Optogenetics Relieves Depression in a Mouse Trial

At left, area in mouse cortex targeted in optogenetics study; at right, Area 25, in human brain, targeted in DBS studies by Mayberg and colleagues.

Not making this up: A team of researchers has used light to make a mouse’s brain run better and relieve the mouse’s mousy version of depression. (Paper — a pdf download — is here.) This is potentially pretty big. For one thing, it’s what science writer John Pavlus would call awesome. For another, it expands and elaborates on remarkable work by neurologist Helen Mayberg and colleagues tweaking human depression circuits with conventional deep brain stimulators. This optogenetic work suggests a less intrusive, even more exacting way to test, define, and tweak such circuits.

The researchers, led by Stanford University’s Karl Deisseroth and UT Southwestern psychiatrist Eric Nestler, used optogenetics — a technique that makes specific neurons sensitive to light and then lets you use light to activate or silence them — to increase activity in a key part of a mouse’s prefrontal cortex.

As the researchers put it,

we used viral vectors to overexpress channel rhodopsin 2 (a light-activated cation channel) in mouse mPFC to optogenetically drive “burst” patterns of cortical firing in vivo and examine the behavioral consequences….. In … mice that expressed a strong depressive-like phenotype [in reaction to chronic social defeat — that is, losing dominance struggles with other mice] …, optogenetic stimulation of mPFC exerted potent antidepressant-like effects, without affecting general locomotor activity, anxiety-like behaviors, or social memory. These results indicate that the activity of the mPFC is a key determinant of depression-like behavior, as well as antidepressant responses.

The Guardian has a good  description of this technique, and YouTube has a vid of Deisseroth, its main developer, describing it. This fancy intervention managed to ramp up the activity of a key part of the mouse’s forebrain and  relieve their depression: That is, after the treatment, the mice, which had been made depressed by repeated “social defeat” experiences, ran mazes better, ate more normally, and did better in social contacts with other mice. They also showed gene expression and other changes in their brains consistent with feeling and doing better.

This follows up on a line of work I’ve been tracking for years: Emory neurologist Helen Mayberg’s experimental manipulation of depression circuits in humans. As I’ve explained before, Mayberg, working on small groups of patients in pilot studies, has relieved otherwise uncurable depression in about 60 percent of patients by snaking wires into their brains and sending low-voltage current to a highly particular spot called Area 25. Area 25 seems to be a hyperactive area in depressed people — a sort of gate that left open. Lightly buzzing Area 25 appears to calm both it and nearby areas such as the amygdala associated with anxiety and fear. And calming it seems to ramp up activity in the forebrain. When it works, anxiety areas ramp down; thinking areas ramp up; patient feels better, starts living again.

Mayberg has suggested several times, including in a recent talk at the Society of Neuroscience annual meeting, that she thought it might be possible to use other means less intrusive than drills and wires — optogenetics in particular — to tweak the circuit she’s been buzzing with her stimulators. (Optogenetics as now done is still pretty intrusive, but seems to have more potential for lower-impact use down the line. It can also be targeted more specifically than DBS can.)

Nestler, Deisseroth and company have now essentially used optogenetics to replicate Mayberg’s work in mice, and it seems to have worked. Their target — a particular area in the mouse’s ventral-medial PFC — is a rough mouse equivalent of Area 25 in humans, which Mayberg targets in her DBS pilot studies.

The usual needs-more-work caveats apply here, of course. Dynamics that affect mouse depression  sometimes carry to people and sometimes don’t. And a key question is which of the many areas downstream of the ventral-medial PFC this affects, and whether this more exacting method actually ends up hitting the same or different areas that the DBS technique hits. Hitting specific areas with accuracy exact might be good. On the other hand, as with antibiotics, sometimes a little slop is a good thing. No one knows. But if Deisseroth et alia or others take this line of work further, they may find out.

Any way you cut it, this is a damned intriguing and potentially very significant piece of work. I’ll be interested to see what happens if — it’s probably more a matter of when — they, or Mayberg, or someone else tries it in humans.

More reading:

Karl Deisseroth’s Oct 2010 Scientific American article on optogenetics

Controlling the Brain with Light (video)

Deisseroth Lab, Stanford University

Light switches on the brain (recent article on Deisseroth’s work by Mo Costandi)

Eric J. Nestler – Wikipedia, the free encyclopedia

Helen Mayberg on Charlie Rose

A Depression Switch? – My New York Times Magazine feature on Mayberg’s work

Your Librarian is Really Huey Lewis

You take an LP album cover and hold it up in front of someone so it looks like your buddy is, say, Huey Lewis. Has to be in a library. Voila: You have a site called Library Sleevefacing, hatched by librarians at Bowling Green State University, god bless ’em. I know it’s extremely nerdy. But I can’t enough of this thing.

Plus now we know why libraries keep all those LPs around even though hardly anyone listens to them.

The man with the news.

Just joking around:

And so on. Go. Dig. It’s worth it to hit the Elton John.

And I love this: The link at each entry leads to the catalog entry, at the library where the photo was taken, of the album being held up. Perfecto.

Sneaking into Google Street View … with your sneakers

Richard Grant, an editor at Faculty 1000, has pulled a weird coup of the hyperlinked, meta-mapped, internet age: Not content to try to find a picture of himself or his house on Google Streetview, he put himself in the picture: made it happen. Involved a camera, quick feet, and a low-speed pursuit of a Google Streetview car-camera in the streets of London. Apparently a little time away from the desk as well. Don’t tell his boss.

I’ll let him tell (and show) it. From his blog Confessions of a Lab Rat, a post aptly titled The Onlooker:

It’s just not cool to simply photograph the Google Street View car any more. And finding yourself on Street View is just so passé.

The trick now is to photograph the Street View car and match it up with the photo it takes of you.

You may remember that last summer I was strolling along Cleveland Street in search of some lunch, when the fabled Google Street car passed me, and looped the block. Indeed, I offered a drink to the first person to spot me.

It looks like I might have to buy myself that drink. Here’s a photo I took:


and here is me, about three seconds after taking it:


Check out Google itself for the full picture. If you look to the right you’ll see that chap in the white shirt has passed the pale concrete slab, and on the left those two pigeons have taken off in the time between my shot, and the Street View.

Hah. Gotcha, Google.

And you thought Cambridge-trained molecular biologists lived unglamorous lives.

NB: I’m a little unsure Brits use “sneakers” the way Yanks do: syn to tennis/athletic shoes. Don’t want Richard to think I’m suggesting he was sneaking around.

Why Do Moms Kill Their Kids?

Why do mothers kill their children? Over at Scientific American, guest blogger Eric Michael Johnson, of Primate Diaries fame, has fashioned a nicely turned essay considering one answer  to this question— or at least a partial answer — offered by researcher Dario Maestripieri: When mothers kill their children, they are reacting to a particularly toxic combination of stress, powerlessness, and social disadvantage.

Maestripieri, Johnson writes,

has spent most of his career studying maternal behavior in primates. In particular, he’s focused on the factors that influence a mother’s motivation towards her young. As a professor of Comparative Human Development, Evolutionary Biology, Neurobiology, and Psychiatry at the University of Chicago he has enjoyed the kind of cross-disciplinary success that most scientists only dream of. His 153 academic papers and six books have been cited more than a thousand times by scholars (including this one) in many of the world’s top scientific journals. His latest paper is scheduled to be published in early 2011 by the American Journal of Primatology. In it Maestripieri lays out the argument he’s built over the last two decades showing how one of the most serious impacts on maternal behavior, one with potentially lethal results, is so common in modern life as to be nearly invisible: stress.

Johnson notes right off that stress is usually a good thing, for it’s really a way to ramp up mind and body to meet a challenge, whether fighting off an attack, calming a screaming toddler, or giving a talk before a big crowd. Most of the time our “stress response” — a heightened energy and vigilance driven by (among other things) a rise in cortisol levels — serves us well. Extended and or intense stress, however, does not. It erodes the body and tends to lead to behaviors that aren’t adaptive.

In this case the maladaptive behavior is the murder of one’s children, and to examine it, Johnson looks at Maestripieri’s work on how stress affects mothering in rhesus macaque monkeys — and how that effect differs in monkeys of different social strata. This area remains ripe despite being heavily harvested. Both Maestripieri and Stephen Suomi, among others, have shown that within the high-stakes hierarchy of rhesus society, status plays a huge role in a monkey’s health, lifespan, and genetic success (that is, whether and how robustly the monkey passes on his or genes). Monkeys with secure positions in higher-status family groups  do better on all these counts because they  get more food and mating opportunities and have more allies in the sometimes violent power struggles through which rhesus work out their social positions.

Being low in this hierarchy has serious consequences, as Maestripieri found when he studied monkeys in a large, wild colony on an island in Puerto Rico:

[T]he team analyzed the colony’s mortality records covering a period of ten years and found that infants born to low-ranking females were much more likely to die in their first year than those born to high-ranking ones. As a result, low-ranking mothers were living in a state of constant panic. They would watch as their offspring were confronted by dangerous group members but they were powerless to do anything about it. Unable to act while their innate warning system screamed at high alert, their anxiety simply grew, expanding out of proportion as a result of the social inequality.

Average change in cortisol levels for pregnant/lactating females in three social ranks. Image reproduced from Hoffman et al. (2010).

I’m not sure the anxiety expanded out of proportion; you could argue that an anxious response is proportional in the sense that it recognizes that the offspring face grave odds. On the other hand, you could consider it out of proportion because it can drive responses that make matters worse. Stressed-out rhesus mothers, for instance, tend to  be overcontrolling or overly harsh with their offspring. This generates anxiety in the young monkey and compromises its social skills. This in turn continues the cycle of low status, social isolation, and stress. As often happens in life,  poor responses help create a self-reinforcing loop.

In any case, Johnson, apparently echoing the researchers, emphasizes that poverty, low social status, and a feeling of helplessness can combine with other problems to create a deadly mix — including heightening the chance that a mother will kill her children.

I don’t doubt it. Johnson cites this as good reason to address root causes of poverty, and I can’t disagree with that either; it is a good reason to address poverty more seriously, and in particular to create economic policies that prevent long stretches of unemployment. A society as wealthy as ours should be able to do these things. Instead we seem to be headed the other way.

So I agree with what we might call the social lessons Johnson draws from these studies. But I wonder if stopping there pulls us up short of some of the more interesting scientific implications of these studies. I wonder if stopping there mires us in a vision of environment that gives it too much primacy. It suggests that environment is deterministic.

Now, I know that Johnson doesn’t think the environment is deterministic; he’s a smart guy schooled in evolutionary biology, and he knows very well that not only do genes play a role in how we respond to our environments, but that our response comes out of a sort of black box — a highly complicated set mechanisms still hidden from us — in which genes and environment experience produce a behavior that in turn determines outcome more directly than environment does. In this case, for instance, the behavior is murder, and the outcome is dead children. Clearly the social environment, the tremendous stress of poverty and social isolation, contributes. But that’s not all that’s going on in the black box. And the problem with stopping with environment as a cause — as an endpoint to a social argument, if not a scientific argument — is that it leaves the black box closed. And I think this is a time when we should be trying to crack open that black box

Unfortunately, the black box here — the one in which genes and experience mysteriously mix to create behavior that determines our fates — is a Pandora’s box politically. We have been long stuck in an argument about nature versus nurture,  genes versus environment, in which the nature/gene argument is associated with conservative and racist views, which emphasize individual agency, and the environment/nurture argument is associated with liberal views that seek to legislate an egalitarian, fair, decent society. I’m all for the latter. I understand the political dangers of overemphasizing agency: of pushing the idea that since behavior shapes our fates, people who want their lives to go well should simply behave differently — as if it’s just as easy for the poor kid to act with confidence, consistency, and strength, to say nothing of skillsets, as it is for his richer, more fortunate peers. That’s a warped view. It  ignores that the poor kid who achieves great success is notable precisely because she defies the odds.

So yes, putting behavior on the table makes for a trickier game. But I think when we end discussions of the scientific links between environment and poor outcomes with a simple call for better environments, we trap the conversation in a place from which we need to move on — and can move on now that we’re getting a better handle on how genes and environment mix to produce behavior. We can begin, for instance, to  reframe how we view genetic variants that clearly affect our responses to environment. We can get a richer view inside the black box and see dynamics that can simultaneously emphasize the environment, one’s genes, and one’s agency. We can recognize that behavior occurs not as the endpoint of a set of prior experiences — a domino that is struck and falls — but as part of a circular dynamic in which behavior is both cause and effect.

This may be an arbitrary caveat to raise about a strong, intelligent, insightful essay I largely agree with. And I don’t know exactly where to go with this discussion, or how Johnson might have left me feeling more satisfied with his treatment. Yet as much I enjoyed the piece, I did finish it feeling slightly unsatisfied. And I think this is because Johnson, in trying to emphasize a link between poor environments and a certain outcome–in this case, poverty and the murder of children — left closed a black box that I think we should take every chance to open.

I would love to see, for instance, those low-ranking, stressed out monkey mothers in the Maestripieri study split by genotype. For as I noted in an article about stressed-out rhesus moms that Suomi studied, neurotic rhesus mothers in low social positions are more likely to raise neurotic, low-status offpsring if the mothers themselves were a)  raised in such circumstances themselves and — a huge and — b) they carry the S-allele of the serotonin transporter gene, which is associated with greater sensitivity to environment in general and social experience in particular. It’s this combination that produces the risk — that creates a disproportionate number of the overanxious, undernurturing moms, the high cortisol levels and low social skills, the self-perpetuating loop of low status and inherited and taught dysfunction.

Figuring out how that works is a lot harder than just pointing to environment. But it seems to me a more interesting problem. And in a world where the “He’s a product of his environment” argument is not exactly carrying the day anyway, perhaps this more complex problem is a more fruitful one to explore politically as well as scientifically.

I say this not knowing where it will lead —except out of a dead-end argument we’ve been having for too long anyway.

[Ed. note, 25 Nov 2010: fixed a mess of typos and confusing diction (some due to voice-recognition software booboos) and a few sloppy constructions. No substantive changes.]

Image: Eugene Delacroix, Medea prepares to kill her children. Courtesy Wikimedia Commons.

The Bright Side of the “Depression-Risk Gene”

The reclamation of the “depression gene” proceeds apace: In a paper titled “Looking on the Bright Side of Serotonin Transporter Gene Variation,” two researchers who helped establish the “depression risk-gene” view of depression assert quite strongly that people with the gene variant in question — the s-allele of the serotonin transporter gene, HTTLPR  — possess greater social sensitivity than do people without this variant, and hold certain cognitive advantages as well.

From the abstract:

Here, we review recent findings that humans and nonhuman primates carrying the s variant of the 5-HTTLPR outperform subjects carrying the long allele in an array of cognitive tasks and show increased social conformity. In addition, studies in 5-HTT knockout rodents are included that provide complementary insights in the beneficial effects of the 5-HTTLPR s-allele. We postulate that hypervigilance, mediated by hyperactivity in corticolimbic structures, may be the common denominator in the anxiety-related traits and (social) cognitive superiority of s-allele carriers and that environmental conditions determine whether a response will turn out to be negative (emotional) or positive (cognitive, in conformity with the social group). Taken together, these findings urge for a conceptual change in the current deficit-oriented connotation of the 5-HTTLPR variants. In fact, these factors may counterbalance or completely offset the negative consequences of the anxiety-related traits. This notion may not only explain the modest effect size of the 5-HTTLPR and inconsistent reports but may also lead to a more refined appreciation of allelic variation in 5-HTT function.

Faithful readers will recognize this as an idea I explored in my Atlantic feature last year, The Orchid Children: that certain ‘risk’ genes, among them the s-allele version of this serotonin transporter gene, create not just risk but a higher overall sensitivity that can create upsides. Many papers have provided data supporting this view. But other than reviews from psychologist Jay Belsky, who was one of the first to assert this notion, few scientists have articulated this idea as boldly and plainly as Judith Homberg and Karl-Peter Lesch do here. That Lesch  first discovered the stress-reactivity created by the s-allele back in 1995 — opening the door to the ‘depression-risk-gene’ view of the s-allele — only heightens the impact of this call to see this ‘depression gene’ differently.

Call it the sensitivity gene, perhaps — or the orchid gene, as I called it in my article.

So what are some of the advantageous traits the s-allele can create? Its benefits (and downsides), Homberg and Lesch assert, rise from “hypervigilance.” By this they essentially mean an increased attention to social dynamics around them.

Physiologically, this shows in an especially reactive amygdala — a couple of deep-brain, almond-sized nuggets  central to fear learning. The amygdala of S-allele carriers show more reaction to things like fearful faces, negative language, and other signs of threat. Yet as Homberg and Lesch point out, the amygdala plays a key role in a wide range of learning, both positive and negative, including (and perhaps especially) in social realms. The amygdala’s extra sensitivity in S-allele carriers may make them more attuned to social dynamics — improving their social cognition, say Homberg and Lesch, and some forms of non-social cognition as well.

These would-be depressives, for instance, do better in a particular “affective” type of go/no-go task, in which you have to stifle an intentional motor response based on the emotional valence of words; this presumably, because S-allele carriers better sense the emotional temperature of language. (Emotionally alert readers, take note — or had you already?)

S-allele carriers (S-S or S-L) have also done better than the more common L-allele carriers (L-L) in some gambling-based decision-making studies. In general they seem more sensitive to context. Rhesus macaques with an S-allele version of the same gene also show stronger cognition in a roughly similar array of tests. Finally, people with S alleles tend to have better episodic memory — memories of things that happened, rather than straight facts — than L-carriers do.

On the cognitive downside, S-allele people aren’t as good as L-allele carriers at remembering a noun if it occurs soon before another noun that is emotionally laden — as if the more charged noun made them forget its predecessor. They also don’t do as well as the infamous Iowa gambling task — possibly because that cognitive game has few emotional cues. There are quite a few cognitive tests in which the variant seems to have no effect.

Add it up, say Lomberg and Lesch, and you have a gene variant that, rather than just Creating depression risk, creates social sensitivity, increased attentiveness, and a “wide range of cognitive functions” that include improved decisions making and cognitive flexibility in many situations. This may provide an evolutionary advantage, since it seems to make people more sensitive to changes in environments and threats of different sorts. “They’re the ones,” as one researchers told me not long ago, “who, back in evolutionary time, would be the first to notice the strangers on the horizon.”

This happens to reach me as I fly to San Diego to attend the first meeting of the Society for Social Neuroscience and then the Society for Neuroscience meeting. I suspect this will be a major topic of discussion.

PS: Forgive the sparse linkage; the slow internet on this plane makes it rather difficult. I’ll try to make up for it later.

Thanks, H.M., for the link at 30,000 feet.

Do mummies have a right to privacy?

Do mummies have a right to privacy? Halloween seems a good time to ponder such questions, so last week I had a talk with medical historian and writer Howard Markel, who thinks about such things. The interview ran at the Responsibility Project. In the excerpt below, Markel notes that when we dig up a mummy, we have most definitely violated the wishes of the person who once inhabited that body. We also discuss whether genotyping mummies — as researchers recently did with King Tut, revealing that his parents were incestuous siblings — carries that violation further.

Dobbs: Why do researchers want to study the DNA of mummies and other old bodies?

Markel: Mummies offer a unique quarry for paleopathologists and historians: well-preserved, albeit long dead, bodies and organs. Ordinarily, after less than a hundred years, there’s not much left to a body other than the skeleton. You can find out a lot from bones through carbon dating and so on. You can also use DNA analysis to search for infectious agents that may have spread to that corpse’s bones. But it’s nothing like the wealth of pathological material you can extract from a preserved body. And the mummification process developed by the Egyptians was remarkably good at preserving human organs and tissues. You can do a better examination on a mummy than on any other human remains I can think of, unless, perhaps, a body frozen in permafrost.

Today, genetic tools let us find out even more. In King Tut’s body, for instance, the DNA analysis showed that he had one of the earliest recorded cases of malaria and an inherited bone disorder. This is valuable health and historical information. The researchers were also able to better establish the lineage of the pharaoh’s family, which is of great importance to Egyptologists because it helps tell us how the pharaohs’ preserved political power and conducted their personal lives.

So analyzing the DNA can increase our knowledge about medicine and diseases. And it can increase our knowledge of the historical record, sometimes in a way nothing else can; all that is of real value. But it’s not free and clear. We all have to ask whether the value we get from such bodily intrusions transcends the ethical, moral, or religious compromises we must make. You have to balance public good against individual privacy rights and considerations.

Dobbs: Did you have any qualms about whether the benefits outweighed the privacy violations in the King Tut case?

Markel: I think with Tut the benefits outweighed the compromises. Moreover, the researchers conducting this study took great pains to consult ethicists and policymakers. That said, I remain of mixed mind about the growing enterprise of exhuming bodies for research.

To start with, digging up bodies automatically gets you into murky territory. Unless they’ve willed their bodies to science, most people expect their bodies to be left alone. And we know the mummies especially expected that. They made those tombs difficult to get into for a reason: They did not want to be disturbed as they went on to the River of the Dead and the afterlife. But we found them, and we have disturbed them repeatedly.

Dobbs: So we have violated their wishes. How do we justify this?

Markel: In Tut’s case, that cow left the barn back in the 1920s, when his tomb was discovered. His remains have been examined numerous times over the past 90 years, and his possessions have been the stuff of museum shows for decades.

But we also have to acknowledge that Tut’s privacy desires have been repeatedly overridden in the name of research and exhibition. Intellectuals want answers to their questions. Historians dig into the past. We love to read other people’s mail; we read their diaries. Sometimes people have given their letters or diaries to posterity, so there’s no gray area. Other times, we are required to weigh the privacy of the dead against the need or desire to extract meaningful historical information. Looking at DNA is essentially an extension of these sorts of incursions.

Read the whole thing here.

Road Trip to Mars, Sex Included

I should note right away there’s no sex in the video posted here, which is from a TED talk about colonizing Mars; no sense in getting you all frustrated. The video is just one thing, along with an article about sex on mars, offered by Journal of Cosmology’s special issue, “Colonizing Mars.”  The Journal of Cosmology really wants us to go to Mars.

The Human Mission to Mars must commence now, and it must be an international effort.  The online scientific Journal of Cosmology, four astronauts, and over 70 top scientists are now leading the way with the publication of over 50 online articles which explain how a mission to the red planet can be successfully accomplished.

That’s from an email I got last week drawing my attention to this special issue. The email ended with a link to an article addressing a particularly touchy aspect of such a mission: What to do about sex. I can’t help but like an email that ends, “We also recommend: Sex on Mars.” But it was so unexpected I actually thought the whole thing was a hoax. Some digging around revealed it was not.

The Journal’s email has seven points. Each gets a paragraph of elaboration. But you get the drift from the talking points:

1. America Has Lost the Race for Space

2. How did the U.S. Lose the Race for Space? Stupidity.

3. The Journal of Cosmology, Former Apollo Astronauts, and Over 70 Top Scientists Step into the Leadership Gap.

4. Onward to Mars: The Greatest Adventure in the History of Humanity. Paid for by Private Companies

5. The Conquest of Mars vs the Iraq War (“The contrasts are stark: $145 billion to conquer an entire planet, vs a trillion dollars to fight a war which has accomplished nothing except to sew destruction, kill and maim a lot of innocent people, and enrich the few.”)

6. The U.S. Government Has No Serious Interest in Conquering Space

7. The Mission to Mars Must Commence Now.

Our battle cry: Onward to Mars.

I read this and thought, cosmologists don’t think small. And why should they? We didn’t get to the moon thinking small. The editors of the Journal of Cosmology certainly don’t. Here’s their mission statement:

Most scientific journals are aimed at specific, narrowly defined areas of research; tailored to those specialists who devote their lives to learning more and more about less and less. The alternative, we are told, is to learn less and less about more and more, and thus “generalists” and interdisciplinary journals are rare indeed, for how many wish to discover how little they know?

The interdisciplinary Journal of Cosmology is devoted to the study of “cosmology” and is dedicated to those men and women of rare genius and curiosity who wish to understand more and more about more and more: The study of existence in its totality.

Previous special issues address the Origins of Life (it came from other planets), the Infinite Universe, and the search for life elsewhere. I’ve not had time to do but skim some of the articles, but this looks worth a browse.

So does the website of the journal’s editor, Harvard astrophysicist Rudolf Schild. His photo essays about the cars and motorcycles he has owned and loved over the years, and of his rather interesting family, makes an interesting tour through recent time.

And of course there’s the article about sex on Mars. Sorry, no pics.

How I Wrote “The Orchid Children,” via Open Notebook

A promising new website about science writing, The Open Notebook, features an interview with me about the genesis of my Atlantic article of last year on the genetics of temperament, “The Orchid Children” (aka “The Science of Success” in online version).

The site, produced by science journalists Siri Carpenter and Jeanne Erdmann,

is a craft-focused site for science journalists. Science journalism is changing, but the ability to recognize and sharpen important ideas, ask incisive questions about complex subjects, and tell accurate, compelling stories—often on shorter deadlines and with fewer reporting and editorial resources than ever before—is all the more important to serious science journalists’ success. Our goal is to promote outstanding craftsmanship.

To do so they’re running interviews with writers about how they came across, pitched, sold, and reported and wrote stories. They toss in extra material such as pitch letters, rough drafts as well. The launch issue includes interviews with Robert Krok about her article about an asteroid heading toward Earth and Dan Ferber on his story on a couple wrestling with the farm next door. There are more to come this week and afterwards. This looks like an intriguing site for anyone interested in writing or the different approaches writers take to finding, selling, developing, and writing stories.

Below is a bit from my interview with Carpenter. One thing I’d like to change: I see that I said that researchers in this field are innately “flashy.” I’m not sure if Carpenter misheard me or I just misspoke. I suspect the latter. But I don’t know why I said such a thing. These people are interesting, to be sure. But flashy? T’ain’t in it.I must have been in a geek fever or something. The things that come out of our mouths.

Below are excerpts from mine. Get the whole thing, and the others, at The Open Notebook

The Orchid Children (published online as “The Science of Success”)

By David Dobbs (Atlantic, December 2009)

In a story selected for The Best American Science & Nature Writing 2010, David Dobbs explores the “orchid hypothesis”: the tantalizing idea that certain variants of some behavioral genes can either increase children’s risk for psychiatric and behavioral problems or enable them to flourish spectacularly. Moving from ornery toddlers to a troop of rebellious monkeys to a reckoning with his own DNA, Dobbs reveals how—depending on environment—an accident of genetics can be either a “trap door” to failure or a “springboard” to success.

Where did you first learn about what you term the “orchid hypothesis”?

While I was at a scientific meeting working on a story about adolescence, I went to a talk on gene-by-environment interactions in toddlers by Ariel Knafo, a psychologist at Hebrew University. It was absolutely fascinating. His results showed that kids who had one version of this dopamine-processing gene, and who also had harsh parenting, got less and less sociable and agreeable over time. The opposite was true for kids with the same gene variant but who had warm parenting. Then at the same meeting, I saw another talk by [NIH’s] Stephen Suomi, which showed the same basic dynamic in rhesus monkeys.

What made you think this research would make a good story?

There was very excited talk in the halls about this research, and it was immediately apparent that this idea—that genes thought to make us more sensitive to bad environment actually make us more sensitive to all environments—was hugely important for how you view genetics and human behavior. I could tell it wasn’t just the people at the center of the research who were interested in this because there was such a diverse group of people, all in a gaggle, talking about Knafo’s talk. It was obviously something that’s drawing wide interest. I did quite a few interviews at that meeting, with people testing or pushing the idea and with people who were hearing of it the first time.


What were your first steps in developing the idea?

Well my first step was talking to a lot of people at the conference—to take advantage of an opportunity to talk to so many in the field. I wanted to see what people thought, and to bullshit-filter the idea. When I got home, I read a bunch of the literature—a couple dozen papers, I would guess, to start with. Then called a few people I know who aren’t in that direct line of work but who were knowledgeable about the idea. I was looking for a reasonable evidence base under this idea, which there was, and the reactions of good, smart scientists to it. The people I talked to acknowledged that this thing has legs. Some offered caveats and things to watch for as well, which was quite useful when I turned to writing the pitch. If it had a thin evidence base or seemed theoretically flimsy, I would have set it aside.


How did you think about the story’s structure?

There were certain elements that I was pretty sure I wanted and some that I got lucky with. For instance, I wasn’t sure what I would do with all this material I had on Suomi’s research, but then while I was working on the story, this amazing monkey coup happened, where one group of monkeys ousted the top group of monkeys, killing a few of them. It was one of those things that, when it happened, I realized this is great for the story. It was quite dramatic. It illustrated some vital things about the ideas in play. And it drew some new thoughts from Suomi. I met with Suomi about two weeks later, and you could see in his face, and hear in the timbre of his voice,  how big a deal it was. It seemed to affect him emotionally as well. Which it would. He follows these monkeys for years, and suddenly they’re killing each other.

There’s a fairly robust literature growing to support the orchid hypothesis. Yet I noticed that in the piece, you really only described in detail the research of a few teams. How did you decide whose research to highlight and whose to gloss over?

Some of that is almost arbitrary. For example, I had three candidates to lead off with. I opened with the work focusing on early childhood because it makes the dynamics easier to understand, and because it included an observation of actual behavior, which brought the whole idea to life. It was also the only controlled experiment that imposed a specific change of environment and watched what happened. Finally, it was possible—though quite difficult—to describe in about 400 words, which is about how much space I had allocated for that part.

Your decision to undergo DNA analysis yourself, and the results of that analysis, make for a lovely and thought-provoking ending. Did you plan to do that from the beginning of your involvement in the story?

I did not plan on it; that’s not the kind of thing I usually do in my stories. Part of the reason I started to think about doing it was sort of the idea that I should put my money where my mouth was—to ask myself, does this really give me that sense of a greater range rather than a steeper slope?

I mentioned to my editor that I was thinking of doing that, and he thought that that would add a lot, but left it to my comfort level. In the first draft, I had it all up at the front of the story. It was his idea to break it in half. This was not the assigning editor, who was Don Peck, but a former staffer named Toby Lester, who sometimes edits features for them. He was an enormous pleasure to work with, and crucial to moving such a complex story from conception to submission in just a couple months.

How long did you spend on the story?

I worked on it full time for about seven to eight weeks, 50-plus hours a week. Maybe roughly four to five weeks of that was research, three to four weeks flat-out writing. Then I spent a week doing revisions after editing.

Why such a short time frame?

The magazine had a hole they wanted to fill, and that’s a very good situation to be in because there’s a sense of urgency about the story, and it gives you an opportunity to help them out of a jam. That can only raise your currency. It’s a good first impression to make. So it met some of my purposes even though it destroyed my summer.

This article spawned a book project for you. How did that process unfold?

I was thinking book from the very beginning, actually—from the first day I ran into the idea at the conference.  After I finished the story in August, I went to New York, interviewed four agents, and chose one—a wonderful young agent named Eric Lupfer. We had about three weeks till the article would come out. We quickly settled on a structure for the book and the proposal, and in about ten days of back-and-forth, we drafted a 10-page proposal. This was hard but fun, and easier than it usually is because we had the article to present as the writing sample for the book. The proposal part just had to describe the book and give an outline.

Incredibly, everything went just as hoped: Eric sent the proposal out the week before the article was printed, with an advance copy attached, and the week the article appeared, generating a lot of buzz, we met with seven different publishers. Several bid, and in the end I signed with Amanda Cook at Houghton Mifflin Harcourt, whom I’d already met and liked and who came highly recommended.

Biden’s Foresight: You’re Not Ready for the Truth

This is Biden, just before the election:

I promise you, you are all gonna be sitting here a year from now going, ‘Oh, my God, why are they there in the polls, why is the polling so down, why is this thing so tough?” Biden said at a fund-raiser in Seattle just before the election. “We’re gonna have to make some incredibly tough decisions in the first two years. So I’m asking you now, I’m asking you now, be prepared to stick with us. Remember the faith you had at this point because you’re going to have to reinforce us.” Predicting a deficit “that may be as high as $750 billion” — how quaint that sounds — Biden told the crowd, “Only thing I’m asking you is, you know, gird your loins.

Quite startling, and speaks to both the unreality of our politics and the lack of staying power from many Democrats.

More from the Atlantic Wire.