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Science , er, Friday - Asbestos, Depression, Origin of Life, & Animal Cooperation
U.S. Cites Emergency in Asbestos-Poisoned Town
By CORNELIA DEAN, The New York Times, June 18, 2009
The Environmental Protection Agency declared a public health emergency on Wednesday in and near Libby, Mont., where over the course of decades asbestos contamination in a vermiculite mine has left hundreds of people dead or sickened from lung diseases.
It was the first health emergency ever declared under the Superfund law, the 1980 statute that governs sites contaminated or threatened by hazardous substances. The Libby site has been designated a Superfund priority since 2002.
A spokeswoman for the E.P.A. said that in anticipation of the declaration, the Department of Health and Human Services had agreed to make $6 million available to the Lincoln County Health Clinic, which provides care to residents of the area, to finance treatment of people with asbestos-related conditions. She said the declaration also authorized the environmental agency to remove vermiculite, whose uses include insulating, from buildings there.
In addition, she said, the agency will begin an effort to inform Americans generally about the risks of insulation made from vermiculite, a natural silicate mineral that forms in flakes. She said that it was not known how many homes nationally contained asbestos-contaminated vermiculite but that estimates ran into the tens of millions.
Vermiculite flakes puff up like popcorn when heated. Because the mineral is chemically inert, fire-resistant, lightweight and odorless, it was once widely used in insulation that was typically poured loosely between attic floor joists or between wall studs.
The Libby mine, originally operated by the Zonolite Company, at one time provided 80 percent of the nation’s vermiculite insulation, according to the E.P.A. W.R. Grace & Company bought the mine in 1963 and, according to the agency, sold vermiculite insulation from there until 1983.
Grace closed the mine in 1990. The company and three of its former executives were acquitted in federal court last month of charges that they had knowingly contaminated Libby with asbestos and then conspired to cover up the deed.
Grace agreed last year to pay the federal government $250 million for cleanup efforts around the mining site. At least 200 people have died of asbestos-related diseases, with hundreds more sickened, in and around Libby, a town of about 2,600 people in Montana’s northwestern corner.
The E.P.A. offers information on dealing with vermiculite insulation at www.epa.gov/region1/enforcement/asbestos/qa.html. The agency recommends that homeowners who have vermiculite insulation assume that it is asbestos-contaminated.
Report on Gene for Depression Is Now Faulted
By BENEDICT CAREY, The New York Times, June 17, 2009
One of the most celebrated findings in modern psychiatry — that a single gene helps determine one’s risk of depression in response to a divorce, a lost job or another serious reversal — has not held up to scientific scrutiny, researchers reported Tuesday.
The original finding, published in 2003, created a sensation among scientists and the public because it offered the first specific, plausible explanation of why some people bounce back after a stressful life event while others plunge into lasting despair.
The new report, by several of the most prominent researchers in the field, does not imply that interactions between genes and life experience are trivial; they are almost certainly fundamental, experts agree.
But it does suggest that nailing down those factors in a precise way is far more difficult than scientists believed even a few years ago, and that the original finding could have been due to chance. The new report is likely to inflame a debate over the direction of the field itself, which has found that the genetics of illnesses like schizophrenia and bipolar disorder remain elusive.
“This gene/life experience paradigm has been very influential in psychiatry, both in the studies people have done and the way data has been interpreted,” said Dr. Kenneth S. Kendler, a professor of psychiatry and human genetics at Virginia Commonwealth University, “and I think this paper really takes the wind out of its sails.”
Others said the new analysis was unjustifiably dismissive. “What is needed is not less research into gene-environment interaction,” Avshalom Caspi, a neuroscientist at Duke University and lead author of the original paper, wrote in an e-mail message, “but more research of better quality.”
The original study was so compelling because it explained how nature and nurture could collude to produce a complex mood problem. It followed 847 people from birth to age 26 and found that those most likely to sink into depression after a stressful event — job loss, sexual abuse, bankruptcy — had a particular variant of a gene involved in the regulation of serotonin, a brain messenger that affects mood. Those in the study with another variant of the gene were significantly more resilient.
“I think what happened is that people who’d been working in this field for so long were desperate to have any solid finding,” Kathleen R. Merikangas, chief of the genetic epidemiology research branch of the National Institute of Mental Health and senior author of the new analysis, said in a phone interview. “It was exciting, and some people thought it was the finding in psychiatry, a major advance.”
The excitement spread quickly. Newspapers and magazines reported the finding. Columnists, commentators and op-ed writers emphasized its importance. The study provided some despairing patients with comfort, and an excuse — “Well, it is in my genes.” It reassured some doctors that they were medicating an organic disorder, and stirred interest in genetic testing for depression risk.
Since then, researchers have tried to replicate the gene finding in more than a dozen studies. Some found similar results; others did not. In the new study, being published Wednesday in The Journal of the American Medical Association, Neil Risch of the University of California, San Francisco, and Dr. Merikangas led a coalition of researchers who identified 14 studies that gathered the same kinds of data as the original study. The authors reanalyzed the data and found “no evidence of an association between the serotonin gene and the risk of depression,” no matter what people’s life experience was, Dr. Merikangas said.
By contrast, she said, a major stressful event, like divorce, in itself raised the risk of depression by 40 percent.
The authors conclude that the widespread acceptance of the original findings was premature, writing that “it is critical that health practitioners and scientists in other disciplines recognize the importance of replication of such findings before they can serve as valid indicators of disease risk” or otherwise change practice.
Dr. Caspi and other psychiatric researchers said it would be equally premature to abandon research into gene-environment interaction, when brain imaging and other kinds of evidence have linked the serotonin gene to stress sensitivity.
“This is an excellent review paper, no one is questioning that,” said Myrna Weissman, a professor of epidemiology and psychiatry at Columbia. “But it ignored extensive evidence from humans and animals linking excessive sensitivity to stress” to the serotonin gene.
Dr. Merikangas said she and her co-authors deliberately confined themselves to studies that could be directly compared to the original. “We were looking for replication,” she said.
In one view of the beginnings of life, depicted in an animation, carbon monoxide molecules condense on hot mineral surfaces underground to form fatty acids, above, which are then expelled from geysers.
New Glimpses of Life’s Puzzling Origins
By NICHOLAS WADE, The New York Times, June 16, 2009
Some 3.9 billion years ago, a shift in the orbit of the Sun’s outer planets sent a surge of large comets and asteroids careening into the inner solar system. Their violent impacts gouged out the large craters still visible on the Moon’s face, heated Earth’s surface into molten rock and boiled off its oceans into an incandescent mist.
Yet rocks that formed on Earth 3.8 billion years ago, almost as soon as the bombardment had stopped, contain possible evidence of biological processes. If life can arise from inorganic matter so quickly and easily, why is it not abundant in the solar system and beyond? If biology is an inherent property of matter, why have chemists so far been unable to reconstruct life, or anything close to it, in the laboratory?
The origins of life on Earth bristle with puzzle and paradox. Which came first, the proteins of living cells or the genetic information that makes them? How could the metabolism of living things get started without an enclosing membrane to keep all the necessary chemicals together? But if life started inside a cell membrane, how did the necessary nutrients get in?
The questions may seem moot, since life did start somehow. But for the small group of researchers who insist on learning exactly how it started, frustration has abounded. Many once-promising leads have led only to years of wasted effort. Scientists as eminent as Francis Crick, the chief theorist of molecular biology, have quietly suggested that life may have formed elsewhere before seeding the planet, so hard does it seem to find a plausible explanation for its emergence on Earth.
In the last few years, however, four surprising advances have renewed confidence that a terrestrial explanation for life’s origins will eventually emerge.
One is a series of discoveries about the cell-like structures that could have formed naturally from fatty chemicals likely to have been present on the primitive Earth. This lead emerged from a long argument between three colleagues as to whether a genetic system or a cell membrane came first in the development of life. They eventually agreed that genetics and membranes had to have evolved together.
The three researchers, Jack W. Szostak, David P. Bartel and P. Luigi Luisi, published a somewhat adventurous manifesto in Nature in 2001, declaring that the way to make a synthetic cell was to get a protocell and a genetic molecule to grow and divide in parallel, with the molecules being encapsulated in the cell. If the molecules gave the cell a survival advantage over other cells, the outcome would be “a sustainable, autonomously replicating system, capable of Darwinian evolution,” they wrote.
“It would be truly alive,” they added.
One of the authors, Dr. Szostak, of the Massachusetts General Hospital, has since managed to achieve a surprising amount of this program.
Simple fatty acids, of the sort likely to have been around on the primitive Earth, will spontaneously form double-layered spheres, much like the double-layered membrane of today’s living cells. These protocells will incorporate new fatty acids fed into the water, and eventually divide.
Living cells are generally impermeable and have elaborate mechanisms for admitting only the nutrients they need. But Dr. Szostak and his colleagues have shown that small molecules can easily enter the protocells. If they combine into larger molecules, however, they cannot get out, just the arrangement a primitive cell would need. If a protocell is made to encapsulate a short piece of DNA and is then fed with nucleotides, the building blocks of DNA, the nucleotides will spontaneously enter the cell and link into another DNA molecule.
At a symposium on evolution at the Cold Spring Harbor Laboratory on Long Island last month, Dr. Szostak said he was “optimistic about getting a chemical replication system going” inside a protocell. He then hopes to integrate a replicating nucleic acid system with dividing protocells.
Dr. Szostak’s experiments have come close to creating a spontaneously dividing cell from chemicals assumed to have existed on the primitive Earth. But some of his ingredients, like the nucleotide building blocks of nucleic acids, are quite complex. Prebiotic chemists, who study the prelife chemistry of the primitive Earth, have long been close to despair over how nucleotides could ever have arisen spontaneously.
Nucleotides consist of a sugar molecule, like ribose or deoxyribose, joined to a base at one end and a phosphate group at the other. Prebiotic chemists discovered with delight that bases like adenine will easily form from simple chemicals like hydrogen cyanide. But years of disappointment followed when the adenine proved incapable of linking naturally to the ribose.
Last month, John Sutherland, a chemist at the University of Manchester in England, reported in Nature his discovery of a quite unexpected route for synthesizing nucleotides from prebiotic chemicals. Instead of making the base and sugar separately from chemicals likely to have existed on the primitive Earth, Dr. Sutherland showed how under the right conditions the base and sugar could be built up as a single unit, and so did not need to be linked.
“I think the Sutherland paper has been the biggest advance in the last five years in terms of prebiotic chemistry,” said Gerald F. Joyce, an expert on the origins of life at the Scripps Research Institute in La Jolla, Calif.
Once a self-replicating system develops from chemicals, this is the beginning of genetic history, since each molecule carries the imprint of its ancestor. Dr. Crick, who was interested in the chemistry that preceded replication, once observed, “After this point, the rest is just history.”
Dr. Joyce has been studying the possible beginning of history by developing RNA molecules with the capacity for replication. RNA, a close cousin of DNA, almost certainly preceded it as the genetic molecule of living cells. Besides carrying information, RNA can also act as an enzyme to promote chemical reactions. Dr. Joyce reported in Science earlier this year that he had developed two RNA molecules that can promote each other’s synthesis from the four kinds of RNA nucleotides.
“We finally have a molecule that’s immortal,” he said, meaning one whose information can be passed on indefinitely. The system is not alive, he says, but performs central functions of life like replication and adapting to new conditions.
“Gerry Joyce is getting ever closer to showing you can have self-replication of RNA species,” Dr. Sutherland said. “So only a pessimist wouldn’t allow him success in a few years.”
Another striking advance has come from new studies of the handedness of molecules. Some chemicals, like the amino acids of which proteins are made, exist in two mirror-image forms, much like the left and right hand. In most naturally occurring conditions they are found in roughly equal mixtures of the two forms. But in a living cell all amino acids are left-handed, and all sugars and nucleotides are right-handed.
Prebiotic chemists have long been at a loss to explain how the first living systems could have extracted just one kind of the handed chemicals from the mixtures on the early Earth. Left-handed nucleotides are a poison because they prevent right-handed nucleotides linking up in a chain to form nucleic acids like RNA or DNA. Dr. Joyce refers to the problem as “original syn,” referring to the chemist’s terms syn and anti for the structures in the handed forms.
The chemists have now been granted an unexpected absolution from their original syn problem. Researchers like Donna Blackmond of Imperial College London have discovered that a mixture of left-handed and right-handed molecules can be converted to just one form by cycles of freezing and melting.
With these four recent advances — Dr. Szostak’s protocells, self-replicating RNA, the natural synthesis of nucleotides, and an explanation for handedness — those who study the origin of life have much to be pleased about, despite the distance yet to go. “At some point some of these threads will start joining together,” Dr. Sutherland said. “I think all of us are far more optimistic now than we were five or 10 years ago.”
One measure of the difficulties ahead, however, is that so far there is little agreement on the kind of environment in which life originated. Some chemists, like Günther Wächtershäuser, argue that life began in volcanic conditions, like those of the deep sea vents. These have the gases and metallic catalysts in which, he argues, the first metabolic processes were likely to have arisen.
But many biologists believe that in the oceans, the necessary constituents of life would always be too diluted. They favor a warm freshwater pond for the origin of life, as did Darwin, where cycles of wetting and evaporation around the edges could produce useful concentrations and chemical processes.
No one knows for sure when life began. The oldest generally accepted evidence for living cells are fossil bacteria 1.9 billion years old from the Gunflint Formation of Ontario. But rocks from two sites in Greenland, containing an unusual mix of carbon isotopes that could be evidence of biological processes, are 3.830 billion years old.
How could life have gotten off to such a quick start, given that the surface of the Earth was probably sterilized by the Late Heavy Bombardment, the rain of gigantic comets and asteroids that pelted the Earth and Moon around 3.9 billion years ago? Stephen Mojzsis, a geologist at the University of Colorado who analyzed one of the Greenland sites, argued in Nature last month that the Late Heavy Bombardment would not have killed everything, as is generally believed. In his view, life could have started much earlier and survived the bombardment in deep sea environments.
Recent evidence from very ancient rocks known as zircons suggests that stable oceans and continental crust had emerged as long as 4.404 billion years ago, a mere 150 million years after the Earth’s formation. So life might have had half a billion years to get started before the cataclysmic bombardment.
But geologists dispute whether the Greenland rocks really offer signs of biological processes, and geochemists have often revised their estimates of the composition of the primitive atmosphere. Leslie Orgel, a pioneer of prebiotic chemistry, used to say, “Just wait a few years, and conditions on the primitive Earth will change again,” said Dr. Joyce, a former student of his.
Chemists and biologists are thus pretty much on their own in figuring out how life started. For lack of fossil evidence, they have no guide as to when, where or how the first forms of life emerged. So they will figure life out only by reinventing it in the laboratory.
A Conversation With Bert Hölldobler: Insects Succeeding Through Cooperation
By CLAUDIA DREIFUS, The New York Times, June 16, 2009
At 72, Bert Hölldobler, a professor of life sciences at Arizona State University and a professor emeritus at the University of Würzburg in Germany, is one of the world’s great ant experts. Along with his collaborator, E. O. Wilson, Dr. Hölldobler won a Pulitzer Prize in 1991 for “The Ants.” The two wrote a second book in 2008, “The Superorganism: The Beauty, Elegance and Strangeness of Insect Societies.”
Q. HOW DID YOU AND EDWARD O. WILSON BECOME COLLABORATORS?
A. I met Ed Wilson in the 1970s when I first came to Harvard. We’d both been interested in ants since we were young boys, he in Alabama, I in Bavaria.
In Germany, there’s a saying, “Every boy goes through a bug phase.” Well, Ed and I, we never grew out of ours! The first time that Ed and I traveled together to Costa Rica, we turned over so many logs together, saw so many new things, that we gathered enough information for six research papers.
As for the friendship: that took time. First, we had collegial respect. We’d have lunch. We’d talk about ants. Like every scientist, we gossiped. Scientists gossip a lot! In German, there’s a saying, “You gossip like a washer-woman!” I always say, “No, I gossip like a scientist!” In Ed’s memoir, he said of me — and this touched me very much — “He’s like the younger brother I never had.”
Q. HOW DO TWO ALPHA BIOLOGISTS WRITE BOOKS TOGETHER?
A. We are very different, but we are remarkably complementary. I am basically the experimentalist. Ed is the synthesizer. When Ed reads a paper, he, very quickly, digests it. I read line by line. And sometimes I’ll say, “Ed, this is wrong.” Then we have lunch and we’ll joke around and soon the ball flies quickly.
Our friendship was really tested with our last book, “The Superorganism.” We agreed on about 89 percent of it. But we disagreed — and we still do — about sections in the chapter on evolution. He’d written the first draft. I said, “Let me rewrite it.” That took me two months. Later, Ed wrote, “You may have saved us a great deal of embarrassment, but I still don’t agree on several key points. Let me add some footnotes and a dissenting view.”
Amazingly, this never affected the friendship. With Ed Wilson, you can have a strong disagreement and still remain good friends.
Q. IN THAT BOOK, YOU AND WILSON WROTE THAT “INSECT SOCIETIES HAVE MUCH TO TEACH US.” LIKE WHAT?
A. Cooperation. The insect societies we study have evolutionary success because they are organized into a division of labor system. Only a relative few species — ants, honeybees, termites — have evolved social systems where you have a few reproductive individuals and hundreds or millions of nonreproductive nest mates.
In ant societies, the nonreproductives do particular tasks that benefit “the queens,” who reproduce. This distributed labor system allows the colonies to grow to enormous numbers. There are some species where there’s fierce internal competition to become the reproductives. Their colonies are usually small and less successful.
So when we say ants can teach us something, it’s not that we should all aspire to live like an ant. That would be horrible. What ants can teach is that networks of labor distribution, where communications are good and where each group’s work benefits the other, are effective. Economists know this.
Q. So to extrapolate to humans, should we all be happy with our place in the system?
A. We are really a different species. But we learn from nature and see some analogies, even though it has no evolutionary connect. We should value the work of a craftsman carpenter at the same level as we value the work of an academic person. Each part done in humans with expertise and done well has the same value.
I’m not saying that everyone should be paid the same. People have tried and it was a dismal failure. Karl Marx was right, but he picked the wrong species. With the ants, he was right. In their world, the individual is nothing, the society is everything.
Q. A LOT OF YOUR RESEARCH IS BASED ON OBSERVING ANT BEHAVIOR IN THE WILD. GIVEN THAT MOST ANTS ARE TINY, HOW DO YOU DO THAT?
A. You just go out and look. Here in Arizona, you don’t have to go very far to find desert ants. You see things. You get ideas. You test them out in the lab. We do a lot of genetic testing. We extract the chemicals that the ants make to learn about their communications systems.
One day I was walking in the mountains south of here and I had this lucky discovery. I saw hundreds of honey ants standing on stilt legs, displaying at each other. I had never seen this before. No one had.
What was going on? Through much observation, we realized that this was a territorial tournament. The ants come in opposing parties, do these displays, and somehow, a head count. If the numbers were more or less equal, everyone goes home after a while. But if one party proves to be weak, this tournament quickly moves to the nest entrance of the weaker group. Then the stronger group goes in and kills their queen.
Q. IS THIS ANT WARFARE?
A. Yes. And that led to the discovery of what I call ant slavery, which is what I’m working on now. I’m pulling together about 26 years’ worth of observation of it.
When the weak group is overrun, the stronger ones capture their pupae and larvae and take them to their own nest. These stolen immature individuals eventually hatch to become workers in the foreign colony. Their lifetime of labor then benefits the raiding group.
We’ve been using genetic testing to prove this. We’ve been looking at large ant colonies and we find again and again individuals who belong to foreign mothers. So these workers were definitely stolen. When I discovered this, this was amazing. This was the first example of slavery found where ants exploit foreign labor of their own species.
Q. WHAT FUNCTION DOES IT SERVE?
A. The same function slavery serves in humans. You get others to do your work for you.
Q. Why do so many humans hate ants?
A. It’s a mistake to think that people don’t like ants. Many children respond to them. They see that there’s a whole society and that ants behave socially.
Q. SO WHY DO THESE LOVELY CREATURES BITE ME WHEN I’M SITTING AT THE BEACH?
A. Because they don’t like you to sit where perhaps they have their trail and they want to forage. They want you to move away. It works.
Q. DO YOU CALL AN EXTERMINATOR WHEN ANTS INFEST YOUR KITCHEN?
A. No, I don’t mind them. Listen, if you have ants in the house, you take a wet towel and detergent and you wipe over their trail. Do this a couple of times and they’ll stay out. People come up after speeches and say, “But what can we do, we have ants?” I say, “Buy a magnifying glass and enjoy watching them.”
By CORNELIA DEAN, The New York Times, June 18, 2009
The Environmental Protection Agency declared a public health emergency on Wednesday in and near Libby, Mont., where over the course of decades asbestos contamination in a vermiculite mine has left hundreds of people dead or sickened from lung diseases.
It was the first health emergency ever declared under the Superfund law, the 1980 statute that governs sites contaminated or threatened by hazardous substances. The Libby site has been designated a Superfund priority since 2002.
A spokeswoman for the E.P.A. said that in anticipation of the declaration, the Department of Health and Human Services had agreed to make $6 million available to the Lincoln County Health Clinic, which provides care to residents of the area, to finance treatment of people with asbestos-related conditions. She said the declaration also authorized the environmental agency to remove vermiculite, whose uses include insulating, from buildings there.
In addition, she said, the agency will begin an effort to inform Americans generally about the risks of insulation made from vermiculite, a natural silicate mineral that forms in flakes. She said that it was not known how many homes nationally contained asbestos-contaminated vermiculite but that estimates ran into the tens of millions.
Vermiculite flakes puff up like popcorn when heated. Because the mineral is chemically inert, fire-resistant, lightweight and odorless, it was once widely used in insulation that was typically poured loosely between attic floor joists or between wall studs.
The Libby mine, originally operated by the Zonolite Company, at one time provided 80 percent of the nation’s vermiculite insulation, according to the E.P.A. W.R. Grace & Company bought the mine in 1963 and, according to the agency, sold vermiculite insulation from there until 1983.
Grace closed the mine in 1990. The company and three of its former executives were acquitted in federal court last month of charges that they had knowingly contaminated Libby with asbestos and then conspired to cover up the deed.
Grace agreed last year to pay the federal government $250 million for cleanup efforts around the mining site. At least 200 people have died of asbestos-related diseases, with hundreds more sickened, in and around Libby, a town of about 2,600 people in Montana’s northwestern corner.
The E.P.A. offers information on dealing with vermiculite insulation at www.epa.gov/region1/enforcement/asbestos/qa.html. The agency recommends that homeowners who have vermiculite insulation assume that it is asbestos-contaminated.
Report on Gene for Depression Is Now Faulted
By BENEDICT CAREY, The New York Times, June 17, 2009
One of the most celebrated findings in modern psychiatry — that a single gene helps determine one’s risk of depression in response to a divorce, a lost job or another serious reversal — has not held up to scientific scrutiny, researchers reported Tuesday.
The original finding, published in 2003, created a sensation among scientists and the public because it offered the first specific, plausible explanation of why some people bounce back after a stressful life event while others plunge into lasting despair.
The new report, by several of the most prominent researchers in the field, does not imply that interactions between genes and life experience are trivial; they are almost certainly fundamental, experts agree.
But it does suggest that nailing down those factors in a precise way is far more difficult than scientists believed even a few years ago, and that the original finding could have been due to chance. The new report is likely to inflame a debate over the direction of the field itself, which has found that the genetics of illnesses like schizophrenia and bipolar disorder remain elusive.
“This gene/life experience paradigm has been very influential in psychiatry, both in the studies people have done and the way data has been interpreted,” said Dr. Kenneth S. Kendler, a professor of psychiatry and human genetics at Virginia Commonwealth University, “and I think this paper really takes the wind out of its sails.”
Others said the new analysis was unjustifiably dismissive. “What is needed is not less research into gene-environment interaction,” Avshalom Caspi, a neuroscientist at Duke University and lead author of the original paper, wrote in an e-mail message, “but more research of better quality.”
The original study was so compelling because it explained how nature and nurture could collude to produce a complex mood problem. It followed 847 people from birth to age 26 and found that those most likely to sink into depression after a stressful event — job loss, sexual abuse, bankruptcy — had a particular variant of a gene involved in the regulation of serotonin, a brain messenger that affects mood. Those in the study with another variant of the gene were significantly more resilient.
“I think what happened is that people who’d been working in this field for so long were desperate to have any solid finding,” Kathleen R. Merikangas, chief of the genetic epidemiology research branch of the National Institute of Mental Health and senior author of the new analysis, said in a phone interview. “It was exciting, and some people thought it was the finding in psychiatry, a major advance.”
The excitement spread quickly. Newspapers and magazines reported the finding. Columnists, commentators and op-ed writers emphasized its importance. The study provided some despairing patients with comfort, and an excuse — “Well, it is in my genes.” It reassured some doctors that they were medicating an organic disorder, and stirred interest in genetic testing for depression risk.
Since then, researchers have tried to replicate the gene finding in more than a dozen studies. Some found similar results; others did not. In the new study, being published Wednesday in The Journal of the American Medical Association, Neil Risch of the University of California, San Francisco, and Dr. Merikangas led a coalition of researchers who identified 14 studies that gathered the same kinds of data as the original study. The authors reanalyzed the data and found “no evidence of an association between the serotonin gene and the risk of depression,” no matter what people’s life experience was, Dr. Merikangas said.
By contrast, she said, a major stressful event, like divorce, in itself raised the risk of depression by 40 percent.
The authors conclude that the widespread acceptance of the original findings was premature, writing that “it is critical that health practitioners and scientists in other disciplines recognize the importance of replication of such findings before they can serve as valid indicators of disease risk” or otherwise change practice.
Dr. Caspi and other psychiatric researchers said it would be equally premature to abandon research into gene-environment interaction, when brain imaging and other kinds of evidence have linked the serotonin gene to stress sensitivity.
“This is an excellent review paper, no one is questioning that,” said Myrna Weissman, a professor of epidemiology and psychiatry at Columbia. “But it ignored extensive evidence from humans and animals linking excessive sensitivity to stress” to the serotonin gene.
Dr. Merikangas said she and her co-authors deliberately confined themselves to studies that could be directly compared to the original. “We were looking for replication,” she said.
In one view of the beginnings of life, depicted in an animation, carbon monoxide molecules condense on hot mineral surfaces underground to form fatty acids, above, which are then expelled from geysers.
New Glimpses of Life’s Puzzling Origins
By NICHOLAS WADE, The New York Times, June 16, 2009
Some 3.9 billion years ago, a shift in the orbit of the Sun’s outer planets sent a surge of large comets and asteroids careening into the inner solar system. Their violent impacts gouged out the large craters still visible on the Moon’s face, heated Earth’s surface into molten rock and boiled off its oceans into an incandescent mist.
Yet rocks that formed on Earth 3.8 billion years ago, almost as soon as the bombardment had stopped, contain possible evidence of biological processes. If life can arise from inorganic matter so quickly and easily, why is it not abundant in the solar system and beyond? If biology is an inherent property of matter, why have chemists so far been unable to reconstruct life, or anything close to it, in the laboratory?
The origins of life on Earth bristle with puzzle and paradox. Which came first, the proteins of living cells or the genetic information that makes them? How could the metabolism of living things get started without an enclosing membrane to keep all the necessary chemicals together? But if life started inside a cell membrane, how did the necessary nutrients get in?
The questions may seem moot, since life did start somehow. But for the small group of researchers who insist on learning exactly how it started, frustration has abounded. Many once-promising leads have led only to years of wasted effort. Scientists as eminent as Francis Crick, the chief theorist of molecular biology, have quietly suggested that life may have formed elsewhere before seeding the planet, so hard does it seem to find a plausible explanation for its emergence on Earth.
In the last few years, however, four surprising advances have renewed confidence that a terrestrial explanation for life’s origins will eventually emerge.
One is a series of discoveries about the cell-like structures that could have formed naturally from fatty chemicals likely to have been present on the primitive Earth. This lead emerged from a long argument between three colleagues as to whether a genetic system or a cell membrane came first in the development of life. They eventually agreed that genetics and membranes had to have evolved together.
The three researchers, Jack W. Szostak, David P. Bartel and P. Luigi Luisi, published a somewhat adventurous manifesto in Nature in 2001, declaring that the way to make a synthetic cell was to get a protocell and a genetic molecule to grow and divide in parallel, with the molecules being encapsulated in the cell. If the molecules gave the cell a survival advantage over other cells, the outcome would be “a sustainable, autonomously replicating system, capable of Darwinian evolution,” they wrote.
“It would be truly alive,” they added.
One of the authors, Dr. Szostak, of the Massachusetts General Hospital, has since managed to achieve a surprising amount of this program.
Simple fatty acids, of the sort likely to have been around on the primitive Earth, will spontaneously form double-layered spheres, much like the double-layered membrane of today’s living cells. These protocells will incorporate new fatty acids fed into the water, and eventually divide.
Living cells are generally impermeable and have elaborate mechanisms for admitting only the nutrients they need. But Dr. Szostak and his colleagues have shown that small molecules can easily enter the protocells. If they combine into larger molecules, however, they cannot get out, just the arrangement a primitive cell would need. If a protocell is made to encapsulate a short piece of DNA and is then fed with nucleotides, the building blocks of DNA, the nucleotides will spontaneously enter the cell and link into another DNA molecule.
At a symposium on evolution at the Cold Spring Harbor Laboratory on Long Island last month, Dr. Szostak said he was “optimistic about getting a chemical replication system going” inside a protocell. He then hopes to integrate a replicating nucleic acid system with dividing protocells.
Dr. Szostak’s experiments have come close to creating a spontaneously dividing cell from chemicals assumed to have existed on the primitive Earth. But some of his ingredients, like the nucleotide building blocks of nucleic acids, are quite complex. Prebiotic chemists, who study the prelife chemistry of the primitive Earth, have long been close to despair over how nucleotides could ever have arisen spontaneously.
Nucleotides consist of a sugar molecule, like ribose or deoxyribose, joined to a base at one end and a phosphate group at the other. Prebiotic chemists discovered with delight that bases like adenine will easily form from simple chemicals like hydrogen cyanide. But years of disappointment followed when the adenine proved incapable of linking naturally to the ribose.
Last month, John Sutherland, a chemist at the University of Manchester in England, reported in Nature his discovery of a quite unexpected route for synthesizing nucleotides from prebiotic chemicals. Instead of making the base and sugar separately from chemicals likely to have existed on the primitive Earth, Dr. Sutherland showed how under the right conditions the base and sugar could be built up as a single unit, and so did not need to be linked.
“I think the Sutherland paper has been the biggest advance in the last five years in terms of prebiotic chemistry,” said Gerald F. Joyce, an expert on the origins of life at the Scripps Research Institute in La Jolla, Calif.
Once a self-replicating system develops from chemicals, this is the beginning of genetic history, since each molecule carries the imprint of its ancestor. Dr. Crick, who was interested in the chemistry that preceded replication, once observed, “After this point, the rest is just history.”
Dr. Joyce has been studying the possible beginning of history by developing RNA molecules with the capacity for replication. RNA, a close cousin of DNA, almost certainly preceded it as the genetic molecule of living cells. Besides carrying information, RNA can also act as an enzyme to promote chemical reactions. Dr. Joyce reported in Science earlier this year that he had developed two RNA molecules that can promote each other’s synthesis from the four kinds of RNA nucleotides.
“We finally have a molecule that’s immortal,” he said, meaning one whose information can be passed on indefinitely. The system is not alive, he says, but performs central functions of life like replication and adapting to new conditions.
“Gerry Joyce is getting ever closer to showing you can have self-replication of RNA species,” Dr. Sutherland said. “So only a pessimist wouldn’t allow him success in a few years.”
Another striking advance has come from new studies of the handedness of molecules. Some chemicals, like the amino acids of which proteins are made, exist in two mirror-image forms, much like the left and right hand. In most naturally occurring conditions they are found in roughly equal mixtures of the two forms. But in a living cell all amino acids are left-handed, and all sugars and nucleotides are right-handed.
Prebiotic chemists have long been at a loss to explain how the first living systems could have extracted just one kind of the handed chemicals from the mixtures on the early Earth. Left-handed nucleotides are a poison because they prevent right-handed nucleotides linking up in a chain to form nucleic acids like RNA or DNA. Dr. Joyce refers to the problem as “original syn,” referring to the chemist’s terms syn and anti for the structures in the handed forms.
The chemists have now been granted an unexpected absolution from their original syn problem. Researchers like Donna Blackmond of Imperial College London have discovered that a mixture of left-handed and right-handed molecules can be converted to just one form by cycles of freezing and melting.
With these four recent advances — Dr. Szostak’s protocells, self-replicating RNA, the natural synthesis of nucleotides, and an explanation for handedness — those who study the origin of life have much to be pleased about, despite the distance yet to go. “At some point some of these threads will start joining together,” Dr. Sutherland said. “I think all of us are far more optimistic now than we were five or 10 years ago.”
One measure of the difficulties ahead, however, is that so far there is little agreement on the kind of environment in which life originated. Some chemists, like Günther Wächtershäuser, argue that life began in volcanic conditions, like those of the deep sea vents. These have the gases and metallic catalysts in which, he argues, the first metabolic processes were likely to have arisen.
But many biologists believe that in the oceans, the necessary constituents of life would always be too diluted. They favor a warm freshwater pond for the origin of life, as did Darwin, where cycles of wetting and evaporation around the edges could produce useful concentrations and chemical processes.
No one knows for sure when life began. The oldest generally accepted evidence for living cells are fossil bacteria 1.9 billion years old from the Gunflint Formation of Ontario. But rocks from two sites in Greenland, containing an unusual mix of carbon isotopes that could be evidence of biological processes, are 3.830 billion years old.
How could life have gotten off to such a quick start, given that the surface of the Earth was probably sterilized by the Late Heavy Bombardment, the rain of gigantic comets and asteroids that pelted the Earth and Moon around 3.9 billion years ago? Stephen Mojzsis, a geologist at the University of Colorado who analyzed one of the Greenland sites, argued in Nature last month that the Late Heavy Bombardment would not have killed everything, as is generally believed. In his view, life could have started much earlier and survived the bombardment in deep sea environments.
Recent evidence from very ancient rocks known as zircons suggests that stable oceans and continental crust had emerged as long as 4.404 billion years ago, a mere 150 million years after the Earth’s formation. So life might have had half a billion years to get started before the cataclysmic bombardment.
But geologists dispute whether the Greenland rocks really offer signs of biological processes, and geochemists have often revised their estimates of the composition of the primitive atmosphere. Leslie Orgel, a pioneer of prebiotic chemistry, used to say, “Just wait a few years, and conditions on the primitive Earth will change again,” said Dr. Joyce, a former student of his.
Chemists and biologists are thus pretty much on their own in figuring out how life started. For lack of fossil evidence, they have no guide as to when, where or how the first forms of life emerged. So they will figure life out only by reinventing it in the laboratory.
A Conversation With Bert Hölldobler: Insects Succeeding Through Cooperation
By CLAUDIA DREIFUS, The New York Times, June 16, 2009
At 72, Bert Hölldobler, a professor of life sciences at Arizona State University and a professor emeritus at the University of Würzburg in Germany, is one of the world’s great ant experts. Along with his collaborator, E. O. Wilson, Dr. Hölldobler won a Pulitzer Prize in 1991 for “The Ants.” The two wrote a second book in 2008, “The Superorganism: The Beauty, Elegance and Strangeness of Insect Societies.”
Q. HOW DID YOU AND EDWARD O. WILSON BECOME COLLABORATORS?
A. I met Ed Wilson in the 1970s when I first came to Harvard. We’d both been interested in ants since we were young boys, he in Alabama, I in Bavaria.
In Germany, there’s a saying, “Every boy goes through a bug phase.” Well, Ed and I, we never grew out of ours! The first time that Ed and I traveled together to Costa Rica, we turned over so many logs together, saw so many new things, that we gathered enough information for six research papers.
As for the friendship: that took time. First, we had collegial respect. We’d have lunch. We’d talk about ants. Like every scientist, we gossiped. Scientists gossip a lot! In German, there’s a saying, “You gossip like a washer-woman!” I always say, “No, I gossip like a scientist!” In Ed’s memoir, he said of me — and this touched me very much — “He’s like the younger brother I never had.”
Q. HOW DO TWO ALPHA BIOLOGISTS WRITE BOOKS TOGETHER?
A. We are very different, but we are remarkably complementary. I am basically the experimentalist. Ed is the synthesizer. When Ed reads a paper, he, very quickly, digests it. I read line by line. And sometimes I’ll say, “Ed, this is wrong.” Then we have lunch and we’ll joke around and soon the ball flies quickly.
Our friendship was really tested with our last book, “The Superorganism.” We agreed on about 89 percent of it. But we disagreed — and we still do — about sections in the chapter on evolution. He’d written the first draft. I said, “Let me rewrite it.” That took me two months. Later, Ed wrote, “You may have saved us a great deal of embarrassment, but I still don’t agree on several key points. Let me add some footnotes and a dissenting view.”
Amazingly, this never affected the friendship. With Ed Wilson, you can have a strong disagreement and still remain good friends.
Q. IN THAT BOOK, YOU AND WILSON WROTE THAT “INSECT SOCIETIES HAVE MUCH TO TEACH US.” LIKE WHAT?
A. Cooperation. The insect societies we study have evolutionary success because they are organized into a division of labor system. Only a relative few species — ants, honeybees, termites — have evolved social systems where you have a few reproductive individuals and hundreds or millions of nonreproductive nest mates.
In ant societies, the nonreproductives do particular tasks that benefit “the queens,” who reproduce. This distributed labor system allows the colonies to grow to enormous numbers. There are some species where there’s fierce internal competition to become the reproductives. Their colonies are usually small and less successful.
So when we say ants can teach us something, it’s not that we should all aspire to live like an ant. That would be horrible. What ants can teach is that networks of labor distribution, where communications are good and where each group’s work benefits the other, are effective. Economists know this.
Q. So to extrapolate to humans, should we all be happy with our place in the system?
A. We are really a different species. But we learn from nature and see some analogies, even though it has no evolutionary connect. We should value the work of a craftsman carpenter at the same level as we value the work of an academic person. Each part done in humans with expertise and done well has the same value.
I’m not saying that everyone should be paid the same. People have tried and it was a dismal failure. Karl Marx was right, but he picked the wrong species. With the ants, he was right. In their world, the individual is nothing, the society is everything.
Q. A LOT OF YOUR RESEARCH IS BASED ON OBSERVING ANT BEHAVIOR IN THE WILD. GIVEN THAT MOST ANTS ARE TINY, HOW DO YOU DO THAT?
A. You just go out and look. Here in Arizona, you don’t have to go very far to find desert ants. You see things. You get ideas. You test them out in the lab. We do a lot of genetic testing. We extract the chemicals that the ants make to learn about their communications systems.
One day I was walking in the mountains south of here and I had this lucky discovery. I saw hundreds of honey ants standing on stilt legs, displaying at each other. I had never seen this before. No one had.
What was going on? Through much observation, we realized that this was a territorial tournament. The ants come in opposing parties, do these displays, and somehow, a head count. If the numbers were more or less equal, everyone goes home after a while. But if one party proves to be weak, this tournament quickly moves to the nest entrance of the weaker group. Then the stronger group goes in and kills their queen.
Q. IS THIS ANT WARFARE?
A. Yes. And that led to the discovery of what I call ant slavery, which is what I’m working on now. I’m pulling together about 26 years’ worth of observation of it.
When the weak group is overrun, the stronger ones capture their pupae and larvae and take them to their own nest. These stolen immature individuals eventually hatch to become workers in the foreign colony. Their lifetime of labor then benefits the raiding group.
We’ve been using genetic testing to prove this. We’ve been looking at large ant colonies and we find again and again individuals who belong to foreign mothers. So these workers were definitely stolen. When I discovered this, this was amazing. This was the first example of slavery found where ants exploit foreign labor of their own species.
Q. WHAT FUNCTION DOES IT SERVE?
A. The same function slavery serves in humans. You get others to do your work for you.
Q. Why do so many humans hate ants?
A. It’s a mistake to think that people don’t like ants. Many children respond to them. They see that there’s a whole society and that ants behave socially.
Q. SO WHY DO THESE LOVELY CREATURES BITE ME WHEN I’M SITTING AT THE BEACH?
A. Because they don’t like you to sit where perhaps they have their trail and they want to forage. They want you to move away. It works.
Q. DO YOU CALL AN EXTERMINATOR WHEN ANTS INFEST YOUR KITCHEN?
A. No, I don’t mind them. Listen, if you have ants in the house, you take a wet towel and detergent and you wipe over their trail. Do this a couple of times and they’ll stay out. People come up after speeches and say, “But what can we do, we have ants?” I say, “Buy a magnifying glass and enjoy watching them.”