I’ve now lived in the U.S. of A. for seven years, but had never been north of the border. So I enthusiastically accepted the invitation of the Canadian Stem Cell Network to give a talk on scientific publishing to their trainees (i.e. grad students and postdocs), last Tuesday at their Annual General Meeting in Calgary. The Weather Channel website predicted moderate temperatures around 50oF, but I just couldn’t believe it and bundled up in my warmest winter coat. Of course those weathermen were right, and I looked pretty silly in puffy down at 15oC/60oF. Several friendly locals, including the breakfast omelette chef, explained that the balmy temperatures were due to the “chinook” winds blowing from the west across the Rockies. Apparently midwinter chinooks can heat Calgary from deep freeze to balmy in a day, and they last for a few days, too. Lucky Calgarians! Still, I remain awed at the early peoples and pioneers who settled in a prairie where winter temperatures routinely drop to -30oC/-20oF (or so they tell me…)

I’m going way off-topic here…

The Stem Cell Network folks wanted me to explain how to get published in the Nature brand journals. Really, the answer is pretty simple – just tackle a very interesting question, and do fabulous work on it coming to novel and convincing conclusions. Easy, no? So how am I supposed to talk about this for 45 minutes??

Thank goodness, when people like the SCN ask this question, what they really want to know is what happens to their paper once they surrender it to our claws. Do we actually read it ? (YES!) Why don’t we peer review all papers? Who are these fearsome anonymous referees, and why do they have to be anonymous anyways? What proportion of submitted papers ends up getting published? Is there any recourse in case of unfair rejections? And so on and so forth – no problem filling that hour. It also gave me a chance to wave the flag for “Action Potential” as our new feedback & discussion forum.

The audience came up with several good questions. The one that stuck with me was about the difficulty in getting negative results published. It can indeed be challenging. Negative results can seem inherently “boring”, even if important. And when a negative result contradicts a previously published positive result, it may face a tough battle in review. The best we editors can do is enlist fair reviewers who don’t have a personal stake in the controversy, but they may still give the challengers a hard time. The stem cell field certainly has its share of entrenched controversies – for example, is there such a thing as “transdifferentiation” (such as from bone marrow stem cell to neuron)? Or, do adult neural “stem cells” really exist in vivo, or are they an artifact of in vitro culture? The definition of stem-cell-ness is based on in vitro criteria, and sorely overdue for an update. Lots of material here for blogging – chime in!

Online since Sunday, November 27th:

Lorenzetti et al., Classical and operant conditioning differentially modify the intrinsic properties of an identified neuron

Voss et al., Sensorimotor attenuation by central motor command signals in the absence of movement

Altier et al., ORL1 receptor–mediated internalization of N-type calcium channels

Aoyama et al., Neuronal glutathione deficiency and age-dependent neurodegeneration in the EAAC1 deficient mouse

Online since November 20th, and printed in the December issue:

Jarsky et al., Conditional dendritic spike propagation following distal synaptic activation of hippocampal CA1 pyramidal neurons

Arumugam et al., NMDA receptors regulate developmental gap junction uncoupling via CREB signaling

Laurent et al., The prolactin-releasing peptide antagonizes the opioid system through its receptor GPR10

Liss et al., K-ATP channels promote the differential degeneration of dopaminergic midbrain neurons

Wang et al., Prior experience of rotation is not required for recognizing objects seen from different angles

… to everyone for the thundering silence on “Action Potential” last week. I was out of town, no internet connection at hand, and had neglected to corral any of my colleagues into blogging duties. Sorry! I spent half the week in Calgary at a stem cell conference, which I’ll blog a little about later. First, let me get the new NN advance online publication papers up here. Thanks for hanging in there…

Two links of interest:

Nature journalist Jim Giles keeps a running diary of SfN here.

The Society for Neuroscience in a press release issued yesterday highlights four posters and slide presentations about meditation research. Guess they like to fan the flames a bit 😉

Our chief editor Sandra Aamodt left me a phone message here in the office on Saturday, reporting from the scene in the Convention Center before the DL lecture. Seems she narrowly avoided being squeezed to death by the crowd! Did she manage to get into the hall and hear the talk? Stay tuned…

Also on Saturday, the New York Times ran an op-ed piece by the DL, titled “Our Faith in Science”. The link ought to work until Friday Nov 18, but let me excerpt what I think are the main points anyways:

“… the ancient version of cosmology I had been taught… held that the moon was a heavenly body that emitted its own light. But through my telescope the moon was clearly just a barren rock, pocked with craters. If the author of that fourth-century treatise were writing today, I’m sure he would write the chapter on cosmology differently. If science proves some belief of Buddhism wrong, then Buddhism will have to change.”

Quite a contrast to the scriptural literalism we hear from so many Christian groups, creationists in particular! Next comes a short discussion of collaborations between Tibetan Buddhist monks and neuroscientists. Richard Davidson’s work, as well as studies under way in the labs of Jonathan Cohen and Margaret Kemeny are briefly mentioned. The point is that science and Buddhism can enrich each other – science sets Buddhism straight on cosmology, and may be able some day to explain the neurological mechanisms at work during successful meditation. Buddhism (indeed all religion) can enrich science by contributing an ethical perspective:

"… we must find a way to bring ethical considerations to bear upon the direction of scientific development, especially in the life sciences. By invoking fundamental ethical principles, I am not advocating a fusion of religious ethics and scientific inquiry. Rather, I am speaking of what I call “secular ethics,” which embrace the principles we share as human beings: compassion, tolerance, consideration of others, the responsible use of knowledge and power. These principles transcend the barriers between religious believers and non-believers; they belong not to one faith, but to all faiths. …"

“… It is all too evident that our moral thinking simply has not been able to keep pace with the speed of scientific advancement. Yet the ramifications of this progress are such that it is no longer adequate to say that the choice of what to do with this knowledge should be left in the hands of individuals. This is a point I intend to make when I speak at the annual meeting of the Society for Neuroscience today in Washington. I will suggest that how science relates to wider humanity is no longer of academic interest alone. This question must assume a sense of urgency for all those who are concerned about the fate of human existence.”

So far, so good. In fact, there are a good number of serious-minded bioethics efforts under way. In the context of stem cell research and cloning, bioethics also gets a lot of public attention. See the fine American Journal of Bioethics blog for the scoop on all things bioethics. Now what does the DL recommend from the Tibetan Buddhist perspective? Nothing specific in the entire piece, unfortunately! He ends with this sentence:

“Scientists should be more than merely technically adept; they should be mindful of their own motivation and the larger goal of what they do: the betterment of humanity.”

Okay… clearly the DL appreciates science and scientific progress. But if, as he suggests, “secular ethics” could take care of the ethical quandaries thrown up by scientific advances, do we need the science/religion dialogue at all?

Here’s this week’s batch – enjoy! As always, comments are welcome.

Lee at al., “NMDA receptor–independent long-term depression correlates with successful aging in rats”

Kao et al., “Neural correlates of actual and predicted memory formation”

Mante et al., “Independence of luminance and contrast in natural scenes and in the early visual system”

Toyofuku et al., “FARP2 triggers signals for Sema3A-mediated axonal repulsion”

Multiple sclerosis (MS) is a heterogeneous disease that affects primarily young adults and often leads to serious disability. We don’t know what causes it, and we cannot cure it. This summer, in our July issue, we editorialized about the tragic crash-and-burn of the promising MS drug natalizumab (marketed as Tysabri®). In a nutshell – after passing preliminary clinical trials with flying colors, and being approved by the FDA in an accelerated procedure, natalizumab had to be pulled after just three months because a few patients came down with PML, a devastating, crippling or deadly, infection of brain oligodendrocytes. PML is caused by the JC virus, which most of us get exposed to at some point, without it ever doing any noticable harm. How exactly natalizumab would activate the somnolent JCV is unknown, in large part because we don’t know enough about its life cycle and physiology. PML is extremely rare, and mice can’t catch it – two facts that unfortunately tend to discourage research.

In response to our editorial, Richard Ransohoff from the Cleveland Clinic wrote us a letter putting forward an interesting hypothesis about the natalizumab – PML link. We had his letter peer-reviewed, and we published it in our October issue. Here’s a summary of the idea:

Natalizumab works by interfering with a specific adhesion molecule that the myelin-attacking T cells in MS need to migrate into the brain. The same molecule also functions in cell adhesion in the bone marrow, where blood and immune cells are generated. It is known that natalizumab, as a side effect, leads to release of immature blood cells into the circulation. It has also been suggested that the specific genetic rearrangement that activates dormant JCV occurs in the bone marrow. Therefore natalizumab could lead to release of large numbers of JCV-infected immature cells in JCV carriers, overwhelming the immunosurveillance mechanisms that usually keep JCV in check.

Although we know that about 80% of the population have been exposed to JCV and carry antibodies to it, it is completely unknown how many carry dormant virus that could be activated. And there is no easy reliable test to find out.

Ransohoff’s letter has triggered a small flurry of follow-up letters, with authors suggesting their own ideas, or variants on the Ransohoff hypothesis. Now, we can’t really publish everyone’s favorite thoughts on the subject in the printed pages of the journal – first, not all of them are as original as Ransohoff’s, and second – it would never end! The journal is really meant for hard data; we publish hypotheses very, very rarely.

But this discussion itself is very much worth having. If there’s any chance at salvaging natalizumab – apparently the most effective treatment for MS that’s ever been available – and the entire class of drugs it represents, it will emerge from frank discussion among the experts. So why not have the discussion here, on our blog, on “Action Potential”? We’d be proud and happy to host your “virtual meeting”.

Seems as though our audience is coming out of the woodwork! Thank you mccm, Gabriel and Thomas for your good wishes, and for leaving email addresses and even website URLs. mccm runs a blog called The Genius, where she/he recently discussed a paper on memory mechanisms published in Nature about a year ago. Gabriel directs us to an upcoming symposium at NYU about imitation behaviors from octopus to man. Very distinguished panelists! Thomas runs BrainEthics, where he welcomes us to the blogosphere with so much enthusiasm that he makes me blush! Thomas, I hope “Action Potential” can live up to your high expectations.