Vaccines could help elephantiasis spread

PARASITIC worms can adjust their survival strategy based on their host's immune response. This means potential vaccines against elephantiasis might make the infection spread more easily through communities.

Elephantiasis infects 120 million people a year in Africa and Asia. Tiny filaria worms carried by mosquitoes block the lymph vessels that normally drain fluid from limbs or genitals, which then swell to grotesque proportions. The only prevention is a yearly dose of worming drugs, but fewer than half the people at risk receive them.

Work is under way on a vaccine, but Simon Babayan at the University of Edinburgh, UK, and colleagues, have discovered that some vaccines may make the worms worse. When filaria worms in mice sense that the mouse is mounting a strong immune reaction, they change their life cycle, producing more offspring in the blood earlier. This helps the worm ensure that it will be picked up and transmitted by another mosquito despite the immune attack (PLoS Biology, DOI: 10.1371/journal.pbio.1000525).

Unfortunately, experimental vaccines rely on the very immune reactions that warn the worms, Babayan says. People who get such a vaccine may defeat their own infection, but the worms' early response means they will pass on more infections.

Babayan says potential vaccines should be tested for whether their targets adapt to them in this way.

Synthetic DNA makers warned of bioterrorism threats

TO MAKE it harder for bioterrorists to build dangerous viruses from scratch, guidelines for firms who supply "custom DNA" are being introduced in the US.

The US and other countries restrict who can work with certain germs, but it might be possible to build some viruses from their genes. A number of firms supply DNA sequences to order. A 2005 investigation by New Scientist raised alarms when it found that only five out of 12 of these firms in North America and Europe always screened orders for sequences that might be used in bioweapons.

The US now wants firms to verify a customer's identity and make sure they are not on a list of banned buyers. It also wants them to screen orders for sequences that are unique to Select Agents, a list of microbes the US deems dangerous.

However, scientists commenting on the draft rules earlier this year fear that sequences from microbes other than Select Agents might also be dangerous. The US Department of Health says not enough is known about them to say which ones should arouse a firm's suspicions. Other potential weaknesses include the fact that the rules are voluntary, and that much custom DNA is made outside the US.

Cloning discovery may kill ethical objection

A key ethical objection to "therapeutic" cloning could be undermined if the results of experiments on abnormal cloned frog embryos are repeated in humans.

Therapeutic cloning involves the harvesting of embryonic stem cells from cloned embryos. Scientists hope the stem cells will provide powerful treatments for disease. But collecting them destroys the embryo - which is destroying a potential life, in some people's view.

However, this ethical problem would be avoided if healthy cells could be extracted from abnormal human embryos doomed to die anyway, and researchers have shown this is possible in frogs.

"If an embryo is certain to die, I can't see why anyone would object to someone taking cells and working with them," says John Gurdon, head of the team at the Welcome Cancer Research Institute in Cambridge, which experimented on the cloned frog embryos. "If it's destined to die within days, it's not a potential human," he says.

However, some pro-lifers disagree, saying they would only be satisfied that the procedure was ethical if the cells could be harvested without killing the defunct embryo. "It's a question of whether it curtails the life expectancy of the embryo," says Josephine Quintavalle of the UK's Pro-Life Alliance. She says that the principle of not killing an embryo is the same, whether its life expectancy is three days or three months.

Spare embryos

Couples undergoing treatment at fertility clinics almost invariably generate spare embryos that are visibly abnormal and doomed to die within two to three days. Now, through his work on frogs, Gurdon has shown that even if an abnormal embryo's fate is sealed, it contains cells which are completely normal and which develop normally into many tissue types.

To demonstrate this, Gurdon created genetically engineered frogs whose cells were equipped with a gene to make the green fluorescent protein (GFP) produced by some jellyfish.

Next, he took gut cells from the frogs and made them into cloned embryos by fusing them into normal frog eggs emptied of their own genetic material.

Half the embryos Gurdon created were complete duds, failing to divide at all. Another quarter developed into "partial embryos" which were clearly and visibly abnormal, with normal cells developing in only one half of the embryo, for example. These embryos all died a day later.

Growing up

But before they did, Gurdon extracted normal cells and grafted them into normal frog embryos. As the embryos developed, Gurdon could spot all tissues that came from the grafted cells, because they carried the GFP gene and so glowed green.

"The surprising result was that some of the cells from the cloned embryos did well and grew for months in the new host embryo," says Gurdon.

If the same was true of defunct human embryos, it might be possible to extract cells from them for crafting into tissues for patients. At the very least, says Gurdon, the cells could be used for research to find out how to fast-forward their development into any type of tissue

Alzheimer's protein may spread through infection

Neurologists have found that the brain plaques associated with Alzheimer's can form when the proteins responsible are injected into the bellies of mice, suggesting that the guilty proteins can get from the body's periphery to wreak havoc in the brain.

A protein called beta-amyloid makes up the brain plaques that accompany the disease. In 2006, Lary Walker at Emory University in Atlanta, Georgia, Mathias Jucker at the University of Tübingen in Germany and colleagues found that they could trigger Alzheimer's-like plaques by injecting samples of plaque-ridden brains into the brains of healthy mice. Now, Jucker and his colleagues at Tübingen have managed to create the same brain plaques by injecting the tissue elsewhere in the bodies of mice.

Mouse models

The group used mice genetically modified to produce large amounts of beta-amyloid, meaning they develop brain plaques similar to those seen in Alzheimer's disease in people. When the mice were around 2 years old, the team removed some of their beta-amyloid-laden brain tissue and injected it into the peritoneum – the lining of the abdomen – of young transgenic mice. Another group of transgenic mice received an injection of healthy brain tissue from normal mice of the same age that had not developed plaques.

Seven months later, before the mice had had a chance to develop plaques of their own accord, the team looked at their brains. The mice injected with healthy brain tissue had normal-looking brains, but those injected with beta-amyloid-heavy tissue had developed full-blown plaques similar to those seen in people with Alzheimer's.

If beta-amyloid in a mouse body's periphery can cause plaques in its brain, could Alzheimer's be transmitted by blood transfusions in humans? There's no evidence to suggest this might be the case, says Jucker. "We don't know if misfolded beta-amyloid can get out of the brain and into the bloodstream, for a start," he says.

Paul Salvaterra, a neurologist at the City of Hope hospital in Duarte, California, points out that Jucker's team only use an indirect measure of Alzheimer's because they focus only on plaques – just one aspect of the disease. "These authors are not studying Alzheimer's disease and certainly not studying infectious Alzheimer's disease," he says. "The type of [disease] they show is only suggestive of some aspects of Alzheimer's disease-related changes in the brain."

The early findings don't yet have implications for the general public, says Jucker, though he cautions that researchers should take care when handling amyloid proteins.