Massive virus discovered in water tower

19:00 27 March 03 NewScientist.com news service

The largest virus ever discovered has been found in a water-cooling tower in Bradford, England. It was lurking inside single-celled organisms called amoebae, but its discoverers believe that it may also be capable of infecting humans.

Although the new virus is a thousand times smaller than a pinhead, its girth of 400 nanometres makes it a mammoth in the microbial world. Most viruses measure between 10 and 100 nanometres, and the newcomer is even bigger than some bacteria.

At first, Didier Raoult at the Mediterranean University in Marseille and his team assumed that was exactly what it was. The virus's outer coating even reacts to a chemical stain that is specific to some bacteria. But when the researchers tried to detect bacterial-specific genes, they could not.

Now Raoult's team have confirmed that the giant - christened Mimivirus because of its similarity to a bacterium - is a virus by comparing its genes with other viral proteins. This comparison suggests that it is closely related to other giant viruses such as smallpox.

Gene giant

But not everyone is yet convinced. Brian Austin, at Heriot-Watt University in Edinburgh, Scotland, says the researchers could be seeing a bacterium that is associated with a virus. "They've left a lot of questions open," he says.

Nonetheless, if the identity of the Mimivirus is confirmed, Austin agrees it would be the largest yet found. And its king-sized characteristics are not just physical, but genetic too.

Its genome, which is 800,000 DNA letters long, is larger than any other virus and several bacteria. It has more than 900 probable genes, easily beating its nearest competitor, called phage D, which has fewer than 300. So far, however, the researchers have little idea what these extra genes do.

Intriguingly, Raoult says that preliminary results have revealed antibodies to the virus in human patients - suggesting that Mimivirus infects humans as well. But he does not know whether the mega-virus actually causes disease.

Journal reference: Science (vol 299, p 2033)

James Randerson

Synapse chip taps into brain chemistry

10:02 24 March 03 Exclusive from New Scientist Print Edition

A microchip that uses chemicals instead of pulses of electricity to stimulate neurons has been created. It could open the way to implants that interact with our nervous system in a far more subtle way than is possible now.

While electrical pulses convey impulses along neurons, the cells communicate with each other and with other cells such as muscles by releasing chemical messengers. These neurotransmitters are released from one side of a cell junction, or synapse, and picked up by receptors on the other side, triggering another electrical pulse.

Since synapses are typically around 50 nanometres across, and each chemical puff contains just a few thousand molecules, building an artificial synapse is a huge challenge. But Mark Peterman and Harvey Fishman at Stanford University in California are getting close. They told a biophysics conference in Texas earlier in March that they have created four "artificial synapses" on a silicon chip one centimetre square.

To cells on the surface of the device, the artificial synapse is simply a hole in the silicon. But each hole opens into a pipeline etched into a plastic layer on the back of the chip, connected at both ends to a reservoir of neurotransmitter. When an electric field is applied, the neurotransmitter is pumped through the pipeline, and a little of it squeezes out of the hole, stimulating nearby cells (see graphic).

At 5000 nanometres wide, these artificial synapses are closer in size to a whole cell than a real synapse, but even so, the pair have fine-tuned the device so that it can stimulate just one cell in the layer above the chip.

Neural prosthetics

The ultimate ambition is to develop neural prosthetics - implanted devices that can interact with our nervous system. Devices that use electrical stimulation are already commonplace, such as the cochlear implants that partially restore hearing.

But electric pulses stimulate nerve cells indiscriminately. Different neurotransmitters, in contrast, have different effects on a given cell. What is more, a single neurotransmitter can affect one cell in one way and a different cell in another. The neurotransmitter used by retinal cells, for example, turns some cells on and others off.

It means that devices that use neurotransmitters could interact with cells in more subtle and precise ways. Biomedical engineer Gerald Loeb from the University of Southern California speculates that powerful devices could be produced by combining chemical and electrical stimulation in one implant.

But there are still formidable obstacles. How densely can you pack the synapses in when each needs its own pipeline? How do you stop the pipelines from clogging with immune cells when the device is implanted? And how often would you need to refill the neurotransmitter reservoir?

To answer this last question, Peterman estimates that a thousand artificial synapses firing a thousand times a second would need as little as half a millilitre of fluid to function for 250 years. The other problems may prove tougher. "But it's early days," Loeb points out.

In the meantime, the most immediate application of the technique could be in tissue research. Drugs could be delivered to individual cells in a tissue sample to see how this affects the entire system.

Jenny Hogan

Anorexia linked to mystery molecule

16:55 27 March 03 NewScientist.com news service

Anorexic women have much higher levels of a mysterious molecule suspected to affect appetite, researchers have shown for the first time. The peptide, called CART, could be a candidate for new appetite-altering drugs, they say.

Levels of CART were 50 per cent higher in blood samples from anorexic women, compared with women without the eating disorder, says Sarah Stanley, an endocrinologist at Imperial College London. CART levels were also found to rise as the women's weight fell.

However, the function of CART in humans is not known. "And because we know so little, it is difficult to know if CART is the cause of the weight loss or the result," Stanley told New Scientist.

The team, based at Imperial College and the Eating Disorders Unit at London's Maudsley Hospital, will now proceed with experiments giving CART to humans to see if it has a real effect on appetite.

"Understanding the biology of anorexia nervosa is terribly important and any chink of light that might be shed on it through molecular research is certainly worth pursuing," says Stephen O'Rahilly, an expert in the molecular mechanisms of obesity at the Cambridge Institute for Medical Research, UK.

Up and down

CART is made in a variety of places in the human body including the brain, pituitary and adrenal glands. Studies in rats have linked the molecule to appetite. But CART both increases and reduces the appetite in rats, depending on which part of the brain it is injected into.

In the latest research, the team measured CART levels in the blood of anorexic women, anorexic women who were in the process of regaining weight, and recovered anorexic women who had maintained a normal body weight for a year. "We found a very, very strong correlation between plasma CART and body mass index," Stanley says.

Next, as well as giving CART to people, the team plans to examine CART levels in obese patients and those who have lost their appetite because they have a malignant disease. CART could also be a possible target for obesity drugs if it proves to reduce appetite, says Stanley.

"CART is definitely expressed in the appropriate parts of the hypothalamus to be involved," O'Rahilly told New Scientist. "But one should be cautious about leaping immediately to therapeutic applications." For example, it is difficult to know if measurements of CART in the blood reflect the situation in the brain, he says.

The findings were presented at the British Endocrine Societies annual meeting in Glasgow, UK.

Shaoni Bhattacharya

Half of all hospital drug injections are wrong

00:01 28 March 03 NewScientist.com news service

Half of all drug injections given intravenously in hospitals are done wrongly, a new study reveals, with third of these being potentially dangerous.

British researchers uncovered the disturbing level of errors when they examined drugs given intravenously by nurses in two hospitals in the UK. They believe the rate of mistakes they found is likely to be representative of practice across Europe and the US.

Nick Barber and Katja Taxis, at the School of Pharmacy, London, tracked the preparation and administration of over 400 intravenous (IV) doses given to patients on 10 different wards in the hospitals. "We were surprised about how commonly errors occurred," say Barber. "But not all of these were serious."

However, the error rate they calculated from their data predicts one serious error every day in every hospital in the UK, which is a concern, he says.

The most common mistakes were injecting doses of concentrated drugs too rapidly and preparing drugs incorrectly, by either using the wrong dose or dissolving them in the wrong solution. All could be fatal in certain circumstances.

Speed kills

For some drugs, the speed at which it enters the body is crucial, Barber explains. If they are injected too fast, they can induce anaphylaxis - a life-threatening allergic reaction.

"This is because there is a load of potent foreign chemical shooting around your body - if it hits the brain or heart it can have a marked effect," he said. But injecting a drug slowly, for example, over three minutes can be physically difficult for health care staff.

One of the three "potentially severe" errors Barber and Taxis in their study was of this type - with the antibiotic vancomycin being given too quickly. However, a pharmacist observer for the study intervened before any harm was done.

The second severe error occurred when a patient was nearly injected with an IV preparation containing five times the correct dose of heparin - which stops the blood clotting. "Wrong dose errors are the ones most likely to cause harm," notes Barber.

The third potentially lethal error was when an intensive care team infusing a patient with adrenalin ran out of the drug and had not prepared a second infusion in time.

Barber says the key to tackling such errors was to improve nurse training. He says there would also be a role for companies to develop a simple pump to help nurses administer drugs slowly.

Journal reference: British Medical Journal (vol 326, p 684)

Shaoni Bhattacharya

Chinese secrecy blamed for super-pneumonia spread

Updated 17:21 28 March 03 NewScientist.com news service

The Chinese government's secrecy has been blamed for the still growing outbreak of super-pneumonia around the world that has infected over 1400 people and killed 54.

The president of Taiwan, which has 10 cases of Severe Acute Respiratory Syndrome (SARS), has been the most outspoken. "SARS first broke out on the Chinese mainland, but the authorities covered up the information, leading to a global epidemic," Chen Shui-bian said on Friday. China initially admitted to five deaths, but a toll of 31, and 800 infections, since November was revealed on Wednesday.

The World Health Organization's pressure on China for more detailed information about its cases of SARS finally bore fruit on Friday. "China has agreed to provide up to date reports and they will be full, frank numbers on a regular basis," said John Mackenzie, the WHO team leader in China.

But WHO officials also warned that more SARS cases are likely to emerge in China, despite claims by the Chinese authorities that the outbreak has been "effectively controlled". Meirion Evans, another member of the WHO expert team, said: "To say it is controlled means that there will be no new cases. At this point it is too early to say that it is controlled anywhere [in the world]."

State secrets

The WHO, seeking Chinese cooperation, is taking a diplomatic approach. But other experts are less constrained. A Beijing-based international health official says it is unlikely that the SARS epidemic in China is restricted to Guangdong, Beijing and Shanxi, as the government claims. "My guess is that it has spread to multiple locations and is affecting people in many places," he told AFP.

The authorities view the release of negative news as damaging to China's international image and a threat to social stability. "Certain communicable diseases are seen as state secrets," the official said.

"It's not a wise policy," warns Hu Jia, director of the Beijing-based Aizhi Institute, a non-governmental body that has been fighting institutional neglect of China's emerging AIDS crisis. "The problem is that keeping the public in the dark also means that public health departments cannot prepare to address the disease if it continues to spread."

On Thursday, the WHO issued new travel guidelines designed to stop the virus's spread. The organisation urged airlines to screen passengers departing from the worst-affected places, where all the deaths have occurred: Hong Kong, Hanoi, Taiwan, Singapore, Canada and Guangdong. Emergency school closures and quarantine measures have also been imposed in Singapore, Hong Kong and Canada.

Prime suspect

The identity of the virus is still unclear. But "data from many network laboratories indicate that a coronavirus is the primary cause of the disease," said Klaus Stöhr, co-ordinator of the WHO collaborative network of SARS research laboratories on Thursday.

"This virus is unlike any known human or animal member of this virus family. But it is consistently found in specimens from SARS patients from many countries. We are very close to knowing for sure," he said.

However, a potential role for a metapneumonovirus, another virus also detected in samples from patients, has not been ruled out. This virus is a member of the paramyxovirus family, which includes pathogens that cause measles and mumps. "From the symptoms, SARS sounds much more like a paramyxovirus than a coronavirus," says Yvonne Cossart, an expert in viruses at the University of Sydney. "So, at the moment, everyone's puzzled."

Teams in four laboratories are currently working on sequencing the new coronavirus, in a bid to determine its origin. Coronaviruses do infect a wide range of animals, says Cossart. Southern China, the location of the first SARS cases, is a hotspot for emerging infectious diseases, such as influenza, which mutate in animals and then cross into people.

Damian Carrington and Emma Young

Adult "cot death" may explain mystery fatalities

18:04 28 March 03 NewScientist.com news service

A significant number of people could be dying from an adult version of "cot death", suggests a new study.

At least 3500 apparently healthy people collapse and die every year from unexplained causes in England alone, researchers have found. And in about 150 of these mystery deaths no cause can be identified, despite a full post-mortem examination.

Tim Bowker, associate medical director of the British Heart Foundation and a consultant cardiologist, led the study and says anecdotal reports of this type of death had baffled doctors for many years.

The researchers suggest that some of the deaths may occur due to electrical or metabolic abnormalities in the heart. However, this problem can only be identified in a living patient.

But the study shows the mystery deaths are a "real entity", Bowker told New Scientist. "And until one gives it a proper label, it is very difficult to take the science forward," he says.

Life saver

He thinks the deaths should be classed as the adult equivalent of sudden infant death syndrome (SIDS), and called sudden adult death syndrome, or SADS. This would lead to more information being collated and help find a "common thread" between cases, he says.

After cot death was officially recognised as SIDS, the number of deaths was cut by 70 per cent within a decade.

Bowker and his colleagues at the University of London asked coroners to look out for mystery deaths over a four month period, and send post-mortem reports and tissue samples. They specifically looked at white Caucasians aged 16 to 64, with no medical history of cardiac disease.

The team found that 80 per cent of the almost 700 unexpected deaths reported could be attributed to underlying coronary disease. A further proportion could be ascribed to some other kind of cardiac disease. But in about four per cent of cases no cause could be found.


Chaotic rhythms

These inexplicable deaths may be due to various causes, Bowker says: "Clearly the heart has stopped, but the structure is normal, so the first thing one should think about is electrical problems."

The beating of the heart is co-ordinated by electrical impulses generated by the flow of ions into and out of its tissues. In some conditions, problems with this electrical circuitry can mean the heart beats in an unusual pattern. "This may lead to chaotic rhythms in the heart, and so it stops," Bowker says.

But there may be other factors, unrelated to the heart, underlying this kind of mystery death. For example, the control of breathing might be lost.

Journal reference: Quarterly Journal of Medicine (vol 96, p 269)

Gulf war syndrome research reveals present danger

19:00 26 March 03 Exclusive from New Scientist Print Edition

A week into the invasion of Iraq and news networks are beaming home images of American and British soldiers donning gas masks and body suits to protect themselves from potential chemical weapons attack.

The troops have practised the drills, and are carrying the best high-tech chemical detectors an army can buy. The US marines even have a brand new piece of kit: pigeons, which act like canaries in a 19th-century coal mine. The birds are so sensitive to nerve agents such as sarin and VX that they fall ill at a whiff of danger.

What the soldiers have not been told is that about one in 10 of them are almost as sensitive to nerve agents as the pigeons. There is now mounting evidence that exposure to minuscule amounts of these chemicals can cause permanent brain damage in susceptible people, and that is exactly what happened 12 years ago when thousands of troops returning from Kuwait started to complain of debilitating symptoms.

Repeated surveys find 30 per cent more sick people among Gulf veterans than in comparable groups who did not serve. But the official position in Britain, Canada and the US is that Gulf war syndrome is not a specific medical condition.

All accept something is wrong with the 1991 veterans, but official research has focused on post-traumatic stress. The US has paid disability compensation to more than 110,000 of the 696,000 troops who fought in that war.

Neural damage

Then in October 2002, the US Department of Defense admitted there is "increasing evidence" that neural damage is affecting the ex-soldiers. It doubled research funding, including work on protective treatments. Veterans called it a "stunning reversal".

Part of the problem has been that veterans report a variety of symptoms which, though serious and chronic, are often vaguely defined. But in September 2002, researchers at the Gulf War Illnesses Research Unit at King's College in London showed that stress cannot explain symptoms displayed by British veterans.

At the same time, a medical team in the US identified three distinct syndromes among US Gulf war veterans. Han Kang and his team at the US Department of Veterans Affairs used a statistical technique called factor analysis that reveals unusual clusters of symptoms. They found syndromes that matched those seen in a smaller group by Robert Haley of the University of Texas Southwestern Medical Center in Dallas, who pioneered the investigation.

Syndrome 1 involves symptoms such as sleep and memory disturbance, while people with syndrome 3 have joint and muscle pain. The most serious is syndrome 2, whose symptoms include confusion and dizziness.

When Haley's team used magnetic resonance spectroscopy (MRS) to study veterans with syndrome 2 they found that they had lost nerve cells in the basal ganglia, structures involved in the brain functions disturbed in those with the syndrome. Veterans with other syndromes had also lost neurons in brain areas that fitted their symptoms. The finding was confirmed in another group by MRS expert Michael Weiner at the University of California at San Francisco.

Chemical weapons alerts

But what caused the damage? Haley found that syndrome 2 veterans are eight times as likely as healthy veterans to have been present when chemical weapons alarms sounded in the Gulf: for example, in January 1991, when Czech experts using sensitive Russian-made equipment detected nerve agent near a US army camp in Saudi Arabia.

Military authorities have denied that any soldiers were damaged by chemical weapons during Desert Storm, as none ever showed symptoms of acute nerve gas poisoning. But Jonathan Tucker of the US Institute of Peace, a congressionally funded think tank in Washington DC, has found dozens of reports of low levels of chemical weapons being detected near troops. These could have been released when allied forces bombed Iraqi arms depots or factories.

Syndrome 2 veterans were also around eight times as likely as healthy comrades to have reacted badly to pyridostigmine, a drug given to soldiers in the Gulf, then and now, to protect against nerve agent attacks. In troops who were both exposed to nerve agent and showed side effects to the drug, the risk of long-term ill effects was five times the risk conferred by each factor separately.

The link, says Haley, is that chemical weapons, and the drug that protects against them, affect the same physiological pathway. Nerve gas sends muscles into fatal spasm by blocking an enzyme that destroys acetylcholine, the neurotransmitter that makes muscles contract. In theory, pyridostigmine protects by blocking the enzyme for a short time, keeping nerve agents from binding to it permanently.

But some people may not be able to cope with having the enzyme blocked at all. Animal experiments show that exposure to enzyme blockers at levels too low to produce acute toxic effects can subtly change acetylcholine activity in the brain, and the animals' long-term behaviour.

Memory and cognition

Rogene Henderson of the University of New Mexico reported in 2002 that low doses of sarin change the distribution of acetylcholine receptors in rats' brains. Affected regions include those used for memory and cognition - which are the functions disturbed in Gulf war veterans.

The effect is more marked in stressed animals, which may explain why soldiers who saw combat show more severe symptoms. Other groups have also shown that nerve agents cause basal ganglion damage in animals.

Why are all soldiers not equally affected by the exposure to nerve agents? Pigeons make good detectors because they do not produce the enzyme paraoxonase which destroys nerve gas. Haley has found that syndrome 2 victims have very low levels of the form of human paraoxonase that is most effective against nerve agents, an observation repeated by Department of Veterans Affairs researchers in New Jersey in a study yet to be published.

In Britain, Bharti Mackness and her team at the Manchester Royal Infirmary have found that British veterans with Gulf war syndrome have half the paraoxonase activity of healthy colleagues.

Evidence that this kind of physical damage underlies Gulf war syndrome has been mounting since 1997. But the US government did not begin to take it seriously until the Department of Veteran's Affairs appointed a new Research Advisory Committee on Gulf war veterans last year.

The Department is now planning a national survey of Gulf veterans based on the newly defined syndromes, while Haley is building a more powerful MRS lab to observe brain damage more precisely. "We will then turn to finding treatments," he says. He has already shown that mice induced to make more paraoxonase are protected from a chemical similar to sarin.

Such progress promises to shed more light on why so many Gulf veterans are sick, and stop it from happening again. But it has come too late to help soldiers exposed to chemical weapons during the current conflict.

Debora MacKenzie