Action Potential

Anyone who follows the sports world is well-aware of the concept of doping, in which athletes participate to establish an edge over the competition. This goes back a long ways and includes more famous examples like the East German Olympic machine, and the sprinter Ben Johnson, but also the more recent examples of Todd Landis, Marion Jones and, of course, Barry Bonds.

Competition seems to do that to people, clouding their judgment, confusing their ideals, pushing them to a point where it seems almost immoral not to give yourself any and every possible advantage. Well, doping is extending beyond the physical and entering the realm of cognitive capacity. A new commentary in Nature, written by Barbara Sahakian and Sharon Morein-Zamir of Cambridge, argues that the increased use of "cognitive-enhancing drugs" poses a number of serious ethical issues that can no longer be ignored.

Basically, healthy, intelligent people are taking things like ritalin and modafinil to obtain a cognitive edge over their peers without fully understanding the health-risks and problems that may accompany their drug use. The goal of this commentary, and of this blog entry, is to encourage a serious dialogue about these issues, allowing us all to shape our views of what it means to enhance our intelligence, and what the implications are (physical or otherwise) if we do so pharmacologically. Adding a separate layer of complexity, should cognitive enhancers only be used by the ill, or is health status irrelevant to the main issue? A few starter questions to begin to ponder:

1. Should adults with severe memory and concentration problems be given cognitive enhancing drugs?

2. If such drugs have only mild side effects, should they be prescribed more widely for other psychiatric disorders?

3. Do the same arguments apply for young children and adolescents with neuropsychiatric disorders, such as those suffering from ADHD?

4. Would you boost your own brain power?

5. How would you react if you knew your colleagues – or your students – were taking cognitive enhancers?

6. How should society react?

Your comments and opinions are welcome here, but additionally, these same questions are posted in a forum on the Nature Network. There, you will have the unique opportunity to interact with the authors of the Nature commentary over the next two weeks. In addition, to better prep you for the coming debate, further reading on this topic are posted here and here.

This current craze reminds me of another pharmaceutical enhancement that has been popular over the past couple of years: the increased use of resveratrol to counteract just about everything having to do with poor health. It's the miracle drug that let's you eat bacon, but not get fat. The reason underlying the French paradox (for those of you who have been living in a cave over the past 2 years, resveratrol is found in red wine). A quick Google search yields a myriad of discussion boards and chats littered with the experimental chemistry of everyday people taking ridiculous amounts of this stuff, without any knowledge as to the safety or long-term repercussions. Most of these math-savvy geniuses simply calculate the proportionate dose for what was given to the mice in David Sinclair's most recent study, and consume that amount per day. Thus, many people are taking this compound in doses on the order of thousands of milligrams (quite a boon for the vitamin and supplement business, who is thoroughly encouraging this practice). Some of these user discussions touch on safety, and whether the resveratrol-containing products that they are buying actually deliver what they promise. However, responses to these concerns are too often ridiculed, or simply waved away as not believable by the other discussion board participants. This resveratrol "craze" is a perfect example of the interaction between science and the public being largely based on ignorance and "gut feelings" about what is correct, as opposed to actual dialogue and education. This is exemplified by postings at this forum (especially those of "gardner"). What are these people thinking? We need to address both the science and the ethics in order to provide appropriate guidelines for the science-challenged public in the form of modest regulation.

It is interesting to compare human enhancement through "work" (diet/exercise as a physical example or education/study as a cognitive example) and through pharmacological means. If both exercise and doping, or studying and enhancers, turn on the same respective sets of genes and modify protein expression patterns in similar fashions, it seems that the ethical questions simply boil down to whether we value popping a pill or taking an injection the same way as we do a good work ethic. We don't value pill-popping over work ethic, so chemical enhancement becomes controversial. This is, of course, placing the health questions/risks aside, because for a more pure debate about the ethics, we can't mix concerns about public health policy with human enhancement.

When a person lies about the means by which they are enhanced, we are outraged (see Barry Bonds), but is this because of the doping or because of the deception? If athletes were more forthcoming with their pharmaceutical transgressions, would the public be somewhat more accepting? (see the forgiveness of Jason Giambi over steroid use as an example...) Therefore, as long as those who use cognitive enhancers do not lie about their actions, granting others full disclosure and allowing all successes to be placed in their proper perspective (for you baseball fans, the application of an "asterisk", if you will?), will society ultimately accept this brain doping as just another personal choice?

Posted by Noah Gray at 01:51 PMon December 19, 2007 | Permalink | Comments (0) | TrackBacks (0)
Categories: Noah Gray, Science Policy

Staying on the genetics theme, a recent Science article suggests that a particular variant of the dopamine receptor (D2) causes some people to poorly learn via negative reinforcement. The A1 allele, as this variant is known, has previously been linked to increased vulnerability of addiction.

The researchers recruited volunteers, who performed a learning task while lying in an fMRI machine. Individuals with the A1 allele (at least one copy) were equally successful at selecting a targeted "good" symbol reinforced with positive feedback (the display of a "smiley face") as those individuals completely lacking the A1 allele. However, when the task was changed such that negative reinforcement drove the learning (subjects were asked to avoid the "bad symbol"), those individuals with the A1 allele failed to perform as well as their A1-lacking colleagues.

Examining the fMRI data, those with the A1 allele had less activity in the frontal cortex and hippocampus, two areas normally responsive during tasks involving negative reinforcement and memory. This reduction was thought to be because posessing the A1 allele can cause up to a 30% reduction in D2 receptor density in individuals, presumably affecting the neural circuitry, and likely influencing the activity within the reward signaling pathways.

With a variety of evidence suggesting that the A1 allele is more prevalent in alcoholics (although there is also plenty of evidence refuting this link), the authors are enthusiastic that they have uncovered an important bridge between addiction and reward reinforcement. Alcoholics tend to repeatedly experience strife, perhaps because they cannot learn from the negative consequences suffered as a result of their actions. Therefore, the thought is that this genetic inability to process negative experiences as learning opportunities can underlie the social and physical consequences of this disease. What a bunch of rubbish.

The current study is based on 26 German males, with 12 of them posessing the A1 allele. So it is not only small, but conducted in a very specific population. Positive reinforcement as the display of a smiley face? Negative reinforcement as the display of a “frowny” face? I bet every alcoholic, with or without the A1 allele, wishes that the worst that would happen to him/her at the end of a rough night of binging is that when they pressed a button, a frowny face would come up (usually that frowny face is attached to a policeman with a large nightstick and handcuffs…). This study seems to be stretching quite a bit, and looks to be more of a headline-grabber than anything. Tellingly, in an accompanying piece, geneticist Neil Risch states:

[The A1 allele] has been a candidate gene for every imaginable psychiatric phenotype for 18 years now, and to my knowledge none of the originally reported associations has held up.

I guess only time will tell whether this study holds true, or is swept into the research purgatory of “irreproducible”, or “controversial” (due to conflicting studies NOT demonstrating a link between A1 and negative reinforcement). Taking Risch at his word, it seems possible that many population genetics researchers studying A1 also possess a copy or two…

Posted by Noah Gray at 04:44 PMon December 18, 2007 | Permalink | Comments (0) | TrackBacks (0)
Categories: Noah Gray, Interesting Neuroscience

With this entry, I hereby retire from reporting on the details surrounding Dr. James Watson's race row. The subject of IQ and race may rage on in this blog, but it is time to move past the tabloid reporting. Fittingly, I felt that we should return to where it all began...with the release of a new book. Here is a review on Dr. Watson's Avoid Boring People by Jerry Coyne, a geneticist at the University of Chicago. Dr. Coyne paints a complex picture of the author, and attempts to be rather candid, succeeding for the most part. In addition, he does not hide his obvious admiration for the man. You can feel free to contrast Dr. Coyne's review with the opinion of another critic. No mercy given by that Nature editor.

With regards to moving on, I have plenty of ideas for new discussions, but would also like to offer up the concept of "reader-generated content." If I receive enough participation, I'm willing to discuss what you find interesting as often as you send me promising topics. For now, let's set the modest goal of one reader-selected topic every 2 weeks, and go from there. If you would rather keep your communications and ideas private, feel free to email me at 'Actionpotential' at natureny dot com.

Posted by Noah Gray at 10:55 AMon December 14, 2007 | Permalink | Comments (0) | TrackBacks (1)
Categories: Noah Gray, Popular Press

I don't know what it is about Jim Watson and my blog posting, but every time I mention him (as I did in my previous entry), something else pops up and I have to talk about him again. While doing my morning reading, I stumbled upon an entry from the DrugMonkey blog that was simply too good to pass up. Jim Watson is more mixed race than anyone thought, with 16% of his genes likely to have come from an African great-grandparent, as reported in the Sunday Times.

[12/12 - MAKE SURE YOU CHECK THE UPDATE. CLICK BELOW TO CONTINUE READING.]

Since Dr. Watson's genome is publicly available, this sort of analysis was easily conducted by deCODE Genetics, a company that specializes in assessing individual genetic risk factors. In addition to being 16% African, Dr. Watson also boasts a healthy 9% proportion of Asian-derived genes. The average person of European descent would have no more than 1% African genes. It would be surprising if Dr. Watson did not already know this, as the proposed relation would be close enough that he could have heard the story surrounding his descent from an older relative. If this were true, it would make his controversial comments all the more remarkable.

Let's not forget that this article was also a blatant advertisement for deCODE's services (see the chart of risk factors listed at the bottom of the article that is a complete add-on and has no bearing on the topic), but I'm more than happy to put up with the advertising for the information, in this case.

Inadvertently, deCODE solved another mystery as well. Dr. Watson has never attempted to hide his healthy fondness for the opposite sex, and with his theory proposing that higher melanin levels lead to a stronger libido, we now have a solid explanation for his strong impulses. Obviously, it's in his genes.

*************

Update: Dec. 12, 2007; 13:30 - Chris Gunter pointed me to a NY Times article on this subject in which a few more tiny details are revealed. The deCODE genetics CEO, Kari Stefansson, confirmed that all the company did was run the publicly-available data on Dr. Watson's genome through their analysis programs, and provides a cautious caveat regarding the results. Dr Stefansson does sound pretty confident (and smug) with his parting shot, though.

On another note, the Times again fails to be upfront with their conflict of interest statements. Near the end of the article, Dr. George Church questions the accuracy of any of the current scanning and analytical services. This is bolstered by fancy sounding titles: "Professor of genetics at the Harvard Medical School and the director of the Center for Computational Genetics." Oooooops!!! Forgot to add this one: co-founder of Knome, Inc., a private company offering genomic scanning and analytical services. It is in Dr. Church's best interests to call into question the techniques and ethics of deCODE, his direct competitor, and position his company as the more responsible option for genomic testing. (Sigh), well, I guess I didn't expect change overnight. When it rains...

Posted by Noah Gray at 10:23 AMon December 11, 2007 | Permalink | Comments (3) | TrackBacks (0)
Categories: Noah Gray, Breaking News, Popular Press

There was a great Op-Ed piece in the NY Times yesterday, written by Dr. Richard Nisbett, that provides a nice set of studies challenging the notion of inherent intelligence differences between races. Dr. Nisbett communicates these findings to the reader in a very clear fashion, providing good information for those of you who followed the news and debate underlying the Watson scandal.

One telling excerpt that I especially appreciated, since it is based on the sheer weight of scientific logic:

That environment can markedly influence I.Q. is demonstrated by the so-called Flynn Effect. James Flynn, a philosopher and I.Q. researcher in New Zealand, has established that in the Western world as a whole, I.Q. increased markedly from 1947 to 2002. In the United States alone, it went up by 18 points. Our genes could not have changed enough over such a brief period to account for the shift; it must have been the result of powerful social factors. And if such factors could produce changes over time for the population as a whole, they could also produce big differences between subpopulations at any given time.

As stated, we know that it is impossible for our genes to change enough in 55 years to account for such vast differences in intelligence (as measured by the IQ test), simply because that time frame spans only 1-2 generations at most! Epic genomic changes do and can occur, but require many generations to take place, events only successfully studied and carried out in organisms with short lifespans and rapid reproductive cycles. But more importantly, doesn't this simply reinforce the fact that the IQ test suffers from serious bias and unreliability issues? 18 points in 55 years??? Either Sesame Street and Baby Einstein are miracle workers, processed foods and high fructose corn syrup are unfairly ignored as "brain foods", video games are better than reading, or the IQ test isn't as accurate as we would like it to be. So let's be a little cautious when comparing these numbers, especially when pointing out differences...

Why these concepts are so challenging for a significant portion of the population to grasp really boggles my mind. To those individuals, if you don't have the time or motivation to read The Mismeasure of Man, I certainly hope that you will at least read the "lite" version (meaning this Op-Ed piece [ONLY 2 PAGES!!!]) to assist you in establishing your opinions on this matter. But perhaps even that is asking too much. Therefore, why don't you wait for the "Op-Cast" to update this week, so you don't even have to read.

Posted by Noah Gray at 11:10 AMon December 10, 2007 | Permalink | Comments (6) | TrackBacks (1)
Categories: Noah Gray, Popular Press

Since the recent fall-out of the recent NY Times OP-Ed piece discussing the use of fMRI to predict the inclinations and feelings of swing voters is still fresh in our minds, I wanted to simply provide the link to a recent PLoS ONE paper that touches on the general concept of the media reporting on science.

Basically, only around 10% of popular press articles actually list the source of funding paying for the research. But of those, only 75% of the time was the type of financial tie obviously cited. I agree with the authors of the article, who state that the explicit reporting of financial ties and potential conflicts of interest by researchers plays a significant part in how the public views science and the scientists. It took a long time, but almost all academic journals now require a "Conflict of Interest" statement to be published with each manuscript. With the explosion in popularity of science blogs and news sites linking stories to scientific findings and articles, the time has come for the popular press to uphold the same sort of standards, better informing the reader of potential bias.

So the publication of this article simply allows me to re-hash what I touched on in that previous entry since, but we probably could have guessed it, now we have the numbers revealing that the NY Times is in no way alone on this matter. Science journalism plays an enormous part in public opinion, which influences the actions of politicians (sometimes), who have some power to control major chunks of research funding. Therefore, public trust and respect are essential for the long-term growth and stability of scientific funding, especially from the government. So let's have the press play their part both in providing full disclosure and refraining from publishing scientifically-dubious (but headline-grabbing) stories, leaving the "spin" for the politicians.

Posted by Noah Gray at 01:18 PMon December 06, 2007 | Permalink | Comments (0) | TrackBacks (1)
Categories: Noah Gray, Interesting Neuroscience, Scientific Publishing, Popular Press

If it exists, it must be a tenuous link, right? Well, at least in C. elegans, it is definitely not. Linda Buck and colleagues revealed, in a recent Nature article that drugs modulating the serotonin system in the worm can increase lifespan. Caloric restriction has been a well-documented means to enhance longevity in animals ranging from rodents to worms. We have only recently begun to mechanistically understand why eating less allows us to live longer (remember the sirtuin genes?)

In this latest study, the authors found that a compound typically used as an antidepressant, called mirtazapine and commercially known in the US as Remeron, increased lifespan in the worm by 31% through an inhibition of the 5-HT2 receptor for the neurotransmitter serotonin. This occurred in a dose-dependent manner. Several compounds in the same family (with similar modes of action) failed to increase lifespan in worms harboring mutations in genes causing a disruption of the serotonin system, like in the synthesis enzyme tryptophan hydroxylase or the serotonin reuptake transporter.

In an attempt to link these mechanisms to those typically associated with lifespan extension in the worm, Buck and colleagues demonstrated that treating worms with the antidepressant after caloric restriction failed to increase lifespan beyond that which occurred following caloric restriction alone. In addition, treatment with the drug had little effect on lifespan in worms expressing mutant proteins required to reap the benefits of caloric restriction.

Since serotonin is a neuromodulator that affects a variety of neuronal functions, including food-intake regulation, altering the serotonin system may cause the worm to enter a state of "perceived starvation" that, despite adequate food intake, would still activate the signaling mechanisms responsible for inducing an extended lifespan.

Whether or not this mechanism will hold up in humans is anyone's guess; the only evidence that it might do so comes from reports of an increased appetite in those taking the same class of antidepressants as was used in the Nature study. If it does turn out to be an evolutionarily conserved pathway in humans, it seems like this mechanism could be a coup for Big Pharma. With antidepressants being prescribed at alarmingly high rates (as of 2002, 11% of women and 5% of men in the non-institutionalized population take anti-depressants), and with those customers living longer because of their prescription filling, Big Pharma could have what Big Tobacco never had: an addictive (at the least psychologically) product that makes more money for the company because it causes its customers to live longer.

Posted by Noah Gray at 04:02 PMon December 04, 2007 | Permalink | Comments (10) | TrackBacks (0)
Categories: Noah Gray, Interesting Neuroscience