Imagine that a cheap, easily manufactured drug became available to combat a deadly, highly contagious disease; a disease that burst red blood cells from within and claimed millions of lives each year. Imagine that this drug saved lives. That even poor countries could afford it. Now, imagine that suddenly the drug no longer worked.

Malaria is quickly approaching such a scenario. The malaria parasites have become increasingly resistant to well-established drugs such as chloroquine and other antimalarials, with no other drugs ready to take their place. Dyann Wirth, director of the Harvard Malaria Initiative and professor of tropical public health in the Department of Immunology and Infectious Diseases, is working to create new drugs and, possibly, a vaccine to fight malaria. The Harvard Malaria Initiative recently received a welcome shot in the fiduciary arm.

The Initiative has received $1 million from ExxonMobil to help develop antimalarial drugs and malarial vaccines and to strengthen programs for malaria prevention and treatment in sub-Saharan countries where malaria wreaks havoc. The grant was one of three given by the company to combat the disease. The other two recipients were Medicines for Malaria Venture, a Swiss non-profit foundation, and Roll Back Malaria, a World Health Organization (WHO) program.

The grant is unusual in that it was given by a large corporation with commercial interests in the areas affected by malaria, not by a pharmaceutical company or government. Wirth is hopeful more companies will recognize the impact public health problems have on their workers and resources and commit money to research. The need for funding for antimalarial drugs is particularly acute, said Wirth, as every major pharmaceutical company has shut down its antimalarial drug research programs one by one over the past 15 years to focus on blockbuster drugs.

"The grant signifies a potential new strategy that involves people with economic interests in solving disease epidemics," said Wirth.

The grant will allow the Harvard Malaria Initiative to earnestly launch an antimalarial drug effort based on new knowledge of the parasite and the human genomes, said Wirth.

"This is the first grant we have been given in this area that will include using knowledge gained from the sequencing of the genomes," she said. "We can begin to look for new targets for drug and, perhaps, vaccine development."

The grant will also help establish a training program for students and scientists from developing countries to encourage them to discover drugs and treatments for their home countries.

"Our goal is to transfer as much of the technology to developing countries as is reasonable," said Wirth.

The research will start in Senegal, where the Initiative has ongoing collaborations, and will expand to include Nigeria and Cameroon.

Malaria is a devastating disease. Biting mosquitoes pass along the parasites that cause malaria. Once inside a human, the parasites burrow into the liver, where they reproduce. The increasing army of bugs eventually leaves the liver to take up residence in red blood cells, where they continue to reproduce until the burgeoning red blood cells explode and release the parasites and their related toxins into the bloodstream.

People ill with malaria usually feel as if they have the flu, with fevers, vomiting and body aches. If left untreated, malaria can cause seizures, coma, and death.

And malaria has become an effective grim reaper in Africa, where 90 percent of all malaria-related deaths this year are expected to occur. More than 300 million new cases are expected worldwide in 2001, and more than one million people will die from the disease, of whom the majority will be young children. A child dies of the disease every 30 seconds.

The kicker is that none of them has to die. Malaria is preventable and, unlike so many other diseases, curable, not just treatable. Which is what makes its research so appealing–and at times frustrating. Despite the potential to cure people with malaria, there are more cases of the disease in Africa than at any other time in history. The record-breaking numbers have much to do with the growing resistance of the parasites and mosquitoes to drugs and pesticides.

Explained Wirth, malaria was not always nearly exclusive to developing countries. The United States mounted its own battle with the disease in the 1950s when it was emerging in Tennessee and other states. In fact, the current Centers for Disease Control and Prevention resulted from the federal government’s antimalaria efforts during this time. The disease was curtailed and eventually eradicated in the United States by careful monitoring and treatment, as well as spraying of pesticides to kill mosquitoes.

These same strategies largely failed in Africa, said Wirth, where the climate allowed for long and intense transmission of the disease and where heavy use of insecticides created new generations of mosquitoes resistant to the chemicals. With mosquitoes impervious to killing agents, the parasites could flourish and become resistant to the drugs meant to inhibit them.

"We are now facing a challenge because the traditional antimalarials are no longer really useful in most parts of the world, so that one is faced with using more expensive, less effective drugs to which parasites will also eventually become resistant," said Wirth.

The parasites are adapting to new drugs with increasing and frightening speed. Researchers estimated it took more than a dozen years for the parasites to become resistant to chloroquine. The latest drug didn’t even get out of clinical trials before the parasites learned to evade the treatment.

One novel strategy on which Wirth is working plays out at the molecular level. If scientists can understand how the parasite becomes resistant, then maybe they can block the resistance.

For example, said Wirth, her lab is studying a protein made by the parasite that actually pumps antimalarial drugs out of the cell, stopping the drugs from ever reaching their targets. If this protein can be tampered with, then theoretically, the drugs should be able to reach their targets.

Another strategy is borrowed from the annals of tuberculosis and HIV treatments, using multiple drugs at the same time.

But, Wirth points out, new drugs need to be created so that combinations can be offered, one more reason she is focusing on drug development.

She is keenly aware that any strategy must be useful to the people who need help the most, those in sub-Saharan Africa.

"In the end, the disease will be solved locally," she said. "Anything we do here will have to be translated to what they do in the field. We need to think in terms of what is affordable and do-able."

For more information about the Harvard Malaria Initiative, visit www.hsph.harvard.edu/malaria.