Scientists fighting malaria are preparing the ground for one of the most audacious attempts ever to wipe out disease: genetically modifying an entire animal species in the wild.

In laboratories around the world, there is increasing confidence that scientists will acquire the ability to spread a synthetic gene throughout the populations of dangerous mosquitoes, making it impossible for them to pass malaria on to humans.

Until now, spreading genes throughout a species was something only evolution was capable of, over millions of years of natural selection. But scientists think it might be possible to transform the malaria-carrying mosquito into a subtly different species - still a bloodsucking nuisance, but no longer a killer - within two to 25 years of releasing the first GM insects.

In a sign of how fast research is moving, specialists in the field are gathering in London next week for a conference to discuss the risks and benefits of releasing GM mosquitoes into the wild.

"We're not talking about one to one replacement of lab mosquitoes for wild mosquitoes," said Tony James, of the University of California in Irvine, who is attending the conference at Imperial College. "There's no question of competition between transgenic and non-transgenic insects. What we're talking about is actually driving the gene through a population. It's an ambitious idea."

http://www.guardian.co.uk/genes/article/0,2763,546082,00.html

-- Anonymous, September 03, 2001

Answers

[Funny you should say that. . .]

ET

The cure the West ignored (Filed: 01/09/2001)

It's the disease they said would be eradicated by 1990, but a decade on malaria still kills two million people every year. Yet since the Seventies, the Chinese have been treating their malaria victims with cheap, simple drug, which could save countless lives across the world. so why haven't we been using it? Alex Spillius reports

MU TU TU might be dangerously ill, but she is a very lucky baby. Her 28-year-old mother has carried her for two hours through the jungle from her Burmese village and across a stream into Thailand, where a mobile clinic is distributing a rare and wonderful thing: a dependable cure for the fatal form of malaria.

Killer: up to 2.5 million people die from malaria, carried by mosquitos, every year

Mu's mother joins a queue of women dressed in bright sarongs and blouses, cradling her six-month-old child, and waits for a white pill which is crushed into water and spooned into an unwilling mouth. Within hours, the fever that was threatening her baby has receded. Mu had been bitten by the female anopheles mosquito, carrier of the potentially deadly falciparum parasite that shatters red blood cells, provoking a fever that rapidly escalates and can bring death within 48 hours. Between 1.5 and 2.5 million people die of falciparum, or cerebral, malaria every year - the young and the pregnant are its most vulnerable victims. Survivors are debilitated for weeks and can carry the parasite for years.

What saved Mu was a cure based on a puny-looking Chinese plant called qinghao. Although unknown in the West outside the scientific community, it promises to change the way we treat a disease which has defied all the drugs that Western companies have thrown at it. In south-east Asia the falciparum parasite has learnt to resist, to varying degrees, the four major anti-malarial drugs, with chloroquine rendered virtually redundant. But malaria strikes most of its victims in sub-Saharan Africa, killing between 3,000 and 4,500 children daily, according to the UN. In parts of the region the parasite has already mutated against three of the drugs, and a recent study in Tanzania found that the disease has just begun resisting the last frontline medicine (prymethanine sulfadoxine), leaving the population exposed to disaster. Tourists are also at risk because they take the same drugs as preventatives.

Col Wilbur Milhous, head of experimental therapeutics at the Walter Reed Army Institute for Research in Washington, describes the qinghao drug's discovery as 'monumental', comparing its potential with that of penicillin. Scientists from the research foundation the Wellcome Trust were the first to test the drug properly in the field. During a 10-year project among 120,000 refugees on the Thai-Burma border, the team has found that when a qinghao extract, known as qinghaosu, is used in tandem with established medications such as mefloquine, it has a near 100 per cent success rate in preventing malarial deaths. By wiping out the parasite in the bloodstream, it has been almost as successful at preventing people contracting the disease.

The Wellcome scientists make a compelling case that a unique opportunity is being wasted to tame, even eradicate, one of the world's biggest killers. Professor Nicholas White, director of Wellcome's South East Asia Research Unit, says, 'I admit I find it hard to be objective on this subject, but I know that if we'd done this work with Aids then everyone would have been using this treatment yesterday. But in malaria things move remarkably slowly, frustratingly slowly.

' Professor White vividly remembers reading the first English account of the magic plant's properties in the Chinese Medical Journal in 1979, in an article entitled Anti-malarial Studies on Qinghaosu. 'For want of a better phrase, I was gobsmacked,' he says. 'Here, on flimsy yellow paper, in rather quaint English, was the description of a new compound, including tests in vitro, on rodents and then on humans. It was all contained in five pages when a Western pharmaceutical company would have spent $300 million and published a document as thick as a brick.' The publication came just at the time when Western confidence in a cure for malaria was evaporating.

In the Fifties it had all been so different - and so full of optimism. The UN's World Health Organisation (WHO) declared war on the mosquito and predicted the elimination of malaria from endemic areas - Asia, South America and Africa - by 1990. One of the biggest health campaigns ever launched saw DDT, an insecticide that killed mosquitoes upon contact, sprayed across the world from mud huts in Burundi to longhouses in Borneo. Malaria cases were treated with chloroquine, an incredibly cheap and efficacious treatment derived from quinine, and by then the second most commonly taken drug in the world after painkillers.

Although an estimated 25 million lives were saved and malaria all but disappeared, the WHO's forecast proved over-confident. The mosquito adjusted to DDT, while the parasite transformed itself to survive and outwit chloroquine. In the early Sixties, signs of resistance were clear in south-east Asia and South America and by the end of the decade the goal of eradication had been abandoned.

But unknown to the West, in the darkest days of the Cultural Revolution, Chairman Mao spared a consortium of young scientists the familiar academic's fate of banishment to rural labour and urged them to find a home-grown antidote to malaria, a scourge in China as elsewhere. They decided to work their way meticulously through China's extensive herbal pharmacopoeia. They soon focused on qinghao, a plant whose leaves, dried and infused in hot water, had been used for 2,000 years as a cure for fever. In a brilliant piece of chemistry, they extracted an active anti-malarial compound, qinghaosu (known as artemisinin in the West), and within eight years announced it ready for manufacture. The authors of the article, whom many Western scientists think worthy of Nobel Prize consideration, were hidden behind the obscurity of the 'Qinghaosu Anti-malaria Coordinating Research Group'.

Two years after the article appeared, Prof White travelled to China and met the article's authors in Shanghai. Perhaps out of respect for a fellow academic, moreover one based in the East - in Thailand's capital, Bangkok - he was given a bottle of the powdered compound. Already established as a rising star in his field, he wanted to begin immediate testing on the compound's properties. But WHO officials, sceptical that Chinese methods might be inadequate or primitive, insisted that it alone should devise a 'safe' version of the drug, one that matched Western standards. Precious years were wasted as Western scientists set about working on their own version of the drug. Prof White says, 'It was, sad to say, totally unnecessary. It would be like the Russians designing a supersonic jet with a pointy tip and calling it Concordski.'

WHO entrusted most of the research to the American army's Walter Reed Institute. The US military moved to the forefront of malaria research after the Second World War, when malaria in tropical zones killed 10 servicemen for every soldier killed in combat. But first, the Americans had to get their hands on the plant, a difficult feat owing to superpower suspicions on the part of the Chinese. Even when the scientists expressed a willingness to co-operate, the Communist Party would step in.

'They were hesitant about sharing information,' says Col Milhous. 'I mean, we were the American army.' But before long, the American researchers found a very close relative of the magic plant growing wild in its own backyard, along the banks of the Potomac River in Washington, called sweet Annie or sweet wormwood, named after its aroma. They then spent the next 10 years creating their own version of the Chinese drug and discovering how exactly it worked. In the early Nineties, the Institute carried out the first of a series of tests needed to get the compound approved for human use, but the laboratory tests did not produce the hoped-for results. Prof Walther Wernsdorfer, an Austrian expert in tropical medicine who was then responsible for the WHO's malaria chemotherapy policy, is not alone in thinking the experiments were not 'laid out in the right way'.

But coming from such an august source as the Walter Reed Institute, the results created a mental block towards qinghaosu in the WHO and many African countries, putting the formula's mass deployment back even further. While the West was wasting time attempting to prove what the Chinese had already demonstrated, Far Eastern countries such as Cambodia, Thailand and Vietnam began buying qinghaosu direct from China and saving countless lives.

By the late Eighties, Prof White and his team of Thai, British and French experts had had enough of waiting for the WHO and the US. Using qinghaosu tablets imported from China, in combination with patented Western anti-malarials chloroquine and mefloquine, they began the first systematic clinical trials in the refugee camps, situated in areas of forests, swamps and mosquitoes. The Burmese refugee population was an ideal testing ground as their confinement meant the drugs' effects could be closely monitored. The results were spectacular and, just as the Chinese had repeatedly claimed, the medicine was stable and produced no side effects.

What makes qinghaosu and its derivatives unique is their molecular structure. 'Under a microscope, the molecule looks like a pair of rimless spectacles. It looks too unstable to last more than a couple of minutes once unleashed in the bloodstream, but in fact it is beautifully balanced and very stable,' marvels Prof White.

The deadly parasite is sustained by a chain between humans and mosquitoes. When the insect's proboscis drills through human skin, it feeds on the nutrients in red blood cells but also absorbs any parasite that might be present. It then nurtures this parasite in its gut before transferring it to the next human it bites. Qinghaosu has two oxygen atoms that detonate the iron found in red blood cells. The explosion is so strong that not only the falciparum parasites but also their offspring - gametocytes - are blown up. The drug's blitz breaks the chain. The idea of using qinghaosu in combination therapy is the same as in using multiple drugs against HIV or tuberculosis - to confuse a disease, so it can't learn to recognise what has hit it and therefore can't mutate into resistant forms. Combined with mefloquine, the qinghaosu acts as artillery, blowing up the parasites while the conventional drugs act as snipers, stalking any survivors.

At present, patients have to take the pills separately, meaning they are far less likely to finish the course, so raising the risk, albeit small, of resistance. What the world urgently needs is an all-in-one tablet acceptable to European and WHO standards. So far, only one has been developed - by the Swiss company Novartis in conjunction with the Chinese - but it will be prohibitively expensive for general use. David Alnwick, manager of the WHO's Roll Back Malaria initiative, comments, 'It's incredibly sad more wasn't done 10 years ago to prevent malaria getting as bad as it is and that more money and resources were not put into better combination drugs. But our view is artemisinin is the most exciting component and that it should be widely used. It is incredibly important.'

Qinghaosu combinations may have worked wonders in Asia, but more research is needed in Africa before sluggish governments are prepared to accept it as standard therapy, especially as it is more expensive than the old favourite chloroquine (about 25 cents a treatment, compared with $2 for a qinghao mefloquine combination). Governments will have to accept that more expensive treatments will reap the dividends of a healthier and more productive population. The WHO will have to persuade pharmaceutical companies to produce cheaper drugs, at risk to their profits.

Prof White concludes, 'We haven't done well in malaria for the past 30 years. There has been a culture of not succeeding and not changing. People don't realise that there is not an endless timescale for this. We're losing effective drugs very quickly. It may already be too late.'

-- Anonymous, September 03, 2001

Thanks OG..Hadn't seen that.. Great article!!.. I'm not much in favor of these mad geneticists experimenting on us by releasing hordes on GM mosquitos..

All the Best
brent

-- Anonymous, September 03, 2001

Me, neither! Good to see ya, Brent. Did you read the thread further down about catnip being a great mosquito repellent, better than Deet? The thread kinda degenerated but you can glean some useful info there too.

-- Anonymous, September 04, 2001

I would prefer the natural medicine over the GM skeeters any day.

The very idea of releasing [let alone creating!] GM skeeters is on the level of cloning designer humans.

-- Anonymous, September 04, 2001

That wonderful line by the robotic gigolo in Artificial Intelligence..."Once you've experienced me, you'll never want a real man again!"

-- Anonymous, September 04, 2001

Hi OG..
Thanks!! .. that was a good thread on Catnip!!.. I'd missed it but found it in the archives..
cheers
brent

-- Anonymous, September 04, 2001