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Observatory: When a Giant Walked the Earth
By HENRY FOUNTAIN, The New York Times, December 6, 2005
Martin A. Whyte is a dinosaur hunter by profession, stalking the remains of the beasts in Yorkshire, England. But no matter where he is, Dr. Whyte is always on the lookout for signs of ancient life.
So it's no surprise that Dr. Whyte, a professor at the University of Sheffield who is also a geologist, discovered a fossil track one summer day in 2003, when he took time from studying the geology of the central Scottish coast to stroll on the beach.
Dr. Whyte's analysis of what made those tracks, however, turned out to be a big surprise - a giant water scorpion from 330 million years ago, long before the age of the dinosaurs. It is the first evidence that these long-extinct arthropods walked on land.
Dr. Whyte said the discovery was serendipitous. "I found myself looking across a stretch of beach," he recalled, "and I saw a rock face with this trackway going across." It consisted of a sinuous series of markings about 20 feet long, made in sand that had turned to rock.
"I knew as soon as I saw it, it was made by some kind of animal," he said.
It was clear from the markings that the creature had three limbs on each side. "Right away that eliminated the reptiles and amphibians," Dr. Whyte said. "I had to consider some sort of arthropod."
The track also had a large central groove, obviously made by a heavy tail. And the animal must have been huge, about 5 feet long and 3 feet wide. Dr. Whyte decided it could only be a species of Hibbertopterus, water scorpions that are distant ancestors of modern creatures like horseshoe crabs.
Just fragments of Hibbertopterus fossils exist. Some are from specimens the size of the one that left the tracks, Dr. Whyte said.
The stride is very short, indicating it moved very slowly and probably in a herky-jerky manner. That its tail dragged- the groove it left partly obscured some of the footprints - is strong evidence that the creature was walking across land. "This animal was in no way buoyed up by water," he said.
At this point in the earth's history, the earliest four-legged animals were coming out of the water onto land. But water scorpions did not make such a transition. Dr. Whyte said this specimen was probably out of the water a short time, as its gill-like breathing apparatus needed to remain wet. So it might have been walking from one body of water to another one nearby.
"The best I can say is it's going from somewhere to somewhere," he said. "It's nice to speculate that it might have come out for spawning or to look for a beach party or whatever. But there's just no evidence for that."
Better Bananas, Nicer Mosquitoes
By DONALD G. McNEIL Jr., The New York Times, December 6, 2005
SEATTLE - Addressing 275 of the world's most brilliant scientists, Bill Gates cracked a joke:
"I've been applying my imagination to the synergies of this," he said. "We could have sorghum that cures latent tuberculosis. We could have mosquitoes that spread vitamin A. And most important, we could have bananas that never need to be kept cold."
They laughed. Perhaps that was to be expected when the world's richest man, who had just promised them $450 million, was delivering a punchline. But it was also germane, because they were gathered to celebrate some of the oddest-sounding projects in the history of science.
Their deadly serious proposals - answers to the Grand Challenges in Global Health that Mr. Gates posed in a 2003 speech in Davos, Switzerland - sounded much like his spoofs: laboratories around the world, some of them led by Nobel Prize winners, proposing to invent bananas and sorghum that make their own vitamin A; chemicals that render mosquitoes unable to smell humans; drugs that hunt down tuberculosis germs in people who do not even know they are infected; and vaccines that are mixed into spores or plastics or sugars and can be delivered in glasses of orange juice or modified goose calls.
What Mr. Gates had outlined at Davos were the greatest obstacles facing doctors in the tropics: Laboratories are few and far between. Vaccines spoil without refrigeration and require syringes, which can transmit AIDS. Mosquitoes develop resistance to all insecticides. Crops that survive in the jungle or desert often have little nutritive value. Infections outwit powerful drugs by lying dormant.
His offer - originally $200 million, raised to $450 million after 1,600 proposals came in - "was to make sure that innovation wasn't reserved just for big-ticket items like cancer and heart disease," said Dr. Carol A. Dahl, the foundation's director of global health technologies, who ran the conference.
The winning teams, which were named in June,came from as far away as Australia and China, withresearch partners all over Africa and Southeast Asia. Over three days in a Seattle hotel, the 43 team leaders delivered 10-minute summaries of their plans, quizzed foundation officials about details of the grants and discussed possible ethical quandaries with bioethicists from the University of Toronto.
(The most common questions were about the one ironclad rule: grantees may patent anything they discover, but must make it available cheaply to poor countries. An ethical concern common to many projects is that they will eventually require clinical trials on impoverished Africans or Asians with little understanding of informed consent.)
In the hallways and over cocktails and dinners - all paid for by the foundation - virologists and neurologists talked with plant biologists and nanoparticle physicists, sometimes finding ways to help one another. For example, a scientist with plans to improve vitamin-fortified "golden rice" asked the designer of a hand-held laboratory to test blood for pathogens whether it could be modified to test blood for iron and vitamins.
Mr. Gates, in an interview, sidestepped a request to name his favorite projects. "Oh, I love all my children," he said.
But he remained brutally realistic about where his "children" - and the money he lavishes on them - were likely to end up. "Eighty percent of these are likely to be dead ends," he said. "But even if we have a 10 percent hit rate, it will all have been worthwhile."
What follows is a selection of the winning projects.
Dried Vaccines
The only scientist to emit a goose honk during his presentation was Robert E. Sievers, who was illustrating inexpensive straws with useful vibrations.
Dr. Sievers, the chief executive of Aktiv-Dry, a Colorado company that turns liquids into superfine powders, is trying to develop a measles vaccine that can be stored dry and inhaled.
He proposed turning it into glassy particles around a matrix of trehalose, the sugar that allows brine shrimp cysts to survive dried out for years but hatch into wriggling creatures in seawater. (The shrimp are perhaps better known as the "amazing live sea monkeys" advertised in comic books.)
For the powder to reach the lungs instead of sticking to the straw or the throat, the particles must be dispersed evenly in the airstream. Vibration helps, and he tested oboe reeds, New Year's noisemakers and goose calls, trying to find something disposable that needs no power, even from batteries.
A longtime chemistry professor at the University of Colorado, Dr. Sievers, 70, had a second career running a company developing pollution-detection instruments when his son, a pediatrician, described how premature newborns were given surfactants to keep their lung sacs from sticking like Cling Wrap.
"They squirt a bolus of water down into the lungs, then they turn the baby over and pour it out," the elder Dr. Sievers said, shaking his head in disbelief. "There had to be a way to improve that."
In the 1990's, he turned his hand to inhalers for surfactants, then for asthma and now for vaccines. "Measles kills 2,000 children a day," he said, briefly tearing up, and then apologizing for it, as he described his new passion for the cause and what his $20 million grant will let him pursue. "That's like a World Trade Center disaster every day. This is what I want to do with the last stretch of my life."
Abraham L. Sonenshein of Tufts University, who received $5 million, wants to use bacterial spores, another form of nature that can survive desert heat or Arctic cold.
"Our ideal vaccine would be a packet of spores that could be emptied into a glass of juice and drunk down," he said
His chosen vehicle, bacillus subtilis, is found all over the world in dirt.
"Safety is a nonissue," he said. "A large fraction of the Japanese population eats it every day for breakfast." The bacteria are used to ferment soybeans for a dish called natto.
But rather than simply drying an existing vaccine, he wants to splice into the subtilis bacterium's DNA the ability to make the fragments of viral protein that provoke the immune reaction.
Dried bacterial spores could survive indefinitely - and then bloom in the gut and start assembling the proteins.
He has already inserted the genes for diphtheria and tetanus vaccines, and is working on adding whooping cough and rotavirus.
Ten years ago, he said, a Tufts colleague came back from a conference on children's diseases and excitedly described how hard it was to keep vaccines cold in villages without electricity.
Dr. Sonenshein, a bacteria expert, said he replied: "Why are you telling me this?"
But as soon as his colleague asked whether spores could help, he understood.
"We worked on it for two years, and then gave it up, because the traditional funding agencies thought it was too speculative," he said. "The project lay fallow for eight years, so I'm very grateful for the grant."
Mosquito Time Bomb
Scott L. O'Neill, a biologist at Australia's University of Queensland, had an inspiration based on two unrelated facts: mosquitoes must be "middle-aged" - about 14 days old - before they can transmit the dengue virus, and wolbachia bacteria kill fruit flies in midlife.
Since 1975, dengue fever has become a major cause of death for young children, especially in Southeast Asia, where Dr. O'Neill has done field work. "The mosquitoes were controlled in the 1960's," he said. "But they're invading new areas."
Wolbachia, parasitic bacteria, live in many insects, eventually killing some of them. But, in what Dr. O'Neill called a "sneaky and spiteful manipulation of their host," they assure their survival into the next generation by infecting embryos as well, and by rendering infertile any embryos that do not come from infected parents.
(They probably kill the hosts by growing prolifically on their nerve cells, and they may render embryos infertile by somehow preventing egg-sperm fusion, Dr. O'Neill said, but those mysteries are still unsolved.)
Most mosquitoes live about a month, but it takes about 14 days for the dengue virus, which the female picks up by biting an infected human, to mature in her gut and reach her salivary glands, ready to be injected into the next human.
Month-old females who have bitten several people are the most dangerous mosquitoes.
Dr. O'Neill, who received $7 million, hopes to find a life-shortening wolbachia strain in fruit flies or to create one by gene modification, and use it to infect mosquitoes, which now harbor benign strains.
If it works, a female will still live long enough to take a blood meal and lay one set of eggs, so there will be little evolutionary pressure on her to resist the bacteria.
But she will die before she can transmit dengue.
Prostitutes in Kenya
Since 1981, when he was a junior researcher at the University of Manitoba, Dr. Francis A. Plummer has studied thousands of prostitutes in Nairobi, Kenya - initially looking for chancroid and gonorrhea, and then, for the AIDS virus, once it was discovered.
Throughout that time, he said, about 5 percent of the women have remained uninfected by H.I.V., despite hundreds of exposures. That has been well known for years, and is also true of women in the business elsewhere, from Gambia to Thailand; what is not known is why.
With colleagues from several Canadian universities and Nairobi University, Dr. Plummer - who now directs Canada's equivalent of the Centers for Disease Control and Prevention - has found that the women have protective immune responses both in their white blood cells and in their vaginal walls.
Constant repeat exposures seem to boost those responses, but if the women stop working in the sex trade and then return, they often get infected, he said.
Many mysteries remain to unravel, and Dr. Plummer was awarded $8 million, which triples his research budget.
Resistance to H.I.V. clearly runs in families, he said, and he wants to analyze the genes of uninfected women and their relatives.
Also, uninfected women seem to have unusually slow immune systems, and he wants to infect some with mild flus to see how they react.
All attempts to make an AIDS vaccine have failed so far, and Dr. Plummer said his study might open up new approaches, like enhancing resistance genes or slowing immune responses.
Improved Cassavas
Cassava, a tuber practically unknown in the West, is the primary food for 250 million Africans - meaning that, in hard times, they eat nothing else for days.
The tuber's strongest point: it can survive for months in the ground as long as it is attached to its leaves. But it has many weak ones. It turns to mush within 48 hours of picking.
It has little protein. And it contains cyanide and slowly poisons those who eat it unless it is pounded and soaked repeatedly to leach the toxins out.
Dr. Richard T. Sayre said he developed his specialty decades ago when a Nigerian student asked for a job in his lab at Ohio State.
"He had been let go by his government and his department, and I hired him as a dishwasher," said Dr. Sayre, who was then studying photosynthesis.
The student, who was from the Biafra region of Nigeria and had nearly starved during the civil war and famine of the 1960's, asked if he could work on detoxifying cassava. He remembered his grandmother throwing ash in her cooking pot to release the cyanide as a gas.
The student later got a degree in soil science, but "we've been doing cassava for 20 years," Dr. Sayre said. Despite Rockefeller Foundation grants and some federal dollars, "it's always been a struggle." With $7.5 million from the foundation, he wants to genetically modify the tuber to store nitrogen as protein rather than as cyanogens, to produce more vitamin A and E and iron and zinc, and to better resist viral attacks.
The foundation is backing three other projects to improve rice, sorghum and bananas, and the scientists shared ideas at the meeting, as well as their common lament: not being taken seriously.
"It's difficult to get funding for banana research," said Dr. James Dale of the Queensland University of Technology, who is trying to improve Uganda's staple food. "Everyone thinks it's dessert."
Lab in a Box
"When I was in high school, the computer was a large machine that users brought data to," said Paul Yager, 51, a bioengineer from the University of Washington. "Now we have more computing power on our belts - in our cellphones - than existed when I was in high school."
Diagnostic laboratories, he said, have missed that change. Data - blood or urine - must still be shipped to them, a serious impediment to third world care.
Dr. Yager said he got interested in the field when he read about a mystery disease outbreak in a refugee camp that could not be treated correctly until blood samples reached Paris.
Dr. Yager's team received $15 million to develop a palm-size battery-powered lab.
His prototype, he said, will test a finger-stick drop of blood for flu, malaria, typhoid, dengue, measles, rickettsia, salmonella and other fever-causing infections - a tall order, because the infecting agents range from minuscule viruses to relatively immense parasites.
Ideally, the blood will be dripped into a well in a 30-layered piece of disposable plastic the size of a thick credit card, divided and sucked down 16 hair-narrow channels, mixing with reagents stored dry in tiny pits on the cards.
Enzymes will split the blood cells, discard the carbohydrates and leave only pathogen proteins or DNA, which will be amplified by the polymerase chain reaction. Fluorescent-tagged antibodies will be mixed in, and the fever diagnosed - all within 10 minutes.
"It's a stretch, but all the pieces are already done," Dr. Yager said, explaining that he was miniaturizing standard lab tests, "trying not to create any new science at all." (A movie of an instant blood-typing card developed by one of his partners, Micronics Inc., can be seen at micronics.net/products/blood.php.)
The biggest obstacles, he said, are keeping the blood cells from sticking in the microscopic channels and making sure there is enough pathogen to measure in each droplet.
"Engineers, being optimists, tell us that those are not drop-dead problems, but challenges," Dr. Yager said.
Legal challenges, he added, are another matter; many steps he must shrink are patented "by some very large players."
Mosquito 'Olfacticides'
Dr. Richard Axel of the Howard Hughes Medical Institute at Columbia University and Dr. Laurence J. Zwiebel of Vanderbilt University are both experts in insects' sense of smell. (Dr. Axel shared a 2004 Nobel Prize for working out how odors arouse the brain.)
Their complementary projects - Dr. Axel received $5 million and Dr. Zwiebel $8.5 million - have identified the genes that produce 79 odor receptors in mosquitoes.
Now they will seek to build what Dr. Zwiebel described as "a stand-alone mosquito-nose platform" - essentially, an antenna fragment in a petri dish - and to implant mosquito odor-receptor genes into fruit flies, which are easier to study.
Then they will test thousands of small molecules on these artificial or fly-borne "noses" to find chemicals that either block or overwhelm them.
Dr. Axel argued at the conference that blocking one receptor - the one that detects the carbon dioxide in human breath - might be enough to discourage biting.
Dr. Zwiebel argued that, since human sweat contains 150 different compounds, a cocktail of several blockers would be needed, both to encourage mosquitoes to bite other carbon dioxide-exhaling animals, like cows, and to make it harder for mosquitoes to evolve resistance to a single blocker.
One advantage of what Dr. Axel termed "olfacticides," which could be sprayed on the skin or soaked into mosquito nets, is that they are unlikely to be as toxic to humans as insecticides are.
A potential disadvantage is that odor-blockers could, for example, render pollinating insects like bees unable to smell plants.
It may also be possible, Dr. Zwiebel said, to find scents even more alluring than human sweat.
"Imagine," he said, "a village with a vat of DDT laced with compounds so attractive that it would become a mosquito motel: they'd check in, but they wouldn't check out."
Infecting Stem Cells
The most contrarian approach was that announced by Dr. David Baltimore, who shared a 1975 Nobel Prize for his work on tumor viruses and said he had been thinking since the 1980's about the frustrations of fighting AIDS.
Because the virus has thwarted every effort to make a vaccine, he said, "I decided there was potential in modifying the immune system so it would do what you want it to do instead of what it wants to do."
His project, for which he received $14 million, will require many steps: First, designing antibodies with two different "heads" that can bind the AIDS virus at two points. Second, genetically re-engineering a lentivirus to instruct white blood cells to produce those antibodies. Third, infecting stem cells with those lentiviruses, implanting them into patients and getting them to produce white blood cells that reproduce the antibodies.
To test each step, his team must create a mouse with a human immune system, something that three other teams getting Gates grants are also trying.
Although AIDS is his initial target, the approach, if it works, could theoretically be used against any infectious disease and someday render vaccination obsolete.
However, he acknowledged that there were still large problems to be solved, like the possibility that H.I.V. could mutate out of reach of his designed antibodies, and the fact that lentiviruses can cause cancer and must be rendered harmless before they are injected into a human immune system for life.
Vaginal Rings
Because some immune response to AIDS is at the site of infection, Dr. Robin John Shattock of the University of London is trying to develop vaccines that can be delivered in gels or a silicone ring that a woman can insert in her vagina, without a doctor's help, to deliver tiny daily doses.
The ring will be adapted from one already used for birth control and can adjust itself to menstrual cycles, which affect immune responses.
Ideally, he said, women will also get microbicides - virus-killing chemicals applied just before sex - through the same rings or gels, so the virus will get a one-two punch.
"We're trying to look at vaccination from a completely new viewpoint and set the bar really, really low," said Dr. Shattock, who received $20 million.
While conventional vaccine engineers try to invent one huge dose that provokes a strong immune reaction and gives lifelong immunity, he explained, he wants to deliver tiny doses conferring brief immunity without inflaming the vaginal wall, because inflammation there raises a woman's risk of infection.
Really? The Claim: Never Drink on an Empty Stomach
By ANAHAD O'CONNOR, The New York Times, December 6, 2005
THE FACTS It's an age-old rule about drinking, one that everyone knows and most people have broken: always fill up on food before filling up on alcohol.
Common wisdom, of course, suggests a simple reason, that drinking on an empty stomach will lead to intoxication more quickly. But just how much of a difference does eating before imbibing really make?
According to several studies and experts on alcohol, a lot. In 1994, one team of Swedish researchers set out to answer the question by having a group of 10 people consume a few drinks on two separate days.
In one case they drank after an overnight fast, and in the other, they drank after they ate a modest breakfast.
On the day the subjects ate, the rate of intoxication was slower, even though the amount of alcohol had not changed. But the subjects also reached significantly lower blood-alcohol levels over all - on average about 70 percent of what they were on the day they skipped breakfast.
In some cases, the study found, having a meal before drinking kept a person from climbing over the legal blood-alcohol limit for driving in most states.
Dr. Harris B. Stratyner, an addiction specialist and associate professor of psychiatry at Mount Sinai Medical Center, said it all had to do with metabolism.
As soon as alcohol is consumed, he said, the body starts to break it down, but some is always absorbed directly into the bloodstream.
Having food in the stomach - particularly proteins, fats and dense carbohydrates - slows that absorption process.
The things that speed it up are carbonated mixers, like soda, and higher temperatures. (Warm drinks are absorbed faster.) Once alcohol is in your blood, Dr. Stratyner said, neither coffee nor a cold shower will get it out any faster.
THE BOTTOM LINE Drinking on an empty stomach makes you drunk faster.
India Accelerating | An Epidemic Spreads
On India's Roads, Cargo and a Deadly Passenger
By AMY WALDMAN, The New York Times, December 6, 2005
NELAMANGALA, India - Hot water: 10 rupees. Cold water: 8 rupees. Toilet: 5 rupees.
Sex: no price specified on the bathhouse wall, but, as the condom painted there suggests, safe.
Sangeetha Hamam, a bathhouse, sits on the national highway near this gritty truck stop about nine miles north of Bangalore. Its mistress is Ranjeetha, a 28-year-old eunuch who lives as a woman. Her lipstick and black dress provide a touch of glamour in the small dark shack.
Her clients are not only truckers, but also Bangalore college students and other city residents. They know to look for sex at highway establishments geared toward truckers. Her customers - as many as 100 on Sundays for her and five other eunuchs - come for a "massage" and the anal sex that follows, but also for the anonymity the location confers.
Ranjeetha knows men will pay more for unprotected sex, but she calculates that the extra money is not worth the risk to her livelihood and life. She knows they can go elsewhere; there are some 45 bathhouses doubling as brothels near this truck stop. She also knows several eunuchs who have died of AIDS.
India has at least 5.1 million people living with H.I.V., the second highest number after South Africa. It is, by all accounts, at a critical stage: it can either prevent the further spread of infection, or watch a more generalized epidemic take hold. Global experts worry that India is both underspending on AIDS and undercounting its H.I.V. cases.
Its national highways are a conduit for the virus, passed by prostitutes and the truckers, migrants and locals who pay them, and brought home to unsuspecting wives in towns or villages. In its largest infrastructure project since independence, India is in the process of widening and upgrading those highways into a true interstate system. The effort will allow the roads to carry more traffic and freight than ever before. But some things are better left uncarried.
The national highways between New Delhi, Calcutta, Chennai, formerly Madras, and Mumbai run through at least six districts where H.I.V. prevalence is above 2.5 percent. Earlier this year, a New York Times reporter and a photographer drove the route, which has been nicknamed the Golden Quadrilateral.
To drive it is to peel back a nation's secret, or not so secret, sex life, and the potent mix of desire, denial and stigma that is helping spread the disease.
India's entry into the global economy over the past 15 years may also be furthering the spread of AIDS. With rising incomes, men have more money for sex; poor women see selling sex as their only access to the new prosperity. Cities are drawing more migrants and prostitutes, and Western influences are liberalizing Indian sexual mores. In response, cultural protectionists are refusing to allow even the national conversation about AIDS to reflect this changing reality.
The notion of a sexually chaste India is a "complete myth," said Ashok Alexander, the director of Avahan, the India AIDS Initiative of the Bill and Melinda Gates Foundation. Its preservation hurts prevention: "You say it's not a big problem, only 'those people' are doing that."
Driving the highway also shows the complications in reaching the various constituencies along it. India's AIDS epidemic is as variegated as the country itself, with a multiplicity of high-risk groups. Intravenous drug users concentrate in northeastern states. Devadasis - poor, lower-caste women consecrated to gods as young girls and then consigned to prostitution - live in the south.
Many of the groups are deeply fragmented and in perpetual motion, making them difficult for educators to reach: the man who owns a single truck; the woman who works at night out of a thatched hut; the lone migrant who shuttles back and forth between his village and urban work.
But a number of AIDS prevention groups have come to see working along the highway as the best hope for targeted interventions.
Avahan is pouring much of its $200 million into efforts along the highway. Another group, Project Concern International, sent young men to walk the Golden Quadrilateral - 3,625 miles long - over the course of a year to raise awareness about AIDS.
They met truckers, villagers, road workers and migrants, and in some places were cheered as heroes. In others, they were chased out for daring to discuss condoms and H.I.V., accused of spreading promiscuity and disease.
Sometimes, construction on the highway blocked the workers' way. But the deeper obstacles were culture, politics and history. The puritanical values of British colonialists repressed sexual expression in this country - essentially criminalizing homosexuality - and stigmatized it in many Indians' eyes as well. Some of the socially conservative Hindu nationalists who governed until 2004 tried to pretend no one was having sex, at least outside marriage.
In truth, sex work has flourished in independent India. Red-light districts operate openly in cities like Mumbai, formerly Bombay, and in its new suburbs and industrial areas. Hundreds of girls and women parade the streets at night near "pharmacies" where quacks peddle fake AIDS remedies.
And advocates battling the spread of AIDS say they have learned that men having sex with men, then with their wives, is surprisingly common, but veiled by stigma.
Ranjeetha, the bathhouse mistress, believes the real danger is not open eunuchs like her, but the men in denial, who work in offices by day and dress in saris at night. "People who lead double lives don't use condoms," she said.
Awareness and Denial
At least 1,000 trucks a day pass through Nelamangala's trans-shipment point, often waiting hours or days for a new load. In the interim, drivers and their helpers patronize bathhouses like Sangeetha, although many of the sex establishments do not paint condoms on the outside, and use none inside.
There are three million to four million trucks on India's roads, at least one million of them traveling long distances. If truckers cannot find sex at trans-shipment points, they can buy it on the roadside, where women signal potential clients with flashlights.
As many as 11 percent of truckers may be H.I.V. positive. In some parts of the country, like Tamil Nadu, the stigma around truckers has grown so strong that fathers forbid their daughters to marry them.
Yet no one has figured out a comprehensive system for education or testing. There are perhaps 3,000 to 4,000 regional transport companies, but most trucks are owner-driven or run by small companies.
The major stopping points, or trans-shipment yards, see so many truckers each day that even if truckers take an AIDS test, there is no way to follow up - an "amnesiac system" in one advocate's words.
In a dusty parking lot at this truck trans-shipment point, an AIDS educator wielded a black dildo and a condom, encircled by truckers who stifled mirth and curiosity.
"Why are you targeting us?" a trucker asked the educator.
Truckers asked if AIDS could be transmitted by mosquito bites. They made ribald jokes about their sex lives, and boasted about not using condoms.
One trucker interrupted to say he knew people who used condoms and still got AIDS.
"Check the expiration date," the educator said.
"We are illiterate, we can't read," the trucker replied.
In the country's north, some drivers say they have never heard of AIDS, although their facial expressions may suggest otherwise. In the south, where AIDS is much more common, denial is trickier. Truckers have heard of AIDS, and often know someone who died from it, and word is starting to travel along with the virus.
But awareness does not always translate to protection. Bhagwan Singh, 47, a trucker who was halting at the Gujarat-Rajasthan border, said he did not use condoms, because he had paid for sex only a few times.
"What happens if I just go once, twice, thrice?" he said. "Only if I'm a regular fellow I might contract such things."
Bringing H.I.V. Home
Once, twice, thrice or more often, whatever the truckers do on the road, or migrants do in cities, is coming home to oblivious wives. Here, the danger of a culture that is simultaneously licentious and conservative, of seasoned husbands and sheltered wives, becomes clear.
This has become especially apparent in India's southern states, which are prospering economically, but have been hit the hardest by AIDS, along with pockets of the isolated northeast.
The states the highway runs through in the south all have H.I.V. infection rates of 1 percent or higher.
In the government hospital in Guntur, a district with a 2.5 percent H.I.V. infection rate, Sambra Ja Lakshmi, 27, a mother of two, was being counseled.
Her husband, a 33-year-old trucker, had done "thousands of kilometers on the national highway," as she put it. Where he got H.I.V. is unknown, but he was so sick he could no longer move. She, a homemaker and mother who barely left her village about 15 miles off the highway, was H.I.V. positive, too.
The counselor, Sunita Murugudu, had heard it before, and knew she would hear it again.
Some 80 percent of truckers' wives who came in for voluntary testing and counseling tested positive, she said, usually because by the time they came in their husbands were on their deathbeds, and denial could no longer be sustained.
G. Karuna, 24, was another woman who fell prey to the peregrinations of her husband, a long-distance driver from a family of truckers. When they both sought treatment for tuberculosis or opportunistic infections at hospitals, they hid his occupation, since many private hospitals now turn truckers away.
After her husband died, his family blamed her, a cruel vengeance some in-laws inflict on the widows. They have made treatment and prevention that much harder.
She was forced to sleep on the path outside; the family refused to share even a loaf of bread that she had touched. Soon their whole village had ostracized her.
Ms. Karuna cried as she told her story, but that story also conveyed an uncommon strength. She had left her husband's family and her village to start a new life on her own. She became an activist with the Social Educational and Economic Development Society, an advocacy group in Guntur, trying to save other truckers' wives.
She showed women pictures of her handsome husband before he sickened, and after.
She told the wives to know what their husbands were doing outside the home, to negotiate the use of condoms with them, to get treated for sexually transmitted diseases. Her husband's relatives still teased her: "Why are you working so hard? You also will die."
Morality and Stigma
In the town of Nippani, outside Lafayette Hospital, a sign warned against unprotected sex, showing a blue demon on a horse slaying a healthy man.
But those who fell prey to that demon were not welcomed, explained a doctor, Sunil Sase. AIDS carried a stigma like leprosy, he said, "so we are not exactly treating the AIDS cases." They were sent to another hospital 50 miles away.
A group working to raise AIDS awareness among prostitutes had been chased from Nippani after being accused of promoting sex. Most of the devadasis and prostitutes, who had been working in the town on the highway for 50 years, had been chased out in a morality crusade. Now they were scattered along the road, impossible to reach with education or condoms.
A mob had pulled one prostitute, Reshma Sheikh, and her 7-year-old son out of her house to try to force them from town. "We have a right to live and work there, we never hurt the sentiments of the people around," she said. She had stayed, only because she had nowhere else to go.
The main group leading the crusade was the Shiv Sena, a Hindu nationalist political party. Sunil Sadashir Dalavi, 32, the local leader, boasted about their success. But he said the women were not the only cause for the spread of AIDS.
"Educated boys don't get jobs, they have extra time, they don't know what to do," he said. "They can't marry till they get a job, they have very strong desires, so they go to these women."
Once the men were married they would not do "these things," he insisted, despite government surveys showing otherwise. The answer to controlling sex was controlling the culture, he said. A lot of local men went to two nearby cinemas that screened sex movies, he said, and then to brothels. "We want to close the 'talkies' down," he said, "so people will not do this."
A Fragmented Industry
In almost every doorway in the red-light district of Chilakaluripet, in Andhra Pradesh, women drape, wearing bright clothes, garish makeup and come-hither expressions that have served to lure both men and disease.
For half a century, the town has been a center of sex work, combining its location on the national highway with women from its Domara community, which has come to specialize in prostitution. Truckers passing through know where to stop; if they do not, there are hotel boys, rickshaw pullers and others willing to guide them.
In recent years, the town and surrounding area have also become a center of H.I.V. infection, and, given the number of long-distance truckers tarrying here, a likely source for its spread elsewhere.
The sex industry has been organized in some cities, like Calcutta, but mostly it is as fragmented as the trucking industry. Chilakaluripet features brothel-based and home-based prostitutes, secret prostitutes and women who sell sex along the highway. A police crackdown on brothels in recent years has further dispersed the women.
Venkaimah, a 25-year-old widow, is part of a "highway brothel" - a small moving coterie of women who work in bushes or fields or restaurants along the road. Her workday starts when the light is gone and the truck traffic heavy. She leaves her two daughters, 10 and 2, behind, and on a good night may get 8 to 10 customers who pay 50 cents to a dollar each.
Some prostitutes now use condoms, but the disease continues to spread. One local organization, Needs Serving Society, estimated that 1,000 people had tested positive for H.I.V. in the town and nearby villages, most of them not prostitutes, but locals who may have patronized them. No one, though, had any real idea of the true number. On one narrow lane alone, 20 prostitutes were infected, said one of them, Konda, 38.
Venkaimah's children motivated her to use condoms - if she did not, she knew that sooner or later they would be orphaned. But loneliness can loosen defenses: like many prostitutes, she had "temporary husbands" - longtime boyfriends - with whom she did not use a condom at all.
Chilakaluripet, known for sex, was now marked by death.
In a courtyard, Venkateswarmma, a mother of two, as thin and brittle as a doll, sat on a cot, unable to move. Her husband, a brothel owner's son, had died 10 days before, infected after sleeping with its employees. She was near death herself, unable to walk for her husband's death ceremony. Her 2-year-old son had already died from AIDS; she would leave behind an 11-year-old boy.
A Mobile Society
For 15 years, Vilas Jaganath Kamkar had been taking the bus from his village in Maharashtra state to Mumbai, its capital, where he worked as a taxicab driver. In 1994, he had taken a wife, Manisha, but he kept working in Mumbai, with monthly visits home.
In this migrant nation, his life was not unique. Nor, in this age of AIDS, was his fate. Migrants may be the hardest group for AIDS educators to reach. As Indian society becomes more mobile, people are leaving villages for urban work at increasing rates.
In Maharashtra, new plants and factories are springing up along the revamped highway. As rural migrants come to work in the factories, poor women follow to sexually service the men. Newly rich locals patronize the abundant supply of women, spawning H.I.V. "hot spots" along the highways.
In cities, the migrants live in slums, three or more to a room, and may move often. Away from their families for months at a time, they seek the companionship not just of prostitutes but of girlfriends, with whom safe sex is often ignored.
Migrants leave home to work, but go home to die. At the hospital in Satara, a prospering city on the highway south of Mumbai, Mr. Kamkar, the taxi driver, now 32, lay breathless on a hospital bed. His luck had run out, and not just because he had contracted H.I.V. Only 25 hospitals and health centers were prescribing antiretroviral drugs. They were available in Guntur, but not 12 miles south in Chilakaluripet. They could be had in Mumbai - but not in Satara.
All Mrs. Kamkar, 25, a mother of two, could do was take her husband back to their village, try to ease his pain and nurse him until the end.
"It's a matter of his destiny," she said.
By HENRY FOUNTAIN, The New York Times, December 6, 2005
Martin A. Whyte is a dinosaur hunter by profession, stalking the remains of the beasts in Yorkshire, England. But no matter where he is, Dr. Whyte is always on the lookout for signs of ancient life.
So it's no surprise that Dr. Whyte, a professor at the University of Sheffield who is also a geologist, discovered a fossil track one summer day in 2003, when he took time from studying the geology of the central Scottish coast to stroll on the beach.
Dr. Whyte's analysis of what made those tracks, however, turned out to be a big surprise - a giant water scorpion from 330 million years ago, long before the age of the dinosaurs. It is the first evidence that these long-extinct arthropods walked on land.
Dr. Whyte said the discovery was serendipitous. "I found myself looking across a stretch of beach," he recalled, "and I saw a rock face with this trackway going across." It consisted of a sinuous series of markings about 20 feet long, made in sand that had turned to rock.
"I knew as soon as I saw it, it was made by some kind of animal," he said.
It was clear from the markings that the creature had three limbs on each side. "Right away that eliminated the reptiles and amphibians," Dr. Whyte said. "I had to consider some sort of arthropod."
The track also had a large central groove, obviously made by a heavy tail. And the animal must have been huge, about 5 feet long and 3 feet wide. Dr. Whyte decided it could only be a species of Hibbertopterus, water scorpions that are distant ancestors of modern creatures like horseshoe crabs.
Just fragments of Hibbertopterus fossils exist. Some are from specimens the size of the one that left the tracks, Dr. Whyte said.
The stride is very short, indicating it moved very slowly and probably in a herky-jerky manner. That its tail dragged- the groove it left partly obscured some of the footprints - is strong evidence that the creature was walking across land. "This animal was in no way buoyed up by water," he said.
At this point in the earth's history, the earliest four-legged animals were coming out of the water onto land. But water scorpions did not make such a transition. Dr. Whyte said this specimen was probably out of the water a short time, as its gill-like breathing apparatus needed to remain wet. So it might have been walking from one body of water to another one nearby.
"The best I can say is it's going from somewhere to somewhere," he said. "It's nice to speculate that it might have come out for spawning or to look for a beach party or whatever. But there's just no evidence for that."
Better Bananas, Nicer Mosquitoes
By DONALD G. McNEIL Jr., The New York Times, December 6, 2005
SEATTLE - Addressing 275 of the world's most brilliant scientists, Bill Gates cracked a joke:
"I've been applying my imagination to the synergies of this," he said. "We could have sorghum that cures latent tuberculosis. We could have mosquitoes that spread vitamin A. And most important, we could have bananas that never need to be kept cold."
They laughed. Perhaps that was to be expected when the world's richest man, who had just promised them $450 million, was delivering a punchline. But it was also germane, because they were gathered to celebrate some of the oddest-sounding projects in the history of science.
Their deadly serious proposals - answers to the Grand Challenges in Global Health that Mr. Gates posed in a 2003 speech in Davos, Switzerland - sounded much like his spoofs: laboratories around the world, some of them led by Nobel Prize winners, proposing to invent bananas and sorghum that make their own vitamin A; chemicals that render mosquitoes unable to smell humans; drugs that hunt down tuberculosis germs in people who do not even know they are infected; and vaccines that are mixed into spores or plastics or sugars and can be delivered in glasses of orange juice or modified goose calls.
What Mr. Gates had outlined at Davos were the greatest obstacles facing doctors in the tropics: Laboratories are few and far between. Vaccines spoil without refrigeration and require syringes, which can transmit AIDS. Mosquitoes develop resistance to all insecticides. Crops that survive in the jungle or desert often have little nutritive value. Infections outwit powerful drugs by lying dormant.
His offer - originally $200 million, raised to $450 million after 1,600 proposals came in - "was to make sure that innovation wasn't reserved just for big-ticket items like cancer and heart disease," said Dr. Carol A. Dahl, the foundation's director of global health technologies, who ran the conference.
The winning teams, which were named in June,came from as far away as Australia and China, withresearch partners all over Africa and Southeast Asia. Over three days in a Seattle hotel, the 43 team leaders delivered 10-minute summaries of their plans, quizzed foundation officials about details of the grants and discussed possible ethical quandaries with bioethicists from the University of Toronto.
(The most common questions were about the one ironclad rule: grantees may patent anything they discover, but must make it available cheaply to poor countries. An ethical concern common to many projects is that they will eventually require clinical trials on impoverished Africans or Asians with little understanding of informed consent.)
In the hallways and over cocktails and dinners - all paid for by the foundation - virologists and neurologists talked with plant biologists and nanoparticle physicists, sometimes finding ways to help one another. For example, a scientist with plans to improve vitamin-fortified "golden rice" asked the designer of a hand-held laboratory to test blood for pathogens whether it could be modified to test blood for iron and vitamins.
Mr. Gates, in an interview, sidestepped a request to name his favorite projects. "Oh, I love all my children," he said.
But he remained brutally realistic about where his "children" - and the money he lavishes on them - were likely to end up. "Eighty percent of these are likely to be dead ends," he said. "But even if we have a 10 percent hit rate, it will all have been worthwhile."
What follows is a selection of the winning projects.
Dried Vaccines
The only scientist to emit a goose honk during his presentation was Robert E. Sievers, who was illustrating inexpensive straws with useful vibrations.
Dr. Sievers, the chief executive of Aktiv-Dry, a Colorado company that turns liquids into superfine powders, is trying to develop a measles vaccine that can be stored dry and inhaled.
He proposed turning it into glassy particles around a matrix of trehalose, the sugar that allows brine shrimp cysts to survive dried out for years but hatch into wriggling creatures in seawater. (The shrimp are perhaps better known as the "amazing live sea monkeys" advertised in comic books.)
For the powder to reach the lungs instead of sticking to the straw or the throat, the particles must be dispersed evenly in the airstream. Vibration helps, and he tested oboe reeds, New Year's noisemakers and goose calls, trying to find something disposable that needs no power, even from batteries.
A longtime chemistry professor at the University of Colorado, Dr. Sievers, 70, had a second career running a company developing pollution-detection instruments when his son, a pediatrician, described how premature newborns were given surfactants to keep their lung sacs from sticking like Cling Wrap.
"They squirt a bolus of water down into the lungs, then they turn the baby over and pour it out," the elder Dr. Sievers said, shaking his head in disbelief. "There had to be a way to improve that."
In the 1990's, he turned his hand to inhalers for surfactants, then for asthma and now for vaccines. "Measles kills 2,000 children a day," he said, briefly tearing up, and then apologizing for it, as he described his new passion for the cause and what his $20 million grant will let him pursue. "That's like a World Trade Center disaster every day. This is what I want to do with the last stretch of my life."
Abraham L. Sonenshein of Tufts University, who received $5 million, wants to use bacterial spores, another form of nature that can survive desert heat or Arctic cold.
"Our ideal vaccine would be a packet of spores that could be emptied into a glass of juice and drunk down," he said
His chosen vehicle, bacillus subtilis, is found all over the world in dirt.
"Safety is a nonissue," he said. "A large fraction of the Japanese population eats it every day for breakfast." The bacteria are used to ferment soybeans for a dish called natto.
But rather than simply drying an existing vaccine, he wants to splice into the subtilis bacterium's DNA the ability to make the fragments of viral protein that provoke the immune reaction.
Dried bacterial spores could survive indefinitely - and then bloom in the gut and start assembling the proteins.
He has already inserted the genes for diphtheria and tetanus vaccines, and is working on adding whooping cough and rotavirus.
Ten years ago, he said, a Tufts colleague came back from a conference on children's diseases and excitedly described how hard it was to keep vaccines cold in villages without electricity.
Dr. Sonenshein, a bacteria expert, said he replied: "Why are you telling me this?"
But as soon as his colleague asked whether spores could help, he understood.
"We worked on it for two years, and then gave it up, because the traditional funding agencies thought it was too speculative," he said. "The project lay fallow for eight years, so I'm very grateful for the grant."
Mosquito Time Bomb
Scott L. O'Neill, a biologist at Australia's University of Queensland, had an inspiration based on two unrelated facts: mosquitoes must be "middle-aged" - about 14 days old - before they can transmit the dengue virus, and wolbachia bacteria kill fruit flies in midlife.
Since 1975, dengue fever has become a major cause of death for young children, especially in Southeast Asia, where Dr. O'Neill has done field work. "The mosquitoes were controlled in the 1960's," he said. "But they're invading new areas."
Wolbachia, parasitic bacteria, live in many insects, eventually killing some of them. But, in what Dr. O'Neill called a "sneaky and spiteful manipulation of their host," they assure their survival into the next generation by infecting embryos as well, and by rendering infertile any embryos that do not come from infected parents.
(They probably kill the hosts by growing prolifically on their nerve cells, and they may render embryos infertile by somehow preventing egg-sperm fusion, Dr. O'Neill said, but those mysteries are still unsolved.)
Most mosquitoes live about a month, but it takes about 14 days for the dengue virus, which the female picks up by biting an infected human, to mature in her gut and reach her salivary glands, ready to be injected into the next human.
Month-old females who have bitten several people are the most dangerous mosquitoes.
Dr. O'Neill, who received $7 million, hopes to find a life-shortening wolbachia strain in fruit flies or to create one by gene modification, and use it to infect mosquitoes, which now harbor benign strains.
If it works, a female will still live long enough to take a blood meal and lay one set of eggs, so there will be little evolutionary pressure on her to resist the bacteria.
But she will die before she can transmit dengue.
Prostitutes in Kenya
Since 1981, when he was a junior researcher at the University of Manitoba, Dr. Francis A. Plummer has studied thousands of prostitutes in Nairobi, Kenya - initially looking for chancroid and gonorrhea, and then, for the AIDS virus, once it was discovered.
Throughout that time, he said, about 5 percent of the women have remained uninfected by H.I.V., despite hundreds of exposures. That has been well known for years, and is also true of women in the business elsewhere, from Gambia to Thailand; what is not known is why.
With colleagues from several Canadian universities and Nairobi University, Dr. Plummer - who now directs Canada's equivalent of the Centers for Disease Control and Prevention - has found that the women have protective immune responses both in their white blood cells and in their vaginal walls.
Constant repeat exposures seem to boost those responses, but if the women stop working in the sex trade and then return, they often get infected, he said.
Many mysteries remain to unravel, and Dr. Plummer was awarded $8 million, which triples his research budget.
Resistance to H.I.V. clearly runs in families, he said, and he wants to analyze the genes of uninfected women and their relatives.
Also, uninfected women seem to have unusually slow immune systems, and he wants to infect some with mild flus to see how they react.
All attempts to make an AIDS vaccine have failed so far, and Dr. Plummer said his study might open up new approaches, like enhancing resistance genes or slowing immune responses.
Improved Cassavas
Cassava, a tuber practically unknown in the West, is the primary food for 250 million Africans - meaning that, in hard times, they eat nothing else for days.
The tuber's strongest point: it can survive for months in the ground as long as it is attached to its leaves. But it has many weak ones. It turns to mush within 48 hours of picking.
It has little protein. And it contains cyanide and slowly poisons those who eat it unless it is pounded and soaked repeatedly to leach the toxins out.
Dr. Richard T. Sayre said he developed his specialty decades ago when a Nigerian student asked for a job in his lab at Ohio State.
"He had been let go by his government and his department, and I hired him as a dishwasher," said Dr. Sayre, who was then studying photosynthesis.
The student, who was from the Biafra region of Nigeria and had nearly starved during the civil war and famine of the 1960's, asked if he could work on detoxifying cassava. He remembered his grandmother throwing ash in her cooking pot to release the cyanide as a gas.
The student later got a degree in soil science, but "we've been doing cassava for 20 years," Dr. Sayre said. Despite Rockefeller Foundation grants and some federal dollars, "it's always been a struggle." With $7.5 million from the foundation, he wants to genetically modify the tuber to store nitrogen as protein rather than as cyanogens, to produce more vitamin A and E and iron and zinc, and to better resist viral attacks.
The foundation is backing three other projects to improve rice, sorghum and bananas, and the scientists shared ideas at the meeting, as well as their common lament: not being taken seriously.
"It's difficult to get funding for banana research," said Dr. James Dale of the Queensland University of Technology, who is trying to improve Uganda's staple food. "Everyone thinks it's dessert."
Lab in a Box
"When I was in high school, the computer was a large machine that users brought data to," said Paul Yager, 51, a bioengineer from the University of Washington. "Now we have more computing power on our belts - in our cellphones - than existed when I was in high school."
Diagnostic laboratories, he said, have missed that change. Data - blood or urine - must still be shipped to them, a serious impediment to third world care.
Dr. Yager said he got interested in the field when he read about a mystery disease outbreak in a refugee camp that could not be treated correctly until blood samples reached Paris.
Dr. Yager's team received $15 million to develop a palm-size battery-powered lab.
His prototype, he said, will test a finger-stick drop of blood for flu, malaria, typhoid, dengue, measles, rickettsia, salmonella and other fever-causing infections - a tall order, because the infecting agents range from minuscule viruses to relatively immense parasites.
Ideally, the blood will be dripped into a well in a 30-layered piece of disposable plastic the size of a thick credit card, divided and sucked down 16 hair-narrow channels, mixing with reagents stored dry in tiny pits on the cards.
Enzymes will split the blood cells, discard the carbohydrates and leave only pathogen proteins or DNA, which will be amplified by the polymerase chain reaction. Fluorescent-tagged antibodies will be mixed in, and the fever diagnosed - all within 10 minutes.
"It's a stretch, but all the pieces are already done," Dr. Yager said, explaining that he was miniaturizing standard lab tests, "trying not to create any new science at all." (A movie of an instant blood-typing card developed by one of his partners, Micronics Inc., can be seen at micronics.net/products/blood.php.)
The biggest obstacles, he said, are keeping the blood cells from sticking in the microscopic channels and making sure there is enough pathogen to measure in each droplet.
"Engineers, being optimists, tell us that those are not drop-dead problems, but challenges," Dr. Yager said.
Legal challenges, he added, are another matter; many steps he must shrink are patented "by some very large players."
Mosquito 'Olfacticides'
Dr. Richard Axel of the Howard Hughes Medical Institute at Columbia University and Dr. Laurence J. Zwiebel of Vanderbilt University are both experts in insects' sense of smell. (Dr. Axel shared a 2004 Nobel Prize for working out how odors arouse the brain.)
Their complementary projects - Dr. Axel received $5 million and Dr. Zwiebel $8.5 million - have identified the genes that produce 79 odor receptors in mosquitoes.
Now they will seek to build what Dr. Zwiebel described as "a stand-alone mosquito-nose platform" - essentially, an antenna fragment in a petri dish - and to implant mosquito odor-receptor genes into fruit flies, which are easier to study.
Then they will test thousands of small molecules on these artificial or fly-borne "noses" to find chemicals that either block or overwhelm them.
Dr. Axel argued at the conference that blocking one receptor - the one that detects the carbon dioxide in human breath - might be enough to discourage biting.
Dr. Zwiebel argued that, since human sweat contains 150 different compounds, a cocktail of several blockers would be needed, both to encourage mosquitoes to bite other carbon dioxide-exhaling animals, like cows, and to make it harder for mosquitoes to evolve resistance to a single blocker.
One advantage of what Dr. Axel termed "olfacticides," which could be sprayed on the skin or soaked into mosquito nets, is that they are unlikely to be as toxic to humans as insecticides are.
A potential disadvantage is that odor-blockers could, for example, render pollinating insects like bees unable to smell plants.
It may also be possible, Dr. Zwiebel said, to find scents even more alluring than human sweat.
"Imagine," he said, "a village with a vat of DDT laced with compounds so attractive that it would become a mosquito motel: they'd check in, but they wouldn't check out."
Infecting Stem Cells
The most contrarian approach was that announced by Dr. David Baltimore, who shared a 1975 Nobel Prize for his work on tumor viruses and said he had been thinking since the 1980's about the frustrations of fighting AIDS.
Because the virus has thwarted every effort to make a vaccine, he said, "I decided there was potential in modifying the immune system so it would do what you want it to do instead of what it wants to do."
His project, for which he received $14 million, will require many steps: First, designing antibodies with two different "heads" that can bind the AIDS virus at two points. Second, genetically re-engineering a lentivirus to instruct white blood cells to produce those antibodies. Third, infecting stem cells with those lentiviruses, implanting them into patients and getting them to produce white blood cells that reproduce the antibodies.
To test each step, his team must create a mouse with a human immune system, something that three other teams getting Gates grants are also trying.
Although AIDS is his initial target, the approach, if it works, could theoretically be used against any infectious disease and someday render vaccination obsolete.
However, he acknowledged that there were still large problems to be solved, like the possibility that H.I.V. could mutate out of reach of his designed antibodies, and the fact that lentiviruses can cause cancer and must be rendered harmless before they are injected into a human immune system for life.
Vaginal Rings
Because some immune response to AIDS is at the site of infection, Dr. Robin John Shattock of the University of London is trying to develop vaccines that can be delivered in gels or a silicone ring that a woman can insert in her vagina, without a doctor's help, to deliver tiny daily doses.
The ring will be adapted from one already used for birth control and can adjust itself to menstrual cycles, which affect immune responses.
Ideally, he said, women will also get microbicides - virus-killing chemicals applied just before sex - through the same rings or gels, so the virus will get a one-two punch.
"We're trying to look at vaccination from a completely new viewpoint and set the bar really, really low," said Dr. Shattock, who received $20 million.
While conventional vaccine engineers try to invent one huge dose that provokes a strong immune reaction and gives lifelong immunity, he explained, he wants to deliver tiny doses conferring brief immunity without inflaming the vaginal wall, because inflammation there raises a woman's risk of infection.
Really? The Claim: Never Drink on an Empty Stomach
By ANAHAD O'CONNOR, The New York Times, December 6, 2005
THE FACTS It's an age-old rule about drinking, one that everyone knows and most people have broken: always fill up on food before filling up on alcohol.
Common wisdom, of course, suggests a simple reason, that drinking on an empty stomach will lead to intoxication more quickly. But just how much of a difference does eating before imbibing really make?
According to several studies and experts on alcohol, a lot. In 1994, one team of Swedish researchers set out to answer the question by having a group of 10 people consume a few drinks on two separate days.
In one case they drank after an overnight fast, and in the other, they drank after they ate a modest breakfast.
On the day the subjects ate, the rate of intoxication was slower, even though the amount of alcohol had not changed. But the subjects also reached significantly lower blood-alcohol levels over all - on average about 70 percent of what they were on the day they skipped breakfast.
In some cases, the study found, having a meal before drinking kept a person from climbing over the legal blood-alcohol limit for driving in most states.
Dr. Harris B. Stratyner, an addiction specialist and associate professor of psychiatry at Mount Sinai Medical Center, said it all had to do with metabolism.
As soon as alcohol is consumed, he said, the body starts to break it down, but some is always absorbed directly into the bloodstream.
Having food in the stomach - particularly proteins, fats and dense carbohydrates - slows that absorption process.
The things that speed it up are carbonated mixers, like soda, and higher temperatures. (Warm drinks are absorbed faster.) Once alcohol is in your blood, Dr. Stratyner said, neither coffee nor a cold shower will get it out any faster.
THE BOTTOM LINE Drinking on an empty stomach makes you drunk faster.
India Accelerating | An Epidemic Spreads
On India's Roads, Cargo and a Deadly Passenger
By AMY WALDMAN, The New York Times, December 6, 2005
NELAMANGALA, India - Hot water: 10 rupees. Cold water: 8 rupees. Toilet: 5 rupees.
Sex: no price specified on the bathhouse wall, but, as the condom painted there suggests, safe.
Sangeetha Hamam, a bathhouse, sits on the national highway near this gritty truck stop about nine miles north of Bangalore. Its mistress is Ranjeetha, a 28-year-old eunuch who lives as a woman. Her lipstick and black dress provide a touch of glamour in the small dark shack.
Her clients are not only truckers, but also Bangalore college students and other city residents. They know to look for sex at highway establishments geared toward truckers. Her customers - as many as 100 on Sundays for her and five other eunuchs - come for a "massage" and the anal sex that follows, but also for the anonymity the location confers.
Ranjeetha knows men will pay more for unprotected sex, but she calculates that the extra money is not worth the risk to her livelihood and life. She knows they can go elsewhere; there are some 45 bathhouses doubling as brothels near this truck stop. She also knows several eunuchs who have died of AIDS.
India has at least 5.1 million people living with H.I.V., the second highest number after South Africa. It is, by all accounts, at a critical stage: it can either prevent the further spread of infection, or watch a more generalized epidemic take hold. Global experts worry that India is both underspending on AIDS and undercounting its H.I.V. cases.
Its national highways are a conduit for the virus, passed by prostitutes and the truckers, migrants and locals who pay them, and brought home to unsuspecting wives in towns or villages. In its largest infrastructure project since independence, India is in the process of widening and upgrading those highways into a true interstate system. The effort will allow the roads to carry more traffic and freight than ever before. But some things are better left uncarried.
The national highways between New Delhi, Calcutta, Chennai, formerly Madras, and Mumbai run through at least six districts where H.I.V. prevalence is above 2.5 percent. Earlier this year, a New York Times reporter and a photographer drove the route, which has been nicknamed the Golden Quadrilateral.
To drive it is to peel back a nation's secret, or not so secret, sex life, and the potent mix of desire, denial and stigma that is helping spread the disease.
India's entry into the global economy over the past 15 years may also be furthering the spread of AIDS. With rising incomes, men have more money for sex; poor women see selling sex as their only access to the new prosperity. Cities are drawing more migrants and prostitutes, and Western influences are liberalizing Indian sexual mores. In response, cultural protectionists are refusing to allow even the national conversation about AIDS to reflect this changing reality.
The notion of a sexually chaste India is a "complete myth," said Ashok Alexander, the director of Avahan, the India AIDS Initiative of the Bill and Melinda Gates Foundation. Its preservation hurts prevention: "You say it's not a big problem, only 'those people' are doing that."
Driving the highway also shows the complications in reaching the various constituencies along it. India's AIDS epidemic is as variegated as the country itself, with a multiplicity of high-risk groups. Intravenous drug users concentrate in northeastern states. Devadasis - poor, lower-caste women consecrated to gods as young girls and then consigned to prostitution - live in the south.
Many of the groups are deeply fragmented and in perpetual motion, making them difficult for educators to reach: the man who owns a single truck; the woman who works at night out of a thatched hut; the lone migrant who shuttles back and forth between his village and urban work.
But a number of AIDS prevention groups have come to see working along the highway as the best hope for targeted interventions.
Avahan is pouring much of its $200 million into efforts along the highway. Another group, Project Concern International, sent young men to walk the Golden Quadrilateral - 3,625 miles long - over the course of a year to raise awareness about AIDS.
They met truckers, villagers, road workers and migrants, and in some places were cheered as heroes. In others, they were chased out for daring to discuss condoms and H.I.V., accused of spreading promiscuity and disease.
Sometimes, construction on the highway blocked the workers' way. But the deeper obstacles were culture, politics and history. The puritanical values of British colonialists repressed sexual expression in this country - essentially criminalizing homosexuality - and stigmatized it in many Indians' eyes as well. Some of the socially conservative Hindu nationalists who governed until 2004 tried to pretend no one was having sex, at least outside marriage.
In truth, sex work has flourished in independent India. Red-light districts operate openly in cities like Mumbai, formerly Bombay, and in its new suburbs and industrial areas. Hundreds of girls and women parade the streets at night near "pharmacies" where quacks peddle fake AIDS remedies.
And advocates battling the spread of AIDS say they have learned that men having sex with men, then with their wives, is surprisingly common, but veiled by stigma.
Ranjeetha, the bathhouse mistress, believes the real danger is not open eunuchs like her, but the men in denial, who work in offices by day and dress in saris at night. "People who lead double lives don't use condoms," she said.
Awareness and Denial
At least 1,000 trucks a day pass through Nelamangala's trans-shipment point, often waiting hours or days for a new load. In the interim, drivers and their helpers patronize bathhouses like Sangeetha, although many of the sex establishments do not paint condoms on the outside, and use none inside.
There are three million to four million trucks on India's roads, at least one million of them traveling long distances. If truckers cannot find sex at trans-shipment points, they can buy it on the roadside, where women signal potential clients with flashlights.
As many as 11 percent of truckers may be H.I.V. positive. In some parts of the country, like Tamil Nadu, the stigma around truckers has grown so strong that fathers forbid their daughters to marry them.
Yet no one has figured out a comprehensive system for education or testing. There are perhaps 3,000 to 4,000 regional transport companies, but most trucks are owner-driven or run by small companies.
The major stopping points, or trans-shipment yards, see so many truckers each day that even if truckers take an AIDS test, there is no way to follow up - an "amnesiac system" in one advocate's words.
In a dusty parking lot at this truck trans-shipment point, an AIDS educator wielded a black dildo and a condom, encircled by truckers who stifled mirth and curiosity.
"Why are you targeting us?" a trucker asked the educator.
Truckers asked if AIDS could be transmitted by mosquito bites. They made ribald jokes about their sex lives, and boasted about not using condoms.
One trucker interrupted to say he knew people who used condoms and still got AIDS.
"Check the expiration date," the educator said.
"We are illiterate, we can't read," the trucker replied.
In the country's north, some drivers say they have never heard of AIDS, although their facial expressions may suggest otherwise. In the south, where AIDS is much more common, denial is trickier. Truckers have heard of AIDS, and often know someone who died from it, and word is starting to travel along with the virus.
But awareness does not always translate to protection. Bhagwan Singh, 47, a trucker who was halting at the Gujarat-Rajasthan border, said he did not use condoms, because he had paid for sex only a few times.
"What happens if I just go once, twice, thrice?" he said. "Only if I'm a regular fellow I might contract such things."
Bringing H.I.V. Home
Once, twice, thrice or more often, whatever the truckers do on the road, or migrants do in cities, is coming home to oblivious wives. Here, the danger of a culture that is simultaneously licentious and conservative, of seasoned husbands and sheltered wives, becomes clear.
This has become especially apparent in India's southern states, which are prospering economically, but have been hit the hardest by AIDS, along with pockets of the isolated northeast.
The states the highway runs through in the south all have H.I.V. infection rates of 1 percent or higher.
In the government hospital in Guntur, a district with a 2.5 percent H.I.V. infection rate, Sambra Ja Lakshmi, 27, a mother of two, was being counseled.
Her husband, a 33-year-old trucker, had done "thousands of kilometers on the national highway," as she put it. Where he got H.I.V. is unknown, but he was so sick he could no longer move. She, a homemaker and mother who barely left her village about 15 miles off the highway, was H.I.V. positive, too.
The counselor, Sunita Murugudu, had heard it before, and knew she would hear it again.
Some 80 percent of truckers' wives who came in for voluntary testing and counseling tested positive, she said, usually because by the time they came in their husbands were on their deathbeds, and denial could no longer be sustained.
G. Karuna, 24, was another woman who fell prey to the peregrinations of her husband, a long-distance driver from a family of truckers. When they both sought treatment for tuberculosis or opportunistic infections at hospitals, they hid his occupation, since many private hospitals now turn truckers away.
After her husband died, his family blamed her, a cruel vengeance some in-laws inflict on the widows. They have made treatment and prevention that much harder.
She was forced to sleep on the path outside; the family refused to share even a loaf of bread that she had touched. Soon their whole village had ostracized her.
Ms. Karuna cried as she told her story, but that story also conveyed an uncommon strength. She had left her husband's family and her village to start a new life on her own. She became an activist with the Social Educational and Economic Development Society, an advocacy group in Guntur, trying to save other truckers' wives.
She showed women pictures of her handsome husband before he sickened, and after.
She told the wives to know what their husbands were doing outside the home, to negotiate the use of condoms with them, to get treated for sexually transmitted diseases. Her husband's relatives still teased her: "Why are you working so hard? You also will die."
Morality and Stigma
In the town of Nippani, outside Lafayette Hospital, a sign warned against unprotected sex, showing a blue demon on a horse slaying a healthy man.
But those who fell prey to that demon were not welcomed, explained a doctor, Sunil Sase. AIDS carried a stigma like leprosy, he said, "so we are not exactly treating the AIDS cases." They were sent to another hospital 50 miles away.
A group working to raise AIDS awareness among prostitutes had been chased from Nippani after being accused of promoting sex. Most of the devadasis and prostitutes, who had been working in the town on the highway for 50 years, had been chased out in a morality crusade. Now they were scattered along the road, impossible to reach with education or condoms.
A mob had pulled one prostitute, Reshma Sheikh, and her 7-year-old son out of her house to try to force them from town. "We have a right to live and work there, we never hurt the sentiments of the people around," she said. She had stayed, only because she had nowhere else to go.
The main group leading the crusade was the Shiv Sena, a Hindu nationalist political party. Sunil Sadashir Dalavi, 32, the local leader, boasted about their success. But he said the women were not the only cause for the spread of AIDS.
"Educated boys don't get jobs, they have extra time, they don't know what to do," he said. "They can't marry till they get a job, they have very strong desires, so they go to these women."
Once the men were married they would not do "these things," he insisted, despite government surveys showing otherwise. The answer to controlling sex was controlling the culture, he said. A lot of local men went to two nearby cinemas that screened sex movies, he said, and then to brothels. "We want to close the 'talkies' down," he said, "so people will not do this."
A Fragmented Industry
In almost every doorway in the red-light district of Chilakaluripet, in Andhra Pradesh, women drape, wearing bright clothes, garish makeup and come-hither expressions that have served to lure both men and disease.
For half a century, the town has been a center of sex work, combining its location on the national highway with women from its Domara community, which has come to specialize in prostitution. Truckers passing through know where to stop; if they do not, there are hotel boys, rickshaw pullers and others willing to guide them.
In recent years, the town and surrounding area have also become a center of H.I.V. infection, and, given the number of long-distance truckers tarrying here, a likely source for its spread elsewhere.
The sex industry has been organized in some cities, like Calcutta, but mostly it is as fragmented as the trucking industry. Chilakaluripet features brothel-based and home-based prostitutes, secret prostitutes and women who sell sex along the highway. A police crackdown on brothels in recent years has further dispersed the women.
Venkaimah, a 25-year-old widow, is part of a "highway brothel" - a small moving coterie of women who work in bushes or fields or restaurants along the road. Her workday starts when the light is gone and the truck traffic heavy. She leaves her two daughters, 10 and 2, behind, and on a good night may get 8 to 10 customers who pay 50 cents to a dollar each.
Some prostitutes now use condoms, but the disease continues to spread. One local organization, Needs Serving Society, estimated that 1,000 people had tested positive for H.I.V. in the town and nearby villages, most of them not prostitutes, but locals who may have patronized them. No one, though, had any real idea of the true number. On one narrow lane alone, 20 prostitutes were infected, said one of them, Konda, 38.
Venkaimah's children motivated her to use condoms - if she did not, she knew that sooner or later they would be orphaned. But loneliness can loosen defenses: like many prostitutes, she had "temporary husbands" - longtime boyfriends - with whom she did not use a condom at all.
Chilakaluripet, known for sex, was now marked by death.
In a courtyard, Venkateswarmma, a mother of two, as thin and brittle as a doll, sat on a cot, unable to move. Her husband, a brothel owner's son, had died 10 days before, infected after sleeping with its employees. She was near death herself, unable to walk for her husband's death ceremony. Her 2-year-old son had already died from AIDS; she would leave behind an 11-year-old boy.
A Mobile Society
For 15 years, Vilas Jaganath Kamkar had been taking the bus from his village in Maharashtra state to Mumbai, its capital, where he worked as a taxicab driver. In 1994, he had taken a wife, Manisha, but he kept working in Mumbai, with monthly visits home.
In this migrant nation, his life was not unique. Nor, in this age of AIDS, was his fate. Migrants may be the hardest group for AIDS educators to reach. As Indian society becomes more mobile, people are leaving villages for urban work at increasing rates.
In Maharashtra, new plants and factories are springing up along the revamped highway. As rural migrants come to work in the factories, poor women follow to sexually service the men. Newly rich locals patronize the abundant supply of women, spawning H.I.V. "hot spots" along the highways.
In cities, the migrants live in slums, three or more to a room, and may move often. Away from their families for months at a time, they seek the companionship not just of prostitutes but of girlfriends, with whom safe sex is often ignored.
Migrants leave home to work, but go home to die. At the hospital in Satara, a prospering city on the highway south of Mumbai, Mr. Kamkar, the taxi driver, now 32, lay breathless on a hospital bed. His luck had run out, and not just because he had contracted H.I.V. Only 25 hospitals and health centers were prescribing antiretroviral drugs. They were available in Guntur, but not 12 miles south in Chilakaluripet. They could be had in Mumbai - but not in Satara.
All Mrs. Kamkar, 25, a mother of two, could do was take her husband back to their village, try to ease his pain and nurse him until the end.
"It's a matter of his destiny," she said.
