Chicago Tribune: Gene map may help conquer malaria

by Ronald Kotulak

An international team of 124 scientists has cracked the genetic code of the world’s most feared insect: the mosquito that transmits the deadly and debilitating disease malaria, killing 3 million people every year.p. Delivering a scientific one-two punch, a second team of more than 50 researchers has deciphered the genetic makeup of the parasite that the mosquito injects into humans, causing malaria.

While years of hard work still remain before new prevention methods, treatments and cures are developed, the reports represent a major turning point in mankind’s war on disease.

For the first time, science’s awesome new power to decipher an organism’s genetic makeup and to manipulate its most fundamental genetic functions is being focused on a huge public health problem.

“All new ways of controlling disease are based on new knowledge,” said biologist Frank H. Collins, a mosquito expert at the University of Notre Dame and a member of the mosquito sequencing team. “This project will generate an extremely rapid acceleration of knowledge in the areas of mosquitoes and the germs they transmit.”

The discoveries reported Wednesday in the journals Science and Nature could also lead to the control of other mosquito-borne diseases, such as West Nile virus, St. Louis encephalitis, dengue, filariasis and yellow fever.

Genetic sequencing

To find an organism’s genes, scientists sequence genetic building blocks, chemicals called nucleotides. There are four of these nucleotide bases—adenine, thymine, cytosine and guanine, or A, T, C and G—and the way they are arranged in sequence determines what kind of genes they will be.

In the Science paper, the team headed by Robert Holt of Celera Genomics, Rockville, Md., used the same equipment to sequence the mosquito genome that it developed to help decipher the human genome 21 months ago.

They found that the Anopheles gambiae mosquito’s genome contained 278 million nucleotide base pairs representing 13,683 genes, a number that is likely to change somewhat as genetic analysis becomes more refined.

Scientists headed by Malcolm Gardner of The Institute for Genomic Research, Rockville, Md., reported in Nature that the malaria parasite genome was made up of 23 million base pairs representing 5,279 genes.

By contrast, the human genome contains 3 billion base pairs. The vast majority of these sequences are inactive, thought to be left over from billions of years of evolution.

“This is a dramatic example of the extraordinary coming of age of microbial and vector [mosquito] sequencing and the important impact that this potentially will have on the genetic approach toward one of the most important diseases of mankind,” said Dr. Anthony Fauchi, director of the National Institute on Allergy and Infectious Diseases.

“It opens up a door that you would not have imagined could have been opened up a few years ago,” he said.

Scientists already are working on ways to use the newly discovered genes of the mosquito and parasite to develop effective insecticides, repellants, mosquito and malaria vaccines, and cures.

“Malaria in Africa is on the rise, as malaria parasites have developed resistance to anti-malarial drugs and mosquitoes have developed resistance to insecticides,” said Don Kennedy, editor in chief of Science.

Building resistance

Malaria was nearly wiped out several decades ago through intensive insecticide spraying programs and chloroquine, a drug that was highly effective in combating the disease. Chloroquine was massively distributed around the globe, and some countries even added it to their salt supplies.

But the mosquito evolved genes that made it resistant to such pest poisons as DDT, and the malaria parasite did the same against chloroquine. Malaria made a raging comeback, becoming one of the world’s top three killers, along with AIDS and tuberculosis. More than 500 million people are infected with malaria, mostly in sub-Saharan Africa.

“Knowing the mosquito genome may help researchers identify genes involved in the insect’s ability to host the parasite, or to locate a human to infect,” Kennedy said.

One of the prime targets scientists are focusing on is the group of genes that enables mosquitoes to detect specific human odors from a distance and to use them as beacons to zero in on their unwary hosts. A repellant that blocks that critical sense of smell would deprive the malaria-causing mosquito of its main source of blood.

Hugh Robertson, a member of the mosquito genome team and an entomologist at the University of Illinois at Urbana-Champaign, has found several smell and taste receptors on Anopheles gambiae.

“We know the mosquitoes can detect a whole bunch of chemicals that we humans release whether we like it or not, such as carbon dioxide and lactic acid,” Robertson said. “We don’t have a choice; we release them, and they take advantage of that.”

Other targets include genes that have made the mosquito and parasite resistant to chemicals and drugs, and genes that help the parasite evade the human immune system.

Anopheles gambiae is a special mosquito: It is the only one that thrives almost exclusively on human blood.

The malaria parasite piggybacks on the mosquito’s penchant for people. It is transmitted from one person to another by mosquitoes in search of blood for each new batch of eggs.

Inside a new victim the parasites infect red blood cells and multiply to the point at which the cell bursts and dies, and then they spread to other cells.

Severe anemia occurs as blood cells are depleted. The parasite also causes blood to coagulate, blocking small blood vessels. When vessels in the brain are cut off, death often ensues. More than 1 million children die of malaria each year.

OCT. 3, 2002

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