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Feds Agree to Toxicity Tests That Cut Animal Testing

The NIH and EPA commit to exploring new technologies designed to phase out lab research on animals

 
ANIMAL'S BEST FRIEND: Government scientists want to make better use of robotic equipment to conduct in vitro testing of human cells and cellular components to identify chemicals with toxic effects and cut back on their use of lab animals.

 
FASTER TOXICITY TESTING: High-throughput microarray spotter machines place liquid enzyme dots on the slides and provide snapshots of all the genes that are active in a cell at a particular time.

Rodents and primates around the world can breathe a little easier. Ditto animal rights activists who have long opposed testing drugs and conducting other experiments on animals. Top officials from the U.S. National Institutes of Health (NIH) and Environmental Protection Agency (EPA) Thursday announced a five-year deal promising to share technology, information and other resources that will improve the toxicity testing of chemical compounds used in food, medicine and other products using robots rather than lab animals.

This joint effort will include experts from the NIH National Toxicology Program (NTP), high-speed, automated screening robots at the NIH Chemical Genomics Center and computational toxicology capabilities available at the EPA Office of Research and Development's National Center for Computational Toxicology (NCCT).

"Today we want to report to you this remarkable collaboration," Elias Zerhouni, director of the NIH, said during a teleconference with reporters held to announce the groundbreaking agreement. He added that the effort—designed to expand the use of in vitro testing of human cells and cellular components to identify chemicals with toxic effects—represents the "birth of a new approach to a crucial problem in public health."

The agencies are hoping to coordinate their resources to better identify toxicity pathways, select chemicals for testing, analyze and interpret data, and promote their findings to scientific and regulatory communities. This is expected to generate data more relevant to humans, expand the number of chemicals tested and reduce the time, money and number of animals involved in current lab studies. The collective budget is yet to be determined, the agencies say.

Animal testing has always been a sore point for scientists and animal-rights advocates, following some high-profile cases of mistreatment of lab animals, such as monkeys discovered in 1981 at the Institute for Behavioral Research in Silver Spring, Md., in deplorable conditions. One of the primary ways to test the toxicology of a compound has been to inject it into a lab animal, see if the animal gets sick, and then conduct an autopsy to observe the damage done to their internal organs. (For more on this, click here. Additional information on animal rights legislation can be found here.)

Scientists present at the news conference agreed that animal testing has yielded some important medical breakthroughs. But Robert Kavlock, director of the NCCT, said that it also is expensive, inefficient and is not always an accurate indicator of how a substance will affect humans.

"The desire here is to see if we could do better," said Francis Collins, director of the NIH's National Human Genome Research Institute. He said the federal government is exploring the feasibility of using high-throughput assays to allow scientists to "look at toxicology in a totally new way."

"The news here is the capacity to test many thousands of compounds, something we haven't had until this collaboration," Samuel Wilson, acting director of the NIH National Institute of Environmental Health Sciences and NTP, said at the press conference. The new research model would allow scientists to test 100,000 compounds in 1,500 different concentrations in about two days compared with years if the testing was done on animals. This sort of "high-throughput" testing will enable researchers to generate more data relevant to humans, and at the same time reduce the amount of animal experimentation. The cross-species extrapolation from animals to humans is "not always as precise as it should be," Wilson said. "This collaboration is a milestone because it gives us the ability to apply a new generation of approaches to determining toxicities."

The scientists were unable to provide a specific time frame for when the technology might produce significant results or predict how many fewer animals would be used in testing if their effort is a success. They stressed that they plan to move quickly to test the new technology and reduce animal testing as soon and as much as possible.

But they acknowledged that some animal testing will continue at least until the technology proves its mettle in large-scale studies or until Congress passes a substance regulation act similar to the European Union's (E.U.) Registration, Evaluation, Authorization and Restriction of Chemicals, or (REACH), which regulates chemicals and their safe use. It is set to take effect in March 2009 and bans such testing.

The officials noted that despite the E.U.'s pending ban, it is unclear whether scientists in Europe have access alternative methods of toxicology testing. Wilson noted that the technology being tested by the EPA and NIH is not yet available in the E.U.

For now, NIH chief Zerhouni said, animal testing will continue in the U.S. in conjunction with the new high-speed, automated screening technology. There are several other approaches under development that would also allow relatively quick, inexpensive testing of a large number of compounds and cells simultaneously. "We plan to use all of these," Christopher Austin, director of the NIH's Chemical Genomics Center, said at the news conference.

As ScientificAmerican.com reported in December, researchers at Rensselaer Polytechnic Institute in Troy, N.Y., the University of California, Berkeley, and Solidus Biosciences, Inc. (a biotech company located at the Rensselaer Incubator Program for start-up businesses) have developed biochips—called MetaChip and DataChip—that mimic what the body does when it ingests a drug. MetaChip is actually a glass slide dotted with 20-nanoliter droplets—each 20 billionths of a liter—of a solution containing human liver enzymes; DataChip is a slide lined with droplets containing cell cultures from the bladder, kidney or liver. Scientists can test the safety of a chemical by putting drops of it onto these slides and measuring the culture's growth or shrinkage over time.

These biochips are used with a high-throughput microarray spotter machine that places the liquid enzyme dots on the slides. The next step involves an optical assay system consisting of a camera connected to a fluorescent light source to take a digital image of the cell culture and highlight living and dead cells. Austin noted, however, that MetaChip and DataChip are not currently capable of handling the volume of testing that the government wants to conduct.

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Scientists and amateurs find new solar system

Photo 

Photo
This artist's rendering of a distant solar system shows the location of two newly discovered planets -- one resembling Jupiter (middle right) and one resembling Saturn (bottom). The question mark indicates where an inner system of planets would be located -- if the solar system contained terrestrial planets similar to Earth. Ohio State University astronomers led an international collaboration that published the discovery in the February 15 issue of the journal Science.

Astronomers and amateur stargazers have used an unusual technique to find a solar system that closely resembles our own and say it may be a new and more productive way to scour the universe for planets -- and life.

They said technique, called microlensing, shows promise for finding many more stars, perhaps with Earthlike planets orbiting them.

"We found a solar system that looks like a scaled-down analog of our solar system," Scott Gaudi of Ohio State University, who led the study, told reporters.

The new solar system, described in Friday's issue of the journal Science, has two planets of similar size and orbit to Jupiter and Saturn. It is the first time microlensing has been used to find two planets orbiting a single star.

The star is smaller, dimmer and fainter than our sun and the two planets are less massive than Jupiter and Saturn, but orbit at distances similar to the distances that Jupiter and Saturn orbit our own sun. "So it looks like a scale model of our solar system," Gaudi said.

The planets were detected orbiting a star, called OGLE-2006-BLG-109L, 5,000 light-years away from Earth. A light-year is the distance light travels in a year, or about 6 trillion miles.

The team of astronomers from 11 countries used a technique called microlensing to spot the planets.

"Microlensing works by using the gravity of the star and the planet to bend and focus light rays from a star behind it," Gaudi said. "If you are looking at one star and another passes in the foreground (gravity from the front star) will focus and bend light rays. That causes the background star to be magnified," he added.

LITTLE BUMPS

Any planets orbiting the star cause "a little bump" in this magnification effect, Gaudi said. In this case, the light from the more distant star was magnified 500 times.

Most of the other 250 or so extrasolar planets that have been seen have been detected using radio velocity -- tiny shifts in radiation, including light, that are caused by the Doppler effect. Most planets detected this way are super-large, super gassy and orbit very close to their suns.

"Microlensing is more sensitive to these cold, distant planets than the radiovelocity method," Gaudi said.

The discovery suggests these planets are common, the researchers said.

"Is there an Earth there in this system? For all we know there could be rocky planets in there but we couldn't find them," Gaudi said. "This could be a true solar system analog."

The 80-odd members of the Optical Gravitational Lensing Experiment worked frantically night after night during the 11-day period from late March through early April 2006 when the two stars were close enough to one another, as viewed from Earth, to cause the microlensing effect.

"We tried to get 24/7 coverage of the event," said Andrew Gould, professor of astronomy at Ohio State University. "It gets to be dawn in one place and we have to get somebody observing in another place."

They included professionals but also two amateurs -- one using a public telescope in Auckland, New Zealand, and Jenny McCormick, whose backyard telescope is listed as Farm Cove Observatory in Auckland, New Zealand, in the report.

"I work from home in our home-built observatory," McCormick told reporters. "It is quite useful. It is very easy to get on collecting data, cooking dinner and ironing clothes."

Survival in Space Unprotected Is Possible--Briefly

But don't linger in the interstellar vacuum, or hold your breath

 

As far as certain death in a science fiction plot line goes, being ejected into the vacuum of space is more than a pretty sure thing. A shove out of the air lock by a mutinous lieutenant or a vicious rip in a space suit, and your average movie victim is guaranteed to die quickly and quietly, though with fewer exploding body parts than screenwriters might have you believe.

In reality, however, animal experiments and human accidents have shown that people can likely survive exposure to vacuum conditions for at least a couple of minutes. Not that you would remain conscious long enough to rescue yourself, but if your predicament was accidental, there could be time for fellow crew members to rescue and repressurize you with few ill effects.

"In any system, there is always the possibility of equipment failure leading to injury or death. That's just the risk you run when you are in a hostile environment and you depend upon the equipment around you," says Dartmouth Medical School professor and former NASA astronaut Jay Buckey, author of the 2006 book Space Physiology. "But if you can get to someone quickly, that is good. Often spacewalks are done with two spacewalkers and there is continuous communication. So if someone is having a problem, hopefully the other can go get them and bring them in."

Vacuums are indeed lethal: Under extremely low pressure air trapped in the lungs expands, tearing the tender gas-exchange tissues. This is especially grave if you are holding your breath or inhaling deeply when the pressure drops. Water in the soft tissues of your body vaporizes, causing gross swelling, though the tight seal of your skin would prevent you from actually bursting apart. Your eyes, likewise, would refrain from exploding, but continued escape of gas and water vapor leads to rapid cooling of the mouth and airways.

Water and dissolved gas in the blood forms bubbles in the major veins, which travel throughout the circulatory system and block blood flow. After about one minute circulation effectively stops. The lack of oxygen to the brain renders you unconscious in less than 15 seconds, eventually killing you. "When the pressure gets very low there is just not enough oxygen. That is really the first and most important concern," Buckey says.

But death is not instantaneous. For example, one 1965 study by researchers at the Brooks Air Force Base in Texas showed that dogs exposed to near vacuum—one three-hundred-eightieth of atmospheric pressure at sea level—for up to 90 seconds always survived. During their exposure, they were unconscious and paralyzed. Gas expelled from their bowels and stomachs caused simultaneous defecation, projectile vomiting and urination. They suffered massive seizures. Their tongues were often coated in ice and the dogs swelled to resemble "an inflated goatskin bag," the authors wrote. But after slight repressurization the dogs shrank back down, began to breathe, and after 10 to 15 minutes at sea level pressure, they managed to walk, though it took a few more minutes for their apparent blindness to wear off.

However, dogs held at near vacuum for just a little bit longer—two full minutes or more—died frequently. If the heart was not still beating upon recompression, they could not be revived and the more rapid the decompression was, the graver the injuries no matter how much time had elapsed in the vacuum.

Chimpanzees can withstand even longer exposures. In a pair of papers from NASA in 1965 and 1967, researchers found that chimpanzees could survive up to 3.5 minutes in near-vacuum conditions with no apparent cognitive defects, as measured by complex tasks months later. One chimp that was exposed for three minutes, however, showed lasting behavioral changes. Another died shortly after exposure, likely due to cardiac arrest.

Although the majority of knowledge on the effects of vacuum exposure comes from animal studies, there have also been several informative—and scary—depressurization accidents involving people. For example, in 1965 a technician inside a vacuum chamber at Johnson Space Center in Houston accidentally depressurized his space suit by disrupting a hose. After 12 to 15 seconds he lost consciousness. He regained it at 27 seconds, after his suit was repressurized to about half that of sea level. The man reported that his last memory before blacking out was of the moisture on his tongue beginning to boil as well as a loss of taste sensation that lingered for four days following the accident, but he was otherwise unharmed.

When it comes to exposure to the interstellar medium, you might survive it with timely help but it probably won't be to your taste.

Scientists unearth most primitive bat ever found

Photo
The fossilized remains of the ancient bat called Onychonycteris finneyi that lived 52 million years ago is shown in this undated handout photo.

The most primitive bat ever found fluttered around about 52 million years ago, but lacked a key feature seen in most bats -- the ability to echolocate, hunting and navigating using a kind of sonar.

A team of scientists announced the discovery on Wednesday of a medium-sized ancient bat called Onychonycteris finneyi that possessed fully developed wings and was completely capable of flying. But they said that based on the evidence from its skeleton it lacked the ability to echolocate.

Kevin Seymour of the Royal Ontario Museum in Canada, one of the scientists who describe it in the journal Nature, said this bat appears to settle a long-standing debate of which came first in bats -- echolocation or flight. The answer is flight.

"It is like this is sort of half way to being a modern bat. It's the most primitive bat that we know. It could clearly fly. But it could not echolocate. The evidence from the skull and throat region shows us none of the features that echolocating bats have," Seymour said in a telephone interview.

Bats are the second most common type of mammal living today, constituting a fifth of all mammal species. Only rodents, which make up half of mammals, are more plentiful.

Bats also are an ancient form of mammals, and scientists have struggled to understand their early evolutionary history. Onychonycteris, unearthed in 2003 in southwestern Wyoming, appears to be filling in some important gaps.

"MISSING LINK"

"It's clearly a bat, but unlike any previously known," Nancy Simmons of the American Museum of Natural History in New York said in a statement. "In many respects it is a missing link between bats and their nonflying ancestors."

Echolocation is a form of sonar used by several mammals to navigate and hunt. They use high-pitched sounds to find the location of objects by the sounds reflected from them. Most bats use it to find flying insects to catch in mid-air. Other mammals with this ability include whales, dolphins and shrews.

The scientists called the fossil of Onychonycteris beautifully preserved, representing a previously unknown bat family. But while they call it the most primitive bat, they said a bat with more modern features, Icaronycteris, lived at the same time. Icaronycteris used echolocation, they said.

Seymour said there is nothing unusual about more primitive forms living alongside more advanced ones. "That's completely normal. Think today of the monotremes living in Australia, the egg-laying mammals," Seymour said. These include the platypus.

The wingspan of Onychonycteris was about 12 inches. It had short, broad wings, suggesting it probably could not fly as quickly as most bats that appeared later. Rather than flapping its wings continuously while flying, it may have alternated flapping and gliding while in the air.

Its teeth suggest its diet consisted mostly of insects, like most bats today. It had claws on all five of its fingers, while modern bats have them on only one or two digits of each hand. Its limb proportions are different from all other bats.

Seymour said scientists are not certain from what type of mammal bats evolved, but it could have been a tree-dwelling insectivore like a shrew.

Bats are one of only three types of vertebrates in the history of Earth to develop the ability to fly, joining the flying reptiles called pterosaurs, which went extinct 65 million years ago, and birds.

Going Out to Eat, but Staying Green


AT the Oko frozen yogurt shop in Park Slope, Brooklyn, the counter and walls are made from sunflower seeds and its awnings have solar panels.

Maury Rubin said that when he opens his third Birdbath organic bakery this spring, in Battery Park City, the roof will be planted with herbs to help air quality and insulate the store. Like the other Birdbaths in lower Manhattan, its furnishings will be made from recycled materials and wheat board.

Gusto Grilled Organics in Greenwich Village has been certified as organic under federal regulations by the Northeast Organic Farming Association of New York and its construction complies with standards set by the U.S. Green Building Council, a national environmental building organization.

Places like these, with a countercultural vibe, are what the phrase “green restaurant” might bring to mind.

But at the 13 New York and Chicago restaurants of Stephen Hanson’s B. R. Guest Restaurants, where you’re more likely to find patrons knocking back margaritas than sipping herbal tea, there’s a sanitation expert to help with recycling, as well as paper takeout containers, and organic eggs and other ingredients (as long as they’re not too expensive or hard to get).

At Del Posto, near the meatpacking district in Manhattan, where there are little stools for purses, biodiesel trucks fueled by its used cooking oil fetch ingredients from an upstate farm and return with the restaurant’s compost.

“There are many ways to be green,” said Joseph Bastianich, an owner.

And many places that are trying. Lately, when restaurateurs create a menu or settle on a design, they’re considering the environment along with the cuisine. Some do it to save money and others to tap into a popular trend, but many do it because they believe in it. Jason Hennings said the ingredients at Black Iron Burger, which he is to open soon in the East Village, will come from New York State, avoiding fuel-burning, cross-country deliveries. “I want this to be an ethical burger,” he said.

The seal of approval for many environmentally concerned dining places around the country comes from the nonprofit Green Restaurant Association, founded by Michael Oshman in 1990, when, he said, there was no green business movement.

Now, his organization, based in Boston, has more than 350 members, which for an annual fee of $500 to $4,000, depending on their size, get a “Green Restaurant” seal for their windows once they replace all polystyrene foam products, agree to recycle as much as possible, and begin to phase in other environmental measures, including composting, conserving water, disposing of grease responsibly and using chlorine-free paper products.

To check on compliance, the association occasionally inspects restaurants, but more often it looks at invoices to confirm that they are buying nontoxic cleaning products, energy efficient light bulbs and the like.

“We have to make these certifications credible,” Mr. Oshman said. “We’ve had issues with some clients, like one who had a contract with a recycler but the recycling company reported that the bins were always empty.”

José Duarte, the chef and owner of Taranta in Boston, said the association didn’t just approve his efforts, it also helped get things done. “When I needed new business cards I wanted them on chlorine-free paper, and the association could tell me which printers to contact,” he said. “Otherwise I would have had to call all over town myself.”

Keeping paper products nontoxic may be environmentally sound, but Mr. Oshman said that, increasingly, the industry is going green to save money.

Mr. Duarte, for instance, said that by composting he has cut down on garbage pickups, reducing his costs by about 45 percent. He said motion sensors in the bathrooms for the fans and lighting have helped cut energy costs by as much as $2,000 a year.

Mr. Oshman said his members “realize that it’s good for business and good practice.” And, he added, “It’s better to do it voluntarily, so it doesn’t get legislated.”

A growing number of municipalities, including Boston, Los Angeles and Santa Monica, Calif., have started citywide composting programs, which New York is considering, according to David Hurd, the director of the city’s Office of Recycling Outreach and Education.

New York already requires businesses to sort trash for recycling, Mr. Hurd said, but the service is not offered by all carting companies, and the law is not well-enforced. So it takes initiative to commit to recycling, as does Community Food & Juice, a small spot in Morningside Heights. And going green can add costs, at least in the beginning. Along with installing energy-saving appliances, Sharab, a lounge under construction in Gainesville, Fla., is using environmentally sound building methods that are often more expensive than conventional ones.

Christopher Fillie, the restaurant’s contractor, specializes in LEED construction (for Leadership in Energy and Environmental Design), which follows standards set by the U.S. Green Building Council, a nonprofit group based in Washington. Mr. Fillie said green construction methods, like using recycled materials and nontoxic paints, may add 10 percent to costs. But that can be offset with savings from energy conservation, utility rebates for more efficient appliances and federal tax credits for solar panels and other equipment.

“There’s a misconception that it’s only some kind of a bleeding heart thing and will be expensive,” Mr. Fillie said. “But the reality is that the cost of doing business poorly is going up — like the cost of energy, for example.”

Some efforts are modest. Community Food & Juice uses solar-powered lamps. To use less gasoline, restaurants, like Pizza Fusion in Fort Lauderdale and Deerfield Beach, Fla., make deliveries with hybrid cars. (Birdbirth uses bicycle-powered rickshaws.) Stage Left restaurant in New Brunswick, N.J., cans its own local tomatoes, and Cava Greens in Denver, which sells tossed salad to go, discounts takeout orders that can be filled in the customer’s own containers.

Some require more ambition. The Pain Quotidien chain of bakery-restaurants, which began using organic ingredients about four years ago, now has a composting plant in Queens for its New York restaurants.

Danielle Venokur’s Manhattan firm, DVGreen, plans parties with caterers like the Cleaver Company, Fancy Girl, ’Wichcraft and FreeFoods NYC, that use organic products, recycle, compost, and take other measures. She even looks for organic flowers.

Robert L. Garafola, New York City’s deputy parks commissioner for management and budget, said his department is encouraging restaurants and snack bars in the parks to follow Green Restaurant Association standards, and will consider how well concessionaires comply when granting future contracts.

Mr. Hanson said he had B. R. Guest’s New York and Chicago restaurants certified by the Green Restaurant Association in part because his company is in a joint venture with the Starwood Capital Group, an international hotel company that already has a green agenda. But, he said, ethics played a role, too.

“It’s also about emotions,” he said. “You have no choice if you have a conscience. I’m thinking about my kids.”

Jason Birnbaum, who owns Doc Green’s Gourmet Salad & Grill, with casual salad bars in Austin, Tex., said the new unit he just completed there was built according to LEED standards and complies with many of the Green Restaurant Association’s requirements.

Whether his customers care about all this is another matter.

“Austin is a very green city, like Seattle and San Francisco,” he said. “For some people it doesn’t matter, but with others, if they like our food and know we’re green they may choose us.”

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