Virus cleans up food poisoning bug

19:00 23 April 03 Exclusive from New Scientist Print Edition

A virus that kills the food-poisoning bacterium E. coli O157:H7 has been discovered in sheep. The virus could help eliminate the bacterium in farm animals, greatly reducing the chance of human infections.

O157:H7, a toxic strain of the normally harmless gut bug E. coli, is a major cause of food poisoning. Three-quarters of cases can be traced directly to livestock, which harbour the bug without becoming ill. Meat can be contaminated when the animals are slaughtered, and manure can also be a source of infections.

So Andrew Brabban at Evergreen State College in Washington state and his team wanted to test different antibiotics to find those which would eliminate the bugs from farm animals. First, they had to infect sheep with E. coli. But they hit an unexpected problem: the bacteria just kept disappearing from the animals. The team re-infected the sheep three times, and every time the bacteria mysteriously vanished.

It turned out that the sheep harbour a bacteria-killing virus, or bacteriophage, that infects certain E. coli strains. When the team tested the phage against the food-poisoning bug in the lab, they found it kills 16 out of 18 toxic strains. "That includes all the big ones you've ever heard about," says Brabban, such as the strain responsible for an outbreak at Jack in the Box fast-food outlets in the US in 1993, which left four people dead. But the phage, christened CEV1, only kills eight out of 73 harmless E. coli strains.

Brabban now hopes to use the phage to wipe out O157:H7 in herds and flocks. In a small trial in sheep, the phage reduced numbers of the toxic bacterium by 99 per cent in just two days, he told a meeting of the Society for General Microbiology in Edinburgh earlier in April.

And using bacteriophages has all sorts of advantages. Phages are far more discriminating than antibiotics, so the natural microbial flora of animals' guts should not be affected. Also, while antibiotics are expensive and must be given to every animal, infecting just one animal with the CEV1 phage is likely to be enough to pass the phage to a whole herd or flock - and the numbers of the phage will rise exponentially as long as there are host bacteria left to infect.

What is more, the phage seems to persist in animals, suggesting it continues to replicate in a harmless E. coli strain after all the O157:H7 bacteria have been destroyed. Finally, while bacteria can develop resistance as they do to antibiotics, the phage can out-evolve them.

Brabban thinks that giving the phage to animals is more practical than using it to treat people. For instance, killing E. coli 0157:H7 releases large quantities of its toxin, which can make a patient's condition worse. And animal treatment would not have to meet the strict safety standards for human therapies, one reason why phage still are not used in the West. However, the team will need to show that the phage will not have an adverse effect on human gut flora if they are passed to people via food.

James Randerson, Edinburgh

Dog stroking can transmit debilitating parasite

19:00 23 April 03 Exclusive from New Scientist Print Edition

People can become infected with a worm that causes blindness simply by stroking the coats of dogs that carry the parasite.

The finding challenges previous assumptions that the worms only spread to people who come into contact with dog faeces, and suggests that owners need to be extra vigilant in washing and worming their pets.

In the US, around 10,000 people a year, mainly children under 12, become infected with Toxocara canis, a nematode worm that grows up to 20 centimetres long in the intestines of dogs.

In Britain the risk seems to be lower: "Fewer than 20 people a year get infected out of 60 million," says Ian Wright, a vet practising in Burnham-on-Sea, Somerset, whose findings are reported in The Veterinary Record (vol 152, p 419). Also, a quarter of the population have antibodies to toxocara, having developed immunity through exposure.

In infected people the worms can grow in the back of the eye, causing lesions which can interfere with vision or be mistaken for tumours. Occasionally they cause blindness. If they migrate to other organs such as the liver or lung they can also cause a form of toxocariasis, whose symptoms include periodic bouts of lethargy, similar to glandular fever.

Sticky eggs

Research by Wright and his co-investigator, Alan Wolfe, suggests that faeces might not be the only route of infection. Of 60 dogs they examined, a quarter had eggs of the worm in their hair. Three of the 71 eggs they recovered contained mature worm embryos which can infect humans. Embryos had begun to develop in 25 per cent of the eggs. They found up to 180 eggs in a gram of dog hair, a much higher density than is found in soil.

The vets say theirs is the first study to examine the coats of dogs as a route of infection. "We looked mainly at the anal region and the backs of the legs," says Wright. The millimetre-long eggs are very sticky and could easily be picked by someone stroking the animal, he says.

The finding points to toxocara infection being a dog ownership problem, Wright says. "It has probably got very little to do with dogs fouling public places." It also shows that dog owners should regularly wash and worm their pets, especially puppies, which are often infected through the placenta if the mother has worms.

Puppies should be wormed every fortnight for the first three months, then once a month for the following three months, says Wright. After six months, dogs develop some immunity and only need worming every six months and washing every fortnight. Wright's most important advice is for people handling dogs: "Wash your hands before meals, and after a good cuddle," he says. And ensure good hygiene if infants and babies share the house with dogs.

A spokesman for the Chartered Institute of Environmental Health, which represents Britain's environmental health inspectors, says the finding should be kept in proportion, as there are so few cases of toxocariasis a year. But he echoed Wright's warnings about the importance of hygiene, both for dogs and for people who handle them.

Andy Coghlan

Genetic "smart bomb" knocks out hepatitis

19:00 20 April 03 NewScientist.com news service

Human liver cells harbouring the hepatitis C virus can be selectively targeted and destroyed by a new gene therapy approach, according to new research.

The key is a genetically-engineered "suicide" gene, delivered aboard a harmless virus, which is triggered only when it enters a hepatitis-infected cell.

The two current treatments for the debilitating liver disease - alpha interferon and ribavarin - can reduce the level of infection, say researchers, but the virus usually comes back.

The new gene therapy approach could one day "offer the potential of a total cure" for many people, says virologist Christopher Richardson, at the Ontario Cancer Institute in Toronto, Canada, and one of the research team. It might also help tackle other viruses, such as HIV.

About 200 million people worldwide are affected by hepatitis C and infections are increasing. In advanced cases, the virus causes the liver to fail completely or become cancerous.

Achilles heel

The research began when Richardson and colleague Eric Hsu identified an "Achilles heel" in hepatitis C - a unique protease enzyme produced by the virus.

Some proteases in human cells trigger proteins to kick-start the process by which the cell commits suicide. So the team removed the genetic code that allows the protein to recognise the human protease and replaced it with code specific to the hepatitis C protease.

The DNA for the modified protein was then smuggled into cells using a harmless adenovirus. If a cell is infected, then the viral protease causes it to order its own death. "It's like a suicide vector, a smart bomb," Richardson told New Scientist.

No rebound

The therapy successfully cleared low and medium level hepatitis C infections in mice with implanted infected human liver cells. In mice suffering high levels of infection, the gene therapy slashed levels of the virus by a factor of 1000

Importantly, the virus did not "rebound" after the gene therapy, as it can do with existing treatments. This is true for at least 28 days after gene therapy and the team is now doing further work to see if this effect lasts longer.

"It's an incredibly novel approach," said Nigel Hughes, chief executive of the British Liver Trust and an adviser on the UK government's strategy to tackle hepatitis C. "But I have some reservations. If you had this massive cascade of cells dying in the human liver, what would the body's response be? Would you create more harm?"

The approach is "futuristic", admits Richardson: "It is very drastic and we would say it should not be used immediately for human trials." An intermediate approach could be to apply the therapy outside the body, he says.

In an ex vivo therapy, relatively healthy liver cells could be extracted from patients with an advanced infection, cultured and then exposed to the gene therapy. This would kill any infected cells, meaning healthy cells could be transplanted back and restore some of the liver's function.

Journal reference: Nature Biotechnology (DOI:10.1038/nbt817)

Shaoni Bhattacharya

Baby teeth revealed as source of stem cells

22:00 21 April 03 NewScientist.com news service

The tooth fairy could soon face competition for baby teeth from scientists who have discovered the teeth are a source of stem cells. The cells could help repair damaged teeth and perhaps even treat neural injuries or degenerative diseases.

Currently, researchers can isolate two types of stem cells. Embryonic stem cells can develop into any cell in the body, but their harvesting requires the destruction of embryos, which pro-life groups oppose. Adult stem cells avoid this problem, but have more limited abilities. Now it appears that the stem cells from children's lost teeth could provide an intermediate and easily accessible source.

"These stem cells seem to grow faster and have more potential to differentiate into other cell types than adult stem cells," says Songtao Shi, a pediatric dentist at the US National Institutes of Health in Bethesda, Maryland. Shi and his colleagues found the baby teeth cells can differentiate into tooth-forming cells called ondontoblasts, and also neural cells and fat cells.

Baby teeth, also called milk teeth or deciduous teeth, appear from the age of about six months and then fall out when children are between six and 13 years old.

Daughter cells

Previous work by Shi in 2000 had already shown that extracted adult wisdom teeth contain stem cells in the pulp at the centre of the tooth (PNAS, vol 97, p 13625). So when his six-year old daughter and her friends started losing their baby teeth, he decided to see if they also contained stem cells.

Whenever a tooth fell out, instead of putting it under the pillow, the parents stored the tooth in a glass of milk in the refrigerator overnight.

To isolate the stem cells, Shi extracted the pulp and cultured the cells for several days, then tested the survivors for markers of stem cell activity. About 12 to 20 cells from a typical incisor tooth turn out to be stem cells.

By culturing the cells in various growth factors, Shi could differentiate the cells into tooth-forming cells, fat cells or neural cells. The differentiated cells survived when implanted under the skin and in the brain of immunocompromised mice.

Shi also found that the cells promote the growth of bone. He suspects the stem cells may play a role in preparing the way for adult teeth. "We don't have evidence at the moment, but we think these stem cells do have a reason to be there."

The discovery of stem cells in baby teeth could give a big boost to oral surgery, says oral biologist Bjorn Reino Olsen, at Harvard Medical School. The cells, once differentiated into odontoblasts, could secrete dentine. This bone-like material could then replace the less biocompatible metal posts that are currently used to anchor implants to the jaw.

Journal reference:Proceedings of the National Academy of Sciences (DOI: 10.1073/pnas.0937635100)

Catherine Zandonella