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Monday, December 20, 2010

A Theory of Mind III: Emotions

Introduction
In laying out the essential ingredients for a theory of mind, I previously elaborated on the crucial roles of language and memory with illustrative examples. A befitting saying proclaims that a stool needs three legs to stand. Emotions represent another important ingredient of our mind. They seem to narrow our choices by focusing or diverting our attention, thus limiting our choices and profoundly affecting our behavior. They strengthen our memory of particularly intense moments. Plenty important decisions in our lives are being made because of the emotions we attach to a loved one. Therefore, emotions constitute a worthy third leg for the theory I strive to construct. Multifarious types of emotions have been recognized. We may distinguish the simple emotions of “affect programs”, like fear and aversion, from the complex, more “cognitively penetrable” ones (see de Sousa, 2003 for review).

Complex Emotions
Complex emotions have been recognized since the middle of the 19th century, when the tragic fate of the railroad construction worker Phineas P. Gage in New England brought the fundamental role of emotions in defining our personality and their roots in the brain to public attention.

Phineas Gage and his tamping iron
(from the collection of Jack and Beverly Wilgus)
Phineas miraculously survived a grave accident at age 25 which destroyed primarily his left frontal lobe. On Sep. 13, 1848, he was tamping blasting powder down into a borehole with a solid iron rod that weighed 13.25 lbs and was 1.25 inches in diameter and 3 feet and 7 inches long. A spark triggered an explosion and the rod shot straight up like a missile, tapered end first, entirely penetrating Phineas' skull. The iron was found later 80 feet away from the site of the accident. Astoundingly, Gage reportedly did not lose consciousness. He was brought home where Dr. John Martyn Harlow found him sitting up and talking. Harlow was an observant physician who diligently recorded Gage's condition and the progress of his recovery. Phineas, by then a cause célèbre, was a changed man. Before the accident, he used to conduct himself in an even-keeled, considerate manner fit to work as a foreman for the railroad. After the accident, his behavior had become more irritable and irate, and he struggled with a lack of focus. Yet, he managed to hold down a job as a stage coach driver in Chile for several years and lived for another twelve. At the age of 37, he developed severe seizures and passed away within a few months.

Informed of Phineas' death, Harlow sought out the family and was able to procure the tamping iron. He gained permission for a brief exhumation of Phineas' remains during which he retrieved the skull. Harlow published his observations on Gage in a scientific journal (Harlow, 1848) as one of the first documented neurological case histories that related anatomical with behavioral findings. Skull and iron are in the possession of the Warren Anatomical Museum at Harvard Medical School today, and several attempts have been made to reconstruct the damage to Phineas' brain. Certainly, his left frontal lobe, but likely also a part of the right frontal lobe, were severely compromised by the rod's impact.

Phineas' terrible accident kindled intense scientific interest in the role that the frontal lobes play in our emotions and specific frontal lobe areas have been associated with distinct aspects of emotional behavior. For example, the anterior cingulate cortex near the juncture of the cortical hemispheres and the frontal orbital cortex, that is the very nose-ward aspect of the cerebral cortex, seem engaged in focus, decision making and judgment, notably of pain and danger, and are considered part of our attention and risk assessment mechanisms. In addition, anterior cingulate cortex influences autonomic functions like blood pressure and heart rate.

The anterior cingulate cortex sends output to insular cortex wedged between the frontal and the temporal lobe under the operculum, and frontal orbital cortex receives input from this region. Insular cortex receives sensory as well as visceral input, integrating information from inside and outside our body. Von Economo first discovered spindle cells there. Spindle cells are a particular morphological type of nerve cell peculiar to a select number of cortical areas of high-level functional specialization among which we also find anterior cingulate cortex. I have written about these cells in my post with the title "Constantin von Economo's Spindle Cells & The Mind" dated Aug. 21, 2009. Moreover, a special functional type of nerve cells, known as mirror neurons, have been found in anterior cingulate cortex (Rizzolatti and Sinigaglia, 2008). They have been implicated in empathy. I have written about them in my post with the title "fMRI III: Religiosity & Brain Activation" published Mar. 31, 2009. Anterior cingulate, frontal orbital and insular cortex are considered extended parts of the limbic system.

Simple Emotions
Simple emotions are processed by members of the limbic system that are phylogenetically older brain structures than the cortical regions discussed above. We widely share them with less developed vertebrates (Ebner, 1969), inspiring Paul McLean's hypothesis of the triune brain (McLean, 1990). Structures laying down long-term episodic memory have been included here. They comprise the hippocampus, composed of dentate gyrus, fornix, fimbria, and subiculum, as well as the parahippocampal gyrus, divided into perirhinal and the entorhinal cortex.  Particularly, the amygdalae, almond-shaped structures composed of histologically and functionally distinct, interconnected subregions at the bottom of the medial temporal lobe of cerebral cortex, are instrumental in startle and fear. They are strongly influenced by the neurotransmitter dopamine (Reynolds, 1983) and known to play an instrumental role in the influence of emotional arousal on the strength of the memory for our experiences (LeDoux, 1998).

The amygdalae provide output to the reticular formation, instrumental to alert and arousal, the striatum, involved in motor control, as well as structures in the brainstem, mesencephalon and diencephalon that control visceral, gustatory, nociceptive, motor and humoral functions. Moreover, they project to hippocampus, entorhinal cortex, prefrontal cortex, sensory cortical areas of all modalities and multimodal sensory association cortex. While the outputs can be either inhibitory or excitatory, inputs to the amygdalae are predominantly excitatory, utilizing the neurotransmitter glutamate. Fear conditioning in rats has been shown to increase their synaptic strength through a plastic mechanism known as long-term potentiation (Paré and others, 2003).

The inputs to the amygdala originate in most cortical and subcortical areas the structures project to, plus the olfactory bulbs (McDonald, 1998). Moreover, in opossums (Kudo and others, 1986), rats (Ottersen and Ben-Ari, 1979; Doron and Ledoux, 2000) and cats (Ottersen and Ben-Ari Y, 1979), the amygdalae also receive multimodal sensory direct input from the diencephalon, notably the visual (lateral posterior nucleus equivalent to the pulvinar in us) and auditory thalamus (medial geniculate body). The medial geniculate body is a relay station of the ascending auditory pathway. The direct connection with the amygdalae facilitates rapid responses to unexpected menacing stimuli. Alas, the input from the auditory thalamus does not appear to exist in us (Munoz-Lopez and others, 2010), and the one from the pulvinar seems to exert less impact on the amygdalae than in rodents (Pessoa and Adolphs, 2010). This paucity may manifest itself in a less abrupt startle reflex, because cortical processing is involved. Regardless, we immediately seem to duck when we hear a loud bang. When others take cover or flight, we do not hesitate either, as the video of this horrific incident shows. We only need to watch the beginning of the clip. Amygdala in action is visible at 10 seconds:


A story on National Public Radio's Talk of the Nation Science Friday with the title "No Fear" broadcast Dec. 18, 2010, informs us about patient S.M. whose amygdalae have been damaged on both sides (Feinstein and others, 2010). She literally knows no fear. The insights she provides may invaluably help advance treatments for people with anxiety and post-traumatic stress disorder.

Conclusion
Perhaps the founder of human ethology Irenäus Eibl-Eibesfeldt most strikingly revealed the prevalent and universal role of emotions in our lives. He developed camera lenses with a mirror that permitted him to record the facial expressions of unsuspecting bystanders unnoticed. By filming people around the world through these right-angle lenses, he and his colleagues were able to identify archetypal face expressions commonly used to communicate emotions across diverse cultures (Eibl-Eibesfeldt, 1989). The raising of the eye brows to signal readiness for social interaction constitutes one impressive example. Pictures of this behavior are shown on the home page of the Film Archive of Human Ethology. It is a wonderfully emotional scene.

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Saturday, November 20, 2010

Epilepsy, Ketogenic Diet & The Mind

In this informative essay entitled "Epilepsy's Big, Fat Miracle" published online in The New York Times Nov. 17, 2010, Fred Vogelstein tells us how a ketogenic diet helped drastically diminish petit-mal seizures in his eight-year old son Sam who suffers from epilepsy. Medication is still needed. But Sam had suffered up to 130 seizures a day, producing short, at times frightening, pauses of consciousness. Since he has been on the diet, their frequency dropped by 75 percent. Experience with patients like Sam tells that he may not need it anymore at some point in the future. Why the diet provides this effect has remained little understand.

A ketogenic diet consists almost entirely of fatty foods and very low sugar. When we deprive our body of sugar for an extended period of time, we begin to metabolize fat. The liver converts fat into ketone bodies that all cells can use instead of glucose to produce the energy they need to function. Nerve cells in the brain do not only utilize the ketone bodies as sources of energy, but also may produce the neurotransmitter glutamate, as a derivative of the intermediate  α-ketoglutarate in the same metabolic energy pathway in the mitochondria that consumes the ketone bodies as well as glucose derivative pyruvate, known as Krebs cycle.

Krebs Cycle (courtesy: Narayanese, WikiUserPedia, YassineMrabet, TotoBaggins)
Glutamate constitutes the most prevalent excitatory neurotransmitter in the brain. Neurotransmitters pass information across the contacts between nerve cells known as synapses.  Glutamate receptors, notably the N-methyl D-aspartate receptor, play a crucial role in the shaping of nerve cell connections. The kainate receptor is known to be excitatory when located postsynaptically and modulate inhibition when located presynaptically. Kainic acid triggers epileptic seizures. During a seizure nerve cells release glutamate in unusually large amounts causing waves of excitation that the nerve cells otherwise do not experience. Under normal conditions, nerve cells manage to adapt their responses to increasing stimulation, keeping the released amounts of glutamate low (read my post with title "Good News for Brain Energy Use" dated Sep. 12, 2009).

However, when we are on a ketogenic diet, the glutamate that can be derived from ketone bodies is at best half of that derived from glucose. The diminished availability of glutamate may make the difference (but also see Morris, 2005).

Addendum
  • A wise biochemist made me aware of the possibility that ketogenic diets may take advantage of yet another metabolic mechanism. By far not all α-ketoglutarate in the Krebs cycle is converted into glutamate. Rather, the larger fraction is turned into succinate in a reaction that also produces guanosine triphosphate (GTP) from guanosine diphosphate (GDP). Neurotransmitter receptors can be divided into two fundamentally two different types: ionotropic and metabotropic. The first type of receptor is coupled to channel proteins in the nerve cell membrane that control ion fluxes instrumental for the generation and propagation of the electrical impulses encoding the information processed in the brain. The afore-mentioned NMDA and kainate receptors are ionotropic. The second type of receptor is coupled to G-proteins that effect molecular signals regulating ionotropic receptor function, gene expression and energy metabolism.  Eight metabotropic glutamate receptors have been identified. The activation of G-proteins depends on GTP. In addition to curtailing the availability of glutamate per se, a ketogenic diet may therefore diminish glutamate's action indirectly, diminishing metabotropic glutamate receptor activity (12/07/10).
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Sunday, October 17, 2010

Sensory Renewal: Goldfish Eyes & Hair Cells

The U.S. Census Bureau reports in its results from the 2006 American Community Survey that 7 million Americans older than five years possess a severe sensory disability. According to the National Eye Institute, 1.75 million Americans are losing vision, owing to age-related macular degeneration. In the year 2020, their ranks will swell to roughly 3 million. Gallaudet University suggests in informative, well-documented data analyses that about 1 million Americans are functionally deaf. Recent breakthroughs in regenerative medicine have decisively progressed toward promising treatments.

Carassius auratus (courtesy G. Blakemore)
I once was involved in research on plasticity of the goldfish retina (a micrograph of a beautifully stained cross section through a chicken retina similar to fish is shown here). Carassius auratus grows in size throughout its lifetime. Many of us may have encountered well-fed goldfish as long as a lower arm. With eyes growing continuously, the retina must keep up. It does not merely stretch. Rather, dividing pluripotent precursor stem cells are retained in a marginal zone, from which the needed retinal cells differentiate.

Retinal ganglion cells constitute the nerve cells that convey visual information from the retina to the optic tectum in the midbrain where their endings terminate in a topographic map of the retina. Because of this retinotopy, an image of the surrounding world cast on the retina retains its spatial relations when it is represented by nerve cell activity in the tectum. As the retina grows, retinotectal nerve fibers are added and new tectal terminations are formed, while old ones continue to process visual information. In our mature visual system nothing like this happens. Once our brain matured, the retinal nerve cells and their connections with the brain remain by and large unchanged.

In addition, the goldfish visual system is capable of an achievement even greater than the continuous addition of functionality. Maier and Wolburg (1979) discovered that goldfish retinae deprived of almost all cells by metabolic poisoning were able to reconstitute themselves from scratch within a few months. As we know now, surviving Müller glia cells and photoreceptor cells convert into multipotent stem cells that serve as dividing progenitors from whose offspring retinal cells differentiate  (Bernardos and others, 2007). The new ganglion cells innervate the optic rectum in roughly topographic fashion. My project was to examine with a functional imaging method whether the newly formed connections with the tectum were functional. Indeed, my colleagues and I found compelling evidence that the novel retinotectal inputs could be activated by visual stimulation.

Destruction & Renewal (Melzer & Powers, 2001)
The figure above shows pseudo-colored nerve cell activation (blue - low; red - high) in slices cut transversely through the fish brain at the level of the optic tectum, that is the outer rim transected by black lines on both sides (the bar in the lower left pertains to 0.5 mm; the fish's top is up; the fish's right side is on the left). The right eye had been injected with ouabain, a metabolic toxin that kills retinal nerve cells. The retinotectal pathway is crossed. Stimulation with black and white stripes of all orientations resulted in strong activation of the optic tectum on the side receiving input from the intact left eye (red band in the tectum on the left). One week after the ouabain injection (1w p.o.), the nerve cell response on the side that used to receive input from the poisoned eye was distinctly reduced (yellow band on the right). Fourteen weeks after ouabain injection (14w p.o.), tectal activation had recovered noticeably, owing to the reconstitution of the poisoned retina and the regrowth of retinotectal connections (Melzer and Powers, 2001).

Alas, the terminally differentiated cells in our mature retina do not possess the goldfish's power of spontaneous regeneration. However, much progress has been made since I conducted my research, unraveling the molecular mechanisms and identifying the genes that reconvert differentiated cells into multipotent stem cells or conditioned pluripotent embryonic stem cells to become progenitors. Recently, Advanced Cell Technology developed the first gene therapy for people with Stargard's macular dystrophy that will soon be tested in clinical trials, aiming to replace dysfunctional pigment epithelium cells in the retina with healthy ones generated from human stem cells.

By contrast, the effort to restore hearing in deaf people has not advanced to clinical trials yet, though stem cells have also shown promise. Oshima and others (2010) successfully directed induced pluripotent stem cells and embryonic stem cells from mice to change into skin cells. The skin cells were subsequently converted into progenitor cells. The researchers were then able to promote these progenitors' offspring to differentiate into hair cell-like cells with stereocilial bundles that exhibited stimulus transduction currents resembling those of immature sensory hair cells in the organ of Corti of the cochlea, that is the inner ear.
Schematic crossection through the organ of Corti showing the hair cells topped by the basilar membrane surrounded by support cells (courtesy Madhero88).
The organ of Corti is situated roughly in the middle of the cochlea running in its turns from base to apex. Sound vibrations are conveyed from the tympanic membrane via three small bones in the middle ear to the cochlea. The cochlea is filled with liquid. The sound vibrations move the organ of corti's tectorial membrane atop the hair cells, deflecting the cilia. The hair cells transduce the deflections into tiny electrochemical currents and pass them onto nerve cell endings of the auditory nerve the fibers of which convey the resulting electrical impulses to the brain. With decreasing sound frequency, the location on the organ of Corti that is stimulated most strongly shifts from the cochlea's base to its apex, providing the mechanical foundation for our ability to discriminate pitch.  The representation of pitch in discrete regions ordered by frequency is called tonotopy and remains preserved in all information-processing stations of the brain's central auditory pathway (I have written about tonotopy in my previous posts dated Sep. 30, 2009, and Oct. 12, 2009).

Only about 14,000 hair cells populate the human organ of Corti. Because of the inability of our hair cells in the inner ear to repair or replace themselves, drug- or sound volume-induced damage irreversibly leads to the persistent loss of hearing in the range of pitch associated with the location of the damage on the organ of Corti. In offering one possible resolution of this predicament, Oshima and others (2010) recently developed a three-step hair cell generation procedure, manipulating molecular signaling pathways that regulate cell fate and proliferation in tissue culture. In the first step, inhibition of the Wnt/TGF-beta pathways commits the stem cells to ectoderm. In the second step, FGF signaling promotes the ectodermal cells into otic progenitors. In the third step, the progenitors divide and differentiate into immature hair cell-like cells in a culture system with stromal cell-derived activity. The findings constitute a proof of concept, demonstrating that the replacement of hair cells from stem cells is possible. Whether the newly generated cells can be implanted in inner ears and form functional connections with nerve cells remains to be established.

Alternatives to the implantation of stem cells may exist. In vertebrates other than mammals lost hair cells are replaced by regeneration from support cells in the surrounding skin, known as phalangeal cells and Deiters' cells. The support cells convert into dividing pluripotent otic progenitor cells. In analogy, methods that may help de- or transdifferentiate support cells into dividing progenitor cells in vivo are being pursued (Izumikawa and others, 2005; Löwenheim and others, 1999). 

Regardless of the obstacles that still need to be overcome, there is now a good chance that stem cell therapies or regenerative medical procedures derived from this research may be able to help people with sensory disabilities regain function.

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Addenda
  • The picture of the retina mentioned above and other astounding renderings of the brain can found in Carl Schoonover's recent book with the title "Portraits of the Mind: Visualizing the Brain from Antiquity to the 21st Century" (11/07/10).
  • Today the Swedish Royal Academy awarded this year's Nobel Prize in Physiology or Medicine to John B. Gurdon from Great Britain and Shinya Yamanaka from Japan for their successes in converting differentiated cells into pluripotent stem cells (10/08/2012).
  • Almost a decade ago, Izumikawa and others (2005) showed in guinea pigs that the administration of adenoviral vectors containing the gene that encodes ATOH1, a transcription factor crucial for hair differentiation, to non-sensory support cells in the organ of Corti resulted in the regeneration of hair cells and recovery of hearing. Helen Thomson reports in her post with the title “Deaf people get gene tweak to restore natural hearing” published online by the New Scientist Apr. 23, 2014, that the first clinical trials using the principle of this method are going forward at the University of Kansas Medical Center (04/25/2013).
  • Schwartz and others (2012) have been testing ACT’s therapy. NPR’s Rob Stein reported in his Morning Edition segment published Oct. 14, 2014, with the title “Embryonic Stem Cells Restore Vision In Preliminary Human Test” for Morning Edition improvement of eyesight in 10 of 18 patients enrolled in the phase I trial (10/15/2014).

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Sunday, October 3, 2010

Morat-Fribourg, 2010

Today, the historic run from Morat to Fribourg in Switzerland was held for the 77th time (erratum: My count was one off, when I posted first). The run over a distance of slightly more than 16 miles (17.170 km) commemorates a decisive battle the Suisse Confederation won against the Burgundians in 1476. The Suisse retained their independence.

Today's race winners are:

Jane Muia (1:03:33.0), Kenya,

and Fredrick Musyo (52:53.4), Kenya,

closely pursued by Daniel Kiptum, Switzerland (52:53.7).

Congratulations! Free will exists!

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Saturday, September 18, 2010

Music & The Mind

Courtesy jcordj66
Today, forty years ago, the legendary Rock & Blues guitarist Jimi Hendrix passed away at the age of 27. He led the genre to unprecedented heights. Countless tried to follow his path.

I missed him on the Isle of Fehmarn. We did not make it. Our mothers did not let us on the train. Three decades later, I had another chance.  We entered a bar on the 600 block of Bourbon Street one day. I believe it was Mango-Mango. I am not sure. A ragged gentleman with a big smile and a front tooth missing immediately captured our attention. He stood on a small podium, playing a white Fender Stratocaster, strung reverse, left-handed and looked like a seasoned version of Jimi Hendrix. He executed Hendrix's pieces with wonderful accuracy, filling our evening without pause. We had a splendid time.

Alas, the gig constituted nothing more than an excellent imitation. The great master himself remains unsurpassed to the day and sorely missed. Thus, Ladies and Gentlemen, let us turn up the volume and remember him with a rare rendition recorded live straight out of Wolgang's vault:



Where Rock Art Lives

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Prologue to A Theory of Mind

Psychologists commonly use theory of mind, or TOM for short, to designate our ability to empathize with others and put ourselves in their position, realizing that their insights can be different. By contrast in my series of mini-monographs, I use theory of mind to examine the fundamental ingredients of our mind and how they bestow us thought and consciousness.

Some may have preferred to call such endeavor a philosophy of mind. However, I am a neuroanatomist and more accustomed to using the scientific method to dissect the brain and examine its functions. The scientific method requires theories grounded in hypotheses derived from observations. These theory must be experimentally testable. They may be verified or refuted. They must be mutable. That is, they must provide opportunities for adaption and expansion according to new insights. Scientific theories that provide useful answers, sufficiently explaining our environment, evolve and survive.

However, traditional philosophers like Martin Heidegger and Hans-Georg Gadamer would not have approved applying scientific theories to matters of the mind. They believed that the mind can be only comprehended using the humanistic method, in German geisteswissenschaftliche method as opposed to naturwissenschaftliche method, distinctly and deliberately separating mind and body. By contrast, I set out to explore the mind with the help of the neurosciences, identifying mental abilities grounded in known brain structures essential to and prerequisite of a theory of mind.

In his acclaimed treatise "Sein und Zeit", Martin Heidegger reasoned that a sense of time bestows a sense of being. Consciousness cannot exist without memory, that is without remembering our history. We recall events in images and stories. Heidegger suggested that history is impossible without language.

Furthermore, Heidegger notes that language comprises more than everyday-usage to describe our actions and the world around us. He cites Goethe's claim that poetic language plays a particularly crucial role in our mind as a tool of expressing our deepest emotions. 

Guided by Heidegger's thoughts, I have therefore begun my theory of mind portraying the significance of language (part I) and memory (part II). Moreover, because we are a social species that would not survive without cooperation and collaboration, empathy plays a crucial role in our ability of maintaining good relationships and would be impossible without our feelings. Hence, part III will explore some fundamental aspects of emotion:


References
You may wish to listen to Heidegger speaking on language and thought here:




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Friday, September 17, 2010

Cave Art: The Dawn of Spirituality

History is of profound importance to us. Without knowing our history, we would not know who we are. Neolithic people shared history in pictures. The paintings discovered in caves of France and Spain awaken experiences, both imagined and real, of wildlife as the pivotal force that could threaten survival in as much as it provided the eternal source of sustenance and comfort. The encounters could mean life or death, hunting and being hunted.

Niaux
I remember vividly seeing the horses in the cave of Niaux in the French Pyrenees. The Bradshaw Foundation provides a video for a small price. Particularly, a simple, seemingly unfinished outline caught my eye. As if the artist just took a break and was about to continue shortly. The Cro-Magnon (Homo sapiens sapiens) were excellent in reproducing shapes. In fine nuance, the black outlines achieve to emphasize the raw, muscular power of the portrayed animals. Even in their simplest form, the outlines beautifully convey resemblance. The paintings are preserved so well that they project their message today as if they were painted yesterday. In fact, the caves remained unperturbed for so long, that we cannot help to expect but the painters to return any moment. The caves are time capsules that need to be preserved in eternity for us to reconnect with our heritage and re-discover where we came from. The paintings bear witness to the emergence of spirituality at the dawn of modern thought.

The caves are closed to visitors today, because our disturbance of the micro-climate destroys the paintings. However, in some caves, like that at Lascaux (Aujoulat, 2005), they have been elaborately reproduced as replicas accessible to everyone. Photographers have documented most. On Sep. 8, 2010, LIFE released in a special edition with the title "Inside Lascaux: Rare, Unpublished" a series of stunning, hitherto-unpublished photographs taken by Ralph Morse in 1947.

The slide show is definitely worth a visit. Our ability to remember the past in pictures and stories constitutes a fundamental ingredient of our mind.

Addenda
  • Another virtual tour of stunning cave art documents the findings in Chauvet's Cave. The cave was discovered only in 1994 (Clotte J, 2010). Carbon-dating suggests that the paintings are roughly 31,000 years old.
  • As the commenter below kindly points out, Werner Herzog directed and produced a stunning movie on Chauvet's Cave with the title "Cave of Forgotten Dreams" which appeared last year. Herzog spoke with Terry Gross about this movie in their interview with the title "Herzog's Doc Brings Prehistoric Paintings To Life" broadcast on National Public Radio's Fresh Air on Apr. 20 and Dec. 9, 2011 (02/16/2012).
  • Using uranium-series dating, Pike and others (2012) provide evidence that some cave paintings in Spain may be roughly 10,000 years older than previously believed, dating back to at least 40,800 years. The finding opens the possibility that Homo sapiens neanderthalensis painted them before Homo sapiens sapiens arrived in Southern Europe. Regardless of who precisely the painters were, abstract thinking may have been with us longer than previously thought (06/14/2012).
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Monday, September 13, 2010

Mary The Elephant & The Mind

Today we commemorate the grizzly death of Mary the elephant. Mary was a member of Sparks Bro. Circus, paying a visit to East Tennessee in 1916, when she attacked and killed her handler.

Justice was dealt swiftly. Mary was sentenced to death in Erwin, Tennessee.  However, the sentence proved difficult to execute. Gun shots were ineffective. Mary was paraded to the rail yard. In the presence of several thousand spectators, an iron chain was fastened around her neck, and the five-ton animal was hoisted up in the air with a heavy duty steam-powered derrick. The first chain broke. Mary died on the second attempt. This photograph preserves the gruesome moment for history. Joan Vannorsdall Schroeder published a detailed account of the sad story entitled "The Day They Hanged an Elephant in East Tennessee" on BlueRidgeCountry.com.

Some suggest the photograph may be a fake. The depiction of the brutish, senseless act long ago only berates the people who live in this beautiful part of the country, serving no good purpose. Hence, let us take the anniversary of this incident to celebrate that our minds have changed in the century that has almost passed since Mary's horrific death.

Early this year, Tilikum the killer whale precipitated the tragic death of his long-time handler at SeaWorld in Orlando, Florida. We shall never fathom what was on his mind. Tim Zimmermann provides a detailed, graphic account of the incident with a possible explanation in his post with the title "The Killer in the Pool" published online by Outside Magazine in July. Perhaps, elephants and orcas should not be kept in captivity for our entertainment. Whatever our stance, Tilikum may consider himself fortunate that he lives today. According to Donna Leinwand's post for USA TODAY with the title "Orca to be spared in trainer's death" dated Feb. 26, 2010, SeaWorld's operators decided already then that Tilikum will remain at SeaWorld unharmed.


Addendum

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Wednesday, September 1, 2010

The Teutoburg Forest & The Mind

In September one year more than two millennia ago, the Battle of Teutoburg Forest unfolded. I found great sources of information on the incident in Jona Lendering's account posted on livius.org and in this wikipedia entry with the title "Clades Variana". The legend of this confrontation between occupying Romans and occupied Germans gained great notoriety in 19th- and early 20th-century Germany, where it was used as rallying point for the rise of fervent nationalism.

At the time of the battle, in Emperor Augustus' reign, the Romans had been present on the Rhine for two centuries, had founded prosperous cities and towns along the river and had pushed their zone of influence into regions North and East. However, governance was not stable and needed consolidation in order to establish an actual province. In 55 year-old Publius Quinctilius Varus, Rome sent an ambitious governor of first-rate pedigree to the region with the task to achieve this aim. Varus was a seasoned administrator, but had little insight into local politics and was inexperienced as a military leader. His first act of governance was to implement a rigorous tax system according to Roman law, without consulting and seeking a consensus with the local warlords. Some apparently had a lot to lose under the new system.  In addition, the consolidation of Roman power East of the Rhine would bring settlement of retired Roman military personnel to the region, limiting the free reign of the local tribes. Under the pretense of fighting for independence from the Romans and of liberating the tribes from the Roman tax yoke, these warlords sought alliances among the German tribes to conspire against Varus. One tribal chieftain formally allied with the Romans became a major clandestine leader of the insurgency. His name was Arminius, chief of the Cheruscans.

Over the centuries of building their empire, the Romans had developed an intriguing policy of binding subdued ethnic tribes to their culture, which proved profoundly successful in solidifying their hold over conquered lands. In an expansionary military campaign, the leading general of the invading force would commonly ask for young children as hostages from the noble families of the subdued tribes. They were routinely sent to Rome where they were hosted by affluent families, providing them with a good education. They spent several years there, before they were allowed to return home, learning to appreciate the ways of the Romans. They would learn to speak, read and write the language. They would assimilate the ways the Romans thought and, certainly, learned to love Roman amenities like the free public baths and swimming pools with their impressive architecture and beautiful mosaics, the seemingly never ending supply of cool clean drinking water dispensed from magnificent fountains in every neighborhood, as well as the in-house toilets and the sewage system. Not to mention the culinary adventures, Roman cuisine offered. Imagine chilled fruits in the summer! People stored ice from Alpine glaciers underground. Moreover, the city offered unlimited entertainment in parades, festivals, sports events, theater and games. Life in Rome must have seemed on a different planet compared with life back home. Rome delivered memories these 'guests' would not forget.

Arminius, courtesy P. Heather
Arminius had spent his youth growing up as a hostage in Rome. He was trained in horsemanship and received the title of equestrian. He knew the Romans well and had collaborated closely with them after his ascend to power at home. The Romans considered him a trusted ally. We do not precisely know what turned this seemingly loyal ally against Varus. But it is likely that Varus with his brash reforms rankled him enormously, because they cut into his income stream. While continuing to profess friendly relations, he and others decided to set a trap for Varus. They staged an uprising against Roman rule on the low-lying Northern planes of Germany. To quell the rebellion, Varus mobilized three legions, approximately 25,000 soldiers, to march under his command North from their quarters on the lower Rhine. Arminius and a small retinue of his warriors accompanied the army. What happened next has remained much speculation. We do not even know for sure, where the ensuing confrontation precisely took place. The most likely location is a small valley known as Kalkrise near the modern city of Osnabrück.

By the time the Roman legions reached this location, the column of the slowly advancing force had stretched out many miles. The advance guard, main body, and rear guard had become disjointed. The troops filed through a corridor flanked by low forested hills. The weather was bad. Rainfall had softened the ground. Progress slowed even further. Arminius and his men disappeared. The insurgents had laid an ambush, and the trap snapped close. Without prior warning, javelins and spears poured from the forest onto the unprotected flanks of the troops drudging along in the morass on the open ground. The awkwardly moving mass of men and materiel mustered little defense. Encouraged, the enemy closed in and wreaked havoc in the midsection of the column. The advance guard met a camouflaged wall of palisades that the insurgents had erected in the weeks before and from which they savagely attacked the arriving legionaries. The soldiers accomplished to re-group, undertook counter-attacks, waged break-outs and put up valiant resistance for four days. But the enemy forces grew continuously. Their onslaught remained unrelenting. The Roman resistance eventually succombed, and the troops were obliterated. Some, among them the cavalry, fled the battlefield. Others reached a fortified forward base. Most fell in battle. Some committed suicide. The Germans customarily tortured and killed captured enemy. Faced with such destiny, Varus and his officers ended their lives.

As a result of the debacle, subsequent Roman administrations rescinded the ambition to extend permanent rule further East and focused on consolidating their power West of the Rhine. It would be false to interpret this policy change as weakness. The Romans were not afraid of another confrontation with the Germanic tribes. Rather, Varus' successors saw no significant gain in such enterprise. Certainly, Arminius was not allowed to enjoy his victory for long. Eight legions defeated his insurgency seven years later. The Romans kept relentlessly on his heels. His pregnant wife was taken as hostage to Rome, and Arminius met a violent end before he reached the age of 40. The rebels began to quarrel amongst themselves, and he was assassinated on the behest of another warlord.

Hermann's Monument
German romanticism inflated the historical significance of Arminius' military success out of proportion, basking in imagined superiority of Germanic culture. After the Napoleonic wars, a colossal statue of Hermann, as he is known in German, was erected in Teutoburg Forest to celebrate German unity. Though Hermann's feat looms as large in German lore as his statue is tall, in fact, Roman influence left far deeper, indelible marks on German history. Under Roman rule, the region would enjoy 200 years of stability and peace, known as Pax Romana or Pax Augusta, a length of time unrivaled to the day. Latin was used as the official language of public administration and spiritual life for more than 1,000 years. Still today, Roman laws regulate landownership in Germany; properties are marked by cornerstones.

The Romans possessed an extraordinary gift for effective public administration and superb civil engineering. Within three days, Augustus in Rome knew of the demise of his legions in Germany. When he was informed of the disaster, the emperor reportedly was so shocked that he choked on his dinner and exclaimed in exasperation, "Varus, bring back my legions!" The sudden loss of three entire legions was no small incident. The Roman Empire maintained 28 at the time. The distance between the battlefield and Rome covers roughly 700 miles. We have to cross the Alps. How could the Emperor be informed so quickly?

The Romans had built a network of highways and a messenger service, not unlike the Pony Express, that afforded them such rapid communication across their sphere of influence. Being informed in timely fashion has been a recipe for success then and now. Alas, intelligence needs to be adequately assessed. Varus had been warned by an informant in advance of Arminius' betrayal, but chose to ignore the warning. Perhaps, the most relevant lesson we can learn from the Battle of Teutoburg Forest today is that in an insurgency partners by necessity possess limited value.

Addendum
  • Even powerful emperors depended on the support of Rome's eminent families represented in the Senate. The size of the home of this senate may illustrate the efficiency of Roman government in Augustus' reign. The building is located on a small elevation at the edge of the Forum.


    Curia Julia
    Outside was the fabled navel of the Earth. The Romans made the decisions that determined the fate of their empire in a building the size of a barn (09/22/10).

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Thursday, July 22, 2010

Science, Art & Deception of the Mind

In his investigative report with the title "The mark of a masterpiece" published July 12, 2010, in The New Yorker, David Grann informs us about the novel use of methods adopted from forensic science to authenticate works of art. Deception seems intricately interwoven with art. Grann's fascinating story informs us about the scientific method and the power of deceit. It tells us about people who become vulnerable to deception and exploitation on their quest for affirmation of their believe because of pride, ego and money. Establishing the provenance of a masterpiece mainly relies on the subjective expertise to date. However, the desire to discover a new masterpiece by a fabled artist may obfuscate judgment and reason. Definitive objective prove is, therefore, highly sought after.

David Grann portrays the art expert Peter Paul Biro. Biro gained distinction in the world of art for using cutting-edge scientific methods to successfully identify fingerprints of famed masters like Turner, Pollock and Leonardo on hitherto-unknown paintings and drawings. He employs spectral microscopy and computer-supported image analysis to derive his conclusions.

We tend to believe that we are able to establish veracity beyond any doubt with hard data produced by objective machines that do not posses vested interests in the outcome of the examination. However, as David Grann's investigation elegantly reveals, the interpretation of the data may entirely lie in the hands of the investigator. He takes sole responsibility of deciding whether the evidence is sufficient to prove the identity of the fingerprint in question.

Because of our fallibility, more than one expert commonly shoulder such decisions. Peter Paul Biro states that he developed his own imaging equipment, which is one of a kind. No other expert could be asked to verify his findings because they lack the experience with the revolutionary methods he devised. The burden of prove rests with him alone.

This situation puts Biro in a unique position of extraordinary responsibility. The scientific method insists on the reproducibility of findings, preferably by independent examination. Additional verification with different methods may be necessary. Peter Paul Biro is intending to use DNA profiles from hair samples for this purpose. As the only expert in his method, he must know that his career and future depend on his truthfulness. Any scientist's credibility is intimately linked to her/his integrity. Deliberate misrepresentation of evidence is a serious offense, destroying the most highly-respected reputation.


Addenda
  • Anyone versed in fluorescence or confocal microscopy could quickly learn how to image fingerprints. You may not even need a microscope. The detective in the video uses a magnifying glass to examine them. A CCD camera with a macrolense on a solid stand will suffice. A a high-quality light source and fiber optics are needed to produce sufficient illumination of the specimen as well as light filters for the wavelengths at which the images need to be captured. For storage and processing we need a computer with frame grabber and software.  In total, the equipment may not cost more than $100,000.-. The software for the described image treatment, that is background correction and subtraction, contrast enhancement and erosion to lay bare patterns, alignment and overlay of images as well as subsequent differentiation can be achieved with Wayne Rasband's ImageJ. The application is java-based freeware and can be downloaded from Wayne's National Institutes of Health site. The site also provides helpful information on equipment. For statistical analysis, we could quantify the number of picture elements, also known as pixels, in which the compared fingerprints overlap and use pixel-by-pixel paired t-tests to assess statistical significance as measures of identity. According to Grann, Biro charges $1,000.- per day for his qualitative analyses of fingerprints. His judgment must account for most of the cost (07/22/10).
  • Bryony Jones reports in her post with the title "Museum discovers 'new' painting" published online by CNN on Mar. 23, 2012, on an excellent example demonstrating how improved X-ray spectrography helped authenticate a Van Gogh painting previously attributed to an imitator. The painting depicts a still-life of summer flowers exhibited in the Kröller-Müller Museum in Otterlo, the Netherlands. It had been examined with less powerful X-ray methods before, and it was known that there was another composition underneath. Using the new imaging method, experts unambiguously uncovered under the still-life two wrestlers entangled in a match known to have been painted by the famous painter. In addition, the method confirmed that the pigments in the paints were consistent with those used by Van Gogh at the time. Modern technology correctly applied helps (03/24/2012).
  • On rare occasions, identification seems straight-forward. The proud new owner of this Renoir rediscovered comments: “One man's trash is another (wo)man's treasure!” (09/12/2012):
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Tuesday, July 6, 2010

The Human Genome: A False Promise?

Genomic medicine, also known as personalized medicine, has become a universal buzz word, perhaps to attract more dollars to biomedical research. Only two months ago the new Director of the National Institutes of Health and former Director of the National Human Genome Research Institute Francis Collins announced the age of personalized medicine in the national media. In short, the sequencing of a person's genome will become less costly and available to everyone in the near future. Based on our genetic makeup, doctors will be able to treat prospective illnesses before they have a chance to afflict us. This country's biomedical research establishment invested billions of dollars in this idea.

Then, three weeks ago the new Director of the National Cancer Institute, scientific adviser to the president, and former Director of the National Institutes of Health Harold Varmus stated in the news that human genomic research is only useful to science at present. Nicholas Wade's article entitled "A Decade Later, Genetic Map Yields Few New Cures" and Andrew Pollack's article entitled "Awaiting the Genome Payoff" were published in The New York Times on Jun. 12 and 14, 2010, respectively, in the wake of what must seem like an about-face at the highest level of leadership in U.S. biomedical research. In both articles, the short-term prospects of personalized medicine seemed less certain.

Alas, understanding the human genome in health and disease is doubtlessly spawning important progress on numerous fronts in medicine. The discovery of modified genes in cancer cells and the proteins they encode is being used to develop novel chemotherapies. In particular, drugs for targeted therapies are currently being tested that may counteract the averse effects of modifications in genes KRAS and BRAF in a variety of cancers. In yet another advance, we may be able to adapt our diet to our personal genetic makeup with a better promise of controlling our weight, diminishing our risk for cardiovascular disease.

By contrast, uncovering the genetic bases of mental disorders like autism and schizophrenia has proved difficult. The findings to date suggest that such disorders are the result of highly complex interactions of a multitude of molecular signaling pathways involving many genes. Whether genomic research can benefit therapies to treat such mental disorders remains to be seen.

Addenda

  • Recent studies uncovered a mutation of the gene ALK in tumor tissue of people with non-small cell lung cancer. ALK encodes the enzyme anaplastic lymphoma receptor tyrosine kinase. The fusion of this gene with the gene EML4 renders a tyrosine kinase persistently active that prevents programmed cell death from curtailing neoplastic growth.  Aaron Saenz describes a potential drug treatment using this important finding in his post entitled "Crizotinib Targets Gene To Stop Lung Cancer Tumors in 90% of Treated Patients" on Singularity Hub dated Jun. 9, 2010. No doubt, the development of drugs specifically targeting such cellular malfunction is highly desirable. However, less than four percent of lung cancer patients carry the EML4-ALK fusion, and the drugs tested to date only slow the progress of the disease. Personalized medicine definitely needs more research, time and money to come to fruition (08/05/10).
  • Peter J. Boyer wrote an informative essay with the title "The Covenant" about Francis Collins and his goals as the new Director of the National Institutes of Health. The essay was published online Sep. 6, 2010, in The New Yorker (09/10/10).
  • Because targeted therapies are expensive and may produce varying results, we may be confronted with difficult choices. This conversation between Paul Raeburn and Leonard Fleck entitled "Looking at the Ethics of Personalized Medicine" broadcast yesterday on NPR's Science Friday informs us about the dilemma inherent in this issue (09/25/10).
  • Julie Steenhuysen's report with the title "Gene tests inadvertently exposing cases of incest" posted yesterday on Reuters provides a striking example for personalized medicine's potential of uncovering information that raises ethical questions (02/11/11).
  • According to Sharon Begley's article on Reuters with the title "DNA pioneer James Watson takes aim at 'cancer establishments'" published online today, the co-discoverer of the molecular structure of DNA, Nobel-laureate, and eminent proponent for the human genome project J.D. Watson now believes that our greatest hope for fighting cancer is the use of antioxidants. That is, boosting antioxidants may help prevent cancer and blocking their actions in tumor cells may help with a cure. His voice lends credence to those who cautioned against excessive expectations in the promise of personalized genomic cancer medicine (01/09/2013).
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