,” after one of your patients asked you to explain what cancer is, not just in clinical terms but rather how we have understood and dealt with it historically. What prompted you to write your new book, “The Gene: An Intimate History”?

SM: The first reason is very personal: it arises from a history of mental illness in my family—a combination of schizophrenia and bipolar disease, which I was very familiar with as a child but began to think about more deeply as I grew up. I had two uncles, a cousin, and several others succumb to variations of schizophrenia and bipolar disease, so it certainly had a big mark on my childhood. I wanted to know the genetic roots of that. How does a disease like this happen? Why is it that some people get the genes but might not get the illness?

The second impetus came from the study of cancer. As you know, I’m an oncologist who studies cancer in the lab. When you study cancer you begin to ask the question, what does the normal cell do? If cancer is a disruption of normalcy, if genes go wrong and make a cell behave in a malignant, dysregulated way, what does the normal genome do? How does it maintain our cells? How does it repair the body? How does it reproduce cells without making errors?

Finally, over the last three to four years, as we began to use novel technologies like CRISPR to study stem cells in the laboratory, I began to realize how simple it has become to manipulate the human genome—obviously in cells, but potentially also in stem cells, and perhaps most importantly, in embryonic stem cells. The realization that all of a sudden we have a technology to change the genome was the third strand.

I had thought about “Gene” for a long time while I was writing the cancer book, because it explores the idea of what normalcy means before it tips over into abnormalcy. In some ways, “Gene” is a prequel to a sequel, like “Star Wars.”

CUMC: As you mention, in this book you share some deeply personal stories about your family, including your mother and aunt, who are identical twins, and various family members on your father’s side who struggled with mental illness. Why did you make this choice?

SM: I think it’s impossible to write a book about heredity without focusing on what heredity means to you. The way I conceived this book was as a way to stitch together the very personal history—our micro history—with a macro history of the gene. We move from a chapter about my cousin, which is a very intense story, to Mendel.

I wanted to make it very clear that this is not a book about genes in the abstract. These are concrete realities that will be carved into your life, into my life, and they already have been. That’s what science is. It invades our lives in these very fundamental ways, and if we ignore it, we do so at our peril.

CUMC: How have genetic discoveries changed our way of thinking about our identities, including our behavior and susceptibility to illness?

SM: Over the course of the last 10-odd years, we’ve begun to ask questions that are very uncomfortable: How much of a role do genes, environment, or chance play in this triangle? If you can change one factor, what will happen?

Historically, we have thought of the environment as being more malleable than genes. Environments may be constant or they may change over time. But what if we changed our genotype so that we wouldn’t have to have an illness? What are the limits of human perfectability, and what do we do to ourselves once we begin to think of ourselves as perfectable? All of these questions lie outside [the scope of] genetics—in culture, science, and history—but they’re also questions that are raised by genetics.

CUMC: What’s next? Will there be another Ken Burns documentary, this time on “The Gene”?

SM: Ken Burns is doing “Gene,” making it our second collaboration. Ken’s an amazing mind. When I wrote the book on cancer, I had never thought that Ken Burns would make a film about it. And I never thought that Ken would approach me again about “The Gene.”

It’s a reminder that we think of these enormous scientific enterprises as lying outside of culture, or having their own culture. But this is part of human history and culture, so the idea that we’ve sequenced the genome is not just a scientific idea. It’s an idea that has human historical impact, just as landing on the moon or discovering the laws of mechanics does. These discoveries have changed the way we think about ourselves, and that’s why I think Ken and PBS have approached my books—to remind us that the idea of [exploring the history of] the gene is no different than making a film about the Civil War. Obviously, the content is completely different, but its impact on human history is very similar.