February 28, 2000
Volume 52, No. 23
Unraveling malaria: the parasitic 'work of art'
By Poul Olson
From an evolutionary perspective, the malaria parasite is a work of art.
After entering the body from a mosquito's salivary glands, the parasite travels to the nutrient-rich environment of the liver, where it multiplies precipitously. Bursting into the bloodstream, thousands of the single-celled organisms called merozoites begin taking over red blood cells and consuming their hemoglobin. As the victim lies feverish in the final stage of the disease, the parasite waits to hitch a ride inside a new mosquito to infect its next victim.
Malaria has long been a scourge of mankind. Almost half of the world's population, living mostly in tropical regions, is at risk for the disease, which kills an estimated 1 million to 3 million people a year.
To the casual observer, Plasmodium, the protozoan organism that causes malaria, may appear deceptively simple. But to scientists who study it--four species of Plasmodium exist in humans--the organism is an enigma consisting of a complex array of some 6,000 genes, only a few of which are understood.
In the past few years, several global initiatives have been launched to develop a vaccine. The University's Vaccine Research Center joined the effort last year with a dedicated malaria research program led by Mary Galinski, an affiliate scientist at Yerkes and a faculty member in the Department of Medicine's infectious diseases division.
With a growing international research team soon to number 10 associates and students, Galinski is hoping to answer some of the fundamental questions about malaria. Of particular interest is decoding Plasmodium's ability to elude the body's immune response by turning a special group of related "variant" genes on and off through a process called antigenic variation. Related studies will examine immune responses to malaria in humans and in primate models, as well as attempt to explain how the parasite evolves and adapts in its hosts.
Galinski came to the Vaccine Research Center in December 1998 after 10 years at the New York University Medical Center. Much of her research, which is largely funded by two grants from the National Institutes of Health, has been focused on simian malaria model systems and studies on the two most dominant species of malaria, P. falciparum and P. vivax.
Because it cannot be cultured, P. vivax is especially difficult to study. Instead, blood must be drawn from an infected host-a challenge Yerkes is uniquely well-suited to meet.
Galinski and her husband, John Barnwell, a parasitologist at the Centers for Disease Control and Prevention and a Yerkes affiliate scientist, are among a handful of scientists in the world who study P. vivax intensively. One of their biggest discoveries in this area has been to identify a specialized protein binding complex that both species are predicted to utilize to attach to their host red blood cells. But despite the progress toward a vaccine--Galinski and her team are in the midst of their first experimental vaccine trial in collaboration with the U.S. Navy and a corporate partner--she said many complexities remain unanswered.
"An organism that can have 50 copies of the same gene to produce a single protein has a distinct evolutionary advantage for survival," she said. "We are bound to learn more of the parasite's tricks in coming years. But to make an effective vaccine may require an entirely new paradigm."
Central to Galinski's malaria research program are Yerkes' primates. "Simian models teach us a lot about the disease as a whole and how it manifests in humans," Galinski said. "All of our work with the primates is very important for building a malaria vaccine program here."
For her part, Galinski is collaborating on assorted projects with scientists around the world and continues her active involvement in the Malaria Foundation International (www.malaria.org), which she established in 1992 to increase support for research on the disease.
As global efforts expand to coordinate malaria research and funding, Galinski predicted that the Yerkes malaria program will play an increasingly central role.
She is particularly hopeful of the new research avenues that will open after the genome is sequenced for Plasmodium.
"Knowing the genome of Plasmodium," said Galinski, "is going to save a huge amount of time in identifying genes and may put us in an entirely different place 10 years from now. We are moving from a one-gene-at-a-time approach to having all 6,000 pieces of the Plasmodium puzzle in front of us. The challenge will be to sort through this massive array of information."