gene patenting

This week's Science Friday focused on gene patenting.  Specifically, a case that has been in court since May of 2009: the American Civil Liberties Union (ACLU) -- along with several cancer patients and organizations of pathologists -- has raised a lawsuit against Myriad Genetics' patenting of the two genes BRCA1 and BRCA2.  Mutations of these genes are indicative of increased risk of breast and ovarian cancer.

The ACLU claims that Myriad's 1994 patent on the genes is illegal, unconstitutional and should be thrown out.  The issue of importance to the cancer patients involved is that Myriad's monopoly on the tests for mutated BRCA1 and 2 prevents patients from getting a second opinion on the results of their tests, and from obtaining a more affordable version of the test.

In my mind, patenting genes is like patenting anything else in medicine.  By invoking a 20-year period of exclusive rights, development of the patented technology or drug is inhibited.  This is the way it has worked with pharmaceuticals for eons: drugs remain produced, distributed and exorbitantly priced by the pharmaceutical companies who patent them, and become eligible for other companies to optimize and distribute generically when that 20-year period is up.

The opposition to this argument is that patenting genes causes more stunting to medical innovation -- and, by default, medical cures -- than does patenting of drugs and other medical technology.  By patenting genes and the single test that has been developed to identify them, patients interested in the risk those genes may pose to them are forced to rely on the interpretation of the patenting company.  In the case of BRCA1 and 2, patients cannot get a second opinion outside of Myriad Genetics; they are forced to rely on the results obtained from Myriad's test and on the interpretation of Myriad's doctors.

My response to this opposition is as follows:

Genes are only a single indication of disease.  It has been reported that  "inherited BRCA1 and BRCA2 mutations account for 5 to 10 percent of breast cancers and 10 to 15 percent of ovarian cancers among white women in the United States" (Campeau et al 2008) -- having the mutations is not a definitive diagnosis of cancer.  It has also been reported that this percentage is even smaller: "[a]pproximately 5-10% of breast carcinomas and 10% of ovarian carcinomas are ascribable to a genetic susceptibility. Of these, about 40% are related to genetic mutations in the genes BRCA1 and BRCA2" (Palma et al 2006).  Take from that statistical discrepancy what you will -- I guarantee there was not a new census taken between 2006 and 2008.

If patenting of genes inhibits patients from getting a second opinion on their genetic tests, it seems that seeking a verification through other diagnostic methods is not only an acceptable option, but a preferable one.  Treatment of breast/ovarian cancers in particular are radically invasive and life-altering; until the BRCA gene identification tests are available "generically", mammograms,  MRI and screenings for other genetic markers of breast/ovarian cancers are not only options but -- in my very humble opinion -- an incredibly good idea before making decisions about radical mastectomy and chemo:

"Clinical testing options for BRCA1 and BRCA2 are limited in the United States. In contrast to genetic testing for BRCA1 and BRCA2, genetic testing for other cancer susceptibility genes (MSH2, MLH1, PTEN, TP53, etc) is available from numerous profit and notfor- profit laboratories, with a range of testing options and prices."

"In addition to DNA sequencing of BRCA1 and BRCA2, genetic testing for other major breast cancer susceptibility genes including CHEK2, PTEN, and TP53 is clinically available in the United States." (Walsh et al 2008)

 Patients at risk for cancer should not limit their diagnosis to the outcome of a single kind of test when there are several out there, and certainly not to a single genetic test which measures only susceptibility.  I do not argue against the legitimacy of a patient's concern, I just don't think that this particular argument is reasonable ground to make illegal the patenting of genes by their discoverers.

I am not sure I agree with the ACLU's argument either:

“What they have really patented,” says Chris Hansen of the ACLU to the New York Times, “is knowledge.” 

Really?  If that is a legitimate statement, then every biomedical patent in the world is a blockade against knowledge, and they should all be overturned.  Patenting is a measure taken to protect and honor the discoveries of researchers.  It gives them the opportunity to make advancements on their own discoveries before the whole world is allowed to take a crack at them.

"Genes are informational. [By] allowing a company to have a patent on the actual sequence you are restricting the free flow of information," Tania Simoncelli, ACLU's science advisor, told Pharmacogenomics Reporter back in May.  Simoncelli's colorful expatiation of this comment can be found here.

THE POINT OF PATENTS IS TO TEMPORARILY RESTRICT THE FLOW OF INFORMATION.  IF YOU WANT TO BRING THE FIRST AMENDMENT INTO THIS, YOU HAVE TO FIGHT ALL PATENTING OF ALL DISCOVERIES EVER.

BIOMEDICAL RESEARCH HAS BEEN PATENTING GENES SINCE THE 1980's AND DOCTORS HAVE BEEN PISSED OFF ABOUT IT SINCE THE 1980's.  IF THE PATENT OFFICE WAS WORRIED ABOUT GENE PATENTING BEING CONTRARY TO THE PUBLIC INTEREST, THEY WOULD NOT ISSUE THEM.

In short, I have yet to find a legitimate argument made by the ACLU against patenting the BRCA1 and 2 genes, much less any gene.  I'm not saying that genes should or should not be patentable; what I'm saying is that the ACLU is making a poor argument, and needs to approach this from more of a patient access angle.

Maybe what needs to happen here is for gene patenting to selectively be restricted to 5 years instead of 20.  Five years is nothing from a scientific standpoint, and wouldn't actually allow researchers the opportunity to make significant headway before the rest of the world chimed in, but it would at least give them a head start without making prospective patients wait an inordinate amount of time for reasonable diagnosis or treatment.  And five years of profit from over-priced tests certainly ain't bad.

in vitro meat and the de-evolution of homo sapiens

Homo sapiens is Latin for wise or knowing man.  I would like to strike "sapiens" from our evolutionary title and replace it with "homo follis", which is Latin for windbag or foolish man.  Can I do that?

Normally, I love technology and am all for its advancement as long as there is an antidote should it prove to be physically or ethically harmful.  There is a line, however, over which technological advancement frequently crosses into the world of promulgating sheer gluttonous sloth.  The antedote in the case of modern animal farming is to change human behavior.  If we consume less meat, farmers aren't pressured to over-produce massive qunatities in order to stay economically competitive.  Less pressure to over-produce means less incentive to abuse farmed animals with antibiotics, hormones, extremely unhealthy food and other revolting living conditions.

But is the American populous ready to make that sacrifice for the sake of being humane?  You bet your ass we're not.  Instead, commercial science has discovered a much more attractive antidote to modern animal farming -- one that requires significantly less effort on the part of the consumer than reducing meat consumption.  For the last decade or so, scientists have been learning how to culture "meat" in a petri dish (Datar & Betti 2009; Edelman et al 2005).  We (the people) are so lazy and so addicted to meat that scientists and economists have fleshed out an analysis of the viability of in vitro meat culturing as a "replacement" for meat farming (In Vitro Meat Consortium 2008).

Is it less of a personal burden to adjust to the taste of stem cell meat than to eat less meat and/or eat more local/grassfed/humanely farmed meat?  The In Vitro Meat Consortium seems to think so, as does PETA:

"As far as we’re concerned, if meat is no longer a piece of a dead animal there’s no ethical objection." 

Really?  Because I'm pretty sure that teaching humanity survival through relying on technology to save us from having to make proactive changes in our behavior has negative ethical implications.  For instance, the backward evolution of our species. 

"Lab-grown meat isn't an easy sell, but there could be benefits. Designer meat would theoretically be free of hormones, antibiotics, and the threat of mad cow disease or bird flu. Omega-3 fatty acids and vitamins could be blasted into the mixture ", says Ian Christe in his article in Popular Mechanics on the subject.

Yes, Ian, you are absolutely correct.  However, HUMANELY FARMED ANIMALS WOULD ALSO BE THEORETICALLY FREE OF HORMONES, ANTIBIOTICS AND THE THREAT OF MAD COW DISEASE OR BIRD FLU.  Additionally, OMEGA-3 FATTY ACIDS AND VITAMINS ARE PRESENT IN FREE-ROAMING UNGULATES WHO ARE NOT PUMPED FULL OF GRAIN-BASED SLOP TO FATTEN THEM UP ALL YEAR ROUND.  And further, WHAT ABOUT ALL THE OTHER SUBSTANCES THAT ARE USED IN THE CULTURING OF THE MEAT; MUST WE ASSUME (like idiots) THEY WILL BE TOTALLY HARMLESS?

So, I must pose the final question: will humanity prefer the financial burden of commercial in vitro meat production, or the burden of changing their consumptive behavior in order to promote humane animal farming?  Unfortunately, I fear the former may win out. 

Lastly, a warm thank you to PETA for supporting the de-evolution of humanity (not that I'm surprised), as well as an alternative to industrially farmed meat that wont actually stop anyone who wants to taste real meat from doing so (tofu dogs have already made this attempt).

phthalates and ADHD

The outstanding debate on whether the benefits of soft plastics outweigh their potential harms continues. 

The group of esters called phthalates are used in an array of products ranging from pill capsules to children's toys to shower curtains.  A research group in Korea has found a strong positive correlation between ADHD behavioral characteristics and phthalate metabolites in the urine of Korean school children.  This is a particularly important study for two reasons: 1) a correlation between ADHD and phthalate exposure during critical periods of development has never been shown, and 2) the metabolite levels found in these children indicates the amount of exposure that can now be replicated in animal models.

"Previous animal studies (6,15,16) have shown that phthalate related metabolites induce hyperactivity in rats. These studies reported that pups treated with phthalate demonstrated 1.4 times the level of hyperactivity at night compared with control subjects. Such hyperactivity was dose-dependent, which is consistent with the results of our study."

"It is possible that the toxicity of phthalates is attributable to degeneration of dopaminergic neurons, leading to the hyperkinetics observed in rats in cases of 6-hydroxydopamine (OHDA) procedures (27). Well-known animal models of ADHD like the OHDA rat model suggest that the dopamine neuronal damage can provoke hyperactivity and impulsivity. Many structural magnetic resonance imaging studies showed striatal volume loss suggesting the dopamine neuronal loss in ADHD patients (28)."

"With DNA macroarray data, researchers have found that phthalate metabolites change
the expression patterns of various genes, including both the dopamine receptor D4 (DRD4) and the dopamine transporter in the midbrain (6). The dopamine receptor D4 and dopamine transporter gene expression modulation can induce changes in extracellular dopamine and neuronal dopamine sensitivity, resulting in hyperactivity and impulsivity in rats."

Here is something particularly interesting: if excessive exposure to phthalates is linked causally to ADHD phenotypes -- which has yet to be explored -- perhaps the time-release medications used to treat ADHD such as Wellbutrin and Ritalin should cease to use phthalates in the enteric coating of their medications.  It seems odd that they are so widely used in films of pharmaceutical capsules if for no other reason than their heavy reputation as endocrine disruptors.  Capsules can contain in the range of 3600 ug phthalates, while most studies estimate that the "safe" exposure range is near 20 ug per kilogram body weight.  That means the "safe" range for most young children is about 750 ug.  Note that phthalates do not bioaccumulate, so exposure levels are dailies.

"The bupropion (Wellbutrin® SR)  release rate has been improved by the introduction of two types of film coated active pellets that release the drug at different pH resulting in novel dissolution profiles. Inert spheres are initially coated with bupropion and hydroxypropyl methylcellulose. The active pellets containing bupropion comprise 70-75 weight % of the dosage form. An enteric coating, applied to about one third of the active drug pellets, is comprised of a film insoluble at low pH, such as hydroxypropyl methylcellulose phthalate. The second coating applied to the other two thirds of active drug pellets is comprised of a combination of a hydrophobic coating agent and methyl acrylic acid copolymer. The two pellet types are then combined in a capsule."

"The novel dosage forms are used to administer methylphenidate (Ritalin) in a pulsatile release manner... Suitable membrane coating materials for effecting delayed release include, but are not limited to: cellulosic polymers such as hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, methyl cellulose, ethyl cellulose, cellulose acetate, cellulose acetate phthalate, cellulose acetate trimellitate, hydroxypropylmethyl cellulose phthalate, cellulose ester-ether phthalate, hydroxypropylcellulose phthalate, alkali salts of cellulose acetate phthalate, alkaline earth salts of cellulose acetate phthalate, hydroxypropylmethyl cellulose hexahydrophthalate, cellulose acetate hexahydrophthalate..."

Journal Club: on the selective degeneration of dopamine neurons in Parkinson's disease

http://www.ncbi.nlm.nih.gov/pubmed/16299504

The therapeutic application of potassium gated ATP channels (K-ATP) in Parkinson's disease arises from their ubiquitous expression in the basal ganglia.  Regulation of these channels evokes cell hyperpolarization in order to prevent cell excitability.  In the mitrochondria, they play a role in translating the metabolic state of the neuron.  This week's journal club discussed an article suggesting that K-ATP channels are necessary for the selective vulnerability of dopamine neurons in the substantia nigra pars compacta (SNpc) relative to the ventral tegmental area (VTA).   Liss et al demonstrate this theory using mitrochondrial complex I inhibitors rotenone and MPP+, both neurotoxins commonly used in developing Parkinson's disease models in rodents.

Rotenone and MPP+ are known to selectively degenerate dopamine neurons of the SNpc, leaving the VTA dopamine neurons primarily in tact.  Liss et al suggest that this phenomenon is due to differential mitochondrial uncoupling (or, disruption of metabolism).  Extensive uncoupling with the application of FCCP resulted in activation of K-ATP channels in both the SNpc and VTA.  Mild uncoupling with FCCP did not activate K-ATP channels in either region.

"Notably, however, mild uncoupling inverted the response of K-ATP channels to complex I inhibition: in this case, VTA DA neurons, but not SN DA neurons, were hyperpolarized and functionally silenced due to K-ATP channel activation. In the presence of 50 nM FCCP, none of the SN DA neurons was significantly affected by 100 nM rotenone (Fig. 5a,b, left; perforatedpatch recording in 50 nM FCCP: 2.33 ± 0.29 Hz; FCCP + rotenone: 1.92 ± 0.36, n ¼ 6; P ¼ 0.40) or 10 mM MPP+ (data not shown). In contrast, the presence of 50 nM FCCP sensitized K-ATP channels of VTA DA neurons to complex I inhibition (Fig. 5a,b, right; 50 nM FCCP: 2.4 ± 0.55 Hz; FCCP + rotenone: 0 ± 0 Hz, n ¼ 6; P ¼ 0.0075)."

"Stereological analysis of all SN pars compacta neurons in hematoxylin-eosin counterstained sections demonstrated genuineMPTP-induced neuronal death in wildtype mice and confirmed the complete rescue of SN neurons in the Kir6.2-/- mice (Fig. 6d, middle panel; Kir6.2+/+ SN: control, 11,882 ± 222; post MPTP, 8,061 ± 632, P ¼ 0.029; Kir6.2 -/- SN: control, 12,288 ± 231; post-MPTP, 12,619 ± 223; P ¼ 0.36; n ¼ 3 each)." ** Kir6.2 -/- mice are a genetic strain not expressing a unit of the K-ATP channel necessary for activation.  This means that blocking the channel's activity prevented SN DA neurons from being lost.

I want to see some apoptosis markers in these SNpc DA neurons due to K-ATP activity.  The comaprison of SNpc and VTA DA neurons is an invaluable resource for identifying mechanisms of the selective degeneration that marks Parkinson's disease.  Because the VTA DA neuron population is so identifiably unaffected by most neurotoxins from which Parkinson's models are developed, the selectivity of the models and the degree of neural degeneration is not only measurable but comparable to many cellular mechanisms of the disease itself.  Uncoupling of the mitochondria speaks to selective metabolic toxicity, and a new target for neuroprotective therapies.

** This was a very complex article using six different mouse strains/treatment groups and analyzing the cell viability using electrophysiology, histology and RT-PCR -- I am reciting only the briefest summary which does not to justice to the extensive work done (although my critique is long-winded, I was impressed with these studies).

on the stifling of creativity

An experiment was conducted by Desmond Morris in 1962 comparing the artistic creativity of young children and chimpanzees.  Remarkably, both chimp and human child became so engrossed in their painting that they showed very little interest in food, sex or other activities that would be expected to divert their interest.  The major revelation of this study was that creativity was, perhaps, a natural potential; yet, for many of us, the urge to create diminishes significantly as we grow older, revealing itself only in the sciences, music, art... and on a more modern note, advertising [trash].

A follow-up study to Morris' added a reward system to the chimps' sessions of abstract expressionism.  The results was that with each reward, the creativity and depth of the painints degenerated until producing only the minimal product necessary to obtain reward from the experimenter (The Biology of Art, Methuen London, 1962).

David Bohm has described this phenomenon as follows:

"In order to do something for a reward, the whole order of the activity, and the energy required for it, are determined by arbitrary requirements that are extraneous to the creative activity itself.  This activity then turns into soemthing mechanical and repititious, or else it mechanically seeks change for its own sake.  The state of intense passion and vibrant tension that goes with creative perception... then dies away.  The whole thing becomes boring and uninteresting so that the kind of energy needed for creative perception and action is lacking.  As a result, even greater rewards or punishments are needed to keep the activity going" (Science, order and creativity; 2000).

I've written about ADHD before, but was inspired to revisit the topic by a seminar forwarded to me:

http://www.ted.com/talks/lang/eng/ken_robinson_says_schools_kill_creativity.html

So my question is this: to what extent is the reward system of education -- any kind of education -- destructive to the development of the self?  Is not the self-consciousness, dissatisfaction and boredom resulting from intervention by directed creativity dangerous to development? Some of what were considered the greatest creative minds of history thwarted standardized education.  From the science realm alone (with which I am most familiar), Copernicus meandered through universities for seven years without bothering to fulfill a degree.  Da Vinci was educated by the royal Medici family, but education in the Italian Renaissance was its own matter entirely.  Tesla boycotted academia at the age of ten.  Thomas Edison never went. 

On the other hand, in more recent history it has become nearly impossible to achieve recognizable creativity without eons of academic vigor.  How is that demand defining the way we structure the reward system of education?  We pump in the sedatives to get this "most troubled" generation through the hoops.  In so doing, we are pummeling creativity from both ends: reward and sedation.  What will become of our next generation of scientists and artists?

autism spectrum disorders, part deux

Another instance where the question begs to be asked: are handwriting patterns differentiated between autistic and Asperger children?

This study found quality of letter formation in the handwriting of children with ASD to be lower than in normally developing children.  The subject hasn't really been addressed since 2001, when Beversdorf et al identified the significant instance of macrographia in patients with ASD, as compared to age- and IQ-matched control subjects.  Both studies have subsumed autism and Asperger into the ASD umbrella -- just as likely for the purposes of procuring a larger test subject sample as for making their results widely applicable:

"Whereas all subjects with autism spectrum disorder met the diagnostic criteria for autism through their reported behavior during childhood, most subjects had demonstrated significant improvement in function over time, such that the distinction between the various forms of autism spectrum disorder was not as clear. Therefore the more general term autism spectrum disorder is used to describe these patients." (Beversdorf)

The original description of Asperger syndrome in 1944 noted difficulties in motor coordination, specifically in handwriting (Frith; translated 1991).  One year before, Leo Kanner published his first paper asserting that some autistic children were quite agile, performing "hair-raising feats of balancing," while others were clumsy "despite dextrous manipulation of objects" (Frith pg. 95). 

I would love to see a study comparing the different aspects of handwriting using both the Revised Physical and Neurological Examination for Subtle Sign (from the Kennedy Krieger Institute study), and the Autism Spectrum Quotient and Empathy Quotient tests used by Baron-Cohen's group to differentiate autism and Asperger syndrome.  Any cerebellar distinctions between autism and Asperger could be very illuminating...

autism spectrum disorders and dsm-v politics

An article in the New York Times this morning by Simon Baron-Cohen addressed the debate in the DSM committee over subsuming the conditions of Autism and Aspergers in the fifth edition of the "psychiatric bible"(promised in 2012).  The committee is deliberating whether or not to eliminate Asperger from the diagnostic manual and characterize its discrete symptoms as a degree of autism in the spectrum (perhaps "intermediate functioning autism").

Autism and Asperger syndrome are both characterized by impaired communication skills, a desire for keenly focused stimuli and strong inclination toward repetition. They are distinguished only by a slower onset of language skills and latency of intelligence in autism, says Baron-Cohen.  He further suggests that this distinction is proving not to be concrete enough, and that the DSM-V committee's struggle with the controversy can be attributed to the lack of physiological distinction of these psychiatric conditions.

I would agree with Baron-Cohen that there is not currently enough genetic distinction between autism and Asperger syndrome to warrant their being entirely separate conditions outside the spectrum disorders umbrella in the DSM-V.  However, I think that defining Asperger syndrome idiosyncratically is important to preserve in the new manual.  Here is why:   

1)  Baron-Cohen mentions his own group's recent identification of 14 Asperger-specific genes,19 genes specific to autism and 7 shared (Chakrabarti et al 2009).  They measured 68 candidate genes in two experiments: the first measured autistic traits in an undiagnosed sample population using the Autism Spectrum Quotient; the second, using the Empathy Quotient.  These two experiments were designed to identify autistic and Asperger cases among the sample:

"We searched for common genetic variants (single nucleotide polymorphisms (SNPs)) on the assumption that autistic traits are continuously distributed in the general population [Constantino & Todd, 2005; Sung et al., 2005]."

"In Experiment 1, autistic traits (measured on AQ and/or EQ) were nominally associated at P<0.05 with SNPs from 19 genes. In Experiment 2, SNPs from 14 genes were nominally associated at P<0.05 with AS."

Six genes were nominally significant in both experiments. This study alone suggests that Asperger syndrome deserves a distinction as a sub-group in the Autism Spectrum Disorders (ASD) category that the DSM-V committee is considering, as opposed to eliminating it entirely, as is also being considered.

The Charkrabarti study is impressive, and the first step in the important attempt to identify the genetic and epigenetic correlates of autism and Asperger separately.  However, there is still an extensive amount of correlative research to be done.  A good amount of this is ongoing through the AutDB Project.

2)  If for no other reason than to preserve the honor of the venerable Hans Asperger.

3)  To keep company the solitary other recognized ASD, Pervasive Developmental Disorder - Not Otherwise Specified (PDD-NOS).*  Perhaps these could both become sub-groups in the ASD category.

It is noteworthy that a great deal of genetic research already refer to their studies as ASD interactions/links/correlations (PubMed or Google Scholar this).  I am terribly eager to find out whether or not this plays a strong role in the decision of the DSM-V committee.


*High- and Low-functioning autism are not classified as spectrum disorder subgroups, although they should be... and perhaps, one day, will be, provided there is a physiological distinction to be drawn between them, Asperger and PDD-NOS.

Journal Club: on Vitamin D and Parkinson's disease

Preface:  After a long hiatus during which I have been doing so much research on Crohn's disease that I haven't written a damn thing about neuroscience, I've decided that it's time to return.  I have officially submitted my graduate school applications, and now need to get myself back into regular science-writing mode.

This week's Movement Disorders Journal Club held some lively discussion on the roles that vitamin D might play in the balance deficits of Parkinson's disease patients.  This was based on data presented for a grant application, so the following will have little to do with Dr. P's actual pilot study.

Vitamin D deficiency appears to be prominent in elderly people who frequently experience falls (Bischoff-Ferrari et al 2004).  The mechanisms by which vitamin D is involved with balance, however, are largely unknown.  Dr. P's studies propose to look at how vitamin D levels correlate with falls and posturography in patients with Parkinson's disease (PD) because post-mortem immunolabeling studies have shown that vitamin D receptors are particularly dense in the substantia nigra pars compacta (SNpc)(Eyles et al 2005).

The SNpc is an area of primary pathology in PD; specifically, it is the beginning of the primary dopamine pathway that extends to the basal ganglia and motor cortex, which ultimately make commands of the muscles.  When this pathway is depleted, as in PD, the lack of dopamine signaling from SNpc cells has ramifications through several terminal brain regions which lead to the rigidity, tremor and poor balance that characterize the disease.

One of the important questions to ask, given the high vitamin D receptor density in the SNpc, is what role vitamin D might play in that region of the brain: Is there a central nervous system mechanism by which vitamin D is involved in alleviating behavioral deficits of PD, or is vitamin D helping patients with more general balance deficits through its effect on muscles?

Dr. P is proposing to address this question on both clinical and basic science levels.  Her clinical studies will address the attenuation of several behavioral and motor impairments as correlated with various vitamin D levels.  Her complementary basic science component proposes to speculate vitamin D's activity in the SNpc of a rodent model.  Naturally, this is super exciting to yours truly, so I have offered my services (as an MD, Dr. P needs a collaborative basic science lab in which to conduct the non-human animal component of her studies).  It stunned me, in fact, to learn how little has been studied regarding the role of vitamin D in the SNpc and nigrostriatal pathway, given the clear indication that its receptors are prevalent.

Although this will not begin for several more months, at least, there will be more to come as the publishable results unfurl.  In the meantime, expose yourself to the sunshine! -- you supposedly benefit more from 15min/day sun exposure than from dietary means (Hall et al 2009; Wolpowitz & Gilchrest 2006).  Fanatic Cook elaborates on this beautifully.

empty thoughts X

I perceive evolution of knowledge not as continually growing and expanding, but as serially destroyed and recreated.

Expansion is a popular chimera of growth. We think of the universe in terms of ever-orbiting away from those centers that we have identified. We think of political change as manifestation of new direction. We think of steps forward in technology as bursting revelations. But are all of these things not brought about by reconfiguring previous conceptions?

Matter is never either created or destroyed, but recycled. On a quantum level, that's almost always true. On a grossly observable level - the level of content - it is created and destroyed all the time. Not a thing has been brought to my attention that would suggest the growth of knowledge proceeding any differently.

why neuroscience?

In preparation for meeting with the future of my academic career next week, I set about answering some silly interview questions. The first of these was, naturally, "why do you want to do research in neuroscience?" So I thought I'd share it, as this is the first time I think I've even put it coherently to myself...

Behavioral evolution. The field of neuroscience contains the tools that most interest me in terms of searching for patterns in the evolution of behavior. The nervous system – central and peripheral – guides all the other systems of the body through interaction with the world. From the primitive neural web of the cnidarian to the ganglia of the higher animal, it is interaction with the world that makes us what we are. I love neuroscience for attempting to associate corporeal and ethereal phenomena. I love seeking out the physiological correlates of consciousness, and the pathological correlates of behavioral dysfunction. I crave the abstraction of physiology into a medium for mind and consciousness. My own autonomic system excites when connections are made between the evolution of that medium and the evolution of the intelligence it propagates.

on the changing face of science

I was inspired to pursue academic science by Santiago Ramon y Cajal, the man who discovered neuroplasticity. He was an academic, but first, a scientist and artist. At the end of the first book I read of him was his epitaph, which became the source of my conviction that real science, unfettered by the politics of academia, still exists.

"Scientists should be adventuresome people, restless and imaginative. They should be generous souls - poets at times, but always romantics - and they have two essential qualities. They scorn material gain and high academic rank, and their noble minds are captivated by lofty ideals."

In this process of bolstering my curriculum vitae to attract graduate schools, I am inundated with the mean face of academic politics. It demands that I be recognizable within the scientific community before I am even part of it. Academia must be able to identify me as unique before they accept the burden of my education, but this uniqueness is rightfully represented only by my publications.

While I am the first author of several abstracts, I have not yet published any articles. And while being a first author before having a PhD is impressive, it is significantly less so than being a co-author on a published article. I have a qualm with this particular rule of hierarchy - and with Academia's perspective on publication in general. To be published as a co-author in a scientific paper, you need be involved as little as collecting a key piece of data without having any clue as to its importance to the paper itself. To be a first author, you are either the primary investigator (head of the lab) or you have performed/analyzed/written a substantial portion of the piece. The latter is my case.


I recently mined a book on this subject by Thomas Bender, Intellect and Public Life: Essays on the Social History of Academic Intellectuals in the United States. Among other discussions is that of Academia's role in determining the evolution of science by publication, and how scientists are evolving to become defined by the magnitude - quality and quantity -of their publications instead of their contributions to scientific stride through their careers.

In Cajal's day (the late 18- and early 1900s), publication was a serious achievement, like Galileo's 550 printed copies of The Starry Messenger. Today, it is not unusual to expect an undergraduate student to have their name planted among a list of authors on a paper or two. This is a blessing and a curse. The circulation of scientific discovery has skyrocketed to a point where many articles are freely accessible to the public. However, credit for scientific discovery has become such a bilious diatribe that publications include up to ten co-authors, and the tiniest inkling of participation in the tiniest piece of the article gets your name on the list. Students are recruited to graduate schools based on their publications. Academic scholars are recruited to run labs based on quantity of publication alone, which may or may not sound absurd only to me. The physicist Richard Feynman was asked to head an engineering lab at Princeton because his name was on an unapplied patent that came out of Los Alamos. During the war, Los Alamos was flooded with some of the brightest minds in physics, and the opportunity was taken to exploit any random idea that popped into their heads. A lot of cool shit went down at Los Alamos.


I can't fairly condemn the evolution of publication's importance to Academia, nor Academia's reliance on publication to determine the worth of a scientist. My hope, however, is that quality does not become lost in quantity. I hope that my curriculum vitae communicates that my lack of publication does not represent my throughput or ingenuity...

I have spent over two years with my boss developing a huge project which has evolved from my own undergraduate thesis. The process has involved a scrupulous amount of project design, methodology, animal model development, endless amounts of research and, as goes without saying, an infinite amount of experimentation. As we have been too busy writing grant proposals and collecting alternative data, we have not yet published anything on the many results of this project. Fortunately, my boss has offered me the opportunity to co-author on a textbook chapter and set aside time to write an article on the novel mouse model I have developed before I submit my graduate applications. My boss reminds me of Cajal.

I maintain, sanguinely, that many graduate institutions still have the integrity to investigate the entire portfolio of a scientist before deeming woth investment. That ideal, however, may prove to be too lofty...

ADHD News

Alright. I adore the Huffington Post. Truly. But this is the most ass-backwards half-written piece I think I've ever seen come out of there: ADHD Meds Abuse.

To paraphrase... "This non-profit study says this (kind of), but this big-pharma study says that (almost) - oh noes!... ... ..."

As a scientist, I take personal offense to this kind of writing. As a human being, I take umbrage to the lack of integrity in an article addressing an epidemic controversy such as ADHD. It's empty. There's not even an argument for or against the methodology of one study or another. There are no details as to how the study was conducted, no questioning the legitimacy of any of it, and the conclusion is that "the study lacks information on whether abusers were teens with ADHD, but anecdotal evidence suggests many are not."

... what? Really? Your conclusion is something that you left until the penultimate sentence to even bring up? And you're not going to expand on it? How the hell did Lindsay Tanner get the frontline with this thing? I'm almost more impressed with the public commentary... <shudders>

In effect, I think this article trammels the purpose of science writing, which is to translate primary literature into layman language. It is NOT to transliterate scientific discovery into utterances of empty and useless dribble. What is the purpose of this article? It can't possibly have had any other intent than to create hysteria, and that is the worst possible use of the media in general. First rule of translating: do not imply or directly suggest things that are completely irrelevant; please use intelligence.

I now firmly believe that if this Remicade business does not send me into remission and I am rejected from graduate school based on medical biases - yes, that is a legitimate possibility - I will have to go into science writing and do my utmost to revolutionize its currently upsetting condition.

on the roles of science

I've been thinking about how the role of scientific endeavor has morphed since the Scientific Revolution. What it's value has been, and what it has become.

One of our current controversial quests is to take advantage of what opportunity stem cells hold. Is the aspect of reality at stake here as great as that of Copernicus' heliocentric system or Giordano Bruno's infinite universe? Sciences battle with the church exists in the stem cell revolution, but is it as prevalent and restrictive as was the Roman Inquisition? The obvious answer is that no, it is not. Science has an easier time evolving in modern society because our paradigm since the Scientific Revolution has been to encourage the pursuit of knowledge. Since the breakdown and reconfiguration of the Church, theory has become a more friendly phenomenon. Theory then evolves into science much more naturally and with less turbulence. Scientific discovery glides into public gaze with less suspicion.

There are more scientists and, as such, more reason for the public to accept that what the scientific community promulgates. This is something that Thomas Kuhn does not talk about, and I wish he would have. He considers the role of individuals within the scientific community who are more bold than others, and who stimulate acts of revolutionary science. The roles of the other community members, however, are somehow uninteresting to Kuhns concepts.

The role of the scientific community, I think, is to speed up the process of insight. The scientific body gravitates toward one emerging framework or its opponent with the same outcome as the battle of superseding geniuses against the Roman Inquisition. Internal discordance now slows the progress of science instead of the fear of a shift in reality or religious allegiance. It's no less turbid than pre-Revolution, but certainly more urbane... there is no sabotage or torture in modern Science. I actually think that by handing the beast to itself, the Church has simply backed away from the recidivism of the tyrannical father and become the comforting grandmother to those who can't handle theoretical threats posed to reality.

So has it become easier for science to thrive since the Revolution? Yes. Has new knowledge become globally welcome instead of globally feared? To those territories who experienced a Scientific Revolution, yes. Has the quelling of that global fear opened new doors for the free emergence of scientific revolution? Perhaps.

Does revolutionary scientific discovery hold the same earth-shattering importance that it once did? Not really.

Does an individual scientist suggest as much importance to the growth and sustenance of the world as they did during the Renaissance? Well...

I like to hope that we do. But I will need more convincing as my career proceeds.

on the emergence and immersion of geniuses

R. Buckminster Fuller is an American architect who is known for patenting the geodesic dome design, and for the discovery of the carbon allotrope which is his namesake. He is - probably more accurately - known for the saying; "everyone is born a genius. Society de-geniuses them."

I think that Fuller's own history is a perfect example of his claim. I also agree strongly with this particular statement. For instance, the C60 allotrope known as the Buckyball or Buckminsterfullerene was actually discovered by Robert Kurl, Sir Harold Koto and Richard Smalley in 1985 . Their 1996 Nobel Prize gives these men their due credit, but in the limpid word of chemistry, the R. Buckminster Fuller is wrongly assumed to be a chemist, and the discoverer of Buckminsterfullerene. The point I aim to make here is that Fuller was incontestably a genius, but he is not known as such for the correct reasons.

Socioeconomic evolution has imbued the term "genius" with melange of defining characteristics with which I don't agree. Before I get in too deep with this assertion, I should clarify that I define genius as one whose unique curiosities become manifest. That's it. Psychometrics has tried admirably to find a way to assess intelligence on a relative scale, allowing the siting of geniuses and savants as they arise. In as much as these tests do have some value to designing our current educational system (with which I also have major discordance), they also serve as a societal breech to the acceptance of the creativity from which genius comes.

I am inclined toward the idea that genius emerges from reaching outside of paradigms, and happens independently of academic guidance. Fuller's genius is identifiable in his childhood endeavors into original architecture, tool design and novel propulsion methods; he was twice expelled from Harvard. Nikola Tesla invented the first paddle-less water wheel at the age of 4; he spent 1 term at the Charles-Ferdinand University in Prague. Francisco Goya; the last of the Old Masters and the first of the Modern. Mozart and Galileo... all geniuses oppressed or quelled by economic demand, marketing and immersion into societal constructs.

I supposed this is my way of letting out some steam from the pneumatic build up of my anxiety and ambivalent contention for graduate school.

I prefer to hope that I have something unique to offer the world of intellect and scientific discovery. While I was never a prodigal child, and have most definitely been the product of academia-induced ADD-promulgated study, there is still a chance that some modicum of genius might arise in the later stages of my own evolution.

In short, it is my profound hope that I am playing out Fuller's apothegm in reverse - that I have first been de-geniused by society, and am now in the midst of my journey toward emergence.

chris kelly + the constitution

On August 4th, the day before President Obama's birthday, Chris Kelly, a writer for the Bill Maher show, wrote a piece on the authenticity of our president as determined by our Constitution, and on the practicality of our Constitution. (that was a commariffic sentence!)

http://www.huffingtonpost.com/chris-kelly/the-constitution-says-oba_b_249730.html

I love the Huffington Post, and I love its impressive array of contributors.

When interpretation is called into question, I almost immediately become bored, feeling that the inherent flaws in relying on interpretation as truth is fragmenting and destructive in itself. There is no direct or obvious interpretation of anything, and so the subject of flawed interpretation is spoiled and dull.

However. I was inspired to propose a response to Kelly's article (to be interpreted as one would perceive Kelly's article). I think that the United States Constitution should be rewritten on a quarterly basis. And by quarterly, I of course mean every 25 years. Additionally, if nobody wants obfuscated avenues of potential conclusion, shouldn't the Constitution be written as a series of premises? "This, That, Therefore such and such at such and such a time, place and intensity." Eh?

I say 25 years because really, how much social evolution can take place in less than that time? The emergence of each new generation seems like the appropriate time to reevaluate norms. The kind of growth that requires a reformation of the nature of the rules is really of a greater ilk than what happens on an annual scale. For instance, the results of great legal cases (which are the brunt of what determine amendments to our current Constitution) should be considered every 25 years, and a consensus should be taken as to which should be implemented in the the Constitution and contribute to the growth of National Law.

How much easier this would be. The clarity - the insane acceptibility. The absence of religious tongue-tying and the degree of misrepresentation and misconstrued allusion! I think the Constitution should be written for toddlers. Clearly, this is the only way the United States will be able to agree with itself as to "what the fathers wanted". Come, now... WE are now the fathers. We beget the carriers of the next stage of humanity's evolution. We are building for posterity. Let us build on foundations that will uphold our direction and progress, not the rickety and wizened inspirations that allowed our nation to become what we have.

This being said, there is a reason I never went into politics. Call me an elitist - I prefer for the decisions to be made my people who actually understand what is going on, what is implied and what is realistic. The populous should be responsible for finding someone trustworthy, and for communicating concerns at a State level. Beyond that, please oh please let the politicians decide whether Obama is trying to kill our grandmothers or not. I hate town halls. If you're going to lobby (and don't be mistaken - I certainly have done my share), please do so in a polite and intelligent fashion. Picketing is for children and hippies.

penrose + consciousness

Sir Roger Penrose is one of my favorite fellows. He's a mathematician who uses his intelligence to design obscure puzzle patterns simultaneously denying the emergence of consciousness from a pattern for god's sake - what more could you want in a man?

He uses an entire book - Shadows of the Mind (the "sequel" to The Emperor's New Mind) - to discuss how consciousness can't arise from a consistent mathematical system. He begins, essentially, with E=mc2: a number of superposed quantum states in the brain "work" until there is a gravitational difference between their energy and mass. The gravitational significance of this difference causes the states to collapse - or unfold - into one. This single conglomerate state then becomes one observable in the gross physical world - as an action potential in a neuron, perhaps.

At this point, Penrose would seem to agree with David Bohm's implicate order: actuality is the result of probabilistic collapses/unfolding of quantum and subquantum states. We observe light similarly. When medium of a laser absorbs particular wavelenths of light, the electrons of its atoms elevate to their highest state of energy. When so many electrons are excited to this high energy state (population inversion), they collapse together to a lower energy level which results in the emission of light, an observable condition created from a quantum conglomeration.

I have always been somewhat fearful of humanity's discovering the substrate of consciousness and applying it to artificial intelligence. It is comforting that Penrose agrees with me (!) that we will not be able to design A.I. with consciousness in the foreseeable future because it's something we are not nearly close enough to understaning, not to mention being able to coalesce and manipulate.

It is possible to suggest, then, that the connect between consciousness and brain is a physiological exploitation of the vast magnitude of activity in collapsed quantum states. This "non-algorithmic ingredient", as Penrose coins it, also jives with Bohm's suggestions of probability's role in the playing-out of the quantum universe in the gross or actual universe. Could we give our fatty brains such credit as to be the medium by which quantum states become consciousness? This is a question Penrose explores in The Emperor's New Mind, and which I will not dare attempt to disect.

Not at the moment, anyway.

More to come, then.

piaget + bohm

When we are infantile, we perceive the world in terms of transformations and continuity. When someone's head disappears behind the playpen wall, it no longer exists. And when someone's arms extend from behind a tree trunk, they are part of that tree trunk. And when that tree appears fairy-sized beside our hand, it is not because the tree is far away, but because you have discovered its untouchable miniature right in our presence. A thing happens to us between this time and adulthood that morphs that cononical perception into an interspersed mass of objects and interactions. Language.

Particularly Indo-European languages (English, French, German, etc.) are primarily based on nouns. We think, communicate and perceive based on what language has done to our interaction with the world. We fragment its natural cohesion just by the way we behold it.

Language was once verb-based... transformation-based. Native American languages, Bengali and other endangered linguistics. These were also peoples who interacted with reality as if it were all actualized in the same condition, and from the same piece of cloth and ultimately still cohesive.

inexhaustible matter

descartes. the man. cogito ergo sum, etc... the dualist.

the nature of matter, he thought, is to expand itself to occupy space and thus be susceptible to physical examination. the nature of the mind is to think. the defining characteristics of these actualities being so isolated, he surmised, they must function entirely individually. and hence consecrated was the mind-body problem.

and if matter and mind are monistic content of the larger whole?

if matter is infinite such that on many levels it is strongly influenced by consciousness, does it not follow that matter and mind may be more highly interactive than our intellectual paradigm allows?

alright. so i blogged eons ago about what it might mean if microtubules were the carriers of consciousness, and communicated by replicative and epigenetic phenomena with DNA. this remains a feasible possibility to me, but i no longer have reason to believe that microtubules and DNA would be the only instance of this mind-matter causality.

if we one day exhume that matter is inexhaustible, then it becomes plausible that mind intervenes its manifestation and directs it. which is not to say that a cup of jello might appear in the hand of a mind that desires it, or that any massive physicality would arise instantaneously. rather, i think it stands to reason that such a relationship would suggest dialectical movement's role in evolution. of everything.

of electromagnetic fields, of life, of geological shifts, of societal constructions and destructions.

societal thought invades a level of materialism that begets a communal EM field which allows the society to move harmoniously while maintaining the presence of its individuals. like plasma.

universal thought invades a level of materialism that commands a shift in organelle function in a species that causes its evolution and simultaneously the subtle evolution of everything with which it interacts.

humanity builds itself on the "shoulders of giants", or rather, their mistakes. have we not always done so at the command of collective consciousness? do inventors not materialize thoughts in response to communal misgivings? do physicists not seek to explain the existence of the world based on the way that our societies now function (or flounder, rather)? and the problems we seek to eliminate in finding the rational answer to the biggest question of them all? if we one day understand the rational of matter, will we not also comprehend our own existence and, in so doing, realize the key to our own harmonious existence?

here is my confound. i do not believe in god, and i do not believe that the universe exists at the will of humanity or its delusioned elitism. without human directive, what is universal thought explained by if not god? where does it come from? the collective minds of every eletron in existence? the Higgs boson?

the only way i can fix this dissonance is by imagining that mind and consciousness it itself something infinite that we as of yet have no means to address. and by that i am comforted enough to sleep at night. killer.

plasma + marxism

A cyclotron accelerator strips atoms of their outer electrons, leaving them with a positive charge. The resulting melange of free electrons and positively charges atoms is called plasma.

Plasma functions in a collective way, oscillating as a whole, yet its components move freely and individually. When two electrons are completely isolated, they maintain an interaction over a long distance. But in a plasma, this long-range interaction is shielded by the presence of an astronomical number of additional particles. Because this demands that all particle interactions become short range, electrons move freely within the collective, with individual movements.

The long-range interaction, however, has not completely vanished. Rather, its shadowed impetus is what allows the plasma to behave coherently.

--

If a society could behave like a plasma, an ideal balance between serving oneself and one's community would emerge. Capitalism brags that it achieves this balance of perfect individual freedom experienced while serving the common good. Pragmatically speaking, however, capitalism exists only in the hope that service to the common good might somehow be fomented from claustrophobic nests of self-committed individuals.

Limitation is a creation of the mind.

Explain the meaning of the statement above. Describe a specific situation in which limitation may, in fact, be quite realistic. Discuss what you think determines when limitation is real and when it is an illusion created by ones psyche.

There is a sturdy platform bridged between the concept of motivation and the achievements it fosters. In the spirit of optimism, there is a school of thought where the only obstacles between oneself and said achievements are the illusions self-created out of doubt and fear. Painting achievement in this light, it is certain that once confidence reigns anything is possible. Unfortunately, there are circumstances in which limitation is quite real, and emerges in a physical form independent of human confidence.

We will examine the case of a young prospective medical student determined to embark on the ravaging adventure of an MSTP dual degree. Wide eyed, and naive of the particular tolls this endeavor will take on her body and mind, she allows herself to be swept into a realm of fantasy in which all the agonizing training is over. She is the proud and excited principle investigator of a neurodegenerative diseases laboratory where multiple studies are undertaken based on the peculiarities she sees in her diagnostically impossible patients. It was all very well worth it, she thinks - now being in her mid-thirties and about to spring a small family into operation, Boxer puppy and all. The limitations were nowhere to be seen; simple incorrigible self-motivation drove her through eight years of MSTP and three more of residency with but a few bouts of fatigue and scratches to her otherwise-intact ego. She got through it all believing that her only limitations were those she imposed on herself through doubt, self-degradation and fear of incompetence. All of these were easily over-ridden by stepping aside to remind herself of her dreams and her ability to see their fruition. ...right?

Well, sadly there are several real limitations to ones ability to succeed in such endeavors. It is not always the case that young prospectives like our optimistic case study can nullify the limitations of their minds with pep-talks and meditation. There are cases where limitation is not illusion, but reality. Our young prospective MSTP student neglected to inform you that she suffers from Crohn's disease and IBS, two conditions which render her indisposed for up to two days at a time at unpredictable frequency. She did not mention that the numbers by which she was to be assessed in qualification for the MSTP dual degree were unformidable, and by no means set her application aglow. She refused to admit to herself that her intelligence was an obstacle, and she refused to resign to her health as a legitimate hole in her stairway to paradise. These, however, were real limitations. It was, in fact, their neglect that was the self-imposed illusion. And so, the young prospective MSTP student was forced to re-enter the present time and condition in order to assess on a more grounded level whether her limitations were real or surmountable.

She remains in limbo, ruminating over and over the possible outcomes of strength of spirit versus strength of body and intellect. It is here where limitation becomes real and must be faced with the understanding that a different stairway may need to be built in order to ascend to that golden future amongst glowing MD-PhDs and their radiating achievements.

Writing Sample #1
00:28:32

something has to skew nature to choose the ones that work

the argument from Intelligent Design is that the perfection that is life on Earth cannot have possibly arisen from undirected material causes. there has to be an information source. okay, so there's an information source. DNA is an information source. the modern theory of particle physics is an information source. what's the problem?

why is this information source obviously the intelligence of an omniscient version of what has become the human mind? of course there is a directive force behind the interaction of particles that fosters their becoming something more complex which can harness its own energy fields -- even chaos behaves in an orderly fashion -- but it is silly to default to the idea that that force must be a god-like (human-like) intelligence that wished to put a bunch of tiny blocks together and make the organic lego organism that is the Cosmos. this is the problem with calling it "Intelligent Design"; of course it's intelligent design, but there is a surfeit of different kinds of intelligence.

biological intelligence, for one, refers to the ability of organic matter to recognize and interact with other matter: an amoeba, for instance, learning by trial and error to escape the terminal of a capillary tube.

chemical intelligence; the particular bonding interactions of atomic and molecular electron orbitals that result in spike or mechanistic function.

quantum intelligence; the collective formation of fields which become either rays of concentrated energy or building blocks of matter.

lower-animal intelligence; communication by means that humans are barely beginning to understand, and for reasons about which we have know way to assert an concrete understanding.

human intelligence is an evolved speculative tool like any other tool which arose from any other type of intelligence. there is absolutely no reason to think that Darwinian evolution is made null by the possibility of a god-like directive in the form of a human-like intellect. come on. of course Darwin's was a harrowingly rudimentary explanation - it was the first to make the suggestions that it did, what do you want from a less-than-omniscient creator?

Newtonianism was replaced by Relativity was replaced by Quantum Mechanics to explain increasing levels of what we are now accepting might be indefinite complexity innate to existence. God was pseudo-replaced by Linneaus/Lamarck were pseudo-replaced by Darwinism is being replaced by so many other theories of complex evolution. the ID controversy is no different than any other; it's not entirely devoid of merit, but like any other theory, if interpreted and marketed by extremists it loses what logic there is to the basic idea... which is that "nature" (defined as the gross systems perception of life) behaves more like an pallet, and something has to skew it to choose which particles or atoms or bacterial colonies or animals to drive into interaction.

i would be more swayed were it called Intelligent Particle Design... or Intelligent Boson Design... or fuck "intelligence" which is the component that is giving the argument its extremist ammunition and call it Boson Design. or Field Intelligence...

even in chaos, collision begets evolution.

of course... i'm still invested in the omnipotent command of DNA and microtubules, anyway.