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Sleek? Well, No. Complex? Yes, Indeed.
By ERICA GOODE, The New York Times, August 29, 2006


It is a good thing the manatee has thick skin.

To the dolphins, the whales, the sea otters go the admiring oohs and ahs, the cries of, “How sleek!” “How beautiful!”

The manatee, sluggish, squinty-eyed and bewhiskered, is more likely to have its rotund bulk compared to “a sweet potato,” its homely, almost fetal looks deemed “prehistoric” — terms applied by startled New Yorkers this month to a Florida manatee that made an unexpected appearance in the Hudson River.

Cleverness is unhesitatingly ascribed to the dolphin. But the manatee is not seen leaping through hoops or performing somersaults on command, and even scientists have suspected it may not be the smartest mammal in the sea. Writing in 1902, a British anatomist, Grafton Elliot Smith, groused that manatee brains — tiny in proportion to the animals’ bodies and smooth as a baby’s cheek — resembled “the brains of idiots.”

Yet the conception of the simple sea cow is being turned on its head by the recent work of Roger L. Reep, a neuroscientist at the University of Florida at Gainesville, and a small group of other manatee researchers, including Gordon B. Bauer, a professor of psychology at New College of Florida, and David Mann, a biologist at the University of South Florida.

In studies over the last decade, they have shown that the endangered Florida manatee (Trichechus manatus latirostris) is as unusual in its physiology, sensory capabilities and brain organization as in its external appearance.

Far from being slow learners, manatees, it turns out, are as adept at experimental tasks as dolphins, though they are slower-moving and, having no taste for fish, more difficult to motivate. They have a highly developed sense of touch, mediated by thick hairs called vibrissae that adorn not just the face, as in other mammals, but the entire body, according to the researchers’ recent work.

And where earlier scientists saw in the manatee’s brain the evidence of deficient intelligence, Dr. Reep sees evolution’s shaping of an animal perfectly adapted to its environment.

Dr. Reep — a co-author, with Robert K. Bonde, a biologist at the Sirenia Project of the United States Geological Survey, of a recently published book, “The Florida Manatee: Biology and Conservation” (University Press of Florida) — argues that the small size of the manatee brain may have little or nothing to do with its intelligence.

Brain size has been linked by some biologists with the elaborateness of the survival strategies an animal must develop to find food and avoid predators. Manatees have the lowest brain-to-body ratio of any mammal. But, as Dr. Reep noted, they are aquatic herbivores, subsisting on sea grass and other vegetation, with no need to catch prey. And with the exception of powerboats piloted by speed-happy Floridians, which kill about 80 manatees a year and maim dozens more, they have no predators.

“Manatees don’t eat anybody, and they’re not eaten by anybody,” Dr. Reep said.

But he also suspects that rather than the manatee’s brain being unusually small for its body, the situation may be the other way around: that its body, for sound evolutionary reasons, has grown unusually large in proportion to its brain.

A large body makes it easier to keep warm in the water — essential for a mammal, like the manatee, with a glacially slow metabolism. It also provides room for the large digestive system necessary to process giant quantities of low-protein, low-calorie food.

The manatee must consume 10 percent of its 800-pound to 1,200-pound body weight daily. Hugh, 22, and Buffett, 19, captive manatees at the Mote Marine Laboratory in Sarasota, Fla., are fed 72 heads of lettuce and 12 bunches of kale a day, their trainers say. And in a 2000 study, Iske Larkin, a researcher in Dr. Reep’s laboratory, used colored kernels of corn to determine that food took an average of seven days to pass through a captive manatee’s intestinal tract — a leisurely digestive pace comparable to that of a koala or a two-toed sloth.

The smooth surface of the manatee’s brain — it generally has only one main vertical fissure, or sulcus, and no surface ridges to speak of — is more puzzling, Dr. Reep concedes. The brains of virtually every other mammal bigger than a small rodent show some degree of folding. And scientists have generally taken the human cortex, a study in ridges and crevasses, as a model of higher-order mental process, assuming accordingly that brain convolution is a sign of intelligence.

“I would make a guess that if you showed a manatee brain to a modern neuroscientist, to this day, most would consider that the manatee is not very smart, that idea is so ingrained,” Dr. Reep said.

But he added that scientists still know almost nothing about what drives the development of brain formation. Evolutionary lineage appears to have an influence. The brains of primates tend to have different patterns of convolution than those of carnivores, for example. And mechanical factors like brain size and the denseness of neural tissue in the cortex may play a role.

Manatees have a relatively thick cerebrum, with multiple layers that may, Dr. Reep suspects, indicate complexity despite a lack of folding.

In any case, he said, brain convolution “doesn’t seem to be correlated with the capacity to do things.”

More to the point, intelligence — in animals or in humans — is hard to define, much less compare between species, Dr. Reep said. Is the intelligence of a gifted concert pianist the same as that of a math whiz? Is a lion’s cunning the same as the cleverness of a Norwegian rat?

The manatee is good at what it needs to be good at.

Sirenia, a biological order that includes the dugong and three extant species of manatees, appear in the fossil record in the early to middle Eocene, about 50 million years ago, around the same time as whales, horses and other mammals, said Daryl P. Domning, a professor of anatomy at Howard University who has collected and studied the fossils of manatees and other sirenians around the world.

Four-legged land mammals that returned to the sea, the sirenians shed their hind legs but retained vestigial pelvic bones and, in two manatee species, nails on their flippers. Manatees count among their close relatives the elephant and the rock hyrax. Another sirenian, Steller’s sea cow, lived in the Bering Sea and exceeded 5,000 pounds. It was hunted into extinction in the 1700’s.

Although dugongs appear in the folklore of Palau, sirenians in general “don’t seem to have inspired the amount of awe that other animals did, like pumas and jaguars and things like that,” Dr. Domning said. “You don’t find them putting up monuments or statues to them.”

Florida manatees, a subspecies of the West Indian manatee, thrive in warm, shallow coastal waters and migrate when the temperature drops. They spend a great deal of time eating, with frequent naps between meals. Their social world is relatively straightforward. Males mate with females in a violent affair that resembles a gang rape; manatee calves stick close to their mothers for about two years, then head off on their own.

Groups of manatees may cluster, playing, grazing and dozing at a warm-water source — a power plant, for example. But they are just as likely to be loners, striking out wherever the warm currents take them, even if that means passing the Statue of Liberty and heading up the East River to Rhode Island, as an earlier northward manatee pioneer, Chessie, did in 1995. (The manatee spotted in the Hudson in early August was seen on Aug. 17 even farther north, off Cape Cod. But two days later it had turned south again to Rhode Island. The last reported sighting was the afternoon of Aug. 25, in Bristol Harbor, R.I. )

The manatee’s sensory capacities and brain organization, researchers are learning, are perfectly suited to its style of life.

In the dim, muddy shallows where manatees feed, for example, sharp eyes are less than useful. And sight is not a manatee’s strong suit, though the heavy-lidded wrinkled dimples that serve as eyes are undoubtedly part of the animal’s charm.

Manatees distinguish colors. The orange of carrots in a trainer’s hand can inspire a captive manatee to an uncharacteristic speed. But they are bad at distinguishing brightness, and they are clumsy, frequently bumping into things.

In 2003, Dr. Bauer and four colleagues, including Debborah Colbert and Joseph Gaspard III of the Mote Marine Laboratory, reported in The International Journal of Comparative Psychology on the visual testing of the Mote manatees, Hugh and Buffett. The manatees were trained to discriminate between two underwater panels of evenly spaced vertical lines, swimming toward the correct panel for a reward of apples, beets, carrots and monkey biscuits. By varying the distance between the lines, the researchers showed that Buffett’s eyesight was about 20/420, similar to a cow’s and far worse than a human’s.

Poor Hugh, Dr. Bauer said, was blind “even by manatee standards.”

Yet far more valuable than sight in murky water is an acute sense of touch, and it is here that manatees excel. Their mastery of the tactile world, Dr. Reep and his colleagues have recently established, comes from the thick, bristly hairs called vibrissae. Unlike normal hair fibers, each vibrissa is a finely calibrated sensory device, its follicle surrounded by a blood-filled pocket or blood sinus. The movement of the hair produces changes in the fluid that are registered by receptors around the hair follicle, which transmit the information to the brain via hundreds of nerve fibers. An increase in blood pressure increases the sensitivity of the hairs.

In research over the last five years, Dr. Reep and his colleagues have shown that manatees have 2,000 facial vibrissae of varying thickness, 600 of them in the so-called oral disk, a circular region between mouth and nose that the manatee uses much like an elephant’s trunk, to grasp or explore objects. Each facial vibrissa is linked with 50 to 200 nerve fibers. An additional 3,000 vibrissae are spaced less densely over the rest of the body.

Rats, dogs, sea lions and other whiskered animals also have vibrissae, but not in such large numbers and typically only on the face. In research not yet published, Diana Sarko, a graduate student in Dr. Reep’s lab, confirmed that another mammal has vibrissae dispersed over its body, the rodent-faced, rabbit-size rock hyrax, the manatee’s distant cousin.

Like the manatee, the hyrax, which inhabits rocky outcroppings, spends much of its time in dim light and has poor vision.

“Rock hyraxes live in little cave dwellings, so they probably use these hairs to navigate in these dark surroundings,” Ms. Sarko said.

In testing, Buffett, Hugh and other captive animals have proved just how acute a manatee’s tactile sense can be. Using the bristles on the oral disk and the upper lips, manatees can detect minute differences in the width of grooves and ridges on an underwater panel. A manatee tested by a team of researchers in Germany could distinguish differences as small as 0.05 millimeters, as well as an elephant performing the same task with its trunk, and almost as well as a human. Hugh and Buffett did even better, outperforming the elephant and, in Buffett’s case, the human.

The findings were presented at the 16th Biennial Conference on the Biology of Marine Mammals in 2005.

A sensory modality that is so important should be prominently represented in the brain. And, confirming an observation first made by a German scientist in 1912, Dr. Reep’s research team has identified large clusters of cells called Rindenkerne in sensory processing areas in the deep layers of the manatee’s cerebral cortex. These clusters, the researchers suspect, are the manatee equivalents of the cell groupings called barrels found in other whiskered species like mice and rats, regions that process sensory information from the vibrissae.

Even more tantalizing is that, in the manatee, these clusters extend into a region of the brain believed to be centrally involved with sound perception.

“Either these things have nothing to do with the hair at all, or the more exciting possibility is that perhaps somatic sensation is so important that the specialized structure is overlapping with processing going on in auditory areas,” Dr. Reep said.

The normal hearing of manatees is known to be quite good in certain ranges, better than that of humans. In studies published in 1999 and 2000, Edmund and Laura Gerstein of Florida Atlantic University found that the underwater hearing of two captive manatees in a pool was sharpest at high frequencies — in the 16-to-18-kilohertz range — findings that have complicated the debate about powerboats. Though Florida has spent years trying to persuade boaters to slow down in areas that manatees frequent, the high frequencies emitted by a boat moving at high speed may be easier for the animals to hear (although having the time to get out of the way is a different matter).

But in a study also presented at the marine mammal meetings, Dr. Bauer, Dr. Reep and colleagues have found hints that manatees can also “hear” low-frequency sounds, perhaps by using the vibrissae on their bodies to detect subtle changes in water movement. Hugh and Buffett were able to determine the location of three-second low-frequency vibrations in the 23-to-1,000-hertz range with up to 100 percent accuracy. The researchers plan to repeat these experiments with the vibrissae covered, to see whether the manatees still score highly.

If they do, it will suggest that they have a capacity unique among mammals and may help biologists explain, among other things, how they navigate back to their favorite patches of sea grass each year and how they monitor the movements of other manatees in cloudy water. Fish and some amphibians have similar sensory systems, mediated by cells running down the sides of their bodies. Called the lateral line, this system is “the reason why we can sneak up behind a fish but cannot grab it,” Dr. Reep writes.

For now, the question of how intertwined the sensory abilities of manatees might be remains unanswered. Yet even what is known reveals a degree of complexity that argues against labeling them as sweet but dumb — peaceable simpletons.

Dr. Domning of Howard could not agree more.

“They’re too smart to jump through hoops the way those dumb dolphins do,” he said.





New Test Speeds Diagnosis of Lethal Avian Flu Strain
By DONALD G. McNEIL Jr., The New York Times, August 29, 2006


In an advance that speeds up diagnosis of the most dangerous avian flu, scientists have developed a detailed influenza test that takes less than 12 hours, federal health officials said yesterday.

The new technology, a microchip covered with bits of genetic material from many different flu strains, cuts the typical time needed for diagnosis of the A(H5N1) flu to less than a day from a week or more. In addition, rather than giving just a yes-or-no result, it usually reveals which flu a human or an animal has.

That means that public health officials investigating, for example, a flu outbreak in poultry or in humans in a remote Asian or African village will be able to decide quickly whether to kill thousands of birds or to treat hundreds of potentially exposed people with expensive antiviral drugs.

Right now, ascertaining whether a flu is of the lethal A(H5N1) strain requires that a sample be frozen and shipped to a highly secure laboratory, usually in a major city like Atlanta or Hong Kong, where the virus can be grown in eggs, isolated and genetically sequenced. That process takes four to five days plus shipping time and runs the risk of samples defrosting in transit and being ruined.

The new test, called FluChip, can be performed in any laboratory that can amplify bits of genetic material; many countries have such laboratories in their national capitals, if not in provincial hospitals. Samples need not be frozen, and because only bits of genetic material are multiplied rather than whole viruses, the work can be done in laboratories with lower biosecurity levels.

Nancy J. Cox, chief of the influenza branch of the Centers for Disease Control and Prevention in Atlanta, said the chip “really allows us to get a lot of information about a virus in a short time.”

Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, which announced the creation of the test, called it an “encouraging advance” that could be “invaluable to international flu surveillance efforts.”

Dr. William B. Karesh, chief field veterinarian for the Wildlife Conservation Society, who led a 2005 expedition to Mongolia to track the lethal avian flu virus as it first moved out of Asia in migrating wild birds, said the new test “sounds fabulous.”

“It could be an incredibly powerful tool,” Dr. Karesh said.

A more advanced version to be used in the field may be ready within two years, said Kathy L. Rowlen, a University of Colorado chemistry professor who led the team that developed the test.

At present, animal and human health experts trying to fight avian flu in remote areas are forced to make important decisions based largely on guesses because it is too risky to wait a week for a laboratory to confirm that a highly dangerous virus is loose.

A dipstick test done on the spot, which a veterinarian working in Indonesia said was as quick and as simple as a home pregnancy test, can tell only if a flu is type A.

Getting more information requires polymerase chain reaction amplification, which Dr. Rowlen described as “separating the genetic material of the virus itself from all the other things you find in a nasal swab, and then making a million copies of it, like using a photocopier.”

That requires a machine costing about $20,000, which can be found in most countries’ national laboratories and in some provincial hospitals, Dr. Karesh said. One he saw in Mongolia was “a kitchen-tabletop-type thing,” he said.

Currently, such machines and follow-up tests can tell in about four hours whether a flu is an H5 strain.

The FluChip, sometimes called a microarray, or gene chip, greatly enhances that technology.

It is coated with 55 short stretches of RNA selected from 5,000 samples of human, bird, pig and horse flus provided by the C.D.C., and including H5N1 and routine human flus of the H3N2 and H1N1 strains. The broken-up DNA in the amplified sample is, in effect, poured across the chip, and fragments stick to the matching bits of RNA. By noting the matches, scientists can deduce which flu it is.

In recent tests, the technology correctly identified 72 percent of samples and partly identified an additional 13 percent, according to the disease centers.

Moreover, as the flu mutates, Dr. Cox said, stretches of RNA from newly emerging strains could be added.

Michael T. Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, called the chip “good news, because it clearly moved ahead the diagnostic tools we have.” It also has the potential to speed up mass testing because dozens of samples can be tested on dozens of chips at once.

But if a flu pandemic were to erupt, Dr. Osterholm warned, the test could quickly be rendered useless because most of the chemicals needed for the preliminary DNA-amplification steps come from abroad, and the chaos that a pandemic would cause would interrupt supplies.

“You can have all the guns you want,” he said, “but if the bullets are offshore, you can’t shoot very much.”





How a Vaccine Search Ended in Triumph
By DONALD G. McNEIL Jr., The New York Times, August 29, 2006


Nuns and Jews, cow warts and rabbit horns.

The common link: they were all crucial elements in the search for the world’s newest vaccine.

There are fascinating stories behind every advance in medicine, be it hand washing or brain surgery. But the 70-year history behind the creation of a vaccine against human papillomavirus, which causes cervical cancer, is more fraught than most with blind alleys, delicate moments, humor and triumph.

Although cervical cancer is being beaten in rich countries thanks to Pap smears, it is still a great killer of the world’s poor. Fulminating tumors that can hemorrhage the womb or burst the intestine make death every bit as agonizing as it was for our great-grandmothers. Even in wealthy countries, aggressive forms appear in rare cases, forcing women barely in their 20’s to get hysterectomies.

For all of those women, the new vaccine approved in June by the Food and Drug Administration could be a lifesaver. But creating it was no easy task. It took decades for scientists to even figure out the cause: the papillomavirus, named for the papilla, or bud, that the tumor creates.

Species as different as birds and whales have their own papillomas. There are more than 100 human strains. Many are harmless. Some cause warts on hands, noses or genitals, and some cause cancer. As a result, blame has been laid on origins like toads, witchcraft and God’s anger at promiscuous women.

Against that background of superstition, the two newest vaccines use technologies that sound almost like science fiction.

Gardasil, made by Merck, uses a yeast to grow the proteins that form the outer shell of the virus; every batch of 360 proteins almost magically assembles itself into a soccer ball exactly mimicking the shell’s shape.

Its rival, Cervarix by GlaxoSmithKline, produces the same protein, with the same power, in an insect virus grown in a broth of caterpillar ovary cells.

But each step forward to those techniques was a triumph of hard science over the pseudoscientific myths that for centuries surrounded the disease.

The first was posited by a doctor in Florence in 1842. He noticed that prostitutes and married women died of cervical cancer, but nuns almost never did. Though he might have discerned that it was sexually transmitted, he was thrown off by another fact: nuns often died of breast cancer. His conclusion was that nuns’ corsets were dangerously tight.

One may laugh, but prominent American scientists made a similar error in the 1970’s, noting that many women with cervical cancer had a history of genital herpes. Instead of realizing that it was a coincidence, they erroneously concluded that the herpes virus was the cause. And they were closer to the mark than 1950’s researchers, who had blamed smegma, which builds up under the foreskin of men who do not wash.

Research that could have led them in the right direction was done in the 1930’s by Dr. Richard Shope of the Rockefeller University, who on a hunting trip heard a friend describe seeing rabbits with “horns,” which were actually large warts.

Dr. Shope asked his friend to send some of the horns. He then ground them up, filtered them through porcelain that let only tiny virus-size particles through, and injected the filtrate into other rabbits, which grew horns in turn.

“Incidentally, that’s where the jackalope myth comes from,” said Dr. William Bonnez, who was part of the University of Rochester’s vaccine development team. (Jackalopes, jackrabbits with antelope horns, are made by taxidermists and appear on things like postcards from Wyoming. But references to horned rabbits go back centuries, and their condition probably stemmed from papilloma infections.)

Dr. Shope’s work showed the cause was a virus, but it was not until the 1980’s that DNA amplification allowed a German researcher, Dr. Harald zur Hausen, to pin down papilloma as the cause.

“That was really the pivotal point,” said Dr. Douglas R. Lowy, chief of the cellular oncology laboratory at the National Cancer Institute and part of a team whose subsequent work led to the vaccine. “Before that, the field suffered from the boy-who-cried-wolf phenomenon, as in people would say, ‘Last year you said it was herpes virus, now you say it’s papilloma; why should we believe you?’ ”

In the interim between Drs. Shope and zur Hausen, another line of inquiry was going on. Researchers were stumped as to why cervical cancer was so rare among Jewish women.

It had been noted as far back as 1901 that at Leeds General Infirmary and London Hospital, cancer of the cervix “was seldom or never met with among the numerous Jewesses,” according to a Lancet article of the time.

More pseudoscientific myths arose trying to explain that. (The Lancet writer, whose thesis was that salt caused cancer, believed that Jews were protected by avoiding bacon.) But it took the founding of Israel, drawing Jewish women from all over the world, to debunk them.

The long-held assumption that circumcision was protective was disproved by high cancer rates among Muslim women, who had circumcised husbands, and by relatively low rates among Soviet Jewish women, who often did not. Another myth, that abstaining from sex during menstruation helped prevent the disease, was dispelled by comparing Orthodox women who abstained to others who did not. As with non-Jews, the apparent risk factors for the few Israeli women with the disease were multiple sexual partners and poverty.

Work by Dr. Joseph Menczer of the Wolfson Medical Center in Israel showed that genes were the crucial factor. A protective configuration of the p53 gene is much more common among Jews, except for those from North Africa, the one subgroup likely to contract cervical cancer.

In the 1980’s, with many teams in hot pursuit of a vaccine, a stumbling block emerged. Human warts contain very little virus.

In Rochester, Dr. Bonnez’s solution was to approach veterinarians treating dairy cows, which grow grapefruit-size warts loaded with virus. He still has a block of 20-year-old cow warts in his freezer.

First, he had to make a blood test for the virus. A control group of people who had never had sex was needed. Once again, nuns were at the fore of cervical cancer research. The Sisters of St. Joseph in Rochester were “really very supportive,” Dr. Bonnez said, answering questionnaires about their sexual histories and giving blood samples.

“People were snickering, ha-ha, nuns, no sex,” he said. “But having a base control group of 50 subjects — that led me to realize the bovine approach was wrong.”

Instead, said Robert Rose, an immunologist working with Dr. Bonnez, the Rochester team tried grafting bits of foreskin collected from hospital circumcisions and infected with genital wart extract into mice lacking the ability to reject foreign tissue. The resulting cysts contained enough human virus to work with.

Ultimately, the two vaccines were the fruit of the labors of dozens of scientists. A patent battle involving the National Cancer Institute, the University of Rochester, Georgetown University and Queensland University in Australia was resolved after 13 years when Merck and Glaxo signed royalty agreements with all four.

Dr. Lowy, of the National Cancer Institute, said one of his most rewarding moments during the years of research also involved rabbits. He was in Paris, at the Pasteur Institute, where a model vaccine was being tested. All the rabbits that had been given the vaccine were disease free, he said, while 95 percent of those that had been given a placebo had cancerous lesions.

“The fact that it worked so well,” he said, “was just incredible.”





Study Shows Hopeful Pause in Steady Loss of Bird Species
By ANDREW C. REVKIN, The New York Times, August 29, 2006


Efforts to protect imperiled bird species have blunted a centuries-long acceleration of human-caused bird extinctions, biologists say.

For the moment.

This is the first time biologists have gauged the effect of conservation efforts by assessing shifts in the prospects of species that were down to their last few members.

Ana S. L. Rodrigues, a zoologist at Cambridge University, summarized the work in the current issue of Science. “It is encouraging that bird conservation actions worldwide are making a noticeable dent in the bleak scenario of global biodiversity loss,” she wrote.

A particularly significant study, she said, was published last month in the journal Oryx by biologists from Birdlife International, a private conservation group in Britain. They identified more than two dozen birds, including the California condor and the Mauritius parakeet, that would probably have become extinct sometime after 1994 without intervention.

In her paper, Dr. Rodrigues assessed the Birdlife International list against the 500-year record of 135 bird extinctions compiled, century by century, by the World Conservation Union, a network of government and private scientists and organizations. The drop to 43 extinctions in the 20th century from 49 in the 19th century was clearly a result of interventions like preserving habitat, breeding or moving birds, and controlling cats and other introduced predators, she said.

Stuart L. Pimm, a professor of conservation ecology at Duke University, cautioned that continuing deforestation in the tropics and other pressures could raise the extinction rate tenfold in the next 10 years.

“It’s a pat on the back, and we need one, but the threat ahead is massive,” Dr. Pimm said. “It’s like we’ve ridden our first wave on a surfboard and feel good about it, but look back and there’s a tsunami coming in.”

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