May 17, 2003 

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Malaria Milestone (video)
October 02, 2002

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Interviewee: Frank Collins, University of Notre Dame.

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Produced by Joyce Gramza

Copyright © ScienCentral, Inc., with additional footage from the Walter and Eliza Hall Institute, TIGR, University of Notre Dame, and ABC News.

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It's a problem that dwarfs America's concern over West Nile Virus. The mosquito-borne disease malaria kills millions of the world's children every year.

As this ScienCentral News video reports, scientists announced a major milestone in the fight against the killer disease.

Worldwide effort

The coinciding publication of the two most important malaria genomes represents the work of hundreds of scientists around the world.

In 1996, researchers led by Malcolm Gardner of The Institute for Genome Research (TIGR) set out to sequence the genome of the malaria parasite, Plasmodium falciparum , with funding from the US Department of Defense, the Wellcome Trust and the National Institutes of Health (NIH). The completed genome, the genome of the related rodent parasite Plasmodium yoelii and research papers from several years of analysis are published in the journal Nature.

The genome sequencing of the major mosquito vector of malaria, Anopheles gambiae, began little more than a year ago. The project was led by Frank Collins, professor of biological sciences at the University of Notre Dame, and funded by the French government and the National Institute on Allergy and Infectious Diseases. The A. gambiae genome is published in the journal Science.

The actual Anopheles genome sequencing work at Celera Genomics took "on the order of six weeks to two months," Collins says. The aggressive pace of the effort testifies to both rapid advances in genome sequencing strategies and technology, and the development of an international consortium to fight malaria with genomics.

The online genome databases are already being mined by malaria researchers, and Gardner says five or six new drug targets have already been identified in P. faliciparum.

More from our interview with Frank Collins:

In the scheme of things, West Nile transmission in the United States is still a relatively small source of illness and death. That's not to minimize the importance of this problem to people who are potentially at risk... But malaria, and the people who die from malaria—that's occurring on a scale that absolutely dwarfs what's occurring with West Nile virus. We're talking about well in excess of a million people a year die of malaria.

Malaria is a big public health problem, unfortunately it's a public health problem that's killing people that we don't really bump into very often—they're all living in the poor areas of the tropics that we don't see. But these are people too! These are often very, very small children and infants that are dying.

One of the things that I've noticed—not only as a malaria researcher, somebody who's had a chance to go to the field, but also as a person who's had a lot of opportunities to take students and young post-doctoral fellows with me to the field—is that you can't go into a setting in rural Africa where you actually see malaria transmission occurring and where you can actually see sick infants and young children in the houses, you can't go there and work on malaria and not come back really energized. I mean, those experiences are life-transforming. All of a sudden that exercise in the lab that may have attracted you to graduate school becomes something that's a real-world problem and one that's really deserving of attention.

Second insect sequenced

This is only the second insect genome to be sequenced. I think it represents a major concern on the part of the funding agencies, particularly [the National Institutes of Health], to begin to look not only at major biological models, like mouse and rat and C. elegans ... but also to look at organisms that are of real importance in terms of human welfare and human health. I think it really says something about priorities that is really encouraging to me, that we see the second insect genome to be sequenced is an insect that's involved in causing a large amount of human disease and death in this world.

Obviously the completion of the second insect genome is going to have an enormous amount of benefit to people who work on insects in general. Remember that with the completion of the Drosophila melanogaster genome a couple of years ago, the discovery that this genome had about a little less than between 15 and 20 thousand genes, a large number of those genes had no known function. We're still dealing with a blueprint about which we still don't know a lot. There are a lot of lines and numbers on these pages that don't really mean anything yet.

A large number of those unknown genes in drosophila have been actually found to have counterparts in the mosquito. The knowledge of those counterparts will help in, I think, more rapidly enabling people to figure out what these unknown genes do. But then again there are sets of genes that are unique to these organisms, so there are genes in Anopheles gambiae that don't seem to have any counterpart in drosophila. These are probably going to be very interesting, some of them at least. They may be genes that are doing things for the mosquito that give it its unique characteristics, many of which we are most concerned about because it's a great transmitter of malaria. Some of these genes are probably involved in determining how the mosquito finds people... There are lots of clues that are going to lead people rapidly in many different directions.

Rapid applications

The primary tools of importance today in the control of malaria—at least tools that are targeted at the mosquito—are those that relate to use of insecticides. In fact, the major strategy that the World Health Organization is advocating for most countries where malaria remains endemic is to use insecticide impregnated bed nets. Unfortunately there are a relatively small number of insecticides that can be used in something like a bed net because of the continuous exposure of the individual sleeping under the net to the insecticide. I mean, a daily exposure of upwards of eight hours a day is something you don't do with every insecticide. So, unfortunately, the class of insecticides that are being used in bed nets is one to which the mosquito Anopheles gambiae and a number of other malaria vectors in the world are rapidly developing resistance. It's clear that this strategy, while valuable, is probably going to be of time-limited utility because of the emergence of resistance.

I think probably the most immediate practical application of knowing the Anopheles gambiae genome is to advance work that is already underway on... the mechanism by which Anopheles gambiae is becoming resistant to the insecticides used in bed nets. The availability of this genome will rapidly speed that up. I'd be astonished if within a matter of a year we don't have a very good handle on what Anopheles gambiae has done to make it resistant to the insecticides used in bed nets. That's going to be information that should rapidly translate into some new way of control that sort of circumvents the emergence of this resistance.

But perhaps even more important, it's something we can use to identify new insecticide targets. We can imagine finding biochemical pathways that are found in mosquitoes that are unique to mosquitoes—not found, for example, in human hosts or other animals that we wouldn't want insecticides to affect. The genome information can give opportunities for the development of rational insecticide design strategies that start off with specific targets in mind, as opposed to sort of the traditional technique for identifying insecticides, which has largely been a kind of random screening approach.

There are a couple of groups working on trying to understand why Anopheles gambiae wants to take its blood meals from people. It basically smells people and goes after them. People are trying to figure out what it is that this mosquito is smelling, how is it doing it—with the idea of being able to use this information to devise strategies that interfere with this process. A very, very targeted control strategy that may affect only Anopheles gambiae and nothing else.

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