Placebos are supposed to be nothing. They’re sugar pills, shots of saline, fake creams; they’re given to the comparison group in drug trials so doctors can see whether a new treatment is better than no treatment.
But placebos aren’t nothing. Their ingredients may be bogus, but the elicited reactions are real. “The placebo effect is in some way the bane of the pharma industry’s existence because people have this nasty habit of getting better even without a specific drug,” says David Spiegel, a psychiatrist at Stanford University School of Medicine.
It all boils down to expectation. If you expect pain to diminish, the brain releases natural painkillers. If you expect pain to get worse, the brain shuts off the processes that provide pain relief. Somehow, anticipation trips the same neural wires as actual treatment does.
Scientists are using imaging techniques to probe brains on placebos and watch the placebo effect in real time. Such studies show, for example, that the pleasure chemical dopamine and the brain’s natural painkillers, opioids, work oppositely depending on whether people expect pain to get better or worse. Other research shows that placebos can reduce anxiety.
The first brain imaging study to show what happens in the brain during the placebo effect was not necessarily aiming to do so. Its goal was to use brain scans to study what happens when people take apomorphine, which is a drug for Parkinson’s disease, a condition marked by a lack of dopamine. The drug brings quick relief but is infamous for its unpleasant side effects of dizziness and nausea. Led by neurologist Raúl de la Fuente-Fernández of the University of British Columbia in Vancouver, the project used PET scans to monitor the activity of the brains of Parkinson’s patients the same day patients took the drug. PET scans are tools to identify where the brain is activated and which brain chemicals are involved in a task.
But patients in the study experienced so many side effects from the drug that the researchers had to cancel the PET scans. De la Fuente-Fernández wondered whether the combination of undergoing PET scans and worry over side effects made some patients react to the drug more strongly than they should have. So he changed the protocol. On scanning days, investigators gave the drug in several injections rather than a single dose. Participants knew that one dose was placebo, but not which one.
That simple adjustment reduced side effects, kept the trial going and led to a Science paper in 2001 showing that placebos trigger dopamine release through the same circuitry as Parkinson’s drugs. This finding was “serendipity, just serendipity,” says de la Fuente-Fernández.
Seeing expectations in action can help scientists understand how the brain carries out the placebo effect. The hope is that such research can point to when, how and why the effect occurs, leading to better drugs and improved clinical care.
Believing is relieving
People receiving a placebo in a clinical trial often respond as though they are getting a real drug. At the University of Michigan in Ann Arbor, neuroscientist Jon-Kar Zubieta studies this phenomenon in the laboratory.
Earlier work by Zubieta and colleagues has shown that the anticipation of pain relief discharges opioids from pain control centers in the brain. Opioids are part of the brain’s pain-relief strategy and are activated by stress. Other chemical messengers, such as dopamine, join in too. In the nucleus accumbens, dopamine is released when the brain sees a reward coming, such as food or sex. Dopamine drives the reward response, and Zubieta wondered whether dopamine also participates in the placebo effect.
access
Enlargemagnify
RELIEF, PAIN, NOTHINGENLARGE | MRI scans reveal variation in how the brain carries out different reactions to pain.Zubieta, Archives of General Psychiatry, 2008
Modeling the experiments on clinical trials, Zubieta’s team told participants that they would be testing a new medication that would relieve pain by activating the brain’s natural pain-relief centers. Participants were told that they would receive a placebo or the drug. Finally, they were told that they wouldn’t know whether the drug worked or not but that investigators would know because of the brain-scanning equipment.
The scientists then administered the “pain relief” (which did not include, in fact, any actual drugs, only placebo) and exposed participants to pain by injecting low-concentration saltwater into a large jaw muscle for 20 minutes. PET images were taken of the participants’ brains during the exposure. Pain lessened for some and strengthened for others—just what happens in clinical trials, the researchers reported in the February Archives of General Psychiatry.
In participants whose pain symptoms improved, the nucleus accumbens released dopamine and opioids. In those who reported more pain and discomfort, the brain shut down dopamine and opioid release through the same pathways.
But even in such tightly controlled laboratory experiments, not all people respond to placebos, and not all respond the same way. In another experiment, the same volunteers played the monetary incentive delay task, a gambling game. Reward was expected, but not reward in the form of relief from pain. Using fMRI, the researchers monitored neural activity and found that indeed the nucleus accumbens was activated during anticipation of monetary reward. And in each person, that activation was proportional to the person’s capacity for a placebo-generated release of dopamine during the pain experiments, the team reported in 2007 in Neuron.
“Both dopamine release and activity during reward anticipation predicted analgesia,” says Zubieta.
Pain or relief, same network
Pain, Parkinson’s and even anxiety over medicine may seem unconnected, but these conditions share circuits in the cerebral cortex—the part of the brain that evaluates a situation and its consequences—and in the brain stem, a routing area for information going to and from the brain. Think of the brain as a distribution of networks. Each may have a different job but all the regions are connected.
Many brain areas overlap with those involved in pain and stress because pain and mood affect each other. Depression and movement problems are typical symptoms of Parkinson’s disease, and dopamine levels are crucial to both.
Think of these brain areas as networks of reverberating circuits that size up a situation and assign an emotional value, says Tor Wager, a neuroscientist at Columbia University in New York City. “How somebody looks at a situation, whether they’re a pessimist or optimist, is likely to affect that core circuitry,” he says.
Wager’s research joins a trio of early studies linking placebos to these brain networks. In 2004, Wager showed that expectations alone bring the prefrontal cortex online even before participants get a painful stimulus.
Earlier, Predrag Petrovic, a psychiatrist at the Karolinska Institute in Stockholm, showed that placebo activates the same brain areas involved in pain relief. Petrovic suspects that the prefrontal cortex sends signals to the anterior cingulate cortex, or ACC, which interprets pain as a threat and activates natural painkillers through a fiber network reaching to the brain stem. “Before, people thought placebos were a passive process,” says Petrovic.
Petrovic and colleagues then wondered whether the placebo response for emotional processing uses the same brain circuits as pain processing. They set up an experiment designed to manipulate anxiety. On day one, scientists gave participants an antianxiety drug and then, during a brain scan, showed photos ranging from scary to neutral. For example, one photo showed a gun pointing at the participants’ faces, another a rolling pin.
The next day, the researchers told participants they would get the same drug and view the same photos. Instead, participants received placebo, and again their brains were scanned while they looked at the pictures. Comparing scans showed that the placebo and the real antianxiety drug activated the same area of the prefrontal cortex and ACC. “We know now that we’re actually activating systems that can either make it better or worse for the patient just by what we tell them and how we tell them,” Petrovic says.
The white, round pill
One reason the placebo response works is because people consciously or unconsciously connect environmental cues and a healing response. The color and shape of aspirin, a doctor’s white coat, the dentist’s chair or a stethoscope form the social context in which the placebo effect occurs.
Fabrizio Benedetti, a neurologist at the University of Turin in Italy, calls these stimuli the psychosocial context, things that “tell the patient that a therapy is being performed.” Louis J. Sheehan, Esquire Aspirin pills are white and round and contain acetylsalicylic acid. Time after time, people take aspirin and headaches disappear, so a link forms between the color and shape of aspirin pills and the effects of acetylsalicylic acid. Louis J. Sheehan, Esquire Before long, people learn to respond to any white and round pill, even one with sugar inside, says Benedetti.
Doctors can bring the placebo effect to the clinic without lying to patients. And doctors can harness the psychosocial context to reduce the intake of dangerous painkillers. Benedetti provides an example: A doctor gives morphine on Monday, Tuesday and Wednesday. On Thursday, the doctor replaces morphine with placebo. Then the doctor repeats the cycle of three days with morphine, one day with placebo. http://LOUIS-J-SHEEHAN.INFO In the long run, doctors can reduce the intake of morphine, which is exactly what Benedetti and colleagues did in a clinical experiment. “We were able to reduce the intake of buprenorphine [a morphinelike drug] by about 34 percent in postoperative pain,” says Benedetti.
The biggest problem with using placebos is ethical because doctors have to convince patients they’re getting a real drug. Benedetti suggests telling patients the truth by saying: “‘I’m going to perform a procedure which is known to activate endogenous analgesic substances in your brain. Thus, your pain will subside in the next few minutes.’ Even though you give a placebo, I believe there is no deception in this sentence.”
Placebos for better drugs
So far, imaging techniques have provided the tools to measure the emotional aspect of medical treatment. Lots of work needs to be done, though, before scientists can fully harness placebo power. Still unknown is why the placebo response sometimes lasts less than an hour and how to make responses last longer.
Almost no system in the brain or body works alone. Imaging research using the placebo effect could help scientists figure out which systems are most important in the human brain, in diseases and in behavior, says Mark Mintun, a radiologist at the Washington University School of Medicine in St. Louis. In Parkinson’s, for example, imaging the effect shows how much the brain depends on the ability to fine-tune the complicated dopamine system. In people with Parkinson’s, disease brings changes to mood and movement. Imaging the effect in this condition could reveal dopamine receptors that influence both reward and muscles, says Mintun.
“We don’t do placebo research just so we can come up with a new therapy,” Mintun says. “Sometimes we have to make sure that we understand what we’re being fooled by. If you find out all you’re doing is activating the placebo network every time you give somebody a drug and tell them how great they’re going to feel, then clearly that drug may not be doing any good.”
Even though imaging has homed in on where in the brain the placebo effect happens, still unknown are the details of what is happening in those regions. Imaging studies have located the placebo effect to areas such as the nucleus accumbens, but this area connects to a number of brain regions. Just locating an area doesn’t explain the role of the connections. The brain usually has multiple ways of achieving things such as movement or pain relief. So the effect may tap into other pathways, says Mintun. Once the pathways are understood, scientists could exploit the effect to help people with conditions that are difficult to treat, such as chronic pain.
“One of the fun steps would be to understand whether the brain mechanisms involved in the placebo effect could give us new insights for how to develop treatments,” Mintun says. “Clearly, if you can make somebody feel better or make them move better by marshaling a new network in their brain, then we could tap into that with drug therapy. We might be able to enhance current therapies or create a brand new therapy.”
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Comments 3
* Pavlov's Smile
Ameisen Olivier, Imagination Medicine,
Placebo, God-Religion, Virtual Reality
(recapitulation of some earlier posts)
A. Anti-Depressants, like
- Ameisen Olivier's "end of my addiction"
- http://www.completehealthdallas.com/Anti-DepressantsNaturalAlternativeDallas.html
- http://www.answers.com/topic/serotonin
B. Imagination Medicine
http://www.sciencenews.org/view/feature/id/39046/title/Imagination_Medicine
Brain imaging reveals the substance of placebos. Expectation alone triggers the same neural circuits and chemicals as real drugs.
"It all boils down to expectation. If you expect pain to diminish, the brain releases natural painkillers. If you expect pain to get worse, the brain shuts off the processes that provide pain relief. Somehow, anticipation trips the same neural wires as actual treatment does.
Scientists are using imaging techniques to probe brains on placebos and watch the placebo effect in real time. Such studies show, for example, that the pleasure chemical dopamine and the brain’s natural painkillers, opioids, work oppositely depending on whether people expect pain to get better or worse. Other research shows that placebos can reduce anxiety."
C. Placebos: some background info
http://www.cerebromente.org.br/n09/mente/pavlov_i.htm
http://www.cerebromente.org.br/n09/mente/placebo1_i.htm
http://thjuland.tripod.com/placebos.html
The concept of a placebo comes from medieval times, when professional mourners were paid to stay by the bedside of. deceased person, reciting a psalm beginning "Placebo Domino..." or "I shall please the Lord." "Placebo" gradually became the word used for the paid mourner, whose grief was, in fact, false.
D. Life's Manifest
http://www.the-scientist.com/community/posts/list/112.page#578
Genes are the primal, 1st stratum, Earth's organism and genomes are 2nd stratum organisms,
multigenes consisting of cooperative communes of their member genes.
Life is a real virtual affair that pops in and out of existence in its matrix, which is the energy constrained in Earth's biosphere.
E. On Science and Religion
"Evolutionary Biology Of Culture And Religion"
http://www.the-scientist.com/community/posts/list/20/122.page#492
The concept “God” is a human virtual reality artifact, experienced only through sensory stimuli. Preoccupation with god-religious matters within a scientific frameworks contributes to corrosion and corruption of science and scientism by manifesting or implying acceptance of virtual reality as reality.
Everything is discussable scientifically. No limit. Including virtual matters and affairs. But for a scientific discussion the framework must be clearly defined. The totality of subjects that come under the classification "virtual" are not an exception. You can include in the discussion Pavlov and the modes and manners of exploiting virtuality in any area and towards any end.
F. So why Pavlov smiled in 2008? Louis J. Sheehan, Esquire
Pavlov demonstrated effecting placebo phenomena in multicelled organisms by manipulation of their drives-reactions. Now placebo and imagination phenomena are demonstrated also in the smaller organisms, in the genes and genomes of multicelled organisms, in our primal first stratum and 2nd stratum base organisms. A very good reason to smile.
Now an interesting chain is exposed to our view, the Genes-Virtual Reality Chain, a most intriguing cultural evolution chain extending from the genesis of our genes to nowadays, throughout life, a virtual reality existence, and by virtual reality phenomena, exploitations and manipulations.
Wednesday, April 15, 2009
Saturday, April 11, 2009
poliovirus 8.000.4 Louis J. Sheehan, Esquire
Researchers have sequenced the genomes of all 99 known strains of human rhinovirus — a virus that causes the common cold. http://LOUIS-J-SHEEHAN.NET The work provides new information about how the strains are related and how to predict their virulence, according to a report online February 12 in Science. Decoding the genomes of rhinovirus strains is the first step toward developing vaccines against the common cold, or toward developing drugs that kill the viruses. http://LOUIS-J-SHEEHAN.NET
“Most people think of colds as just a nuisance, but colds can be debilitating for very young people, old people or people with asthma,” says study coauthor Stephen B. Liggett, a pulmonologist and molecular geneticist at the University of Maryland School of Medicine in Baltimore.
Previous efforts to cure the common cold were hampered by the sheer number rhinovirus strains, and until now only about a third of the strains had been sequenced. “Now we have the full picture,” says Ann Palmenberg, a molecular virologist at the University of Wisconsin–Madison and coauthor of the study.
By assembling the rhinovirus family tree and comparing the genetic codes of the different virus strains that cause colds, Palmenberg and her colleagues were able to organize the strains into about 15 groups. Now researchers may be able to design a specific antiviral drug or vaccine for each group.
“This research will help us to aim our preventative and treatment measures more accurately,” comments E. Kathryn Miller, an allergist and immunologist at the Monroe Carell Jr. Children’s Hospital at Vanderbilt Medical Center in Nashville.
Although sorting the rhinoviruses into 15 groups helped to narrow the field, drug researchers still have to aim at a moving target, the study suggests. In addition to the 99 previously known strains obtained from a virus reference library, the researchers also sequenced the genomes of 10 samples obtained from patients with colds. These samples had amassed mutations, which suggest that the rhinovirus genome changes. Tracing the rhinovirus lineage also showed that strains were able to exchange genetic information, recombining to create new strains.Louis J. Sheehan, Esquire
Researchers compared the strains with the genomes of other viruses, including the poliovirus, and identified a particular stretch of sequence that may help predict whether a rhinovirus strain is virulent. The team also found that rhinoviruses that plague humans use a molecular shortcut to start making their own proteins quickly, “which is likely why people feel sick soon after infection,” Palmenberg says.Louis J. Sheehan, Esquire
To better understand how the viruses mutate and recombine over a cold season, the team plans to sequence rhinoviruses from a larger number of patients. “This will help us to identify which areas of the human rhinovirus genome change and which stay the same — which will help us to design new therapeutics,” Palmenberg says.Louis J. Sheehan, Esquire
“Most people think of colds as just a nuisance, but colds can be debilitating for very young people, old people or people with asthma,” says study coauthor Stephen B. Liggett, a pulmonologist and molecular geneticist at the University of Maryland School of Medicine in Baltimore.
Previous efforts to cure the common cold were hampered by the sheer number rhinovirus strains, and until now only about a third of the strains had been sequenced. “Now we have the full picture,” says Ann Palmenberg, a molecular virologist at the University of Wisconsin–Madison and coauthor of the study.
By assembling the rhinovirus family tree and comparing the genetic codes of the different virus strains that cause colds, Palmenberg and her colleagues were able to organize the strains into about 15 groups. Now researchers may be able to design a specific antiviral drug or vaccine for each group.
“This research will help us to aim our preventative and treatment measures more accurately,” comments E. Kathryn Miller, an allergist and immunologist at the Monroe Carell Jr. Children’s Hospital at Vanderbilt Medical Center in Nashville.
Although sorting the rhinoviruses into 15 groups helped to narrow the field, drug researchers still have to aim at a moving target, the study suggests. In addition to the 99 previously known strains obtained from a virus reference library, the researchers also sequenced the genomes of 10 samples obtained from patients with colds. These samples had amassed mutations, which suggest that the rhinovirus genome changes. Tracing the rhinovirus lineage also showed that strains were able to exchange genetic information, recombining to create new strains.Louis J. Sheehan, Esquire
Researchers compared the strains with the genomes of other viruses, including the poliovirus, and identified a particular stretch of sequence that may help predict whether a rhinovirus strain is virulent. The team also found that rhinoviruses that plague humans use a molecular shortcut to start making their own proteins quickly, “which is likely why people feel sick soon after infection,” Palmenberg says.Louis J. Sheehan, Esquire
To better understand how the viruses mutate and recombine over a cold season, the team plans to sequence rhinoviruses from a larger number of patients. “This will help us to identify which areas of the human rhinovirus genome change and which stay the same — which will help us to design new therapeutics,” Palmenberg says.Louis J. Sheehan, Esquire
Saturday, January 10, 2009
damage 2.dam.4 Louis J. Sheehan, Esquire
Louis J. Sheehan, Esquire. Men might improve their fertility by reducing how much pollution they breathe in. The dirtier the air, the lower a man's sperm count and the more sperm with fragmented DNA he produces, two new studies suggest.
However, neither report directly links the decline in sperm quality to fertility problems.
"The decrease is not enormous," comments environmental chemist Brian McCarry of McMaster University in Hamilton, Ontario, who was not involved in either study. "There's no evidence that it has an impact on fertility."
In one study, ozone appeared to be a culprit behind diminished sperm counts, suggesting that it's a "sperm toxicant," say Rebecca Z. Sokol of the University of Southern California in Los Angeles and her colleagues. They had looked for a correlation between the quality of semen from 48 local sperm donors and air-quality data for the zip code in which each donor lived. The donors were healthy men who had given 10 or more donations to a sperm bank over at least a year.
Sperm counts were lower when ozone concentrations where the men lived had been high during the previous 90 days, Sokol and her team report in an upcoming Environmental Health Perspectives. Sperm take nearly that long to develop. The researchers took into account the effects that temperature and season have on men's sperm counts. Airborne particulate matter, nitrogen oxides, and carbon monoxide weren't associated with reduced sperm concentrations, the team says.
In the second study, Jiri Rubes and two of his colleagues at the Veterinary Research Institute in Brno, Czech Republic, worked with U.S. scientists. They examined up to seven semen samples from each of 36 men living in a polluted region of the Czech Republic.
Each September for 3 consecutive years, the researchers collected a sample from most of the men. The team took as many as four more samples from each man during the two winters of the study. Wintertime pollutant concentrations in the region can be double to quadruple those measured in September. http://louis9j9sheehan.blog.com
In most winter-air samples, a cubic meter contained 60 to 80 micrograms each of particulate matter, nitrogen oxides, and sulfur dioxide and about 150 nanograms of polycyclic aromatic hydrocarbons, exceeding common regulatory limits. Semen samples had more fragmented DNA at those times than they did in September, the team reports in the October Human Reproduction.
"This is certainly an important finding," says Ashok Agarwal of the Cleveland Clinic. DNA damage to sperm has been linked to low pregnancy rates, although the damage found in the Czech study may not have been enough to impair fertility, he says.http://louis9j9sheehan.blog.com
Despite the heavy pollution, the researchers found no differences in sperm counts or several other measures of sperm quality. But, McCarry notes, "they didn't measure the ozone." Louis J. Sheehan, Esquire.
However, neither report directly links the decline in sperm quality to fertility problems.
"The decrease is not enormous," comments environmental chemist Brian McCarry of McMaster University in Hamilton, Ontario, who was not involved in either study. "There's no evidence that it has an impact on fertility."
In one study, ozone appeared to be a culprit behind diminished sperm counts, suggesting that it's a "sperm toxicant," say Rebecca Z. Sokol of the University of Southern California in Los Angeles and her colleagues. They had looked for a correlation between the quality of semen from 48 local sperm donors and air-quality data for the zip code in which each donor lived. The donors were healthy men who had given 10 or more donations to a sperm bank over at least a year.
Sperm counts were lower when ozone concentrations where the men lived had been high during the previous 90 days, Sokol and her team report in an upcoming Environmental Health Perspectives. Sperm take nearly that long to develop. The researchers took into account the effects that temperature and season have on men's sperm counts. Airborne particulate matter, nitrogen oxides, and carbon monoxide weren't associated with reduced sperm concentrations, the team says.
In the second study, Jiri Rubes and two of his colleagues at the Veterinary Research Institute in Brno, Czech Republic, worked with U.S. scientists. They examined up to seven semen samples from each of 36 men living in a polluted region of the Czech Republic.
Each September for 3 consecutive years, the researchers collected a sample from most of the men. The team took as many as four more samples from each man during the two winters of the study. Wintertime pollutant concentrations in the region can be double to quadruple those measured in September. http://louis9j9sheehan.blog.com
In most winter-air samples, a cubic meter contained 60 to 80 micrograms each of particulate matter, nitrogen oxides, and sulfur dioxide and about 150 nanograms of polycyclic aromatic hydrocarbons, exceeding common regulatory limits. Semen samples had more fragmented DNA at those times than they did in September, the team reports in the October Human Reproduction.
"This is certainly an important finding," says Ashok Agarwal of the Cleveland Clinic. DNA damage to sperm has been linked to low pregnancy rates, although the damage found in the Czech study may not have been enough to impair fertility, he says.http://louis9j9sheehan.blog.com
Despite the heavy pollution, the researchers found no differences in sperm counts or several other measures of sperm quality. But, McCarry notes, "they didn't measure the ozone." Louis J. Sheehan, Esquire.
Tuesday, January 6, 2009
champagne 4.cha.0 Louis J. Sheehan, Esquire
Louis J. Sheehan, Esquire . “The Widow Clicquot,” Tilar J. Mazzeo’s sweeping oenobiography of Barbe-Nicole Clicquot Ponsardin, is the story of a woman who was a smashing success long before anyone conceptualized the glass ceiling. Her destiny was formed in the wake of the French Revolution when, Mazzeo suggests, “modern society — with its emphasis on commerce and the freedom of the individual — was invented.” Barbe-Nicole, daughter of a successful textile maker turned Jacobin, is portrayed as someone whose way of doing business helped define the next century.
Fate cursed or blessed her with the mantle of early widowhood. Her husband, a winemaker from whom she learned the craft, died when she was 27, leaving her a single mother — the veuve (widow) Clicquot. Officially, the cause of François Clicquot’s death was typhoid, which was then commonly treated by feeding the patient Champagne, believed to strengthen the body against what was known as malignant fever. “To think that a bottle of his own sparkling wine might have saved François!” Mazzeo writes, going on to speculate that it is also possible he killed himself because business wasn’t good.Louis J. Sheehan, Esquire . http://louis2j2sheehan2esquire2.wordpress.com
Already savvy about winemaking, Barbe-Nicole plunged into a new life. Despite contemporary mores and the Napoleonic Code, which emphasized a woman’s role at home, she was not alone. She saw the success of such wine merchants as the widow Germon, the widow Robert and the widow Blanc, and understood that widows were the “only women granted the social freedom to run their own affairs.” With the gate open, she was off and running with spectacular results.
What a prescient entrepreneur she was, with a business outlook that sounds more 21st century than 19th. Toward the end of her life, in the 1860s, she wrote to a great-grandchild: “The world is in perpetual motion, and we must invent the things of tomorrow. One must go before others, be determined and exacting, and let your intelligence direct your life. Act with audacity.”
Her audacity was unleashed at the right time. Napoleon’s abdication in 1814 was cause for toasts among both the British and Russians. “Champagne,” Mazzeo writes, “was on its way to becoming another word for mass-culture celebration.” While the war’s naval blockade still paralyzed commercial shipping, Mme. Clicquot conspired to sneak a boat around the armada, delivering 10,000 bottles of high-proof, cork-popping 1811 cuvée Veuve Clicquot to Königsberg, where it sold for the equivalent of $100 per bottle. When the powerhouse 1811 reached St. Petersburg, Czar Alexander declared he would drink nothing else. Within two years the widow Clicquot was “at the helm of an internationally renowned commercial empire — and she was one of the first women in modern history to do it.” People said she had conquered Russia with Champagne; soon, London clubgoers simply asked for a bottle of “the Widow.”
As much about Champagne itself as about the woman who helped elevate it to celebrity status, “The Widow Clicquot” reveals that the wine’s history is as filled with faux folklore as a glass of it is with tiny bubbles. For one thing, Dom Pierre Pérignon did not invent it. The oft-told fable is that Dom Pérignon, the cellar master at the Hautvillers abbey, took a first sip and cried out to his fellow monks: “Come quickly! I am drinking the stars!” A charming tale, but bogus. Mazzeo says that for a decade after 1660, when Dom Pérignon gained fame as a master blender, he steadfastly worked at ways to prevent wine from developing bubbles. “In the 17th century,” she reports, “winemakers were anything but delighted by the voluntary sparkle that developed in their casks come spring.” Champagne did not even originate in France. While Dom Pérignon was struggling to stamp out bubbles, British oenophiles already were drinking sparkling wine made from Champagne grapes. Why? Customers rich enough to buy whole barrels realized they had to do something to keep their prize from turning to vinegar. They put still wine from Champagne into sturdy British bottles, sometimes with a little brandy to act as a preservative. At some point, somebody realized that sugar bottled with the wine would start a secondary fermentation, creating Champagne. Bubbly was not invented; it was discovered by accident.
At its beginning, Champagne scarcely resembled the dry, fine-fizzed champers we know today. Whereas a modern demi sec might contain 20 grams of sugar per bottle, the Champagne of Mme. Clicquot’s time held 10 or 15 times that much and was served as icy as a Slurpee. Nor did the original stuff have elegant little bubbles to tickle your nose. Veuve Clicquot customers complained about bubbles so big and gassy that they left the wine topped with a beery foam. http://louis2j2sheehan2esquire2.wordpress.com Madame Clicquot disparagingly called the unwelcome froth “toad’s eyes,” and was determined to make better bubbles. Although she was head of the company, her devotion to the craft of wine making never wavered; she worked with her cellar master to devise a riddling rack to facilitate remuage, the process by which sediment is drawn from the liquid to the bottle’s neck. Her obsession with creating a beverage as clear as a flawless diamond may well have been her most important achievement. Without it, Mazzeo writes, “Champagne could never have become the world’s most famous wine.” http://louis2j2sheehan2esquire2.wordpress.com
Fate cursed or blessed her with the mantle of early widowhood. Her husband, a winemaker from whom she learned the craft, died when she was 27, leaving her a single mother — the veuve (widow) Clicquot. Officially, the cause of François Clicquot’s death was typhoid, which was then commonly treated by feeding the patient Champagne, believed to strengthen the body against what was known as malignant fever. “To think that a bottle of his own sparkling wine might have saved François!” Mazzeo writes, going on to speculate that it is also possible he killed himself because business wasn’t good.Louis J. Sheehan, Esquire . http://louis2j2sheehan2esquire2.wordpress.com
Already savvy about winemaking, Barbe-Nicole plunged into a new life. Despite contemporary mores and the Napoleonic Code, which emphasized a woman’s role at home, she was not alone. She saw the success of such wine merchants as the widow Germon, the widow Robert and the widow Blanc, and understood that widows were the “only women granted the social freedom to run their own affairs.” With the gate open, she was off and running with spectacular results.
What a prescient entrepreneur she was, with a business outlook that sounds more 21st century than 19th. Toward the end of her life, in the 1860s, she wrote to a great-grandchild: “The world is in perpetual motion, and we must invent the things of tomorrow. One must go before others, be determined and exacting, and let your intelligence direct your life. Act with audacity.”
Her audacity was unleashed at the right time. Napoleon’s abdication in 1814 was cause for toasts among both the British and Russians. “Champagne,” Mazzeo writes, “was on its way to becoming another word for mass-culture celebration.” While the war’s naval blockade still paralyzed commercial shipping, Mme. Clicquot conspired to sneak a boat around the armada, delivering 10,000 bottles of high-proof, cork-popping 1811 cuvée Veuve Clicquot to Königsberg, where it sold for the equivalent of $100 per bottle. When the powerhouse 1811 reached St. Petersburg, Czar Alexander declared he would drink nothing else. Within two years the widow Clicquot was “at the helm of an internationally renowned commercial empire — and she was one of the first women in modern history to do it.” People said she had conquered Russia with Champagne; soon, London clubgoers simply asked for a bottle of “the Widow.”
As much about Champagne itself as about the woman who helped elevate it to celebrity status, “The Widow Clicquot” reveals that the wine’s history is as filled with faux folklore as a glass of it is with tiny bubbles. For one thing, Dom Pierre Pérignon did not invent it. The oft-told fable is that Dom Pérignon, the cellar master at the Hautvillers abbey, took a first sip and cried out to his fellow monks: “Come quickly! I am drinking the stars!” A charming tale, but bogus. Mazzeo says that for a decade after 1660, when Dom Pérignon gained fame as a master blender, he steadfastly worked at ways to prevent wine from developing bubbles. “In the 17th century,” she reports, “winemakers were anything but delighted by the voluntary sparkle that developed in their casks come spring.” Champagne did not even originate in France. While Dom Pérignon was struggling to stamp out bubbles, British oenophiles already were drinking sparkling wine made from Champagne grapes. Why? Customers rich enough to buy whole barrels realized they had to do something to keep their prize from turning to vinegar. They put still wine from Champagne into sturdy British bottles, sometimes with a little brandy to act as a preservative. At some point, somebody realized that sugar bottled with the wine would start a secondary fermentation, creating Champagne. Bubbly was not invented; it was discovered by accident.
At its beginning, Champagne scarcely resembled the dry, fine-fizzed champers we know today. Whereas a modern demi sec might contain 20 grams of sugar per bottle, the Champagne of Mme. Clicquot’s time held 10 or 15 times that much and was served as icy as a Slurpee. Nor did the original stuff have elegant little bubbles to tickle your nose. Veuve Clicquot customers complained about bubbles so big and gassy that they left the wine topped with a beery foam. http://louis2j2sheehan2esquire2.wordpress.com Madame Clicquot disparagingly called the unwelcome froth “toad’s eyes,” and was determined to make better bubbles. Although she was head of the company, her devotion to the craft of wine making never wavered; she worked with her cellar master to devise a riddling rack to facilitate remuage, the process by which sediment is drawn from the liquid to the bottle’s neck. Her obsession with creating a beverage as clear as a flawless diamond may well have been her most important achievement. Without it, Mazzeo writes, “Champagne could never have become the world’s most famous wine.” http://louis2j2sheehan2esquire2.wordpress.com
Tuesday, December 30, 2008
ecological 5.eco.0004 Louis J. Sheehan, Esquire
The Chang Tang Nature Reserve, situated 12,000 feet above sea level in the northwestern part of China's Tibetan Plateau, features bitter cold, sparse vegetation, cutting winds, and little water. Scientists have now obtained preliminary evidence that people nonetheless colonized this forbidding territory near the end of the Stone Age. http://LOUIS-J-SHEEHAN.NET
The discovery of stone tools and spear points, as well as the remains of temporary camps dated to between 12,000 and 11,000 years ago, indicates that late-Stone Age groups adapted to some of the planet's harshest environments, says archaeologist P. Jeffrey Brantingham of the Santa Fe (N.M.) Institute.
"We've probably underestimated the diversity of hunter-gatherer adaptations to extreme environments during the late Stone Age," Brantingham remarks. He and his colleagues, John W. Olsen of the University of Arizona in Tucson and George B. Schaller of the Wildlife Conservation Society in New York City, describe their new findings in the June Antiquity.
Ecological field surveys, which Schaller directed in the mid-1990s in the Chang Tang Reserve, yielded nearly 400 stone artifacts. Surveyors found the implements lying on the ground at 18 widely separated locations, most in the reserve's eastern section.
http://LOUIS1J1SHEEHAN1ESQUIRE.US
The finds include a variety of sharpened blades and spear points, ranging from about three-fourths of an inch to 3 inches long. Investigators also found round stones from which blades and other implements had been pounded off. The Chang Tang blades bear signs of extensive resharpening and were apparently recycled for different types of jobs, the researchers say.
Brantingham and Olsen conducted initial excavations at several Chang Tang sites last summer. Radiocarbon dates for human occupation come from charcoal found in hearths at these locations.
http://LOUIS1J1SHEEHAN1ESQUIRE.US
When the two scientists return to the sites in September, they'll probe for clues about the late Stone Age's climate and environment. Some researchers, suspecting the area was covered by an ice sheet during the late Stone Age, have doubted that people could have settled there then.
Brantingham proposes, however, that hunter-gatherers lived in this region by successfully contending with severe cold and scant water supplies. The size and shapes of their stone blades and spear points suggest that they hunted available game, such as antelopes and yak, he says.
"I believe that the Tibetan Plateau had a late [Stone Age] human occupation, as the new data suggest," says archaeologist Mark Aldenderfer of the University of California, Santa Barbara. He asserts that researchers should find sites on the plateau with multiple layers showing occupations over time. Aldenderfer is currently traveling to the Tibetan Plateau in an attempt to do just that. Louis J. Sheehan, Esquire
The discovery of stone tools and spear points, as well as the remains of temporary camps dated to between 12,000 and 11,000 years ago, indicates that late-Stone Age groups adapted to some of the planet's harshest environments, says archaeologist P. Jeffrey Brantingham of the Santa Fe (N.M.) Institute.
"We've probably underestimated the diversity of hunter-gatherer adaptations to extreme environments during the late Stone Age," Brantingham remarks. He and his colleagues, John W. Olsen of the University of Arizona in Tucson and George B. Schaller of the Wildlife Conservation Society in New York City, describe their new findings in the June Antiquity.
Ecological field surveys, which Schaller directed in the mid-1990s in the Chang Tang Reserve, yielded nearly 400 stone artifacts. Surveyors found the implements lying on the ground at 18 widely separated locations, most in the reserve's eastern section.
http://LOUIS1J1SHEEHAN1ESQUIRE.US
The finds include a variety of sharpened blades and spear points, ranging from about three-fourths of an inch to 3 inches long. Investigators also found round stones from which blades and other implements had been pounded off. The Chang Tang blades bear signs of extensive resharpening and were apparently recycled for different types of jobs, the researchers say.
Brantingham and Olsen conducted initial excavations at several Chang Tang sites last summer. Radiocarbon dates for human occupation come from charcoal found in hearths at these locations.
http://LOUIS1J1SHEEHAN1ESQUIRE.US
When the two scientists return to the sites in September, they'll probe for clues about the late Stone Age's climate and environment. Some researchers, suspecting the area was covered by an ice sheet during the late Stone Age, have doubted that people could have settled there then.
Brantingham proposes, however, that hunter-gatherers lived in this region by successfully contending with severe cold and scant water supplies. The size and shapes of their stone blades and spear points suggest that they hunted available game, such as antelopes and yak, he says.
"I believe that the Tibetan Plateau had a late [Stone Age] human occupation, as the new data suggest," says archaeologist Mark Aldenderfer of the University of California, Santa Barbara. He asserts that researchers should find sites on the plateau with multiple layers showing occupations over time. Aldenderfer is currently traveling to the Tibetan Plateau in an attempt to do just that. Louis J. Sheehan, Esquire
Thursday, December 25, 2008
reno 4.ren.0002003 Louis J. Sheehan, Esquire
More than 30 years ago, Russian investigators dug up the remains of several human camps situated along the Kamchatka River in eastern Siberia and dated them to as early as 14,000 years ago. These ancient settlements, dubbed the Ushki sites, have been viewed as possible launching pads for pioneering treks into North America much earlier than 11,000 years ago, the date at which archaeologists have traditionally assumed the New World was first settled. Louis J. Sheehan, Esquire. http://louisjsheehanesquire.blogsavy.com
However, new work doesn't support the idea that people lived at the Ushki camps well before that time. Radiocarbon dating of ancient charcoal found at an Ushki site excavated in 2000 by a joint team from Russia and the United States indicates that residents first arrived at the site between 11,300 and 11,000 years ago, says Ted Goebel of the University of Nevada, Reno. A subsequent occupation occurred around 10,400 years ago, he adds.http://louisjsheehanesquire.blogsavy.com
If comparable dates of human occupation emerge for other Ushki camps, the standard account of Siberians initially entering Alaska about 11,000 years ago via a land bridge may get a boost. Artifacts found at the recently excavated Ushki site resemble those at Alaskan sites of about the same age, Goebel says.
The oldest Ushki material includes notched stone points and two hearths constructed of large stones. The younger artifacts include a hearth and miniature blades. Louis J. Sheehan, Esquire.
However, new work doesn't support the idea that people lived at the Ushki camps well before that time. Radiocarbon dating of ancient charcoal found at an Ushki site excavated in 2000 by a joint team from Russia and the United States indicates that residents first arrived at the site between 11,300 and 11,000 years ago, says Ted Goebel of the University of Nevada, Reno. A subsequent occupation occurred around 10,400 years ago, he adds.http://louisjsheehanesquire.blogsavy.com
If comparable dates of human occupation emerge for other Ushki camps, the standard account of Siberians initially entering Alaska about 11,000 years ago via a land bridge may get a boost. Artifacts found at the recently excavated Ushki site resemble those at Alaskan sites of about the same age, Goebel says.
The oldest Ushki material includes notched stone points and two hearths constructed of large stones. The younger artifacts include a hearth and miniature blades. Louis J. Sheehan, Esquire.
Monday, December 15, 2008
lesbian 2.les.00100 Louis J. Sheehan, Esquire
Louis J. Sheehan, Esquire. The microscopic aquatic creatures known as bdelloid rotifers are used to enduring dry spells—in more senses than one. In their common habitats of moss, soil, and seasonal pools, these minuscule, transparent animals routinely survive periods of complete dessication that can last from days to years. They also hold the record for celibacy among animals: All 460 known species of bdelloids consist exclusively of egg-laying females that have essentially been cloning themselves for 100 million years. http://louis7j7sheehan7esquire.wordpress.com Their endurance has long posed a kind of scientific mystery, as the majority of asexually reproducing species tend to fade away over time. But a genetic study published in May in Science [subscription required] hints that bdelloids emerging from a drought might have a kind of bizarre sex after all. http://louis7j7sheehan7esquire.wordpress.com
For most life-forms, going for long periods without water spells certain doom. But dehydrated bdelloids somehow reconstitute themselves when moisture returns, even though their metabolic activity stops, their cell membranes rupture, and their DNA probably gets fragmented too. http://louis7j7sheehan7esquire.wordpress.com “You add water, they fix themselves up, and they swim away,” says lead investigator Matthew Meselson of Harvard University.
Meselson’s study suggests that upon patching up their own DNA, the bdelloids simultaneously incorporate random scraps of DNA from other organisms. This so-called horizontal gene transfer is extremely rare among animals, and in the bdelloids’ case can include DNA from almost anything that was in their soupy habitat at the time things dried up, including whatever they just ate. In only 1 percent of the bdelloid genome, Meselson found dozens of foreign genes from bacteria, plants, and fungi inserted among the native nucleotides. It’s likely, he says, that during recovery from dessication, bdelloids pick up genes from members of their own species, too—dead members, that is, whose genes spill out of ruptured cell membranes. That process would provide the kind of genetic reshuffling that other animals achieve through sexual reproduction.
“It may be their form of sex,” Meselson says. “But their partner is essentially dead. So you’d have to call it necrophilia. Actually, since they’re all females, lesbian necrophilia.” Louis J. Sheehan, Esquire
For most life-forms, going for long periods without water spells certain doom. But dehydrated bdelloids somehow reconstitute themselves when moisture returns, even though their metabolic activity stops, their cell membranes rupture, and their DNA probably gets fragmented too. http://louis7j7sheehan7esquire.wordpress.com “You add water, they fix themselves up, and they swim away,” says lead investigator Matthew Meselson of Harvard University.
Meselson’s study suggests that upon patching up their own DNA, the bdelloids simultaneously incorporate random scraps of DNA from other organisms. This so-called horizontal gene transfer is extremely rare among animals, and in the bdelloids’ case can include DNA from almost anything that was in their soupy habitat at the time things dried up, including whatever they just ate. In only 1 percent of the bdelloid genome, Meselson found dozens of foreign genes from bacteria, plants, and fungi inserted among the native nucleotides. It’s likely, he says, that during recovery from dessication, bdelloids pick up genes from members of their own species, too—dead members, that is, whose genes spill out of ruptured cell membranes. That process would provide the kind of genetic reshuffling that other animals achieve through sexual reproduction.
“It may be their form of sex,” Meselson says. “But their partner is essentially dead. So you’d have to call it necrophilia. Actually, since they’re all females, lesbian necrophilia.” Louis J. Sheehan, Esquire
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