Water & the Mind

“All day I've faced the barren waste
Without the taste of water.....cool, water.
Ole Dan and I, with throats burned dry ,
and souls that cry
for water....cool, clear water.”

Hank Williams

We need water to live. In the developed world, we take abundant water supply for granted. However, where I live the recent past demonstrated in all harshness that we are cradling ourselves in a false sense of security. Water is in fact in short supply. In contrast to the Southwestern states of the U.S., the Southeastern states look emerald green most of the year when you look down on the beautiful land of rolling mountains from an airplane. You would never believe that there is not enough water for this land!

However, severe drought struck this land two years ago. After several years of insufficient rainfall, hardly any came. The grass turned brown already in June, the hack berry trees dropped their leaves in August. Our willow dropped a ton of whip-like branches and is half dead today. Metropolitan Atlanta was much worse off. A major source of the city's potable water, Lake Lanier, reached historic low levels (Shaila Dewan and Brenda Goodman for The New York Times, Oct. 23, 2007, "New to Being Dry the South Struggles to Adapt"). Severe restrictions for the use of water were imposed.

Legal fights ensued between users in the region. The states of Florida, Alabama and Georgia, sharing the Chattahoochee River basin, began to quarrel about water rights with the U.S. Army Corps of Engineers (Shaila Dewan for The New York Times, Aug. 15, 2009, "River Basin Fight Pits Atlanta Against Neighbors"). The Corps administers the river's flow. Georgia became so desperate that lawmakers briefly resurrected a 19^th century border dispute with its neighbor Tennessee in a vain attempt to gain access to the Tennessee River (Shaila Dewan and Brenda Goodman for The New York Times, Feb. 22, 2008, "Georgia Claims a Sliver of the Tennessee River").

The state of Tennessee was not much better off (Adam Nossiter for The New York Times, Jul. 4, 2007, "Drought Saps the Southeast, and its Farmers"). Water had to be trucked in with fire engines for a number of communities where the wells were running dry. Entire counties declared water emergencies. On top of this calamity, deep cracks were discovered in the bedrock under several large dams the Tennessee Valley Authority had built in the wake of the Great Depression, e.g. Wolf Creek Dam (Ian Urbina and Bob Dreihaus for The New York Times, Mar. 4, 2007, "Fears for a Dam's Safety Put Tourist Area on Edge"). Water had to be released, leaving the intake pipes of a number of lakeside communities on dry ground. Obviously, improved water management was direly needed.

This year, by contrast, we saw record rainfall down here. Georgia and Tennessee experienced catastrophic flash floods (Robbie Brown and Liz Robbins for The New York Times, Sep. 24, 2009, "Georgians Grappling With Flood Damage"). Our house is built on an unfinished basement. In normal years, the dirt is dry for nine months. This year it never dried. The grass in the yard never turned brown. The hackberry trees have only begun to shed their leaves this month.

Unfortunately, this year's abundance of water could not be stored. The water levels behind the damaged dams had to be kept below capacity because of the repair work underway. The repairs are substantial, will cost hundreds of millions of dollars and will take several years to complete. Meanwhile, millions of gallons of precious water are flushed down the spill ways. For the first time, I saw all spill ways wide open at Percy Priest Dam. A truly majestic sight!

Clearly, we cannot afford to waste our most vital resource without paying a price. Tonight at 20 hours EDT, Guy Laliberté, the founder of Cirque du Soleil, will host a multi-media show from the International Space Station. The show entitled "Moving Stars and Earth for Water" will raise awareness to this simple, but important fact.

You may wish to tune in online here tonight:

Ensuring everyone has access to water | ONE DROP Foundation
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Addenda

• Guy is back!

• On the weekend of May 2, 2010, a 500-year flood of the Cumberland River system in Tennessee overwhelmed the U.S. Army Corps of Engineers' ability of containing the rising waters below catastrophic levels. The Corps had to release water, flooding its own facilities downstream, to protect the integrity of its dams. Eleven lives were lost. More than 2000 families suffered flood damage to their homes. Nashville's downtown was underwater to an extent unseen in 80 years. One of the two water treatment plants that supply the city with drinking water was out of order for several weeks. The estimated economic losses in the metropolitan area top two billion dollars. The Tennessean devotes a continuously updated online report entitled "Nashville Flood" on the incident and its impact. The dam and levee system in the region is underfunded and has not seen large-scale upgrades since its inception. Obviously, improved water control is direly needed (08/05/10).
• Southeastern cities manage their drinking water on shoe-string budgets. According to an Associated Press report with the title "New Orleans Issues Boil-Water Order" published online in The Wall Street Journal today, citizens of New Orleans are advised to boil their tap water before consumption this weekend, because mechanical failure forced a water treatment plant to shut down (11/20/10).

Echolocation, Science & Power

The Italian scientist Lazzaro Spallanzani  attained fame beyond his country already in his life time. He studied philosophy at the University of Bologna, became member of the clergy, and taught logic, metaphysics, and Greek at the universities of Reggio, Modena and and eventually assumed the chair in natural history at Pavia. His studies contributed profoundly to the understanding of a broad range of natural phenomena spanning geology, biology and physiology. Late in his career, he became fascinated with bats, wondering how they could navigate so elegantly in full darkness complicated environments wrought with obstacles.

Spallanzani proved himself as an observant experimenter. He attacked his question methodically with a series of tedious behavioral experiments, systemically ruling out one sense after another. He observed bats flying skillfully passed nooks and crannies in a L-shaped basement. Occlusion of the eyes did not appear to degrade the bats' performance, neither did covering the skin with a paste nor occluding the nose. His findings were first published as a collection of letters by Anton-Maria Vasalli (1794). A few years later, the Swiss zoologist Charles Jurine observed that occlusion of the ears rendered bats entirely disoriented. Spallanzani confirmed this observation, but was unable to explain how bats would use hearing for navigation. He had speculated earlier that the animals perhaps possessed a sixth sense unbeknownst to human kind.

Professor Spallanzani's hypothesis was met by strong and powerful resistance in the scientific community. One of the most eminent zoologists of his time, Georges Cuvier, argued against the validity of the experiments (Cuvier, 1795).  Interestingly, Cuvier's arguments were entirely based on conjecture. He did not conduct a single experiment to disprove Spallanzani's results. Instead, he appealed to common knowledge. He reasoned that everybody knows that bats, in as much as blind people, orient themselves with the sense of touch.

History would prove Cuvier wrong on both accounts. Neither bats (Griffin, 2001) nor blind people ( Wall Emerson and Ashmead, 2008) use their sense of touch for navigation in space. However, Cuvier's reputation was domineering. His influence on science was overarching. Roughly for the next century and a half researchers devoted their attention on the bats' sense of touch, until the Americans Donald R. Griffin and Robert Galambos and the Dutchman Sven Dijkgraaf discovered echolocation. That is, they unequivocally demonstrated that bats use the echos of ultrasound they emit to navigate their environment in flight and catch prey (Griffin, 2001). Griffin wrote an informative popular book about his findings entitled "Listening in the Dark: The Acoustic Orientation of Bats and Men". Vigorous research continues to the day to elucidate the nerve cell mechanisms that underlie this fascinating behavior.

I was exposed to some aspects of bat research when I was a student. The processing of ultrasound frequencies used for echolocation constitutes a prominent feature in the auditory pathway of echolocating bats (Neuweiler and others, 1980). My pilot study helped visualize this prominence with a functional imaging method (Melzer P, 1985).

The colors in the picture show ultrasound-related activation in a transverse slice through the brain of an echolocating bat. The ear on the opposite side was exposed to sound pips of this bat's individual echolocation frequency. Two regions in the auditory midbrain known as inferior colliculus (white circle) responded to the ultrasound most prominently.

Spallanzani's observations were influenced by the fact that he used pipistrelle bats (Pipistrellus pipistrellus) for his study. They emit their echolocation calls through the mouth, and his attempts to occlude the mouth noticeably compromised navigation. Had he used the more common horseshoe bat (Rhinolophus ferrumequinum), he would have been surprised to discover that the nose was doing the job.

Addendum

• The co-discoverer of bat echolocation Robert Galambos, PhD, MD, passed away a month ago at the age of 96.  Douglas Martin provides a concise summary of his career in The New York Times today with the title "Robert Galambos, Neuroscientist Who Showed How Bats Navigate, Dies at 96".  He was a profound experimentalist. In an inseminating recent paper (Galambos, 2003), he described four elegant experiments that demonstrate the principles of empirical neuroscience in most illustrative fashion (07/16/10).

References

• Cuvier G (1795) Conjectures sur le sixiéme sens qu'on a cru remarquer dans les chauve-souris. Mag. Encyclopéd 6:297-301.
• Galambos R (2003) Four favorite experiments and why I like them. Int J Psychophysiol 48:133-140.
• Griffin DR (2001) Return to the magic well: Echolocation behavior of bats and responses of insect prey. BioScience 51:555–556.
• Griffin DR (1958) Listening in the dark: The acoustic orientation of Bats and men. Yale Univ Press.
  
• Melzer P (1985) A deoxyglucose study on auditory responses in the bat Rhinolophus rouxi. Brain Res Bull 15:677-681.
• Neuweiler G, Bruns V, Schuller G (1980) Ears adapted for the detection of motion, or how echolocating bats have exploited the capacities of the mammalian auditory system. J Acoust Soc Am 68:741-753.
• Vasalli A-M (1794) Lettere sopra il Sospetto di un Nuovo Senso nei Pipistrelli . . . Con le Risposte dell’Abate. Stamperia Reale (Torino).
• Wall Emerson R, Ashmead D (2008) Visual Experience and the concept of compensatory spatial hearing abilities. In: Blindness and brain plasticity in navigation and object perception (Rieser JJ, Ashmead DH, Ebner FF, Corn AL, eds). Taylor & Francis (New York):pp367-380.
  

Meet Bert the kitchen bat!

Color Blindness, Gene Therapy & Brain Plasticity

Prologue
In my post dated May 28, 2009, I wrote about the squirrel monkey Miss Baker. She was the first primate to successfully complete a space voyage half a century ago. Yesterday, two other squirrel monkeys, Dalton and Sam, accomplished another first. That is, they were the first to successfully undergo gene therapy, repairing color blindness.

Our color vision is provided by photoreceptor cells in the eye's retina known as cones. Three types of cones have been identified. Each type is particularly sensitive to either blue, green, or red light, depending on the molecular structure of their photopigments known as opsins. While two copies of the gene encoding the blue-sensitive opsin are located on a pair of somatic chromosomes, the genes for green and red exist in only one copy on x chromosomes. If they are damaged, we are not able to distinguish between green and red. Particularly males are vulnerable because a spare is unavailable. Thus, color blindness affects 8 percent of white men, but less than 0.5 percent of white women. By contrast, most male new world monkeys, including squirrel monkeys, are color-blind.

The Therapy
Yesterday, Katherine Mancuso and her colleagues published a letter in the journal Nature online in which the authors provide evidence that two adult male squirrel monkeys, Dalton and Sam, gained color vision within about half a year after they had been treated with gene therapy (Mancuso and others, 2009). That is, their eyes had been injected with an engineered virus encoding the missing long wavelength-sensitive opsin or green fluorescent protein (GFP). The recombinant DNA was supposed to be inserted into cone DNA. The GFP served as an independent marker for successful insertion. The hope was that the cones with the engineered DNA would synthesize the missing opsin, eventually enabling the monkeys to see differences between red and green.

Dalton and Sam were experts in visual discrimination tasks. They had been trained in a modified Cambridge Colour Test before the intervention and were experienced participants. The test consisted of colored dot patterns embedded in gray dots similar to tests with numbers or letters laid out in colored dots for people. Dalton and Sam began to distinguish red and green in the sixth month after the virus injection.

The authors monitored retinal function using wide-field color multifocal electroretinography. This type of electrophysiological recording describes stimulus reception, transduction and processing in the retina. Retinal responses to red were undetectable four months after the intervention, but had risen to prominence at ten months and were further enhanced at 18 months. At that time, the monkeys could distinguish between 16 hues of red and green. GFP was expressed in roughly 15–36 percent of the cones. Taken together, the findings of this study constitute a promising prove of concept for the great potential gene therapy may hold for the restoration of retinal function.

Brain Plasticity
The question remains how Dalton and Sam could correctly interpret visual cues they had never seen before. Could the nerve cell connections in the visual system reorganize on a scale required to process the novel sensory input?

Around 1960, the Nobel Prize-laureates Torsten Wiesel and David Hubel had discovered that the cerebral cortex reorganized profoundly in response to sensory deprivation in a limited window of time during brain maturation. Primary visual cortex consists of interdigitated domains in which neurons respond mainly to input from one eye. In their pioneering study, Wiesel and Hubel occluded one eye in newborn kittens and observed that the other eye's cortical domain enlarged into the deprived territory (Wiesel and Hubel, 1963). The effect could be reversed, if the eye occlusion was reversed within a critical period. Reversal in adults had no effect. Much research ensued to uncover the underlying mechanisms.

By contrast, Dalton and Sam were adult at the time of the intervention. The authors took their findings to suggest that the visual system remains highly plastic even in maturity. However, compared with monocular deprivation color-blindness seems to pose a minor challenge to the visual system. In the gene therapy study, the neural circuitry necessary for color discrimination may have already been in place at the time of the intervention. Existing connections may have only needed strengthening to attune the neurons to the novel inputs, precipitating the monkeys' correct decision in the test. It is puzzling, however, that it took the monkeys months to improve the new skill.

To better understand the neural mechanisms involved in the monkeys' novel ability to discriminate color, it is crucial to find out precisely when after the intervention the photoreceptors become sensitive to new wavelengths of light.

References

• Mancuso K, Hauswirth WW, Li Q, Connor TB, Kuchenbecker JA, Mauck MC, Neitz J, Neitz M (2009) Gene therapy for red-green colour blindness in adult primates. Nature:online.
• Wiesel TN, Hubel DH (1963) Single-cell responses in striate cortex of kittens deprived of vision in one eye. J Neurophysiol 26:1003-1017.

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