March of the microbe hunters

DRDE's kit provides instantaneous test for typhoid from patient's blood serum. (INSET) Brad spectrum insect repellent creams, lotions and wall paint, have scope for civilian spin-off.

THE FAX machine in the office of H. V. Batra, head of Microbiology at the Defence Research and Development Establishment (DRDE), Gwalior, Madhya Pradesh, comes to life, spewing out an urgent message from the Chief Medical Officer of Mayurbhanj district in Orissa.

A sudden epidemic suspected to be Leptospirosis has broken out in the a few villages. Quick measures are needed to treat the victims as well as a rapid diagnostic tool to scan the dozens of patients who are streaming into the primary health centres with identical symptoms.

The CMO is aware that DRDE has developed a diagnostic kit that uses the dot-ELISA method to definitely identify the `leptospira' within a couple of hours rather than days. Within hours Dr Batra and a fellow scientist are on their way, carrying a few hundred kits . They will eventually spend over a week in Orissa, helping local health agencies to contain the epidemic, suggesting the best chemical prophylaxis to control the number of new patients and assisting with the treatment of those afflicted.

As the Orissa government was to acknowledge later, it was timely, precious help. It ensured almost all of the 37 who succumbed to the infection, ultimately recovered.

On the frontlines of disease control, at the cutting edge of biotechnology, entomology, microbiology and toxicology it is difficult to draw neat lines separating core `customers' from the wider world of the suffering. DRDE's primary role is to provide research and development muscle to the Indian armed forces as they increasingly contend with the new realities of biological and other weapons of mass destruction.

Yet the work pursued here against challenging defence projects have invariably spilled into the civilian sector and spin-offs from the institution's primary focus areas have resulted in the development of internationally recognized technologies for disease control.

Anthrax was for long restricted to herbivorous animals. Now thanks to the global environment of terrorism, pulmonary anthrax caused by the inhalation of anthrax spores is yet another weapon in the hands of extremist organizations.

The work of equipping the Indian armed forces with the ability to take on this new threat has had one happy side effect: DRDE scientists have developed a system that can provide a confirmed diagnosis of the `anthracis' toxin in a human within 2 hours.

After extensive evaluation the World Health Organization ordered over 5000 anthrax detection kits for its work in Asia and Africa. A combined ELISA-type kit under advanced development, will provide a combined test for leptospirosis, typhoid and malaria. The Hindu reported last month ( on February 24) that DRDE has also released recently a quick and accurate test kit for typhoid that costs less than Rs 10 per test, and provides a result in minutes.

Preventing malaria rather than detecting it is the mandate of the lab's Entomology division. Indian troops stationed on the North Eastern borders have been provided the DRDE-developed multi-insect repellant DEPA acronym for diethylphenyl acetitamide in the form of a lotion ( and shortly as creams and sprays).

The patented technology with a Bureau of Indian Standards ISI certification is manufactured for the Army by a private agency, but somewhat surprisingly the vast civilian market is not being explored. " We scientists are lousy marketers" admits DRDE's Director K. Sekhar , a chemical technologist and propulsion expert who came to Gwalior from the Indian Missile Programme. Getting the fruits of costly research, often products that are not available even for those able to import, is an urgent mandate for the lab since he came on board.

Some of the requirements posed by the military may sound hilarious but for the scientists here it is just another challenge. "We developed rodent baits for the Navy" explains Dr. Shri Prakash, "But they came up with an unusual request: once it consumed the attractant tablet the rat tended to scurry up into the cable ducts where it could still do severe damage.

So they wanted us to develop a bait that prevented the rodent from entering the ducts. It took us a few months but we did come up with a formulation that paralysed the hind legs of the rodent".

The Naval Stores Organization was also a prime customer for another DRDE product that could well have wide commercial applications: a slow-release insecticide paint that provides protection for two years or more against a variety of pests including cockroaches and termites. Another mundane task with far reaching applications resulted in a kit that rapidly verified the resistance of insects to specific insecticides. "Largely due to excessive spraying, many flying insects develop resistance to certain formulations" explains Dr. Gopalan, "A quick check will reveal which insecticide is still effective and this can save a lot of ineffective spraying".

Away from insects, rodents and other domestic nuisances, scientists at the biotechnology and toxicology divisions of DRDE, deal routinely with dreaded toxins and biological warfare agents that seem to leap straight from the pages of a Robin Cook thriller.

The four best known toxins used in biological warfare are botulinum shiga ( induces dysentery), staphylococcus and perfringens (induces gas gangrene), I learn in matter of fact voice of Dr. Lokendra Singh. How to detect them, clear an area under attack and how to save those affected these are all in a day's work for DRDE scientists as they labour behind closed doors of secure lab rooms.

The second part of this report will deal with DRDE's work in perfecting chemical and biological defence systems, even as they work on many civilian applications that flow from this work.

Chemical linked to male infertility

A chemical widely used in industry and present in ground water, has now been found in the semen fluid of infertile men, reports a Queen's University research scientist.

Poh-Gek Forkert's study of male mechanics who use trichloroethylene (TCE) in the workplace shows the presence of TCE in their semen. F indings are reported in the journal Drug Metabolism and Disposition.

TCE is a volatile chemical used extensively in the automotive and metal industries as a de-greasing agent. It is also found in adhesives, lubricants, paints, varnishes, paint strippers, pesticides, spot removers and rug cleaning fluids, and has been detected in both underground and surface water sources.

Already linked to liver, kidney and lung damage, TCE has not until now been linked to reproductive disorders. "Our earlier studies on mice showed damage to reproductive tissue following TCE exposure, and the findings suggested impaired fertility," says Forkert. "We were interested in determining if there is also a link between TCE exposure and infertility in humans."

In the most recent study, seminal fluid from mechanics who had been exposed to TCE in the workplace — and who had previously been diagnosed with infertility — was analysed for TCE and its by-products (metabolites). All the semen samples contained TCE and metabolites.

"Taken together, results of our studies in mice and humans support the premise that TCE is metabolised in the human reproductive tract, and can adversely affect the normal development of sperm," says Forkert.

New heart muscle cells from bone marrow

Cells produced by the bone marrow can form new heart-muscle cells and help to replace those cells damaged by heart attack.

MAYO CLINIC researchers have proven that cells produced by the bone marrow can form new heart-muscle cells in adults, providing an important boost to research that could enable the body to replace heart muscle damaged by heart attack.

The findings were published in Circulation.

"Until recently, the heart has been seen as an organ that cannot be healed," says Noel Caplice, a cardiologist who led the study. "Heart-attack damage to the myocardium, or heart muscle, was earlier considered irreversible. This study points the way to a process that could lead to heart repair."

The researchers studied four female patients with leukemia who had survived 35-600 days after receiving bone-marrow transplants from male donors.

Heart tissue samples were examined at autopsy using special staining techniques, which showed that a small portion of the heart-muscle cells, or cardiomyocytes, contained male genetic material and had therefore originated from the donor marrow.

The study is important because it is the first confirmation that progenitor cells from outside the heart are capable of forming new heart muscle cells.

"These progenitor cells are produced by the bone marrow and circulate in the blood," explains Dr. Caplice. "They are like stem cells in that they have potential to develop into various kinds of cells.

Given the right biological signals, we have now shown they can become heart cells."

Dr. Caplice says the study has significant implications for future research. "Under normal conditions, with less than one per cent of heart-muscle cells originating from these progenitor cells, they obviously are not adding much to the heart's pumping strength.

But if we can determine the signalling mechanism that causes progenitor cells to develop into cardiomyocytes, we may be able to boost the response and induce more of them to proceed in that direction.

A growth hormone delivered to the heart could perhaps lead to formation of new muscle around an area of scar tissue, so the heart could actually be healed after being damaged by heart attack.

This study provides an important validation of the potential for this new line of research," Dr. Caplice concludes.

Hair secrets shed light on cancer

Scientists have uncovered the subtle chemical signals that stimulate the production of hairs.

The discovery may help explain how diverse structures, such as teeth and lungs, are formed, and how, when things go wrong, some forms of skin cancer develop.

It may also help to explain why some people go bald.

Some immature stem cells are genetically programmed to develop into either hair or skin tissue.

A team from the Howard Hughes Medical Institute at Rockefeller University, New York, has worked out the chemical pathway that determines which route each cell will take.

They discovered that the early stages of the process are controlled by the delicate interplay of two natural proteins.

The proteins, called Wnt and noggin, trigger a complex reaction that changes a stem cell's shape so that it can separate from adjoining cells and move downward - a developmental step that is essential for the formation of a hair follicle.

Cancer spread

Wnt has already been linked to the spread of some cancers, such as colon and breast cancer.

The researchers hope their work may shed new light on how a cancer cell spreads from its host tumour.

Stem cells destined to become hair contain two proteins - beta-catenin and Lef-1 - that are not found in stem cells that develop into skin tissue.

These two proteins appear to work together to produce changes in the stem cells that cause it to "morph" into hair.

The Rockefeller scientists previously provided evidence for this theory showing that mice which over-produced beta-catenin had extremely luxuriant fur.

Their latest research has revealed that Wnt and noggin play a crucial role in the accumulation of beta-catenin and Lef-1 within stem cells.

Stick together

The build up of these two proteins then reduces the production of another protein that keeps stem cells bound together.

If the stem cells remain firmly stuck to each other, they go on to form skin tissue.

But in the absence of this molecular glue, they are able to separate out and begin the process of turning into hair cells.

The researchers believe their description of the chemistry behind structural changes in a stem cell may ultimately shed light on several developmental and disease processes.

For instance, they suspect that a lack of molecular glue - and thus an inability to interact properly with other cells - may in part explain why some cells become cancerous.

For example, squamous cell skin cancers are large masses of cells that fold downwards.

Researcher Dr Colin Jamora told BBC News Online: "Manipulation of these natural factors may in the future be valuable in either stimulating the onset of hair growth or in preventing the formation of unwanted hair."

Thomas Lober, a science information officer at Cancer Research UK, emphasized the potentially wider significance of the study.

He said: "This research underlines the importance of studying basic biological processes like the formation of our hair follicles, and how these can inform our understanding of complex diseases like cancer.

"Cancer cells can exploit faulty cell-to-cell contact to move away from the original tumour and invade other tissues.

"A better grasp of how these cell contacts work may identify new targets for research into preventing cancer spread."

Curry spice combats alcohol-related liver disease

15:14 19 March 03 NewScientist.com news service

A vital ingredient of curry prevents alcohol-related liver disease, a study of rats has found.

Curcumin, the substance that gives the spice turmeric its distinctive yellow colour, stopped the changes caused by excessive alcohol consumption that lead to liver damage.

The research adds to the repertoire of benefits already shown by curcumin, which include anti-oxidant properties and anti-cancer activity. However, the research does not mean that people eating curries can safely drink more alcohol, warns Kalle Jokelainen, one of the team of Finnish and American researchers.

"Curcumin is not harmful, and it may protect your liver from liver disease if you have very high amounts - but this has only been seen in rats," he says.

Furthermore, the doses used in the experiments were much greater than would ever be used in cooking with turmeric, he says. Alcoholic liver disease is a serious problem, he says, but the answer is to drink less.

Bacterial toxins

Jokelainen, at Helsinki University Central Hospital, said that curcumin somehow blocks the activation of a key molecule called nuclear factor kappa B (NFkB).

This molecule directs the chain of events that leads to inflammation and death of tissue. It is activated by many stimuli including radiation, heat shock and endotoxins - the toxins associated with bacteria.

"If you drink too much, that leads to leaky gut syndrome," Jokelainen told New Scientist. "Somehow endotoxins from the gut reach the blood and are carried to the liver. The liver is a filter and inactivates the endotoxin, but the price paid is that NFkB is activated."

The team gave rats fish oil with either ethanol or dextrose added for four weeks. The rats that also received doses of curcumin did not develop the fatty livers, necrosis and inflammation seen in those not given the spice extract.

Journal reference: American Journal of Physiology - Gastrointestinal and Liver Physiology (Vol 284, p 321)

Undercover genes slip into the brain

14:48 20 March 03 Exclusive from New Scientist Print Edition

A molecular Trojan horse that can slip past the brain's defences has proved to be very effective at delivering genes to the brains of primates. It could be used to treat a host of brain disorders, from Parkinson's to epilepsy.

Treating the brain is very difficult because of the "blood-brain barrier" created by the tight junctions between the cells lining the capillaries. Only molecules recognised by the cell receptors can get in, unless they are very small.

The viruses most gene therapists use to deliver genes are too big, and have to be injected directly instead. Even then, the genes are not expressed widely and evenly throughout the brain.

"Quite frankly, the existing delivery systems have been woeful failures," says William Pardridge of the University of California, Los Angeles. Instead, his team has been perfecting a way to get genes into the brain hidden inside fatty spheres called liposomes.

First the team coats the liposomes with a polymer called polyethylene glycol (PEG), without which they would be purged from the blood within minutes. Next, antibodies that latch on to some of the brain-capillary receptors are tethered to a few of the PEG strands. The antibodies trick the receptors into letting the liposomes pass, where they can deliver their cargo to brain cells.

Bright light

Pardridge's team has already shown that the technique works in rats, by delivering the gene for the luminescent protein luciferase (New Scientist print edition, 10 June 2000). Now the team has tested the liposomes in rhesus monkeys, using antibodies specific to primate brain receptors. Not only did it work, but the amount of luciferase produced was 50 times greater than in rats (Molecular Therapy, vol 7, p 11).

"I haven't seen anything like this for viral or non-viral vectors," says Savio Woo, director of gene therapy at the Mount Sinai School of Medicine in New York. "To reach the central nervous system through the blood-brain barrier in a non-human primate with this kind of efficiency - that's absolutely fantastic."

The liposomes do not appear to have any toxic side effects, though they do deliver genes to other organs besides the brain. But the team has shown that by choosing the right switch to turn on the gene, the gene will be active only in the desired tissues.

Because the genes are not integrated into the genome, weekly or monthly injections would be needed for long-term treatment. But Pardridge sees this as an advantage, because there's no risk of genes lodging permanently in the wrong place and triggering cancer - a worry with some gene therapy viruses.

The method shows promise for treating Parkinson's. The team gave rats a neurotoxin that causes Parkinson's-like symptoms by cutting production of the key enzyme tyrosine hydroxylase.

Four weeks later, the team injected the rats with liposomes containing a gene that boosts production of the enzyme. Three days after that, the rats' abnormal movements were reduced by 70 per cent.

The liposomes can also deliver cargoes other than genes, including drugs and "antisense" RNA. The lifespans of mice with brain tumours doubled when the liposomes were used to deliver antisense RNA to block production of a growth factor.

And in studies yet to be published, the team has exploited a mechanism called RNA interference, delivering fragments of double-stranded RNA that "silence" cancer genes.

Killer pneumonia likely to be new bug

NewScientist.com news service

A new microbe that has jumped from animals to humans is likely to be the cause of the deadly pneumonia that has spread rapidly around the globe. This is the conclusion of international scientists who have tested for virtually every known human pathogen without success.

The highly infectious illness - dubbed Severe Acute Respiratory Syndrome (SARS) - has so far claimed at least nine lives from a total of over 500 cases. The outbreak has prompted serious concern at the World Health Organization and other health authorities.

The recent spread around the world stems from a single case in Hanoi, Vietnam. The Far East has been worst hit, with Vietnam now having 54 cases, Hong Kong having 123 and Singapore having 23, according to reports on Tuesday.

An earlier outbreak in China's Guangdong province, which resulted in over 300 cases and five deaths, is thought to be linked. Other countries affected by the outbreak include Canada, Australia, Thailand, Taiwan, UK, Slovenia, Germany and Israel.

Scientists in 11 international laboratories, coordinated by the WHO, are working flat out to identify the cause of the illness. WHO spokesman Ian Simpson told New Scientist: "The list of things tested for is vast. Everything which has ever been known to cause respiratory infections has been tested for, plus some others not known to cause respiratory infections. It's looking increasingly unlikely that it's caused by something we know about already."

Prime suspect

Influenza had been a prime suspect, and a fearsome prospect given its history of pandemics, but all known strains of influenza and its components have been tested without success. In addition, "pretty much all other viruses known to affect humans and most common bacterial infections" have been tested, Simpson says.

Pneumonia is an inflammation of the lungs caused by a bacterial, viral or fungal infection. Atypical pneumonia, as SARS was initially called, is usually caused by bacteria such as Legionella pneumophila, Chlamydia pneumoniae and Mycoplasma pneumoniae.

Simpson said organisms like Chlamydia and Legionella had not shown up in tests. But he added that the WHO was not completely ruling out anything and scientists were "triple and quadruple testing".

Chlamydia was implicated via lung x-rays in two deaths in the Chinese outbreak. However, Simpson said the Chinese authorities were now questioning this conclusion.

He said: "They now wonder whether that is correct. An awful lot of the population would test positive anyway if you just did a random Chlamydia test." WHO experts are now flying out to China to help the authorities review their evidence.

Bioweapon agent

Among the bacteria being tested, although not commonly associated with respiratory illnesses, is Neisseria meningitidis which causes meningitis. In addition, tests have been carried out for organisms like plague and Brucellosis - pathogens commonly considered as potential bioweapons.

"The reason [for testing biothreat agents] is just because they exist and people are scratching their heads for anything. Nobody can absolutely rule out the possibility of it being a biological agent, but if it is most people here would eat their hats," said Simpson.

He said laboratories were re-testing samples and examining the possibility that the culprit organism could be an entirely new emerging disease like AIDS, Ebola or Nipah virus, probably having crossed over to humans from animals.

Dozen countries now fear fatal pneumonia

NewScientist.com news service

The spread of a highly infectious and deadly pneumonia continued around the globe on Monday, with the number of countries with confirmed or suspected cases rising to 12.

Unconfirmed cases have now emerged in the UK, Australia, Switzerland and Slovenia, all connected with travel to the Far East. Health authorities on all continents are taking the risk of importing the disease extremely seriously. The US, South Africa and Russia, amongst others, have put their health authorities on nationwide alert.

Eight cases in Canada, including two deaths, and two cases in Germany were announced over the weekend. However, the situation is a fast changing one and suspected cases in Indonesia and the Philippines have now been ruled out.

The mystery illness, which has been labelled Severe Acute Respiratory Syndrome (SARS), has swept around the world since the first of 48 cases was recognised in Hanoi, Vietnam on 26 February.

This case in turn may be linked to an earlier outbreak involving over 300 cases in China. In total, the illness is implicated in nine deaths and 500 infections. Most are in the Far East, with more than 100 cases in Hong Kong, 21 in Singapore, three cases in Taiwan and one in Thailand.

Air filters

The World Health Organization is not recommending travel restrictions at present. But it has issued guidelines to help airlines identify passengers who might be carrying the contagious disease.

This includes anyone with a fever above 38°C, a respiratory symptom such as cough or shortness of breath and either close contact with a person with SARS or recent history of travel to affected areas. Based on information from Canada and Hanoi, SARS appears to have an incubation period between two to seven days.

In a statement, the WHO acknowledges that: "The speed of international travel creates a risk of rapid spread to additional areas."

Hong Kong-based carrier Cathay Pacific said it had initiated "precautionary health measures". Its principal medical officer John Merritt told AFP that air filters in planes "remove many of the droplets and particles that are responsible for spreading infection". But he added that "it is important for passengers who appear to be ill to be denied boarding and referred for medical assessment."

The suspected UK case is in a man who flew from Hong Kong to Manchester, and is now in hospital. The airline concerned has been notified, the UK Public Health Laboratory Service stated, although the available evidence suggests the infection is only passed on in cases of close contact, to family members or health care workers, for example.

Bacteria, virus, fungus

Pneumonia is an inflammation of the lungs caused by a bacterial, viral, or fungal infection. Atypical pneumonia, as SARS was initially called, is usually caused by bacteria such as Legionella pneumophila, Chlamydia pneumoniae and Mycoplasma pneumoniae.

But the organism responsible for the SARS outbreak is yet to be identified. Chlamydia was implicated via lung X-rays in two deaths in the outbreak in China's Guangdong province, although a link to the Vietnam and Hong Kong outbreaks has yet to be confirmed.

The WHO is now co-ordinating a major international effort to find the cause, with 11 laboratories working on the project in 10 different countries. "These are the world's best laboratories working together to see if they can find a diagnosis for this disease," David Heymann, WHO's executive director for communicable diseases, told AFP News.

He said influenza was unlikely to be the cause of SARS, as flu spreads faster. Hong Kong bird flu has already been ruled out as a possible cause. Experts have also suggested that because the Guangdong outbreak eventually subsided, the disease may not have the potential for a very large epidemic, as others have feared.

Deadly pneumonia has spread globally

NewScientist.com news service

The threat from a highly contagious form of pneumonia is now global, with at least nine countries thought to be affected.

Eight cases in Canada, including two deaths, and two cases in Germany were announced over the weekend. In total, the illness is suspected to have killed nine people and infected more than 470.

Over 300 of the cases have been China, where the first deaths from severe "atypical" pneumonia were reported in mid-February. The remaining 170 have centred on outbreaks in Hanoi, Vietnam, and Hong Kong, or can be traced to people who recently visited the region. The two groups of cases may be linked via a US businessman, who died after visiting both areas.

The cause of the illness, dubbed Severe Acute Respiratory Syndrome (SARS), is still unknown. But some victims are responding to a combination of anti-viral drugs and steroids, Hong Kong's health minister said on Monday.

Emergency guidance

On Saturday, the WHO issued emergency guidance for airlines and passengers. It recommends that any individual with a high fever and a respiratory symptom, such as a cough, and who has had close contact with a person diagnosed with SARS or who has recently returned from an affected country, should seek medical advice.

"The syndrome is now a worldwide health threat," said WHO secretary general Gro Harlem Brundtland. "The world needs to work together to find its cause, cure the sick, and stop its spread."

The guidance follow a issued a rare WHO global alert to health authorities on 11 March, as reported by New Scientist. The WHO's concern reflects the ease with which deadly infections can now travel the globe, thanks to the frequency of international travel.

In-flight illness

The Canadian cluster of cases included six people from the same family. In Germany, a doctor who had treated a patient in Singapore and who developed symptoms on a flight from New York to Frankfurt was taken to an isolation ward immediately after landing. He was accompanied by his wife and mother-in-law, who is now suffering from a high fever.

Laboratories in the US, Hong Kong and Japan are trying to identify the agent responsible. "At the moment, nobody knows the cause," says Bill Rawlinson, a medical virologist at the Prince of Wales Hospital in Sydney, and a member of the advisory committee to the WHO influenza reference laboratory in Melbourne. "But at the moment it's considered unlikely to be influenza."

The highly contagious and virulent nature of the infection suggests the agent could be a mutated form of an existing human pathogen, rather than one that has jumped from infecting animals to humans, says Peter Collignon, director of microbiology and infectious disease at Canberra Hospital, Australia.

"The number one priority is to work out what the agent is. Then we can work out how to stop it spreading and whether vaccines can be used," he says.

While infectious disease researchers rush to find the cause, health officials around the world are racing to track down people who may have come into contact with victims, and bracing themselves for their first cases.

Bone marrow experiments suggest diabetes cure

NewScientist.com news service

Stem cells from bone marrow can transform into insulin-producing cells, scientists have shown, suggesting a future cure for diabetes.

The experiments in mice are the first to show that bone marrow cells can be converted to beta cells. These are the pancreatic cells responsible for producing insulin, the hormone that regulates the body's blood sugar levels.

Transplants of pancreatic cells have been tried between people, but the supplies are restricted and recipients have to take strong anti-rejection medication. Embryonic stem cells have also be converted into insulin-producing cells, but also produce immune-rejection, in addition to ethical concerns.

But taking bone marrow cells from a patient, developing them into beta cells and then reimplanting them would have none of these difficulties. Also, much of the technology for bone marrow transplantation is already well developed, says study leader Mehboob Hussain, at the New York University School of Medicine.

"I am absolutely excited by the potential applications of our findings," he said. "In our body, there is an additional, easily available source of cells that are capable of becoming insulin-producing cells."

Green light

People who suffer diabetes are unable to regulate their body's blood sugar levels. There are two types of the disease. In type 1 diabetes the body's own immune system mistakenly destroys the beta cells which are crucial in producing insulin. In type 2 diabetes beta cells are present but do not secrete insulin fast enough to maintain normal blood sugar control.

The experiments of Hussain and his colleagues set out to show that bone marrow cells could become beta cells. To do this, they extracted bone marrow cells from male mice and injected them into the tail veins of female mice, in which the male cell would be easy to detect. The females had been exposed to radiation to destroy their bone marrow and beta cell function.

In addition, the team engineered the genes of the male cells to signal that insulin was being produced by making a green fluorescent protein. After four to six weeks, the team found glowing green cells in the females' pancreases.

However, Hussain noted that only between 1.7 and 3.0 per cent of the beta cells in the pancreas came from the bone marrow stem cells. A level between 10 and15 per cent would be needed to cure diabetes, he says, and the team's ongoing experiments have come close to this.

Markus Stoffel and Vivian Lee, diabetes experts from the Rockfeller University, New York, say the study is "elegant". The potential of bone marrow cells to avoid immune rejection problems is the greatest advantage, they say.

Journal reference: Journal of Clinical Investigation (vol 111, p 843)

Search for source of Ebola begins

NewScientist.com news service

Scientists are flying out to equatorial Africa to sample birds in an attempt to identify the mysterious reservoir of the Ebola virus, which has caused repeated fatal outbreaks in the region.

The most recent, in the Republic of Congo, was first detected on 4 January. On Friday, health ministry official Joseph Mboussa, said the death toll had risen to 106, out of a total of 120 cases.

The haemorrhagic fever can kill up to 90 per cent of its victims. In Congo, people are thought to have contracted the virus through contact with infected gorilla meat.

But scientists do not know the identity of the long-term reservoir of the disease, from which the gorillas caught the disease. "And as long as we haven't established the source of reservoir of the Ebola virus, it's an illusion to think of an appropriate cure," warned William Karesh, of the US Wildlife Conservation Society recently.

Structural similarities

Birds were implicated as a possible host to the deadly virus by David Sanders and Scott Jeffers at Purdue University, Indiana, and Anthony Sanchez, at the US Centers of Disease Control in Atlanta, Georgia, who showed in December that there are strong structural similarities between Ebola and some bird retroviruses.

"The biochemistry of entry of Ebola [into a cell] is really similar to bird retroviruses. It is clear that they have a common ancestor." Sanders told New Scientist."We suggest the possibility that the current natural reservoir is a bird host - it's consistent with Ebola's epidemiology."

The central African rift valley separates the ranges of bird species into distinct western and eastern groupings. Ebola outbreaks occur in central and western Africa but not in the east - consistent with being confined to the bird populations on one side of the rift valley.

Sanders says gorillas or other primates cannot be the long-term reservoir of Ebola because they die too quickly, meaning the virus would die out too.

Gloves and masks

Now Townsend Peterson, an ornithologist at the University of Kansas, Nate Rice at Purdue, and colleagues are flying out to Equatorial Guinea, with all arriving by the end of March.

In addition to ecological research projects, they will be collecting samples of liver and spleen tissue from about 100 bird species. The researchers will be protected by gloves and masks.

Peterson says his previous work tracking the ecology of outbreaks of filoviruses - the group to which Ebola belongs - had suggested that mammals were a more likely reservoir. Bats are one possibility. But Sander's study means that "birds certainly merit examination", he says.

The samples will be sent to Sanchez, a molecular virologist at the CDC, who will test for the viral proteins that identify Ebola. "There is this link with avian retroviruses," he told New Scientist: "It's a long shot - but we'll see what happens."

Dengue fever continues relentless climb

NewScientist.com news service

Outbreaks of dengue fever have risen around the world since the start of 2003, continuing the relentless spread of the once rare tropical disease.

Sharp increases in dengue fever, and its deadly complication dengue haemorrhagic fever (DHF), have been seen across the globe, from Vietnam, Malaysia, Indonesia, Australia to South America.

Akib Kamaluddin, head of South Sulawesi's health office in Indonesia, says the mosquito-borne disease has caused 23 deaths in the first two months of 2003, compared to 38 in the whole of 2002.

In Malaysia, a new strain has caused a massive jump in cases. In 2002, there were over 11,000 cases of dengue fever or DHF. But by 22 February there had already been 3410 recorded cases, with 11 deaths.

And in Vietnam, over 1700 people in Vietnam contracted in the January and February - a 66 per cent rise on the same months in 2002. Three people have died.

Mosquito control

Dengue fever was first recognised in the 1950s, and its dramatic rise since has been blamed on inadequate mosquito control in tropical and subtropical regions. The main culprit is city-dwelling Aedes aegypti, which has become more prevalent as nations have rapidly urbanised.

The disease is now endemic in over 100 countries, and according to the World Health Organization, 40 per cent of the world's population is now at risk. There are estimated to be as many as 50 million cases a year. Although it rarely kills, dengue fever causes a severe flu-like illness that can lead to hospitalisation.

There are four closely-related strains of the virus that causes dengue fever. Contracting the disease confers lifelong immunity, but only to that strain. The rise in cases in Malaysia is partly because the DEN3 strain is new to the country.

Paradoxically, people with immunity to one strain have an increased risk of developing the more lethal DHF if they then catch a different strain. This has added to the difficulties in developing a vaccine, because such a drug must not increase the risk of more serious disease.

Rainwater receptacles

"The big problem with dengue is that the lack of a vaccine. Therefore we have to use vector control - mobilise communities to restrict mosquito breeding sites," says Harold Townson, president of the Royal Society for Tropical Medicine and Hygiene, in London, UK.

A. aegypti breeding was encouraged by discarded containers such as tin cans and tyres which collect water, as well as receptacles left to collect rainwater, he told New Scientist.

Malaysian health minister Chua Jui Meng agrees, saying the rise in public apathy in keeping the environment clean, as well as an exceptionally heavy rainy season, has worsened the dengue outbreak. He told AFP news the government had served 30,000 notices to people to stop mosquitoes breeding on their premises and taken 550 people to court.

In Cairns, Australia, there have been 16 confirmed cases, with 60 more suspected cases reported. Twenty cases have been reported in the Paraguayan city of Pedro Juan Caballero.

Townson says it is too early to say if the 2003 increases represent a major new wave of the disease, but he adds: "It certainly shows no major sign of abating."

RNA sends message from fetus

NewScientist.com news service

Tests on blood taken from a pregnant woman can reveal which genes are switched on in the placenta. The finding paves the way for non-invasive, safer, pre-natal tests for a range of disorders, including Down's syndrome and pre-eclampsia.

In blood samples from pregnant women, researchers isolated molecules produced only by genes in the placenta. The molecules, messenger RNA, give genetic information about the fetus, not the mother, because genetically the placenta is part of the baby.

"While DNA is the genetic blueprint, mRNA will tell you which genes are actually being expressed," says team leader Dennis Lo at the Chinese University of Hong Kong. "And many diseases, genetic or otherwise, might be associated with abnormalities in RNA expression."

Almost all current tests for fetal chromosome, genetic and biochemical disorders depend on invasive procedures to provide fetal cells for culture or DNA analysis, points out Malcolm Ferguson-Smith of the University of Cambridge, UK.

These tests can be risky. For every two fetuses identified as suffering from Down's syndrome using a cell-sampling test, five healthy babies miscarry as a direct result of the procedure. The new findings have "considerable potential for non-invasive prenatal screening and diagnosis," Ferguson-Smith writes in a commentary on the research.

Fluorescent probes

Lo's team used fluorescent probes to measure levels of mRNA encoding two hormones, human placenta lactogen and human chorionic gonadotropin (hCG). Elevated levels of hCG are associated with Down's syndrome, so tests for hCG mRNA might form a safer method of diagnosis than amniocentesis, says Lo.

Previous work has shown that a high level of fetal DNA in the mother's bloodstream is also associated with Down's syndrome. But tests based on analysing this DNA have two major drawbacks.

First, maternal and fetal DNA is so similar that the two can only be easily distinguished if the child is male. Second, elevated foetal DNA levels could indicate a wide range of disorders. But these disorders are also likely to produce increased levels of fetal RNA in the mother's blood, says Lo. "And we would expect different diseases to have specific patterns of RNA expression," he says.

The next step is to isolate other types of mRNA produced in the placenta, but not by the mother. "We should pick 10 or 20 and then document their levels in relation to different diseases," says Lo.

Journal reference: Proceedings of the National Academy of Sciences (DOI: 10.1073/pnas.0637450100)

Composting toilets key to global sanitation, say scientists

NewScientist.com news service

Giving large sewer systems to communities in the developing world could be disastrous for them and their environments, sanitation scientists are telling the World Water Forum in Kyoto, Japan. Their advice flies in the face of United Nations targets to hook up more than a billion people to sewers in the next decade.

Government ministers and water experts are meeting to hammer out plans for meeting the UN target of halving the number of people in the world who lack clean drinking water and modern sanitation by 2015. Allowing for population growth, that means connecting 400,000 people every day for the next 12 years.

But scientists at the forum say installing conventional sewer systems that empty into rivers could create a public health disaster, rather than solving one. Instead, they want to recycle sewage from poor villages and shanty towns so it can fertilise fields.

"Conventional sewer systems are just not the right answer," said Bengt Johansson, of the Swedish International Development Agency. "They are very expensive; they pollute rivers; they use a lot of water for flushing that could be set aside for drinking; and they deprive farm soils of the nutrients in sewage."

The UN Environment Programme agrees. "Nobody planning these sewers is thinking about the pollution," said a spokesman.

Compost heap

The solution, say aid agency experts, is "ecological sanitation", or EcoSan. This involves composting sewage and is cheap, water efficient and non-polluting. "It is not a second best," said Johansson. "I have an EcoSan system in my summer house outside Stockholm. It works very well."

And Michael Rouse, formerly the UK's chief drinking water inspector, recently said that if Britain were planning sewage disposal from scratch today, "we wouldn't flush it away - we would collect the solids and compost it".

The Japan Toilet Association is displaying examples of EcoSan technology here. Some are toilets that store and compost the sewage. Some are community systems that separate urine, faeces and washing water and recycle them separately, irrigating and fertilising fields. Some even ferment sewage to make biogas for cooking.

But despite a host of innovative technologies for supplying water and handling sewage, the meeting is dominated by water industrialists pushing for extra investment in large infrastructure projects.

In addition to large sewage projects, they are pushing for a revival in the construction of large dams, which is certain to be controversial. Many such projects have been on hold since a World Bank moratorium imposed in the mid-1990s, but that moratorium was lifted in February.

Gene tests could scupper bioterrorists

New Scientist.com News Stories

A new gene-based technology may soon allow exposure to mystery biological weapons to be identified in a few hours.

Experts say that if this early detection means treatment is highly effective, then the harm that can be caused by biological weapons would be substantially lessened, reducing their attractiveness to attackers.

A person's cells react almost immediately after exposure, according to US army scientists, and the combination of genes expressed is unique for each biological agent. So by examining gene expression, it is possible to rapidly identify the agent, as well as the level of exposure, and tailor treatment accordingly.

Marti Jett, at the Walter Reed Army Institute of Research in Silver Spring, Maryland, and colleagues identified unique patterns of gene expression in primates and pigs following exposure to a range of bioterror agents. They believe a handheld test for humans could be developed within a year or two.

Jett told New Scientist that if victims of an anthrax attack, for example, were identified within 36 hours of low dose exposure they have a 100 per cent chance of survival, compared with only 50 per cent if diagnosis takes place after three days.

"It sounds rather wonderful," says John Oxford, a virologist at Queen Mary, University of London. If such a method of early detection was widely available, "it would knock the bottom out of bioterrorism - they would have to go back to the old Semtex", he says.

Plague and cholera

Jett's team exposed non-human primates to low doses of eight potential bioweapons: anthrax, plague, brucellosis, Venezuelan equine encephalitis, dengue fever, Staphylococcal enterotoxin B (SEB), cholera and botulinum toxin.

At the doses given, symptoms appeared only after three days. Without treatment, the primates would be dead by seven or eight days. But the team saw characteristic changes in gene pattern, detected by the analysis of messenger RNA in blood samples, as early as 24 hours.

And Jett thinks it will be possible to cut this time to just six hours. Such tests could be vital in situations where people were in the vicinity of a biological attack but unsure if they were exposed.

Experiments giving different doses of SEB to pigs showed that gene expression not only indicated the agent but also the level of exposure, successfully distinguishing lethal and non-lethal levels.

Handheld device

Many of the activated genes are in the white blood cells, the first line of the body's immune defence. The most useful are genes that are not usually expressed in healthy individuals.

As few as 50 genes are indicative of each pathogen, says Jett, but for reliable identification a few thousand should be tested. The team used laboratory equipment that could analyse about 40,000 genes per sample. A commercial handheld device analysing 400 genes will be on the market within a year, Jett says, and companies are developing portable devices that can analyse far more.

The team is now testing the gene expression resulting from normal diseases, to ensure that these will not be confused with bioweapon exposure. For example, the initial symptoms of anthrax and influenza are similar.

"If this technology can be applied to the huge natural killers of mankind like influenza, then it would be a really significant discovery," Oxford adds. "They're on to a winner in every sense."

Jett's team's findings were presented at the recent American Society for Microbiology's biodefense research meeting in Baltimore, Maryland.