TORONTO — Ebola has been an extraordinary challenge for science.
Over nearly four decades, the virus has triggered sporadic outbreaks in remote places, melting back into nature before scientists can mount many real-time studies to delve into its mysteries.
One of the deadliest of known viruses, Ebola can only be studied in laboratories with the most stringent biosafety and biosecurity protections in place. The community of Ebola scientists is small, and most of the scientists who do this work also rush to the scene of outbreaks, manning treatment centres or mobile laboratories.
During outbreaks, priority has always — and necessarily — focused on treating patients and stopping transmission. In those settings, research has never been the top priority. As a result, many fundamental facts about Ebola were unknown when the current West African outbreak exploded. And 20,000 cases into that outbreak, many, many questions remain unanswered.
Here are a few:
Question: Where does Ebola live between outbreaks? Is this prolonged epidemic seeding the virus into animal species, increasing the risk of more frequent human outbreaks in West Africa?
It is believed Ebola viruses naturally live in some bat species. Human outbreaks probably occur when people interact with infected bats; bats are eaten in some cultures.
Non-human primates can also be infected and can transmit the virus to people who butcher or prepare primate meat for cooking. Last summer's Ebola outbreak in the Democratic Republic of Congo is thought to have started with a woman who butchered an infected animal.
But notice the lack of certainty in the sentences above. There are still holes in the story about where Ebola lives, what triggers a spill over into people and why that doesn't happen more often.
It's also unclear if the current high concentrations of Ebola in West Africa — unlike anything ever seen before — might be changing the dynamics of the virus in nature. Could this outbreak result in the virus becoming endemic in one or some animal species, increasing the risk of more frequent forays into people?
This is one of the questions Dr. Jeremy Farrar would like answered. The director of Britain's Wellcome Trust medical charity, Farrar thinks it's important to figure this, to get a better sense of the risk Ebola poses in future to West Africa.
But he knows people are currently too busy trying to extinguish the outbreak to attempt to answer this question. "There's not many people looking for dead monkeys at the moment."
Question: What happens to Ebola survivors? Are there long-term health consequences from an Ebola infection?
Prior to this outbreak, the combined total of all known Ebola infections was fewer than 2,400 people. Of those, only about 800 survived the roughly two dozen outbreaks that date back to 1976. Most live in villages in central Africa. They have not been heavily studied.
As a result, there isn't a lot known about whether there are long-term health problems associated with having contracted Ebola. But the pool of Ebola survivors has more than doubled due to this outbreak; of the more than 20,000 cases so far, about 1,200 have survived to date.
"The sense of the long-term effect on people's health is fragmental at best," says Gary Kobinger, an Ebola expert who heads the special pathogens team at Canada's National Microbiology Laboratory in Winnipeg.
"And so this (outbreak) is going to give a lot more opportunity to learn more about if there is any long-term side-effects from an acute disease."
Another unknown relates to what happens to babies born of women who were infected during their pregnancies, says Dr. Allison McGeer, who heads to Liberia this weekend for her third stint in the field helping the containment effort.
There have been many reports of spontaneous abortions in pregnant women infected with Ebola, and many deaths. But McGeer, an infection control specialist at Toronto's Mount Sinai Hospital, says more than 10 pregnant women are known to have survived infections in this outbreak. And the births of their babies will be watched with interest and concern.
Question: Do survivors have life-long immunity to the strain of Ebola that infected them? If the experimental vaccines work, how long will the protection they generate last?
It is hoped that people who survive Ebola will be protected against the particular strain of the virus for life. (It is not thought that infection with Ebola Zaire would protect against infection with one of the other types of the virus, Ebola Sudan or Ebola Bundibugyo, however.) But whether that's actually the case isn't yet clear.
That is one of the questions West African survivors could help science answer. Study of blood samples from survivors in years to come could illuminate how long immune protection to natural infection lasts.
"People who are survivors, there will be a lot to learn from them. Because their immunity is actually from a real infection," Kobinger says.
Likewise, researchers will want to follow people who receive one of the experimental vaccines to see how quickly the antibodies generated by the serums wane. There are concerns the vaccines won't provide long-term protection.
Question: What are the most essential components of effective treatment in low-resource settings? How much better would survival rates be if treatment centres could routinely deliver this level of care?
In the current epidemic, the World Health Organization and countries providing volunteer help have elected to evacuate foreign medical workers who have become infected with Ebola in West Africa.
As a result of those evacuations — and three secondary infections in health-care workers who treated them — about two dozen infected people have been cared for in hospitals in the United States, Spain, Britain, France, Norway, Germany, Italy and Switzerland.
These cases are providing doctors in Western hospitals an invaluable chance to learn about how Ebola ravages the body and what treatments aid survival. The survival rate among these patients is about 80 per cent, almost the inverse of what is seen in West Africa.
The care given in American or European hospitals — which treat one or two patients at a time with large teams of doctors, round-the-clock nursing and the ability to run batteries of tests — cannot be replicated in West Africa, where overworked medical teams may not even have the capacity to give all patients intravenous fluids, even though they are thought to be critical to survival.
Figuring out the basic minimum in deliverable care is critical to lowering the death toll in West Africa, says Farrar.
"We know that if you land in Atlanta, you'll probably do quite well. But that's true of every disease. What we don't know is what are the critical one, two, three, four, five things that if you've got very limited resources — which, in truth, we're always going to have in low-income countries — what are the five things you absolutely need?"
"Is it fluids? Is it oxygen? Is it antibiotics? Is it an antiviral drug? What is it? And when?"
Question: How does transmission actually occur? Are there some types of contact that are more likely to result in spread of the virus than others? Why doesn't transmission happen more often?
Figuring out how a virus spreads seems pretty basic, right? But in reality, it's really tough to study, for Ebola or any virus, McGeer says.
With some pathogens, scientists can do what are called challenge studies; they can deliberately infect some people, or expose healthy people to infected people, and see how often and under what kinds of circumstances infection occurs.
But you cannot do that type of work with a virus as deadly as Ebola.
Infected people excrete Ebola viruses in bodily fluids such as blood, vomit and diarrhea. But traces of virus have also been found in saliva, breast milk, tears and semen. It seems likely that some of these are more important as routes of transmission, but the evidence is sparse.
And it seems clear that some types of contact or some events are bigger drivers of transmission than others. It's accepted that African funeral rites — which involve washing and kissing the deceased — play a huge role in spread of Ebola. The bodies of people who have died of Ebola teem with viruses. That's why safe burials are a key to Ebola outbreak control.
But Christopher Dye, a World Health Organization epidemiologist, wonders if there are other events that increase the risk of transmission. Identifying these types of episodes or contacts would help authorities refine containment plans, says Dye, who is the WHO's director of strategy for Ebola.
Knowing more about how Ebola spreads could shed some light on puzzling events in this outbreak, says Michael Osterholm, director of the Center for Infectious Diseases Research and Policy at the University of Minnesota.
There have been several episodes in which it seemed clear there would be significant spread, but those fears were not realized. People who stayed for days in a Dallas, Tex., apartment where Liberian visitor Thomas Duncan had been sick with Ebola did not contract the disease. Attendees at the funeral of an imam who died from Ebola in Mali did not become infected. A Nigerian doctor who treated patients — even performed operations — while sick with Ebola had high-risk contact with many health-care workers and friends, but infected only a few.
"We don't really understand transmission," Osterholm admits.
Question: Why is the virus so brutal to humans?
Ebola expert Heinz Feldmann says the Ebola's genetics aren't really well understood.
"What makes it less or more virulent? What makes it less or more transmissible? We don't know," says Feldmann, head of virology at the U.S. National Institute of Allergy and Infectious Diseases's Rocky Mountain Laboratories in Hamilton, Mont.
The current outbreak has led to an explosion of interest in Ebola, with scientists from other disciplines being drawn to a field that until recently was the purview of a very small number of researchers, Feldmann among them. He finds the questions some of them are asking sobering.
"I'm looking at every paper, every commentary and I say: Oh, man! We worked 20 years on this virus and what do we actually know? We don't know anything. We can't answer the basic questions that these people are asking."
Question: Will Ebola become endemic in West Africa?
All previous Ebola outbreaks have been stopped, generally within a few months. The current one has gone on for at least a year at this point and the end is not in sight.
That leads some experts to worry that it won't be possible to completely halt this epidemic. They envisage a scenario where parts of West Africa may have to deal with Ebola for months or years to come.
"The fear is if the job doesn't get done in 2015 ... then I think we would be reasonably talking about endemic (Ebola)," says Dye.
Dr. Joanne Liu, international president of Doctors without Borders, contemplates that possibility with dread.
The epidemic has ground the region's fragile health-care systems to a virtual halt. But that can't last forever. Figuring out how to safely deliver babies and treat victims of road accidents and remove burst appendixes while any one of those patients might also be infected with Ebola would be extraordinarily challenging, but crucial. And Liu shudders at the thought of concurrent Ebola and measles outbreaks.
"We might need to learn to live with Ebola. And that's something new," she admits.
Question: How long will the world remain interested in Ebola? How long will there be funding to pursue answers?
Ebola is definitely the disease du jour. But front burner issues rarely stay there long. Will international interest flag before key questions about Ebola are answered?
Those seeking answers fear that is likely.
"The Department of We-Don't-Know is so huge," says Liu. "It's so vast what we need to learn about Ebola. And I'm not sure how long the motivation to do better will last."
Veteran Ebola fighter Pierre Rollin of the U.S. Centers for Disease Control points to the example of SARS. The 2004 outbreak of severe acute respiratory syndrome infected 8,422 people around the globe and claimed 916 lives.
For a time, SARS was a hot research field. Today, it's the research equivalent of Latin.
"For SARS, nobody cares anymore. Nobody works on a (SARS) vaccine anymore. It's just a dead issue. It was a big balloon because a lot of countries were affected, and then what? Nobody is talking about it anymore," Rollin says.
"How long is that going to stay?" he asks of the Ebola interest. "Let's say we have a huge outbreak of flu in two months. Everybody's going to shift to flu."
