BART KNOLS thrusts his arm into a plastic chamber the size of a meat safe.
Immediately a couple of hundred hungry mosquitoes trapped inside smell his blood
and start biting. Welcome to feeding time at Mbita Point, a malaria research
station on the shores of Lake Victoria, Kenya鈥攐ne of the most
malaria-infested places on Earth.
More mosquitoes bite more researchers at Mbita Point than in any other lab on
Earth. But Knols is not worried. These mosquitoes were bred in the laboratory
and are free of the malaria parasite. And just in case anyone picks up the
disease outside鈥攚here half the local population are carriers鈥攅ach
researcher has a personally fed stock of insects for their work. 鈥淚f these
mosquitoes are carrying the malaria parasite, they got it from me,鈥� says
Knols.
Most nights, several of the 16 researchers here lie down with their own
mosquitoes and wait for the biting to begin. The prize is to find new
solutions鈥攑erhaps the ultimate solution鈥攖o one of the world鈥檚 most
lethal, widespread and rapidly growing diseases.
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Forty years ago, a generation of medical crusaders believed they were on the
verge of eradicating malaria for ever. With a blitz of drugs to kill the
parasite and a rain of DDT to wipe out its principal carrier, the
Anopheles mosquito, they thought malaria was well on the way to the dustbin
of medical history. But it wasn鈥檛 to be. The mosquito began to develop
resistance to DDT. And the parasite responsible for most deaths, Plasmodium
falciparum, became resistant to most of the drugs.
Today, the malarial mosquito鈥檚 kingdom is growing again. More than 40 per
cent of the world鈥檚 population live in areas where they are at risk from the
disease. Deforestation and irrigation projects are creating new habitats where
mosquito larvae can flourish. And global warming is taking the disease into
regions that were once too cold. Half a billion people suffer periodic bouts of
malaria fever and the disease kills an estimated 2 million people every
year.
Ecologists such as Knols, whose research station is an outpost of the
Nairobi-based International Centre of Insect Physiology and Ecology, say the
long-term solution lies in probing the lifestyle of the malarial mosquito
itself. 鈥淲hy does it bite humans? Why does it prefer some humans to others?
What, besides human blood, does it eat? What repels it? What triggers swarming
and mating? And, crucially, how can we intervene to disrupt its ability to
infect humans? These are the kinds of questions we urgently need answers to if
we are to outsmart the disease,鈥� says Knols.
His strategy for finding those answers is a unique facility at Mbita Point
called a malariasphere. It comprises a typical African hut, built by local
women, of crude plaster with open eaves and a thatched roof, enclosed within an
old greenhouse that has mosquito netting in place of glass. Inside the
greenhouse, a random collection of weeds grows around the hut, along with some
typical backyard crops such as sweet potato and banana, and a pond. The
malariasphere contains everything a mosquito could want鈥攊ncluding a
volunteer researcher to sleep in the hut and shed blood for the cause.
鈥淓verything is like an African shamba, except that we can control what
mosquitoes are in there,鈥� says Knols. 鈥淎nd of course, we monitor everything.鈥�
Here, over the next three years, Knols hopes to manipulate the environment to
find ways of reducing the number of times his volunteers get bitten during their
night-time vigils. 鈥淚t sounds simple, but it has never been done before,鈥� he
says. 鈥淲hy? Because to medics, mosquitoes are just flying syringes, barely
worthy of research. But to us they are the key to unlocking the malaria
辫谤辞产濒别尘.鈥�
The research world is excited. 鈥淥ur ignorance of the basic biology of
Anopheles gambiae seems nearly encyclopedic,鈥� says Ellis McKenzie, an
applied biologist at Harvard. 鈥淏art has come up with an experimental environment
that is sufficiently controlled but sufficiently realistic to serve as a factory
for insights.鈥� The US government鈥檚 National Institutes of 午夜福利1000集合 (NIH) also
supports the project generously and has devoted $2.7 million to it.
The first full run of the enclosed malariasphere was completed in April this
year. It comprised 27 days鈥攍ong enough to cover a complete mosquito life
cycle. 鈥淲e introduced blood-fed female mosquitoes on day 1,鈥� says Knols. 鈥淏y day
3 they had laid eggs on the pond; on day 5 we had larvae. The first adult
mosquitoes appeared on day 11. On day 17 a volunteer researcher, Basilio Njiri,
went in and stayed for four nights. On day 22 we had the first of the new
generation of eggs being laid.鈥�
The second run is now under way, and this time the researchers released 1000
eggs in two sites, to see how they develop into biting females. 鈥淚 don鈥檛 think
anyone in the world has ever been able to do this and we鈥檙e very excited about
it,鈥� says Knols. He hopes to find out how larval densities affect the numbers of
transmitting females, allowing them to predict outbreaks of malaria transmission
before thousands of biting insects emerge.
And already the researchers have uncovered a few surprises about the precise
timing of each stage in the insect鈥檚 life. This is exactly the sort of
information Knols needs. He believes that there may be a chance to intervene at
each stage of the life cycle (see Diagram).
A vital phase may last only a few hours during one night,
when a newly adult female finds a mate鈥攇enerally
by locating male swarms at dusk鈥攁nd then homes in on a good source of
blood to provide the protein needed for her eggs to grow. Or it might have to
include the next three days when, gorged on human blood, she will rest, usually
on the indoor walls of her victim鈥檚 hut, before heading off to find a pond on
which to lay her eggs.
There are already ways to disrupt these activities. Draping mosquito nets
around people鈥檚 beds stops the insects biting, and spraying hut walls with
insecticide may kill the resting female before she can lay her eggs. But the
malariasphere experiments should uncover other potential interventions.
The World 午夜福利1000集合 Organization has put all its money on bed nets. WHO believes
that its recently launched 鈥淩oll back malaria鈥� campaign could save half a
million lives a year. Its aim is that, within a decade, every child in Africa
will go to bed protected by a net impregnated with the pesticide
pyrethrin鈥� a chemical widely used in the rich world to fight head
lice.
But sceptics, including Knols, say the strategy will probably fail. Some
doctors worry that by reducing exposure to the parasite among the very young,
bed nets could reduce the build-up of natural resistance, and end up killing
more children. Many ecologists believe mosquitoes will change their behaviour to
get round the use of nets. 鈥淎t the moment the insects bite at night. But if the
nets were widely used, you would soon get behavioural selection. Insects that
bit earlier, or in the morning, would have an advantage,鈥� says Knols.
As well as this, resistance to pyrethrin is spreading fast, in parts of
French-speaking West Africa in particular. 鈥淲e seem to have learned very little
from the DDT story,鈥� says Knols. What is required for long-term success, says
Knols, is to fight the disease on a much broader front, combining all the tools
to hand. That might mean using bed nets and traps as well as making improvements
to the huts, perhaps by closing the traditional open eaves, and developing
biocontrol methods to attack larvae and adult flies.
The key, Knols says, may even lie outside the hut鈥攂eyond the reach of
wall-spraying and bed nets. 鈥淗ow do the females locate the male swarms? We don鈥檛
know. But maybe we could use pheromones to disrupt them.鈥� Both males and females
feed on nectar鈥攖he males exclusively and the females when they are not
gorging on blood. But which flowers? And does the location of the flowers
influence where the mosquitoes live and which huts they invade? 鈥淎gain, we know
very little about all this. But if we could set nectar traps, we might be able
to infect the mosquitoes with a fungus to kill or sterilise them.鈥�
Resistance is useless
Another innovative ecological idea is using natural products to kill larvae
on breeding ponds. Oil from the neem tree, for instance, seems to reduce the
number of larvae. And Knol鈥檚 team is testing a bacterium鈥擝acillus
sphaericus鈥攖hat seems to have a similar effect. 鈥淲e have to find
alternatives to the chemical pesticides that mosquitoes are growing resistant
to, or which like DDT are horribly toxic,鈥� he says. 鈥淣atural pesticides seem to
work better. If you use a plant you expose the mosquito to perhaps 25 compounds,
so it is far less easy for the insect to develop resistance.鈥�
Another approach is to prevent the mosquitoes getting into the houses, where
they are most likely to bite. Burning mosquito coils in the hut is an old
standby. There is also a long, though half-forgotten tradition of using certain
plants to repel the insects, either by planting them near the hut or burning
them to release repellent fumes. 鈥淲e want to tie down and improve on what people
have always done. If we find out the plants that work, we should be able to make
mosquito-repellent mixtures. Householders could make them for themselves. One
idea is for local maize refineries to install a simple steam distiller, so that
whenever farmers go to the mill, they could take a plant and come home with a
jar of repellent.鈥�
But first the most effective plants have to be found. An Ethiopian
researcher, Aklilu Seyoum, is reviving an old Mbita Point herb garden that
contains a host of mosquito-repellers. He intends to find out how much of an
effect this kind of plant has on mosquitoes鈥� biting rates. 鈥淲e asked the local
community what they used and collected 19 plants on the basis of what they said.
We distilled them to get the essential oils and put the oils on our skins in the
lab to see how the insects reacted,鈥� he says. One plant, collected by Swiss
researcher Barbara Frei from the slopes of Mount Kenya while she was working for
the centre, looks so promising that she is working with a European
pharmaceuticals company to turn it into a commercial product.
鈥淚t certainly works better than DEET,鈥� says Knols, referring to the
insect-repellent developed by the US government half a century ago and still
used by millions of tourists every year. Although the packets of the standard 10
per cent diethyl toluamide formation say it can ward off mosquitoes for eight
hours, Knols reckons that against African insects in their natural surroundings
it is typically effective for less than 15 minutes.
Better repellent compounds could be complemented by chemicals to attract
mosquitoes away from houses. In one ingenious rig next to the malariasphere,
researcher Richard Mukabana has three people sleeping at a time, each in their
own separate wing of a tent. He introduces mosquitoes to the middle segment of
the tent, where fans suck in air from the three wings. In this mosquito version
of Blind Date, the insects get to choose who attracts them most before
they head off looking for blood. As they do so, they are trapped in nets and
counted. As the tent鈥檚 guest list grows, Mukabana expects to build up a detailed
picture of what attracts the mosquitoes and why. 鈥淲e are pretty certain odours
are the key,鈥� he says.
The next step will be to deconstruct the human. 鈥淲e might put in a heater to
see if temperature matters, or a cylinder of carbon dioxide to simulate exhaled
breath.鈥� Scientists should soon have some answers to every camper鈥檚 question:
why do mosquitoes always seem to head for one inhabitant of a tent? And how do
you choose your sleeping partner to ensure a bite-free night? They might even
come up with a chemical substitute for an attractive bedmate, in the form of an
odour trap (see 鈥淭he cheesy feet challenge鈥�). One other thing Knols
would like to know is whether the parasite releases any sign of its infection,
so that carriers of the disease are any more or less attractive to
mosquitoes.
One day, he says, he would like to start working with mosquitoes infected
with malaria parasites. But that raises ethical issues. The NIH refuses to fund
research that includes volunteers or researchers being bitten by
malaria-carrying mosquitoes. The WHO will, but only under strict rules of no
added risk鈥� something that would be impossible to argue is the case in the
confines of the malariasphere.
Another aim for the future is to scale up the work. The NIH wants
village-size malariaspheres. But Knols has even bigger plans. Lake Victoria is
dotted with islands, some occupied and others not. Each has its own largely
self-contained mosquito population. He wants to turn one or more of these
islands into a giant malariasphere, and is already collecting baseline data on
the mosquito population of nearby Ngode Island in preparation.
Overambitious? Surely not, says Knols. Around the shores of Lake Victoria
almost every adult carries the parasite and across Africa huge numbers of
children are dying of the disease. Without a real breakthrough, the outlook is
bleak indeed. Malaria research worldwide is chronically underfunded. 鈥淎 thousand
times more is spent on AIDS research than malaria research,鈥� he points out.
鈥淔lorida and California alone spend more on controlling mosquitoes that are
merely a nuisance and pose no health threat, than is spent globally on malaria
谤别蝉别补谤肠丑.鈥�
DILIGENT readers of New Scientist will have come across Bart Knols
before. Five years ago his smelly feet made news. As a graduate student at
Wageningen Agricultural University in the Netherlands, he sat in his underwear
beneath a net while mosquitoes were allowed in one at a time to bite him. The
insects headed straight for his feet鈥攗ntil he washed them. Then he brought
in a pungent cheese that smelt like his unwashed feet鈥攁 Limburger. Just
like his feet, the cheese attracted the hungry insects. It turned out that both
nourished bacteria that produced similar fatty acids to which the mosquitoes
were partial.
This feet-first research led to the idea of an odour trap to keep mosquitoes
away from humans. A large European pharmaceuticals company has since patented
the idea, using an extract from a different cheese as a trap. 鈥淭he two cheeses
smell very similar,鈥� says Knols, who admits to missing a trick by failing to
patent his trap. He now sees odour traps as just one of the many potential
innovative solutions to the malaria problem under test at Mbita Point.