"Once people get the concept, they can't unlearn it"

Roxanne Khamsi is an award-winning science journalist, a contributing writer at The Atlantic, and the author of our October book of the month, Beyond Inheritance. I caught up with her this past week to discuss the book and this new view of genetics that she outlines—one that could really turn our understanding of medicine upside down.

Here’s a lightly edited transcript of our conversation.

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How did Beyond Inheritance come together?

I started my science writing career as a professional writer around 2002. About 15 years later, I was the chief news editor at Nature Medicine, which is a biomedical research journal. It was my job there to do a roundup of the year's biggest achievements in science, and I came across a paper in the New England Journal of Medicine about how they had found mutant cells in the blood of people over the age of 70 that were linked not only to a heightened risk of cancer, but also to a heightened risk of heart disease and stroke. And it was a moment where I just remember getting so excited, because it was a moment where it kind of challenged the way I had been thinking about genetics. 

I’d been reporting on rare diseases and inherited genetic predispositions to things like obesity or even schizophrenia, but I had never thought about genetic variation and mutation in the body as a driver of acquired disease. So from that moment onward, I was really curious about how we can think about genetic disease as something that's not only inherited but something that we can pick up throughout the course of our lives. We all know that cancer is an acquired disease, often because we acquire mutations that can cause tumors to grow. But the more I dug, the more I saw that it's not just cancer that has this paradigm.

Because that’s really what your book is trying to explore, right? We have an underlying attachment to inheritance as the dominant way our genetic imprint is created—but the more we know about genetics, the more we're seeing mutations happening in all kinds of ways throughout our lives, both in ways that are influenced by outside forces, and also just the way the body turns itself over across time. So, if you start to see us as this constantly evolving collection of genes, you can start to see new directions for medicine, for health, for how we make our way through life.

I'm smiling a bit as we're talking because I'm remembering other threads of this lineage of the idea for the book. As you know, I wrote for you when you were at MIT Technology Review about how brain cells are not all genetically uniform, and how that could contribute to things like schizophrenia or autism. So I think there were some of the seeds of that; I was scratching an itch there. I'm thinking back to a piece that did even before that about elements in our DNA that jump around—the “jumping genes” that Barbara McClintock was famous for shining a light on, and partly she got a Nobel Prize for that. That kind of made me more curious about the dynamic nature of our DNA.

By the time I got to the end of the book, this approach seemed so obvious that I couldn't even really remember what I thought beforehand. It was like you'd exposed a thing that was in plain sight the whole time; I couldn’t even understand why I would have thought that our DNA was singular and static. Is that an unusual response, or is it something you've heard from other people?

I’m so happy to hear that! When I was first working on the book, I kept the idea very close to my chest because it seemed like such an blatantly obvious idea that hadn't been put out there. But the more I dug into it, the more I felt confident that no one else was going to write this book because the history was so hidden. So a lot of the book ended up being a lot more historical than I anticipated because the threads of this idea that our DNA is dynamic actually have existed for a century or more. When I reveal to people this concept that our DNA is evolving as we live and breathe, I usually have a kind of an uphill battle of getting them to understand what I'm saying, because the shift is so profound.

But I do feel that once people kind of get the concept, they can't unlearn it. But I feel like it requires a book in order to understand why that paradigm shift—or that epiphany, I should say—is so radical within so many fields of medicine.

Scientists themselves have a hard time unlearning this concept. I talk in the book about how there's this condition called Long QT syndrome, which causes irregular heartbeats and can be fatal. Up until 2013, which is not that long ago, they assumed all cases were hereditary and passed down from parents to children, and even after doctors found pretty convincing evidence in the blood samples from a patient that seemed to indicate that's not the case the scientific community wanted to see it from the heart tissue specifically. When you're under the reign of Gregor Mendel, you have a hard time thinking about non-hereditary forms of disease.

In the book you talk about lots of different conditions, diseases, syndromes, things that people live with or suffer from. And you obviously spoke to a lot of people who have those conditions and people who study those conditions or treat those conditions. What were the ones that stuck with you deepest? Which ones sort of squeezed your heart most?

That's an unfair question, what tragedy made my heart hurt the most, because a lot of these are hard stories to hear. I got some advice about a decade ago, when someone told me it's OK to cry on the phone with your sources. Ever since then—I don't let them see me tearing up or being emotional—but I'm on the other end silently crying, hitting mute. Even when I recorded the audio book, I had to do something like four takes of the chapter in which I discuss the story of a family whose daughter was born with Long QT syndrome. 

You said there was a lot more history in the book than you thought there would be. So, what was the reporting and writing like?

If you're really a curious science journalist, you will want to trace the origin of an idea back to its first instance. So I did that with the idea of liver regeneration. For example, I think it's Higgins in 1931—don't quote me on the exact date—who first had the insight that the liver can so massively regenerate: you can take 70% of the liver and then within a short period of time you've got most of your liver back.

There was also stuff that didn't end up in the book. There's PNH, which is paroxysmal nocturnal hemoglobinuria, is a disease where—because mutant clones of your blood cells appear—and have a reaction that starts destroying your blood cells and changes the color of your urine. I found a book called Der Schwarze Urin, basically “the dark urine” published decades ago, that referenced a Prussian councilman. I spent a long time trying to understand the Latin text. 

Spelunking to find original material, original sources.

Yes. Wilhelm Roux is a scientist I write about in the book who adopted the ideas of Darwin and evolution to cells in the body. He was writing in the 1880s about how cells could compete against one another in the body within the bounds of natural selection. It turns out Nietzsche was a fan of Roux's writing in a big way, and there was a quote from Nietzsche that I include in the book that says “uniformity is delirium,” which is just one of my favorite quotes of all time. But I couldn't find it! I kept chasing the trail of crumbs, but I couldn't actually find the original. I ended up finding a French translation of the German, but then I couldn't actually find that first German source. 

I was actually in a co-working space when I found somebody who runs a Nietzsche fan club online. The website looks like it was made in 1992, no graphics or anything like that. He helped me find the original sourcing of that quote, and I stood up and punched the air in triumph. And all these coders looked at me like, "What did you do that was so great?" And I was like, "I found the source of a Nietzsche quote!" I think they thought I was literally a deranged person.

There’s a lot of science in this book. Where did you have to apply the most effort to understanding new things? 

That's an easy answer, and my editor would say the same thing. Chapter three is all about how our immune system requires mutation in order to make antibodies that we need to defend against pathogens. So it's all about the upside of mutation, with the caveat that autoimmunity is where that process goes wrong. You would think that after having spent several years reporting on all the immunology involved in COVID, that I had the adaptive and the innate immune response kind of finally understood after not grasping it in college or high school biology. But there's so much complexity in the immune system, and there's feedback loops—your immune cells actually learn not to keep trying to make the same antibodies that they've made that have worked before, they iterate to make even better ones—and just understanding that was an uphill battle. 

But it’s not just me! I talked about this to Michel Nussenzweig [professor of molecular immunology at the Rockefeller University] and I found out from one of his postdocs that Michele Nussenzweig's dad had actually published a Nature paper about this very same concept that Michel wasn't really that familiar with, or had forgotten about. Forget the history of science and scientists. Families don’t even know what their parents were doing!

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Beyond Inheritance probably ranks as one of the more science-heavy reads I’ve picked for Curious Reading Club. Biology is one of the harder disciplines for me to grasp, partly because it can machine gun you with very specific terms and concepts and jargon. You had to tiptoe through all that complexity, bring the reader through it. How did you approach it?

As you can probably imagine, that was the hardest part of this book. I used to teach—and I still teach sometimes—workshops to scientists on avoiding jargon. I was a professor when I was at Nature Medicine, and I was also teaching four years at the Alan Alda Center [at Stony Brook]: Alan is an actor turned science communicator/educator… such a wonderful person. I had already had the inclination to avoid jargon, but it was really drilled into me by the Alda Center team. So I think the hardest thing for me in this book was making it so that a scientist could enjoy it and somebody who didn't know a thing about biology could read it. I do think it's possible that if you write clearly enough, you can be specific without being too technical. 

My goal was to capture all this novelty in medicine in a way that a scientist who really wanted to know more could look at the references in the back of the book, and somebody who just wanted to know what was going on could just get to the next mystery.

You're writing something a lay reader can get their hands around, but you're not dumbing stuff down or manipulating it in order to make it understandable.

I'm thinking about fiction as you're saying this, and I'm thinking about The Handmaid's Tale. I grew up in Boston, and if you're not from Boston, you might not pick up on all the streets that she's mentioning here and there. But if you are from Boston and you read it, you're like, “oh hey!” I think it's possible in both non-fiction and fiction to kind of pepper things with enough signposts that people who are an expert in that area can know where you're at. But the signposts shouldn't be in a different language; they should just be pictures, very easy to understand.

I think the harder challenge in this book was that I wanted the book to be taken very seriously. But my hairdresser looked at the cover and he said "Oh, it looks like a party invitation.”

I was extremely offended because while there are women that write genetics books, there are relatively few compared to the number of men. So I was a little mortified that he thought it looked like an e-vite invitation. But the more I thought about it, I was like, you know what? The essence of this book, in a way, is inviting scientists from different centuries and different decades and different fields to get to know one another because they haven't been able to before. There's cancer biologists, there's immunologists, there's hematologists, and now there's you know doctors that study the liver, the brain, aging. They're all verging on this idea that non-inherited mutations have a huge impact on the course of these diseases, but they just haven't talked to each other enough. And I think that it was necessary for a book to bring it all together, so that you could see the grandness of the idea.

During the pandemic there were a lot of questions about why I got sick from COVID and my friend didn't, or vice versa. It intensified the questions amongst the public and myself about why certain people get sick, and how much of that is chance. I think that this book kind of starts to pick at how the randomness and non-randomness of the mutations we pick up through our lives can influence whether we get sick or not.

This is the bigger picture of the book: what it means in the future. Where is this understanding heading, what can it tell us? As we expand that view of ourselves, what do you see becoming possible? 

Two weeks ago I was at the American Society of Human Genetics meeting, which paradoxically was in Montreal, but that’s where I live so that was nice. And I was shocked at how adamant some of the people presenting were that we are going to be getting our genomes sequenced at the doctor's office, and then every time the doctor is going to start referring to our DNA. There’s already a test available, although it’s almost $1,000 and I wouldn't recommend people run out and get it; this is early stages of science—where you can find out if you have a threshold number of mutant blood cells circulating in your blood that can contribute to cancer. So I think we're going to be checking in on our DNA more frequently than we have in the past. 

We're all raised to think our DNA is the same in all our cells. So how can we develop a disease that's genetic if we weren't born with it? There's a question of environmental exposure—in the last months of wrapping up edits, I found out that we now can look at somebody's DNA who's been exposed to tobacco, and based on the pattern of mutations, you can actually discern whether they were smoking tobacco or chewing tobacco. We just have this kind of granularity in terms of understanding toxins and how they interfere with our DNA that we haven't before, so that’s going to open up a whole other discussion. 

I've also seen a stark change where almost the majority of families with kids that have a rare disease now are families in which there were no other relatives that had it. So many of them are what are called de novo germline mutation cases, but it's a blurring of lines between what is an inherited mutation versus what's one that's acquired? Because in some of these cases, it was a mutation that occurred in the sperm or ovaries of the parent... so it's technically inherited, but nobody else in the family tree has it.

And this is part of the complexity and the beauty of biology, right? Unlike some other sciences, there are so many complex and seemingly random things happening—we don’t know the answers. 

If I were to write a physics book, it might have felt like I was taking you to a Swiss watch factory, showing you how each watch is made, what the rules are, show how it’s replicable. But I wrote a biology book, so instead I took you to Vegas and I opened up the slot machines, and said “Check it out! Every time you pull the lever, something different happens.” Somebody who's going to enjoy this book is somebody who enjoys marveling at chaos, and all that can happen as a result.

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I’m sure there are people who will take their response to all this new genetic information to extremes, and I’m sure there are people who will profit from it too. But what do you think ordinary people will need to know, to understand? 

One example that comes to mind is a condition I write about in the book called VEXAS syndrome. Back in 2020, when the whole world was focused on COVID, there was a study published in the New England Journal of Medicine, in which they had identified a wholly unheard-of disease in which you have cells that have acquired a mutation, and they rise up in your blood and raise your risk of fever and runaway inflammation. It's slow burning, fatal, and it often strikes men who are older. The power of this knowledge is that we can now just know about different diseases we have never even considered, would never have known about, because we finally can look at cells individually and their genetic changes and track them over time better. So we're not only going to have insight into how common diseases have an acquired genetic component, or how mutation can over time in your life can cause common diseases, but we're also going to have insight into how mutation can be the underlier of diseases that we didn't even know before. That's something that might be powerful.

Companies are already looking at cells in people that have diseases of all different sorts that are resistant to those diseases, and they're already developing drugs based on targeting—replicating what those mutant cells do well. So in some ways, it won't just be about preventing mutation from happening, but learning about the good mutations that happen within us to kind of fight all of the bad stuff that's happening within.

So what books inspired you as you wrote Beyond Inheritance? 

I have Siddarth Mukherjee's The Gene over here, which is a really well liked book, and I think what he did was introduce a concept and the intellectual history of the concept. In some ways I was also trying to do an intellectual history, but I think the challenge I didn't realize that I was facing at the time was that I was also trying to introduce a concept at the same time. The Beak of the Finch was another one that I had, by Jonathan Weiner. I looked to that during the course of this book because it's about Darwin and it's about evolution. 

What about books that you appreciate a lot outside that? Are there ones you turn to again and again?

I will be really upfront: when I was a child, like in elementary school, I decided I wouldn't watch the same movie twice or read the same book twice because life is too short. But that’s not entirely true. I've read a couple of Orwell's books a few times because he's great, and I think I read a couple of Milan Kundera's books a few times because I was really into him in college and thought I'd break the rule for that. But generally, I don't go back to a book once I read it. 

So if the question is are there books that have inspired me? I mean, there's obviously the big hits: The Immortal Life of Henrietta Lacks is a great, loved book for so many good reasons. Lab Girl by Hope Jahrhen, also an amazing book. Those are examples where the author put herself in the book in a way that I didn't. Immediately after I sent the book off, I read Everything Is Tuberculosis by John Green. I thought that was just really well done, and he's not someone I traditionally had thought of as a science journalist, or science writer, so that was a pleasant surprise. And When We Cease to Understand The World, by Benjamin Labatut—you read that right? It's a really originally written book. It has so much kinetic energy in the sentences.

I don't know. I love books. I read them all the time, but the answer is that I don't necessarily have one that stays by my bedside.

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Thanks to Roxanne for her time and for her work! Next week we’ll start digging in deeper to November’s book of the month, The Castle by Jon Ronson—a very different prospect, but one that I hope you really enjoy.

Remember: If you aren’t already a member of the club or don’t have a copy of The Castle, you can sign up now to receive one.

And if you ever want to get a copy of one of our previous picks, there’s a limited number available via our online store.

Onwards

Bobbie