Human malaria parasites develop in two ways in the red blood cells of an infected person. Most of them undergo repeated asexual cycles of multiplication in which a single small form called a merozoite invades a red cell, grows, and divides within it to form 10 to 20 daughter merozoites within a 48-hour period. These escape from the now-destroyed host cell and invade new red cells. This cycle is responsible for the disease. A small proportion of merozoites, after invading a red cell, develop into altogether different forms--the male and female gametocytes. These are the forms that will infect a mosquito and hence are responsible for the transmission of the infection in nature.

Two aspects of the biology of malaria parasites are under study by Trager, Williams, and Gill. Both were made possible by the development in this laboratory of methods for continuous in vitro cultivation of Plasmodium falciparum, most important of the human malaria parasites. The first is concerned with the nature of the dependence of the parasite on its living host cell. Here we have succeeded in obtaining extracellular development in a nonliving medium of a complete asexual cycle from merozoite back to infective merozoites. This shows that neither the complex process of entry into a red cell nor the intactness of the cell is essential to the differentiation and multiplication of a merozoite; rather it is the milieu in which the merozoite finds itself. Analysis of the essential constituents of this milieu becomes possible. We have found that the erythrocyte membrane is essential to the maturation of the parasites; doubling the amount of sonicated membrane in the medium resulted in approximate doubling of the number of parasites that developed. Furthermore, this axenic development occurs in the absence of a parasitophorous membrane. This membrane is formed when a merozoite enters an erythrocyte and is derived in part from invaginated erythrocyte plasma membrane. We are in a position to begin investigating the functions of this membrane, not at present understood.

The second aspect deals with what triggers the gametocyte pathway of development. Since it is known that a single merozoite can give rise in its offspring to male and female gametocytes as well as the asexual forms, there must be some environmental cue. We have found enhanced gametocyte formation in vitro in young erythrocytes, a finding that fits well the long-known presence of newly formed gametocytes in the bone marrow of infected people. This finding may lead to clues as to the nature of the cellular trigger for gametocyte formation.

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