John Connor would really like to cure Ebola. He’s a microbiologist at Boston University, working in an interdisciplinary unit with BU computer scientists and engineers, Boston-area biotech companies, and researchers at the University of Texas Medical Branch in Galveston to answer a bunch of questions—how to speed up diagnosis, what the best target is inside the virus, how to develop a vaccine. So Connor’s team, for example, is looking at the RNA that Ebola uses to make copies of itself in the body. Based on isolating that, they hope to create a vaccine that could target not only the five different known types of Ebola, but also the related Marburg virus as well. But first they have to identify the right chunk of RNA.
"A vaccine that could protect against all the known types of Ebola has to be complex,” Connor said. “Each flavor is distinct enough that the immune response has to be specially trained. But our lab is working with the Galveston team to come up with a vaccine that would work with a single injection. We're encouraged by results."
But right now, that research—and all the rest of the work on Ebola therapies—is still preliminary, or experimental. The thing hampering efforts to quell the ongoing Ebola outbreak in Africa and treat Kent Brantly and Nancy Writebol, two Americans with the disease now at Emory University Hospital in Georgia, is that the FDA has approved no medications or therapies specific to Ebola. The monoclonal antibody treatment reportedly used in treatments so far was experimental. The only accepted approach, broadly, is rehydration, time, and hope.
Researchers and laboratories around the world are working to change that. “A lot of other labs and companies are investigating approaches and therapies and show significant progress,” Connor says. “In the development process, if you start with one idea and it fails, that’s a problem. But if we all have 20 ideas and 15 fail, we still have five successes.” Right now, just one success would look pretty good at the special isolation ward at Emory. Writebol’s son Jeremy said Wednesday that his mother was “tired from her travel but is fighting the virus.” And university officials have refused to discuss their patients’ symptoms, prognosis, or course of treatment—they’ve said only that “treatment is going as planned.”
Ebola is a threadlike filovirus that causes hemorrhagic symptoms; it spreads through bodily fluids such as blood, waste and semen and attacks white blood cells, stalwarts of the immune system, and the platelets that allow blood to clot. Symptoms include fever, weakness, muscle pain, headache, and sore throat, followed by rash, impaired kidney and liver function, and in severe cases, internal and external bleeding. Ebola causes direct and indirect tissue damage—direct because it attacks cells in the liver and indirect through the body’s inflammatory immune response—so that requires extensive monitoring of the heart, blood pressure and blood. Depending on the timing of diagnosis and severity of infection, additional treatment may call for kidney dialysis or blood transfusions. The virus has a fatality rate between 60 and 90 percent—that’s incredibly deadly. In previous outbreaks, the speed with which the virus kills has limited its spread, as people infected with it died before they could spread it widely. But this time that hasn’t been the case.
In practice, what all that means is that doctors don’t have much they can do for Ebola patients. World Health Organization and Centers for Disease Control and Prevention protocols call for “supportive therapy,” which includes measuring and balancing fluids, watching vital signs, and treating patients for any related infections. Think of it as an intensive care unit setting, said Peter Hotez, a virologist and founding dean of Baylor College of Medicine National School of Tropical Medicine.1 “All body fluids are monitored, such as urine, and fluid hydration through a typical IV replaces daily fluid loss from perspiration as well as the volume lost because of the disease” through vomiting, diarrhea and sometimes bleeding.
With so few clinical weapons at their disposal, doctors and public health workers have to use other strategies—like prevention and containment. Atlanta-based Delta Air Lines has notified passengers that health concerns may delay travel to and from West Africa. Travelers flying out of Roberts International Airport in Monrovia, Liberia, may be required to complete a health screening before entering the airport, and people traveling to and from certain cities in Liberia, Nigeria, Sierra Leone and Guinea are now allowed to postpone their trips without paying change fees, Delta said. And meanwhile, governments around the world are deploying more and more people to enforce quarantines in Africa and help treat the sick.
The hunt for better diagnostics and therapies goes on, of course. Besides the vaccine work, Connor’s team is working on something they call a “nanoparticle detector.” It’s a gadget that can tell, simply and quickly, if someone has Ebola, based on nothing more than a blood sample. The team has already tested it on molecular proxies for the virus; they’re just about to start using the actual germ. “Any therapy will work better the earlier you can start it,” Connor says. “So the better the diagnostics, the sooner you can treat and the more likely you will have a successful outcome.”
Meanwhile, in Atlanta, Georgia State University microbiologists are working on an alternative method for vaccine development. Typically vaccine makers grow virus in chicken eggs, but it’d be safer and cheaper to instead build the molecules that an immune system responds to—the basic mechanism of a vaccine. So the Georgia State team is working with fusion proteins, linked together synthetically to resemble those natural targets. “As you can imagine, one of the difficulties with Ebola is that not every lab can handle it, and limited places can test vaccines. This takes a long time and strict procedures,” said George Pierce of GSU’s Environmental Research Center. “The great aspect of the fusion process is that the 15 amino acids we identified can’t cause the disease but can illicit an immune response. It doesn’t need special precautions in the lab.”
If it worked, the lab’s fusion protein process could create millions of doses in just one week. But Pierce’s group started this work four years ago, and there’s still more testing to do. “Tons of teams across the country are researching Ebola, and we think no one approach will work,” Pierce said. “But we’re leaving no stone unturned, and at the end of the day, we’re going to solve Ebola.”
1UPDATE 1:30 p.m. ET 08/07/14: This story was updated to correct the name of the school.
