In 1925, Spain’s Catalan Government set up a humble hospital in the Ebro Delta region. The hospital treated patients suffering from malaria. Ildefonso Canicio, a doctor at the hospital, spent decades diagnosing and treating patients. By drawing blood from patients, and placing a drop on a microscope slide, he could determine whether the blood contained Plasmodium, the parasite that causes malaria. Canicio threw away most of his slides, but he kept a few slides from the 1940s. Little did he know that seventy years later, these slides would provide insight into the global migratory patterns of the malaria Plasmodium.
To fight malaria in the present day, researchers are looking to the past to understand how the parasite evolved over time, specifically exploring how human movements transmitted the parasite across the globe. Malaria was successfully eradicated from Europe after World War II. Thus, researchers have had to search for old, badly preserved slides from Europe’s pre-eradication era, hoping to find clues about the now-extinct parasite.
Carles Lalueza-Fox, a paleo-genomics researcher at the Institute of Evolutionary Biology in Barcelona, reached out to Canicio’s family who gave him three slides to analyze. Back at the lab, he quickly realized that analyzing the slides would be difficult. “There were just a few drops of blood in the samples. Once they were extracted and sequenced, they were gone. The slides were fragile and covered with stains and oils,” said Lalueza-Fox.
Despite the fragility and small size of the samples, Lalueza-Fox and his team successfully obtained a huge amount of genetic data from Plasmodium mitochondrial DNA (mtDNA). Unlike nuclear DNA, mtDNA is inherited only from the mother, so it is better suited for determining the maternal lineage and genealogy of a species. “As far as I know, this is the first study where such old slides were used and such an amount of genetic data from the pathogens was retrieved,” Lalueza-Fox added.
Using the reconstructed European Plasmodium mtDNA genomes, Lalueza-Fox and his team shed light on certain controversies surrounding the parasite’s evolutionary history. “It was not clearly understood how the pathogen spread along different continents, because Europe was central to some of these dispersals but no data from Europe was available,” noted Lalueza-Fox.
His team found surprising genetic similarities between European Plasmodium mtDNA and Indian Plasmodium mtDNA. Lalueza-Fox believes that malaria was transmitted from India to Europe when the Persian Empire expanded into India in the sixth century BCE. The team also found evidence that European, Central American, and South American parasites are genetically similar–indicating that, the exchange of food, plants, culture, technology, and, of course, disease between the Old World and the Americas in the fifteenth and sixteenth centuries may have helped spread malaria.
Lalueza-Fox is now attempting to construct the nuclear genome of the European Plasmodium parasite. “So far, we have about 40 percent of the nuclear genome of the P. falciparum. I reckon we need four or five more slides,” Lalueza-Fox said. In Lalueza-Fox’s opinion, understanding the nature of parasites from one hundred years ago is critical for understanding the resistance of modern parasites to treatment. His team will continue to search for the missing pieces of the Plasmodium “puzzle,” researching the extinct parasite to enhance our understanding of malaria.