Action Potential

A tangent related to the primate cloning paper has understandably received less attention, but deserves its own thread. In the same issue of Nature containing that paper, an accompanying editorial described how Nature, for the first time, implemented a relatively new policy by seeking the independent confirmation of this particular "high-risk" finding (or "strong claim") during the review process.

Obviously, successfully cloning a primate is a strong claim. This policy is mainly in response to the travesty that occurred over fraudulent claims by South Korean researcher Woo Suk Hwang that he and his team had cloned human embryonic stem cells (published in Science in 2004 and 2005). That prompted Science to adopt a risk assessment template to target those findings that could be false, and thus necessitate further inquiry prior to publication. The Nature policy is similar. Therefore, when these top journals decide that a certain study is bound to have an astronomical impact, extra care and effort to scrutinize the original data, even independently replicate the findings, are required to avoid potential damage to the scientific community.

The Hwang affair no doubt damaged the community and was a complete embarrassment for Science. So this idea seems like a win-win situation for all involved - the journal, the authors, and the public. But I am a bit troubled over the idea of weighting certain discoveries and fields as being more important than others. I understand that stem cell cloning technology trumps rodent whisker barrel physiology in the eyes of the public, the politicians, and (arguably) the entire research community, but it seems like these types of policies have the potential to start as a trickle and eventually become more of an alarming flow. Once this procedure begins to demonstrate its merits and ease of implementation, what's to stop the editorial board from casting a wider net with the strategy and start loosening the definition of "extraordinary findings"? I guess I am just uncomfortable with the bizarre scenario of journals soliciting experiments and orchestrating scientific research between groups, just to make sure that they are not embarrassed.

Don't get me wrong, this policy will save a lot of people a lot of grief, if wielded with a strong and disciplined hand. I just don't want it to become a regular part of the review process.

Posted by Noah Gray at 06:00 PMon November 30, 2007 | Permalink | Comments (4) | TrackBacks (1)
Categories: Noah Gray, Scientific Publishing

Since we had a long and involved conversation on the role of embryonic stem cells in research, as well as how this issue is politicized by both sides of the debate (with additional discussion here), recent news insists that we post a follow-up on Action Potential.

Two papers (one published online by Cell and the other in Science) proclaimed last week that adult cells could be reprogrammed into an entity indistinguishable from embryonic stem cells, using a recipe of only 4 additional factors (different genes in each paper, with some overlap). Although it is virtually impossible to conduct the necessary gold-standard tests on humans as to whether they are indeed pluripotent, the fact that these reprogrammed cells could be used to rapidly produce up to 10 different lines for research purposes is, at the very least, outrageously encouraging.

With the cells so easy to come by (derived from skin and fluid in the joint) and with the fabulous success rates of the researchers, it is only a matter of (short) time before these techniques replace the former practice of deriving pluripotent cells from discarded embryos. Removing the embryo from the equation thus removes the ethical concerns, and should relax Dr. Condic and the religious right. After all, the argument stating that a lack of progress in stem cell-related therapies is a good reason to abandon it (don't get me started on that one again...) hardly holds water when the obvious ethical concerns are removed. Who cares if human foreskin and synovial (joint) fluid cells die "in vain" as we dabble with stem cells in disease treatment. I am unaware of any prominent Foreskin Banks offering to place circumcision refuse in liquid nitrogen for the donor/owner until further notice, a good indication that this tissue does not carry the same "moral weight." Therefore, the new research results should be seen as a victory by all; stem cells that are both more ethical and more practical. The phrase "stem cells" may even cease to be dirty words in even the most conservative political circles.

But wait, don't lament for the Revelations-reading, hellfire-and-brimstone-spewing few that thrive on condemning the liberal godless scientist. In that same week, a study in Nature also announced the successful cloning of a primate. Combining this technology with the reprogramming tricks described above could (in theory) open the door to "personalized" medicine as is imagined in science fiction. In essence, cloned pluripotent cell lines could be made from any individual, providing for the creation of cells that are a genetic match to the patient. Therefore, immune suppression, as is needed after a transplant, would be unnecessary when receiving tissue grafts (or organs??) derived from one's own reprogrammed skin, since the cloned cells would actually be from the patient, not a stranger with different DNA. But having this kind of genetic power could eventually lead to the cloning of a human being.

Let the cloning debate resume where the stem cell debate dies...

Posted by Noah Gray at 02:11 PMon November 28, 2007 | Permalink | Comments (2) | TrackBacks (0)
Categories: Noah Gray, Interesting Neuroscience

While we are discussing infants, development and nature vs. nurture, it is fitting that Nature just published a new article describing the social evaluation skills of pre-verbal infants (6-10 months old). In a nicely-designed experiment, researchers allowed infants to view a toy as it was made to climb over an obstacle. Near the top, another toy would either help the first toy complete the ascent, or impede its progress by pushing it back. When then allowed to choose one of the second two toys for playtime, the infants overwhelmingly chose the "helpful" toy over the "hurtful" toy. In addition, infants were much more likely to choose "neutral" toys (ones that neither helped nor hindered the first toy's progress) over hurtful toys and helpful toys over neutral toys. Interestingly, these preference biases evaporated when the eyes (very prominent on the toys) were removed. This suggests that if the babies did not recognize the toys as "individuals", partiality to helpfulness made little sense, and was thus irrelevant.

These results led the psychologists to conclude that social evaluation skills were inherent to the infants' repertoire of basic knowledge, something that did not need to be explicitly taught. Obviously this study does not definitively prove that statement, and others have been quick to point out that babies can and do learn a lot through observation between birth and 6 months of age. Therefore, it is still entirely possible that the ability to discriminate between those playmates that will be at worst neutral, and at best helpful, is learned. More work will be required to end this debate, but regardless of the answer, I find this result to be fascinating. Learned or innate, it is cool that infants can process this information and seemingly act in a manner to engage in or avoid relationships that could potentially be beneficial or damaging, respectively, to them in the future. I mean, who wants to play with a bully?

As a social creature, humans need to be constantly evaluating social cues to provide for a successful navigation through our intricate little world while minimizing conflict. This skill has existed for thousands of years, with individuals persistently assessing potential threats and possible alliances in order to increase the odds of survival. We even learn to avoid dangerous encounters with other creatures based on particular cues and circumstantial evidence (anyone who has ever hiked in Glacier National Park can tell you exactly how NOT to run into a bear). It is therefore no surprise that other animals do this routinely as well. This is done not just to identify conspecifics who may hurt or harm them, but also with regards to other species. Several different animals have distinct alarm calls depending on exactly which predator is near, since escaping predation is not a one-strategy-fits-all venture. I'm telling you all of this because I also wanted to mention another study I recently read about that probably doesn't deserve its own entry, but is still interesting. It involves behavior pattern selection, so I think it kind of fits.

Researchers from the UK and Nairobi determined that elephants could distinguish between at least two different Kenyan ethnic groups and identify them by olfactory and color cues independently. The young men from one herding tribe spear elephants as a demonstration of strength and virility, while a second group of farmers pose little to no threat. Elephants reacted aggressively and exhibited more fear when detecting the odor from garments worn by the spearing tribe, or encountering the distinct colors typically worn by these tribesmen. Little response was elicited from either the odor of the farmers' garments or the color of their clothing. Interestingly, prior experience of the pachyderm family to spearing had no effect on the extent or nature of the reaction by the group as a whole, but individual experience (actually having been speared in the past) did elicit stronger reactions by those wounded elephants to the herding people. Therefore, elephants demonstrated an ability to categorize humans into subgroups and react appropriately, depending on the threat level being faced.

Given the advantage that this type of processing could confer, the researchers predict that this discriminatory ability will prove to be widespread among animals with appropriate perceptual and cognitive capacities. So perhaps it would not be surprising at all if human infants do have some innate ability to discriminate and process cues in order to determine their best course of action. But certainly, that skill will be modified by experience.

Posted by Noah Gray at 06:37 PMon November 21, 2007 | Permalink | Comments (1) | TrackBacks (1)
Categories: Noah Gray, Interesting Neuroscience

No, this isn't another post about Jim Watson; the title is just a shameless ploy to draw in the search engine crowd... It is relevant though, as you'll soon see. I've been meaning to talk about this next topic for a couple of weeks now, but have been distracted with unexpected news stories, editorial discussions regarding the review process, etc. A recent study in PNAS has demonstrated a significant interaction between nature and nurture that influences intelligence.

It has long been stated that breast-fed babies perform better on IQ tests, suggesting that brain development is enhanced by this "nurturing" factor. The augmentation in development could arise from the particular fatty acids that are found in human milk, but not in cow's milk or in baby formula. But in order to take advantage of those extra fatty acids, one must be able to metabolize and process them. This is done in part by an enzyme called FADS2, which contains various polymorphisms in the human population. Repeating the same study in thousands of children from both England and New Zealand, researchers determined that in order to take advantage of the potential benefits offered by consuming breast milk, the infant must have one copy of the "C" allele. Those infants with 2 copies of the "G" allele might as well have been fed formula, because the 7 IQ points conferred by breastfeeding was absent in the "GG" babies. About 10% of the population is thought to lack any copies of the C allele.

The study went on to rule out alternative explanations, such as gene-exposure correlation, intrauterine growth, social class, maternal cognitive ability and maternal genotype effects on breastfeeding and breast milk. These results really change the climate of the mini-debate exploring the benefits of breast feeding. Many have suggested that the advantages enjoyed by breast-fed babies may arise because those mothers take a different, more hands-on approach to child-rearing, as opposed to the mothers giving their babies formula and TV. Actually, an interesting follow-up study would be to test the language skills of breast-fed infants that watch Baby Einstein videos...

Evolutionarily speaking, it is curious that the GG allele has stuck around. Natural selection should have weeded out this less advantageous polymorphism, with the greater intelligence of the C-possessing population allowing them to compete victoriously over their less-intelligent brethren. But, logically, with the GG genotype persistent at 10%, it must have conferred an as-of-yet unidentified reproductive advantage to those individuals, allowing this genetic combination to perpetuate. Remember, you don't have to be a science geek / nerd to procreate (...wait a minute...of course!!! Intelligence can sometimes be a reproductive curse!!! Just ask the men at Caltech, where only 29% of the student enrollment is female...)

So is the nature vs. nurture debate dead? Are we stuck with another unsatisfying denouement in science where the answer is "somewhere in between?" Perhaps, but for those extremists amongst you who long for contrast and want nothing to do with the gray zone, you'll hate this next story. Staying with the breast-feeding theme, it seems that first-time macaque mothers bias their milk composition in favor of their sons. Examining over 100 animals, researchers from UCLA determined that milk was richer and more nutritive when mothers nursed their sons, as opposed to daughters. Therefore, the maternal energy investment was greater for male offspring. This makes sense, since for males, reproductive output correlates with the strength and size of the animal, allowing it to successfully compete for more mates. Females inherit the reproductive status of their mother, a sort of macaque caste system. Therefore, the mother obtains a greater Darwinian advantage by massively investing her own resources in the nourishment of her sons, while little is gained from producing richer milk for daughters.

Since the milk consumed by the males has a much higher fat content, perhaps we can extrapolate from the other study and presume that brain development in the male macaque is also enhanced, leading to a slight advantage in their intellect. If so, then on which side of the debate is this last finding? Obviously nature (genetics) determines the sex, but infant gender influences the treatment by the mother, altering the nourishment (nurture). I guess once again, it falls somewhere in between. Oh yea, only if the monkey is not "GG".

Posted by Noah Gray at 06:11 PMon November 20, 2007 | Permalink | Comments (2) | TrackBacks (0)
Categories: Noah Gray, Interesting Neuroscience

Discussion is heating up regarding a new proposal that could change the face of peer review in neuroscience. At the PubMed Plus leadership conference this past June, sponsored by the Society for Neuroscience, the creation of a Neuroscience Peer Review Consortium was proposed.

Here is a message from SfN president David Van Essen describing the vision for this new entity:

After an article is rejected by one journal and authors are ready to submit a revised manuscript to another journal, they will have the opportunity and the option to request that the reviews from the first journal be passed directly to the new journal (assuming that both journals are part of the consortium). In many cases, the second journal will be able to reach a decision faster and more efficiently, thereby benefiting authors as well as the overly stressed manuscript reviewing system.

This revolutionary proposal is now a reality, at least for a trial run from January to December 2008. It will clearly benefit just about everyone in the community, including authors, reviewers and editors. The idea came from journal editors who saw that many technically solid manuscripts were being rejected because of space limitations or because the articles were not appropriate for their journals. After rejection, a new submission leads to another time-consuming review process, often with new referees, swelling the workload of the community.

But to make this new system work, the member journals had to agree on certain protocols to ensure that the inner workings of the journals are roughly similar. That way, the transfer process can go smoothly. One of those criteria got me thinking about our current review process. That is the "Confidential Comments" box. In order to join the consortium, journals will have to forego confidential comments.

For those of you who have not done much reviewing, many journals provide the opportunity not only to include a review of the manuscript for the authors, but also to communicate any additional feelings or opinions directly to the editors with confidence that the authors will not see these comments.

Although it is already clearly stated in our reviewing guidelines that the confidential comments and authors' comments should match, sometimes they do not, which can put the editors in a difficult position. Obviously, ethical concerns and other issues of this sort need to be dealt with in a more private manner (as the consortium rules permit), but these issues only arise rarely.

We have had long discussions (arguments) in our editorial meetings about the benefits and disadvantages of confidential comments, and now want to hear what the community thinks. What is your opinion as an author? As a reviewer? Why should we continue to invite confidential comments? Why should they be banned? How can we improve our use of confidential comments to help us make good decisions while maintaining transparency with authors about the reasons for our decisions?

Further discussion here.

Posted by Noah Gray at 12:31 PMon November 16, 2007 | Permalink | Comments (39) | TrackBacks (1)
Categories: Noah Gray, Scientific Publishing

Everyone is fascinated by science. When discoveries advancing our knowledge of the brain are made, these get extra attention. Why? Because we want to understand how we think, feel and function. When scientists discuss their research with the general public, people usually believe them, not dwelling on the details, but instead focusing on what implications a particular study might have on their own thoughts or opinions. This makes sense, because the general public is not in a position to evaluate the technical merits of most neuroscience manuscripts. That is why we have the peer review system and academic journals, like Nature Neuroscience. Once the study is reviewed favorably and is published, the general public can then be told of the exciting new progress.

Watson's recent scandal proved the danger of working outside this system; by making statements regarding race and inherent intelligence, the Nobel laureate was abusing the respect given to him as a preeminent thinker on genetic issues by the general public. Nobody expects the carpenter in Arkansas to call Dr. Watson on his bluff, challenging him to cite the non-existent studies backing up those outrageous statements. Instead, the non-scientist takes the scientist at his word, and walks away believing that researchers had proven the inferiority of intelligence in those of African descent, wondering why s/he wasn't told this sooner.

Well, this was an isolated incident, right? Dr. Watson is known to be controversial, he doesn't like to hide his opinions, blah blah blah, and all those other silly excuses people make for him. An exception to the rule. Well, on Sunday, the New York Times published an Op-Ed piece stating that scientists can reveal the true feelings and impressions of swing voters simply by examining brain imaging data. Besides falsely claiming that a simple relationship exists between the site of brain activity and "state of mind / emotion", the piece also contained many subtle (and not so subtle) political opinions designed to sway the opinions of the reader. Well, it was an Op-Ed piece, so they are allowed to do that, but masking those opinions in "hard science" is not only wrong but extremely irresponsible. Luckily, a swift reply was concocted by several experts in fMRI technology in an effort to set the record straight. As the letter points out:

This is so because brain regions are typically engaged by many mental states, and thus a one-to-one mapping between a brain region and a mental state is not possible.

But does anyone believe that the letter will be as widely read or discussed as the original piece? These researchers were basically publishing non-peer-reviewed data. Even worse, there is also an obvious conflict-of-interest, with the authors linked to a company, FKF Applied Research, which specializes in "NeuroMarketing." This, from the company website, describes what they sell:

Academic research, as well as the proprietary work we have done for Fortune 500 companies, shows clearly that what people say in focus groups and in response to poll questions is not always what they actually think, feel and act upon. fMRI scans, using our specially developed analytical methods, allow us to see beyond subjects' self-report and to understand the deeper emotions and thoughts that are driving (or impeding) behavior.

Therefore, the piece was also a blatant advertisement promoting the use of fMRI data to help sell, for example, soft drinks. If these researchers can determine the secret opinions that men have about Hilary Clinton, then certainly these researchers can figure out why those same men prefer Coke to Pepsi!! Shame on the New York Times for allowing the authors that amount of latitude. Although it was an opinion piece, it is hard to imagine the editors not recognizing this poorly-veiled attempt to bypass not only the typical academic process, but also the NY Times advertising department (can you blame the authors? Ad rates are pretty expensive these days).

But hey, I'm sure it was a cool piece to run! Good for business right? Who cares if it misleads the public about what we know about neuroscience. The record can be corrected later, with a short letter that won't change anything buried somewhere on the website! No problem! Oh, and by the way, this is not the first time that the Times and these authors have teamed up to present the miracles of using fMRI in politics.

If we really want the general public to understand science and scientific process, researchers, and especially the media, need to do a better job of properly informing, not over-hyping results or hawking unproven marketing strategies supposedly founded on hard science. An angry public is one that is not being accurately informed. An angry public is one that will not support broader increases in research funding. Stagnate or reduced research funding means less progress. Hopefully the Times will learn from this and realize the importance of these issues and accept the massive responsibility that comes with bringing science to the masses.

Posted by Noah Gray at 11:22 AMon November 14, 2007 | Permalink | Comments (4) | TrackBacks (1)
Categories: Noah Gray, Popular Press

Science blogging is becoming a fairly large entity, if you haven't noticed. NPG alone sponsors seventeen of them. Launched in January 2006, Scienceblogs.com has had over 50,000 posts and 555,000 comments on 66 blogs. This is a good thing for both the general public and for science, as again the internet proves its worth by easily bringing together populations of people who may have only rarely mixed otherwise.

Science blogging is so popular that it now has its own anthology. Bora Zivkovic, a blogger on Scienceblogs and the community manager for PLoS ONE, was the editor of the first anthology citing the best science blogs last year, and he's now accepting nominations for this year’s edition. It is time to perform your civic duty and vote, if you feel a strong desire to do so. Nature would love to see a number of its blogs represented in this list, I guess as a means to establish legitimacy or something. I, for one, will decline to vote.

Motivation comes in terms of carrots and sticks, with publication in an anthology representing a carrot, in this case. I prefer the stick. One of my most cherished exchanges during the short tenure I have had writing on this blog was my argument with Drugmonkey regarding the role that Nature Neuroscience and other prestigious journals play in perpetuating paranoia in the research community. I represent this negative feedback and criticism as a stick. But frankly, receiving criticism is exactly why I write. I want to overcome the activation energy required to make someone state, on the record, their opinion on a particular topic. I see this as a challenge, and every comment is a small victory. Participating in a debate can be one of the more motivating intellectual exercises, causing people to believe things even more passionately once engaged in the deliberation than before it started. Therefore, my carrot is the stick.

So if you are feeling nice enough to nominate one of my postings for this anthology, I appreciate the thought, but I would much rather have you comment on that entry and enrich this small community with your thoughts. To me, that would be a more valuable compliment.

Posted by Noah Gray at 05:37 PMon November 12, 2007 | Permalink | Comments (2) | TrackBacks (0)
Categories: Noah Gray, Random Thoughts

Well, it's the last day of the meeting and time to start sharing what you have learned. I invite all SfN attendees to comment on an interesting talk, poster, experience, etc... that they had or saw at the meeting. I'd like to take advantage of this forum to get an interesting discussion going regarding anything from specific research findings, science policy, or gossip. Questions are also welcome. To get the ball rolling, I am going to repeat a comment here that was submitted under the previous blog entry, from Dmitry:

In case you also are at the SfN conference and were present today on a wonderful talk by Gazzaniga, I've got one stupid question. He finished by telling some story about his son losing a row competition and it was supposed to be an advice for young scientists. Unfortunately I didn't completely get the point (because of my English not being perfect). Could you briefly retell it?

If anyone can help out, it would be appreciated. So let's have it, I'm interested in hearing your thoughts from the meeting.

Posted by Noah Gray at 08:04 AMon November 07, 2007 | Permalink | Comments (1) | TrackBacks (0)
Categories: Noah Gray, Random Thoughts

I decided that all of Action Potential's many readers down at SfN are probably in need of a little lift at the halfway point of the mother of all neuroscience meetings. It has been almost 3 days of non-stop data input and your brain, if not full, wishes it were. So let's take a brief interlude from the rigors of neuroscience to discuss a lighter and more relaxed topic: Creationism.

If you didn't detect the sarcasm in all of that, you aren't reading enough of my posts. Anyway, I came across an article in the NY Times a week or so back that really gave me a chuckle. Homer Jacobson, a retired chemistry professor from Brooklyn College did a Google search on himself and, to his horror, found several links to creationist websites using his work as scientific evidence that life was no accident.

The NY Times article lists darwinismrefuted.com and evolution-facts.org as two sites using the arguments of Dr. Jacobson's paper (entitled "Information, reproduction and the origin of life" and published in American Scientist) as evidence that the molecules destined to form RNA and proteins, and eventually the proto-cell, would never have found each other in the primordial soup without the assistance of a supreme being. I clicked through those sites, and found them to be scarier than attending the Alzheimer’s Disease Social: Alzheimer Idol Karaoke Night (for those of you at the SfN meeting who are interested, it will be on Tuesday night, 18:30, at the San Diego Marriott). An entry from one of the websites discussed work published in 1997 on the function of chaperone proteins during protein folding. To quote the author of the commentary, Matt J. Carlson:

The cooperative interdependency of the GroEL and GroES proteins and the chaperoning role they take in the life of misfolded proteins reveal the enormous complexity (to say the least) of just one tiny part of a more vastly complex living system. To credit "chance" with such intricate actions and interactions seems much less reasonable than to acknowledge "intelligent design," and I only know one Designer skillful enough for the job.

That last line just kills me. Other entries include cartoons and poems stating that monkeys come from monkeys and commentaries personally attacking Darwin for not giving enough credit for his theories to Russel Wallace, who seemed to have simultaneously and independently crafted a theory similar to "natural selection" (Wallace had mailed Darwin a manuscript clumsily titled "On the tendency of varieties to depart indefinitely from the original type", prompting Darwin to work fast to finish his own book before potentially getting scooped; perhaps both of them should have read and commented on a previous entry of mine...)

But that's not the best part of the story. Upon re-reading his original paper, Dr. Jacobson found several errors that had gone undetected for decades. Therefore, 20 years post-retirement, and at age 82, he retracted the 52 year old paper. In the retraction letter he stated:

I am deeply embarrassed to have been the originator of such misstatements.

There you have it, justice is done and Jacobson's scientific evidence refuting Darwin is no more. But don't think that this minor creationist setback will quell all future Midwestern uprisings burning science textbooks containing teachings of evolution. People always find a way to support their beliefs, for example, by taking advantage of a recent finding in physics; because the speed of light is not constant, this could imply that all geological means of dating are flawed and the world may only be 6000 years old. And Darwinism cannot account for the Cambrian explosion. And the origin of DNA cannot be explained by non-design. Here's a good piece of advice for everyone, with a post-1995 addendum: Don't believe everything you read, especially on the internet.

Posted by Noah Gray at 04:45 PMon November 05, 2007 | Permalink | Comments (2) | TrackBacks (0)
Categories: Noah Gray, Popular Press