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  • richardmitnick 11:19 am on June 13, 2017 Permalink | Reply
    Tags: , During fetal development blood cells are born in the liver and though that task later migrates to the bone marrow, If your liver fails there’s no machine to replace all its different functions and the best you can hope for is a transplant, , NYT, The Liver, The Liver if chopped down to a fraction of its initial size will rapidly regenerate and perform as if brand-new, The liver is our largest internal organ, The organ is always flush with blood   

    From NYT: “The Liver: A ‘Blob’ That Runs the Body” 

    New York Times

    The New York Times

    JUNE 12, 2017
    NATALIE ANGIER

    1
    Guyco

    The underrated, unloved liver performs more
    than 300 vital functions. No wonder the ancients
    believed it to be the home of the human soul.

    To the Mesopotamians, the liver was the body’s premier organ, the seat of the human soul and emotions. The ancient Greeks linked the liver to pleasure: The words hepatic and hedonic are thought to share the same root.

    The Elizabethans referred to their monarch not as the head of state but as its liver, and woe to any people saddled with a lily-livered leader, whose bloodless cowardice would surely prove their undoing.

    Yet even the most ardent liverati of history may have underestimated the scope and complexity of the organ. Its powers are so profound that the old toss-away line, “What am I, chopped liver?” can be seen as a kind of humblebrag.

    After all, a healthy liver is the one organ in the adult body that, if chopped down to a fraction of its initial size, will rapidly regenerate and perform as if brand-new. Which is a lucky thing, for the liver’s to-do list is second only to that of the brain and numbers well over 300 items, including systematically reworking the food we eat into usable building blocks for our cells; neutralizing the many potentially harmful substances that we incidentally or deliberately ingest; generating a vast pharmacopoeia of hormones, enzymes, clotting factors and immune molecules; controlling blood chemistry; and really, we’re just getting started.

    “We have mechanical ventilators to breathe for you if your lungs fail, dialysis machines if your kidneys fail, and the heart is mostly just a pump, so we have an artificial heart,” said Dr. Anna Lok, president of the American Association for the Study of Liver Diseases and director of clinical hepatology at the University of Michigan.

    “But if your liver fails, there’s no machine to replace all its different functions, and the best you can hope for is a transplant.”

    And while scientists admit it hardly seems possible, the closer they look, the longer the liver’s inventory of talents and tasks becomes.

    In one recent study [Cell], researchers were astonished to discover that the liver grows and shrinks by up to 40 percent every 24 hours, while the organs around it barely budge.

    Others have found that signals from the liver may help dictate our dietary choices, particularly our cravings for sweets, like a ripe peach or a tall glass of Newman’s Own Virgin Limeade — which our local supermarket chain has, to our personal devastation, suddenly stopped selling, so please, liver, get a grip.

    Scientists have also discovered that hepatocytes, the metabolically active cells that constitute 80 percent of the liver, possess traits not seen in any other normal cells of the body. For example, whereas most cells have two sets of chromosomes — two sets of genetic instructions on how a cell should behave — hepatocytes can enfold and deftly manipulate up to eight sets of chromosomes, and all without falling apart or turning cancerous.

    That sort of composed chromosomal excess, said Dr. Markus Grompe, who studies the phenomenon at Oregon Health and Science University, is “superunique,” and most likely helps account for the liver’s regenerative prowess.

    Scientists hope that the new insights into liver development and performance will yield novel therapies for the more than 100 disorders that afflict the organ, many of which are on the rise worldwide, in concert with soaring rates of obesity and diabetes.

    “It’s a funny thing,” said Valerie Gouon-Evans, a liver specialist at the Mount Sinai School of Medicine. “The liver is not a very sexy organ. It doesn’t look important. It just looks like a big blob.

    “But it is quietly vital, the control tower of the body,” and the hepatocytes that it is composed of “are astonishing.”

    The liver is our largest internal organ, weighing three and a half-pounds and measuring six inches long. The reddish-brown mass of four unevenly sized lobes sprawls like a beached sea lion across the upper right side of the abdominal cavity, beneath the diaphragm and atop the stomach.

    The organ is always flush with blood, holding about 13 percent of the body’s supply at any given time. Many of the liver’s unusual features are linked to its intimate association with blood.

    During fetal development, blood cells are born in the liver, and though that task later migrates to the bone marrow, the liver never loses its taste for the bodywide biochemical gossip that only the circulatory system can bring.

    Most organs have a single source of blood. The liver alone has two blood supplies, the hepatic artery conveying oxygen-rich blood from the heart, the hepatic portal vein dropping off blood drained from the intestines and spleen. That portal blood delivers semi-processed foodstuffs in need of hepatic massaging, conversion, detoxification, storage, secretion, elimination.

    “Everything you put in your mouth must go through the liver before it does anything useful elsewhere in the body,” Dr. Lok said.

    The liver likes its bloodlines leaky. In contrast to the well-sealed vessels that prevent direct contact between blood and most tissues of the body, the arteries and veins that snake through the liver are stippled with holes, which means they drizzle blood right onto the hepatocytes.

    The liver cells in turn are covered with microvilli — fingerlike protrusions that “massively enlarge” the cell surface area in contact with blood, said Dr. Markus Heim, a liver researcher at the University of Basel.

    “Hepatocytes are swimming in blood,” he said. “That’s what makes them so incredibly efficient at taking up substances from the blood.”

    As the master sampler of circulating blood, the liver keeps track of the body’s moment-to-moment energy demands, releasing glucose as needed from its stash of stored glycogen, along with any vitamins, minerals, lipids, amino acids or other micronutrients that might be required.

    New research suggests the liver may take a proactive, as well as a reactive, role in the control of appetite and food choice.

    Humans are famously fond of sweets, for example, presumably a legacy of our fruit-eating primate ancestors. But to gorge on sugar-rich foods, even in the relatively healthy format of a bucketful of Rainier cherries, could mean neglecting other worthy menu items.

    Reporting in the journal Cell Metabolism, Matthew Gillum of the University of Copenhagen and his colleagues showed that after exposure to a high-sugar drink, the liver seeks to dampen further sugar indulgence by releasing a signaling hormone called fibroblast growth factor 21, or FGF21.

    The effort is not always successful. For reasons that remain unclear, the hormone comes in active and feeble varieties, and the researchers found that people with a mutant version of FGF21 confessed to a lifelong passion for sweets.

    The scientists are searching for other liver-borne hormones that might influence the hunger for protein or fat.

    “It makes sense that the liver could be a nexus of metabolic control,” Dr. Gillum said. “At some level it knows more than the brain does about energy availability, and whether you’re eating too many pears.”

    The liver also keeps track of time. In a recent issue of the journal Cell, Ulrich Schibler of the University of Geneva and his colleagues described their studies of the oscillating liver, and how it swells and shrinks each day, depending on an animal’s normal circadian rhythms and feeding schedule.

    The researchers found that in mice, which normally eat at night and sleep during the day, the size of the liver expands by nearly half after dark and then retrenches come daylight. The scientists also determined the cause of the changing dimensions.

    “We wanted to know, is it just extra water or glycogen?” Dr. Schibler said. “Because that would be boring.”

    The researchers found that in mice, which normally eat at night and sleep during the day, the size of the liver expands by nearly half after dark and then retrenches come daylight. The scientists also determined the cause of the changing dimensions.

    “We wanted to know, is it just extra water or glycogen?” Dr. Schibler said. “Because that would be boring.”

    It wasn’t boring. “The total gemish, the total soup of the liver turns out to be different,” he said. Protein production in mouse hepatocytes rises sharply at night, followed by equivalent protein destruction during the day.

    Evidence suggests that a similar extravaganza of protein creation and destruction occurs in the human liver, too, but the timing is flipped to match our largely diurnal pattern.

    The researchers do not yet know why the liver oscillates, but Dr. Schibler suggested it’s part of the organ’s fastidious maintenance program.

    “The liver gets a lot of bad stuff coming through,” he said. “If you damage some of its components, you need to replace them.” By having a rhythm to that replacement, he said, “you keep the liver in a good state.”

    Adding to the liver’s repair protocol, Dr. Grompe of Oregon Health and Science University said, is the extreme plasticity of hepatocytes.

    He and others have shown that, through their extraordinary ability to handle multiple sets of chromosomes and still perform and divide normally, liver cells become almost like immune cells — genetically diverse enough to handle nearly any poison thrown at them.

    “Our ancestors didn’t have healthy refrigerated food,” he said. “They ate a lot of crap, probably literally, and the liver in prehistoric times was continuously bombarded with toxins. You need every mechanism there is to adapt to that.”

    The liver rose to the evolutionary challenge. So yes, I’m chopped liver — and proud.

    See the full article here .

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  • richardmitnick 6:49 am on May 30, 2017 Permalink | Reply
    Tags: , , Grand Canyon, NYT   

    From NYT: “A Creationist Wants Rocks to Study. The Grand Canyon Says No” 

    New York Times

    The New York Times

    MAY 29, 2017
    FERNANDA SANTOS

    1
    Officials at the Grand Canyon are in a dispute with a geologist who is a creationist and wants rocks from the canyon to study. Credit Richard Perry/The New York Times

    Did Noah’s flood create the Grand Canyon? Not a chance, say mainstream scientists, who maintain that the canyon’s layers of rocks were carved and chiseled by a persistent flow of water beginning some five million years ago. But Andrew A. Snelling — a geologist by training, a creationist by conviction — has a minority view, and he hoped to prove himself right.

    In November 2013, Dr. Snelling — he has a doctorate in geology from the University of Sydney, in Australia, where he was born — asked administrators of Grand Canyon National Park for permission to remove some 60 half-pound rocks from certain areas along the edges of the Colorado River, which snakes through the canyon.

    Last July, the administrators denied his request. This month, Dr. Snelling sued them, the National Park Service and the Interior Department, claiming the denial amounted to discrimination against his religious beliefs.

    In an interview on Thursday, Gary McCaleb, senior counsel for Alliance Defending Freedom, the conservative Christian legal defense group that is representing Dr. Snelling, said, “It’s one thing to debate the science, but to deny access to the data not based on the quality of a proposal or the nature of the inquiry, but on what you might do with it is an abuse of government power.”

    Heather Swift, a spokeswoman for the Interior Department, referred questions about the lawsuit to the Justice Department, which did not respond to a request for comment. Mr. McCaleb said that Parks Service officials reached out to him recently and that both sides would meet soon.

    As a young-Earth creationist, Dr. Snelling embraces a literal interpretation of the Bible’s Book of Genesis: God created the universe, Earth and all life in it in six days, and the flood caused rapid geological transformations. By these measures, Earth is not billions of years old, but only several thousand.

    His beliefs did not come up in his permit request, but he was no stranger to park officials, as he had guided many Biblical-themed rafting trips through the canyon and done research there. According to the lawsuit, the officials subjected him to cumbersome requirements, such as providing coordinates and photographs of each of the places from which he planned to collect rocks and submitting his proposal to peer reviews.

    The park also commissioned reviews of its own. One of them, by Peter Huntoon, a professor emeritus at the University of Wyoming, said the problem was not so much Dr. Snelling’s perspective, but the park’s adherence to its “narrowly defined institutional mandate predicated in part on the fact that ours is a secular society as per our Constitution.”

    See the full article here .

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  • richardmitnick 6:54 am on May 25, 2017 Permalink | Reply
    Tags: , , NYT, Rare Gene Mutations Inspire New Heart Drugs   

    From NYT: “Rare Gene Mutations Inspire New Heart Drugs” 

    New York Times

    The New York Times

    MAY 24, 2017
    GINA KOLATA

    1
    Anna Feurer learned she had unusually low triglyceride levels after having bloodwork at a corporate health fair. The discovery prompted researchers to recruit her and her family for a research study of their genetic makeup. Credit Jess T. Dugan for The New York Times.

    What if you carried a genetic mutation that left you nearly impervious to heart disease? What if scientists could bottle that miracle and use it to treat everyone else?

    In a series of studies, the most recent published on Wednesday, scientists have described two rare genetic mutations that reduce levels of triglycerides, a type of blood fat, far below normal. People carrying these genes seem invulnerable to heart disease, even if they have other risk factors.

    Drugs that mimic the effects of these mutations are already on the way, and many experts believe that one day they will become the next blockbuster heart treatments. Tens of millions of Americans have elevated triglyceride levels. Large genetic studies have consistently suggested a direct link to heart disease.

    Added to the existing arsenal of cholesterol-reducers and blood pressure medications, the new medications “will drive the final nail in the coffin of heart disease,” predicted Dr. John Kastelein, a professor of vascular medicine at the University of Amsterdam who was not involved in the new research.

    These experimental triglyceride-reducers are in early stages of development, however, and human trials have only just begun. At the moment, the optimism of researchers is rooted less in clinical trial data than in the fact that nature has produced strong evidence they should work.

    People like Anna Feurer may be walking proof.

    In 1994, Mrs. Feurer, then 40, attended a health fair held by her employer, Ralston Purina, in St. Louis. She rolled up her sleeve and let a technician take blood to measure her cholesterol.

    Later, the company doctor called her in and told her that her triglyceride levels were almost inconceivably low. And so were her levels of LDL, which raises the risk of heart disease, and HDL, which is linked to a lower risk. The results were so unusual that he encouraged her to see a specialist.

    “It was all an accident,” Mrs. Feurer recalled in an interview. That her single blood sample could lead to new treatments is “definitely amazing.”

    She went to Dr. Gustav Schonfeld at Washington University in Saint Louis. He asked Mrs. Feurer if she and others in her family might participate in a research study. She agreed, recruiting her immediate family and even a few cousins and aunts.

    Some had strikingly low triglyceride levels, some had normal levels, and some were in between, Dr. Schonfeld found. He tried for years to locate the gene responsible but failed. (Dr. Schonfeld died in 2011.)

    In 2009, he sent Mrs. Feurer’s DNA to Dr. Sekar Kathiresan, a cardiologist at Massachusetts General Hospital. He discovered that she carried mutations in both copies of a gene, ANGPTL3, involved in triglyceride metabolism. (Each individual carries two copies of a given gene, one from each parent.)

    As it turned out, three of her nine siblings also had no working copy of the gene and extremely low triglyceride levels. Three others had one mutated gene and one normal gene; these siblings had low triglyceride levels, but nowhere near as low as those with no functioning gene.

    The other three siblings had inherited two normal ANGPTL3 genes and had normal triglyceride levels.

    “The big question was, ‘Does this loss-of-function mutation reduce coronary risk?’” Dr. Daniel Rader of the University of Pennsylvania, who is an author of three of the recently published studies, said.

    Dr. Nathan O. Stitziel, a cardiologist at Washington University in Saint Louis, said the evidence so far was that people with Mrs. Feurer’s mutation, at least, seemed to be protected.

    Dr. Stitziel and his colleagues scanned Mrs. Feurer’s coronary arteries and those of two siblings who also had two mutated ANGPTL3 genes. Each one was free of plaque, the researchers recently reported in the Journal of the American College of Cardiology.

    One sibling had been a heavy smoker, had high blood pressure and even had Type 2 diabetes, a powerful risk factor for heart disease. Yet there was no plaque in his arteries.

    Dr. Stitziel went on to lead an international group of researchers who looked for mutations that destroyed the gene in 180,180 people. It was a rare event, occurring in just one in 309 people.

    But Dr. Stitziel and his colleagues discovered the mutation reduced heart attack risk by a third.

    The second line of evidence for these drugs originated with a study of Old Order Amish in Lancaster, Pa. About 5 percent appeared to have arteries that were clear of plaque and low levels of triglycerides.

    As it turned out, these lucky people had inherited a single mutated copy of another gene related to triglyceride production, called ApoC3. Researchers wanted desperately to find people who had inherited two mutated copies to see whether short-circuiting the gene might be safe.

    They began by searching genetic data collected from more than 200,000 people around the world — but to no avail. Then the scientists tried a different tack, focusing on participants in a heart disease study in Pakistan, where first cousins often marry and mutations like these are more easily handed down.

    The strategy worked. After combing the world and turning up nothing, the investigators discovered more than 100 in Pakistan who had mutations in both ApoC3 genes. And these people were healthy, with low levels of triglycerides, researchers reported last month in the journal Nature.

    Now, with surprising speed, companies are starting to test experimental drugs that mimic a loss of ApoC3 by blocking the ApoC3 protein.

    In addition, two companies, Regeneron and Ionis Pharmaceuticals, are now testing drugs based on the mutations in the same gene that was found in the Feurer family, company scientists and academic researchers reported on Wednesday in The New England Journal of Medicine.

    Both companies reported that in preliminary studies, drugs based on these mutations reduced triglycerides in people with elevated levels. Both also reported studies of the drugs in mice showing the drugs protected the animals from heart disease.

    “The basic bottom line is that the reductions in triglycerides with these things is pretty unprecedented,” George Yancopoulos, president and chief scientific officer at Regeneron, said. Still, it’s not yet clear to what extent this will prevent heart attacks.

    Even more significant may be the way in which these drugs were identified. Finding people who are impervious to a disease like heart disease can open a door to letting the rest of the population share their genetic luck.

    “It’s a huge advance,” said Dr. Christie Mitchell Ballantyne, chief of cardiology and cardiovascular research at Baylor College of Medicine and a consultant for Regeneron (although not for the triglyceride studies). “That doesn’t mean it’s easy.”

    Still, he added, “what we are seeing is a new approach toward drug development.”

    See the full article here .

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  • richardmitnick 2:08 pm on May 22, 2017 Permalink | Reply
    Tags: , , , In ‘Enormous Success’ Scientists Tie 52 Genes to Human Intelligence, NYT   

    From NYT: “In ‘Enormous Success,’ Scientists Tie 52 Genes to Human Intelligence” 

    New York Times

    The New York Times

    MAY 22, 2017
    Carl Zimmer

    1
    Blood samples from some participants in a new study of genes linked to intelligence were held at the U.K. Biobank, above. Credit Wellcome Trust

    In a significant advance in the study of mental ability, a team of European and American scientists announced on Monday that they had identified 52 genes linked to intelligence in nearly 80,000 people.

    These genes do not determine intelligence, however. Their combined influence is minuscule, the researchers said [Nature Genetics], suggesting that thousands more are likely to be involved and still await discovery. Just as important, intelligence is profoundly shaped by the environment.

    Still, the findings could make it possible to begin new experiments into the biological basis of reasoning and problem-solving, experts said. They could even help researchers determine which interventions would be most effective for children struggling to learn.

    “This represents an enormous success,” said Paige Harden, a psychologist at the University of Texas, who was not involved in the study.

    For over a century, psychologists have studied intelligence by asking people questions. Their exams have evolved into batteries of tests, each probing a different mental ability, such as verbal reasoning or memorization.

    In a typical test, the tasks might include imagining an object rotating, picking out a shape to complete a figure, and then pressing a button as fast as possible whenever a particular type of word appears.

    Each test-taker may get varying scores for different abilities. But over all, these scores tend to hang together — people who score low on one measure tend to score low on the others, and vice versa. Psychologists sometimes refer to this similarity as general intelligence.

    It’s still not clear what in the brain accounts for intelligence. Neuroscientists have compared the brains of people with high and low test scores for clues, and they’ve found a few.

    Brain size explains a small part of the variation, for example, although there are plenty of people with small brains who score higher than others with bigger brains.

    Other studies hint that intelligence has something to do with how efficiently a brain can send signals from one region to another.

    Danielle Posthuma, a geneticist at Vrije University Amsterdam and senior author of the new paper, first became interested in the study of intelligence in the 1990s. “I’ve always been intrigued by how it works,” she said. “Is it a matter of connections in the brain, or neurotransmitters that aren’t sufficient?”

    Dr. Posthuma wanted to find the genes that influence intelligence. She started by studying identical twins who share the same DNA. Identical twins tended to have more similar intelligence test scores than fraternal twins, she and her colleagues found.

    Hundreds of other studies have come to the same conclusion, showing a clear genetic influence on intelligence [Nature Genetics]. But that doesn’t mean that intelligence is determined by genes alone.

    Our environment exerts its own effects, only some of which scientists understand well. Lead in drinking water, for instance, can drag down test scores. In places where food doesn’t contain iodine, giving supplements to children can raise scores.

    Advances in DNA sequencing technology raised the possibility that researchers could find individual genes underlying differences in intelligence test scores. Some candidates were identified in small populations, but their effects did not reappear in studies on larger groups.

    So scientists turned to what’s now called the genome-wide association study: They sequence bits of genetic material scattered across the DNA of many unrelated people, then look to see whether people who share a particular condition — say, a high intelligence test score — also share the same genetic marker.

    In 2014, Dr. Posthuma was part of a large-scale study of over 150,000 people that revealed 108 genes linked to schizophrenia. But she and her colleagues had less luck with intelligence, which has proved a hard nut to crack for a few reasons.

    Standard intelligence tests can take a long time to complete, making it hard to gather results on huge numbers of people. Scientists can try combining smaller studies, but they often have to merge different tests together, potentially masking the effects of genes.

    As a result, the first generation of genome-wide association studies on intelligence failed to find any genes. Later studies managed to turn up promising results, but when researchers turned to other groups of people, the effect of the genes again disappeared.

    But in the past couple of years, larger studies relying on new statistical methods finally have produced compelling evidence that particular genes really are involved in shaping human intelligence.

    “There’s a huge amount of real innovation going on,” said Stuart J. Ritchie, a geneticist at the University of Edinburgh who was not involved in the new study.

    Dr. Posthuma and other experts decided to merge data from 13 earlier studies, forming a vast database of genetic markers and intelligence test scores. After so many years of frustration, Dr. Posthuma was pessimistic it would work.

    “I thought, ‘Of course we’re not going to find anything,’” she said.

    She was wrong. To her surprise, 52 genes emerged with firm links to intelligence. A dozen had turned up in earlier studies, but 40 were entirely new.

    But all of these genes together account for just a small percentage of the variation in intelligence test scores, the researchers found; each variant raises or lowers I.Q. by only a small fraction of a point.

    “It means there’s a long way to go, and there are going to be a lot of other genes that are going to be important,” Dr. Posthuma said.

    Christopher F. Chabris, a co-author of the new study at Geisinger Health System in Danville, Pa., was optimistic that many of those missing genes would come to light, thanks to even larger studies involving hundreds of thousands, perhaps millions, of people.

    “It’s just like astronomy getting better with bigger telescopes,” he said.

    In the new study, Dr. Posthuma and her colleagues limited their research to people of European descent because that raised the odds of finding common genetic variants linked to intelligence.

    But other gene studies have shown that variants in one population can fail to predict what people are like in other populations. Different variants turn out to be important in different groups, and this may well be the case with intelligence.

    “If you try to predict height using the genes we’ve identified in Europeans in Africans, you’d predict all Africans are five inches shorter than Europeans, which isn’t true,” Dr. Posthuma said.

    Studies like the one published today don’t mean that intelligence is fixed by our genes, experts noted. “If we understand the biology of something, that doesn’t mean we’re putting it down to determinism,” Dr. Ritchie said.

    As an analogy, he noted that nearsightedness is strongly influenced by genes. But we can change the environment — in the form of eyeglasses — to improve people’s eyesight.

    Dr. Harden predicted that an emerging understanding of the genetics of intelligence would make it possible to find better ways to help children develop intellectually. Knowing people’s genetic variations would help scientists measure how effective different strategies are.

    Still, Dr. Harden said, we don’t have to wait for such studies to change people’s environments for the better. “We know that lead harms children’s intellectual abilities,” she said. “There’s low-hanging policy fruit here.”

    For her part, Dr. Posthuma wants to make sense of the 52 genes she and her colleagues discovered. There are intriguing overlaps between their influence on intelligence and on other traits.

    The genetic variants that raise intelligence also tend to pop up more frequently in people who have never smoked. Some of them also are found more often in people who take up smoking but quit successfully.

    As for what the genes actually do, Dr. Posthuma can’t say. Four of them are known to control the development of cells, for example, and three do an assortment of things inside neurons.

    To understand what makes these genes special, scientists may need to run experiments on brain cells. One possibility would be to take cells from people with variants that predict high and low intelligence.

    She and her colleagues might coax them to develop into neurons, which could then grow into “mini-brains” — clusters of neurons that exchange signals in the laboratory. Researchers could then see if their genetic differences made them behave differently.

    “We can’t do it overnight,” Dr. Posthuma said, “but it’s something I hope to be able to do in the future.”

    See the full article here .

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  • richardmitnick 7:19 am on May 16, 2017 Permalink | Reply
    Tags: Magglio Boscarino, , NYT, Pompe disease, When the Immune System Thwarts Lifesaving Drugs   

    From NYT: “When the Immune System Thwarts Lifesaving Drugs” 

    New York Times

    The New York Times

    MAY 15, 2017
    GINA KOLATA

    1
    Magglio Boscarino, who has the genetic disorder Pompe disease, with his mother Becka at home, above, and at school. Credit Max Whittaker for The New York Times

    The miracle treatment that should have saved Becka Boscarino’s baby boy almost killed him.

    Doctors diagnosed her newborn son, Magglio, with Pompe disease, a rare and deadly genetic disorder that leads to a buildup of glycogen in the body. Left untreated, the baby would probably die before his first birthday.

    There is just one treatment: a series of infusions. But after the boy received his fifth dose, he turned blue, stopped breathing and slipped into anaphylactic shock.

    The problem? Eventually doctors discovered that Magglio’s body was producing antibodies to the very drug saving his life.

    It is a problem few patients and doctors have ever heard of; indeed, the phenomenon has not been systematically studied. But experts say what happened to Magglio has happened to many other patients taking many other drugs.

    The body’s immune system produces antibodies, blood proteins, in order to attack molecules the body recognizes as alien, often carried on viruses and bacteria. But antibodies also are deployed against other foreign substances, and this may include drugs given to patients.

    Antibodies directed against a particular drug can attach to the drug and completely neutralize its effects in the body. But there is no way to know in advance which patient is most likely to make them, or which drug is likely to trigger such a reaction in a large number of patients.

    “Once a drug is approved and out in the market, it is pretty rare that a clinician would measure antibodies,” said Dr. Mary Crow, a rheumatologist and physician in chief at the Hospital for Special Surgery in New York City. “There is no commercially available test.”

    In a paper published in March by The New England Journal of Medicine, Pfizer reported that in the final phase of testing a new drug to lower cholesterol, many of the 30,000 patients taking it had stopped responding to it.

    Their cholesterol levels, which had plunged when they began taking the drug, were rising again. As it turned out, the subjects had begun making antibodies to the drug.

    2
    Magglio needs a ventilator to breathe and plays on a baseball team for children with disabilities. His mother helps him bat. Credit Max Whittaker for The New York Times

    Pfizer was forced to stop the trial and pull the drug after investing billions of dollars. (Similar drugs, made by Amgen and Sanofi Regeneron did not elicit such antibodies and are now being sold.)

    The problem seems almost intractable.

    Drugs containing proteins can provoke these immune system reactions. Steve Danehy, a Pfizer spokesman, said that up to 87 percent of patients taking drugs known as monoclonal antibodies, for instance, will develop antibodies of their own that block the drug. (Pifzer’s experimental drug was a monoclonal.)

    Patients and their doctors often have no idea what has happened; patients notice only that a drug they take has stopped working. Doctors will switch them to a similar drug and hope for the best.

    But that strategy only works when there are alternatives. For some diseases, there are none.

    For the small subset of gout patients whose disease is extremely severe, for example, antibodies are “really a huge problem,” said Dr. Robert Terkeltaub, a gout specialist at the University of California, San Diego. There is only one drug that can help, and most patients develop antibodies that eventually block it.

    Medicine Stops Working

    For patients like Magglio Boscarino, finding a way to tamp down the immune system’s response to these drugs is a matter of life or death.

    He had seemed fine at birth, but soon developed what looked like a bad cold and congestion. When he did not get better, his doctors X-rayed his chest and discovered a very large heart.

    By the time Magglio was 6 months old, he was weak and lacked muscle tone. Then came the diagnosis of Pompe disease and the beginning of his treatments, infusions with an enzyme his body was failing to make.

    At first, Magglio improved. Within a few months, he was learning to sit up and to use his arms. His enlarged heart was shrinking. But his fifth treatment was a disaster.

    He fell into anaphylactic shock and stopped breathing. The doctors gave him oxygen and epinephrine, and eventually he recovered. They did not realize the drug was at fault, however, and two weeks later Magglio received another infusion — with the same result.

    3
    Becka Boscarino, and her son, Magglio at home. Magglio has Pompe disease, which causes a buildup of glycogen in the body. Untreated, it usually kills within the first year. Credit Max Whittaker for The New York Times

    Then doctors realized what the problem was. But because Magglio’s disease would worsen and kill him if he did not get the drug, his doctors kept hoping he might be able to tolerate repeated infusions.

    For a year and a half, the treatments continued, and Magglio suffered severe reactions even as his disease was progressing. Soon he could not breathe on his own, and a tube was inserted in his trachea. He could not sit up. At 2 years old, he had heart failure.

    “He was dying,” Ms. Boscarino said. “It was awful, so awful,”

    Magglio was hardly alone: Most babies with Pompe disease who received the only available treatment soon produced antibodies that rendered it useless.

    “We tried everything, but these babies did not make it,” said Dr. Priya Kishnani, a professor of pediatrics at Duke University.

    Dr. Kishnani realized she had to find a way to trick the immune system so it would leave the infused protein alone. Her idea was to give the babies a chemotherapy drug, rituximab, that wipes out cells that develop into antibody producers.

    Along with it, she tried giving the children methotrexate, which destroys many of the body’s white blood cells, and infusions of antibodies from pooled donors’ serum so the children would have a way to fight off infections.

    And for babies like Magglio, who already were making antibodies that blocked the drug they need, she added another drug — bortezomib — to eliminate those antibody-producing cells.

    As the children’s immune systems were brought under control, the treatments began to work again. “It was breathtaking,” Dr. Kishnani said. “We were able to rescue these babies.”

    Broadening the Approach

    The principles tried in children with this rare genetic condition may soon be applied to a wide range of patients. “I feel that Pompe opened up the field,” Dr. Kishnani said. “The more we talked about it, the more awareness there was of the role of antibodies.”

    4
    “The good news is that he is still alive,” Ms. Boscarino said. “But he is a complete rag doll. He mouths words a lot. He does not have a voice so he uses his eyes to use a computer screen to talk for him.” Credit Max Whittaker for The New York Times

    Already, scientists have begun clinical trials testing ways to help patients with very severe gout who make antibodies blocking their treatment. In one, investigators are altering the dose of the drug used to treat the disease and how often it is given.

    In another trial, researchers at Selecta Biosciences are testing an antibody-suppressing drug packaged in a biodegradable nanoparticle to be taken along with the drug the patient needs.

    At Brigham and Women’s Hospital in Boston, cardiologist Dr. Paul Ridker, who directed the Pfizer study, is taking a different tack.

    He wants to do a large genetic study to see if he can predict which patients will develop antibodies to the Pfizer drug and perhaps to other drugs that the immune system might see as foreign.

    “We probably have the best opportunity ever afforded to understand the cause of these antibodies,” Dr. Ridker said. “That would be very valuable for the development of future drugs if you could say, ‘This one patient out of 20 should not take this drug.’”

    It would mean, too, that drugs that might have been abandoned could be developed for the patients who can tolerate them.

    Magglio received the treatment to tamp down his immune system developed in Dr. Kishnani’s lab, and it seems to have worked. “The good news is that he is still alive,” his mother said.

    “But he is a complete rag doll. He mouths words a lot. He does not have a voice so he uses his eyes to use a computer screen to talk for him.”

    Magglio needs a ventilator to breathe, as he has since he was 9 months old. But he has his own sign language, using his tongue, his mother said.

    Still, he goes to school — general education, 4th grade — and even plays on a baseball team for children with disabilities. His mother helps him bat.

    “He’s a big Yankees fan,” Ms. Boscarino says.

    See the full article here .

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  • richardmitnick 6:34 am on May 16, 2017 Permalink | Reply
    Tags: , Brenda Milner, Eminent Brain Scientist, Is ‘Still Nosy’ at 98, NYT,   

    From NYT: Women in STEM- “Brenda Milner, Eminent Brain Scientist, Is ‘Still Nosy’ at 98” 

    New York Times

    The New York Times

    MAY 15, 2017
    BENEDICT CAREY

    1
    Dr. Brenda Milner in her office at the Montreal Neurological Institute and Hospital last month. Credit Aaron Vincent Elkaim for The New York Times

    The driving instructor wiped his brow with a handkerchief, and not just because of the heat. His student — a grown woman, squinting over the dashboard — was ramming the curb in an effort to parallel park.

    “We reached an agreement, right then and there: He let me pass the test, and I promised never to drive,” Brenda Milner said, smiling to herself at the decades-old memory. “You see, my spatial skills aren’t so good. That’s primarily a right-brain function.”

    Dr. Milner, a professor of psychology in the department of neurology and neurosurgery at McGill University in Montreal, is best known for discovering the seat of memory in the brain, the foundational finding of cognitive neuroscience. But she also has a knack for picking up on subtle quirks of human behavior and linking them to brain function — in the same way she had her own, during the driving test.

    At 98, Dr. Milner is not letting up in a nearly 70-year career to clarify the function of many brain regions — frontal lobes, and temporal; vision centers and tactile; the left hemisphere and the right — usually by painstakingly testing people with brain lesions, often from surgery. Her prominence long ago transcended gender, and she is impatient with those who expect her to be a social activist. It’s science first with Dr. Milner, say close colleagues, in her lab and her life.

    Perched recently on a chair in her small office, resplendent in a black satin dress and gold floral pin and banked by moldering towers of old files, she volleyed questions rather than answering them. “People think because I’m 98 years old I must be emerita,” she said. “Well, not at all. I’m still nosy, you know, curious.”

    Dr. Milner continues working, because she sees no reason not to. Neither McGill nor the affiliated Montreal Neurological Institute and Hospital has asked her to step aside. She has funding: In 2014 she won three prominent achievement awards, which came with money for research. She has a project: a continuing study to investigate how the healthy brain’s intellectual left hemisphere coordinates with its more aesthetic right one in thinking and memory.

    And she has adapted to the life as an undeniably senior senior researcher. “I come into the office about three days a week or so, that is plenty,” Dr. Milner said.

    “And I have some rules,” she added. “I will take on postdoctoral students, but not graduate students. Graduate students need to know you’ll be around for five years or so, and well” — she chuckled, looking up at the ceiling — “well, it’s very difficult if they have to switch to someone else, you know.”

    Dr. Milner’s current project is, appropriately enough, an attempt to weave together two of brain science’s richest strands of research, both of which she helped originate a lifetime ago.

    One is the biology of memory.

    Dr. Milner changed the course of brain science for good as a newly minted Ph.D. in the 1950s by identifying the specific brain organ that is crucial to memory formation.

    She did so by observing the behavior of a 29-year-old Connecticut man who had recently undergone an operation to relieve severe epileptic seizures. The operation was an experiment: On a hunch, the surgeon suctioned out two trenches of tissue from the man’s brain, one from each of his medial temporal lobes, located deep below the skull about level with the ears. The seizures subsided.

    But the patient, an assembly line worker named Henry Molaison, was forever altered. He could no longer form new memories.

    Concerned and intrigued, the surgeon contacted Dr. Wilder Penfield and Dr. Milner at the Montreal Neurological Institute, who had previously reported on two cases of amnesia in patients treated there. Thus began a now-famous collaboration.

    She started taking the night train from Montreal to give a battery of tests to Mr. Molaison, who was known in research reports as H. M. to protect his privacy.

    In a landmark 1957 paper Dr. Milner wrote with Mr. Molaison’s surgeon, she concluded that the medial temporal areas — including, importantly, an organ called the hippocampus — must be critical to memory formation. That finding, though slow to sink in, would upend the accepted teaching at the time, which held that no single area was critical to supporting memory.

    Dr. Milner continued to work with Mr. Molaison and later showed that his motor memory was intact: He remembered how to perform certain physical drawing tests, even if he had no memory of learning them.

    The finding, reported in 1962, demonstrated that there are at least two systems in the brain for processing memory: one that is explicit and handles names, faces and experiences; and another that is implicit and incorporates skills, like riding a bike or playing a guitar.

    “I clearly remember to this day my excitement, sitting there with H. M. and watching this beautiful learning curve develop right there in front of me,” Dr. Milner said. “I knew very well I was witnessing something important.”

    The other strand her new research project incorporates is so-called hemispheric specialization: how the brain’s two halves, the right and the left, divide up its mental labor.

    In the early 1960s, scientists including Dr. Milner had shown that the brain’s left hemisphere specializes in language and reasoning, and that the right makes holistic, more aesthetic judgments — it is more sensual than intellectual.

    Still, in people with brain injuries, particularly to the frontal lobes behind the forehead, the two hemispheres could compensate by working together in subtle ways.

    In an era before precise imaging technology, standard pencil-and-paper testing could not easily detect the deficits caused by specific injuries.

    In a series of studies, and using the same knack for exhaustive observation, Dr. Milner demonstrated that several kinds of tests could help characterize frontal lobe injuries. One of these, for example, is called the verbal fluency test, which assesses a person’s ability to generate words in certain categories or beginning with certain letters — a test of left hemisphere integrity.

    “She didn’t just give the person a test and mark down the score,” Dr. Marilyn Jones-Gotman, a longtime friend and colleague, said. “No, she sat down with people, paid attention to everything they did and said, and wrote it all down. That all went into the record, and gave you clues to what was actually going on in their minds that the scores by themselves couldn’t.”

    The new project is aimed at understanding how hemispheric coordination aids memory retrieval under normal circumstances, in people without brain injuries. Dr. Milner leads a research team that has been taking exhaustive M.R.I. brain images from participants while they solve problems and take memory tests.

    Does the artistic right hemisphere provide clues to help its more logic-oriented other half retrieve words? If so, which kinds of clues seem most powerful?

    In one experiment, participants in the brain scanner tried to recall a list of words they had just studied. Some of those words were concrete, like dog or house, conjuring specific imagery; others, like concept or strategy, were not. The scans carefully track activation across hemispheres moment to moment, as retrieval happens.

    “We’re just going through the data from our current study now,” Dr. Milner said, gesturing through the open doorway to Ami Tsuchida, who was working on a computer

    For this particular experiment, Dr. Tsuchida said, “We’re looking at the pattern of interactions between left and right hippocampus for words rated as highly imageable relative to those rated as not very imageable” to see if there’s any difference.

    The findings hold tremendous potential to help people with early dementia, some brain injuries and even learning disabilities.

    “People with early signs of dementia can have trouble with imagery, and by the time the disease is advanced they’ve lost that ability,” said Joelle Crane, a clinical psychologist at the Montreal Neurological Institute. “One area this new work might help us with is in training people to learn in a more visual way.”

    For Dr. Milner, after a lifetime exploring the brain, the motive for the work is personal as well as professional. “I live very close; it’s a 10-minute walk up the hill,” she said. “So it gives me a good reason to come in regularly.”

    See the full article here .

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  • richardmitnick 10:45 am on April 20, 2017 Permalink | Reply
    Tags: , , NYT   

    From NYT: “Is It O.K. to Tinker With the Environment to Fight Climate Change?” 

    New York Times

    The New York Times

    APRIL 18, 2017
    JON GERTNER

    Scientists are investigating whether releasing tons of particulates into the atmosphere might be good for the planet. Not everyone thinks this is a good idea.

    1

    For the past few years, the Harvard professor David Keith has been sketching this vision: Ten Gulfstream jets, outfitted with special engines that allow them to fly safely around the stratosphere at an altitude of 70,000 feet, take off from a runway near the Equator. Their cargo includes thousands of pounds of a chemical compound — liquid sulfur, let’s suppose — that can be sprayed as a gas from the aircraft. It is not a one-time event; the flights take place throughout the year, dispersing a load that amounts to 25,000 tons. If things go right, the gas converts to an aerosol of particles that remain aloft and scatter sunlight for two years. The payoff? A slowing of the earth’s warming — for as long as the Gulfstream flights continue.

    Keith argues that such a project, usually known as solar geoengineering, is technologically feasible and — with a back-of-the-envelope cost of under $1 billion annually — ought to be fairly cheap from a cost-benefit perspective, considering the economic damages potentially forestalled: It might do good for a world unable to cut carbon-dioxide emissions enough to prevent further temperature increases later this century.

    What surprised me, then, as Keith paced around his Harvard office one morning in early March, was his listing all the reasons humans might not want to hack the environment. “Actually, I’m writing a paper on this right now,” he said. Most of his thoughts were related to the possible dangers of trying to engineer our way out of a climate problem of nearly unimaginable scientific, political and moral complexity. Solar geoengineering might lead to what some economists call “lock-in,” referring to the momentum that a new technology, even one with serious flaws, can assume after it gains a foothold in the market. The qwerty keyboard is one commonly cited example; the internal combustion engine is another. Once we start putting sulfate particles in the atmosphere, he mused, would we really be able to stop?

    Another concern, he said, is “just the ethics about messing with nature.” Tall, wiry and kinetic, with thinning hair and a thick beard that gives him the look of the backcountry skier he is, Keith proudly showed me the framed badge that his father, a biologist, wore when he attended the landmark United Nations Conference on the Human Environment in Stockholm in 1972. Now 53, Keith has taken more wilderness trips — hiking, rock climbing, canoeing — than he can properly recall, and for their recent honeymoon, he and his wife were dropped off by helicopter 60 miles from the nearest road in northern British Columbia. “It was quite rainy,” he told me, “and that ended up making it even better.” So the prospect of intentionally changing the climate, he confessed, is not just unpleasant — “it initially struck me as nuts.”

    It still strikes him as a moral hazard, to use a term he borrows from economics. A planet cooled by an umbrella of aerosol particles — an umbrella that works by reflecting back into space, say, 1 percent of the sun’s incoming energy — might give societies less incentive to adopt greener technologies and radically cut carbon emissions. That would be disastrous, Keith said. The whole point of geoengineering is not to give us license to forget about the buildup of CO₂. It’s to lessen the ill effects of the buildup and give us time to transition to cleaner energy.

    Beyond these conceivable dangers, though, a more fundamental problem lurks: Solar geoengineering simply might not work. It has been a subject of intense debate among climate scientists for roughly a decade. But most of what we know about its potential effects derives from either computer simulations or studies on volcanic eruptions like that of Mount Pinatubo in 1991, which generated millions of tons of sunlight-scattering particulates and might have cooled the planet by as much as 0.5 degrees Celsius, or nearly 1 degree Fahrenheit. The lack of support for solar geoengineering’s efficacy informs Keith’s thinking about what we should do next. Actively tinkering with our environment — fueling up the Gulfstream jets and trying to cool things down — is not something he intends to try anytime soon, if ever. But conducting research is another matter.

    A decade ago, when Keith was among the few American scientists to advocate starting a geoengineering research program, he was often treated at science conferences as an outlier. “People would sort of inch away or, really, tell me I shouldn’t be doing this,” he said. Geoengineering was seen as a scientific taboo and Keith its dark visionary. “The preconception was that I was some kind of Dr. Strangelove figure,” he told me — “which I didn’t like.”

    Attitudes appear to have changed over the past few years, at least in part because of the continuing academic debates and computer-modeling studies. The National Academy of Sciences endorsed the pursuit of solar geoengineering research in 2015, a stance also taken in a later report by the Obama administration. A few influential environmental groups, like the Natural Resources Defense Council and the Environmental Defense Fund, now favor research.

    In the meantime, Keith’s own work at Harvard has progressed. This month, he is helping to start Harvard’s Solar Geoengineering Research Program, a broad endeavor that begins with $7 million in funding and intends to reach $20 million over seven years. One backer is the Hewlett Foundation; another is Bill Gates, whom Keith regularly advises on climate change. Keith is planning to conduct a field experiment early next year by putting particles into the stratosphere over Tucson.

    The new Harvard program is not merely intent on getting its concepts out of the lab and into the field, though; a large share of its money will also be directed to physical and social scientists at the university, who will evaluate solar geoengineering’s environmental dangers — and be willing to challenge its ethics and practicality. Keith told me, “It’s really important that we have a big chunk of the research go to groups whose job will be to find all the ways that it won’t work.” In other words, the technology that Keith has long believed could help us ease our predicament — “the nuclear option” for climate, as one opponent described it to me, to be considered only when all else has failed — will finally be investigated to see whether it is a reasonable idea. At the same time, it will be examined under the premise that it may in fact be a very, very bad one.

    Climate change already presents a demoralizing array of challenges — melting ice sheets and species extinctions — but the ultimate severity of its impacts depends greatly on how drastically technology and societies can change over the next few decades. The growth of solar and wind power in recent years, along with an apparent decrease in coal use, suggest that the global community will succeed in curtailing CO₂ emissions. Still, that may not happen nearly fast enough to avert some dangerous consequences. As Keith likes to point out, simply reducing emissions doesn’t reverse global warming. In fact, even if annual global CO₂ emissions decrease somewhat, the total atmospheric CO₂ may continue to increase, because the gas is so slow to dissipate. We may still be living with damaging amounts of atmospheric carbon dioxide a half-century from now, with calamitous repercussions. The last time atmospheric CO₂ levels were as elevated as they are today, three million years ago, sea levels were most likely 45 feet higher, and giant camels roamed above the Arctic Circle.

    Recently, I met with Daniel Schrag, who is the head of the Harvard University Center for the Environment, an interdisciplinary teaching and research department. Schrag, who helped recruit Keith to Harvard, painted a bleak picture of our odds of keeping global temperatures from rising beyond levels considered safe by many climate scientists. When you evaluate the time scales involved in actually switching our energy systems to cleaner fuels, Schrag told me, “the really depressing thing is you start to understand why any of these kinds of projections — for 2030 or 2050 — are absurd.” He went on: “Are they impossible? No. I want to give people hope, too. I’d love to make this happen. And we have made a lot of progress on some things, on solar, on wind. But the reality is we haven’t even started doing the hard stuff.”

    Schrag described any kind of geoengineering as “at best an imperfect solution that is operationally extremely challenging.” Yet to Schrag and Keith, the political and technical difficulties associated with a rapid transition to a zero-carbon-emissions world make it sensible to look into geoengineering research. There happens to be a number of different plans for how to actually do it, however — including the fantastical (pumping seawater onto Antarctica to combat sea-level rise) and the impractical (fertilizing oceans with iron to foster the growth of algae, which would absorb more CO₂). Some proposals involve taking carbon out of the air, using either immense plant farms or absorption machines. (Keith is involved with such sequestration technology, which faces significant hurdles in terms of cost and feasibility.) Another possible approach would inject salt crystals into clouds over the ocean to brighten them and cool targeted areas, like the dying Great Barrier Reef. Still, the feeling among Keith and his colleagues is that aerosols sprayed into the atmosphere might be the most economically and technologically viable approach of all — and might yield the most powerful global effect.

    It is not a new idea. In 2000, Keith published a long academic paper on the history of weather and climate modification, noting that an Institute of Rainmaking was established in Leningrad in 1932 and that American engineers began a cloud-seeding campaign in Vietnam a few decades later. A report issued in 1965 by President Lyndon B. Johnson’s administration called attention to the dangers of increasing concentrations of CO₂ and, anticipating Keith’s research, speculated that a logical response might be to change the albedo, or reflectivity, of the earth. To Keith’s knowledge, though, there have been only two actual field experiments so far. One, by a Russian scientist in 2009, released aerosols into the lower atmosphere via helicopter and appears to have generated no useful data. “It was a stunt,” Keith says. Another was a modest attempt at cloud brightening a few years ago by a team at the Scripps Institution of Oceanography at the University of California, San Diego.

    Downstairs from Keith’s Harvard office, there is a lab cluttered with students fiddling with pipettes and arcane scientific instruments. When I visited in early March, Zhen Dai, a graduate student who works with Keith, was engaged with a tabletop apparatus, a maze of tubes and pumps and sensors, meant to study how chemical compounds interact with the stratosphere. For the moment, Keith’s group is leaning toward beginning its field experiments with ice crystals and calcium carbonate — limestone — that has been milled to particles a half-micron in diameter, or less than 1/100th the width of a human hair. They may eventually try a sulfur compound too. The experiment is called Scopex, which stands for Stratospheric Controlled Perturbation Experiment. An instrument that can disperse an aerosol of particles — say, several ounces of limestone dust — will be housed in a gondola that hangs beneath a balloon that ascends to 70,000 feet. The whole custom-built contraption, whose two small propellers will be steered from the ground, will also include a variety of sensors to collect data on any aerosol plume. Keith’s group will measure the sunlight-scattering properties of the plume and evaluate how its particles interact with atmospheric gases, especially ozone. The resulting data will be used by computer models to try to predict larger-scale effects.

    But whether a scientist should be deliberately putting foreign substances into the atmosphere, even for a small experiment like this, is a delicate question. There is also the difficulty of deciding on how big the atmospheric plumes should get. When does an experiment become an actual trial run? Ultimately, how will the scientists know if geoengineering really works without scaling it up all the way?

    Keith cites precedents for his thinking: a company that scatters cremation ashes from a high-altitude balloon, and jet engines, whose exhaust contains sulfates. But the crux of the problem that Harvard’s Solar Geoengineering Research Program wrestles with is intentionality. Frank Keutsch, a professor of atmospheric sciences at Harvard who is designing and running the Scopex experiments with Keith, told me: “This effort with David is very different from all my other work, because for those other field experiments, we’ve tried to measure the atmosphere and look at processes that are already there. You’re not actually changing nature.” But in this case, Keutsch agrees, they will be.

    During one of our conversations, Keith suggested that I try to flip my thinking for a moment. “What if humanity had never gotten into fossil fuels,” he posed, “and the world had gone directly to generating energy from solar or wind power?” But then, he added, what if in this imaginary cleaner world there was a big natural seep of a heat-trapping gas from within the earth? Such events have happened before. “It would have all the same consequences that we’re worried about now, except that it’s not us doing the CO₂ emissions,” Keith said. In that case, the reaction to using geoengineering to cool the planet might be one of relief and enthusiasm.

    In other words, decoupling mankind’s actions — the “sin,” as Keith put it, of burning fossil fuels — from our present dilemma can demonstrate the value of climate intervention. “No matter what, if we emit CO₂, we are hurting future generations,” Keith said. “And it may or may not be true that doing some solar geo would over all be a wise thing to do, but we don’t know yet. That’s the reason to do research.”

    There are risks, undeniably — some small, others potentially large and terrifying. David Santillo, a senior scientist at Greenpeace, told me that some modeling studies suggest that putting aerosols in the atmosphere, which might alter local climates and rain patterns and would certainly affect the amount of sunlight hitting the earth, could have a significant impact on biodiversity. “There’s a lot more we can do in theoretical terms and in modeling terms,” Santillo said of the Harvard experiments, “before anyone should go out and do this kind of proof-of-concept work.” Alan Robock, a professor of atmospheric sciences at Rutgers, has compiled an exhaustive list of possible dangers. He thinks that small-scale projects like the Scopex experiment could be useful, but that we don’t know the impacts of large-scale geoengineering on agriculture or whether it might deplete the ozone layer (as volcanic eruptions do). Robock’s list goes on from there: Solar geoengineering would probably reduce solar-electricity generation. It would do nothing to reduce the increasing acidification of the oceans, caused by seawater absorbing carbon dioxide. A real prospect exists, too, that if solar geoengineering efforts were to stop abruptly for any reason, the world could face a rapid warming even more dangerous than what’s happening now — perhaps too fast for any ecological adaptation.

    Keith is well aware of Robock’s concerns. He also makes the distinction that advocating research is not the same as advocating geoengineering. But the line can blur. Keith struck me as having a fair measure of optimism that his research can yield insights into materials and processes that can reduce the impacts of global warming while averting huge risks. For instance, he is already encouraged by computer models that suggest the Arctic ice cap, which has shrunk this year to the smallest size observed during the satellite era, could regrow under cooler conditions brought on by light-scattering aerosols. He also believes that the most common accusation directed against geoengineering — that it might disrupt precipitation patterns and lead to widespread droughts — will prove largely unfounded.

    But Keith is not trained as an atmospheric scientist; he’s a hands-on physicist-engineer who likes to take machinery apart. There are deep unknowns here. Keutsch, for one, seems uncertain about what he will discover when the group actually tries spraying particulates high above the earth. The reduction of sunlight could adversely affect the earth’s water cycle, for example. “It really is unclear to me if this approach is feasible,” he says, “and at this point we know far too little about the risks. But if we want to know whether it works, we have to find out.”

    Finally, what if something goes wrong either in research or in deployment? David Battisti, an atmospheric scientist at the University of Washington, told me, “It’s not obvious to me that we can reduce the uncertainty to anywhere near a tolerable level — that is, to the level that there won’t be unintended consequences that are really serious.” While Battisti thought Keith’s small Scopex experiment posed little danger — “The atmosphere will restore itself,” he said — he noted that the whole point of the Harvard researchers’ work is to determine whether solar geoengineering could be done “forever,” on a large-scale, round-the-clock basis. When I asked Battisti if he had issues with going deeper into geoengineering research, as opposed to geoengineering itself, he said: “Name a technology humans have developed that they haven’t used. I can’t think of any. So we can work on this for sure. But we are in this dilemma: Once we do develop this technology, it will be tempting to use it.”

    Suppose Keith’s research shows that solar geoengineering works. What then? The world would need to agree where to set the global thermostat. If there is no consensus, could developed nations impose a geoengineering regimen on poorer nations? On the second point, if this technology works, it would arguably be unethical not to use it, because the world’s poorest populations, facing drought and rising seas, may suffer the worst effects of a changing climate.

    In recent months, a group under the auspices of the Carnegie Council in New York, led by Janos Pasztor, a former United Nations climate official, has begun to work through the thorny international issues of governance and ethics. Pasztor told me that this effort will most likely take four years. And it is not lost on him — or anyone I spoke with in Keith’s Harvard group — that the idea of engineering our environment is taking hold as we are contemplating the engineering of ourselves through novel gene-editing technologies. “They both have an effect on shaping the pathway where human beings are now and where will they be,” says Sheila Jasanoff, a professor of science and technology studies at Harvard who sometimes collaborates with Keith. Jasanoff also points out that each technology potentially enables rogue agents to act without societal consent.

    This is a widespread concern. We might reach a point at which some countries pursue geoengineering, and nothing — neither costs nor treaties nor current technologies — can stop them. Pasztor sketched out another possibility to me: “You could even have a nightmare scenario, where a country decides to do geoengineering and another country decides to do counter-geoengineering.” Such a countermeasure could take the form of an intentional release of a heat-trapping gas far more potent than CO₂, like a hydrochlorofluorocarbon. One of Schrag’s main concerns, in fact, is that geoengineering a lower global temperature might preserve ecosystems and limit sea-level rise while producing irreconcilable geopolitical frictions. “One thing I can’t figure out,” he told me, “is how do you protect the Greenland ice sheet and still have Russia have access to its northern ports, which they really like?” Either Greenland and Siberia will melt, or perhaps both can stay frozen. You probably can’t split the difference.

    For the moment, and perhaps for 10 or 20 years more, these are mere hypotheticals. But the impacts of climate change were once hypotheticals, too. Now they’ve become possibilities and probabilities. And yet, as Tom Ackerman, an atmospheric scientist at the University of Washington, said at a recent discussion among policy makers that I attended in Washington: “We are doing an experiment now that we don’t understand.” He was not talking about geoengineering; he was observing that the uncertainty about the potential risks of geoengineering can obscure the fact that there is uncertainty, too, about the escalating disasters that may soon result from climate change.

    His comment reminded me of a claim made more than a half-century ago, long before the buildup of CO₂ in the atmosphere had become the central environmental and economic problem of our time. Two scientists, Roger Revelle and Hans Suess, wrote in a scientific paper, “Human beings are now carrying out a large-scale geophysical experiment of a kind that could not have happened in the past nor be reproduced in the future.”

    If anything could sway a fence-sitter to consider whether geoengineering research makes sense, perhaps it is this. The fact is, we are living through a test already.

    See the full article here .

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  • richardmitnick 8:24 am on April 19, 2017 Permalink | Reply
    Tags: , Climate Change Reroutes a Yukon River in a Geological Instant, , , , Kaskawulsh Glacier, NYT, Slims River Valley   

    From NYT: “Climate Change Reroutes a Yukon River in a Geological Instant” 

    New York Times

    The New York Times

    APRIL 17, 2017
    JOHN SCHWARTZ

    1
    An aerial view of the ice canyon that now carries meltwater from the Kaskawulsh Glacier, on the right, away from the Slims River. “River piracy” refers to one river capturing and diverting the flow of another. Credit Dan Shugar/University of Washington-Tacoma

    In the blink of a geological eye, climate change has helped reverse the flow of water melting from a glacier in Canada’s Yukon, a hijacking that scientists call “river piracy.”

    This engaging term refers to one river capturing and diverting the flow of another. It occurred last spring at the Kaskawulsh Glacier, one of Canada’s largest, with a suddenness that startled scientists.

    A process that would ordinarily take thousands of years — or more — happened in just a few months in 2016.

    Much of the meltwater from the glacier normally flows to the north into the Bering Sea via the Slims and Yukon Rivers. A rapidly retreating and thinning glacier — accelerated by global warming — caused the water to redirect to the south, and into the Pacific Ocean.

    Last year’s unusually warm spring produced melting waters that cut a canyon through the ice, diverting more water into the Alsek River, which flows to the south and on into Pacific, robbing the headwaters to the north.

    2
    Jim Best, a researcher, measuring water levels on the lower-flowing Slims River in early September. Credit Dan Shugar/University of Washington-Tacoma

    The scientists concluded that the river theft “is likely to be permanent.”

    Daniel Shugar, an assistant professor of geoscience at the University of Washington-Tacoma, and colleagues described the phenomenon in a paper published on Monday in the journal Nature Geoscience.

    River piracy has been identified since the 19th century by geologists, and has generally been associated with events such as tectonic shifts and erosion occurring thousands or even millions of years ago. Those earlier episodes of glacial retreat left evidence of numerous abandoned river valleys, identified through the geological record.

    In finding what appears to be the first example of river piracy observed in modern times, Professor Shugar and colleagues used more recent technology, including drones, to survey the landscape and monitor the changes in the water coursing away from the Kaskawulsh Glacier.

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    Kaskawulsh glacier junction from air
    29 August 2014
    Author Gstest

    The phenomenon is unlikely to occur so dramatically elsewhere, Professor Shugar said in a telephone interview, because the glacier itself was forming a high point in the landscape and serving as a drainage divide for water to flow one way or another. As climate change causes more glaciers to melt, however, he said “we may see differences in the river networks and where rivers decide to go.”

    Changes in the flow of rivers can have enormous consequences for the landscape and ecosystems of the affected areas, as well as water supplies. When the shift abruptly reduced water levels in Kluane Lake, the Canadian Broadcasting Corporation reported, it left docks for lakeside vacation cabins — which can be reached only by water — high and dry.

    The riverbed of the Slims River basin, now nearly dry, experienced frequent and extensive afternoon dust storms through the spring and summer of last year, the paper stated.

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    The ice-walled canyon at the terminus of the Kaskawulsh Glacier, with recently collapsed ice blocks. This canyon now carries almost all meltwater from the toe of the glacier down the Kaskawulsh Valley and toward the Gulf of Alaska. Credit Jim Best/University of Illinois

    The impacts of climate change, like sea level rise or the shrinkage of a major glacier, are generally measured over decades, not months as in this case. “It’s not something you could see if you were just standing on the beach for a couple of months,” Professor Shugar said.

    The researchers concluded that the rerouted flow from the glacier shows that “radical reorganizations of drainage can occur in a geologic instant, although they may also be driven by longer-term climate change.” Or, as a writer for the CBC put it in a story about the phenomenon last year, “It’s a reminder that glacier-caused change is not always glacial-paced.”

    4
    Looking up the Slims River Valley, from the south end of Kluane Lake. The river used to flow down the valley from the Kaskawulsh glacier. (Sue Thomas)

    The underlying message of the new research is clear, said Dr. Shugar in a telephone interview. “We may be surprised by what climate change has in store for us — and some of the effects might be much more rapid than we are expecting.”

    The Nature Geoscience paper is accompanied by an essay from Rachel M. Headley, an assistant professor of geoscience and glacier expert at the University of Wisconsin-Parkside.

    “That the authors were able to capture this type of event almost as it was happening is significant in and of itself,” she said in an interview via email. As for the deeper significance of the incident, she said, “While one remote glacial river changing its course in the Yukon might not seem like a particularly big deal, glacier melt is a source of water for many people, and the sediments and nutrients that glacier rivers carry can influence onshore and offshore ecological environments, as well as agriculture.”

    Her article in Nature Geoscience concludes that this “unique impact of climate change” could have broad consequences. “As the world warms and more glaciers melt, populations dependent upon glacial meltwater should pay special attention to these processes.”

    Another glacier expert not involved in the research, Brian Menounos of the University of Northern British Columbia, said that while glaciers have waxed and waned as a result of natural forces over the eons, the new paper and his own research underscore the fact that the recent large-scale retreat of glaciers shows humans and the greenhouse gases they produce are reshaping the planet. “Clearly, we’re implicated in many of those changes,” he said.

    See the full article here .

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  • richardmitnick 7:43 am on April 4, 2017 Permalink | Reply
    Tags: , , NYT, We Have Some God News on the California Drought. Take a Look   

    From NYT: “We Have Some God News on the California Drought. Take a Look.” 

    New York Times

    The New York Times

    1

    MARCH 22, 2017
    MIKE McPHATE
    DEREK WATKINS
    JIM WILSON

    The majestic beauty of California’s Sierra Nevada never fails to impress. But the mountain range, which stretches hundreds of miles, is much more than a stunning vista. It’s a linchpin that helps make living in an arid state possible.

    That’s because one of California’s most important water supplies is melted snow. Each spring and summer, the Sierra sends runoff down its slopes that recharges rivers and reservoirs, allowing crops to be irrigated and drinking glasses to be filled.

    Knowing with precision how much snow has accumulated is crucial for farmers and water managers.

    That’s where a mapping project at NASA’s Jet Propulsion Laboratory known as the Airborne Snow Observatory comes in.

    2

    Using measurements gathered by specialized instruments on a plane, scientists have been able to gain an unprecedented understanding of the amount of water present in the Sierra’s snow.

    This year, after California’s very wet winter, the totals have been remarkably big.

    Using the NASA data, we compared this year’s snowpack with that of 2015, when the state was in the grip of drought (which, at least officially, is still ongoing). In the interactive maps below, the white areas had a meter, or 3.3 feet, or more of snow on the ground in March.

    High in the mountains, this year’s snow blankets the ground in layers tens of feet deep in many places.

    At the lower elevations around the Hetch Hetchy reservoir, which collects most of the melting snow runoff in this area and supplies water to millions, there was almost no snow to speak of in 2015. This year, the snowpack reached down to within a few hundred feet of the reservoir’s edge.

    These maps show parts of the Tuolumne Basin, which in late February was blanketed by 1.2 million acre-feet of snow-water equivalent, or the amount of water that would result if the snow were instantly melted.

    That’s about 10 times the amount as the same time in 2015, said Thomas Painter, a snow hydrologist at the NASA Jet Propulsion Laboratory/California Institute of Technology, who leads the NASA program.

    He added, “And it keeps on coming.”

    The pattern has held for the central Sierra region as a whole:

    3

    The airborne observatory has been detecting snow depths in the mountains ranging from a few feet at lower elevations to more than 70 feet in avalanche areas.

    “Some of the snowdrifts have faces of 25 to 40 feet,” said Jeffrey Payne, a water resources manager at the Friant Water Authority who has analyzed the NASA data. “So we’ve got some pretty serious snow.”

    4
    Strong winds created huge snowdrifts near the western cliffs of the Minarets in the central Sierra Nevada. Photo by Jim Wilson/The New York Times

    4
    Trees on a slope in the snow-covered eastern Sierra Nevada. Photo by Jim Wilson/The New York Times

    Ski resorts that typically close in the spring are so deeply blanketed that they have been making plans to extend their seasons.
    Officials at Squaw Valley, in the Lake Tahoe area, and Mammoth Mountain, below, in the eastern Sierra, said they anticipated staying open well into summer.

    6
    Skiers at Mammoth Mountain. Photo by Jim Wilson/The New York Times

    7
    A snow-covered ridge on the western slope of the central Sierras. Photo by Jim Wilson/The New York Times

    The snow observatory project, which began flights over the Sierra in 2013, is a groundbreaking initiative in California, where aging infrastructure, a warming climate and rapid population growth have made water management a high-stakes job.

    For decades, state officials have estimated snowpack levels by extrapolating from ground-based data gathered at points across the range.

    The margin of error, unsurprisingly, has been huge.

    “It’s like turning on your TV screen and four of the pixels turn on, and you can only use those four every single time you watch ‘Breaking Bad,’” Dr. Painter said.

    Every one to four weeks, the NASA crew circles above the Sierra Nevada in an airplane that fires laser pulses toward the ground. By measuring how fast the pulses bounce back, the scientists are able to create detailed topographical maps.

    Compare those with maps of the mountains when bare and factor in the snow’s density, and they can tell how much water is present.

    With the view from the sky, Dr. Painter said, “we turn on the whole screen, every pixel.”

    8
    Thomas Painter on the steps of the plane NASA uses to gauge snow depth. Photo by Jim Wilson/The New York Times

    9
    Dr. Painter with a device that uses laser beams to precisely measure topography.

    The observatory also measures the reflection of sunlight off the snow, which is critical to understanding how much energy the snow absorbs and how fast it could melt.

    Mr. Payne of the Friant Water Authority, which manages water for agricultural land in the San Joaquin Valley, said the new snow data was game-changing for farmers, who will be able to plan their crops with greater confidence.

    “We need to be smarter about how we approach water resource management,” Mr. Payne said. “And this new technology is sort of a beacon of hope.”

    For now, the observatory is taking measurements for most of the central Sierra Nevada. The hope is to get more buy-in from state officials and expand to the whole range, Dr. Painter said.

    It has been an increasingly easy sell.

    “It really has gotten to the point now where we don’t call on anyone,” Dr. Painter said. “We are simply responding to phone calls.”

    See the full article here .

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  • richardmitnick 7:19 am on March 28, 2017 Permalink | Reply
    Tags: , , , , NYT,   

    From NYT: “A Dream of Clean Energy at a Very High Price”, a Now Too Old Subject 

    New York Times

    The New York Times

    MARCH 27, 2017
    HENRY FOUNTAIN

    1
    Source: ITER Organization Mika Gröndahl/The New York Times

    SAINT-PAUL-LEZ-DURANCE, France — At a dusty construction site here amid the limestone ridges of Provence, workers scurry around immense slabs of concrete arranged in a ring like a modern-day Stonehenge.

    It looks like the beginnings of a large commercial power plant, but it is not. The project, called ITER, is an enormous, and enormously complex and costly, physics experiment. But if it succeeds, it could determine the power plants of the future and make an invaluable contribution to reducing planet-warming emissions.

    ITER, short for International Thermonuclear Experimental Reactor (and pronounced EAT-er), is being built to test a long-held dream: that nuclear fusion, the atomic reaction that takes place in the sun and in hydrogen bombs, can be controlled to generate power.

    First discussed in 1985 at a United States-Soviet Union summit, the multinational effort, in which the European Union has a 45 percent stake and the United States, Russia, China and three other partners 9 percent each, has long been cited as a crucial step toward a future of near-limitless electric power.

    ITER will produce heat, not electricity. But if it works — if it produces more energy than it consumes, which smaller fusion experiments so far have not been able to do — it could lead to plants that generate electricity without the climate-affecting carbon emissions of fossil-fuel plants or most of the hazards of existing nuclear reactors that split atoms rather than join them.

    Success, however, has always seemed just a few decades away for ITER. The project has progressed in fits and starts for years, plagued by design and management problems that have led to long delays and ballooning costs.

    ITER is moving ahead now, with a director-general, Bernard Bigot, who took over two years ago after an independent analysis that was highly critical of the project. Dr. Bigot, who previously ran France’s atomic energy agency, has earned high marks for resolving management problems and developing a realistic schedule based more on physics and engineering and less on politics.

    “I do believe we are moving at full speed and maybe accelerating,” Dr. Bigot said in an interview.

    The site here is now studded with tower cranes as crews work on the concrete structures that will support and surround the heart of the experiment, a doughnut-shaped chamber called a tokamak. This is where the fusion reactions will take place, within a plasma, a roiling cloud of ionized atoms so hot that it can be contained only by extremely strong magnetic fields.

    2
    By The New York Times

    Pieces of the tokamak and other components, including giant superconducting electromagnets and a structure that at approximately 100 feet in diameter and 100 feet tall will be the largest stainless-steel vacuum vessel ever made, are being fabricated in the participating countries. Assembly is set to begin next year in a giant hall erected next to the tokamak site.

    3
    At the ITER construction site, immense slabs of concrete lie in a ring like a modern-day Stonehenge. Credit ITER Organization

    There are major technical hurdles in a project where the manufacturing and construction are on the scale of shipbuilding but the parts need to fit with the precision of a fine watch.

    “It’s a challenge,” said Dr. Bigot, who devotes much of his time to issues related to integrating parts from various countries. “We need to be very sensitive about quality.”

    Even if the project proceeds smoothly, the goal of “first plasma,” using pure hydrogen that does not undergo fusion, would not be reached for another eight years. A so-called burning plasma, which contains a fraction of an ounce of fusible fuel in the form of two hydrogen isotopes, deuterium and tritium, and can be sustained for perhaps six or seven minutes and release large amounts of energy, would not be achieved until 2035 at the earliest.

    That is a half century after the subject of cooperating on a fusion project came up at a meeting in Geneva between President Ronald Reagan and the Soviet leader Mikhail S. Gorbachev. A functional commercial fusion power plant would be even further down the road.

    “Fusion is very hard,” said Riccardo Betti, a researcher at the University of Rochester who has followed the ITER project for years. “Plasma is not your friend. It tries to do everything it can to really displease you.”

    Fusion is also very expensive. ITER estimates the cost of design and construction at about 20 billion euros (currently about $22 billion). But the actual cost of components may be higher in some of the participating countries, like the United States, because of high labor costs. The eventual total United States contribution, which includes an enormous central electromagnet capable, it is said, of lifting an aircraft carrier, has been estimated at about $4 billion.

    Despite the recent progress there are still plenty of doubts about ITER, especially in the United States, which left the project for five years at the turn of the century and where funding through the Energy Department has long been a political football.

    The department confirmed its support for ITER in a report last year and Congress approved $115 million for it. It is unclear, though, how the project will fare in the Trump administration, which has proposed a cut of roughly 20 percent to the department’s Office of Science, which funds basic research including ITER. (The department also funds another long-troubled fusion project, which uses lasers, at Lawrence Livermore National Laboratory in California.)

    Dr. Bigot met with the new energy secretary, Rick Perry, last week in Washington, and said he found Mr. Perry “very open to listening” about ITER and its long-term goals. “But he has to make some short-term choices” with his budget, Dr. Bigot said.

    Energy Department press aides did not respond to requests for comment.

    Some in Congress, including Senator Lamar Alexander, Republican of Tennessee, while lauding Dr. Bigot’s efforts, argue that the project already consumes too much of the Energy Department’s basic research budget of about $5 billion.

    “I remain concerned that continuing to support the ITER project would come at the expense of other Office of Science priorities that the Department of Energy has said are more important — and that I consider more important,” Mr. Alexander said in a statement.

    While it is not clear what would happen to the project if the United States withdrew, Dr. Bigot argues that it is in every participating country’s interest to see it through. “You have a chance to know if fusion works or not,” he said. “If you miss this chance, maybe it will never come again.”

    But even scientists who support ITER are concerned about the impact it has on other research.

    “People around the country who work on projects that are the scientific basis for fusion are worried that they’re in a no-win situation,” said William Dorland, a physicist at the University of Maryland who is chairman of the plasma science committee of the National Academy of Sciences. “If ITER goes forward, it might eat up all the money. If it doesn’t expand and the U.S. pulls out, it may pull down a lot of good science in the downdraft.”

    In the ITER tokamak, deuterium and tritium nuclei will fuse to form helium, losing a small amount of mass that is converted into a huge amount of energy. Most of the energy will be carried away by neutrons, which will escape the plasma and strike the walls of the tokamak, producing heat.

    In a fusion power plant, that heat would be used to make steam to turn a turbine to generate electricity, much as existing power plants do using other sources of heat, like burning coal. ITER’s heat will be dissipated through cooling towers.

    There is no risk of a runaway reaction and meltdown as with nuclear fission and, while radioactive waste is produced, it is not nearly as long-lived as the spent fuel rods and irradiated components of a fission reactor.

    To fuse, atomic nuclei must move very fast — they must be extremely hot — to overcome natural repulsive forces and collide. In the sun, the extreme gravitational field does much of the work. Nuclei need to be at a temperature of about 15 million degrees Celsius.

    In a tokamak, without such a strong gravitational pull, the atoms need to be about 10 times hotter. So enormous amounts of energy are required to heat the plasma, using pulsating magnetic fields and other sources like microwaves. Just a few feet away, on the other hand, the windings of the superconducting electromagnets need to be cooled to a few degrees above absolute zero. Needless to say, the material and technical challenges are extreme.

    Although all fusion reactors to date have produced less energy than they use, physicists are expecting that ITER will benefit from its larger size, and will produce about 10 times more power than it consumes. But they will face many challenges, chief among them developing the ability to prevent instabilities in the edges of the plasma that can damage the experiment.

    Even in its early stages of construction, the project seems overwhelmingly complex. Embedded in the concrete surfaces are thousands of steel plates. They seem to be scattered at random throughout the structure, but actually are precisely located. ITER is being built to French nuclear plant standards, which prohibit drilling into concrete. So the plates — eventually about 80,000 of them — are where other components of the structure will be attached as construction progresses.

    A mistake or two now could wreak havoc a few years down the road, but Dr. Bigot said that in this and other work on ITER, the key to avoiding errors was taking time.

    “People consider that it’s long,” he said, referring to critics of the project timetable. “But if you want full control of quality, you need time.”

    See the full article here .

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