Harvard Malaria Initiative: A Partnership Facing a Deadly Disease

Malaria is a disease that most Americans don't think about often. They don't have to, unless they're traveling to a foreign country where malaria is endemic, for in the US malaria has been almost unknown since 1953. Unlike the rest of us, Dyann Wirth, professor of immunology and infectious disease, spends a great deal of her time thinking about malaria, and about how to stop it.

Wirth directs the Harvard Malaria Initiative, a partnership of academics, governmental agencies, and private companies working to wipe out the disease worldwide. Forty percent of the world's population lives in the more than 100 countries where malaria is spread by the bite of the Anopheles mosquito. The disease, which kills more than 2.7 million people annually, sickens more than 500 million. In some malarial areas, as many as one-third of hospital beds are occupied by sufferers of the disease. Each bout of illness is estimated to cost a working adult 10 productive working days.

The world nearly eradicated malaria once. In the 1950s and early 1960s, international antimalarial efforts stopped just short of success, and now there is more human malaria in the world than at any previous time in history.

Not only is there more malaria than ever before, the parasites that cause the illness are getting harder to kill. They are evolving in response to human attempts to treat the disease, becoming resistant to antimalarial drugs. "Chloroquine was the most efficacious drug we had for malaria," said Wirth, "but within 20 years of its first use, resistant parasites appeared. Another drug, mefloquine, took 20 years to develop, and resistance to it took only five years to appear. If we're in a race to develop new antimalarial drugs faster than the parasites are developing resistance, then we're falling behind and are in danger of losing the race." In this contest, the consequences of loss are deadly. Wirth, however, is not going to concede victory.

The Harvard Malaria Initiative, founded in 1997, builds upon two decades of Wirth's research on the innermost workings of malaria parasites. "This is a new endeavor for our lab in some ways," said Wirth. "We've thoroughly investigated the mechanisms by which the parasites expel antimalarial drugs and change to become drug resistant. What we're doing through this initiative is hurrying to apply this research to the development of new drugs to fight malaria."

The partnership of the initiative is intended to be productive. Wirth explained, "The intent is for this to be beneficial for all involved. Here at the school, we'll be supported in our research, the results of which we'll make available to our pharmaceutical partners. They will produce new antimalarial drugs that we'll use to combat malaria worldwide. In addition, our research will probably enable the production of 'spin-off' drugs, based on the discoveries that we make, that will be useful for cancer and other health problems.

"It's a partnership of complementary specialties. We're geared towards basic research. Pharmaceutical companies are expert in drug production. Most drug companies would be willing to market a new antimalarial drug, but they aren't willing to take the economic risk inherent in trying to discover that drug. In academia, however, that kind of basic research is the norm. By teaming up with pharmaceutical companies, we share the risks and rewards. They hope to make a profit, we hope to advance our knowledge, and we all hope to fight malaria."

The short-term plan is to focus on finding new antimalarials and to continue the work of understanding how the parasites become drug resistant, with the goal of reversing drug resistance. In the further future, Wirth envisions an increasing use of genomics in drug discovery: "The genome of the Plasmodium falciparum parasite, the microbe that causes the most serious of the world's malaria, are being sequenced. Understanding the genetic constitution of the parasite holds a great potential for the identification of new targets for antimalarial drugs. As we pursue the genomic aspects of malaria research, we also hope to increase our collaborations with other researchers and laboratories at HSPH and throughout Harvard."

The Harvard Malaria Initiative provides researchers and drug developers new opportunities to rid the world of this ancient foe. "The disease is worse today than at any time in history," said Wirth. "And that's frustrating. Yet we know much more about the organism, and we're much more advanced in being able to develop interventions than ever before. Now is the time for us take concerted action and fight back against malaria."

-- See also coverage from Harvard University Gazette, January 28, 1999.

Dyann Wirth, director of the Harvard Malaria Initiative, has been elected as this year's president of the American Society of Tropical Medicine and Hygiene.

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