KSJ Tracker December 5, 2013

Esquire: A 'whole new way of killing cancer'?

[Editor's note: See more here with Esquire's response calling this post "grotesque," and my reply.]

If you're looking for "a whole new way of killing cancer," don't turn to the journals. You'll find it in Esquire.

There Tom Junod and Mark Warren write about a scientist who says the difference between others' research and his is "the difference between medieval alchemy and chemistry."  Trained as a mathematician, he picked up biology from textbooks. "Molecular biology, after pure math, struck him as ridiculously easy," Junod and Warren write.

Some of this puffery seems to come from the mouth of the scientist, Eric Schadt (photo)--chair of the Mount Sinai School of Medicine's Department of Genetics and Genomic Sciences in New York and director of its Icahn Institute for Genomics and Multiscale Biology. But Junod and Warren make no effort to tone it down.

Eric SchadtAnd they are quick to add their own accolades. He worked for Merck, where it was true at one point that "half the drugs in development started in Schadt's lab," they write. "Then he told Merck they wouldn't work."

That's because Schadt's research had taught him "that the underlying faith of molecular biology—of all biology, since Watson and Crick had elucidated the structure of the DNA molecule—was false." Molecular biology is not only ridiculously easy; it's a fraud.

We can say one thing about the story: it leaves little doubt where Schadt stands.

Schadt's road-to-Damascus vision was that pursuing links between genes and disease "was a strategy doomed to fail, because disease arose not from single genes or pathways but rather out of vast networks of genes and pathways whose interactions could be understood only by supercomputers guided by abstruse algorithms." The only hint in the story that some had doubts was that Merck declined to bankroll Schadt's new strategy, after he'd spent millions developing drugs that wouldn't work. Or so Junod and Warren report.

But that didn't stop him for long. He soon found "a gambler" to support him. "Well, not really—he heard from Mount Sinai, a century-and-a-half-old hospital and medical school on the East Side of Manhattan," Junod and Warren write. With $150 million from the investor and philanthropist Carl Icahn, Mount Sinai hired Schadt to "claim the future of biology."

It goes on like this. The problem, as you've probably figured out by now, is that this account of Schadt's peerless intelligence appears to rest solely on what the reporters were told by Schadt himself. How do we know that he is anywhere near as smart as he claims to be? What we'd like to read is whether Schadt's view of his own intelligence is shared by any other biologists, who are in a position to know far more about his work and influence than Junod and Warren. As far as we can tell from the piece, the writers naively accepted everything Schadt said, without making any effort to check it out.

In 2009, The New York Times published a short profile of Schadt, in which Lee Hood, a pioneer in the study of pathways and networks of genes, said that Schadt "has the ability to take what everyone knows and think about it in novel ways. He is exceptional at thinking outside the box." That is far more persuasive and helpful than Junod's and Warren's "the underlying faith of molecular biology...was false." Indeed, Hood and Schadt were two of the co-founders of a company Merck bought, which is how Schadt wound up there. The short profile in the Times, which has none of the flash and radiance of Junod and Warren's prose, tells us a few important things that Esquire should have told us as well--but perhaps interviews with others would disrupt that crackling narrative. And what's more important? I suspect Junod and Warren would say, "The narrative!" I would argue for the reporting, even at the risk of slowing the narrative a trifle.

Instead, Junod and Warren are asking us to take their word for it: This guy's a crackerjack, and we wouldn't be writing about him if he weren't. Now close your trap and let us tell the story. The authors' reliance on our trust is unfortunately undermined by their swaggering storytelling, their hyperbole, and the constant straining for the edgy metaphor. They sound like a couple of guys eager for a barroom wager: I'll bet our guy Schadt is smarter than any damn scientist you can find!

It isn't enough for them that Schadt is a smart guy with a good idea; he has to be the smartest guy with the best idea--the only idea! To fit Junod's and Warren's mold, Schadt can't merely challenge his colleagues, he has to prove their entire careers are built on a lie.

This wasn't the first time Esquire put this in such stark terms. Junod and Warren were partly cribbing from Junod's 2011 profile of Schadt in Esquire. Entitled "Adventures in Extreme Science," the story carried this subhed: "From Crick and Watson through J. Craig Venter, we had all our eggs in one basket — molecular biology, gene mapping, whatever you want to call it. It failed. And now we're counting on this guy."

Schadt's networks of networks do take molecular biology into a new area, but they don't prove it failed. Quite the opposite: Schadt could not do his work if the human genome had not been sequenced. Molecular biology is the universe in which Schadt operates; gene sequencing and mapping are the tools he must have to do his research. Schadt is doing what all scientists do--building on the success and failures of the past. Molecular biology might not have cured all disease--apparently the standard by which Schadt wants to judge it--but it has succeeded brilliantly at providing the tools and the data Schadt needs to construct his networks.

If Junod and Warren understand this, they are unwilling to admit it. And let's face it: The story of a revolutionary scientist overthrowing decades of work costing hundreds of billions of dollars is a far more exciting narrative than the story of preliminary research that is likely to be years away from doing anyone any good. By Schadt's and Junod's own standard--curing disease--Schadt has so far failed more completely than molecular biologists. They've cured a few; he hasn't cured a single one.

Looking back through the record just a little bit, it seems there are reasons to be skeptical of Junod's work. If you're a fan of Michael Stipe and R.E.M., you might remember this, from an Esquire profile of Stipe originally published in 2001 and republished online Jan. 4, 2013:

He had sat down in the booth of the old-line coffee shop in L. A., declined the waitress's offer of eggs and coffee, and then unscrewed the top of the sugar jar and eaten heartily, first with a spoon and then, as the jar emptied, simply by tipping it into his mouth.

Whether you remember it or not, you might be interested to know that Junod later admitted making it up. Junod and Esquire's editor, David Granger, defended themselves by pointing to this in the subhed:

He is the singer for a great band, but he's a bit... generic. Hell, in order to make him a great mythic rock-'n'-roller, it's almost as if you have to make half the story up. So that's what we did. But only half.

And where is it written that Junod and Granger have to make him a mythic rock-'n'-roller? If he's generic, by which they must mean dull, they should do a profile of someone else. They also noted that the original story linked to annotation that showed what was true and what was false. That link does not appear in this year's re-publication. At the time, Peter Carlson of The Washington Post wrote, "Basically, every scene involving Stipe's eccentric or idiotic behavior is fiction."

On the other hand, Junod is a two-time winner of the National Magazine Award and a 10-time finalist, according to Wikipedia. So what do we conclude? Magazine editors prefer overheated prose to facts? I can't figure it out.

The Schadt story--which runs about 13,000 words--was headlined, "There's a Whole New Way of Killing Cancer. Stephanie Lee Is the Test Case. An Amazing Story by Tom Junod & Mark Warren." (Raeburn's rule: When the editors have to tell you it's an amazing story, it probably isn't.) The story appeared online around the end of October. I can't find a date on it, but Esquire published an update on Nov. 20 entitled "Patient Zero: One Month Later." (The story's URL suggests it appears in the December issue of the magazine.)

To keep readers' attention for 13,000 words, Junod and Warren needed rich central characters--there are only two of them, Schadt and a patient named Stephanie Lee--and a crackling narrative. And on those points, they deliver. The story is gripping, and the characters are engaging.

But what we really want to know is what is Schadt's whole new way of killing cancer? And did it save Stephanie Lee's life?

*    *    *

The story begins with Warren receiving an email on May 7 of this year from Stephanie Lee, whom he had met in 2005 in Mississippi when working on a story called "Mississippi Goddamn," about how Hurricane Katrina had affected military families. Lee told him she had just found out she had colon cancer. We quickly learn that Lee, "a fine-boned beauty with an intimidating reserve of tensile strength, a single mother whose face settled easily into stoicism and whose eyes lit up with challenge and dare," had lost her husband in Iraq two months earlier, when she was seven months' pregnant, and that she gave birth to a daughter three days after Katrina. Warren and Lee kept in touch through Facebook. Shortly after she messaged Warren that she had colon cancer, she found out that it was stage four.  Warren says he "was on the phone with her the day she was told she was going to die."

We then cut to the introduction of Schadt, where we learn not only about his scientific career and disdain for molecular biologists, but his idiosyncrasies. "No matter the season, he still shows up at both work and most social functions in a uniform of white polo shirt and hiking shorts. He still drives fast enough to terrify his colleagues, though instead of going to work in California on a motorcycle at a hundred miles per hour, he now runs two miles to catch a train to New York City, where he then runs another mile and a half to his office." He is "squat and powerful, his imposingly lumpy brow a phrenologist's dream and his nose the size of a crab apple," they write. Schadt now has everything he needs to pursue his vision, they write, except patients: "He needed someone like Stephanie Lee."

The story now seesaws between Schadt and Lee. Junod and Warren treat Lee with more care and measured language than they expend on Schadt, and I think we understand why. Schadt is a public figure, accustomed to seeing his name in print; Lee is not. What's curious, however, is Lee's attachment to Warren. They seem to be more than Facebook friends. They seem like close friends. Junod and Warren don't say that, but one wonders: How did Lee, who lives in Ocean Springs, Mississippi, on the Gulf, connect with Schadt on the Upper East Side of Manhattan? When they cut back to Schadt, they write, "On June 22, two days after he'd found out about her diagnosis, Schadt called her in Mississippi and told her about a research study he was conducting..." But how did he find out? I guessed that Warren and Junod must have put them in touch. And in an interview on WNYC's Leonard Lopate Show on Nov. 27, Junod said that's what happened. That's something they should have told us in the story.

Lee was accepted into that study. Junod and Warren carefully emphasize an important point here: The study is intended to study tumor genes to identify vulnerabilities that can be exploited with drugs to kill the tumors. Its purpose was not to save the lives of its subjects, but to assemble data that could help save the lives of many others later on. For Schadt, who was not a doctor, Lee was not a patient. She was a subject.

We then get much, much more about Lee and her treatment in Mississippi, where she is receiving the best available therapies--what's known as the "standard of care." Nothing Schadt's research might suggest as a possible treatment could be tried until the conventional treatment had failed.

Back in New York, where it has taken more than a month to obtain Lee's tissue samples for study, Junod and Warren walk us through the initial analyses. Here, Junod and Warren betray their fascination with big numbers. Schadt and his team are going to compare Lee's genes with the genes in her tumors, from which they would learn something about her cancer and the mutations that led to it. But the data "would contain millions of bits of genetic information" and "would exist right on the edge of incoherence." Schadt and his colleagues "would strive both to make sense of it and complicate it." The genes in Lee's tumors would be compared with reference databases and plotted against Schadt's network models with their "billions and even trillions of connections." The result would be similar to a model on Schadt's screen, "a blue sphere of genetic entanglement that resembled nothing less than the universe itself." The "mutant particularities of Stephanie's cancer" would "cohere into a malign galaxy the relative size of Andromeda."

This gives us a powerful image--or does it? Do we understand anything about Lee's case by knowing that the data can be made to look like some blue and red concatenation of dots? We're now probably 10,000 words into this story--and we still know little about Lee's tumors, little about what Schadt has found out, and nothing about whether any of his billions of data points will help her.

By Oct. 1, Schadt had an answer: There was nothing they could do.

Schadt admitted "that he was 'not a cancer expert'" and sought out those at Mount Sinai who were. And now, very late in the story, we are told for the first time that three of the mutations in Lee's tumor genes were transferred to a fruit fly for further study--not by Schadt, but by Ross Cagan, another researcher at Mount Sinai. Was he one of those molecular biologists still relying on the old paradigm that Schadt had proven to be false? We're not told. But now Lee's hope of a cure seems to rest with Cagan--not with Schadt, who had found molecular biology to be ridiculously easy. Have Junod and Warren pulled a bait-and-switch on us? Even Cagan's promising lead, however, will not be acted on until Lee has surgery to remove tumors that have spread to her liver--the treatment she likely would have received if she had never connected with Schadt.

But other doctors who reviewed the case suggested that Schadt and Cagan might have more time to continue the work, because Lee had a 40 percent chance to survive for five years. Here Junod and Warren's interest in adding drama to their narrative leads them into a heartless error. "Of course, after three or four years, the patient would die; they always do." That line is offensive. It's untrue, and it's a cruel thing to say to readers with cancer. It's a cruel thing to say to Stephanie Lee. If people with cancer have a 40 percent chance of five-year survival, then they don't always die after three or four years.

The story ends with Lee facing surgery in New Orleans. In the Nov. 20 update, Junod and Warren write that the surgery was successful, and that more tumor tissue had been frozen and sent to Mount Sinai, where it would undergo further analysis. Schadt emails the writers to say "I hope that we look back on this five years from now and just smile at all that has been done since, how this was really the beginning of it all."

That's how they wrap up the update. After all the time we've spent reading about the smartest biologist in the world (or something close to that), we are left with a single clue that actually came from somebody else's laboratory. The writers describe Lee as Patient Zero, because they think of her as the epicenter of "a whole new way of killing cancer."

That was the story's promise, and that was the promise for Stephanie Lee. And Junod and Warren have let all of us down. Lee believes the work at Mount Sinai will be her salvation. When her surgeon came to check on her after the operation, he asked if she had any questions:

She didn’t ask about pain or recovery or risk. "Please freeze my tissue so they can analyze it in New York” was the only thing she said.

The story is a disappointment. There is no new way of killing cancer. Not yet. For Lee, it's more than a disappointment. It's a false hope. She thinks the research in New York will save her life.

Schadt, Junod and Warren report, says her chance is one in a thousand.

-Paul Raeburn

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