Unless you have your own transport, the only way to the National School of Medicine is to cram into a bush taxi at Bamako鈥檚 football stadium, or to hitch a ride up the winding hillside. Here, overlooking the dusty city, is a forlorn village and baking wasteland of rotting mango stones, chicken bones and paper. But across the road, in a flower-shrouded campus, is an oasis of high technology where Ogobara Doumbo and Y茅ya Tour茅 head the Malaria Research and Training Centre, a model of world-class science in this poorest of countries. In an air-conditioned chill, researchers from all over Africa work late into the evening amid rows of personal computers and the gleaming paraphernalia of molecular biology.
The technical facilities are essential, but these are not what make the MRTC unique. Chris Plowe, a researcher from the University of Maryland in Baltimore, who regularly collaborates with the Malian scientists, sums up its defining quality: 鈥淯nlike many research facilities in Africa, where Western scientists swoop in, collect samples and swoop out again, and where African scientists play relatively minor roles, the Bamako lab is one of the few where a truly African institution is doing cutting-edge scientific research.鈥
Malaria is never far from the minds of most Malians. About a million children die of the disease every year in sub-Saharan Africa and Mali is among the worst-affected countries. In the rice-growing region on the Niger Delta around Mopti, near the Dogon country, one in five children dies before the age of five, with malaria the biggest single cause of those deaths. And the challenge of overcoming it today is as daunting as ever. 鈥淭he Plasmodium parasite is very crafty,鈥 says Doumbo. Drug-resistant strains are spreading rapidly. The main drug used to treat the disease, chloroquine, has now failed in east Africa, causing child deaths in the region to rocket.
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The only affordable line of defence that remains is Fansidar, a mixture of pyrimethamine and sulfadoxine, but that is expected to last for only about another five years before the parasite sidesteps it too. In Mali, even though chloroquine still works, Fansidat has been used in some villages, giving the parasites a head start to develop resistance before the drug is really needed.
So the centre is trying to keep a few steps ahead with research that has made it a hub for Africa. The lab has 30 staff, and about 20 students from African countries currently in training. 鈥淥ur staff seminars boil with ideas,鈥 says Doumbo.
The origins of the MRTC are international, but the Malians鈥 role has always been critical 鈥 and the leaders have been careful to maintain its independence in their foreign collaborations. It grew out of the Department of Epidemiology and Parasitic Infections, set up within the medical school in 1973 by Philippe Ranque, a French scientist now based at WHO who trained both Tour茅 and Doumbo. 鈥淗e believed in the capabilities of Malian scientists,鈥 says Doumbo. The MRTC evolved in 1992 out of partnerships between the Malian scientists, the US National Institutes of Health, and Mario Coluzzi, the 鈥渇ather鈥 of mosquito chromosome genetics at the University of Rome. Its principal support has come from the US Agency for International Development, the NIH 鈥 which has appointed a full-time resident scientist 鈥 and from the WHO鈥檚 programme of research and training in tropical diseases. However, the international links are only half the story. The centre works closely with Mali鈥檚 national malaria programme. 鈥淲e have a good relationship with the Ministry of Health,鈥 says Tour茅. The deans of the medical school have helped, too, allowing the MRTC to manage its own affairs and sign its own papers. 鈥淭his is the only way to run a lab in Africa,鈥 says Doumbo. 鈥淚t鈥檚 the future.鈥
In the epidemiology group, Doumbo and others, including Don Krogstad, a frequent collaborator from Tulane University in New Orleans, are tracking the spread of resistance to the available drugs. Among their tactics is a method for testing DNA from the malaria parasite, taken from samples of infected blood, to detect specific point mutations in the genes encoding certain enzymes. The mutations correlate with resistance to particular drugs. By testing large numbers of samples, the researchers build up a map of the areas where many parasites are resistant to each drug. The results, fed back to the health ministry, determine which drugs are used where. One of the benefits is that Fansidar is now used only where chloroquine has failed.
The test they use, centred on the polymerase chain reaction, amplifies up tiny amounts of parasite DNA. Originally developed by scientists in the US, it has been adapted at the MRTC so that it will work on real parasites in field conditions. It can process two batches of 16 samples in a day, whereas the conventional technique relies on culturing live parasites and may take up to a week to produce results on a single sample. Equally important, it works with just a single drop of blood, blotted onto paper from a fingerprick, sparing children a larger bleed.
Doumbo and his colleagues are also looking for ways to prevent the serious and complicated forms of malaria 鈥 such as anaemia and the coma that results from invasion of the parasites into the blood vessels supplying the brain. 鈥淲e find that these cases occur at the end of the transmission period,鈥 says Doumbo, 鈥渨hich is a paradox.鈥 In the dry season, while the mosquitoes are not active, people鈥檚 immunity to the parasite decreases. So it would be logical to expect the most severe cases of disease to happen at the beginning of the transmission period, not the end. Now the team think they may have found an explanation and have developed a technique to test their idea. According to their hypothesis, the parasite 鈥渦ses鈥 the transmission period to evolve more potent strains and these then become more common towards the end of the season.
Meanwhile, Y茅ya Tour茅鈥檚 entomology group focuses on ways to understand 鈥 and so control 鈥 Anopheles gambiae, the mosquito that carries and spreads malaria parasites in the region. Tour茅鈥檚 ground-breaking discovery has been to explain how mosquitoes from the same species, which appear identical, can live in such contrasting habitats and behave so differently, transmitting parasites in some habitats and not in others.
As a graduate student, Tour茅 had suspected that the range of habitats was too broad for a single species. When he was working briefly in Rome with Coluzzi, they tested his hunch. He was right: there are different forms of A. gambiae which will not mate, despite their identical appearance. The difference, it turned out, was in the chromosomes 鈥 suggesting that separate species may be emerging.
Now, Tour茅鈥檚 group is trying to find out why some mosquitoes are more likely than others to be infected with malaria parasites. And they are also keen to learn more about a natural trait 鈥 known as refractoriness 鈥 that prevents the malaria parasites from developing in the insect鈥檚 gut. Like many collaborators in the US and Europe, the team wants to learn how to exploit this trait. 鈥淲e want to isolate the mosquito gene that blocks parasite development,鈥 says Madama Bouar茅, a molecular biologist. The long-term goal is to introduce or manipulate genes in the mosquitoes that would make them refractory during the transmission period 鈥 so blocking the spread of the parasite. In theory, a 鈥渟eed鈥 population of 鈥渄esigner鈥 mosquitoes could be released into the wild, complete with genetic characteristics that would make them overtake natural mosquito populations and stop malaria in its tracks (see 鈥淢osquitoes that kill malaria鈥, New 杏吧原创, 5 August).
Distant prospect though this might be, much of the centre鈥檚 work is at a more pragmatic level (See 鈥淭he Art and science of staying alive鈥). For example, the researchers are trying to persuade some traditional healers to carry chloroquine in their medicine bags. In the Tuareg region in the north of the country, they are working with village dyers to treat curtains with insecticide.
Although each specialist group focuses on one aspect of the problem, the centre functions as a whole. 鈥淲e even have an anthropologist here,鈥 says Doumbo. Both he and Tour茅 attribute the lab鈥檚 success to a tradition of exacting standards inherited from Ranque. 鈥淗e was tough with his graduate students,鈥 says Doumbo. 鈥淗e told us to come back with a PhD from abroad or he wouldn鈥檛 take us on.鈥 Like Ranque, Tour茅 and Doumbo expect their graduate students to take personal responsibility for their research. 鈥淗ere there are no Sundays or Bank Holidays if there鈥檚 work to he done,鈥 says Doumbo. 鈥淚n Africa, scientists often think that they work for the government. I don鈥檛 work like that. When I come here on a Saturday evening, it鈥檚 not for the government.鈥
When postdocs return from training abroad, they are expected to focus on solving real problems. 鈥淲e don鈥檛 want people to do research on a single protein,鈥 says Doumbo. 鈥淭hat鈥檚 easy, but what use is it to us?鈥 For the postdocs, such as Abdoulaye Djimde, this is not a constraint: the impact of malaria is simply too close. Djimde gave up a successful pharmacy business to concentrate on research after his brother died of malaria. And, recently, when he woke in the night with something burning his skin, he found his baby son, sleeping next to him, running a soaring malarial fever. Luckily he knew what to do to save his son鈥檚 life. 鈥淚n the country, 40 kilometres by donkey cart from a hospital, the child would have died.鈥
In a country where three-quarters of women are illiterate and traditional roles die hard, the few female scientists have had to make sacrifices. 鈥淚 live with my parents here,鈥 says Oumou Niar茅, a biologist at the centre. 鈥淚t鈥檚 difficult to find a husband who understands. But I like what I do. I鈥檇 get bored if I had to stay home all the time. My father is very supportive. But it鈥檚 not easy; I often work from 7 in the morning to 8 at night.鈥
The brain drain is an ever-present threat. 鈥淪alaries in Mali are ridiculous,鈥 says Tour茅. An experienced postdoc can expect to earn at most $200 a month, he says. Access to information is better than in most laboratories in Africa 鈥 there is a decent library with the MedLine database on CD-ROM. Researchers use e-mail to keep in touch with colleagues, using the small satellite provided for African health researchers by SatelLife, a group of American physicians. But conditions are not ideal 鈥 the Equator is so close that there are only two periods in the day when the satellite pass lasts long enough to download and send mail.
Stability is also a luxury. Only four members of the department have secure jobs. The rest are paid from grants. 鈥淲e鈥檙e constantly fighting to get research funding,鈥 says Tour茅, taking time off to grab lunch in his office before he shuts himself away again with Doumbo and Krogstad to finish yet another grant application. Most of the equipment was bought with grants from USAID and international agencies, says Tour茅. And for Bob Gwadz of the NIH, who is responsible for finding the money to support the five-year collaboration between the NIH and the Bamako lab, the availability of good facilities and grants undoubtedly helps to keep Malian scientists. But Tour茅 knows that the lab has earned its place on the map, and that the effort is paying off. Reaching for his now-cold lunch, he smiles and says, 鈥淚 sometimes think it鈥檚 harder in the US to get research money than here.鈥
The art and science of staying alive
BABIES and children in Mali often die because even simple illnesses go untreated. So researchers and doctors at the Malaria Research and Training Centre have set out to train villagers in rural areas in the basics of first aid. They identify the people in the village who can read and then teach them, for instance, how to recognise malaria and how to treat life-threatening diarrhoea.
Now, with the help of a grant from the Self Help programme sponsored through Mali鈥檚 US Embassy, the project has shifted into higher gear by building and stocking village dispensaries. The villages contribute one-third of the cost in the form of labour and local materials, and the embassy provides the rest, including the initial medicines. The dispensaries are intended to be self-sustaining, and villages charge 15 per cent over cost price for the medicines to cover wages and help to buy new drugs.
Many villages have enthusiastically developed the idea. One group of 12 small villages made 5000 mud bricks in a month to build a wall that would keep out grazing animals, so that they could plant orchards, sell the fruit for cash and use the money to sustain the dispensary.
鈥 Uganda is the eighth African country to get a permanent connection to the Internet. Others already hooked up are Algeria, Egypt, Mozambique, South Africa, Tunisia, Zambia and Zimbabwe. Kampala has now been connected to the Net by a satellite link to the US, operated by a company called InfoMail. Until now, e-mail messages from and to Uganda were stored and forwarded daily in batches
鈥 In Nairobi, competition between e-mail service providers is intense. Some four new companies have set up in the past year to offer customers online shopping and, in one case, Reuters wire services. Shem Ochuodho, director of the African Regional Centre for Computing based in Nairobi, wants to see rural schools hooked up to the centre with computers, batteries and a radio link