In 2010, Pardis Sabeti, a senior associate member of the Broad Institute and head of its viral-genome efforts, proposed a genetic study of the deadly Ebola virus. To test, treat and stop Ebola, the disease had to be studied at the molecular level.
“I’ve always been fascinated by infectious microbes,” Sabeti said, “because they are so dangerous and deadly on a global scale. They are mysterious and powerful forces to be reckoned with. I have a deep passion for medicine, and in particular for infectious disease. I’ve also had people close to me die of infectious disease. That makes it personal as well.”
Requiring samples from people infected with the virus, Sabeti’s study became possible only in 2014, when West Africa suffered the largest Ebola outbreak in history, killing more than 10,000 people in Liberia, Sierra Leone and Guinea before the epidemic waned.
Out of tragedy came a medical advance: Sabeti and her colleagues at the Broad Institute—along with several scientists who died from the virus—worked to help track Ebola’s mutations and shape the global response to it.
By the time the Ebola epidemic had taken hold, Sabeti had spent years studying Lassa, a lesser-known but similarly deadly virus affecting West Africa. Thousands of patients had already benefited from the five years she spent developing diagnostic tools for the disease. Sabeti’s reputation was well-established—beyond being a brilliant scientist who was only the third woman to graduate summa cum laude from Harvard Medical School, she had also single-handedly burnished a new approach to computational genomics, exploring when mutations arise in genomes and what that means for the evolution of pathogens.
“I had a formative experience being assigned as an undergraduate advisee of Eric Lander,” Sabeti said. “That pretty much solidified my love for genetics. I also deeply enjoy the discovery and pursuit that’s part of being a scientist. At its foundation, it’s actually a creative process.”
Sabeti’s work on Ebola began soon after the epidemic reached Sierra Leone, when she and her team received an email of the test results from a patient testing positive for Ebola. Pulling together her colleagues in what she called the Ebola War Room—a conference room at the Broad Institute headquarters—Sabeti plotted not only her genome study, but also how her team could help send advanced diagnostic tools to the affected countries.
In early June 2014, scientists in Sierra Leone shipped tiny tubes of human blood serum by DHL Express to the Broad Institute, where scientists tested the samples for Ebola, isolated the virus’s RNA, prepared the RNA to be decoded and finally ran the Ebola code through one of the fastest DNA sequencers in the world. Throughout, Sabeti reminded her team of safety first. As she put it, infectious disease is “a challenging area, where we can be leaders, but we can only be leaders if an error is never made.” Broad Institute computers created a finished genetic code, and within two weeks, Sabeti and her team were analyzing it so they could share their findings.
“The simple fact of having data in near real time is so important and needed,” Sabeti said. “We made all of our own data publicly available immediately as we generated it. As newcomers to outbreaks, we discovered that this was not the cultural norm, and our actions helped push the idea forward that we need to work collaboratively and openly in an outbreak.”
Within two months, Sabeti and her team had analyzed 99 Ebola genomes and published their findings in Science magazine. The genomes from the 2014 outbreak, they found, had more than 300 genetic changes compared to genomes from past outbreaks. They also discovered, in a widely reported finding, that the virus began in one person and spread rapidly after 12 people attended the same funeral. The team’s data, shared broadly with scientists around the world, represented a fourfold increase in the amount of Ebola genomic data available to that point and a departure from the way most infectious disease research was done—in silos, not shared. Now, Broad Institute scientists are helping train doctors in West Africa to sequence Ebola genomes so they can track the virus in real time, streamlining the response to any future outbreak.
“We have the tools and the technology at our disposal to be one step ahead of viruses,” Sabeti said. “What we need to do is to be committed to working together in order to stop outbreaks. We should demand more of ourselves, because we will only win if we work together.”