http://www.boston.com/dailyglobe2/345/science/Looking_for_the_genetic_roots_of_a_killer+.shtml

Looking for the genetic roots of a killer

By Nick Thompson, Globe Correspondent, 12/11/2001

Luck rarely seems to shine on the people of Burkina Faso. They live in a landlocked African country with a per-capita income of less than a dollar a day, barren land, and warring neighbors. Formerly called Upper Volta, military strongman Thomas Sankara renamed the country in 1984 to a phrase meaning land of the good-natured people.

Not long thereafter, Sankara was murdered by his close friend, Blaise Compaore, the country's current dictator.

But, amid the turmoil and poverty, the people of Burkina Faso may have something that the rest of the world wants and desperately needs - a gene that thwarts malaria.

One out of every 10 people in Burkina Faso has a gene that significantly reduces the risk of dying from the mosquito-borne blood disorder, according to a team of Italian researchers led by David Modiano of the University of Rome La Sapienza.

The discovery might help scientists make a vaccine that could potentially save millions of lives a year: Just last year, the 2 million to 3 million Africans who lost their lives to malaria exceeded, by a factor of four, the total number of Americans killed abroad in combat in this country's history.

And, because better health often leads to more wealth, some analysts say a cure for malaria could also help lift Africa out of its economic morass.

That might be a good thing for more than just Africans, many specialists say. Jeffrey Sachs, a Harvard economist who has made combating malaria a keystone to his campaign for global economic health, said, ''As Sept. 11 demonstrated, we are so interconnected in our fates that we can't truly believe that we can let impoverishment fester in different parts of the world and remain safe.''

Malaria enters a person's body when a female anopheles mosquito, often called a ''flying syringe,'' bites through a person's skin, injecting saliva full of tiny parasites called malaria sporozoites. These sporozoites then make a quick beeline for the liver. Once inside the liver, safe from the body's immune system, the sporozoites multiply and morph into what are called merozoites over the next week or two. These new demons then bust out of the liver and hunt down the red blood cells that transport oxygen through our bodies.

The malaria merozoites gradually digest the hemoglobin in the red blood cells over the course of a couple of days, multiplying rapidly as they feast. Once they have consumed nearly the entire red blood cell, about 25 malaria merozoites break out, and repeat the cycle. Each time they break out, the merozoites can cause massive fevers, throbbing headaches, and chills. Meanwhile, when a mosquito dines on the infected person, the mosquito sucks up the parasite and turns itself into yet another deadly flying syringe.

Malaria is a clever disease that has bedeviled leading scientists for a century. Because red blood cells are less sophisticated than most cells - they're basically bags of hemoglobin with no DNA - they can't signal the body's immune system that they've been invaded, giving the disease protection. The most obvious way for humans to counterpunch against malaria involves simply zapping all the mosquitoes with pesticide. The most successful eradication effort occurred in the late 1950s when health officials sprayed DDT throughout much of the developing world. That tactic, however, came to a near halt in the '60s, both because the parasites had started to mutate, rendering DDT less effective, and because Rachel Carson published her ground-breaking work, ''Silent Spring,'' which described the way DDT killed songbirds.

A second strategy has helped minimize malaria in the United States since the mid-20th century: Draining the swamps where mosquitoes lay their eggs, outfitting every house with screen doors, building mosquito nets above beds to protect potential victims during the night when malarial mosquitoes most like to prey.

But screen doors, nets, and drainage projects cost too much money for many countries. One of the best, and most cost-effective ways, to combat malaria consists of coating bed nets in a safe pesticide. But, at an estimated $5 an application, even this can overwhelm countries with annual national spending on health care as low as a dollar per person.

Population growth in the Third World merely adds to the problem. Mosquitoes thrive in chaos and areas where the ecosystem hasn't found its balance of predators, prey, and stable niches. A tire track left by a tank, or even a boot, that fill with water make great places to lay eggs and prosper, as does the edge of a recently chopped-down forest.

''Disturbances are great for pesky nuisance species such as mosquitoes,'' said Paul Epstein, associate director of Harvard Medical School's Center for Health and the Global Environment.

As a result, most scientific effort right now is focused on finding a vaccine. Existing drugs such as Malarone or Larium can provide temporary immunity to travelers, but most Africans can't afford them and don't want to take them every day in perpetuity. That's why the Italian researchers' finding of hereditary immunity in Burkina Faso just published in Nature could prove an important break. According to Rick Fairhurst, a malaria researcher at the National Institutes of Health, it shows that somehow Mother Nature was able to protect up to 90 percent of the population in one area by mutating a single amino acid.

The trick, of course, is finding out how the protection works. Right now researchers just know that people in Burkina Faso with a rare kind of hemoglobin can resist malaria, even if no one knows exactly why. Researchers also can't say for sure why that mutation hasn't spread throughout the continent. After all, Africans with the mutated form of hemoglobin should pass their genes down through generations with much greater frequency. Perhaps the people in the particular ethnic group in Burkina Faso with the mutation are simply too isolated from the rest of the continent; perhaps something bad comes paired with the mutation. For example, another African genetic mutation guards against malaria at the same time that it dramatically increases the risk of deadly sickle-cell anemia.

But regardless of what scientists can learn about this genetic mutation, some new breakthrough seems increasingly possible. Ten years ago, researchers essentially neglected malaria - the NIH only spent $10 million on malaria compared to, for example, $1 billion on AIDS. Now malaria spending has advanced because of a confluence of factors, including increased charitable giving and scientific budgets, as well as growing recognition that poverty can threaten national security. The NIH's malaria budget has shot up, and the World Bank, World Health Organization, and private foundations now pour hundreds of millions of dollars into research.

Nonetheless, malaria still mainly affects poor people, a fact that dramatically hinders research. About 1,000 people contract malaria each year in the United States, but almost all caught it overseas. Of the few mosquito species that transmit malaria, by far the most dangerous live in Africa.

As a result, with all the disease concentrated abroad, American drug companies have stayed mostly on the sidelines, forcing publicly funded scientists to do almost all of the work.

''We've come up with a lot of vaccines in this laboratory,'' said Louis Miller, who runs the malaria laboratories at the NIH's National Institute of Allergy and Infectious Diseases. ''But it's usually in collaboration with small biotechnology companies and, let me put it this way, industry is run by people who have to make a living and who are beholden to their stockholders. They can't take on a problem that won't return a high profit to them.''

Not only does that limit hope for eradicating the disease, but the finances also may have created a self-fulfilling cycle. Industry can't work to cure malaria because of the poverty in infested countries. And this poverty stems in no small part from the malaria infestation itself.

According to Sachs, pervasive malaria can reduce a country's economic growth by about 1.3 percent annually, a number that can have a colossal impact in the long run, even when compared to other factors such as market openness and political democracy.

Few factors have played such a large role in blocking economic development as has malaria, Sachs said.

Sachs, of course, noted that malaria may correlate with poverty to an extent simply because rich countries can combat it. But, Sachs said, malaria impacts wealth more than wealth impacts malaria and he stresses the debilitating effect that malaria can have: Forcing families to have many children so some are likely to survive to adulthood, keeping people from work and possibly causing long-term debilitation, and driving away foreign investment since malaria cripples tourism, kills workers, and impedes trade. For example, developers refused to build the Panama Canal until a massive effort had eradicated malaria from the region.

Some economists, of course, disagree, though mostly about scale. The idea that malaria could reduce GDP growth by as much as 1.3 percent per year is hard to believe, said Sachs' colleague at Harvard, Robert Barro. But Barro does agree that there is evidence that health overall contributes to economic growth.

In fact, one would have to look hard to find someone who wouldn't want to root out malaria, given the moral, economic, and political consequences. The battlefront might last a long time, and the going might be rough, but the anopheles mosquito is a killer that surely deserves to be brought to justice.

-- Anonymous, December 11, 2001