Wednesday, January 9, 2008

Louis J Sheehan Esquire 30074

For an eternity, our universe lay dormant—a frozen, featureless netherworld. Then, about 15 billion years ago, the cosmos got an abrupt wake-up call.

According to the standard theory, the universe was born some 15 billion years ago in a hot, expanding fireball, an event scientists call the Big Bang. The universe then underwent a brief spurt of faster-than-light expansion, called inflation, before settling down to the much slower, steady expansion observed today.

If a theory ain't broken, why fix it? Even in its most primitive form, which does not include inflation, the Big Bang theory correctly predicts the cosmic abundance of helium and deuterium and the temperature of the radiation left over from the birth of the universe.

The classical Big Bang picture was first proposed in the late 1920s. Two decades ago, researchers realized that the scenario needed to be modified.

In its original form, the model would lead to a universe vastly different from the one we live in. For instance, the theory doesn't provide a way for stars, galaxies, and larger structures to arise, notes Steinhardt. Moreover, the Big Bang model would tend to produce a cosmos whose composition and density would vary widely from place to place and whose overall geometry would be warped or curved.

That's in stark contrast to numerous observations, which reveal a universe that is the same, on the large scale, in all directions and has just the right amount of matter and energy to keep it perfectly flat.

In 1980, Guth amended the Big Bang theory to account for these discrepancies. Refined by several researchers over the past 2 decades, Guth's model posits that the infant cosmos underwent a brief but enormous episode of inflation, ballooning at a rate faster than the speed of light. In just 10–32 seconds, the universe expanded its girth by a factor of about 100 trillion trillion, more than it has in the billions of years that have elapsed since.

The inflation model accomplishes several feats. It explains why widely separated parts of the universe—regions so far apart that all communication between them is impossible—can nonetheless look as similar as the closest of neighbors. Inflation theory suggests that when the universe began, these regions were indeed neighbors and then rapidly spread far apart.

Inflation also makes the universe flat. Any curvature to space-time would have been stretched out by this era of faster-than-light expansion.

Furthermore, the ballooning would have provided a way for chance subatomic fluctuations in the early universe to inflate to macroscopic proportions. Over time, gravity could then have molded these variations into the spidery network of galaxies and voids seen in the universe today.

The Big Bang model combined with inflation matches several important observations, including the detailed structure of the radiation called the cosmic microwave background, which is left over from the universe's birth. Data gathered by several balloon-borne and ground-based telescopes fit the predictions of the inflation model.

Yet some cosmologists view inflation as a mysterious, ad hoc device. For instance, notes Steinhardt, no one knows what type of force triggered the onset of inflation or what ended it. "We've been searching for several years to find either a more natural way of incorporating inflation or an alternative model based on new physics," he says.

String theory

Inflation, Steinhardt says, is based on quantum field theory, which views every elementary particle as a pointlike object. In the past decade, however, physicists have begun thinking about elementary particles in a new way, based on a model called string theory.

According to this view, electrons, quarks, and all the other elementary particles in the universe behave as point particles when observed at a distance, but each is actually composed of tiny loops or strings of energy. The different vibrations of a string, like the different notes that can be plucked on a violin, correspond to different particles.

"It's a beautiful idea because it says that all of the particles we see actually arise from a single object—string," says Ovrut.

Each string vibrates in a space-time that has 11 dimensions—7 dimensions beyond the usual 3 of space and 1 of time. The newest twist on string theory, dubbed M theory, allows for more-complex objects: surfaces rather than just strings. These surfaces are known as membranes, or just branes.

Many physicists are studying branes in the hope of linking gravity and the other fundamental forces of nature to the elementary particles that communicate these forces. According to Steinhardt and his colleagues, certain types of branes may turn out to have profound consequences for cosmology.

Instead of working with the 11 dimensions implied by M theory, the researchers have focused on branes that exist in 5 dimensions. In this model, the other 6 dimensions are tightly curled up and can be ignored. Certain branes that exist in this abstract five-dimensional space can be represented by infinitely long, parallel planes and seem to have a close correspondence to our universe.

In this construct, our cosmos could have plenty of company. Other would-be universes—also represented by branes—may be floating through the fifth dimension. These branes would remain invisible because particles and light can't travel through the fifth dimension. However, gravity can couple matter across that dimension, and collisions between branes are possible.

In the ekpyrotic scenario, the fifth dimension is finite in size and bounded on either side by a three-dimensional brane. One of these boundary branes was the surface that was to become our own cosmos, and the other represents another universe. In the version of the theory first described last April, a third brane peels off the opposing boundary brane and bangs into ours. In the collision, it melds with our brane, igniting the Big Bang.

"There is a certain sense in which this is like two pieces of putty slamming into each other and heating up," says Ovrut.

Critics of the scenario, as well as Steinhardt's team, have noted that the universe created by the impact contracts rather than expands. If so, it wouldn't have generated a cosmos like ours.

In a modified version of the ekpyrotic theory, posted Aug. 26 on the Internet (, Steinhardt, Nathan Seiberg of the Institute of Advanced Study in Princeton, N.J., and their collaborators say such concerns are now unwarranted. According to their calculations, the new model can produce a collision without having to rely on one invisible brane peeling off from another.

Instead, one of the boundary branes moves slowly but steadily toward the other, attracted by an exchange of lower-dimension branes between the two. As the boundary brane moves, it shrinks the fifth dimension. When the two boundary branes touch, the fifth dimension collapses completely, an event the researchers call the Big Crunch.

As in the earlier version of the theory, the collision triggers the Big Bang. However after the impact, the two boundary branes bounce off each other and move apart, recreating the fifth dimension. This rebound starts the expansion of our universe.

In either version of the theory, the laws that govern elementary particle physics require that the boundary branes be flat as a pancake before they collide and that they stay that way afterwards. Consequently, the universe generated by the collision is flat. An episode of inflation isn't needed to stretch out any curvature since none ever existed.

Because the impact is so uniform—exactly the same force is applied up and down the flat boundary between the two branes— widely separated parts of the universe get the same kick and thus evolve in exactly the same way after the collision. This accounts for the uniformity of distant reaches of the cosmos without having to invoke an episode of inflation.

Due to quantum effects, which make the boundary between the branes slightly uneven, some parts of our brane would be struck ever so slightly earlier or later than other parts. This would create tiny temperature differences within the struck brane that, like those in the standard Big Bang model, become the seeds for galaxy formation. The collision also causes the brane to stretch or expand, accounting for the expansion of the universe observed today.

The researchers "make a graceful transition from the Big Crunch to the Big Bang," says David N. Spergel of Princeton University. "This is arguably a `new ekpyrotic universe' that appears to be more elegant than the old model."

Which theory?

According to Steinhardt, the ekpyrotic theory does everything that Big Bang plus inflation accomplishes. "It's just that we happened to discover one theory first—20 years ago," he says.

"What [the ekpyrotic theory] has going for it is a much closer relationship to string theory than any formulation we currently have of inflation," says Guth. "String theory is simply the only hope we currently have for a quantum theory of gravity, and obviously gravity has to be quantized to be consistent with the rest of what we know about physics."

Nonetheless, "I'm still somewhat skeptical about the whole thing," Guth adds. "They need to make very strong assumptions about the initial conditions—they're really starting out with a universe that's already infinite and uniform."

Another developer of the inflation model, Andrei Linde of Stanford University, takes a much dimmer view of the new work and has posted several papers on the Internet lambasting the ekpyrotic model. He says that to produce galaxies, Steinhardt and his colleagues have to choose a highly specialized, unrealistic form of interaction between branes. Moreover, Linde claims that the branes in the ekpyrotic model are not truly uniform in structure and therefore can't account for the large-scale uniformity of the universe.

"Instead of a theory, we have only wishful thinking," he says.

Steinhardt and his colleagues have posted responses on the Internet.

A slow process

Making a universe in ekpyrotic theory requires patience, notes Ovrut. Because the attractive force between branes is so small, they move at a snail's pace, and it could take an extraordinarily long time for a collision to occur, he says.

In effect, says Ovrut, the new theory replaces the very short growth spurt of inflation with a very long lead time for a collision.

As a bonus, he notes, the collision described by ekpyrotic theory not only generates cosmic structure, it also creates the known families of quarks and other fundamental particles.

"What's very beautiful about these brane models is that one can actually compute the spectrum of [elementary] particles, and what you get is something like our real world," notes Ovrut.

At least one empirical test of the ekpyrotic theory may soon be possible. The test would examine gravitational waves, the radiation produced when massive objects accelerate.

Big Bang plus inflation predicts that gravitational waves can have extremely long wavelengths, while the ekpyrotic theory does not. Long-wavelength gravitational waves would leave a distinctive fingerprint on the cosmic microwave background.

Future experiments with a new generation of space, balloon-borne, and ground-based telescopes may be able to detect that fingerprint, says Ovrut.

Other aspects of the ekpyrotic model are still being scrutinized.

"I worry a lot about the details," says Ovrut. "This is a theory that's really still in its infancy."

While hiking in California's Sierra Nevada Mountains, Seth Donahue ran into quite a few bears. The lumbering omnivores filled Dr. Donahue, a biomedical engineer, with curiosity rather than fear.

Why don't bears suffer from osteoporosis during hibernation, he asked himself during one wilderness encounter nearly a decade ago? Even a few weeks of inactivity for humans, and most animals, are enough to soften and weaken bones. But bears snooze as much as six months a year and wake up robust and ready to rumble.

Dr. Donahue, now 39 and a professor at Michigan Technological University, figured there might be a substance in bears that helps keep their bones strong. If he could find it, he might also find better treatments for osteoporosis in humans.

Osteoporosis affects tens of millions of Americans, and drugs to treat the disease represent a multibillion-dollar market. But most of the medicines don't restore bone -- they only slow its deterioration.

Dr. Donahue found that bears have a uniquely potent form of a substance called parathyroid hormone, which helps maintain bones. The ursine version of the substance spurs bone growth when it normally wouldn't occur, offsetting the deterioration that one would expect for a bear snoozing away in the woods.

Dr. Donahue's group has sequenced the gene for the bear parathyroid hormone and has had a small amount of it made synthetically. He's applied for a government grant to fund the lab's efforts to insert the gene into bacteria and coaxed them to produce the substance.

But how do you get a hormone sample from a bear in the first place? Very carefully. At first, Dr. Donahue relied on a colleague at Virginia Tech for blood samples taken from a half-dozen bears tracked with radio tags.

Even hibernating bears need to be anesthetized before a needle is inserted to draw their blood, or they might awaken, distorting the results and putting the researchers at risk. "It's not like rats where you can get 100 animals and bring them into the lab and do whatever you want with them," Dr. Donahue said.

Later, he teamed up with Washington State University's Charles Robbins, who was studying changes in the hearts of hibernating bears. Dr. Robbins had a group of black bears raised in captivity that were comfortable around humans and were used to having tests performed. That gave Dr. Donahue's lab an easier way to get blood samples.

Despite the hurdles, Dr. Donahue, it turns out, wasn't the first scientist to be curious about bear bones. In 1990, a Boise, Idaho, orthopedic surgeon named Tim Floyd captured a few bears, anesthetized them and biopsied a large bone in their hips.

Dr. Floyd's findings were provocative, Dr. Donahue said, because they suggested that bears didn't lose bone during hibernation. Dr. Floyd entered private practice and didn't pursue his findings. But when he learned of Dr. Donahue's work, Dr. Floyd kicked in some of his own money to keep it rolling. Dr. Donahue also receives support from the National Institutes of Health and the Michigan Universities Commercialization Initiative.

Dr. Donahue published his first results in 2003 when he was doing post-doctoral research at Penn State University. The results were perplexing because they seemed to suggest that bears were actually losing bone during hibernation. "At that point my hopes weren't as high, but I was still interested," Dr. Donahue said.

He kept at it, and published a paper later in 2003, after he had moved to Michigan Tech, showing that bone growth in hibernating bears was equal to the rate of loss. After the bears wake up in the spring, the bone grows even more rapidly.

Washing mouse bone cells with blood taken from bears in different seasons supported the idea that the winter samples had boosted bone formation, according to another paper he published in 2006.

Dr. Donahue's research on bears has advanced far enough toward a treatment for humans to capture commercial interest. Apjohn, a company founded by drug giant Pfizer when it closed Upjohn facilities in Kalamazoo, Mich., and Michigan Tech have an agreement to commercialize Dr. Donahue's technology. To do that, they've created a company called Aursos, a name derived from ursos, Latin for bears.

Apjohn's Ron Shebuski, who once studied snake venom and vampire bat saliva as a researcher at Merck, praised Dr. Donahue's elegant and sometimes risky work on parathyroid hormone in bears. "Seth is just a maniac on this stuff," he said.

Most available osteoporosis drugs, such as Merck's Fosamax, slow the breakdown of bone, but they don't do much to build it up. An exception is Eli Lilly's Forteo, a shortened version of the human parathyroid hormone, with about $500 million in sales. Forteo can build bone, but the drug, taken in a daily injection, carries a black-box warning about cancer risks because of tumors found in rats treated with the medicine.

Dr. Donahue, now on sabbatical in Ireland, says his lab just finished treating some rats with a synthetic version of human parathyroid hormone -- not unlike Forteo -- and others with bear parathyroid hormone to see which did a better job building up bone. Next up are studies in female rats whose ovaries have been removed, creating a menopause-like condition.

Dr. Donahue is unlikely to see any bears while in Ireland; they're extinct there. But he did admit to taking an interest in the bones of one that died thousands of years ago in an Irish cave. Meanwhile, despite his hiking inspiration, when it comes to his research, he laughs: "Nearly 10 years later, I haven't been out in the field once."

It's no wonder that more Americans are gulping fish oil. Hardly a month goes by without a study suggesting that the omega-3 fatty acids in fish oil can fend off disease -- including heart attacks, strokes, Alzheimer's disease, depression, rheumatoid arthritis, asthma, psoriasis and even attention-deficit hyperactivity disorder.

The problem is, to get the health benefits seen in clinical trials, you probably need to take fistfuls of capsules.

"The kind of benefits seen in most of the clinical trials with omega-3 generally have involved much higher doses than you see recommended on supplement labels," says Charles Serhan, a Harvard Medical School expert on omega-3's activity. "But although a large number of studies have used industrial-level doses," he adds, "we don't have rigorous scientific evidence about what the doses should be."

Regardless of the recommended dose, the need to stockpile bottles of supplements may diminish as more foods are fortified with omega-3 and as research shows ways of enhancing the benefits with other therapies.

While most of the scientific data on the health effects of fish oil aren't definitive, the federal National Institutes of Health concluded after a massive review three years ago that consuming omega-3 fatty acids cuts the risk of death from heart attacks and other cardiovascular causes, can reduce the joint pain of rheumatoid arthritis and "appears" important for proper brain development and function.

Because of news like that, the market for fish-oil supplements is booming. U.S. omega-3 supplement sales reached an estimated $600 million last year, up 20% from a year earlier, says the Global Organization for EPA and DHA Omega-3s, a Salt Lake City trade group. (The two key omega-3 fatty acids are called EPA and DHA.) Omega-3 fatty acids now rank as the fifth-best-selling dietary supplement, behind multivitamins, calcium and vitamins C and E.

In trials aimed at lowering high blood levels of triglycerides, a contributor to heart disease, patients took four particularly potent capsules that contained a total of more than three grams of EPA and DHA a day. You would have to pop a daily dozen of the typical omega-3 capsules on the market to get that much -- four to six times the suggested daily "serving" usually specified on their labels. That many capsules could cost you more than $2 a day, and it is a lot more than you are likely to get from consuming fish: You would need more than six servings a day of tuna, or about three of salmon, to get that much EPA and DHA.

Clinical trials suggest that fish oil can fend off a variety of ailments, but the omega-3 doses used in the studies have varied widely.
• Heart disease: one gram or more
• Rheumatoid arthritis: two grams or more
• Brain health: one-half gram or more

Fish may good for you, but you can get risky doses of mercury and other toxins by consuming lots of it. That is one reason the American Heart Association recommends that people who need to lower triglycerides to ward off heart attacks take omega-3 capsules. The suggested dose is two to four grams of EPA and DHA a day, which supplements can provide toxin-free. For healthy adults seeking merely to cut cardiac risks, the heart association says eating fatty fish, such as salmon, at least twice a week is probably enough.

But how much omega-3 should you take if you are trying to ease the joint inflammation of rheumatoid arthritis? Or ward off Alzheimer's disease? Or alleviate depression?
Louis J Sheehan
Louis J Sheehan, Esquire

Unfortunately, there aren't enough clinical data to give firm answers. But the omega-3 literature affords hints. Results in various rheumatoid-arthritis trials indicate that you need to take more than two grams, perhaps 10 typical capsules, of omega-3 fatty acids a day to significantly curtail joint inflammation and pain.

For maintaining brain health, the overall data on omega-3's potential are inconclusive, according to the NIH. But a recent Dutch study showed that about 400 milligrams of EPA and DHA a day -- which you can get from two typical omega-3 capsules -- helped elderly men maintain mental acuity. The study found that the more omega-3 ingested, the greater the benefit.

In the depression data, two things stand out: EPA appears more effective than DHA. And about one gram of EPA seems optimal -- more isn't better.

All this suggests that you may have to take a half dozen or more typical omega-3 pills a day to get the kind of benefits observed in clinical trials with fish oil. But soon it may get easier to get such hefty doses without taking so many pills. A growing number of foods are fortified with omega-3, everything from yogurt to orange juice, including more than 1,200 such products launched in 2006 alone, according to the London-based market researcher Datamonitor. Such foods typically don't contain much omega-3 -- a fortified egg might contain half as much as a typical capsule. But as more fortified foods come to market, it will be easier to get omega-3 in your diet.

There is another reason popping fish-oil capsules by the fistful may be overkill. Many scientists believe omega-3's benefits flow primarily from its ability to damp low-level inflammation, which is thought to be a key culprit in just about every major scourge of aging, from clogged arteries to Alzheimer's. Studies over the past few years suggest that taking small doses of aspirin daily, which many people do to prevent heart attacks, magnifies the anti-inflammatory effect of taking fish oil.

Indeed, some of the most dramatic evidence of fish oil's heart benefits came from a 1999 Italian study in which patients who had recently had heart attacks showed a 45% reduction in subsequent "sudden cardiac death" when given modest fish-oil doses (the amount in about three typical omega-3 capsules). The supplements' striking effectiveness may well have been magnified by the fact that many of the patients were also taking aspirin daily.

Aspirin's effect on omega-3 isn't clear yet, though. So for now, big doses of the supplement probably are necessary to get the health benefits.

Omega-3 appears to be safe, even at the high doses used in clinical trials. But large doses can have side effects. Perhaps the best source on that issue is the prescribing information for Lovaza. Sold by GlaxoSmithKline PLC unit Reliant Pharmaceuticals Inc., Lovaza is prescribed for "very high" triglycerides.

In Lovaza's clinical trials, patients took four capsules a day with a total of 3.4 grams of EPA and DHA. The most common "adverse event," reported by about 5% of patients, was belching. Some 4% reported infections, compared with 2% on a placebo, but it's not clear whether fish oil caused the difference. While some research suggests that taking fish oil prolongs bleeding time, no bleeding problems were reported in the Lovaza trials.

There's no evidence Lovaza works better or is purer than high-end omega-3 dietary supplements -- such as those made by Nordic Naturals Inc., of Watsonville, Calif. -- which cost less than half as much as Lovaza does per gram of EPA and DHA.

A 2004 analysis of 44 kinds of omega-3 supplements by ConsumerLab.com1, based in Scarsdale, N.Y., found that none had unsafe levels of mercury or PCBs. And Lovaza wasn't used in most of the promising clinical trials with omega-3.

Mountains of uncollected trash smoldering on the streets of Naples are illuminating an unsightly reality about southern Italy: A combination of a weak state and powerful organized crime makes some areas of the country ungovernable.

In Naples, that combination has created a toxic mix that has paralyzed the city of more than two million, created serious health risks and revealed the inability of the government to tackle even the most basic urban problems. The Camorra, as the Naples Mafia is known, maintains a tight grip on the lucrative trash business, and as the situation has worsened, the Camorra's profit and power have risen.
[A large pile of trash littered a street in central Naples yesterday.]
A large pile of trash littered a street in central Naples yesterday.

Trash hasn't been picked up on the streets since Dec. 31, when the last of dumps in the area, which had been operating beyond capacity, couldn't accept more trash. And for several weeks before that, pickups had been sporadic at best. On Sunday, army units were called in to remove trash from school buildings so that students could return after the winter break. The gravity of the situation has led to a series of desperate but still useless measures taken by authorities.

In the Pianura neighborhood, authorities recently decided to reopen a dump that had been closed 11 years earlier. That sparked violent daily clashes with local residents.

To prevent police from reopening the dump, residents have felled tree trunks onto streets, commandeered city buses and set them ablaze, and poured oil onto roads. Yesterday evening, police finally withdrew from the area.

But while residents protest, trash piles up, blocking streets and entrances to buildings. Some piles reach to the third floor of apartment buildings. The city creates an estimated 8,000 metric tons of trash daily. Many of the heaps are set on fire, releasing dioxin and other noxious fumes. Naples's trash problem has become an embarrassment for the government of Prime Minister Romano Prodi, which, like its predecessors, has been powerless to bring about change. "Everyone is looking at us, and it's sad that Italy is presenting this negative image," he said Saturday. He also said his government was working on a plan to fix the situation "once and for all" and his government has been holding a series of meetings as it tries to come up with a plan.

However, the clashes are merely the latest chapter in an environmental crisis that began more than 13 years ago when the Campania region's dumps reached capacity. Since then, the Camorra has been able to tighten its control on the trash business, burrowing its way so deeply into the system that it has defeated every attempt by the state to fix the situation.

The national government first declared an emergency in 1994, appointing a special commissioner with broad powers to fix what was already a mounting crisis by building more than a dozen trash incinerators in the area. Since then, there has been a succession of six special commissioners. One trash incinerator has been built.
[A man worked his way through uncollected garbage on the streets of the Casoria district, on the outskirts of Naples, Sunday.]
A man worked his way through uncollected garbage on the streets of the Casoria district, on the outskirts of Naples, Sunday.

Franco Roberti, a prosecutor in Naples who has been investigating the trash crisis and its connections to organized crime, estimates that of the €1 billion, or about $1.5 billion, of public money spent in the Naples area on trash hauling and disposal, "the Camorra pockets about half." Working either through companies it owns directly or through intermediaries, it controls all the garbage trucks that transport the trash, as well as the dumps themselves.

The state of emergency has only benefited the Camorra, Mr. Roberti says, because it allows city governments to hand out public contracts quickly, bypassing the checks that would otherwise be necessary to ensure that hauling and collection companies aren't connected to organized crime.

The current crisis, Mr. Roberti says, is partly the result of a situation the Camorra created. For decades, it has run the highly illegal but lucrative business of hauling toxic waste from Italy's industrial north and dumping it in Campania, either in regular city dumps or simply in the open. Illegally hauling trash from the north to Campania caused the region's dumps to fill up more quickly, but also turned many municipal dumps into repositories of untreated toxic waste. Some worry that after years of this practice, toxins may be leaching into the groundwater around Naples.

Over the years local residents resisted efforts to build incinerators. However, authorities also blame the Camorra for fomenting many protests in order to block the incinerators, which could have threatened its control of the dumps and the transport system. "I have the sense that no one in Rome really understands how urgent this is or how difficult it will be to fix," says Mr. Roberti.

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