What don’t we know about Ebola?
Since its emergence in 1976, Ebola has been largely viewed as a remote threat, a sporadic problem of the developing world. There are fewer than half a dozen facilities in the United States equipped to safely study the virulent pathogen—and we are one of the disease’s most active investigators. In 2014, the disease received a paltry forty-two million dollars of funding from the National Institutes of Health for both vaccines and therapeutics.
In some ways, we’re only aware of how much we don’t understand because of the little that we do. No one has identified Ebola’s “natural reservoir”—the animal species that carry the dormant pathogen during lulls between human outbreaks. Finding the hidden pool of the virus would go a long way toward eradicating it. At first, researchers thought that the hosts were chimpanzees, gorillas, and other primates. Now it is clear that these animals get sick and die too quickly to hold on to the virus for long. Although Ebola may be carried without symptoms in fruit bats for extended periods, as the media has widely reported, additional candidates keep emerging—a certain strain of the virus was found to be harbored by pigs in the Philippines in 2008, for example. To discover the source of Ebola, we should send trained field workers into the bush to test, isolate, and then kill infected animals to remove them as a food source and limit their capacity to transmit the virus.There is precedent for this kind of strategy. In the bird flu outbreaks of 2005 through 2007, certain flocks of chickens in Asia carried deadly strains of influenza. Chinese public-health officials were able to target and slaughter them, snuffing out an epidemic that otherwise could have spread with great speed and ferocity, and significantly reducing the chance of flare-ups afterward.
Although we know that bodily fluids are contagious, we still don’t have a definitive picture of how the virus enters the body’s cells. But learning the biology of Ebola infections is necessary for designing and deploying effective drugs and vaccines. Unlike H.I.V., which can only infect a limited set of cell types in the body, Ebola is promiscuous and attacks white blood cells, the cells that line our vessels, and cells that make up our liver, adrenal glands, and airways. Research studies have suggested at least three potential paths that the virus can take to invade our tissues. In one sequence, Ebola attaches to a protein on the surface of a cell that is meant to transport cholesterol. After Ebola has hijacked the surface protein, it sneaks into the cell and rapidly proliferates. (That transport protein is ubiquitous in the body, because all our organs require cholesterol in order to function normally.) Other experiments have indicated that Ebola can commandeer a protein called TIM-1, which is widely distributed in conjunctiva, the insides of our eyelids, and in our cornea. Despite taking precautions with gloves and facemasks, health-care workers who have become infected may have inadvertently brushed a finger near their eye, giving the virus access to TIM-1.
Ebola may have a third, and particularly nefarious, way of overtaking the body. There is a type of white blood cell called a dendritic cell, which normally chews up and destroys invading microbes. When Ebola comes into contact with the mucous membranes of our mouth or a break in the skin, the dendritic cell goes to work against it. But Ebola disarms the cell and uses this crucial bodily defender as a factory to spew out its progeny. We need to understand the mechanisms by which Ebola invades dendritic cells, evades destruction, and then turns the immune system against itself. Deciphering the dendritic pathway could help to alleviate Ebola’s cascading brutality in human hosts.
We have the technology and know-how to map these three pathways of entry and find others that the virus may use. Once we understand the biology of Ebola infection, we’ll be able to work more quickly toward effective drugs and vaccines, and get a clearer idea of the value of current therapies like ZMapp. For other diseases, we’ve developed advanced methods to fabricate antibodies that may protect cells from invasion. If administered to Ebola patients, such antibodies could limit the proliferation of the virus. (This approach has helped to combat AIDS: we know that H.I.V. initially enters blood cells through two protein portals. Therapeutic agents like Maraviroc have been created that successfully limit entry.) Most importantly, understanding Ebola entry informs the design of vaccines that build blocking capacity before infection. Vaccines are the ultimate answer to microbial epidemics.
Finally, unravelling the biology of Ebola will signal how to fight the pathogen’s most lethal symptoms. Shock, the sudden and severe drop in blood flow that most often kills Ebola patients, is likely triggered by inflammatory molecules called cytokines, which are released by infected dendritic cells. Verifying that model and identifying which cytokines are the culprits would open up new treatment opportunities for preventing shock. We already use drugs that neutralize toxic cytokines on patients with inflammatory diseases such as colitis and rheumatoid arthritis. These could well be used for Ebola patients.
We currently only have a general understanding of the biology of Ebola, and we are lacking key specifics that would enable us to combat it more effectively. This outbreak must not be viewed as an unthreatening “orphan infection,” a rare occurrence without global impact. The current epidemic will not abate quickly, and billions of dollars are needed in the field to limit the spread of the virus. But smart investment in research today will be repaid manifold in saved lives. In the United States, the money for Ebola has largely been a spinoff from the larger bioterrorism effort. Now representatives have awakened to its urgency, and there are calls from both sides of the Congressional aisle to revisit the level of federal research support in November after the midterm elections. Ending Ebola begins by ending our ignorance.