An Ebola victim is buried in a Muslim cemetery in the city of Beni, in the Democratic Republic of the Congo.
Photograph by Jerome Delay / AP
By Richard Preston
This July, the World Health Organization declared that an outbreak of Ebola in the provinces of Ituri and North-Kivu, in the eastern Democratic Republic of the Congo, was a “public health emergency of international concern.” This particular strain of the virus, which first appeared in the region in 2018 and hasn’t been given a formal name—I’ll call it Kivu Ebola—is a variant of a species known as the Zaire Ebola virus. As of last Saturday, 2,753 cases of Kivu Ebola have been reported, with 1,843 deaths. There appear to be many undiscovered cases in the region, too. Ella Watson-Stryker, a social scientist with Doctors Without Borders, who has been studying the outbreak, said that around half of all Ebola patients admitted to treatment centers in eastern Congo aren’t part of any known chain of transmission. In other words, the infected person has caught Ebola from somebody whom disease investigators haven’t yet identified. “A lot of transmission is not being seen, but nobody knows the exact amount,” Watson-Stryker told me.
Ebola virus is a microscopic parasite that replicates inside the cells of a host. The outbreak in eastern Congo began more than a year ago, in or near a town called Mangina, when a few particles of Ebola virus apparently moved out of some wild creature, Ebola’s natural host—in this case, probably a bat—and entered the bloodstream of an as yet unidentified person. From that person, the virus began spreading through the local population. Ebola can overwhelm the human immune system in a matter of days. Symptoms typically include vomiting, diarrhea, coughing, rash, dementia, hemorrhages, and hiccups. Death occurs like the slamming of a door, when the patient abruptly goes into shock.
The Kivu Ebola outbreak area is in a conflict zone, beset by armed militias and ethnic violence. Local people often don’t trust the international medical organizations that run the Ebola treatment centers. There have been at least a hundred and ninety-four attacks on local health workers, seven of whom have been killed. Watson-Stryker, the researcher, said that social media complicates containment and treatment efforts. Conspiracy theories about medical workers and false information about how the virus is spread are ricocheting around popular platforms like WhatsApp. “The problem is the post-factual reality that exists in social media,” she said.
An effective experimental vaccine for Ebola exists, and more than a hundred and seventy-five thousand people have received it. Even so, the virus is finding new victims and extending its geographic range. Three cases of Ebola recently appeared in Uganda, and there have now been four cases in the Congolese city of Goma, which has roughly two million residents and is situated on the border with Rwanda. The W.H.O. recently estimated that more than two hundred million dollars in emergency funding would be needed to bring the virus under control. That money hasn’t been raised yet.
An Ebola particle is a very small, filament-shaped object, made of six different structural proteins. Ebola’s genetic code, or genome, is contained in a strand of ribonucleic acid, or RNA, that is coiled tightly in the core of the particle. The genome, which has some nineteen thousand letters in it, holds the master designs of Ebola’s proteins.
RNA viruses—which range from Ebola to measles and influenza— tend to produce errors, or mutations, in their code when they copy themselves. Most mutations are either bad for the virus or have no effect on it. Every now and then, however, a virus gets a mutation that benefits it. In fact, the production of errors during copying plays an important role in the long-term survival of viruses. As time goes by and the virus makes inaccurate copies of itself, slightly different varieties of the virus arise. The different varieties are called lineages. They can be imagined as moths of the same species whose wings are slightly different colors. Some wing colors help a moth camouflage itself more effectively, be eaten less often by predators, and survive longer than moths of other colors. Those types of moths go on to reproduce successfully, while moths of other colors eventually die out, until the population of moths has changed color entirely. This is the process of evolution.
Considered as a life-form, the Kivu Ebola isn’t a single organism but, rather, an immense swarm of particles that jumps from victim to victim. Each particle in the swarm possesses a biological drive to copy itself. As the particles copy themselves, they compete with all the other particles for survival. Ebola particles copy themselves every eighteen hours. This is the generation time of the virus—the time it takes for a particle of Ebola to get inside a human cell and potentially create thousands of identical copies of itself in the cell. The copies then exit the infected cell and drift into the bloodstream, infecting more cells. Early in the disease, Ebola patients tend to get sicker in downward lurches. In some patients, the lurches are spaced roughly eighteen hours apart, as each new generation of particles floods the body. An infected person’s bodily fluids are lethally infectious, because they are filled with Ebola particles. If some of those particles get into new people, the virus spreads.
By now, the Kivu Ebola swarm has been going through its eighteen-hour replication cycle in humans for more than a year. Some virologists wonder whether Kivu Ebola could start evolving, or whether it has already started to evolve, in a way that makes it more dangerous to people—perhaps by becoming more contagious, in which case it would get much harder to control. These questions introduce a new aspect to the international emergency.
During the Ebola epidemic that ravaged West Africa in 2014 and 2015, that form of Ebola showed possible signs of evolving. Virologists are still trying to determine the significance of what happened. The epidemic began in a village in Guinea, in December, 2013, when some particles of Ebola apparently went from a bat into a small boy. That strain of the virus, now referred to as Makona Ebola, killed the boy and most of his family, and then began spreading. In the end, around thirty thousand people were infected and more than eleven thousand died before Makona Ebola was finally brought under control and eliminated from the human population. (There were eleven cases in the United States.)
As the epidemic progressed, a team of researchers, led by Pardis Sabeti, a genomic scientist at Harvard and the Broad Institute, studied the genetic code of various samples of Ebola taken from the blood of people who had been infected. They found that the virus began mutating as soon as it got into people. “From the outset, I was intrigued by the large number of mutations we found,” Sabeti told me. Makona Ebola quickly developed into several basic varieties. Then, in late May, 2014, one of the lineages took off like a wildfire and spread rapidly all over Sierra Leone and Liberia. This lineage is named the A82V Makona Variant of Ebola. For simplicity, I’ll call it the Makona mutant. The majority of patients in the epidemic were infected with the Makona mutant, including all eleven individuals in the United States. Meanwhile, the other lineages of Ebola died out. It seemed that the Makona mutant had somehow beaten them in a contest for survival.
Sabeti and other research groups noted that the change in the code of the Makona mutant happened in a single letter, which was part of the genetic recipe that causes the Ebola particle to be covered in roughly three hundred soft, squishy knobs. The knobs, called glycoproteins, are essential for the particle’s survival; they help it stick to cells and get inside cells, where it can reproduce. Sabeti wondered if the change in the knob protein could help this particular lineage of Ebola survive and prosper. “The mutation showed up at an inflection point in the outbreak, just as the outbreak exploded,” Sabeti said. “This was really intriguing.” It seemed that there might be something different about the knobs on the outside of the Makona mutant.
In 2016, a research team at the University of Massachusetts Medical School, led by a doctor named Jeremy Luban, ran some experiments on the Makona-knob protein. The team found that the knobs on the Makona mutant were four to five times better at invading human cells than those on the earlier strain of Makona. The Makona mutant stuck to human cells like a magnet, and the knobs seemed able to open a cell’s outer membrane, with the ease of a slide opening the teeth of a zipper, to allow the virus inside. “But what the significance of this mutation is for the outbreak, and how deadly this virus is, are still open questions,” Luban told me. “In biology, there is almost no such thing as proof.” Luban is planning more experiments to try to find out whether the Makona mutant was, in fact, more devastating or contagious than its predecessor.
A British team led by a virologist at the University of Nottingham named Jonathan Ball found that the Makona mutant seemed to be around twice as infectious in human cells than the earlier version of the virus had been. It also was less infectious in bat cells. The Makona mutant seemed to be evolving away from bats and turning into a virus suited for human cells. “I wasn’t at all surprised by this,” Ball said. “If you put a virus in a different system, you quickly see that the virus adapts to the new environment. I was surprised that other people were surprised.” Ball stressed that the experiments had been done in test tubes, using knobs of Ebola grafted onto a harmless virus. “We can’t show how the [real] virus will actually behave in a human,” he said. “You can’t do that experiment.” Many scientists, including Ball and Luban, aren’t so sure that the Makona mutant was any more dangerous than any other form of Ebola. The Makona mutant most likely spread far and wide because of social and behavioral factors, but it may have spread faster and more widely than it would have otherwise because of a change in one part of its genome.
What about the Kivu Ebola? The violence in the outbreak area makes doing scientific research there difficult. Nevertheless, a Congolese team of genomic researchers at the National Institute for Biomedical Research, at the University of Kinshasa, working with international colleagues, has been collecting blood samples from the outbreak and reading the genetic code of the Ebola. The Kivu Ebola, so far, has mutated into four lineages. Three of the four are active in the population. The swarm is exploring people’s immune systems and jumping from one victim to the next. So far, none of the three active varieties has become dominant. “The virus has been brewing in that area for a while,” Sabeti said. “If you give Ebola enough time to transmit from human to human, then an unpredictable event can occur. How likely is it that Ebola could change suddenly? We don’t have a good answer to that question.”
Right now, there may be around six hundred people in eastern Congo who have Kivu Ebola particles replicating in their bodies. As Ebola re-creates itself, many of the resulting particles are deformed duds and can’t replicate further. The ones that can copy themselves are infective. The Kivu swarm, with its three new lineages of Ebola, may amount to about one or two quadrillion infective particles of the virus. If these particles were collected in one place, they would fill three teaspoons and would weigh about fifteen grams. That small space contains numberless genetic possibilities. The longer the outbreak is allowed to continue, the greater the chances that Ebola will mutate, get better at spreading in humans, and vastly enlarge its circle of victims.