Gene genie: how geneticists are unlocking the secrets of disease and mental illness

WIRED speaks to the Pulitzer-prize winning author Siddhartha Mukherjee about his new book and the century-long quest to define the gene

01 Sep 2016

Mukherjee is exploring the links between stem cells and cancerous blood diseases in his new book, The Gene: An Intimate History

Peter Judson

A cancer physician and stem-cell biologist at Columbia University, Siddhartha Mukherjee investigates the links between stem cells and cancerous blood diseases. In 2011, his book, Emperor of All Maladies: A Biography of Cancer, won a Pulitzer Prize for general non-fiction. Now he returns with The Gene: An Intimate History (Bodley Head), a wide-ranging exploration of genetics.

In it, Mukherjee explores heredity through his family history of mental illness, and describes the centuries-long quest to define the gene. WIRED talks to Mukherjee about his new book, the new era of "neogenics", and what it signals for the future.
WIRED: What prompted you to write this book?

Siddhartha Mukherjee: There were three threads that came together. The first was the history of mental illness in my family - particularly schizophrenia and bipolar disease. The second strand was equally important: I'm also a cancer biologist. As cancer genetics came alive, the question was, "What do normal genes do?" If genes can be perverted into those kinds of behaviours in cancer, how do normal genes act?1 

The third strand was that in the past four or five years, we've begun to manipulate the human genome with a dexterity that we didn't possess before. That demanded its own response: what does life look like once the human genome becomes so easy to manipulate? These three things came together in The Gene.
What frequent misunderstandings do people have about genetics and heredity?

One of the most unsettlingly beautiful things about the human genome is that even though it has some powerful influences on fate, destiny, illness and even things like personality and temperament, a lot of it is left up to chance. I think this is what people get wrong about genetics - the profound level of determination of the gene, but also the way chance, randomness, triggers or environments can play a role.2
In the past, misunderstanding the gene's complexity has driven atrocities such as eugenics, which you explore in the book. Was it important to you that you mapped out this history in such detail?

The Gene and my book on cancer are mechanisms to investigate how human knowledge happens. My suspicion is that the content of scientific knowledge changes over time, but the form remains the same. The kinds of mistakes that we make - the desire to solve complex problems using simple solutions - is sometimes true, but sometimes leads us down very wrong roads.
Progress has ushered in an era of "neogenics". Is neogenics a "moral" version of its predecessor, eugenics?

I don't believe that neogenics is necessarily more moral; I think it's more scientifically accurate. Right now, it's not clear what the moral universe looks like with neogenics. On the other hand, we will use these technologies to have an impact on diseases that we cannot otherwise treat. Imagine how wonderful it would be to take a disease that lacks medical therapy and use either gene therapy or in utero diagnosis to reduce the risk? But, if we intervene on an illness, are we going to change an identity? And are we going to change who we are if we intervene on genes?
CRISPR obviously poses huge possibilities and questions in this realm.

What CRISPR allows us to do is to add information to the genome, enhance the genome in a way no other technology can. It's unique in its capacity to do that. And that's where I think people's concerns are the highest: can we really safely add information to the human genome, in a way that doesn't have long-term consequences? I think it's important when we have conversations about what CRISPR does, that we divide up what the applications are, and what the impact is. That conversation needs to be had beyond the world of science.
In your research on the genetic regulation of blood-forming stem cells, you've met these issues.

We began to use CRISPR technologies about two-and-a-half years ago, making changes in human stem cells, and it wasn't that hard to do. So, if you can make these changes in human stem cells, and change the way people suffer from various blood diseases, for instance, what might be the effect of making those changes in embryonic cells? It's a question we haven't studied, but it became clear that it wouldn't be hard to study - that these technologies might be easier to come by than I had anticipated.
What questions remained after writing this book?

The question that kept coming back to me is to what extent is it true that fate is predictable by individual genomes, and if we know that, what do we do about it? Also, what happens when you start making changes to the gene? That's the moment that we're in. And the question is, can we do this responsibly?

1. Mukherjee says increasingly sophisticated genetic diagnoses may identify more "previvors" - people who discover they're at risk of a disease before they develop it, such as breast cancer.

2. The author uses twin studies to reveal how disorders are shaped. "In identical twins, there's a 50 per cent chance that if one twin has schizophrenia, the other will, too," he says. "The other 50 per cent is something we don't understand."