How Do You Stop Flesh-Eating Bacteria? Apply Some Clay

How Do You Stop Flesh-Eating Bacteria? Apply Some Clay

French green clay worked in the wilds of Africa's Ivory Coast—and now is proving its worth in the lab—as an effective treatment for dangerous bacteria

	ANTIBACTERIAL CLAY:  Researchers have discovered several clays that kill—or prevent from growing—bacteria, including antibiotic-resistant strains.

In the 1990s French humanitarian Line Brunet de Courssou began treating Buruli ulcer—violent, flesh-eating eruptions of Mycobacterium ulcerans—with two imported French green clays. The application of one type of clay to such lesions produced a pain that some patients equated to childbirth and, after several days, purplish skin tissue surrounding the open wound. A subsequent application of a second variety, this one mixed with shea butter (a fat), produced no pain and helped heal the oozing wound, replacing it with flexible scar tissue over the course of several months.

For centuries the French have used such green clays, rich in iron, for healing wounds. And the clays have proved capable of treating these M. ulcerans outbreaks, for which the only other cure is surgical removal or amputation. But scientific proof was lacking, so Brunet de Courssou enlisted the aid of mineralogist Lynda Williams of Arizona State University (A.S.U.) in Tempe to take pictures of the microscopic structure of the clays and try to figure out the source of their healing powers.

"This clay was unique in that they were very small particle size, 200 nanometers," or one four-hundredth the width of a human hair, Williams says. Their suppliers—French companies Agriletz and Agricur—could not say where the clays came from, but French mineralogists believe they might have formed from volcanic ash deposits in the Massif Central, an upland area in south-central France . "The suppliers themselves either don't know where they come from," Williams says, "or won't tell us."

Intrigued, Williams arranged to test the clays against Escherichia coli, the ubiquitous food pathogen. "That's when we first discovered that the first clay promoted bacterial growth and the second killed it," though she declines to identify either clay specifically. "The suppliers do not have any more antibacterial clay, we tested all of their supplies, so naming them is irrelevant."

But E. coli cultures mixed with the original batch of one of the clays disappeared entirely. "Something in this clay, whether it be physical or chemical, is killing this bacteria," says A.S.U. microbiologist Shelley Haydel, who was enlisted by Williams to help probe both clays' properties.

Haydel then tested the germ-killing clay against a variety of bacteria, ranging from Salmonella to antibiotic-resistant Staphylococcus aureus. "The strains that we are using are the same ones that pharmaceutical companies use to test their antibiotics," Haydel says. "All of the gram-negative pathogenic bacteria to humans that we've tested, we can kill completely."

Further, as with certain antibiotics such as tetracycline, the clay inhibited the growth of the bacteria that it could not destroy. "The number of cells we start with is 10⁷ Staph. aureus," Haydel says. "After 24 hours, that level reduces tenfold."

How the clay does this remains a mystery, however. Chemical testing revealed no particular minerals or metals in the clay that might explain its antibacterial properties, and even after leaching with water it retains its power. In fact, the clay kills pathogens even when heated to more than 1,000 degrees Fahrenheit (550 degrees Celsius), though it loses its germ-fighting ability when heated to more than 1,650 degrees F (900 degrees C).

Such heating destroys the clay's structure and leaves behind only the heaviest elements, such as radioactive cesium and selenium, along with poisonous arsenic. "But they are all below the minimum inhibitory concentration for E. coli," Williams notes. "They can tolerate 200 parts per million and we're talking about 50 ppm."

Williams says the clay's antibacterial effect appears to be chemical rather than physical, because its strength diminishes as it loses positively charged molecules and it does not smother the bacteria or cause its cell walls to burst. "After six hours, you can see a [bacterial cell] surface that is kind of wormy or grainy," Williams says. "It doesn't look like something is precipitating at the surface. Maybe something is going into the cell and damaging it that way."

It is also possible that the clay, which is, after all, a mix of many different elements in a malleable mass, combines several different properties to fight bacterial infection. "Is it a couple of things acting synergistically?" Haydel asks. "We just don't know."

Adds Williams: "I think these clays are buffering water to keep whatever's toxic to bacteria in there. If we remove the clay from water, I think it's not going to work."

The original batch of clay has already lost its curative power. "We went back and got some from the same batch and it didn't kill," Williams says. "This clay has been sitting outside in a pile for 10 years. It could have oxidized and maybe the oxidation state has affected the antibacterial properties."

Many more years of research will be required to determine what, if anything, gives the clay its ability to curb bacteria, and the researchers have yet to publish their results in a peer-reviewed journal. But they say there's clearly something to the ancient remedy: Two other clays with similar properties have already been identified. "They're all different mineralogically, though they have a general structure in common," Williams says. "We're trying to compare the properties of these antibacterial clays and see what's going on."

In the meantime, the clay treatment continues to be the only one available for flesh-dissolving M. ulcerans infections in Africa, a disease the World Health Organization has identified as an emerging health threat. And it is possible that the clays simply prompt the human immune system to respond to the infection, a response M. ulcerans normally suppresses.

Even so, the clays may well prove more useful than previously thought. "Even if you removed the antibacterial properties, do the clays have any effect on wound healing? What is the body's response? Are you stimulating tissue regeneration?" Haydel asks. "We already use maggots and leeches in hospitals. Why don't we use clays?"

 

Fastball-Strength Cosmic Rays Traced to Black Holes

Fastball-Strength Cosmic Rays Traced to Black Holes

First detailed mapping of high-energy cosmic rays points to galactic black holes as their source

	COSMIC RAY TRACING:  Schematic depiction of the first ultrahigh-energy cosmic ray (red) picked out by all four fluorescence telescope stations (colored pie shapes) at the Pierre Auger Observatory in Argentina, which also includes a vast array of particle detectors (red, orange and white dots).

Researchers have made a key breakthrough in a decades-old cosmic mystery by potentially identifying the source of ultrahigh-energy cosmic rays, rare but immensely powerful subatomic particles that strike our atmosphere each with the force of a fast-pitch baseball. A study published in Science finds that these rays pierce the atmosphere not from any which way but rather in the direction of nearby active galactic nuclei (AGNs), bright galactic cores that researchers believe are powered by supermassive black holes guzzling mass quantities of matter.

The discovery comes from a network of more than 1,400 ground-based particle detectors and two-dozen telescopes covering 1,200 square miles (3,000 square kilometers) of the western Argentine plains, an area nearly the size of Rhode Island. Yet to be completed, the Pierre Auger Cosmic Ray Observatory South has nonetheless become the first experiment to piece together the trajectories of rare high-energy cosmic rays, first discovered in 1962.

"Nature has been very generous with us," says astrophysicist Antoine Letessier-Selvon of the University of Paris 6 and 7, part of a 160-person data analysis subgroup within the nearly 400-member Auger collaboration.

Cosmic rays are protons or atomic nuclei that travel through space at near light speed. When they strike Earth's atmosphere, they detonate in a burst of lighter particles, or air shower, extending up to 15 square miles (40 square kilometers). The highest energy cosmic rays pack a punch of more than 10²⁰ electron volts (referred to as 100 exa-electrons volts, or EeV), which is 100 million times the energy produced by the largest particle accelerators and roughly equivalent to that of a well-thrown baseball.

"It is extremely difficult to understand how particles are accelerated that high," Letessier-Selvon says. Researchers say only a few sources were conceivable, including speculative remnants of the big bang or vast hiccups of matter in the early universe as well as AGNs, which were at least known to exist.

PEEKABOO:  This water-filled particle detector, part of the Pierre Auger Observatory in Argentina, is one of more than 1,400 stations (out of a planned 1,600) currently deployed at grid points in a Rhode Island-size array.

Complicating the problem, high-energy cosmic rays strike Earth at an average rate of about once per square kilometer per century, hence the sprawling Auger Observatory, which will contain 1,600 particle detectors when finished. (Auger North, to be located in the U.S., is planned for observations in the Northern Hemisphere.)

On the plus side, whereas lower energy cosmic rays become jumbled like billiard balls on their journeys, the highest energy rays fly relatively straight and true. By observing air showers from multiple vantage points, Auger instruments triangulated the flight paths of nearly a million cosmic ray showers since January 2004, the group reports.

A record 77 of the rays were the high-energy variety, registering 40 EeV, the threshold at which they begin to scatter off of the cosmic microwave background radiation. Of these, the 27 most energetic—exceeding 57 EeV—were tightly matched with parts of the sky that included AGNs lying within a few hundred million light-years of Earth.

"We're now convinced that they're not produced in the galaxy," Letessier-Selvon says. The exact source remains uncertain, he explains, because the team had to estimate the bending of the charged rays in the Milky Way's magnetic field, which should come into sharper focus as the observatory detects more events.

"It's pretty suggestive of a particular origin of these cosmic rays," namely AGNs, says astrophysicist Roger Blandford of Stanford University, who was not part of the collaboration, adding that massive, spinning black holes had always been to him "the least implausible source." 

To power the rays, Blandford says, an AGN's central black hole would have to produce a massive electric field very far from itself, because otherwise the cauldron of photons around the hole would scatter the cosmic rays and blunt their energy.

He adds researchers would never have guessed that black holes might have such powers if not for high-energy cosmic rays. "Nature does tricks we didn't know were possible," he says. "But it is happening and it's marvelous." Auger should eventually pinpoint the rays' origins definitely, he says. "They have the capacity to answer these questions beyond all reasonable doubt." 

Got Smarts? Mother's Milk May Pump Up Baby's IQ

Got Smarts? Mother's Milk May Pump Up Baby's IQ

According to new research, if the suckling infant has a certain version of a gene that helps process fatty acids

	HIGH IQ SUCKS:  Babies with a certain version of a gene for breaking down fatty acids can have their intelligence affected by whether they receive breast milk or infant formula.

The argument over whether intelligence is innate or environmentally influenced has raged for more than a century. One of the most recent issues in the nature versus nurture debate is the effect of breast-feeding on IQ.

Research shows that the fatty acids in human milk may influence brain development. Using that data as a springboard, a group of scientists, led by a team at the King's College London Institute of Psychiatry, set out to determine how the makeup of infants interacts with their mothers' milk to affect intelligence. 

Their findings, published in Proceedings of the National Academy of Science USA: breastfeeding can boost a baby's intelligence quotient if the newborn has a certain version of a gene, called FADS2 (fatty acid desaturase 2), which affects how fatty acids are processed.

"We were searching for an empirical example that would allow us to show scientists that it is possible to use the environment as a tool, to uncover novel genes that are important for human outcomes—including diseases," says study co-author Terrie Moffitt, a psychiatry professor of at King's College. "Our chain of logic from environment to genetic marker allowed us to discover for the first time the link between the FADS2 gene and the IQ, an important child health outcome."

The genetic marker that Moffitt refers to is located in the FADS2 gene, which has two primary variations. The new study, based on 1,000 New Zealander children (a portion of whom were breast-fed) in the early 1970s as well as on more than 2,000 breast-fed kids who lived in the U.K. in the mid 1990s, showed that 90 percent of the subjects had at least one copy of the more common version of FADS2 and 50 percent of them had two copies.

The researchers found that breast-fed infants with at least one or more of the common variation had an IQ score that was, on average, six to seven points higher than that of a nonnursed kid with similar genetics. But breast-feeding did not appear to affect those children (10 percent of the population) with only the less common variant. The scientists ruled out other factors, including birth weight and the mother's social class and IQ, finding that they had no impact.

"Those who were breast-fed scored on average three points above the population mean of 100 on the IQ test, whereas those who were not breast-fed scored about three points below the population mean," Moffitt says. In other words, breast-feeding led to a gain of a few IQ points, whereas those using baby formula in lieu of mom's milk led to a slight dip.

As for the study's implications on the nature / nurture debate, Linda Gottfredson, a professor of education at the University of Delaware, says that a person's DNA is not really a blueprint, as it is commonly portrayed. "[Genes] are more like playbooks," she says. "It's not nature or nurture, but your genes operate frequently by making you more susceptible or less susceptible to certain environmental conditions." Hence, the withdrawal of breast milk from the diets of babies with a certain genetic predisposition resulted in a negative effect on intelligence.

The exact mechanism by which the enzyme coded by FADS2 might influence IQ is not known, but Moffitt suggests two possible roles: The gene variants may affect the conversion of dietary precursors to long-chain polyunsaturated fatty acids, which aggregate in the brain in the early months after birth. Alternatively, the presence of long-chain polyunsaturated fatty acids may act on the gene itself, causing it to turn on or off, thereby affecting the metabolic pathway the acids use.

The authors note that since the time that study subjects were breast-fed, many baby formula manufacturers have begun adding fatty acid supplements to their products, potentially giving them an IQ boosting effect.

"What's critical about this paper is that we haven't known entirely what are the mechanisms by which breast-feeding supports higher IQ," says Joseph Hibbeln, lead clinical investigator at the Unit of Nutrition in Psychiatry at the National Institute on Alcohol Abuse and Alcoholism. "This really helps to dissect one of those mechanisms: that is…, if your body can't make [fatty acids] efficiently, you better get it through the breast milk to support optimal IQ." 

Comet draws scientific, amateur interest

Comet draws scientific, amateur interest

A comet that unexpectedly brightened in the last couple of weeks and is now visible to the naked eye is attracting professional and amateur interest.

Paul Lewis, director of astronomy outreach at the University of Tennessee, is drawing students to the roof of the Nielsen Physics Building for special viewings of Comet 17P/Holmes.

The comet is exploding and its coma, a cloud of gas and dust illuminated by the sun, has grown to be bigger than the planet Jupiter. The comet lacks the tail usually associated with such celestial bodies but can be seen in the northern sky, in the constellation Perseus, as a fuzzy spot of light about as bright as the stars in the Big Dipper.

"This is truly a celestial surprise," Lewis said. "Absolutely amazing."

Until Oct. 23, the comet had been visible to modern astronomers only with a telescope, but that night it suddenly erupted and expanded.

A similar burst in 1892 led to the comet's discovery by Edwin Holmes.

"This is a once-in-a-lifetime event to witness, along the lines of when Comet Shoemaker-Levy 9 smashed into Jupiter back in 1994," Lewis said.

Scientists speculate the comet has exploded because there are sinkholes in its nucleus, giving it a honeycomb-like structure. The collapse exposed comet ice to the sun, which transformed the ice into gas.

"What comets do when they are near the sun is very unpredictable," Lewis said. "We expect to see a coma cloud and a tail, but this is more like an explosion, and we are seeing the bubble of gas and dust as it expands away from the center of the blast."

Experts aren't sure how long the comet's show will last but estimate it could be weeks if not months. Using a telescope or binoculars help bring the comet's details into view, they said.

 

Comet Holmes is seen among the stars of the constellation Perseus in the North-Eastern sky...

Army’s Aggressive Surgeon Is Too Aggressive for Some

Army’s Aggressive Surgeon Is Too Aggressive for Some 

 

CRITICAL CARE Col. John Holcomb, a top trauma surgeon in the Army. 

Since the war in Iraq began, Col. John Holcomb has been working to change the way the military takes care of its wounded.

TOLL With 29,000 American injuries from hostile fire in Iraq and Afghanistan, said Col. John Holcomb, doctors must run clinical trials to ensure that patients are receiving the best treatments.

Along the way he has suffered a few dings himself.

A tall medical doctor with a Southern lilt and close-cropped gray hair, Colonel Holcomb, 48, has spent his entire 27-year career in the Army, earning a reputation as one of the military’s top trauma surgeons. Since 2001, he has headed the Army’s Institute of Surgical Research, based on the campus of the Brooke Army Medical Center here.

Under his watch, Army surgeons have become aggressive users of a controversial drug called Factor VII, which promotes clotting in cases of severe bleeding. He has also guided a redesign of the transport system for wounded soldiers, encouraging helicopter pilots to take the severely injured to the hospitals best able to treat them, even if they are not the closest.

Colonel Holcomb also strongly advocates conducting clinical trials to improve trauma care. It is an ethically tricky area, because trauma research can involve trying novel treatments on severely injured patients who cannot give informed consent. But he argues that any ethical problems pale in comparison to the toll that traumatic injuries take on civilians and soldiers every day.

He is fond of quoting a surprising statistic: trauma is the third-leading cause of death in the United States, taking 160,000 lives in 2004, more than any other cause except heart disease and cancer. Because it primarily affects the young, trauma leads all diseases in terms of life-years lost.

And besides the 4,000 American deaths in Iraq and Afghanistan, there have been 29,000 injuries from hostile fire, including 9,000 severe enough to require transport to hospitals outside the war zones.

In the face of that toll, Colonel Holcomb said, doctors must run clinical trials to ensure that patients are receiving the best treatments. Without those trials, even basic questions — which patients should be put on breathing tubes, for example — remain unanswered.

In an interview in his office at Brooke, Colonel Holcomb said he was determined to generate data that would help military and civilian surgeons answer those questions.

“We run a research institute,” he said. “Everything we do, we try to drive on data.”

Colonel Holcomb’s backers, who include surgeons both in and out of the military, say he is an exceptionally hard-working physician whose single-minded focus on wounded soldiers has led to improvements in the way the military treats its injured.

“John Holcomb is making a huge contribution to the advancement of trauma care in this country,” said Dr. Brent Eastman, the chairman of trauma for Scripps Health in San Diego and a regent of the American College of Surgeons.

But Colonel Holcomb is not without critics, who say his efforts, however well intended, may be doing more harm than good.

Dr. Andrew F. Schorr, a former military physician who is associate director of critical care medicine at Washington Hospital Center in Washington, said he believed that Colonel Holcomb had pushed military surgeons to use Factor VII despite a lack of data on its benefits — and some evidence that it can increase the risk of blood clots that cause strokes. Factor VII is a naturally occurring protein that helps the blood clot; an artificial version is produced by the Danish company Novo Nordisk under the name NovoSeven.

“I certainly disagree with his approach to Factor VII,” Dr. Schorr said.

Colonel Holcomb has also been criticized for his advocacy of an experimental blood substitute called PolyHeme, which recently failed a clinical trial in trauma patients. The trial, which ran from late 2003 until last year, was conducted on people who were severely injured and could not give consent to the experiment.

The trial followed an earlier failed test of PolyHeme in patients undergoing surgery for aneurysms. In the earlier trial, 54 percent of people who took it went on to suffer serious adverse events, compared with 28 percent who did not.

But the Brooke Army Medical Center and Colonel Holcomb did not disclose the results of the earlier trial to the public when they agreed to participate in the new trial. “Up to now, PolyHeme has not caused any clinically bad problems,” researchers for Brooke wrote in materials prepared for a public meeting, according to a 2006 article in The Wall Street Journal.

“He knew about this data, and he should never have approved the trial for his center and allowed the Army to participate in it,” said Keith Berman, a medical products consultant who specializes in research on blood substitutes. “Many, many centers declined to participate in this trial.”