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Well: Probiotics: Looking Underneath the Yogurt Label
By TARA PARKER-POPE, The New York Times, September 29, 2009
When the label tells you the food you are buying “contains probiotics,” are you getting health benefits or just marketing hype? Perhaps a bit of both.
Probiotics are live micro-organisms that work by restoring the balance of intestinal bacteria and raising resistance to harmful germs. Taken in sufficient amounts, they can promote digestive health and help shorten the duration of colds. But while there are thousands of different probiotics, only a handful have been proved effective in clinical trials. Which strain of bacteria a given product includes is often difficult to figure out.
There is no standard labeling requirement to help buyers make sense of probiotic products. The word “probiotic” on the label is not enough information to tell whether a given product will be effective for a particular health concern. Just as a doctor would prescribe different antibiotics for strep throat or tuberculosis, different probiotic species and strains confer different health benefits.
“It’s a huge problem for the consumer to try to make heads or tails of whether the products that are out there really work,” said Dr. Shira Doron, an assistant professor of medicine at Tufts.
Consider Lactobacillus, a probiotic that comes in a number of strains, among them: Lactobacillus GG (often called LGG), which can be found in the diet supplement Culturelle as well as several milk products in Finland; L. casei DN114 001, included in Dannon products; and L. casei Shirota, found in Yakult, a popular probiotic drink from Japan.
Studies show that all of these strains are associated with reducing diarrhea; LGG, among the most studied, has also shown a benefit in treating atopic eczema and milk allergy in infants and children, according to a 2008 report in The Journal of Clinical Gastroenterology. Meanwhile, both LGG and Dannon’s L. casei strain have been shown in studies of children attending day care to reduce illness.
“Lactobacillus is just the bacterium,” said Gregor Reid, director of the Canadian Research and Development Center for Probiotics. “To say a product contains Lactobacillus is like saying you’re bringing George Clooney to a party. It may be the actor, or it may be an 85-year-old guy from Atlanta who just happens to be named George Clooney. With probiotics, there are strain-to-strain differences.”
The outcome of a recent legal case may help. Dannon, one of the biggest sellers of probiotic yogurts, settled a class-action lawsuit this month over its Activia yogurts and DanActive yogurt drinks, which claimed to help regulate digestion and stimulate the immune system. As part of the $35 million settlement, Dannon agreed to reimburse dissatisfied consumers and make labeling changes, among them adding the scientific names of probiotic strains it uses.
Dannon says that it settled the suit to avoid litigation and that it stands by all of its product claims. The company’s Web site lists numerous scientific studies of its patented probiotic strains.
“A scientific approach has been central to our business for decades,” said a spokesman, Michael Neuwirth, who added, “The essence of the claims of Activia and DanActive remain unchanged.”
So what health problems can probiotics really help? After gathering at a Yale workshop to review the available evidence, a panel of 12 experts concluded that there was strong evidence that several probiotic strains could reduce diarrhea, including that associated with antibiotic use. Several studies have also suggested that certain probiotics may be useful for irritable bowel syndrome, with the strongest recommendation for Bifidobacterium infantis 35624, the probiotic in the Procter & Gamble supplement Align. (Two members of the panel had ties to Procter & Gamble; three others had ties to other companies that sell probiotics.)
A variety of other claims for probiotics, like lowering cholesterol and blood pressure, preventing cavities and reducing cancer risk, were not reviewed by the panel.
And scientists continue to debate whether probiotics offer a meaningful benefit to the immune system.
“The evidence for the general immune strengthening is just not there,” said Barry R. Goldin, a Tufts professor who helped discover LGG but no longer receives royalties from the patent.
But the gastrointestinal tract is an important part of the immune system, and studies show that intestinal bacteria play an essential role in immune defenses. These bacteria not only aid digestion but essentially help form a protective barrier inside the intestine.
The Yale group, whose report appeared in The Journal of Clinical Gastroenterology in July 2008, concluded that the “immune response is definitely affected by the administration of probiotics.” But it did not decide whether probiotics were useful for general disease prevention and maintaining overall health, saying more study was needed. The group reported that many studies suggested that certain probiotics reduced duration of colds, along with time away from work and day care.
“Such findings,” the authors wrote, “suggest that probiotics might be of value for incorporation into the daily diet of healthy people for the purpose of staying healthy.”
Consumers interested in probiotics should look for products that list the specific strain on the label and offer readers easy access to scientific studies supporting the claims. A good place to find studies on various probiotic strains is the Web site www.PubMed.gov.
Fossil Skeleton From Africa Predates Lucy
By JOHN NOBLE WILFORD, The New York Times, October 2, 2009
Lucy, meet Ardi.
Ardi, short for Ardipithecus ramidus, is the newest fossil skeleton out of Africa to take its place in the gallery of human origins. At an age of 4.4 million years, it lived well before and was much more primitive than the famous 3.2-million-year-old Lucy, of the species Australopithecus afarensis.
Since finding fragments of the older hominid in 1992, an international team of scientists has been searching for more specimens and on Thursday presented a fairly complete skeleton and their first full analysis. By replacing Lucy as the earliest known skeleton from the human branch of the primate family tree, the scientists said, Ardi opened a window to “the early evolutionary steps that our ancestors took after we diverged from our common ancestor with chimpanzees.”
The older hominid was already so different from chimps that it suggested “no modern ape is a realistic proxy for characterizing early hominid evolution,” they wrote.
The Ardipithecus specimen, an adult female, probably stood four feet tall and weighed about 120 pounds, almost a foot taller and twice the weight of Lucy. Its brain was no larger than a modern chimp’s. It retained an agility for tree-climbing but already walked upright on two legs, a transforming innovation in hominids, though not as efficiently as Lucy’s kin.
Ardi’s feet had yet to develop the arch-like structure that came later with Lucy and on to humans. The hands were more like those of extinct apes. And its very long arms and short legs resembled the proportions of extinct apes, or even monkeys.
Tim D. White of the University of California, Berkeley, a leader of the team, said in an interview this week that the genus Ardipithecus appeared to resolve many uncertainties about “the initial stage of evolutionary adaptation” after the hominid lineage split from that of the chimpanzees. No fossil trace of the last common ancestor, which lived some time before six million years ago, according to genetic studies, has yet come to light.
The other two significant stages occurred with the rise of Australopithecus, which lived from about four million to one million years ago, and then the emergence of Homo, our own genus, before two million years ago. The ancestral relationship of Ardipithecus to Australopithecus has not been determined, but Lucy’s australopithecine kin are generally recognized as the ancestral group from which Homo evolved.
Scientists not involved in the new research hailed its importance, placing the Ardi skeleton on a pedestal alongside notable figures of hominid evolution like Lucy and the 1.6-million-year-old Turkana Boy from Kenya, an almost complete specimen of Homo erectus with anatomy remarkably similar to modern Homo sapiens.
David Pilbeam, a professor of human evolution at Harvard University who had no role in the discovery, said in an e-mail message that the Ardi skeleton represented “a genus plausibly ancestral to Australopithecus” and began “to fill in the temporal and structural ‘space’ between the apelike common ancestor and Australopithecus.”
Andrew Hill, a paleoanthropologist at Yale University who was also not involved in the research, noted that Dr. White had kept “this skeleton in his closet for the last 15 years or so, but I think it has been worth the wait.” In some ways the specimen’s features are surprising, Dr. Hill added, “but it makes a very satisfactory animal for understanding the changes that have taken place along the human lineage.”
The first comprehensive reports describing the skeleton and related findings, the result of 17 years of study, are being published Friday in the journal Science. Eleven papers by 47 authors from 10 countries describe the analysis of more than 110 Ardipithecus specimens from a minimum of 36 different individuals, including Ardi.
The paleoanthropologists wrote in one of the articles that Ardipithecus was “so rife with anatomical surprises that no one could have imagined it without direct fossil evidence.”
A bounty of animal and plant material — “every seed, every piece of fossil wood, every scrap of bone,” Dr. White said — was gathered to set the scene of the cooler, more humid woodland habitat in which these hominids had lived.
This was one of the first surprises, said Giday WoldeGabriel, a geologist at Los Alamos National Laboratory, because it upset the hypothesis that upright walking had evolved as an adaptation to life on grassy savanna.
The discovery site, on what is now an arid floodplain along the middle stretch of the Awash River in Ethiopia, is 140 miles northeast of Addis Ababa and 45 miles south of Hadar, where Lucy was found in 1974 by Donald Johanson, with whom Dr. White collaborated in analyzing those fossils.
Gen Suwa, a paleoanthropologist now at the University of Tokyo, made the first discovery in 1992: a single upper molar. Yohannes Haile-Selassie, an Ethiopian curator of anthropology at the Cleveland Museum of Natural History, uncovered the first skeletal bones. A preliminary report on the new species was published in 1994.
But the fossils, which are housed at the anthropology museum in Addis Ababa, were so plentiful, fragmentary and potentially significant that Dr. White held back from further public discussion of the research, even while discoveries of older fossils were being made.
One discovery was of an earlier species of Ardipithecus from elsewhere in Ethiopia. Other finds, perhaps from more than six million years ago and given other species names, were excavated in Chad and Kenya. Their bones indicate that they also walked upright, scientists say, but the fossils are too few to draw any definitive conclusions.
Ardi’s skull, Dr. Pilbeam said, appears to be more similar to the older Chad hominid than to younger australopithecines. This indicates that the fossils from Chad and Ethiopia possibly represent species of the Ardipithecus genus, or closely related genera.
From the new research, scientists inferred that Ardi was female, based on its small and lightly built skull and its canine teeth, which are small compared with other individuals at the site.
Dr. Suwa, a specialist in fossil teeth, said the more than 145 teeth collected at the site were of the size and shape and had wear patterns showing that the individuals were omnivorous eaters of plants and nuts, as well as small mammals, but were not as big consumers of fruits as are living chimps and gorillas. Ardi probably fed in trees and on the ground.
Dr. Suwa also noted that males had stubby canine teeth, more like those of modern humans, in contrast to the projecting tusklike upper canines of chimps and gorillas, suggesting that Ardipithecus teeth no longer functioned as weapons or displays in male-male or male-female conflicts. In fact, the male and female upper canines are similar.
This was seen as further evidence that the species had already evolved a distinctive trait of early prehumans. C. Owen Lovejoy, an anatomist at Kent State University and lead author of two of the journal reports, speculated that these hominids had a social system that involved less competition among males and that this suggested the beginning of pair bonding between males and females.
Dr. Pilbeam disputed this conjecture, saying, “This is a restatement of Owen Lovejoy’s ideas going back almost three decades, which I found unpersuasive then and still do.”
In his articles and an interview, Dr. Lovejoy described the five years he spent analyzing the Ardipithecus pelvis, which appeared to be in transition between a structure originally suited for life in trees and one modified for early upright walking. By contrast, the pelvis of the Lucy species had already evolved nearly all of the adaptations for bipedality.
Although the lower pelvis is still primitive, Dr. Lovejoy found, changes in the upper pelvis enabled the species to walk on two legs with a straightened hip, “but probably with less speed and efficiency than humans.” A few scientists think this walking evidence to be only circumstantial. The lower part of the pelvis, “still almost entirely apelike,” indicates retention of powerful hamstring muscles for climbing.
Dr. White, Berhane Asfaw of the Rift Valley Research Service in Ethiopia and other team members concluded that “despite the genetic similarities of living humans and chimpanzees, the ancestor we last shared probably differed substantially from any extant African ape.”
As Dr. Hill of Yale said, “It is always new specimens, particularly those from little known time periods or geographic areas, that provoke the greatest changes in our ideas.”
Looking ahead, Dr. White lamented that there were so few sites in Africa known to have fossil deposits six million to seven million years old. “We are getting so close to that common ancestor of hominids and chimps, and we’d love to find an earlier skeleton,” he said.
Evolution Run in Reverse? A Study Says It’s a One-Way Street
By CARL ZIMMER, The New York Times, September 29, 2009
Evolutionary biologists have long wondered if history can run backward. Is it possible for the proteins in our bodies to return to the old shapes and jobs they had millions of years ago?
Examining the evolution of one protein, a team of scientists declares the answer is no, saying new mutations make it practically impossible for evolution to reverse direction. “They burn the bridge that evolution just crossed,” said Joseph W. Thornton, a biology professor at the University of Oregon and co-author of a paper on the team’s findings in the current issue of Nature.
The Belgian biologist Louis Dollo was the first scientist to ponder reverse evolution. “An organism never returns to its former state,” he declared in 1905, a statement later dubbed Dollo’s law.
To see if he was right, biologists have reconstructed evolutionary history. In 2003, for example, a team of scientists studied wings on stick insects. They found that the insects’ common ancestor had wings, but some of its descendants lost them. Later, some of those flightless insects evolved wings again.
Yet this study did not necessarily refute Dollo’s law. The stick insects may indeed have evolved a new set of wings, but it is not clear whether this change appeared as reverse evolution at the molecular level. Did the insects go back to the exact original biochemistry for building wings, or find a new route, essentially evolving new proteins?
Dr. Thornton and his colleagues took a close look at the possibility of reverse evolution at this molecular level. They studied a protein called a glucocorticoid receptor that helps humans and most other vertebrates cope with stress by grabbing a hormone called cortisol and then switching on stress-defense genes.
By comparing the receptor to related proteins, the scientists reconstructed its history. Some 450 million years ago, it started out with a different shape that allowed it to grab tightly to other hormones, but only weakly to cortisol. Over the next 40 million years, the receptor changed shape, so that it became very sensitive to cortisol but could no longer grab other hormones.
During those 40 million years, Dr. Thornton found, the receptor changed in 37 spots, only 2 of which made the receptor sensitive to cortisol. Another 5 prevented it from grabbing other hormones. When he made these 7 changes to the ancestral receptor, it behaved just like a new glucocorticoid receptor.
Dr. Thornton reasoned that if he carried out the reverse operation, he could turn a new glucocorticoid receptor into an ancestral one. So he and his colleagues reversed these key mutations to their old form.
To Dr. Thornton’s surprise, the experiment failed. “All we got was a completely dead receptor,” he said.
To figure out why they could go forward but not backward, Dr. Thornton and his colleagues looked closely again at the old and new receptors. They discovered five additional mutations that were crucial to the transition. If they reversed these five mutations as well, the new receptor behaved like an old one.
Based on these results, Dr. Thornton and his colleagues concluded that the evolution of the receptor unfolded in two chapters. In the first, the receptor acquired the seven key mutations that made it sensitive to cortisol and not to other hormones. In the second, it acquired the five extra mutations, which Dr. Thornton called “restrictive” mutations.
These restrictive mutations may have fine-tuned how the receptor grabbed cortisol. Or they may have had no effect at all. In either case, these five mutations added twists and tails to the receptor. When Dr. Thornton tried to return the receptor to its original form, these twists and tails got in the way.
Dr. Thornton argues that once the restrictive mutations evolved, they made it practically impossible for the receptor to evolve back to its original form. The five key mutations could not be reversed first, because the receptor would be rendered useless. Nor could the seven restrictive mutations be reversed first. Those mutations had little effect on how the receptor grabbed hormones. So there was no way that natural selection could favor individuals with reversed mutations.
For now it is an open question whether other proteins have an equally hard time evolving backward. But Dr. Thornton suspects they do.
“I would never say evolution is never reversible,” Dr. Thornton said. But he thinks it can only go backward when the evolution of the trait is simple, like when a single mutation is involved. When new traits are produced by several mutations that influence one another, he argues, that complexity shuts off reverse evolution. “We know that kind of complexity is very common,” he said.
If this molecular Dollo’s law holds up, Dr. Thornton believes it says something important about the course of evolutionary history. Natural selection can achieve many things, but it is hemmed in. Even harmless, random mutations can block its path.
“The biology we ended up with was not inevitable,” he said. “It was just one roll of the evolutionary dice.”
Finding Order in the Apparent Chaos of Currents
By BINA VENKATARAMAN, The New York Times, September 29, 2009
Suppose a blob of dioxin-rich pesticide is spilled into Monterey Bay. It might quickly disperse to the Pacific Ocean. But hours later, a spill of the same size at the same spot could circle near the coastline, posing a greater danger to marine life. The briny surface waters of the bay churn so chaotically that a slight shift in the place or time an oil drop, a buoy — or even a person — falls in can dictate whether it is swept out to the open ocean or swirls near the shore.
But the results are not unpredictable. A team of scientists studying Monterey Bay since 2000 has found that underlying its complex, seemingly jumbled currents is a structure that guides the dispersal patterns, a structure that changes over time.
With the aid of high-frequency radar that tracks the speed and direction of the flowing waters, and computers that rapidly perform millions of calculations, the scientists found that a hidden skeleton guided whether floating debris lingered or exited the bay.
Over the past 10 years, scientists have made enormous strides in their ability to identify and make images of the underlying mechanics of flowing air and water, and to predict how objects move through these flows.
Assisted by instruments that can track in fine detail how parcels of fluid move, and by low-cost computers that can crunch vast amounts of data quickly, researchers have found hidden structures beyond Monterey Bay, structures that explain why aircraft meet unexpected turbulence, why the air flow around a car causes drag and how blood pumps from the heart’s ventricles. In December, the journal Chaos will highlight the research under way to track the moving skeletons embedded in complex flows, known as Lagrangian coherent structures.
“There’s been an explosion of interest in this area,” said David K. Campbell, editor in chief of Chaos, a physicist and provost at Boston University. “Why it’s become more interesting is that experimentalists can now watch these structures emerge.”
The patterns of flow have fascinated thinkers for centuries. In the 1500s, Leonardo da Vinci sketched the swirling eddies he saw in rivers and the vortexes of blood he imagined in the aortic valve. Just as those visible patterns of flow change quickly, eluding our ability to predict the fate of objects caught up in them, the hidden structures of flow also move and morph over time.
The concept of the structures grew out of dynamical systems theory, a branch of mathematics used to understand complicated phenomena that change over time. The discovery of the structures in a wide range of real-world cases has shown that they play a key role in complex and chaotic fluid flows in the atmosphere and ocean.
The structures are invisible because they often exist only as dividing lines between parts of a flow that are moving at different speeds and in different directions. In the ocean, the path of a drop of water on one side of such a structure might diverge from the path of a drop of water on the other side; they will drift farther apart as time passes.
“They aren’t something you can walk up to and touch,” Jerrold E. Marsden, an engineering and mathematics professor at Caltech, said of the structures. “But they are not purely mathematical constructions, either.”
As an analogy, Dr. Marsden suggests imagining a line that divides a part of a city that has been affected by a disease outbreak from a part that has not. The line is not a fence or a road, but it still marks a physical barrier. And as the outbreak spreads, the line will change.
To find the structures, scientists must track flow, not by watching it go by but from the perspective of the droplets of water or molecules of air moving in it. “It’s like being a surfer,” Dr. Campbell said. “You want to catch the wave and move with the wave.”
In the laboratory, researchers shine lasers on tiny particles caught in a flow, capturing their speed and trajectory with fast, high-resolution digital cameras similar to the way tracer rounds from machine guns track the path of bullets. In the ocean or atmosphere, scientists rely on instantaneous data from high-frequency radar, laser detection systems, buoys and satellites. In the human body, phase-contrast magnetic resonance imaging has helped researchers map the complex patterns of blood flow in detail. Computers take in the data from all those sources, applying algorithms that unveil the flow structures.
“We’re just recognizing that these things exist and are playing a role in a variety of scenarios,” said Thomas Peacock, a mechanical engineering professor at M.I.T. who is evaluating how Lagrangian coherent structures affect vehicle performance and efficiency. “The idea is that cars, airplanes and submarines down the line would be fitted with sensors that will help them adapt to these structures.”
Studies of the air flow patterns surrounding Hong Kong International Airport have shown that Lagrangian coherent structures cause unexpected jolts to planes during landing attempts, forcing pilots to waste fuel while they revert to holding patterns. George Haller, an engineering professor at McGill University in Montreal who forged the mathematical criteria for finding such structures in fluid flows, is working with the airport’s officials to design a tool that allows pilots to see and navigate around the structures. It will rely on data from laser scans, analyzed by computers as planes approach the airport.
At Stanford, researchers are mapping blood flow in patients with abdominal aortic aneurysms to see whether frequent exercise changes the flow structures in ways that correlate to slower bulging of the artery.
The scientists studying Monterey Bay found a Lagrangian coherent structure that acts as a moving ridge, separating a region of the bay that spreads pollutants out to sea and a region that recirculates them in the bay. They watched this ridge drift and change over 22 days and found that if computed in real time, it could be used to predict one-day windows when pollutants could do less damage to the bay environment.
The scientists proposed building a holding tank for the fertilizers and pesticides that wash from farmland into the neighboring watershed that could release pollutants only at times when they would quickly drift into the ocean, where they would be so diluted they would pose less harm to marine life. In a later experiment, scientists found that the path of buoys dispatched in the bay followed the path predicted by the computer simulations.
Researchers who studied the waters along the southeastern coast of Florida found a similar structure that they argued could be used to reduce the effects of pollution near Hollywood Beach, south of Fort Lauderdale.
Their research in Monterey Bay piqued the interest of Art Allen, a physical oceanographer for the Coast Guard who thinks that Lagrangian coherent structures could improve search-and-rescue operations for people lost at sea by offering more precision than current techniques.
Researchers in private industry and the French Navy have expressed interest in using models of the structures to track the spread of oil after spills in coastal areas, said Francois Lekien, an applied mathematics professor at the École Polytechnique at the Université Libre de Bruxelles in Belgium who was a co-author of the bay studies.
Strategies based on Lagrangian coherent structures have yet to be tested to see if they curb coastal pollution. And they have several limitations. Scientists cannot yet predict what happens to pollutants that do not float on the ocean surface. The models do not yet account for the interaction with wind patterns that also guide how floating objects or people drift at sea. The method also requires continuing, detailed data akin to what was available in Monterey Bay, which has an ocean monitoring program that far surpasses that of most coastal areas.
Even if the structures in flow do not guide engineering or pollution strategies as well as researchers hope, many scientists believe that unearthing and visualizing them provides useful insights. For example, the structures identified in coastal waters have exposed flaws in our intuition about flow. “There are myths out there that it’s O.K. to dump pollutants at high tide,” said Dr. Marsden, co-author of the Monterey Bay and coastal Florida studies. “But it’s really these structures that will determine where pollutants end up.”
Finding the structures in various settings has also given researchers a fresh perspective on what remains a great scientific puzzle: the dynamics of flow.
“In complex systems such as the atmosphere, there are a lot of things that people can’t explain offhand,” Dr. Haller said. “People used to attribute this to randomness or chaos. But it turns out, when you look at data sets and find these structures, you can actually explain those patterns.”
By TARA PARKER-POPE, The New York Times, September 29, 2009
When the label tells you the food you are buying “contains probiotics,” are you getting health benefits or just marketing hype? Perhaps a bit of both.
Probiotics are live micro-organisms that work by restoring the balance of intestinal bacteria and raising resistance to harmful germs. Taken in sufficient amounts, they can promote digestive health and help shorten the duration of colds. But while there are thousands of different probiotics, only a handful have been proved effective in clinical trials. Which strain of bacteria a given product includes is often difficult to figure out.
There is no standard labeling requirement to help buyers make sense of probiotic products. The word “probiotic” on the label is not enough information to tell whether a given product will be effective for a particular health concern. Just as a doctor would prescribe different antibiotics for strep throat or tuberculosis, different probiotic species and strains confer different health benefits.
“It’s a huge problem for the consumer to try to make heads or tails of whether the products that are out there really work,” said Dr. Shira Doron, an assistant professor of medicine at Tufts.
Consider Lactobacillus, a probiotic that comes in a number of strains, among them: Lactobacillus GG (often called LGG), which can be found in the diet supplement Culturelle as well as several milk products in Finland; L. casei DN114 001, included in Dannon products; and L. casei Shirota, found in Yakult, a popular probiotic drink from Japan.
Studies show that all of these strains are associated with reducing diarrhea; LGG, among the most studied, has also shown a benefit in treating atopic eczema and milk allergy in infants and children, according to a 2008 report in The Journal of Clinical Gastroenterology. Meanwhile, both LGG and Dannon’s L. casei strain have been shown in studies of children attending day care to reduce illness.
“Lactobacillus is just the bacterium,” said Gregor Reid, director of the Canadian Research and Development Center for Probiotics. “To say a product contains Lactobacillus is like saying you’re bringing George Clooney to a party. It may be the actor, or it may be an 85-year-old guy from Atlanta who just happens to be named George Clooney. With probiotics, there are strain-to-strain differences.”
The outcome of a recent legal case may help. Dannon, one of the biggest sellers of probiotic yogurts, settled a class-action lawsuit this month over its Activia yogurts and DanActive yogurt drinks, which claimed to help regulate digestion and stimulate the immune system. As part of the $35 million settlement, Dannon agreed to reimburse dissatisfied consumers and make labeling changes, among them adding the scientific names of probiotic strains it uses.
Dannon says that it settled the suit to avoid litigation and that it stands by all of its product claims. The company’s Web site lists numerous scientific studies of its patented probiotic strains.
“A scientific approach has been central to our business for decades,” said a spokesman, Michael Neuwirth, who added, “The essence of the claims of Activia and DanActive remain unchanged.”
So what health problems can probiotics really help? After gathering at a Yale workshop to review the available evidence, a panel of 12 experts concluded that there was strong evidence that several probiotic strains could reduce diarrhea, including that associated with antibiotic use. Several studies have also suggested that certain probiotics may be useful for irritable bowel syndrome, with the strongest recommendation for Bifidobacterium infantis 35624, the probiotic in the Procter & Gamble supplement Align. (Two members of the panel had ties to Procter & Gamble; three others had ties to other companies that sell probiotics.)
A variety of other claims for probiotics, like lowering cholesterol and blood pressure, preventing cavities and reducing cancer risk, were not reviewed by the panel.
And scientists continue to debate whether probiotics offer a meaningful benefit to the immune system.
“The evidence for the general immune strengthening is just not there,” said Barry R. Goldin, a Tufts professor who helped discover LGG but no longer receives royalties from the patent.
But the gastrointestinal tract is an important part of the immune system, and studies show that intestinal bacteria play an essential role in immune defenses. These bacteria not only aid digestion but essentially help form a protective barrier inside the intestine.
The Yale group, whose report appeared in The Journal of Clinical Gastroenterology in July 2008, concluded that the “immune response is definitely affected by the administration of probiotics.” But it did not decide whether probiotics were useful for general disease prevention and maintaining overall health, saying more study was needed. The group reported that many studies suggested that certain probiotics reduced duration of colds, along with time away from work and day care.
“Such findings,” the authors wrote, “suggest that probiotics might be of value for incorporation into the daily diet of healthy people for the purpose of staying healthy.”
Consumers interested in probiotics should look for products that list the specific strain on the label and offer readers easy access to scientific studies supporting the claims. A good place to find studies on various probiotic strains is the Web site www.PubMed.gov.
Fossil Skeleton From Africa Predates Lucy
By JOHN NOBLE WILFORD, The New York Times, October 2, 2009
Lucy, meet Ardi.
Ardi, short for Ardipithecus ramidus, is the newest fossil skeleton out of Africa to take its place in the gallery of human origins. At an age of 4.4 million years, it lived well before and was much more primitive than the famous 3.2-million-year-old Lucy, of the species Australopithecus afarensis.
Since finding fragments of the older hominid in 1992, an international team of scientists has been searching for more specimens and on Thursday presented a fairly complete skeleton and their first full analysis. By replacing Lucy as the earliest known skeleton from the human branch of the primate family tree, the scientists said, Ardi opened a window to “the early evolutionary steps that our ancestors took after we diverged from our common ancestor with chimpanzees.”
The older hominid was already so different from chimps that it suggested “no modern ape is a realistic proxy for characterizing early hominid evolution,” they wrote.
The Ardipithecus specimen, an adult female, probably stood four feet tall and weighed about 120 pounds, almost a foot taller and twice the weight of Lucy. Its brain was no larger than a modern chimp’s. It retained an agility for tree-climbing but already walked upright on two legs, a transforming innovation in hominids, though not as efficiently as Lucy’s kin.
Ardi’s feet had yet to develop the arch-like structure that came later with Lucy and on to humans. The hands were more like those of extinct apes. And its very long arms and short legs resembled the proportions of extinct apes, or even monkeys.
Tim D. White of the University of California, Berkeley, a leader of the team, said in an interview this week that the genus Ardipithecus appeared to resolve many uncertainties about “the initial stage of evolutionary adaptation” after the hominid lineage split from that of the chimpanzees. No fossil trace of the last common ancestor, which lived some time before six million years ago, according to genetic studies, has yet come to light.
The other two significant stages occurred with the rise of Australopithecus, which lived from about four million to one million years ago, and then the emergence of Homo, our own genus, before two million years ago. The ancestral relationship of Ardipithecus to Australopithecus has not been determined, but Lucy’s australopithecine kin are generally recognized as the ancestral group from which Homo evolved.
Scientists not involved in the new research hailed its importance, placing the Ardi skeleton on a pedestal alongside notable figures of hominid evolution like Lucy and the 1.6-million-year-old Turkana Boy from Kenya, an almost complete specimen of Homo erectus with anatomy remarkably similar to modern Homo sapiens.
David Pilbeam, a professor of human evolution at Harvard University who had no role in the discovery, said in an e-mail message that the Ardi skeleton represented “a genus plausibly ancestral to Australopithecus” and began “to fill in the temporal and structural ‘space’ between the apelike common ancestor and Australopithecus.”
Andrew Hill, a paleoanthropologist at Yale University who was also not involved in the research, noted that Dr. White had kept “this skeleton in his closet for the last 15 years or so, but I think it has been worth the wait.” In some ways the specimen’s features are surprising, Dr. Hill added, “but it makes a very satisfactory animal for understanding the changes that have taken place along the human lineage.”
The first comprehensive reports describing the skeleton and related findings, the result of 17 years of study, are being published Friday in the journal Science. Eleven papers by 47 authors from 10 countries describe the analysis of more than 110 Ardipithecus specimens from a minimum of 36 different individuals, including Ardi.
The paleoanthropologists wrote in one of the articles that Ardipithecus was “so rife with anatomical surprises that no one could have imagined it without direct fossil evidence.”
A bounty of animal and plant material — “every seed, every piece of fossil wood, every scrap of bone,” Dr. White said — was gathered to set the scene of the cooler, more humid woodland habitat in which these hominids had lived.
This was one of the first surprises, said Giday WoldeGabriel, a geologist at Los Alamos National Laboratory, because it upset the hypothesis that upright walking had evolved as an adaptation to life on grassy savanna.
The discovery site, on what is now an arid floodplain along the middle stretch of the Awash River in Ethiopia, is 140 miles northeast of Addis Ababa and 45 miles south of Hadar, where Lucy was found in 1974 by Donald Johanson, with whom Dr. White collaborated in analyzing those fossils.
Gen Suwa, a paleoanthropologist now at the University of Tokyo, made the first discovery in 1992: a single upper molar. Yohannes Haile-Selassie, an Ethiopian curator of anthropology at the Cleveland Museum of Natural History, uncovered the first skeletal bones. A preliminary report on the new species was published in 1994.
But the fossils, which are housed at the anthropology museum in Addis Ababa, were so plentiful, fragmentary and potentially significant that Dr. White held back from further public discussion of the research, even while discoveries of older fossils were being made.
One discovery was of an earlier species of Ardipithecus from elsewhere in Ethiopia. Other finds, perhaps from more than six million years ago and given other species names, were excavated in Chad and Kenya. Their bones indicate that they also walked upright, scientists say, but the fossils are too few to draw any definitive conclusions.
Ardi’s skull, Dr. Pilbeam said, appears to be more similar to the older Chad hominid than to younger australopithecines. This indicates that the fossils from Chad and Ethiopia possibly represent species of the Ardipithecus genus, or closely related genera.
From the new research, scientists inferred that Ardi was female, based on its small and lightly built skull and its canine teeth, which are small compared with other individuals at the site.
Dr. Suwa, a specialist in fossil teeth, said the more than 145 teeth collected at the site were of the size and shape and had wear patterns showing that the individuals were omnivorous eaters of plants and nuts, as well as small mammals, but were not as big consumers of fruits as are living chimps and gorillas. Ardi probably fed in trees and on the ground.
Dr. Suwa also noted that males had stubby canine teeth, more like those of modern humans, in contrast to the projecting tusklike upper canines of chimps and gorillas, suggesting that Ardipithecus teeth no longer functioned as weapons or displays in male-male or male-female conflicts. In fact, the male and female upper canines are similar.
This was seen as further evidence that the species had already evolved a distinctive trait of early prehumans. C. Owen Lovejoy, an anatomist at Kent State University and lead author of two of the journal reports, speculated that these hominids had a social system that involved less competition among males and that this suggested the beginning of pair bonding between males and females.
Dr. Pilbeam disputed this conjecture, saying, “This is a restatement of Owen Lovejoy’s ideas going back almost three decades, which I found unpersuasive then and still do.”
In his articles and an interview, Dr. Lovejoy described the five years he spent analyzing the Ardipithecus pelvis, which appeared to be in transition between a structure originally suited for life in trees and one modified for early upright walking. By contrast, the pelvis of the Lucy species had already evolved nearly all of the adaptations for bipedality.
Although the lower pelvis is still primitive, Dr. Lovejoy found, changes in the upper pelvis enabled the species to walk on two legs with a straightened hip, “but probably with less speed and efficiency than humans.” A few scientists think this walking evidence to be only circumstantial. The lower part of the pelvis, “still almost entirely apelike,” indicates retention of powerful hamstring muscles for climbing.
Dr. White, Berhane Asfaw of the Rift Valley Research Service in Ethiopia and other team members concluded that “despite the genetic similarities of living humans and chimpanzees, the ancestor we last shared probably differed substantially from any extant African ape.”
As Dr. Hill of Yale said, “It is always new specimens, particularly those from little known time periods or geographic areas, that provoke the greatest changes in our ideas.”
Looking ahead, Dr. White lamented that there were so few sites in Africa known to have fossil deposits six million to seven million years old. “We are getting so close to that common ancestor of hominids and chimps, and we’d love to find an earlier skeleton,” he said.
Evolution Run in Reverse? A Study Says It’s a One-Way Street
By CARL ZIMMER, The New York Times, September 29, 2009
Evolutionary biologists have long wondered if history can run backward. Is it possible for the proteins in our bodies to return to the old shapes and jobs they had millions of years ago?
Examining the evolution of one protein, a team of scientists declares the answer is no, saying new mutations make it practically impossible for evolution to reverse direction. “They burn the bridge that evolution just crossed,” said Joseph W. Thornton, a biology professor at the University of Oregon and co-author of a paper on the team’s findings in the current issue of Nature.
The Belgian biologist Louis Dollo was the first scientist to ponder reverse evolution. “An organism never returns to its former state,” he declared in 1905, a statement later dubbed Dollo’s law.
To see if he was right, biologists have reconstructed evolutionary history. In 2003, for example, a team of scientists studied wings on stick insects. They found that the insects’ common ancestor had wings, but some of its descendants lost them. Later, some of those flightless insects evolved wings again.
Yet this study did not necessarily refute Dollo’s law. The stick insects may indeed have evolved a new set of wings, but it is not clear whether this change appeared as reverse evolution at the molecular level. Did the insects go back to the exact original biochemistry for building wings, or find a new route, essentially evolving new proteins?
Dr. Thornton and his colleagues took a close look at the possibility of reverse evolution at this molecular level. They studied a protein called a glucocorticoid receptor that helps humans and most other vertebrates cope with stress by grabbing a hormone called cortisol and then switching on stress-defense genes.
By comparing the receptor to related proteins, the scientists reconstructed its history. Some 450 million years ago, it started out with a different shape that allowed it to grab tightly to other hormones, but only weakly to cortisol. Over the next 40 million years, the receptor changed shape, so that it became very sensitive to cortisol but could no longer grab other hormones.
During those 40 million years, Dr. Thornton found, the receptor changed in 37 spots, only 2 of which made the receptor sensitive to cortisol. Another 5 prevented it from grabbing other hormones. When he made these 7 changes to the ancestral receptor, it behaved just like a new glucocorticoid receptor.
Dr. Thornton reasoned that if he carried out the reverse operation, he could turn a new glucocorticoid receptor into an ancestral one. So he and his colleagues reversed these key mutations to their old form.
To Dr. Thornton’s surprise, the experiment failed. “All we got was a completely dead receptor,” he said.
To figure out why they could go forward but not backward, Dr. Thornton and his colleagues looked closely again at the old and new receptors. They discovered five additional mutations that were crucial to the transition. If they reversed these five mutations as well, the new receptor behaved like an old one.
Based on these results, Dr. Thornton and his colleagues concluded that the evolution of the receptor unfolded in two chapters. In the first, the receptor acquired the seven key mutations that made it sensitive to cortisol and not to other hormones. In the second, it acquired the five extra mutations, which Dr. Thornton called “restrictive” mutations.
These restrictive mutations may have fine-tuned how the receptor grabbed cortisol. Or they may have had no effect at all. In either case, these five mutations added twists and tails to the receptor. When Dr. Thornton tried to return the receptor to its original form, these twists and tails got in the way.
Dr. Thornton argues that once the restrictive mutations evolved, they made it practically impossible for the receptor to evolve back to its original form. The five key mutations could not be reversed first, because the receptor would be rendered useless. Nor could the seven restrictive mutations be reversed first. Those mutations had little effect on how the receptor grabbed hormones. So there was no way that natural selection could favor individuals with reversed mutations.
For now it is an open question whether other proteins have an equally hard time evolving backward. But Dr. Thornton suspects they do.
“I would never say evolution is never reversible,” Dr. Thornton said. But he thinks it can only go backward when the evolution of the trait is simple, like when a single mutation is involved. When new traits are produced by several mutations that influence one another, he argues, that complexity shuts off reverse evolution. “We know that kind of complexity is very common,” he said.
If this molecular Dollo’s law holds up, Dr. Thornton believes it says something important about the course of evolutionary history. Natural selection can achieve many things, but it is hemmed in. Even harmless, random mutations can block its path.
“The biology we ended up with was not inevitable,” he said. “It was just one roll of the evolutionary dice.”
Finding Order in the Apparent Chaos of Currents
By BINA VENKATARAMAN, The New York Times, September 29, 2009
Suppose a blob of dioxin-rich pesticide is spilled into Monterey Bay. It might quickly disperse to the Pacific Ocean. But hours later, a spill of the same size at the same spot could circle near the coastline, posing a greater danger to marine life. The briny surface waters of the bay churn so chaotically that a slight shift in the place or time an oil drop, a buoy — or even a person — falls in can dictate whether it is swept out to the open ocean or swirls near the shore.
But the results are not unpredictable. A team of scientists studying Monterey Bay since 2000 has found that underlying its complex, seemingly jumbled currents is a structure that guides the dispersal patterns, a structure that changes over time.
With the aid of high-frequency radar that tracks the speed and direction of the flowing waters, and computers that rapidly perform millions of calculations, the scientists found that a hidden skeleton guided whether floating debris lingered or exited the bay.
Over the past 10 years, scientists have made enormous strides in their ability to identify and make images of the underlying mechanics of flowing air and water, and to predict how objects move through these flows.
Assisted by instruments that can track in fine detail how parcels of fluid move, and by low-cost computers that can crunch vast amounts of data quickly, researchers have found hidden structures beyond Monterey Bay, structures that explain why aircraft meet unexpected turbulence, why the air flow around a car causes drag and how blood pumps from the heart’s ventricles. In December, the journal Chaos will highlight the research under way to track the moving skeletons embedded in complex flows, known as Lagrangian coherent structures.
“There’s been an explosion of interest in this area,” said David K. Campbell, editor in chief of Chaos, a physicist and provost at Boston University. “Why it’s become more interesting is that experimentalists can now watch these structures emerge.”
The patterns of flow have fascinated thinkers for centuries. In the 1500s, Leonardo da Vinci sketched the swirling eddies he saw in rivers and the vortexes of blood he imagined in the aortic valve. Just as those visible patterns of flow change quickly, eluding our ability to predict the fate of objects caught up in them, the hidden structures of flow also move and morph over time.
The concept of the structures grew out of dynamical systems theory, a branch of mathematics used to understand complicated phenomena that change over time. The discovery of the structures in a wide range of real-world cases has shown that they play a key role in complex and chaotic fluid flows in the atmosphere and ocean.
The structures are invisible because they often exist only as dividing lines between parts of a flow that are moving at different speeds and in different directions. In the ocean, the path of a drop of water on one side of such a structure might diverge from the path of a drop of water on the other side; they will drift farther apart as time passes.
“They aren’t something you can walk up to and touch,” Jerrold E. Marsden, an engineering and mathematics professor at Caltech, said of the structures. “But they are not purely mathematical constructions, either.”
As an analogy, Dr. Marsden suggests imagining a line that divides a part of a city that has been affected by a disease outbreak from a part that has not. The line is not a fence or a road, but it still marks a physical barrier. And as the outbreak spreads, the line will change.
To find the structures, scientists must track flow, not by watching it go by but from the perspective of the droplets of water or molecules of air moving in it. “It’s like being a surfer,” Dr. Campbell said. “You want to catch the wave and move with the wave.”
In the laboratory, researchers shine lasers on tiny particles caught in a flow, capturing their speed and trajectory with fast, high-resolution digital cameras similar to the way tracer rounds from machine guns track the path of bullets. In the ocean or atmosphere, scientists rely on instantaneous data from high-frequency radar, laser detection systems, buoys and satellites. In the human body, phase-contrast magnetic resonance imaging has helped researchers map the complex patterns of blood flow in detail. Computers take in the data from all those sources, applying algorithms that unveil the flow structures.
“We’re just recognizing that these things exist and are playing a role in a variety of scenarios,” said Thomas Peacock, a mechanical engineering professor at M.I.T. who is evaluating how Lagrangian coherent structures affect vehicle performance and efficiency. “The idea is that cars, airplanes and submarines down the line would be fitted with sensors that will help them adapt to these structures.”
Studies of the air flow patterns surrounding Hong Kong International Airport have shown that Lagrangian coherent structures cause unexpected jolts to planes during landing attempts, forcing pilots to waste fuel while they revert to holding patterns. George Haller, an engineering professor at McGill University in Montreal who forged the mathematical criteria for finding such structures in fluid flows, is working with the airport’s officials to design a tool that allows pilots to see and navigate around the structures. It will rely on data from laser scans, analyzed by computers as planes approach the airport.
At Stanford, researchers are mapping blood flow in patients with abdominal aortic aneurysms to see whether frequent exercise changes the flow structures in ways that correlate to slower bulging of the artery.
The scientists studying Monterey Bay found a Lagrangian coherent structure that acts as a moving ridge, separating a region of the bay that spreads pollutants out to sea and a region that recirculates them in the bay. They watched this ridge drift and change over 22 days and found that if computed in real time, it could be used to predict one-day windows when pollutants could do less damage to the bay environment.
The scientists proposed building a holding tank for the fertilizers and pesticides that wash from farmland into the neighboring watershed that could release pollutants only at times when they would quickly drift into the ocean, where they would be so diluted they would pose less harm to marine life. In a later experiment, scientists found that the path of buoys dispatched in the bay followed the path predicted by the computer simulations.
Researchers who studied the waters along the southeastern coast of Florida found a similar structure that they argued could be used to reduce the effects of pollution near Hollywood Beach, south of Fort Lauderdale.
Their research in Monterey Bay piqued the interest of Art Allen, a physical oceanographer for the Coast Guard who thinks that Lagrangian coherent structures could improve search-and-rescue operations for people lost at sea by offering more precision than current techniques.
Researchers in private industry and the French Navy have expressed interest in using models of the structures to track the spread of oil after spills in coastal areas, said Francois Lekien, an applied mathematics professor at the École Polytechnique at the Université Libre de Bruxelles in Belgium who was a co-author of the bay studies.
Strategies based on Lagrangian coherent structures have yet to be tested to see if they curb coastal pollution. And they have several limitations. Scientists cannot yet predict what happens to pollutants that do not float on the ocean surface. The models do not yet account for the interaction with wind patterns that also guide how floating objects or people drift at sea. The method also requires continuing, detailed data akin to what was available in Monterey Bay, which has an ocean monitoring program that far surpasses that of most coastal areas.
Even if the structures in flow do not guide engineering or pollution strategies as well as researchers hope, many scientists believe that unearthing and visualizing them provides useful insights. For example, the structures identified in coastal waters have exposed flaws in our intuition about flow. “There are myths out there that it’s O.K. to dump pollutants at high tide,” said Dr. Marsden, co-author of the Monterey Bay and coastal Florida studies. “But it’s really these structures that will determine where pollutants end up.”
Finding the structures in various settings has also given researchers a fresh perspective on what remains a great scientific puzzle: the dynamics of flow.
“In complex systems such as the atmosphere, there are a lot of things that people can’t explain offhand,” Dr. Haller said. “People used to attribute this to randomness or chaos. But it turns out, when you look at data sets and find these structures, you can actually explain those patterns.”
