Special Report: How vaccine scares cast shadows over science

By Kate Kelland, Health and Science Correspondent

HELSINKI (Reuters) - At a Finnish medical convention in January 2011, a colleague approached neurologist Markku Partinen, laid a hand on his shoulder and said: "Markku, it's going to be a bad year for you."

In the following months, other scientists ridiculed him, questioned his methods and motives, and raised doubts about his mental stability. Colleagues began crossing the street to avoid him, he says.

Partinen, director of the Helsinki Sleep Clinic and Research Centre, had raised the alarm about a GlaxoSmithKline vaccine called Pandemrix. He had discovered the drug, used to protect people from H1N1 swine flu, may be linked to a jump in cases of narcolepsy, a rare sleep disorder, in children and young people. He knew his findings might help limit the risks of narcolepsy for other children around the world, but was fearful nonetheless. The work was bound to generate scientific suspicion and public anxiety. Indeed, he struggled to get his paper on the vaccine published.

His story underscores an increasingly tough challenge for scientists balancing compelling data with public concern over vaccines and their side effects. Treatments which stimulate immunity to disease are highly controversial. In the past couple of decades - especially after a British doctor made now-discredited claims linking the measles-mumps-rubella (MMR) vaccine to autism - the field has become even more charged. After the false alarm sounded by British doctor Andrew Wakefield, some scientists say they are more hesitant to credit reports of potential side effects from vaccines.

Wakefield's 1998 paper suggesting a link between the MMR vaccine and autism was debunked after repeated scientific studies found no such connection, and was retracted by The Lancet medical journal in 2010. In that year, Wakefield was also struck off Britain's medical register by the General Medical Council for repeatedly breaching "fundamental principles" of research medicine, and he is no longer licensed to work in the UK as a doctor. But he still has thousands of passionate followers, especially in the United States, who question the use of any vaccine and applaud any new evidence that vaccines have unintended consequences.

"Wakefield has done so much damage. We've seen it with all these anti-vaccine people, and now we also see the damage he has done to science," Partinen said.

Partinen's findings have now been replicated and confirmed by at least four independent teams of international scientists. Studies in Sweden, Finland, Ireland, Norway and Britain have also shown the risk of developing narcolepsy is between seven and 13 times higher in children who were immunized with Pandemrix than in those who were not. European drug regulators have recommended the vaccine no longer be used in anyone under 20.

GlaxoSmithKline acknowledges the statistical association, but alongside many more research teams around the world, the company is investigating what might cause the link.

Emmanuel Mignot, a psychiatrist and narcolepsy expert at Stanford University in the United States, is being funded by GSK to investigate further. He says scientists now face a dilemma: even when you publish sound scientific findings, you could attract criticism "like Wakefield", he says.

"And at the same time, I really feel strongly that there's nothing worse than to suppress information - that's how you create paranoia in the public."

Wakefield, who now lives in Austin, Texas, told Reuters he stands by his 1998 Lancet paper. He also says he was the subject of "false allegations" in a subsequent investigation by the British Medical Journal and denies his research was fraudulent. A defamation lawsuit he took out in Texas against the British Medical Journal, its editor Fiona Godlee and writer Brian Deer was dismissed last year when the court said it did not have jurisdiction. Wakefield is appealing that decision.

Godlee said Deer and the BMJ stand by their reporting and their editorial commentary on the Wakefield case "and we believe that Dr. Wakefield's claims are meritless." She described his latest legal challenge as "frivolous" and "yet another instance of him trying to use litigation to harass and silence his critics."

ANTI-VAXXERS

Vaccines have been controversial almost since they were invented in the late 18th century. When British physician Edward Jenner showed he could protect children from smallpox if he infected them with cowpox, the objectors included clergy who believed vaccination was not Christian because it came from an animal.

Today, most doctors and scientists view the technique as one of the greatest breakthroughs in modern medicine. No other medical intervention has done more to save lives and fight disease.

Yet over the past couple of decades, a growing number of people have again become suspicious. The MMR scare "created a sense of fear of vaccines that has extended well beyond autism to a general fear that we're just giving too many vaccines too soon," says Paul Offit, an American pediatrician and vaccine scientist who blasted Wakefield in his book, "Autism's False Prophets."

Wakefield's dedicated following in the anti-vaccination movement - "anti-vaxxers" for short - believe all vaccines are dangerous and should be avoided. For example, Idaho-based group Vaccination Liberation declares on its website that "vaccines are toxic" and that there is no proof vaccinations are safe or effective. It says Wakefield was subjected to a "chain of persecution" and a "witch hunt."

Partinen rejects any comparison between himself and the man who sparked the MMR-autism scandal, calling Wakefield a "fake".

At a medical center on the outskirts of Helsinki, another Finnish scientist agrees with Partinen's results and is probing the mechanics of the Pandemrix-narcolepsy link, which she thinks may have to do with the vaccine's super-charging effect on the immune system.

Outi Vaarala previously worked in research on autoimmune diseases and diabetes. Since crossing over into the field of vaccinology, she says she has found herself harangued in emails and phone calls by people on one side accusing her of undermining trust in vaccines, or on the other begging her to join an anti-vaccine crusade.

"There's not the kind of open discussion we used to have. You're afraid you will lose your whole career if you say something bad," says Vaarala. "When you're dealing with vaccine it suddenly becomes like working in politics, or religion."

"SERVES YOU RIGHT"

For the parents of Swedish teenager Emelie Olsson, the row over vaccines complicates their struggle to come to terms with all that has happened to their family in the past few years.

Emelie is one of at least 800 people across Europe who developed narcolepsy, an incurable, life-long sleep disorder, after having the Pandemrix shot. In total, 30 million doses of the shot were given to people in 47 countries during the 2009/2010 H1N1 swine flu pandemic. It was not used in the United States.

An engaging 14-year-old, Emelie used to enjoy singing in a choir, taking tennis lessons, playing piano and kicking about with her friends. She now struggles to stay awake during the day and battles with terrors and hallucinations that deprive her of sleep and make her scream out in the night.

Her parents, Marie and Charles, still believe children should be vaccinated against diseases that put their lives at risk. The anti-vaccination movement denounces their views.

A blog post on the website "CureZone", which says it is dedicated to "educating instead of medicating", seeks to use Emelie's story as a "cautionary tale" against all flu vaccines. "Don't be fooled. Don't be brainwashed," says the post, by a blogger named "befurther". "Don't end up like Emelie and her parents."

Charles Olsson says some anti-vaccine campaigners have told him in comments online that he is to blame for Emelie's condition because he should not have allowed her to have the flu vaccine. "They even tell you: 'It serves you right,'" he said in their Stockholm apartment on a dark and snowy winter's afternoon.

He cites one post in Swedish on a Facebook page about vaccination where he was discussing what had happened to Emelie. A contributor called Peter W wrote: "Everyone is directly responsible for the vaccines that they take, parents as well, when recommending shooting poison into their newborn babies."

Marie says it feels uncomfortable that "we, people who are in favor of vaccines, have almost become marketing tools for the anti-vaccine movement."

BALANCING RISKS

Offit, the American pediatrician, says one reason the vaccine debate is so polarized is that people find it hard to balance risks. He helped invent a shot against rotavirus, a diarrheal disease that kills hundreds of thousands of children a year in poor countries.

Even at his state-of-the-art Children's Hospital of Philadelphia, he sees children die of diseases that could be prevented through immunization.

During the 2009/2010 pandemic, he saw five children die of H1N1 flu and saw parents baffled and crushed with grief.

"All those children's parents had chosen not to vaccinate them, and all of them said, 'I can't believe this happened to me,'" he told Reuters. "Vaccines are medical products. They have a benefit and - like any product that has a benefit - they could also have a risk. But from the public's standpoint it's difficult. For them, any risk is a bad thing."

Offit says he's had hate mail and death threats, and needed an armed guard at meetings at the CDC during the years he has spent arguing against the anti-vaccination movement.

Vaccination rates, which fell after the MMR scare, have now recovered. But millions of children were unvaccinated, which scientists say explains why some diseases that were nearly eradicated in wealthy countries have rebounded.

Last year, the U.S. Centers for Disease Control and Prevention (CDC) reported an outbreak of whooping cough in the United States that was the most severe in more than half a century.

Hitting an 18-year high, there were 2,016 cases of measles in England and Wales in 2012, according to the UK Health Protection Agency, the highest annual total since 1994.

BIG PROBLEMS

Partinen attended another Helsinki medical conference last month, two years after he had been warned about difficult times ahead. But this time he was leading the first Nordic Symposium on Narcolepsy and its links to the H1N1 swine flu vaccine.

"When we found this, we wanted to publish our results and spread the news to the world because we knew Pandemrix was also being used in other countries," he said. "But there were big problems."

Having double- and triple-checked his findings, Partinen approached the New England Journal of Medicine, one of the world's most respected medical journals, and submitted his study for publication. He says the journal asked for several revisions to the paper, then finally declined to accept it.

"After that we sent it to The Lancet," he said, stressing that this was the same journal which published the now discredited Wakefield paper.

While it is not unusual for such high-level medical journals to reject many papers, Partinen said he was shocked by the strength of The Lancet's resistance to his.

"It was quite exceptional, they asked for revision and revision and revision," Partinen said. "Then they said they'd made an editorial decision - that they couldn't publish it because we didn't know the (biological) mechanism (behind the link between narcolepsy and Pandemrix)."

Partinen argues that scientists don't know the biological mechanisms behind a whole host of diseases - multiple sclerosis and diabetes to name just two - yet The Lancet is full of peer-reviewed papers about those.

Neither The Lancet nor the New England Medical Journal would comment on their editorial decisions.

By the time Partinen's study was published - March 2012, in the open-access journal of the Public Library of Science, PLoS One - many more scientists had replicated his findings, the H1N1 flu pandemic that Pandemrix was designed to protect against had been declared over, and the vaccine's use had been restricted.

For those with narcolepsy it was already too late.

"There is no doubt any more that there is a link," Partinen said. "But it's taken three years to get here."

(This story has been refiled to add a dropped word in the first paragraph)

(Edited by Simon Robinson and Sara Ledwith)

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Special report: Scientists race to avoid climate change harvest

Combines harvest soybeans at a farm in Tangara da Serra, Mato Grosso state in western Brazil, March 5, 2009.

Credit: Reuters/Paulo Whitaker

By David Fogarty

CANBERRA | Fri Jun 10, 2011 12:47pm EDT

CANBERRA (Reuters) - Charlie Bragg gazes across his lush fields where fat lambs are grazing, his reservoirs filled with water, and issues a sigh of relief. Things are normal this year and that's a bit unusual of late.

His 7,000-acre farm near the Australian town of Cootamundra is testament to the plight facing farmers around the globe: increasingly wilder weather is making food production more unpredictable. It's the new normal they must prepare for.

Bragg's farm in New South Wales state has been in the family for generations and has weather records for the area stretching back 110 years. After seven years of costly drought, the weather switched last year to unseasonably wet with flooding rains.

"It's screaming to me that things are getting hotter and drier at different times of the year," said the 40-year-old Bragg during a recent visit to his property, about two hours drive to the west of Canberra, the Australian capital.

"Our summers are getting wetter and if this trend continues, then we will have to find different means of farming," he said.

Across the globe, rising temperatures and more intense droughts, floods and storms are forcing a rethink in how to grow food, from breeding hardier crop varieties and changing planting times to complete genetic overhauls of plants.

Growing populations, changing diets and insatiable demand for grains, meat and vegetables is putting pressure on global food production and prices like never before.

Soaring food prices, civil unrest and worries about weather have spurred a global race to create more productive crops that can thrive in a warmer -- and more prosperous -- world.

The World Bank estimates 925 million people are hungry in the world today. The figure has been rising since 1995-97 due to rising food prices, a succession of economic crises, and a neglect of agricultural innovation, especially relevant to the poor.

It is going to get much worse for the hungry because global food prices will more than double within 20 years, aid agency Oxfam International said in a June 1 report. Flat-lining yields, a scramble for fertile land and water, and environmental crises are reversing decades of progress against hunger, it said.

The challenge is to speed up the creation of new crops more adaptable to climate change and capable of much greater yields. A laboratory in the leafy heart of Canberra could hold some of the answers.

Inside, hundreds of seedlings on a conveyor belt file through a high-tech chamber, each plant bar-coded and scanned for signs of genetic superiority. A selection process that took months in the past, now takes a fraction of the time.

"I call this digital agriculture," said plant scientist Bob Furbank of Australia's Commonwealth Scientific and Industrial Research Organization (CSIRO). The 3-meter high PlantScan chamber uses 3D laser radar and other devices to measure size, growth and water use.

"It's like the plant Olympics. We have to rapidly pick the best of the best," Furbank, scientific director of CSIRO's Plant Phenomics center in Canberra, said on a recent visit to the laboratory brimming with high-tech equipment after a multi-million dollar refit.

The center is part of renewed global efforts to create a new generation of crops that will dramatically boost yields, particularly for wheat and rice.

Investment into creating a new generation of staple crops, especially wheat and rice, has lagged since the Green Revolution of the 1960s, which led to years of bumper harvests, easing worries about lack of food.

The new green revolutionaries must find ways of doubling yields as the global population, set to hit 7 billion later this year, heads for 9 billion by 2050, with greater affluence changing diets and triggering ever greater demand.

THE HEAT IS ON

To feed 2 billion more mouths by 2050, food production will have to increase by 70 percent, the U.N.'s Food and Agriculture Organization (FAO) says.

Climate change is perhaps the greatest threat to meeting the target as rising temperatures and droughts dry out farmlands or more intense floods and storms inundate them.

"What we expect in the future is there will be much more unexpected events, much more extreme climate change," said Concepcion Calpe, a senior economist with the FAO in Rome.

Boosting yields has become almost an obsession with governments, seed companies such as Syngenta and Monsanto, and scientific bodies such as Australia's CSIRO.

Global yield growth of wheat and rice has stagnated at 0.6 percent to 0.7 percent annually over the past 10 years -- about half the production growth rate of 1.2 to 1.4 percent annually needed from now to 2050, the FAO says.

Scientists say they are running out of time to boost yields.

With greenhouse gas emissions rising quickly, the world is already on track to exceed a 2 degrees Celsius threshold that scientists say risks triggering dangerous climate change. The planet has already warmed about 0.8 degrees Celsius on average since 1900.

Unless emissions growth is slammed into hard reverse, the world could be 2 to 3 degrees warmer on average by 2050, and much more by 2100.

Computer climate models show large areas of Australia, Africa, the United States, eastern Brazil and southern Europe drying out in the coming decades. But Russia, Canada and Indochina would become wetter, potentially benefiting crop production or allowing new crops to be grown in previously cooler climes.

Overall, for many major cereal crop-growing regions, the future will hinge on drought and heat-tolerant varieties, better weather forecasts and a likely shift in cropping to new areas.

A U.S. study published last month in the journal Science found climate change was already exerting a considerable drag on the yield growth of crops.

The authors used crop yield models with and without changes in temperature and rainfall to show global falls in wheat output of 5.5 percent and 3.8 percent for corn as a result of climate change from 1980-2008.

That was equivalent to the entire annual corn crop of Mexico, or the wheat crop of France, the European Union's biggest producer, it said.

SEEDS OF CHANGE

The global forecast is for increasingly bad weather, amid spiraling demand from an expanding global middle class.

"2.5 billion people entering the world's middle class is a lot more important than climate change," said Jeffrey Currie, global head of commodities for Goldman Sachs in London.

The World Bank's food price index, which measures global prices, jumped 36 percent in April from a year ago to near its 2008 peak, before dropping again.

"While it might not be the primary cause, it definitely is an underlying cause for some of the instability you're seeing in North Africa and the Middle East right now," said Rick Leach, chief executive of the World Food Program USA. "The very poor can spend up to 80 percent of their income on food," he said, adding: "We're now moving into a period of extreme worry in terms of the implications of food price increases."

More than 680 million people in Asia and the Pacific region live on less than US$1.25 a day, the International Fund for Agricultural Development, a U.N. agency, says. More than 70 per cent of these are in South Asia -- Bangladesh, India, Nepal and Pakistan -- making the region among the most vulnerable to food price inflation and climate change.

The World Bank in February said rising food prices had pushed an estimated 44 million more people into extreme poverty over the course of eight months, triggering unrest.

That is putting ever mounting pressure on governments, agronomists and the farm industry to come up with ways of growing more food on less land and under harsher conditions.

"Everything we do in terms of developing our technology, bringing that to growers worldwide, is really about addressing the need to grow more from less," said Davor Pisk, chief operating officer for Syngenta, the world's largest agrochemicals firm.

The Swiss firm's seeds business has flourished, growing to $2.8 billion in 2010, out of total sales of $11.6 billion, in large part for demand for Genetically Modified (GM) seeds to meet soaring demand in the United States for corn ethanol and for soyoil and soymeal in China.

Corn and soy, major elements of animal feed and biofuels, have attracted significant investment for new GM food varieties that have substantially boosted yields. Corn and soybean are also much simpler genetically than wheat and rice.

Syngenta has developed corn and soy varieties that repel pests, fungi and are tolerant to a range of chemicals that kill weeds -- all threats expected to get worse during climate change. It has also just released a hybrid called Agrisure Artesian that has resistance to drought.

"What we're confident of being able to demonstrate is that we can achieve a 15 percent decline in percentage of losses due to drought. So if you like, we get 15 percent yield preservation," Pisk said. The next generation of varieties would aim for 25 percent.

GM is just one part of a suite of technologies growers need to meet demand and fight the impact of climate change, he said.

The problem is knowing just what sort of future lies ahead for farmers and exactly what varieties were needed for different growing areas.

Computer climate models have become quite good at showing how temperatures will change across the globe, but are less precise on how rainfall and storm patterns will change, particularly at local levels.

SEARCH FOR BETTER YIELDS

If you can't predict the weather then you can try to beat it -- with new genetic strains of grain plants that will boost yields.

But crop yields would have to rise a lot faster than they have been. Scientists say yields will have to increase by around 1.5 percent a year to match the growth in the world's population of around 1 percent a year. That may sound small, but the current pace of yield growth is well below that.

Overall, rice yields have more than doubled over the past half-century from 1.85 metric tones per hectare in 1960 to 4.29 metric tones in 2011/12, USDA data shows.

But the International Rice Research Institute (IRRI) in the Philippines says rice yields will have to rise another 11 percent to about 4.8 metric tones per ha by 2018/19 just to keep rice prices steady.

By comparison, corn yields have risen from 1.95 metric tones per ha in 1960 to 5.22 metric tones in 2011/12, propelled by soaring demand for animal feed and ethanol. Wheat yields have gained more modestly to 3 metric tones in 2011/12 from 1.15 metric tones in 1960.

The production of rice, the staple for more than half the world's population, has kept pace so far with consumption, thanks to advances made in the Green Revolution. But yields will have to keep rising and stocks kept at healthy levels to avoid the kind of panic purchases by governments and export restrictions that helped drive the food price crisis of 2008.

The danger is that climate change could cause yields to drop, in some cases dramatically so, according to a study by the International Food Policy Research Institute.

Its modeling of the impact of climate change on cereal crops showed yields in 2050 are likely to be lower than they were in 2000, with the most vulnerable being wheat.

But developing a new variety of higher-yielding wheat takes a minimum of seven to 10 years, mostly because it has highly complex genetics. It's one reason why wheat, and to a similar extent rice, have fallen behind in yield growth and investment.

"In breeding new varieties for use in 20 years' time, we need to have the necessary genes now. And I think that's going to be tricky," said Greg Rebetzke, a wheat breeder for CSIRO in Canberra. One trick is to boost the early growth of wheat plants. The dwarfing genes that triggered the Green Revolution cut the height of wheat plants and allowed the plant to focus on filling the grain head. But the shoot that emerges from the seed is too short, limiting planting depth and access to water deeper in the soil. Rebetzke said CSIRO has found "alternative dwarfing genes" with no negative effects on early growth, which are "a major thrust in our breeding effort."

FUTURE RICE PLANT

To the north of London, the world's oldest agricultural research station is working on ways to boost British wheat potential yields to 20 or even 25 tonnes in the long-term, far above the 8 tonnes produced there now.

The 1.6 ha Broadbalk field on Rothamsted farm dates back to 1843 when its founder, John Bennet Lawes, decided to test the power of artificial fertilisers. He had built the world's first fertilizer factory a year earlier.

Walking in the same field where those trials started, project team leader Martin Parry explained how his team at Rothamsted and in the United States were looking at ways to super-charge photosynthesis in wheat by doubling the amount of CO2 inside the plant.

Parry, like many agronomists, believes a new global effort akin to what happened in the 1970s is needed to feed the world, beyond the promise of technology.

"We're going to have to do it much more effectively. We're going to have use our resources like fertilizer much more efficiently and we'll have to do it with less land," he said.

Developing countries will be a big focus in those efforts.

According to the USDA, yields for major crops, including corn, wheat, soybean and rice, are more than 40 percent lower in developing nations than rich nations, highlighting the paradox that production is lowest where demand is greatest.

The biggest breakthrough on the yields front could come in creating a new type of rice plant, the staple for many countries in the developing world.

"We expect the weather conditions and temperature to be more severe in the coming years," said IRRI Director-General Robert Zeigler during a recent open day at the institute, near Manila.

"That's why we need to develop more rice varieties that can tolerate flooding, drought, higher temperature, and can also tolerate salt water," he said as farmers chatted with scientists at the institute to learn about new varieties.

IRRI has already released commercial varieties that are drought and flood tolerant, limiting losses during bad weather.

Salt-water tolerance will also be crucial as seas rise and more powerful storms push seawater further into fertile river deltas, such as the Mekong Delta in Vietnam and large areas of coastal Bangladesh. Faster growing varieties can also help farmers get in a crop before the typhoon season starts.

IRRI, the CSIRO, as well as researchers in Britain and elsewhere are working on creating supercharged rice to try to double yields, by boosting the rate of photosynthesis.

The project, funded by the Bill and Melinda Gates Foundation, could take 20 years, said CSIRO's Furbank, but will also lead to new ways to ramp up wheat yields as well.

Crucial as well to bridging the yield gap is better agronomy, or farm management practices. Syngenta has developed a way to boost rice yields in India by an average of 30 percent as well as cutting labor. Its Tegra system uses seeds coated with an insecticide, mechanical planting of seedlings and training for farmers. That can make a huge difference in a country of 1.2 billion people where two-thirds of the population are employed by the farm sector and where a failed monsoon can send shockwaves through international markets. "It should be an agronomy revolution," Calpe, the FAO economist said. "This has been missing tremendously in a lot of countries."

(Additional reporting by Gerard Wynn in London, Erik Dela Cruz in Manila, and Naveen Thukral in Singapore; Editing by Bill Tarrant)

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Special Report: An end to AIDS?

A Kenyan woman prepares ribbons ahead of World Aids Day at Beacon of Hope centre, a non-government organization formed to address women's problem of HIV/AIDS in Nairobi, November 25, 2004.

Credit: Reuters/Antony Njuguna/Files

By Kate Kelland

LONDON | Fri Jun 3, 2011 3:37am EDT

LONDON (Reuters) - For his doctors, Timothy Ray Brown was a shot in the dark. An HIV-positive American who was cured by a unique type of bone marrow transplant, the man known as "the Berlin patient" has become an icon of what scientists hope could be the next phase of the AIDS pandemic: its end.

Dramatic scientific advances since HIV was first discovered 30 years ago this week mean the virus is no longer a death sentence. Thanks to tests that detect HIV early, new antiretroviral AIDS drugs that can control the virus for decades, and a range of ways to stop it being spread, 33.3 million people around the world are learning to live with HIV.

People like Vuyiseka Dubula, an HIV-positive AIDS activist and mother in Cape Town, South Africa, can expect relatively normal, full lives. "I'm not thinking about death at all," she says. "I'm taking my treatment and I'm living my life."

Nonetheless, on the 30th birthday of HIV, the global scientific community is setting out with renewed vigor to try to kill it. The drive is partly about science, and partly about money. Treating HIV patients with lifelong courses of sophisticated drugs is becoming unaffordable.

Caring for HIV patients in developing countries alone already costs around $13 billion a year and that could treble over the next 20 years.

In tough economic times, the need to find a cure has become even more urgent, says Francoise Barre Sinoussi, who won a Nobel prize for her work in identifying Human Immunodeficiency Virus (HIV). "We have to think about the long term, including a strategy to find a cure," she says. "We have to keep on searching until we find one."

The Berlin patient is proof they could. His case has injected new energy into a field where people for years believed talk of a cure was irresponsible.

THE CURE THAT WORKED

Timothy Ray Brown was living in Berlin when besides being HIV-positive, he had a relapse of leukemia. He was dying. In 2007, his doctor, Gero Huetter, made a radical suggestion: a bone marrow transplant using cells from a donor with a rare genetic mutation, known as CCR5 delta 32. Scientists had known for a few years that people with this gene mutation had proved resistant to HIV.

"We really didn't know when we started this project what would happen," Huetter, an oncologist and hematologist who now works at the University of Heidelberg in southern Germany, told Reuters. The treatment could well have finished Brown off. Instead he remains the only human ever to be cured of AIDS. "He has no replicating virus and he isn't taking any medication. And he will now probably never have any problems with HIV," says Huetter. Brown has since moved to San Francisco.

Most experts say it is inconceivable Brown's treatment could be a way of curing all patients. The procedure was expensive, complex and risky. To do this in others, exact match donors would have to be found in the tiny proportion of people -- most of them of northern European descent -- who have the mutation that makes them resistant to the virus.

Dr Robert Gallo, of the Institute of Virology at the University of Maryland, puts it bluntly. "It's not practical and it can kill people," he said last year.

Sinoussi is more expansive. "It's clearly unrealistic to think that this medically heavy, extremely costly, barely reproducible approach could be replicated and scaled-up ... but from a scientist's point of view, it has shown at least that a cure is possible," she says.

The International AIDS Society will this month formally add the aim of finding a cure to its HIV strategy of prevention, treatment and care.

A group of scientist-activists is also launching a global working group to draw up a scientific plan of attack and persuade governments and research institutions to commit more funds. Money is starting to flow. The U.S. National Institutes of Health is asking for proposals for an $8.5 million collaborative research grant to search for a cure, and the Foundation for AIDS Research, or amfAR, has just announced its first round of four grants to research groups "to develop strategies for eradicating HIV infection."

THE COST OF TREATMENT

Until recently, people in HIV and AIDS circles feared that to direct funds toward the search for a cure risked detracting from the fight to get HIV-positive people treated. Even today, only just over five million of the 12 million or so people who need the drugs actually get them.

HIV first surfaced in 1981, when scientists at the U.S. Centers for Disease Control and Prevention discovered it was the cause of acquired immunodeficiency syndrome (AIDS). An article in the CDC's Morbidity and Mortality Weekly Report of that June referred to "five young men, all active homosexuals" from Los Angeles as the first documented cases. "That was the summer of '81. For the world it was the beginning of the era of HIV/AIDS, even though we didn't know it was HIV then," says Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases, who has made AIDS research his life's work.

In the subsequent three decades, the disease ignorantly branded "the gay plague" has become one of the most vicious pandemics in human history. Transmitted in semen, blood and breast milk, HIV has devastated poorer regions, particularly sub-Saharan Africa, where the vast majority of HIV-positive people live. As more tests and treatment have become available, the number of new infections has been falling. But for every two with HIV who get a chance to start on AIDS drugs, five more join the "newly infected" list. United Nations data show that despite an array of potential prevention measures -- from male circumcision to sophisticated vaginal or anal microbicide gels -- more than 7,100 new people catch the virus every day.

Treatment costs per patient can range from around $150 a year in poor countries, where drugs are available as cheap generics, to more than $20,000 a year in the United States.

The overall sums are huge. A recent study as part of a non-governmental campaign called AIDS2031 suggests that low and middle-income countries will need $35 billion a year to properly address the pandemic by 2031. That's almost three times the current level of around $13 billion a year. Add in the costs of treatment in rich countries and experts estimate the costs of HIV 20 years from now will reach $50 to $60 billion a year.

"It's clear that we have to look at another possible way of managing of the epidemic beyond just treating everyone forever," says Sharon Lewin, a leading HIV doctor and researcher from Monash University in Melbourne, Australia.

In some ways, we have been here before. Early AIDS drugs such as AZT came to market in the late 1980s, but within a decade they were overtaken by powerful cocktail treatments known as HAART, or highly active antiretroviral treatment. HAART had a dramatic effect -- rapidly driving the virus out of patients' blood and prompting some to say a cure was just around the corner.

But then scientists discovered HIV could lie low in pools or reservoirs of latent infection that even powerful drugs could not reach. Talk of a cure all but died out.

"Scientifically we had no means to say we were on the way to finding a cure," says Bertrand Audoin, executive director of the Geneva-based International AIDS Society. "Scientists ... don't want to make any more false promises. They didn't want to talk about a cure again because it really wasn't anywhere on the horizon."

GENE THERAPY

The ultimate goal would allow patients to stop taking AIDS drugs, knocking a hole in a $12 billion-a-year market dominated by Californian drugmaker Gilead and the likes of Pfizer, GlaxoSmithKline and Merck.

It's unlikely to happen anytime soon, but Brown's case has opened the door to new ideas. "What it proved was that if you make someone's cells resistant to HIV...then all the last bits of HIV, that hang around for a long time in patients on treatment, did in fact decay and disappear," says Lewin.

Now scientists working on mimicking the effect of the Berlin patient's transplant have had some success. One experimental technique uses gene therapy to take out certain cells, make them resistant to HIV and then put them back into patients in the hope they will survive and spread.

At an HIV conference in Boston earlier this year, American researchers presented data on six patients who had large numbers of white blood cells known as CD4 cells removed, manipulated to knock out the existing CCR5 gene, and then replaced.

"It works like scissors and cuts a piece of genetic information out of the DNA, and then closes the gap," says Huetter. "Then every cell arising from this mother cell has this same mutation."

Early results showed the mutated cells managed to survive inside the bodies of the patients at low levels, remaining present for more than three months in five. "This was a proof of concept," says Lewin. Another potential avenue is a small group of patients known as "elite controllers", who despite being infected with HIV are able to keep it under control simply with their own immune systems. Researchers hope these patients could one day be the clue to developing a successful HIV/AIDS vaccine or functional cure.

Scientists are also exploring ways to "wake up" HIV cells and kill them. As discovered in the late 1990s, HIV has a way of getting deep into the immune system itself -- into what are known as resting memory T-cells -- and going to sleep there. Hidden away, it effectively avoids drugs and the body's own immune response.

"Once it goes to sleep in a cell it can stay there forever, which is really the main reason why we can't cure HIV with current drugs," says Lewin. Her team in Melbourne and another group in the United States are about to start the first human trials using a drug called SAHA or vorinostat, made by Merck and currently used in cancer treatment, which has shown promise in being able to wake up dormant HIV.

WHAT ABOUT PREVENTION?

As scientists begin to talk up a cure, the old question of whether that's the right goal has re-emerged. Seth Berkley, a medical epidemiologist and head of the U.S.-based International AIDS Vaccine Initiative (IAVI) is concerned.

"From a science point of view, it's a fabulous thing to do. It's a great target and a lot of science will be learned. But from a public health point of view, the primary thing you need to do is stop the flow of new infections," says Berkley. "We need a prevention revolution. That is absolutely critical."

Vuyiseka Dubula agrees. The South African activist finds talk of a cure for HIV distracting, almost disconcerting. "This research might not yield results soon, and even when it does, access to that cure is still going to be a big issue," she says. "So in the meantime, while we don't have the answer on whether HIV can be cured or not, we need to save lives."

(Additional reporting by Julie Steenhuysen in Chicago, editing by Sara Ledwith and Simon Robinson)

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