By 2006, when Sabeti became just the third woman in the history of Harvard Medical School to graduate summa cum laude, she was working with Lander at the Broad Institute. Using the massive amounts of data being made available by next-generation genetic sequencing, Sabeti and her colleagues developed a tool to pore through the entire human genome (as opposed to just a handful of haplotypes) to locate gene variations that appeared to have been under recent selection pressure.
In a 2007 paper also published in Nature, they zeroed in on three clear examples in which genes involved in a common biological process underwent selection in the same population. The first gene pair, SLC24A5 and SLC45A2, played a role in skin pigmentation in Europeans. The second pair, EDAR and EDA2R, was involved in the development of hair follicles in Asians. And the third gene pair, LARGE and DMD, was related to susceptibility to infection by the Lassa virus in West Africa.
Sabeti’s background in malaria and interest in infectious diseases pushed her to focus on Lassa, an acute viral hemorrhagic fever first identified in the Nigerian town of Lassa in the late 1960s. The U.S. Centers for Disease Control and Prevention identifies Lassa virus as one of only a handful of Category A agents, which “pose a risk to national security” because they’re deadly, can be easily transmitted between humans and “might cause public panic or social disruption.” Like the Ebola virus, Lassa virus is often referred to as an emerging pathogen, because the documented human cases have occurred relatively recently.
As Sabeti would quickly discover, working with Lassa presented a unique set of challenges. “I realized that I had become interested in a [virus that has]...very few people working on it,” she says. “In order to do that I just had to figure out how to do it myself.”
By now an assistant professor at Harvard’s Center for Systems Biology, Sabeti spent some of her junior faculty startup funds as well as money from an $875,000, five-year science and engineering fellowship from the Packard Foundation setting up a collaboration with a medical facility in Nigeria, the Irrua Specialist Teaching Hospital.
Sabeti’s decision to conduct fieldwork on a dreaded pathogen in a dangerous country 5,000 miles away was a bold move, especially considering she was best known as a computational geneticist. “I had tremendous challenges,” she says. “Universities are not always thrilled about having someone actively working with a deadly virus.”
Yet Sabeti’s holistic approach led to unexpected results. The financial support she provided to the Irrua hospital enabled caregivers to diagnose more patients and to offer treatment with the powerful antiviral drug ribavirin. “As the hospital got more and more proficient...we got more and more patients from a larger area,” Sabeti says. Soon the researchers had collected blood samples from more than a thousand people, including many plagued by fevers of unknown origin, and “every person with a fever was trying to get to this hospital” for treatment, Sabeti recalls. Based on the analyses of blood samples, and her reading of the literature, she began to suspect that many more people had been exposed to both Lassa and Ebola than had been previously believed.
Those data form the backbone of a provocative, just-published paper in Science, “Emerging Disease or Emerging Diagnosis?” She and her co-authors speculate that Ebola and Lassa might not be emerging diseases at all, but instead represent the “emerging diagnosis of a disease that has long been common but overlooked” and had “interacted with humans for far longer than generally thought.”
If this hypothesis is correct, it will have an enormous impact in how medical experts think about, and develop treatments and interventions for, diseases such as Lassa and Ebola: In addition to caring for those sick enough to end up in the hospital, researchers can study why some people are relatively unaffected by the virus. If the LARGE gene mutation common in West Africa was selected for because it helped humans resist infection with Lassa virus, mimicking changes caused by the gene could pave the way for treatments, or perhaps even a Lassa vaccine.
Thousands of patients in Nigeria have already benefited from Sabeti’s work, says Christian Happi, director of the Infectious Diseases Laboratory at the hospital in Irrua. “That simple action—to go out into the field, in a rural setting in Nigeria, to go down there to provide diagnostics and help with treatment in this rural community, very far away, with no infrastructure—it’s incredible,” Happi says. “Apart from being dedicated, generous with her time, generous with her knowledge—generous with everything, really—she just really wants to be involved. That type of generosity is a quality that not many people have.”