plasticity

Guest Blog: Physiological Plasticity of Tenrecs

dr. dolittle — Wed, 22 Apr 2015 12:32:46 +0000

Guest Blog: Physiological Plasticity of Tenrecs

Dr. Frank van Breukelen, Comparative Physiologist, University of Nevada, Las Vegas

Dr. Frank van Breukelen is an Associate Professor in the School of Life Sciences at the University of Nevada, Las Vegas. He was invited to tell us about a new research project in this laboratory about some really cool mammals called tenrecs.

Here is the post:

In a recent post, Dr. Dolittle mentioned a talk that we gave at the Experimental Biology meetings in Boston. We discussed some of our recent data on tenrecs in a symposium about physiological plasticity- the ability of an animal to change its physiology in response to changes in the environment. We’ve had the tenrecs for less than a year but we’re finding suggests that they may one of the most plastic mammals ever investigated.

Tenrecs are a group of ~35 species and all but 3 of these species lives in Madagascar. Tenrecs are Afrotherians meaning that they’re related to such diverse mammals as elephants, manatees, and aardvarks. They share features with what we suspect is our earliest placental mammals. They even have a cloaca- a single urogenital opening like reptiles, amphibians, birds, and fishes. The only other mammals to have a cloaca are the monotremes- the egg laying mammals like the platypus or echidna. There’s tremendous diversity in tenrecs. Some look like hedgehogs, rats, mice, shrews, otters, and others are just really bizarre looking like the streaked tenrecs. We work with common tenrecs (Tenrec ecaudatus). A colleague, Dr. Barry Lovegrove of South Africa, published a paper in 2014 that demonstrated that unlike every other known small hibernator, this particular species of tenrec does not periodically arouse from hibernation. Most of my work is on mammalian hibernation using ground squirrels. Torpor is the depressed metabolic state of hibernation. Ground squirrels go into torpor and core body temperatures can go to as low as -2.9 °C e.g. below the freezing point of water. But these squirrels arouse every one to three weeks and maintain a body temperature of 36 °C for 12-20 h before going back into torpor. Soil temperatures in Madagascar are much warmer and where Barry and his students did their work, the coldest temperatures were above 20 °C. Based on all of our previous work, we thought that if we cooled tenrecs down, they’d have to arouse from torpor.

Common tenrec (Tenrec ecaudatus)

In June, we brought in some tenrecs from the wild. They were already torpid. To make a long story short, they don’t have classic interbout arousals. The tenrecs are able to warm a bit here and there but their hibernation represents a very unique and novel form. The tenrecs are always torpid during the Austral (Southern Hemisphere) winter. They may be more or less torpid. If we housed the animals at cold temperatures of 12 °C, they were more torpid. If we housed them at 28 °C, they were less torpid. If we handled them, they were less torpid. But they were always torpid.

Our data suggest that they may be doing what we call the plesiomorphic (evolutionarily ancestral) form of hibernation. There are enormous mismatches in processes that we always thought were linked. For instance, we see large changes in heart rate with half the change in oxygen consumption. Such differences would suggest major problems with maintaining homeostasis (the idea of keeping a relatively constant internal environment). There are no hard data for hibernating tenrecs, but we know that in ground squirrels as many as 20-50% of adult squirrels and as many as 70% of juvenile squirrels may die each winter during hibernation. In other words, hibernation is tough on squirrels. We think it’s even tougher on tenrecs but only time and data will tell that tale.

Tenrecs came out of hibernation at very different times. Animals gradually become more and more active over the course of weeks. Ground squirrels don’t do this and another colleague of mine could tell you within days of when his squirrels will emerge from their burrows each year. Our tenrecs came out of hibernation as early as August and as late as December. They ate enormous amounts. Even though many weighed less than 250 g in August, they would gain 20-30 g per day with one tenrec actually gaining >50 g in a day. This even happened in adults! That growth plasticity is very unusual in mammals.
Reproduction in tenrecs is really bizarre. T. ecaudatus have been reported to have litters of up to 32 babies. Our litters were not that big but we still found some crazy stuff. Baby tenrecs will eat from their mother’s mouth within the first week of life. Some of our baby tenrecs grew to adult size (over 400 g) in less than 5 weeks! Baby tenrecs can communicate by stridulation where they rub their spines together.
What was most interesting for us was that these tenrecs have variable body temperature. When we house tenrecs at low ambient temperature like 12 °C, some tenrecs defended their body temperature between ~28 and 32 °C. Others let their body temperature oscillate [see figure below]. When a tenrec had a body temperature of 14 °C, they were still active and able to run. Even more crazy was that the next day, an animal that was defending its body temperature could be oscillating and vice versa. On top of it all, we had animals during the active season that could go into torpor at any temperature from 12-28 °C. Their body temperature would be near ambient and their oxygen consumption would be very low.

Graph depicting the body temperature of two tenrecs (female #3 and male #4) showing the variable nature of thermoregulation in the active season. Tenrecs may show very different responses depending on day. The green points represent ambient temperature (12 °C).

Some of our tenrecs are already hibernating for the season and others are not. We’re working to try and understand the energetics of hibernation and the role of protein metabolism during hibernation. Since the tenrecs have variable body temperature, we can directly test some of the major hypotheses for the evolution of endothermy and homeothermy (warm-bloodedness).

dr. dolittle Wed, 04/22/2015 - 08:32

Your genetic info -- not free, easy, or clear

ddobbs — Thu, 01 Apr 2010 09:03:53 +0000

Your genetic info -- not free, easy, or clear

After I wrote in my Atlantic article about getting my serotonin transporter gene assayed (which revealed that I carry that gene's apparently more plastic short-short form), I started getting a lot of email â several a week â from readers asking how to have their SERT gene tested. This led to an interesting hunt.

It was a hard question to answer. I couldn't just tell people to do what I did, for a psychiatric researcher/MD I'd known for years, who specializes in depression and serotonin, had done mine as a sort of favor to science and journalism. That researcher also stood by, had I needed it, to offer counseling and more information about the result's implications â an important point.

Obviously I couldn't pass that researcher's name out to several dozen strangers. Yet the readers who wrote wanted the information for the same reason I did: They wanted to know whether they had a genetic variant that by the conventional reading simply increased your risk of depression, but by another reading â the hypothesis explored in my article â conferred a broader sensitivity to experience, which can be a good thing.

As I well knew, this is powerful information. It opens a big box with lots of compartments. Those compartments hold things like the recently raised (but far from settled) question of how solid a connection the S/S variant holds to depression. They hold the question of how a person might interpret the results, and whether they have the emotional, intellectual, and social assets to make the most of the information; as well as the whole pile of broader issues raised by the growing availability of spitomics.

Challenging territory. Yet in this case the biggest challenge my serotonin-curious readers encountered was just getting the test in the first place. For try as we might, we could not find a place to run a SERT assay. People would try various companies, such as 23andme, and report back that they'd struck out. I suspect this is because the lawyers at such companies likely advise against giving test results regarding mental illness to people whose very interest in the test suggested they might be prone to depression.

So I started suggesting the long route to my solution: Try to find a psychiatrist at a research university interested in serotonin and convince that person, with your doctor's help if need be, to run the assay. That too proved elusive.

But one particular reader (I'll call her Natalie, which is not her real name) refused to give up. She wrote me back in early February saying her therapist had given her the Atlantic article, and she wanted to know her SERT type. She suspected she was indeed S/S. So off she went a-hunting. She struck out with the major gene-testing services, but after several back-and-forths and dead ends, seemed very close to getting an assay done at a nearby research university. The psychiatrist there, having read the article, seemed game, and set up an appointment. When she visited him, medical history in hand, the psychiatrist "was conscientious, thorough, and very interested, but understandably cautious." She liked him. But he ultimately declined to prescribe the test. He told her, she wrote me, that

the general body of research was inconclusive and contradictory, [and] professional organizations (such as AMA for geneticists) advised against it. Presently doing the test "would do more harm than good" and I should check back every few years when perhaps the test would provide concrete information. I think he was highly ethical and also covering his ass.

I think she's right. It's easy to understand this doctor's response. Some have lately questioned whether the S/S confers risk. Even if you believe the S/S does confer risk (and the field is very much split on this), do you want to deliver that news to someone whose depression might lead them to take the news badly? The view of S/S as a 'risk' gene rather than a plasticity gene remains the prevailing paradigm. And it seemed to drive the no-test decision Natalie and other readers encountered âeven though, in Natalie's case, she had shown the researcher the article and told him she was viewing the potential results as a sign of sensitivity rather than just risk.

But just at this point, where the road seemed to peter out completely, Karen found, hidden in the weeds, a lab that would run the SERT assay. Why would they do it?. Because, they said, "Researchers have found that mutations in some genes specifically change how effectively SSRIs may act," and that in the SERT gene, "[p]patients who have the short allele are less likely to respond to SSRIs or may take longer to respond."

This is true â but only in some trials, but not in others. The data on the SERT gene's effect on SSRI response is mixed. Yet it's interesting that the company lean on this to offer the test.

No matter to Natalie. She's primed to see what she's got. "I can tell you right now I am hoping for the short-short," she says. "The process is in the works for me, so now we shall see. This is so much fun."

I obviously think people should be able to get this information â though they should get it with some informed counseling. But this entire hunt, and the various reasons to give or not give people this information about themselves, raises a mess of intriguing and often slippery issues. The genetic testing industry, and the understandable excitement about the potential and power of genomic information, generally assumes that we either don't know a gene's meaning or that we do. But the case of the SERT gene shows that a gene's meaning can be far from certain -- and that it can change substantially as researchers do more work on it and view the existing data from different angles. Here we have a gene variant â possibly the most prominent in behavioral science, certainly in psychiatry â that, depending on whom you ask, is bad news, no news, or news whose meaning ... depends.

As the genome's parts come into view, their meaning sometimes shift. How will the fast-spreading, fast-growing gene-information industry handle this movement? How do you give people advice about a gene whose meaning seems to be changing? How, say, would a pre-conception gene counseling service, something along the lines of Counsyl, handle this dilemma?

This isn't something we'll figure out in a few blog posts; it's something the industry and the broader genomics community will need to consider carefully over the next few years, even as it rapidly grows. I'll be talking about and leading discussions on these questions at the upcoming GET conference in Cambridge and then at a closed workshop at the Institute for the Future â a start. Your own ideas â as well as pointers to other explorations of these questions â are most welcome in the comments or via the Twittersphere.

ddobbs Thu, 04/01/2010 - 05:03

"Your genetic info -- not free, easy, or clear."

And not useful, either.

They know the gene for Rett syndrome. Anything useful come of that yet?

They know the gene for Huntington's disease. Got a cure yet?

They know the gene for the familial form of ALS a/k/a Lou Gehrig's disease. Even though the familial form is only around 10% or so - nothing useful there either.

And so it goes.

They find "the gene for" whatever it may, but it does absolutely no good. They have, as the British like to say, the wrong end of the stick. Disgusting.

I disagree with this drama. I am old enough to remember when we didn't have the tech to know the sex of an unborn child. And then we did and then we had the same kind of discussion you and others like to engage in. As hard as it is to believe, people thought it would be "hard to handle" and they would need counseling. Scenarios were given such as, "Suppose this is the 4th child and all are girls and dad wants a boy. He might leave. Mom will get depressed and abandon the kids." It is the same kind of paternalistic, only we of the intelligentsia can handle this theme. Then one day everyone knew the sex of the unborn and the world went on spinning and dads didn't leave and moms didn't get depressed and run away.

It really isn't hard to explain: 1. This is not a given. 2. You control the eventual outcome because genes and environment are both important. 3. The only information this gives you is a roadmap for what actions you might take, what food you might eat, or how many music lessons you need to develop perfect pitch. 4. New information is being learned every day and this result could be overturned. 5. Check the following website for updates.

And yes - this info is useful. Even for HD or breast cancer. Suppose there was an alternative to the inevitable? There is in many cases. I'm taking low dose naltrexone not only for the chronic immune illness I have (and which is has stopped completely) but also because there is evidence it acts prophylactically on cancer. And it is being looked at for HD since it has been hugely successful in MS. (This isn't junk science. Clinical trials at Stanford, NIH, Penn State will show that.)

I'd say those who diss this and say, "no use" are pessimists who aren't thinking or curious and live in the past. Science moves forward by pushing boundaries. Don't shove it into the box labeled,"You need counseling." That's not helpful. And if you can't embrace and see the future without the sky falling in, find a way to prop it up instead.

I believe in the people and their power to learn. But they won't learn if they are told they can't be taught by those that clasp the knowledge close and will not teach or share.

Shamans see the coiled snake all the time and teach the tribes what life lessons it gives them. We call it DNA. It has much to teach and we have much to learn but we can't be afraid of its power and put it on a pedestal and keep it from the people.

Sit vis vobiscum

Why should people not be able to find out their genetic make up if they wish? Failure to allow open access to information moves science into the realm of religion and creates more problems than it solves.

Interesting articles you have very informative though for nobrains it seem hard to understand ! though i already read your articles over and over lol! maybe its not me ;) but you have interesting articles !

I find this very intriguing, thank you for the article, David. I have felt for years that I was prone to depression simply because both of my parents have had it. To know that there might be a gene out there that can prove just that boggles my mind. I would love to be tested for the S/S, but I doubt that insurance would cover it and I don't have the money to pay for it. While I understand that there are many facilities that won't do the procedure, do you suppose that there might be one that does? Where did Karen go?

Does the "orchid-dandelion" metaphor work for you? My duel with David Shenk

ddobbs — Mon, 14 Dec 2009 10:27:17 +0000

Does the "orchid-dandelion" metaphor work for you? My duel with David Shenk

Dear Readers, here's your chance to weigh in:

Over at the Atlantic, David Shenk, a sharp writer who keeps a blog there called "The Genius in Us All," has posted a gentlemanly smackdown ("Metaphor fight! Shenk and Dobbs square off") that he and I had via email last week regarding the "orchid-dandelion" metaphor I used in my recent Atlantic piece, "Orchid Children" (online version title: "The Science of Success"). Every metaphor has its limits, and David Shenk, a highly capable writer, recognizes that well. Yet he thinks this orchid-dandelion metaphor is fatally flawed, at least as I use it; I think its strengths outweigh its limitations. One thing led to another ...

Our exchange on the subject is below. Out of curiosity -- and because I'm fixin' to write a book on the topic -- I'd love to know what readers think of this. Does the orchid-dandelion cast the temperamental differences too starkly? Or is it a useful shorthand for the differences in temperamental sensitivity that these behavioral genes appear to create? Chime in in the comments. And if you still feel restless after doing so here, you can go to Shenk's site and put in your two cents there as well.

NB: Stage directions and art grab by David Shenk.
NB2: No real blood was spilled in the writing of this post.
NB3: I typed my entries with my left hand -- and I am not left-handed.

Here's Shenk's post:

In response to this month's Atlantic feature "The Science of Success," by David Dobbs, which I admired, I invited Dobbs to engage in short back-and-forth over one particular gripe I had. He graciously accepted. Children, avert your eyes. This is literary brawling the likes of which haven't been seen since Norman Mailer head-butted Gore Vidal.

Shenk alights from behind a doorway with his first jab:

Congratulations on your beautifully rendered "Orchid" piece. You do a superb job of illustrating the notion that the same gene can yield very different results in different circumstances. I particularly admire the way you end the piece -- falling back on the essential truth of the parent helping to constantly flip little genetic switches in the child. I consider this piece a landmark step forward in the difficult transition of helping the public understand what genetic expression is all about.

My one not-so-small quibble is that I think you let the metaphor get away from you a bit. While the "orchid" metaphor is a provocative way to illustrate that certain genes or combinations of genes might increase plasticity, the "dandelion" half of the metaphor strongly suggests that "most of us" don't have very much plasticity -- i.e., that the dandelion kids don't have much potential to be either down-and-out or enormously successful. Being familiar with some of your previous work, I don't think that's the message you intend to send.

Correct me if I'm wrong, but I don't think that you actually believe that science has demonstrated that most of us are destined to a hardy mediocrity. If you are taking that position, I'll respectfully disagree and let's debate that point.

Your earlier work (which helped to inspire my forthcoming book) suggests that you have a very keen understanding of the extraordinary plasticity built into virtually all of us. I submit that this doesn't contradict the science in your new piece. We can recognize certain extraordinary orchid alleles without rhetorically ghettoizing the other alleles as not-very-plastic dandelion weeds. After all, the studies you cite are presenting population percentages -- they are not showing a clean separation between individuals with or without the alleles. Clearly, as this science marches on, we're going to be stumbling onto specific genes and combinations that seem to have a particular influence in one direction or another. But as we do, I think we need to be careful not to overstate their lessons. We don't want to leave readers with the impression that, without a particular allele, a person is protected from being depressed or barred from having super-talent.

To sum up, and I know this inconvenient for you, I suggest that you need to drop the "dandelion" half of the metaphor. It's a vivid contrast to the orchid metaphor, but I believe it's too misleading.

Dobbs side-steps, casually finishes his drink, and winds up:

Thanks for the nod and the good questions.

Your main concern seems to be about plasticity -- specifically, whether my contrast between so-called orchids and deadlines is meant to suggest that the dandelions are less plastic overall.
It's a good question, and it lets me make two distinctions that need to be made in a fuller account of this hypothesis. One regards how clean or absolute a distinction we should make between so-called orchid people and so-called dandelions. The other regards whether the plasticity spoken of in this orchid hypothesis is the same plasticity that you and others (including myself) write about as the key to learning and gaining expertise.

Let's talk about the distinction between orchards and dandelions first, and then what sort of plasticity this orchid hypothesis is mainly concerned with.

Every metaphor has its limits, and one of the limits of the orchid versus dandelions metaphor is that it implies a binary, A or B. division of personality types determined by behavioral gene variants: you're either orchid or dandelion. That's not quite accurate, for there are several genes in question here, and because we each get a mix of variants among them, it would be a rare person that was all orchid, so to speak, or all dandelion.

To explain: Behavioral geneticists have identified somewhere from 5 to 15 (depending on whom you ask) genes whose variants are important in shaping temperament and behavior. (The serotonin transporter gene, or SERT gene, which is associated with depression, among other things, is the most well known. But there are several others, such as the MAOA gene, which affects aggression and sociability, and the DRD4 gene, which affects behaviors on both the attention-distractibility spectrum and sociability in cooperation.)

For argument's sake, let's say there are 10. In all ten, the 'dandelion' form is the most common, with the orchid forms accounting for about 20 to 35 percent. So for any given one of these genes, you're more likely to have the dandelion variant than the orchid. However, odds being what they are, you are also likely to have the orchid form in at least some of these genes. And since the overall effects on temperamental plasticity are presumed to be multigenic, more orchid genes you have, the more temperamentally malleable and mercurial you will be. In addition, the particular combination of genes in which you have the orchid form will color the nature of your malleability.

Put that all together and you see that pretty much everyone has some malleable variants in them, with the mix varying quite a bit. I might have four orchid varients among the Big Ten, my wife might have two, and my brother five. So everyone -- if this isn't getting too cute -- some orchid in him and quite a bit of dandelion. So it's not that a person is either plastic or not. The malleability runs along a spectrum, and is a matter of hue as well as intensity. And the consequences of that malleability, of course, depend heavily on experience, context, etc. But the more malleable folks are shaped more dramatically by their experience and react more dramatically, in temperament and behavior, than the less malleable.

Okay, so that's orchids versus dandelions -- a spectrum issue, not a black-and-white one.

But what exactly is more plastic and reactive in orchids? Is this the same plasticity we talk of when we talk about learning and the mastery of skills and expertise?

Well -- no. One is temperamental plasticity; the other is cognitive plasticity. There is surely some overlap. But at least by the terms of this orchid or sensitivity hypothesis, the genetic underpinnings and dynamics of temperamental plasticity are not those of cognitive plasticity. Having the more plastic "S/S" form of the serotonin transporter gene, for instance, will tie your vulnerability to depression more closely to your experience, but it will not make you either smarter or duller, or faster or slower to learn -- especially when the learning involved is primarily cognitive or skill-based, such as learning catalysts, chess, HTML coding, or a good topsin backhand.

So I am not suggesting -- and I don't believe those working up this hypothesis suggest -- that those with so-called dandelion genes are destined to a hearty mediocrity. Rather, the hypothesis asserts that, as with orchids, a dandelion's ultimate endpoint and accomplishments will be determined by a complex mixture of temperament and cognitive and other skills -- but the dandelion's path to wherever will likely be bit steadier and less likely pushed up or down by great or horrible fortune.

Bell rings. Shenk retreats to his corner to tape a small cut. Tosses away gloves, pulls out sword:

Thanks for engaging. Before I dig in again, I want to first repeat that I applaud you for exploring the dimensions of this new hypothesis and working to translate it to public consciousness. When you discuss stuff like multigenic effects and temperamental plasticity, and describe genes as "shaping" rather than causing, and talk about the spectrum of effects, you are conveying some very important nuances about how genes actually work. Even though many scientists understand this stuff, the public has no real clue, and a shocking number of science writers are so far resistant to abandon outdated metaphors and determinist phrases.

I have to be honest that I'm not entirely sold on all particulars of the nuanced science you're conveying. But that's for another forum, and for time and more studies to clarify. What I want to focus on here is what I see as the only serious problem with your message, which is your metaphor as you are currently using it. And I have a specific suggestion about how to fix what I perceive as the problem.

You say above that every metaphor has its limits, and I completely agree. Metaphors can only be used to convey a basic essence; on closer inspection, the analogy to the more complex reality never holds. I have no intention of holding you to an unrealistic standard. My problem is with the essence of your metaphor (as you are using it). In your Atlantic piece, the very purpose of the metaphor is to convey that there are two distinct types of kids, the orchids who have much temperamental plasticity and the dandelions who have little. The very first line in the piece is, "Most of us have genes that make us as hardy as dandelions."

What you're acknowledging in your note above is that the orchid kids/dandelion kids distinction is not real; that in reality, there are *orchid genes* and *dandelion genes*, and at the particular mix we each inherit will affect how plastic our temperament is.

So this is my plea, as you begin expanding this into a book: if you decide to stick with the orchid/dandelion metaphor, don't apply it to people. Instead, apply it only to the genetic ingredients in people. I realize this approach has less literary cachet, and may constrain your evolutionary argument. But it also doesn't build in a dramatic misperception from the get-go.

The other option, of course, is to choose a new metaphor altogether.

Dobbs reveals spikes on his shoes, takes long leap toward Shenk's abdomen:

I can understand your problems with my message and the metaphor -- and I may (or may not) yet change either the way I use this orchid-dandelion comparison or use something else. That said, I'm not convinced the problems are as serious as you think. I could be wrong about this, of course, and would love to hear what other readers think -- if very many are confused, thrown off, etc., I certainly want to know.

But, as I say, I see the problems as less serious than you do.

First, the metaphor is used in the Atlantic piece not primarily to distinguish between stable dandelions and more plastic orchids, but to use that admittedly stark (possibly overly stark?) contrast to replace the conventional one between supposedly stable 'protective-gene' people and fragile or vulnerable (rather than malleable) holders of 'risk' genes. The reactive and less reactive replace the vulnerable and the resilient.

(As to the first words of the piece: The passage you quote is actually a sort of deck to the article, added by the editors. It is a bit misleading, and arguably too stark and absolute, and if I had to do it over again, I would have changed the language there so it was less so. I failed to because it was added very late in the going, and I didn't examine it hard enough amid my concentration on reviewing again the story and some last-minute changes in it. My bad; I can see how it frames the metaphor as you say, very A or B.)

That said, I think most people recognize that decks or editorial synposes, like titles, contain some oversimplification, and that readers need to see the article for the full story.

More important, I think most people accept contrasting terms such as orchid v dandelion, when used to refer to people, as types that represent either end of a spectrum. That's the case when we talk of extroverts and introverts, for instance; we use those terms all the time, and everyone understands that we're talking about people on one half of spectrum or another. Likewise, I'd guess, with orchids and dandelions. There's obviously a danger if a writer presents these outright as distinct types with no overlap. You seem to feel I've done so; possibly so. I disagree. I think if a writer provides the fuller story behind a contrast like this, most readers understand that the shorthand refers to types at either end, not two mutually exclusive categories with no overlap.

That said, I'm pondering this and will continue to consider whether the orchid-dandelion scheme is the best way to denote this difference in temperament. A metaphor or distinction like orchid versus dandelion can have great value in giving people a concise image or idea around which to gather a broader and more complex idea; the many, many readers who have reacted strongly and with good understanding of this story -- readers who get its essence quite clearly -- makes me think the orchid-dandelion contrast has that value here.

At the same time, that strength is a weakness (whoa! meta-alert!) if the metaphor leads people to an inaccurate or wrong idea -- and that has happened with a few readers as well. (Though most of the misunderstanding seems to come from people who have not actually read the article.) Before deciding whether to abandon the orchid-dandelion language, I've love to get a better sense of that balance (that is, how many readers it worked well for and how many it misled) -- and to consider as well how a book-length treatment might overcome any shortcomings.

In any case, your cautions and criticisms rise from healthy concerns, and while I'm not sure we'll meet more than halfway, I value the prod, the critique, and the attention to subtleties of language, whether in title, flap copy, or text. With luck, readers will chime in and give us both a better read on how well the orchid-dandelion distinction works for them.

Shenk:

Sounds fair. Thanks for the dialogue.

Dobbs:

Thank you.

Both men collapse on floor. Medics rush in with protein smoothies and the latest issue of Nature Genetics.

ddobbs Mon, 12/14/2009 - 05:27