infection, in other words, as well as a disease of macaques.
But the case of BW was considered anomalous, just a one-time situation resulting from quirky circumstances. Many people spend nights out in the Malaysian jungle—local villagers while hunting, for instance—but few of them are American visitors, surveying or spying or whatever, and able later to get good medical diagnoses of their feverish ailments. That’s roughly where things stood with Plasmodium knowlesi for thirty-five years, until two microbiologists in Malaysian Borneo, a married couple named Balbir Singh and Janet Cox-Singh, began looking into some peculiar patterns of malaria occurrence around a certain community in the Bornean interior.
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Singh and Cox-Singh had arrived in Borneo by roundabout routes. He was born in Peninsular Malaysia, into a Sikh family with roots in the Punjab, and went to England for a university education. Eventually he got his PhD in Liverpool. Janet Cox came from Belfast to Liverpool, also to do a doctorate. They met at the Liverpool School of Tropical Medicine, in 1984, and found themselves sharing an interest in malaria, among other things. (The Liverpool School of Tropical Medicine, old and august, was a logical place to nurture such interest; Ronald Ross himself, after leaving the Indian Medical Service and before the Ross Institute was founded in London, had been a professor there.) Some years later, now married and with two young daughters, Singh and Cox-Singh moved back (for him) to the East: specifically, to Kelantan, on the east coast of Peninsular Malaysia. Then in 1999, offered a chance to do research under the auspices of a new medical school, they relocated to Sarawak, one of Malaysia’s two Borneo states, establishing their lab within the University of Malaysia Sarawak, in Kuching, an exotic old city on the Sarawak River. Rajah Brooke had a palace there in the mid-nineteenth century. Alfred Russel Wallace passed through. It’s a charming place if you want little backstreet hotels and riverboat commerce and Bornean jungle out your back door. Kuching means “cat,” hence the nickname “Cat City,” and at the gateway to its Chinatown sits a huge concrete feline. Singh and Cox-Singh, though, didn’t choose it for local color. They were tracking malaria. Soon after settling, they heard about some strange data coming from Kapit, a community along an upper tributary of the Rajang River in Sarawak.
Kapit town is the seat of Kapit Division, an area populated mainly by Iban people who live in traditional longhouses, travel the river by dugout, hunt in the forest, and raise rice and corn in gardens along the forest edges. Plasmodium vivax and P. falciparum are the most commonly reported malarial organisms in Sarawak, with P. malariae third in order, accounting for a small fraction. The blood-borne stages of those three can be distinguished under a microscope, rather quickly and easily, in a smear of blood on a slide—which was how malaria had been diagnosed for decades. But the reported statistics seemed skewed; a large portion of all the P. malariae cases in Sarawak, Singh and Cox-Singh learned, were coming from Kapit. Why? The division had a remarkably high incidence, it seemed, of this particular malaria. Furthermore, most of the Kapit cases were severe enough to require hospital treatment—rather than being mild or scarcely noticeable, as typical for P. malariae. Again, why? And the Kapit victims were mainly adults, who should have been immune because of prior exposure—rather than children, who as nonimmunes were the usual victims of P. malariae. What was going on?
Balbir Singh traveled by boat up to Kapit and took samples from eight patients, pricking the finger of each person and blotting the drop of blood onto a piece of filter paper. Back in Kuching, he and a young research assistant named Anand Radhakrishnan ran the samples through a molecular test using PCR, which was the new standard in malaria diagnostics, as in so many other areas, and a far more precise method of identification than peering at infected blood cells through a microscope.
PCR amplification of DNA fragments, followed by sequencing (reading out the genetic spelling) of those fragments, plumbs far deeper than microscopy. It allows a researcher to see below the level of cellular structure to the letter-by-letter genetic code. That code is written in nucleotides, which are components of the DNA and RNA molecules. Each nucleotide consists of a nitrogenous base linked with a sugar molecule and one or more bits of phosphate. If DNA resembles a spiral staircase supported by two helical strands, those nitrogenous bases are