The human brain is, for want of a better word, ginormous. Sure, it’s only about as big as a cantaloupe, but it’s made of the hungriest cells in the human body. Keeping the brain supplied with energy is a huge challenge. In my new column in Discover, I describe how scientists have discovered some of the molecular tricks we’ve evolved to feed our neurological beast. Check it out.

In tomorrow’s New York Times, I’ve got a story about evolutionary biologists who make New York their Galapagos Islands. Working on this story was great fun–I traipsed around Manhattan parks and medians, checking out mice and ants and salamanders. I spoke to other researchers who study plants, fish, and bacteria in and around the city. All of them observe evolution unfolding in what might seem like a very unnatural place. But after four billion years, nothing can stop evolution. Not even New York.

The Times has posted some of Damon Winter’s wonderful photographs for the story along with some audio from some of the scientists I describe. You can also listen to the new podcast, which features the story too (link to come).

[ Photo: Creative Commons: NatalieTracy on Flickr ]

I’ve never met John McPhee, but he’s always been lurking around my office. I’ve got a number of his books, and I always keep an eye out for his latest piece in the New Yorker. I can’t count the number of times reading a few lines of his stuff helped get me revved up again for writing.

Recently, Alexis Madrigal of the Atlantic invited me to participate in a Neiman Storyboard series called “Why’s This So Good?” Writers pick out a good piece of long-form journalism and try to figure out what makes it so. Having just revisited out McPhee’s sprawling 1987 epic on engineering the Mississippi, “Atchafalaya,” I chose it for my object of study. Here’s my take. And, if you have a free moment to quaff 28,000 words, here’s McPhee’s piece.

It’s been very gratifying to listen to the conversation that’s been triggered by my essay in this Sunday’s New York Times on scientific self-correction. Here, for example, is an essay on the nature of errors in science by physicist Marcelo Gleiser at National Public Radio. Cognitive scientist Jon Brock muses on how to get null results published.

I also got an email from Eliot Smith, the editor of the Journal of Personality and Social Psychology who accepted the controversial clairvoyance paper I described in my essay. I wrote that three teams of scientists failed to replicate the results and that all three studies were rejected by the journal because they don’t accept simple replication studies.

Mr. Zimmer

Your recent Times column stated the following:

Best regards,
Eliot Smith

I’ve passed on Smith’s message to my editor at the Times, and I’ll also take this opporunity here to apologize for the error.

I’m not sure how meaningful it is in the context of my essay, since my point was that policies against publishing replication studies get in the way of science’s self-correction. But a mistake is a mistake.

In the late 1800s, prominent astronomers declared that Mars was criss-crossed by canals–evidence, they declared, of an advanced civilization. But in the early 1900s, astronomers gazed through more powerful telescopes and discovered that the canals were mirages.

The astronomer Percival Lowell, who had become the leading champion of the canals, scoffed at the new findings He declared that the criticism came “solely from those who without experience find it hard to believe or from lack of suitable conditions find it impossible to see.”

Although the new evidence led many astronomers to abandon Lowell’s position, he never retracted his claim. It wasn’t until five decades after his death in 1916 that space probes finally went into orbit around Mars and sent back close-up pictures of a canal-free Red Planet.

I’ve always been fascinated by the way science casts aside bad ideas. For most of us, it’s easy to assume that science shakes them off quickly, but the truth is that it can take quite a while for the process to play out. Recently I was invited to contribute a piece to the new “Sunday Review” section of the New York Times, which just debuted this week. I wrote an essay on this phenomenon, which has been dubbed  ”de-discovery.” I drew on three recent examples of high-profile research that many other scientists have declared to be wrong–arsenic life, clairvoyance, and a link from chronic fatigue syndrome to a virus called XMRV.

To keep my essay from exploding into a novella, I had to limit myself to just these three examples–but I could have picked many others. You just need to check out a blog like Retraction Watch to see how important this part of the scientific process is today. The first draft of my essay actually started out with a fourth example, which I decided to cut it in the end. It’s a peculiar case of a de-discovery of a de-discovery.

In 1981, the late Harvard paleontologist Stephen Jay Gould published an influential book about racism and science, called The Mismeasure of Man. Gould argued that social influences could lead scientists to misinterpret their data to suit their beliefs about European superiority. One of his key examples was the work of a nineteenth century anthropologist named Samuel George Morton.

Morton collected 1,000 human skulls from around the world and measured the size of their brain cavities with seeds or lead shot. Gould re-analyzed Morton’s data and published his results in 1978 in the journal Science. He declared that Morton fudged his measurements to ensure that Caucasians would end up with the biggest brains.

In 2000, a freshman at the University of Pennsylvania named Jason Lewis started to measure Morton’s skulls for a research project of his own. He was interested in the ways different human populations adapt to different climates—including changes in the shapes of their skulls. It was then that Lewis learned from his advisors about the controversies swirling around the skulls. (He was born a year after The Mismeasure of Man was published.)

As Lewis carried out his own measurements, he gradually realized that Gould had been wrong. He then set out to systematically investigate the matter—taking three years to measure Morton’s skulls, and then another five years to work through Gould’s claims.

Lewis, who just finished earning his Ph.D at Stanford University, wrote up the results with his colleagues and submitted a paper in 2008 to the journal Current Anthropology, which had published a less detailed critique of Gould’s paper in the 1980s. The journal rejected Lewis’s paper, eventually informing him that it was not important enough.

The researchers had better luck with PLOS Biology, which published their paper earlier this month. Lewis and his colleagues presented evidence that Morton did not bias his findings at all. Instead, the researchers conclude, it was Gould who used shoddy statistics. There are many sound scientific reasons to reject racist views of human biology, they argue, but an unfair trashing of Morton’s research isn’t one of them.

“Our analysis of Gould’s claims reveals that most of Gould’s criticisms are poorly supported or falsified,” they write.

When I was researching my essay, I asked Lewis about what he thought of science’s self-correcting process now that he’s finally done with his exploration of Gould and Morton. He has decidedly mixed feelings.

“We can come back thirty years later and get the story straight,” he told me. “But it takes thirty years.”

As I write in my essay in the Times, there are certainly ways to make dediscovery a smoother, faster process. But in an age of instant viral communication, I think we’re going to remain frustrated by inescapable lags.

[Image: Wikipedia. Thanks to folks on Twitter for pointing me to Martian canals as a textbook case of slow dediscovery]

I just got back yesterday from the annual meeting of the Society for the Study of Evolution. It took place in a big hotel on the outskirts of Norman, Oklahoma, during a windy heat wave that felt like the Hair Dryer of the Gods. It had been a few years since I had last been to an SSE meeting, and I was struck by how genomic everything has gotten. No matter how obscure the species scientists are studying, they seem to have outrageous heaps of DNA sequence to analyze. A few years ago, they would have been content with a few scraps. Fortunately, SSE hasn’t turned its back on good old natural history. There were lots of fascinating discoveries on offer, about species that I had assumed had been studied to death. My favorite was a talk about the rough-skinned newt, the most ridiculously poisonous animal in America.

The scientific tale of the rough-skinned newt begins five decades ago, with a story about three dead hunters in Oregon. Reportedly, the bodies of the hunters were discovered around a camp fire. They showed no signs of injury, and nothing had been stolen. The only strange thing about the scene was the coffee pot. Curled up inside was a newt.

In the 1960s, a biologist named Butch Brodie got curious about the story. The newt in the coffee pot–known as the rough-skinned newt–has a dull brown back, but when it is disturbed, it bends its head backward like a contortionist to reveal an orange belly as bright as candy corn. Bright colors are common among poisonous animals. It’s a signal that says, in effect, “If you know what’s good for you, you’ll leave me alone.” Brodie wondered if the newts were toxic, too.

Toxic, it turns out, doesn’t do the newts justice. They are little death machines. The newts produce a chemical in their skin called tetrodotoxin, or TTX for short, that’s made by other poisonous animals like pufferfish. Locking onto sodium channels on the surface of neurons, TTX blocks signals in the nervous system, leading to a quick death. In fact, TTX is 10,000 times deadlier than cyanide. While we may never know for sure what killed those three Oregon hunters, we do know that a single rough-skinned newt could have easily produced enough TTX to kill them, and have plenty of poison left over to kill dozens more.

Now, if the whole idea of evolution makes you uneasy, you might react by saying, “That couldn’t possibly have evolved.” Experience has shown that this is not a wise thing to say. Brodie said something different: the most plausible explanation for a ridiculously poisonous animal is that it is locked in a coevolutionary arms race with a ridiculously well-defended predator. Another biologist mentioned to him that he’d seen garter snakes dining on rough-skinned newts, and so Brodie investigated. He discovered that garter snakes in rough-skinned newt territory have evolved peculiar shape to the receptors on their neurons that TTX would normally grab.

The coevolution of newts and snakes became a family business. Brodie’s son, Edmund, grew up catching newts, and today he’s a biologist at the University of Virginia. Father and son and colleagues have discovered that snakes have independently evolved the same mutations to their receptors in some populations, while evolving other mutations with the same effect in other populations. They’ve also found that both newts and snakes pay a cost for their weaponry. The newts put in a lot of energy into making TTX that could be directed to growing and making baby newts. The evolved receptors in garter snakes don’t just protect them from TTX; they also leave the snakes slower than vulnerable snakes. They’ve studied newts and snakes up and down the west coast of North America and found a huge range of TTX potency and resistance. That’s what you’d expect from a coevolutionary process in which local populations are adapting to each other in different environments, with different costs and benefits to escalating the fight.

This story is so irresistible that I’ve written about it twice: first, ten years ago in Evolution: The Triumph of an Idea,, and then in updated form last year in The Tangled Bank. I figured that the Brodies et al had pretty much discovered all there was to know about these creatures. But in Oklahoma, I discovered that they had missed what is arguably the coolest part of the whole story.

Think about it: you’re a female newt, you’ve fended off attackers with a staggering amounts of poison in your skin, and now you want to pass on your genes to your descendants. You lay a heap of eggs in a pond, and what happens? A bunch of pond creatures come rushing in and have a feast of amphibian caviar.

What could you possibly do to ensure at least some of your offspring survived? Well, you have an awful lot of TTX in your system. You have enough of the stuff to give your eggs a parting gift to help them out there in the cruel, predator-infested world. Make your eggs poisonous.

That is exactly what female newts do. In fact, they load their eggs with TTX. To figure out if this poison provided a defense against predators, the Brodies and their students traveled to a group of ponds in central Oregon that are home to thousands of rough-skinned newts apiece. They collected dragonflies and other aquatic predators from the ponds and put them in buckets filled with newt eggs, along with muck from the pond bottoms. The scientists found that almost none of the predators would touch the newt eggs. Since these predators eat plenty of eggs of other species, this result shows that TTX does indeed help the newt eggs survive.

But there was one exception. Caddisfly larvae turned out to relish the newt eggs. In fact, the caddisflies actually grew bigger if they were supplied with newt eggs and pond muck than with pond muck alone. And yet the Brodies and their students estimate that there’s enough TTX in one newt egg to kill somewhere between 500 and 3700 caddisflies.

You know where this is going. At the evolution meeting, one of their students, Brian Gall, described feeding newt skin to caddisflies both from the central Oregon ponds and from ponds elsewhere without newts. The newt-free caddisflies would happily munch on newt skin from which all the TTX was removed. But if there was more than a trace TTX in the skin, they refused to eat. The caddisflies that fed on newt eggs, on the other hand, would eat the most toxic skin Gall could provide.

It appears that the caddisflies have evolved much like the garter snakes. In ponds where rough-skinned newts lived, the caddisflies have evolved defenses against TTX. In fact, Gall reported, the caddisflies appear to put the snakes to shame. Evolved snakes are 34 times more resistant to TTX than vulnerable ones. The caddisflies have increased their resistance 175 times.

It’s not clear whether the caddisflies and the newts are truly co-evolving, however. The Brodies will have to find out whether adding extra TTX to eggs increases their survival in the presence of caddisflies. Another intriguing possibility arises from their discovery that the caddisflies actually harbor some of the TTX they eat in their tissues for weeks after eating the eggs. Perhaps the caddisflies are stealing the poison to protect themselves, as happens in monarch butterflies eating toxic milkweed.

In other words, this wonderfully deadly story isn’t over yet.

[For more information, see this new paper in Can. J. Zool., and Understanding Evolution, an educational web site. Ed Brodie tells much of the story pre-caddisfly in a chapter of the new book, In The Light of Evolution (full disclosure: I wrote a chapter in it, too, which you can read as a pdf here)]

Image: California Herps

The Wall Street Journal asked me to review another book. This time around it’s Virolution, by Frank Ryan. It’s about a lot of things that I’m pretty crazy about (like the viruses that make up a lot of our genome). But I wasn’t crazy about the book itself, I’m afraid. Still, the review was a good opportunity to talk about what our inner viruses may mean for our well-being. Check it out.

Pain is a paradox. It feels like the most real, objective experience we can have, and yet it can be weirdly malleable. It’s better to think of pain, like memory or vision, not as a simple reflection of the world, but as a strategy we’ve evolved to stay alive. Thinking this way can help make sense of the awful experience of chronic pain, when this urgent signal refers to nothing except a brain caught in its own feedback loops. In my latest column for Discover, I take a look at the latest understanding of pain, and some promising research that uses these insights to search for a new, more rational pain-killer. Check it out.

[Image: Boy With A Rooster by Adriano Cecioni, 1868. Photo from Kate Eliot/Flickr via Creative Commons License]

On Friday, as the E. coli outbreak gained horrific speed in Germany, Newsweek asked me to write about how this epidemic came to be. Scientists still have a lot to figure out about it, but some things are clear–in particular, that the bacteria have great scope for evolution into new deadly strains, thanks in part to the shuttling of viruses between them. (In my book Microcosm, I explain how this is true not just for E. coli, but for much of life.) My piece appears in the new issue of Newsweek, which you can read online here. (One late-breaking piece of news that didn’t make it in, by the way, is the finding yesterday that the new outbreak appears to have come from bean sprouts.)

While I was working on my Newsweek piece, a reporter for the BBC called me up for an article on the good side of E. coli. I explained how much of how we understand about life itself came out of research on this typically harmless bug, and that the biotechnology industry was build upon its biology. That piece came out over the weekend. Check it out.

[Image: glass microbe by Luke Jerram]

One of the most important things that virus-hunters do is “de-discover” links between viruses and diseases. In other words, they follow up on studies that indicate a link and see if it can really hold up. Last year, a team of scientists published a paper in Science in which they reported that 67% of people they studied who suffer from chronic fatigue syndrome carried a virus in their system known as XMRV. Only 3.7% of healthy people did. That association then morphed into the idea that XMRV actually causes chronic fatigue (a condition that afflicts an estimated 60 million people worldwide). Some people with chronic fatigue have sought anti-viral medicines based on the finding, declaring that they’ve felt better as a result. But when a lot of other scientists tried to find XMRV, they failed to do so.

Today Science itself is publishing two papers that cast even more doubt on the link. In one study, scientists looked at 61 samples from the same medical practice where the original samples had come from. They couldn’t find any XMRV in people with chronic fatigue.

Another study supports what a lot of experts have been saying recently: that XMRV was not actually infecting the cells of people with chronic fatigue, but merely contaminated the samples once they were in labs. The researchers came to this conclusion through some evolutionary detective work.

XMRV was first discovered in 2006 in a line of human prostate cells, and since then it’s been reported to be present in 6 to 27% of human prostate cells. Before the link to chronic fatigue was claimed last year, some researchers argued that XMRV can also cause prostate cancer.

XMRV belongs to a family of viruses that infect mice and can sometimes even integrate their genes into their host’s genome. Yet Vinay Pathak of the National Cancer Institute and his colleagues could not find XMRV in mice. What they did find, however, were two previously unknown viruses that were strikingly similar to parts of XMRV. In fact, XMRV looks like a hybrid of the two viruses.

How could the viruses come together? And how could they end up in human prostate cancer cells? A crucial clue is the fact that scientists who study prostate cancer cell lines have to inject them into mice to keep them alive. They then “passage” the cells from one mouse to another. Pathak and his colleagues went back to the prostate cancer cells that scientists reared in mice in the early 1990s and couldn’t find XMRV. But they did find one of the two precursor viruses. Only in later generations of the cancer cells did they find true XMRV.

The scientists concluded that as prostate cancer cells were injected in mice, viruses migrated from the mice to the cancer cells. Then the viruses were carried to the next mouse inside the cancer cells.  At some point during these passages, two different mouse viruses recombined in the human prostate cells to produce XMRV. Thus, rather than being a virus that naturally circulates in humans or mice (or both), XMRV is a virus that emerged in human cell cultures in labs and can contaminate samples that scientists bring into their labs.

These two papers have prompted Science editor-in-chief Bruce Alberts to publish an expression of concern.” He writes that the initial findings of an XMRV-chronic fatigue link are ”now seriously in question.” Amy Docker Marcus of the Wall Street Journal reports that Science asked the authors of the initial study to retract the paper, but they’re not backing down.

The next (and perhaps final) stage in this saga will come in the next few months. As I reported in the New York Times last fall, the National Institutes of Health launched a replication study in which the original XMRV team and other researchers who failed to find the virus will all search for the virus again, using exactly the same set of agreed-upon protocols.

For more on this story, check out Marcus’s excellent reporting over the past few months for the Journal, plus this piece in Nature.

The World Science Festival is going to kick off on Wednesday in New York (I’ll be speaking Thursday on a panel, on telling the stories of science in print and online.) The festival organizers have been publishing a blog on some of the topics that will be explored next week. Riffing on the session on sleep, I’ve just contributed a piece on some wonderful recent research on what it means for us to be asleep and to be awake–and the surprising porous wall that divides the two states of mind. Check it out.

[Image: Wikipedia]

It’s been six months since #arseniclife became one of my favorite hashtags on Twitter. Over at Slate, I look at how the online conversation has changed the way scientists do their work. Check it out.