Burgh is one of a growing number of patients who have been dosing themselves with a simple laboratory chemical that has never before been used to treat cancer in people. Most are doing so without the help of doctors, and none is enrolled in any systematic clinical trial of the substance. Instead, they are buying it over the internet, and sharing their experiences of it in online chatrooms. For them, the unlicensed, untested drug represents their last best chance of survival.

That’s not the way cancer specialists see it. For them, the activities of Burgh and those like him are indicative of what could become a dangerous new trend, in which groups of seriously ill people get together online to discuss, source and try untested drugs whose safety and efficacy is uncertain.

The drug in this case, known as DCA, is a widely available chemical that cannot be patented. In basic laboratory tests and experiments in rats it has shown promise as an anti-cancer agent, but in people it may yet show side effects that could further damage the lives of people who take it. Scientists investigating the potential of DCA as a cancer treatment fear that any deaths or injury caused by its premature, unregulated use could damage their work – and the welfare of patients far into the future.

Burgh’s quest to cure himself began last month, shortly after he was told the cancer in his thigh had spread to his lungs. "My prognosis is very poor," he says. "Standard chemotherapy would give me only a slim chance of survival at five years." So he turned to DCA, after reading about the promising lab experiments in New Scientist (20 January, p 13).

DCA, or dichloroacetic acid, is an analogue of acetic acid in which chlorine atoms replace two of the three hydrogen atoms on the methyl group. Because it is a corrosive acid, it must be "buffered" to damp down the acidity, and it is usually administered as sodium dichloroacetate.

In January, a study by Evangelos Michelakis and his colleagues at the department of medicine at the University of Alberta in Edmonton, Canada, suggested that DCA could shrink several types of tumour in rats, by exploiting a previously ignored metabolic pathway in the cell (see "How DCA could affect cancer", below). "I was intrigued by the proposed mechanism," says Burgh (not his real name; this article uses a pseudonym to protect his privacy). "The biochemistry made sense to me. I subsequently read dozens of articles and abstracts on DCA before I decided I wanted to try it."

On 27 February, he self-administered his first dose, and for the next month took DCA twice a day, monitoring his blood and urine for signs of any problems, and visiting his oncologist, who was aware of what he was doing, once a week.

Because DCA is not an approved drug in the US, the UK or anywhere else, Burgh had to find his own supply. Using his contacts he obtained raw DCA, then asked a chemist friend to buffer it and check its purity.

Burgh is not alone in his attempts to procure the drug. Already, within weeks of Michelakis’s paper being published, a substantial online community has grown up, largely centred on the website www.thedcasite.com which declares itself to be a gateway for information on DCA. At least eight of the individuals who have posted contributions on the site’s chatroom, including Burgh, claimed to be taking DCA or giving it to a close relative. By 21 March, the chatroom had 135 active members – most of them from the US, Canada, the UK and Australia – plus posts from numerous unregistered users, many swapping tips on how to get hold of DCA, how to prepare the chemical for human consumption, and what supplements they should be taking to minimise side effects.

"This is pretty much <<<More>>>

One in four US women between the ages of 14 and 59 years is infected with human papillomavirus – a sexually transmitted virus that can cause genital warts and cervical cancer – according to new government figures.

The survey found that around a quarter of teenage girls and half of women in their early 20s carry the virus.

Doctors say that the new findings show that HPV infection is common and that there is a need to vaccinate young girls against high-risk strains of the virus. But some campaigners argue that vaccination should not be encouraged for all girls because it only protects against a small subset of HPV strains.

Telltale DNA

Eileen Dunne of the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, US, and colleagues analysed self-collected vaginal swabs from roughly 2000 women aged between 14 and 59 years. They tested for HPV infection by analysing DNA in the swab samples, looking for genes that belong to the virus.

About 27% of the women tested positive for HPV infection, which equates to around 25 million women in the US, the team says.

More than 2% of the participants tested positive for HPV 16, HPV 18, or both, two strains of the virus known to cause cervical cancer. High-risk strains of HPV are found in 99% of women with the disease.

Dunne’s group also found that around 1% of the women had HPV 6 and/or HPV 11, which are known to cause genital warts.

In 2006, the CDC’s advisory committee on immunisation provisionally recommended the HPV vaccine Gardasil – which protects against types 6, 11, 16 and 18 – for all girls aged 11 or 12.

Kevin Ault of Emory University in Atlanta, who has conducted clinical trials of the vaccine, notes that only 4% of the participants in Dunne’s study already carried one of the four types of HPV that the vaccine protects against. "To me that means that 96% of the women might benefit from the vaccine," which could prevent them from catching the strain, says Ault.

The fact that nearly a quarter of girls between the ages of 14 and 19 years tested positive for HPV "shows how important it is to vaccinate people early", says Rachel Winer of the University of Washington in Seattle, Washington, US.

Natural defences

But opponents of mandatory HPV vaccination programmes for US schoolgirls say that the new findings do not demonstrate that they are needed.

The body naturally clears most HPV infections on its own, including types 16 and 18, says Dawn Richardson, president of Parents Requesting Open Vaccine Education, based in Austin, Texas. The parent group recently held a demonstration against attempts to make the vaccine mandatory for schoolgirls aged 11 and 12 years in the state.

Richardson adds that Gardasil only protects against two of the HPV types that can cause cervical cancer, which means that girls who receive the jab are still vulnerable to other high-risk types of the virus that cause these tumours.

A MYSTERIOUS protein extracted from pregnant women’s urine can slow the progression of an AIDS-like disease in laboratory animals. It can also destroy cells from tumours that afflict some AIDS patients and boost the production of immune cells, virologist Robert Gallo of the University of Maryland in Baltimore told the AAAS.

"We’re still in the early days. We don’t even know what the active component is exactly," says Gallo. "But we may have the basis here for a whole new avenue of AIDS drugs."

The winding route to the discovery started with a chance observation by Gallo and his colleagues while they were studying Kaposi’s sarcoma, a skin cancer that often claims the lives of patients with AIDS. Kaposi’s sarcoma is particularly common in gay men with the disease, and is thought to be triggered by a herpes virus.

A drug designed to combat genital herpes can also reduce levels of HIV in the blood by 70%, a small trial in Africa has revealed. The herpes medication, valacyclovir, also appears to reduce levels of HIV in the genital tract.

The researchers behind the study suggest that valacyclovir, and other herpes drugs, might dramatically reduce the spread of HIV. Philippe Mayaud of the London School of Hygiene and Tropical Medicine, UK, and colleagues recruited 140 women infected with both HIV and herpes in the West African nation of Burkina Faso.

All of the women had high levels of CD4 immune cells, meaning they were still relatively healthy and ineligible to receive antiretroviral HIV drugs under World Health Organization guidelines.

In addition, none of the women had visible symptoms of herpes so they would not normally be given herpes medication such as valacyclovir.

Sustained effect

The researchers gave half of the women valacyclovir and the other half women placebo pills. At the end of three months, copies of HIV in those who received valacyclovir had dropped from 25,000 copies per millilitre of blood to 8000 per millilitre – a 70% reduction.

This is the same effect one would expect if the women had been given an anti-HIV drug such as Zidovudine (AZT), according to Mayaud. Levels of HIV found in the blood of women who received the placebo, by comparison, had increased slightly on average.

Because all of the women were healthy to start with, there was no difference in symptoms during the 3-month period. But Mayaud says that such a dramatic drop in virus particles could potentially delay the onset of AIDS.

"It’s important to know if the effect is sustained over a long period," he adds, stressing the need for long-term studies of valacyclovir’s effect on HIV infection.

Researchers believe that valacyclovir indirectly reduces HIV infection by decreasing copies of the herpes virus. They note that untreated herpes can cause lesions in the genital region, which subsequently attract a type of immune cell that harbours HIV.

Halting spread

Mayaud points out that the women who received valacyclovir also had half as many copies of HIV in their genital tracts compared to those who received the placebo. This also suggests that valacyclovir has the potential to reduce the spread of HIV, he says.

In Africa, between five and nine out of 10 HIV-infected patients are also infected with herpes. In Europe, the figure is between three and seven out of 10.

Lawrence Corey at the University of Washington in Seattle, Washington, US, says this is good reason to explore herpes drugs as a treatment for HIV. "Because so many people in the world are co-infected we should spend more time on that," he told New Scientist.

Mayaud adds that some herpes drugs, such as acyclovir, cost just $40 per year while the triple-drug regimens normally used to lower HIV levels in patients cost anywhere from $150 to $300 per year.

However, it remains unclear whether valacyclovir would offer an additional benefit if taken with a triple-drug HIV treatment.

A seaweed extract called carrageenan strongly inhibits human papillomavirus – known to cause cervical cancer – from entering human cells in the lab, a new study shows. The compound, derived from red algae, is already used as a thickening agent in infant feeding formulas and in sexual lubricants. The researchers hope their findings could one day help prevent the spread of the virus.

Human papillomavirus is sexually transmitted and certain high-risk strains are linked to cervical cancer. Condoms can prevent its spread to a certain degree. And a new vaccine called Gardasil – recently been recommended for girls aged 11 to 12 by an influential US advisory panel – is almost 100% effective in protecting against the most dangerous HPV strains. However, the three-dose vaccination course costs $360, which puts many women off. And this is especially expensive for women in developing countries.

Developing an inexpensive gel, or microbicide, to block HPV might help stop its spread, says the John Schiller at the National Cancer Institute in Maryland, US.

His team tested various compounds in the lab, screening for the ones that interfered most with the virus’ ability to invade human cells. The researchers found that carrageenan strongly inhibited different HPV strains’ ability to attach and therefore enter human cells. "We were floored by how much better it worked than anything else we have tested," says Schiller.

Serendipity

The researchers note that although lab tests have shown some strains of HIV and herpes as vulnerable to carrageenan, genital HPV appears about a thousand-fold more susceptible to the compound. Their tests also showed that carrageenan was effective against HPV strains 16 and 18 – two of the most dangerous in terms of cervical cancer risk.

Carrageenan is already used a thickening agent in foods such as baby formula, and is perfectly safe to ingest. The researchers note it is serendipitous that some sexual lubricants already contain the compound. But these are not yet proven to be effective in preventing the spread of HPV, stresses team member Cynthia Thompson.

She says pharmaceutical companies will have to pursue this idea with future tests and then apply for approval from drug regulators to market their products as HPV blockers.

Roughly 50% of sexually active women between the ages of 18 and 22 are infected with human papillomavirus (HPV) at some point, although their own immune systems can clear infections caused by the less aggressive stra

Doctors could soon have a new weapon for fighting one of the toughest malignancies – ovarian cancer.

Tests conducted in mice show that a virus engineered to target cancer cells and kill them can completely suppress these tumours if it is given quickly enough. The authors hope to begin human clinical trials of the therapy within two years.

Scientists began exploring the idea of using specially modified viruses to fight ovarian cancer in the early 1990s, trying modified adenoviruses and herpes viruses. These were "safe but not effective" in treating the disease because they were not aggressive enough, explains David Bartlett of the University of Pittsburgh School of Medicine in Pennsylvania, US.

Preferred viruses

His team instead focused its efforts on the vaccinia virus group, which has previously been used to vaccinate people against smallpox and is generally safe to humans. These viruses are more potent than adenoviruses and herpes viruses because they carry an enzyme called DNA polymerase to kick-start viral replication within cells.

Bartlett’s team created a modified vaccinia virus that would target and kill cancer cells. They did this by removing genes in the virus that help it to produce a growth protein. This means that the virus survives best in cancer cells that can supply it with large quantities of this growth protein, as opposed to non-cancerous cells that only produce very small amounts.

The vaccinia virus was also engineered to carry a gene for an enzyme called cytosine deaminase that causes cell suicide in the cells it infects.

The researchers injected mice with ovarian cancer cells and then either gave them an immediate injection of the engineered vaccinia virus, or waited 30 or 60 days before infecting them with the virus. A fourth group of mice injected with cancer cells were not given any treatment.

Survival boost

Of the mice given the immediate injection, 90% were still alive 180 days later and showed no signs of tumour growth, says Bartlett. Some 10% of the mice given the virus 30 days after being injected with ovarian cancer cells survived to that point as well.

The mice that received vaccinia virus injections 60 days after exposure to the cells lived on average to 125 days – around 50% longer than their control counterparts – though all mice in these groups were eventually killed by the cancer.

The findings were presented on Saturday at the annual meeting of the American Society of Gene Therapy in Baltimore, Maryland, US.

This year, more than 20,000 US women are expected to be diagnosed with ovarian cancer and 15,000 will die from the illness, according to figures from the American Cancer Society.

Promising treatment

Bartlett hopes that his treatment could one day be adopted to treat women, particularly to obliterate ovarian cancer cells that linger after surgery.

Ovarian cancer is a "particularly good target" for this kind of therapy, according to David Curiel of the University of Alabama at Birmingham, who plans to start human clinical trials using adenoviruses to treat the illness in the autumn.

He explains that at a certain stage of the disease the tumour cells may spread within the peritoneum, a membrane that forms the lining of the abdominal cavity. Because the peritoneum is a confined space, the therapeutic viruses can be delivered and concentrated within that area.

Curiel says Bartlett’s approach is also promising because it involves "arming" the virus with a gene to kill cancer cells.

However, one potential problem is that the human immune system may be able to detect vaccinia viruses and stamp them out before they can have the desired effect.

This is a particular concern in people who have previously been immunised against smallpox because their immune systems will already be primed to identify and destroy vaccinia virus. Bartlett’s group is currently trying to overcome this problem.

Not everyone agrees. Russell thinks infected tumour cells are often killed before the virus has had time to replicate. This might account for the difficulty in getting viruses to spread efficiently within tumours. "It’s a question of how far the virus gets in the time allowed to it to propagate, and how much tumour remains for the immune system to have to mop up," he says. "The immune system will only be effective if there is minimal residual disease. There isn’t much evidence that it can get rid of a big established tumour." His team plans to use immunosuppressant drugs to temporarily knock out the immune system.

Hunting down tumours

In the end, there is unlikely to be a single universally effective strategy for evading the immune system. "This is a complicated subject and varies from one virus to another," says Brown. And it’s not the only challenge. Oncolytic virotherapy has so far worked best when the virus is injected directly into the tumour, but most cancer deaths are caused by cancers that spread from their original site. What patients really need is a treatment that can kill tumours wherever they are in the body.

Much early work was with adenoviruses, which target the mucous membranes of the nose and throat to cause the all-too-familiar symptoms of the common cold, or herpes simplex, which targets skin and nerve cells. Some researchers are trying to adapt these viruses to spread throughout the body via the bloodstream. Earlier this year, a team at the Memorial Sloan-Kettering Cancer Center in New York treated 12 patients with skin cancer that had spread to the liver by injecting a herpes strain into the liver artery. The results are encouraging; it is the first time that injecting an oncolytic virus into the bloodstream has produced an anti-tumour response.

"But the best way to approach systemic delivery is to use viruses that have evolved to spread through the bloodstream, instead of re-engineering viruses to do something they don’t naturally do," says Kirn. Several groups around the world, including Kirn’s company Jennerex, say they have perfected systemic delivery of vaccinia in animals. Human trials should start before the end of the year.

Meanwhile, Russell’s group has high hopes for the weakened measles strain that is routinely used in vaccinations. The team has genetically engineered the virus so that the proteins it uses to bind to and enter cells can be replaced by antibodies targeting various cancer types.

For virotherapy researchers, dodging the immune system and hunting down cancers around the body is just the beginning. They have a grander vision. "For the first time in cancer treatment history, we have the opportunity to kill by multiple mechanisms in a single product," says Kirn. By arming different viruses with different cargoes, such as a drug, a radioisotope, an antibody or a gene that codes for a cancer-fighting protein, researchers could in theory produce a limitless number of new treatment agents.

Part of the aim is to kill tumour cells that are not actively dividing. Oncolytic viruses are not very good at replicating inside and killing resting cells, but they can infect them and release a payload. The first "armed" oncolytic viruses are already in early trials. Most carry a gene for GM-CSF, a protein intended to stimulate the immune system to attack tumours.

Despite the progress being made, some doubt that oncolytic viruses will prove to be a magic bullet. "It is unlikely that the oncolytic viruses currently available will be able to fully eradicate tumours on their own," says Henk van der Poel of the Netherlands Cancer Institute in Amsterdam. "Their greatest potential will be as part of a multi-modal treatment regime."

Those in the field agree that virotherapy is not about to revolutionise cancer treatment just yet, but they are quietly optimistic about its prospects. "It’s a novel platform that’s going through some of the same issues as monoclonal antibodies did," says Kirn. "Ten or 15 years ago, some people said monoclonal antibodies were dead, but a few individuals stuck at it and now they are a very important part of our anti-cancer armamentarium."

AN EXPERIMENTAL gel can prevent herpes infection in mice. If it works as well in people, one application would protect women for several days.

Genital herpes is caused by the herpes simplex virus. In the US, 1 in 5 people are infected. The virus can lie dormant in nerve cells, periodically reactivating and causing a recurrence of symptoms. There are treatments but no cure – people remain infected for life and can infect partners. While vaccines against herpes are in development, none has proved fully effective.

Now Judy Lieberman’s team at Harvard Medical School has harnessed the power of RNA interference to block herpes infection. A gel containing small interfering RNAs (siRNAs) that trigger the destruction of viral genes is applied to the vagina, where they are absorbed and remain active for at least 10 days. The gel completely blocked infection in mice, Lieberman told a meeting in Boston recently.

If it works in people too, the long-lasting protection would be a great advantage, she says. "The problem with microbicides is that people don’t remember to use them before they have sex."

An antimicrobial gel like this would have an enormous value in the developing world, for women whose partners refuse to use a condom, says Victor Ambros of Dartmouth College in New Hampshire. "An antimicrobial cream is something women could use and control." The hope is that the siRNA approach might work for preventing HIV infection too.

Initial studies suggest that besides prevention, the gel might also be useful for treating herpes infections. Other teams are developing siRNA gels for treating the persistent viral infections that cause cervical cancer (New Scientist, 27 November 2004, p 15), and siRNA inhalers for treating the respiratory infection RSV.

Applying siRNAs directly to accessible tissues such as the lungs avoids the as yet unsolved problem of getting them to organs within the body. If this can be overcome, RNA interference has great potential for treating a huge range of diseases.

Major human trials of microbicide creams and gels to fight against

HIV

infection are to start in Africa, where over 26 million people already have the disease.

If successful, the vaginal creams could provide a powerful weapon against the spread of HIV far sooner than any vaccine. Animal studies have already shown that two of the frontrunners can prevent HIV infection in about 50 to 75 per cent of cases.

"The best thing to do would be to use a condom and a microbicide. But for those women who can’t negotiate a condom, a microbicide is clearly better than nothing," says Janet Darbyshire, director of the UK’s Medical Research Council’s clinical trials unit.

"Even if the microbicides are only partially protective, they could have a major public health impact," she says. Research has shown that a microbicide only 60 per cent effective could prevent as many as 2.5 million infections worldwide over three years, even if only 20 per cent of people with access to it used it and half the time they did not use condoms.

"The face of AIDS is the face of a poor young woman," says Robin Gorna, HIV/AIDS team leader for the UK government’s Department for International Development (DfID). "In sub-Saharan Africa women are 1.2 times more likely to be infected than men. In some cities women are five times more likely to get HIV."

Vaginal lesions

About 60 microbicides -applied to the vagina about 30 minutes before sexual intercourse – are being developed. Fourteen have already undergone human safety trials, and six are poised to enter phase three trials to test their efficacy. DfID and the MRC are launching large-scale effectiveness trials of two of the six.

Making sure the substances are effective in stopping HIV infection and yet are not toxic is an important issue. A previously mooted microbicide called nonoxynol-9 was rejected after the discovery that it also caused lesions in the vaginal wall, making women more susceptible to infection.

"They have to be absolutely harmless to women using them on a regular basis," says Jonathan Weber at Imperial College, London, UK who is co-chairing an international meeting on microbicides in London this weekend.

He believes the problems with nonoxynol-9 will not apply to the new microbicides. Dextrin sulphate, being developed UK company ML Laboratories, and PRO-2000, from US-based Indevus Pharmaceuticals, are both sugar polymers.

"These work by a completely different mode of action," Weber explains. Nonoxynol-9 works by deactivating HIV before it enters a cell, while the two new microbicides stop infection by blocking HIV’s entry into a cell.

Virus envelope

Dextrin sulphate and PRO-2000 protected rhesus macaques given HIV vaginally from becoming infected 50 to 75 per cent of the time.

Weber says PRO-2000 is active against all virus envelopes – the coating surrounding a virus. It has been shown to protect against Herpes simplex virus and may offer protection against other sexually transmitted diseases.

The DfID/MRC human trials will launch in Africa in the third or fourth quarter of 2004. They will take place in eight sites in five African countries, including South Africa, Tanzania and Cameroon. Each trial will need over 12,000 women in order to give clinically meaningful results.

The trials should give results by early 2008, says Darbyshire, so microbicides could be available to women by 2010 – much sooner than any AIDS vaccine.

Teenagers are facing a health timebomb, warned a UK report on Monday. Under-age

sex

, binge-drinking,

drug

abuse, smoking and poor

diet

are contributing to epidemics of

obesity

, ill-health and sexually transmitted diseases among UK teens.

The British Medical Association (BMA) analysis paints an alarming picture of teenage health in the UK.

Nearly one in five 15-year-olds are overweight or obese. Psychological problems such as depression and anorexia now afflict one fifth of adolescents, says the report.

These problems are being fuelled by an increasingly impoverished diet, insufficient exercise, excessive alcohol and drug consumption, and tobacco smoking. According to the BMA, less than 15 per cent of girls aged 13 to 15 eat the recommended amount of fruit and vegetables.

Almost a quarter of 15 and 16-year-olds will have smoked cigarettes in the past week. And a fifth will have taken an illegal drug in the last month, says the document.

Sexual health in adolescents is also deteriorating, says the BMA. As many as one in ten young women aged 16 to 19 may be infected with Chlamydia, which can lead to infertility and ectopic pregnancy. The rate of teenage pregnancy is also high – but stable – at around 3 per cent.

"It seems that adolescents are the only group whose health is getting worse," says Russell Viner, consultant in adolescent medicine at Great Ormond Street Hospital in London.

Fast-food industry

"Better drugs are protecting older people from disease and vaccinations have brought huge improvements for infants," Viner told New Scientist. "But for people in their teens there are social health problems which mean worrying rates of accidents, suicide, drug use, pregnancy and sexually transmitted diseases."

The rapid rise in obesity is being blamed by some experts on the fast-food industry and a society focused increasingly around car use.

Philip James, adviser to the House of Commons select committee on obesity, told New Scientist: "The whole environment is geared towards selling off playing fields and preventing people from walking or cycling to work or school.

"As a society we’ve abandoned any pretence of nurturing children in an appropriate environment," he adds. "We’ve told them to eat what they like and do what they like and failed to inculcate them with good habits."

Basic social skills

The BMA is calling for a comprehensive plan to tackle the root causes of deteriorating teenage health. It recommends a ban on alcohol advertising and an increase in the price of cigarettes to reduce their affordability to teenagers.

It says mental health can be improved by teaching teenagers basic social skills and through anti-bullying policies in schools. Sexual health can be improved by enhancing sex education and through easier access to contraception and confidential advice.

Vivienne Nathanson, the BMA’s head of science and ethics, says: "Services targeting the needs of adolescents are almost non-existent. We must invest properly in sexual health and provide services that young people feel comfortable using if we are to reduce the burgeoning levels of sexually transmitted diseases.