Why scientists are infuriated with a New Yorker article on epigenetics

To say scientists are unhappy about the New Yorker's recent feature on epigenetic research might be an understatement. Here are some complaints, assembled by the biologist Jerry Coyne on his blog:

"The New Yorker article is so wildly wrong that it defies rational analysis," writes Walter Gilbert, a biochemist who has won the Nobel prize.

"It is unfortunate to inflict this article, without proper scientific review, on the audience of The New Yorker," writes Sidney Altman, another Nobel Laureate.

"It really is a horribly damaging piece," writes John Greally, a genetics researcher at the Albert Einstein College of Medicine.

Yikes.

The piece in question is "Same But Different," a 6,000-word feature on the science of epigenetics by physician and science writer Siddhartha Mukherjee. He's best known for his 2010 book The Emperor of All Maladies: A Biography of Cancer. It won him the Pulitzer prize.

Here's the beef scientists have with Mukherjee and the New Yorker

The article is the type of piece the New Yorker usually is very good at: diving deep into a crevice of science and connecting it to veins of either history, politics, or the poetry of everyday life.

Mukherjee starts off with a personal tale. His mother and aunt are identical twins, and he muses on how their life experiences made them different people later on. He then connects this personal mystery with other mysteries in nature: Why are two ants genetically near identical but one is a worker and one is a boss?

In the story, what links these mysteries is the science of epigenetics, which, basically, explores how the environment can leave a lasting mark1 on how our genes work.

DNA is the instruction manual for life. So epigenetics may determine how likely those instructions are to be read. Understanding epigenetics is important because it could help us understand how we become more susceptible to disease (or not) over our lifetimes. And there's some not-yet-conclusive evidence that epigenetic information is inheritable. As Vox's Susannah Locke has explained, epigenetics means a person may pass on genes as well as experiences to a child.

It's cool stuff.

But the article seems to have hit a nerve with some researchers who feel "epigenetics" has become a buzzword that’s distorting the science.

What Mukherjee (mainly) gets wrong, according to the scientists, is his explanation of how this process is thought to work. Mukherjee's explanation is anchored in a discussion of histones, which are tiny proteins that act as a kind of a scaffolding for DNA. He leans heavily on the work of David Allis, a researcher at Rockefeller University, who has these histones open and close specific sections of DNA, which he says changes the output of the genes.

"The coils of DNA seemed to open and close in response to histone modifications — inhaling, exhaling, inhaling, like life," Mukherjee writes.

Next, Mukherjee notes (more vaguely) that scientists have found "other systems, too, that could scratch different kinds of code on the genome."

There are two main points the scientists are clamoring over.

One is that they say Allis's theory that histones actually change the output of genes is far from proven. In a second post on Coyne's blog, Greally and Mark Ptashne, a biologist at Sloan Kettering, write, "there is no evidence that coiling and uncoiling of DNA has a causal effect on gene activity."

The second is the critics say those glossed-over "other systems" are actually the prevailing theory on how it all works, and should be at least discussed at greater length.

The big, overarching, concept Mukherjee missed is "transcription factors," which are proteins that can turn specific genes on and off. It's these factors that scientists say should be the main focus of the explanation of how our genes are differentiated. And despite decades of research on them, transcription factors are hardly mentioned at all in the piece.

Steve Henikoff, a molecular biologist, writes on Coyne's blog:

Mukherjee seemed not to realize that transcription factors occupy the top of the hierarchy of epigenetic information, that this has been widely accepted in the broader chromatin [i.e. DNA] field, and that histone modifications at most act as cogs in the machinery that enforces the often complex programs specified by the binding of transcription factors.

(To note: The scientists have other concerns with the piece. You can read more about those here.)

Telling the "whole story" versus telling "one story"

I asked Mukherjee over email about the criticisms, and he sent me a very long point-by-point response to each comment collected by Coyne. Overall, he stands by the story. In summary, he says this:

"In re-reading the piece in the light of the critics, I realize that I did not emphasize the role of transcriptional factors and regulation adequately," Mukherjee writes in the email. "This was an error. I thought, sincerely, that I had talked about gene regulation, but an increased emphasis would have helped the piece, and not caused the polarizing response." (He also mentioned that the New Yorker article is an excerpt from an upcoming book, which will cover these topics more thoroughly.)

And for it's part, the New Yorker is standing by the story, too.

"None of it [the Mukherjee feature] negates the fundamental importance of transcription factors, and the foundational work on gene regulation done by a previous generation of scientists (or by scientists working on gene regulation today)," a New Yorker spokesperson told me in an email.

I can't fully analyze all the critics' concerns in this post. But this seems clear: If Murherkjee is guilty of something, it's omission. He didn't make it clear that other, prominent, scientists would choose to tell this story in a different way.

There are a lot of challenges in science writing, but one of the main ones is this: Research more often yields streams of caveats, not elegant conclusions. This fact makes trouble for another truth: As a writer, it's your job to take a reader from the beginning to the end of a piece as elegantly as possible.

There could be a lot of reasons why Mukherjee decided to focus on histones rather than transcription factors. They perhaps make for a more visual, compelling illustration of the inner workings of a cell. Maybe Allis was just a great interview, and a more compelling character upon which to carry the story's narrative.

These choices are compounded by this: "The original piece was almost twice its current length, with a lengthy historical section mentioning gene regulation," Mukherjee writes me. The print New Yorker only has so much space.

These choices aren't always easy, but in journalism, they're necessary. We can only tell one story at a time.