The Viral Storm

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Authors: Nathan Wolfe
malaria of orangutans in Borneo, I’d had the good fortune to spend a year working with some of the world’s foremost experts on malaria evolution at the CDC in Atlanta. There I had the luxury of spending afternoons with Bill Collins, perhaps the world’s greatest expert on the malaria parasites of primates, discussing how malaria might have originated. Among the prominent themes of our chats was the importance of wild apes.
    At the time, we knew that wild apes had a number of seemingly distinct malaria parasites. One of them was particularly intriguing. Plasmodium reichenowi was named after a famous German parasitologist, Eduard Reichenow, who had first documented the parasites in chimpanzees and gorillas in central Africa. Reichenow and his contemporaries saw a number of these particular parasites, collector’s items for the German researcher, and correctly identified them through examination by microscope as closely related to our own Plasmodium falciparum . In the 1990s, during my time at the CDC, molecular techniques were paving the way to detailed examination of these parasites, allowing us to compare them accurately to our own parasites and providing much greater evolutionary resolution than a microscope could ever offer. Sadly, all of the parasites of Reichenow’s time had been lost, and all that remained was a single lone specimen.
    Initial work with this lone P. reichenowi parasite showed that in fact it was the closest of the many primate malarias to our own deadly human malaria, P. falciparum . Yet with only a single specimen, it remained impossible to say much about the origins of these parasites. Perhaps, long ago, the common ancestor had a parasite that over millions of years had gradually evolved into distinct lineages of P. reichenowi and P. falciparum , a hypothesis favored by some at the time. Or perhaps the ape parasite simply resulted from the transmission of the common human parasite to wild apes at some point in fairly recent evolutionary history. A third possibility, neglected by most considering the huge number of humans and the incredible proliferation of P. falciparum among them compared to the existence of only a few dozen known parasites in apes, was that perhaps P. falciparum was in fact an ape parasite that had moved over to human populations.
    Bill and I understood that to truly address the evolutionary history of these parasites we’d need to get more samples from wild apes, ideally many. As a young doctoral student, I was ambitious yet still naïve about the difficulties associated with getting these kinds of samples. But I promised Bill I’d do it and set about planning ways to sample apes in the wild.
    Unbeknownst to me at the time, I was about to be called away by my soon-to-be postdoctoral mentor Don Burke to conduct research in Cameroon. I was unaware at the time that I’d spend nearly five years establishing a long-term infectious-disease-monitoring site there in Cameroon. Eventually, though, I did follow through on my promise to Bill and got those ape samples. Ultimately, in collaboration with sanctuaries in Cameroon that helped to provide homes to orphan chimpanzees, we discovered that ape malaria parasites were not as uncommon as people had suspected. By teaming up with Fabian Leendertz, a veterinary virologist who had done similar work in the Ivory Coast, molecular parasitologist Steve Rich, and the legendary evolutionary biologist Francisco Ayala, we took an important step toward cracking the origin of this disease.
    Together we were able to compare the genes in hundreds of human P. falciparum samples that already existed with around eight new P. reichenowi specimens from chimpanzees in locations throughout west Africa. The genetic comparison surprised us all. Amazingly, we found that the entire diversity of P. falciparum (the human malaria) was dwarfed by the diversity of the handful of P. reichenowi chimpanzee parasites we’d managed to uncover. This discovery told us

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