Is It Worth Imagining Airborne Ebola?

Back in September, when the West African Ebola outbreak was getting worse with every passing week, a lot of people began to worry that the virus could spread by air. And even if it couldn’t spread by air yet, they worried that it might be on the verge of mutating into an airborne form.

When I talked to virus experts, they saw little ground for either concern. The epidemiology of the outbreak, like previous ones, had the sort of pattern you’d expect from a virus that spreads mainly through contact with body fluids. A look at the evolutionary history of viruses indicates that a fluid-adapted virus would be unlikely to switch to going airborne with just a couple mutations. (I wrote in the New York Times about these conversations here and here.)

The anxiety over airborne Ebola has faded. The outbreak itself has dwindled down dramatically, although driving it down to zero may prove hard. But a new “Opinion/Hypothesis” piece published in the journal mBio, called “Transmission of Ebola Viruses: What We Know and Do Not Know,” has breathed some new life into the old worry.

The piece was written by Michael Osterholm of the University of Minnesota and a number of other researchers. Back in September, Osterholm wrote a controversial op-ed in the New York Times, declaring, “If certain mutations occurred, it would mean that just breathing would put one at risk of contracting Ebola.”

In the new mBio piece, Osterholm and his colleagues survey a number of past studies on how Ebola spreads. These studies don’t tell us as much as we’d like. We know less about Ebola than we do about, say, influenza, because it’s a lot rarer and a lot deadlier. Scientists thus have fewer opportunities to study it, and when they do, they have to take enormous precautions. But the evidence we do have offers a pretty clear picture, Osterholm and his colleagues write: “Available data indicate that direct physical contact and exposure to infected body fluids are the primary modes of Ebola virus transmission.”

Those fluids may be the blood of a sick patient, or diarrhea, vomit, or sweat. People can get infected by touching those fluids, but it’s also conceivable that the virus can reach a new victim in a spray of fluid. The droplets in these fluids don’t travel far, so they don’t create airborne transmission in the same sense that a virus like measles is airborne–with tiny aerosols drifting on air currents. Some animal studies have shown that Ebola can spread without direct contact, but they don’t demonstrate clear evidence that aerosols delivered the virus. Still, Osterholm and his colleagues note that when Ebola victims are autopsied, the viruses sometimes turn out to be present in their lungs. A cough or a sneeze could conceivably deliver virus-laden aerosols.

While that’s theoretically possible, Osterholm and his colleagues acknowledge that this route has never been documented in humans. “This could be because such transmission does not occur or because such transmission has not been recognized, since the number of studies that have carefully examined transmission patterns is small,” they write.

There are other factors in Ebola outbreaks that we still don’t understand well. Some evidence suggests that certain people may become “superspreaders,” transmitting Ebola to many more people than usual, but we don’t know what’s responsible for these differences. It’s also possible that different strains of Ebola have genetic differences that cause some to spread faster than others. Some preliminary studies suggest that people who got sick in the West African outbreak build up more viruses in their bodies than people in earlier outbreaks.

After surveying what we do and don’t know about Ebola transmission, the authors offer what they call a hypothesis: Ebola might indeed be able to become airborne. Infected people might cough up virus-laden droplets, which other people might then breathe into their lungs, setting off an infection. Mutations could make this route easier for the virus to take. “We agree this is an improbable (although not impossible) scenario,” Osterholm and his colleagues acknowledge, but they point out that Ebola has sprung many surprises on us in the past. “We should not assume that Ebola viruses are not capable of surprising us again at some point in the future,” they conclude.

I got in touch with some other experts to see what they thought about this new piece. The most positive of them was Pardis Sabeti, a Harvard scientist who has been analyzing the genes of Ebola viruses to track their evolution. “I think that overall it is a really nice and thorough review,” she told me. She agreed it was important to figure out whether different Ebola lineages spread differently. As for airborne Ebola, she considered it unlikely although not impossible. “We should continually monitor its properties as it continues to evolve,” she said.

But other researchers were less enthusiastic. “I don’t see any new data that really sheds any new light on things in terms of the outbreak,” said Thomas Giesbert of the University of Texas. Most of the scientists I reached out to found the hypothesis of airborne Ebola even less impressive. “I guess you can make hypothesis about anything, and a ‘hypothesis’ about ‘potential’ isn’t very strong,” said Edward Holmes of the University of Sydney. “It fails to deliver,” said Vincent Munster of the National Institutes of Health.

Vincent Racaniello of Columbia was even harsher: “It can be viewed as a scare tactic, although to what ends I do not know,” he said.

Racaniello and the other critics note that there’s no evidence of that the Ebola virus has evolved in any significant way during the latest outbreak. And the fact that no one has found compelling evidence of aerosol transmission since the virus was discovered in 1976 suggests that shifting to that route is a major challenge, not an easy evolutionary maneuver.

In fact, viruses in general don’t show the massive evolutionary potential that Osterholm and his colleagues see in Ebola. Smallpox and influenza have infected billions of people by airborne transmission for thousands of years, and there’s no evidence that they have evolved a new route. Poliovirus and norovirus take the oral route, as they always have.

“No human virus has ever changed the way it is transmitted – at least in the 100 years or so we have been studying them,” said Racaniello. “There is no reason to believe that Ebolaviruses will become respiratory pathogens.”

(For more, see this blog post Racaniello published this weekend. For more on viruses generally, see my book A Planet of Viruses.)

How The Measles Virus Became A Master of Contagion

Here are two recent stories about viruses. They started out alike, and ended up very differently.

In October, a woman in Guinea died of Ebola, leaving behind two daughters, one of them two years old, the other five. A relative named Aminata Gueye Tamboura  took the orphaned children back to her home in northwest Mali–a 700-mile journey. Tamboura didn’t know it then, but the younger girl, named Fanta Conde, was infected with Ebola as well. For three days, they traveled on buses and in taxis as Fanta grew ill, developing a scorching fever and a perpetual nosebleed. Soon after arriving in Mali, she died.

Yet Tamboura never became infected with Ebola. Nor did Fanta’s sister or her uncle, who also made the trip. Nor did anyone else who shared the buses and taxis with Fanta, or who encountered Fanta elsewhere on her doomed journey. After Fanta’s death, the entire country of Mali braced for a devastating outbreak. But the outbreak never came.

The other story began in December. Someone–we don’t know who–paid a visit to Disneyland in California. That person, who we’ll call Patient Zero, was infected with the measles virus. But Patient Zero probably didn’t realize that he or she was incubating it, because the obvious symptoms, such as a rash and a high fever, wouldn’t emerge for several days. Strolling around Disneyland, Patient Zero cast off the measles virus in all directions, infecting dozens of people. Those people later developed measles, and may have spread the virus to others. By the end of January, the Disneyland outbreak had reached 94 cases, and that number is certain to rise higher.

These two stories show just how different viruses can be. For all the fear that Ebola can inspire, it’s a pretty bad transmitter. Measles, on the other hand, is among the most contagious viruses on Earth. There’s no single secret to measles’s power of contagion. Its adaptations for spreading are sprinkled across its whole life cycle.

While the biology of measles has only come into focus in the past few years, physicians have long been aware of its contagiousness. In 1846, a Danish doctor named Peter Panum recorded the first detailed account of a measles outbreak during his stay on the Faroe Islands, located between Scotland and Iceland. The disease leaped from one village to another. Out of the blue, someone would develop a blotchy pink rash that would spread across the entire body. A fever would ignite. “The patients were bathed in perspiration,” Panum wrote, “and, when the bedding was raised or the shin exposed, vapors literally rose from them like clouds.”

Because the Faroe Islands were so remote, Panum had an easy time observing the disease spread from person to person. He developed an eerie power of prediction. If one person developed a rash from measles, Panum knew that everyone else in the patient’s house would get sick two weeks later.

Panum noticed other predictable patterns, too. On average, he estimated, every infected person infected seven to nine other people. Today, the estimate for the average number of infections spread from each sick person is higher–between 12 and 18. By comparison, the figure for Ebola is only about two.

1908 image of measles rash via Wellcome Institute
1908 image of measles rash via Wellcome Institute

What made Panum’s observations all the more impressive is that he made them without knowing what was causing the measles outbreak. Scientists would not come to understand the nature of viruses for another five decades. The measles virus itself would not be discovered till in 1954, over a century after Panum’s stay on the Faroe Islands.

For the past five decades, scientists have been studying the measles virus, and yet many details of its life cycle are only now coming to light. As a virus, it has to do three things in order to avoid extinction: it has to invade a new host, make copies of itself, and get those copies to another host. At every step of the way, scientists are finding, the measles virus cranks up its chances of successful spread.

An immune cell infected with measles viruses. The viruses are engineered to produce a green-glowing protein. Photo by Paul Duprex
An immune cell infected with measles viruses. The viruses are engineered to produce a green-glowing protein. Photo by Paul Duprex

People get infected with measles viruses by breathing them into their lungs. The lining of the lungs contains immune cells that destroy incoming invaders and kill off infected cells. The measles virus boldly attacks these very sentinels. It uses a molecular key to open a passage into the immune cells. Once inside, it starts making new viruses that infect other immune cells. The virus-laden cells then creep from the windpipe to the lymph nodes, which are crowded with still more immune cells. It’s like a walk in Disneyland, except inside a person’s body. From the lymph nodes, infected immune cells spread the virus throughout the body. If the virus manages to slip into the nervous system, it can cause permanent brain damage.

After several days of multiplying, the virus starts making preparations to leave its host. Some of the infected immune cells creep up into the nose. The interior lining of the nose is made up of sheets of epithelial cells. The immune cells nuzzle up to the epithelial cells. A protein on their surface, made by the viruses, fuses them to the epithelial cells, allowing the virus to cross over. Now the measles virus is another step closer to leaving its host and finding a new one.

Each infected epithelial cell start making huge numbers of new measles viruses, which it dumps out into the nasal cavity, where they can get exhaled. Meanwhile, the infection also damages the upper airway, causing infected cells to rip free and get coughed out of the body.

People sick with measles release clouds of virus-laden droplets. The big droplets fall quickly to the ground or other surfaces, where they can stay infectious for hours. The small droplets meanwhile rise into the air, where they are lofted by currents and can deliver measles to people far away.

The sheer number of viruses produced by each sick person, along with the adaptations the viruses have for penetrating deep into the airway, make them tremendously contagious. If someone gets sick with measles, up to ninety percent of people in the same home who aren’t already immune will get sick, too. And because infected people can transmit the virus for days before symptoms emerge, the virus can spread to many homes before anyone realizes an outbreak is underway.

The late-arriving symptoms of measles are the outward sign that people’s immune systems are starting to fight the virus. Much of the battle takes place between uninfected immune cells and infected ones. The fight decimates the immune system. Even after people have conquered a measles infection, it can take weeks for their immune system to get back to full strength.

In this fragile state, people become vulnerable to other diseases such as pneumonia. The danger posed by these infections depends on how much care patients can get. In industrialized countries, only a tenth of 1 percent of people who get measles die. In developing countries, the rate is 5 to 10 percent. In refugee camps, the figure can be as high as 25 percent.

While people cope with these post-infection troubles, the virus has moved on to its next hosts. The contagion of measles is part of a “one-and-done” strategy that the viruses have evolved. After people recover from measles infections, their immune systems will protect them for life. As a result, the virus needs to be highly contagious for its long-term survival.

This strategy also means that measles vaccines can be extremely effective. By teaching people’s immune systems what the measles virus looks like, vaccines provide protection for life.

All these features of the measles virus add up to a startling paradox. Despite being far more contagious than the Ebola virus, the measles virus is a far better candidate for complete eradication from the face of the Earth.

Ebola viruses mainly circulate between animals (scientists suspect bats are their normal host). Every few years, they get into humans and cause an outbreak.  Bringing Ebola outbreaks to a halt doesn’t mean that the virus has become extinct. It just means that it has retreated back to its regular host.

Measles, on the other hand, only infects humans. If we could make our species measles-free, that would mean the virus had become extinct, never to return. And the life cycle of measles actually makes it possible to block its transmission from person to person. It’s very rare for infections to last more than a couple weeks, so that there isn’t the risk of people surreptitiously spreading the disease for years. People who do get sick won’t get sick again, taking them out of the pool of potential hosts. And we are fortunate to have a safe, effective way to break measles transmission: a vaccine.

While the eradication of measles is possible, that doesn’t mean it will be easy. It requires long-term commitment from the entire world. If a country immunizes less than 95 percent of its population, the virus can still spread efficiently from person to person.

Despite these challenge, the world has made giant advances against measles in the past few decades. Before the development of measles vaccines in the early 1960s, 7 to 8 million children died around the world every year. In 2014, that figure was down to 145,000 deaths. The World Health Organization estimates that between 2000 and 2013, measles vaccination prevented 15.6 million deaths. In the coming decade, new vaccination campaigns may drive down deaths from measles even more.

But the Disneyland outbreak demonstrates just how quickly the measles virus can undo years of public health efforts. By 2000, the United States had reduced measles to the point that it could no longer circulate on its own inside the country. A few cases cropped up each year, imported by people traveling from other countries where measles is still a problem. But in recent years measles cases have bounced back–helped by a growing number of unvaccinated people.

The rate of measles vaccination is slipping year after year. In Arizona charter schools, 9 percent of kindergarteners have been exempted from vaccination. People who don’t vaccinate their children tend to live close by each other, creating pockets of vulnerability where measles outbreaks can endure, as the virus finds one host after another. The vulnerable also include children who are either too young or too sick with other diseases to get a vaccine.

It’s possible that the Disneyland outbreak will mark a turning point–a recognition that vaccination is a social contract we make to each other, so that we don’t allow the virus to infect our fellow citizens. Perhaps we will someday even eradicate measles from the face of the Earth. That will unquestionably be a boon for humanity. But it’s also possible that it could open the way to a new disease.

That’s because the measles virus has cousins.

Measles belongs to a cluster of viruses called morbilliviruses. They infect a wide range of animals, from whales to wildebeest, from pandas to primates. It appears that morbilliviruses use the same strategy as measles–coming in through immune cells and going out through epithelial cells. And they’re also just as contagious. Some studies suggest that measles started out several thousand years ago as one of these wild morbilliviruses. According to one theory, after we domesticated cattle, a cow morbillivirus jumped into humans. As human populations grew dense, the new measles virus found a comfortable new home.

Scientists have documented virtually no cases of morbilliviruses spreading from animals to humans. Given the staggering contagiousness of morbilliviruses, that’s pretty amazing. It’s possible that our immunity to measles also protects us from other morbilliviruses. These animal viruses may sometimes make incursions into our species, but the conditions are so harsh that they never have time to adapt to our biology.

If that’s true, it’s possible that the eradication of measles would open up a new ecological niche that another animal morbillivirus could invade. This possibility doesn’t mean that we should stop fighting measles. Instead, we should broaden our efforts. Even as we eradicate measles, we should become better acquainted with related viruses and prepare for the possibility that they may become new threats. With the lessons we learn from eradicating measles, we can be ready to battle the next master of contagion.


For more information about viruses, see my book A Planet of Viruses. 

Thanks to Paul Duprex of Boston University for images and fact-checking.

Our Inner Viruses: Forty Million Years In the Making

Each year, billions of people get infected with viruses–with common ones like influenza and cold viruses, and rarer ones like polio and Ebola. The viruses don’t stay all that long inside of us. In most cases, our immune systems wipe them out, except for a few refugees that manage to escape to a new host and keep their species alive. In some cases, the viruses kill their unfortunate hosts, and end their own existence as well. But in some exquisitely rare cases, viruses meld with the genome of their hosts and become part of the genetic legacy their hosts pass down to future generations.

Scientists know this melding has happened because viruses have distinctive genes. When scientists scan the human genome, they sometimes come across a stretch of DNA that bears the hallmarks of viruses. The easiest type of virus to recognize are retroviruses, a group that includes HIV. Retroviruses make copies of themselves by infecting cells and then using an enzyme to insert their genes into their host cell’s DNA. The cell then reads the inserted DNA and makes new molecules that assemble into new viruses.

Most of the time, retroviruses behave like other viruses, jumping from host to host. But sometimes a retrovirus will end up in the genome of an egg or sperm. If it then ends up in a new embryo, the embryo will carry a copy of the virus in every single cell–including its own egg or sperm. And on and on, from parents to children to grandchildren.

If the virus DNA remains intact, it still has the capacity to multiply. It may produce new viruses that break out of a cell, and even leap into a new host. But over the generations, the virus DNA may mutate and degrade. It may no longer be able to escape its own cell. But the virus may still have a bit of life left to it: it can make new viruses that insert their genes back into the genome at a new location. Here’s a simplified diagram of how it works…

Dewannieux and Heidmann 2013
Dewannieux and Heidmann 2013

This process has generated a huge amount of viral DNA in the human genome. We carry about 100,000 pieces of DNA that came from retroviruses–known as endogenous retroviruses. All told, they come to an estimated 5 to 8 percent of the entire human genome. That’s several times more DNA that makes up all 20,000 of our protein-coding genes.

When biologists started sequencing the genomes of other species, they discovered that it’s taken millions of years to pile up all this viral DNA. They found some of the same endogenous retroviruses in the genome of chimpanzees, for example. Since our ancestors split from theirs about seven million years ago, this shared viral DNA must come from our common ancestor.

Gkikas Magiorkinis, a University of Oxford virologist, and his colleagues have now carried out large-scale survey of endogenous retroviruses in humans, apes, and Old World monkeys–a group of species that all descend from a common primate ancestor that lived some 40 million years ago. They catalogued the viruses in each species and compared them to the versions in the other primates. They were able to reconstruct the history of our viral DNA in unprecedented detail, even coming up with estimates for the rate at which the viruses inserted new copies into our genome.

The scientists can trace our viral DNA to 30 to 35 separate invasions. Once each virus established itself in our ancestors’ DNA, it produced copies of itself scattered through the genome. The rate at which new copies were inserted rose and fell over time, and at different rates in different branches of the primate tree. Here’s an overall look at the history of the viruses. (“Loci” here refers to new copies of viruses inserted into the genome in a given interval of time.)

Magiorkinis et al, Retrovirology 2015
Magiorkinis et al, Retrovirology 2015

Our monkey-like ancestors 40 million years ago acquired new virus copies at a fast clip–much faster than in our own lineage in the past couple million years. One virus in particular, known as HERV-H, was responsible for most of the new copies. It may have evolved adaptations that made it into a superspreader inside the genome.

In the Old World monkeys–represented in the new study by baboons and macaques–the rate of new virus copies pretty much stayed the same over the past 30 million years. But the apes tell a different story. The rate dropped in every ape branch. The same shift occurred in parallel in the ancestors of humans, chimpanzees, gorillas, orangutans, and gibbons.

It’s possible that some of this decline had something to do with the fact that we have been fighting back against our inner viruses for millions of years. A newly inserted virus may disrupt an essential gene, and the result may be that its cell may become cancerous. Scientists have documented this threat by studying mice, which are often the victims of retrovirus-driven cancer. And they’ve also found that mammal cells can minimize this risk in many ways. One way is to coil up virus DNA so that it can’t get copied. Another way is to make special proteins that damage newly made virus genes.

One thing that apes have in common is that they’re big. If you’re a big animal, that means you have more cells, and more cells should mean you have a bigger risk of developing cancer. Yet we don’t. The risk of cancer in a human is no greater than a mouse. It’s possible that an increase in body size drives the evolution of new defenses against cancer. And those defenses may include doing a better job of keeping viruses in check.

But Magiorkinis and his colleagues suspect that getting big can only explain some of the decline. In the human lineage in particular, viruses have slowed down drastically. Here’s a graph from their new study that tracks the frequency of new virus copies in the human genome over time:

Magiorkinis et al, Retrovirology 2015
Magiorkinis et al, Retrovirology 2015

In the past million years, only a single virus has continued to multiply–known as HERV-K. Today, you can find some HERV-K copies in some people and not in others. The pattern of these copies suggests that as recently as 250,000 years ago, HERV-K was still making new copies.

It’s possible that HERV-K is completely dead now. There’s no evidence that HERV-K or any other endogenous retrovirus is actively spreading or causing cancer. It’s hard to say at this point why humans have put the brakes on endogenous retroviruses. But Magiorkinis has one suggestion: our ancestors may have reduced their odds of picking up new viruses.

Retroviruses like HIV can be spread by blood. Other primates use their teeth as weapon, either to kill prey or to fight other primates. If their victim has an infection, they can get infected, too. Ancient humans evolved to gather food with tools rather than teeth. Males stopped chomping other males, a shift that is reflected in the shrinking canine teeth of our ancestors. By making ourselves less vulnerable to blood-borne viruses, we put a stop to the influx of retroviruses overrunning our genomes.

There’s no way of telling if we are done with new endogenous retroviruses for good now, or if HIV or some other new retrovirus will manage to work its way into our genes. But the history of our inner viruses is still important to our health. Scientists have found HERV-K proteins made in tumors, suggesting that cancer cells may harness some of the biochemical power in these ancient parasites. Knowing their past can let us understand how they’ll affect us in the future.

(For more information, see my book A Planet of Viruses.)

Reference: Magiorkinis et al, “The decline of human endogenous retroviruses: extinction and survival.” Retrovirology.

The common–and fairly awesome–cold virus

Like me, you may be snuffling with a cold today. You’re infected–typically in your nose–with a virus. The dominant cold-causing virusers are known as rhinoviruses, and they’re quite lovely. Here’s I’ve embedded a video of one, which lets you orbit the virus like you’re visiting an alien moon:

The Good Viruses?

When I talk about my book A Planet of Viruses, people often ask me if there are any viruses that are actually good for you. In an Ebola-obsessed age, it may be hard to imagine how the answer could be yes. But–yes! Or, at least, possibly yes. In my New York Times column this week, I write about a provocative new study that suggests a virus can play the same nurturing role as the microbiome, encouraging the growth of a healthy gut and a robust immune system. Check it out.

Norovirus: The Perfect Pathogen Emerges From the Shadows

As the year comes to a close, people are starting to puke. The notorious stomach bug known as norovirus is starting its annual rampage,, which will last from late fall through winter. A couple years ago, in the midst of another norovirus season, I wrote about the virus’s spectacular biology on the Loom. Noroviruses (unlike the Ebola virus) are extraordinarily rugged, able to waft through the air and survive for days on surfaces where it can cause a new infection. In a scientific review, one CDC scientist went so far as to declare, “noroviruses are perhaps the perfect human pathogen.”

This exquisite potency makes noroviruses a massive burden on our collective health. According to the latest estimates, noroviruses infect about 20 million Americans every year, and many more worldwide. But despite the scale of their threat, the fight against noroviruses has been slow. That’s because no one has been able to rear human noroviruses in the lab. To run experiments to see how noroviruses makes us sick, to develop vaccines, and to test out antiviral drugs, scientists desperately want a recipe for brewing up batches of noroviruses.

The inability to raise noroviruses stems, in turn, from our ignorance about some of the most important aspects of their biology. Scientists know that the virus attacks the gut, but they haven’t known for sure which kind of cell it attacks, or how it does so. They know that different noroviruses are more dangerous to people with different blood types–despite the fact that norovirus does not cause blood disease.

But now a team of scientists led by Stephanie Karst of the University of Florida may have cut through a lot of these mysteries. Karst and her colleagues have figured out how noroviruses get into our cells. And it turns out that some of our harmless gut bacteria are helping the viruses get there.

For years, scientists had assumed that noroviruses infected the cells that make up the inner lining of the intestines. After all, those cells (called epithelial cells) were the first ones that the viruses would encounter when they arrived in the gut.

If noroviruses infected epithelial cells, scientists could also explain the puzzling link to blood types. Our blood types are determined by the type of carbohydrates that festoon our red blood cells. But our gut epithelial cells also put the same carbohydrates on their surface too. Noriviruses can bind to these carbohydrates (known officially as human blood group antigens, or HBGAs).

Add up all the evidence, and you got a pretty straightforward scenario: noroviruses arrive in the gut, latch onto the HBGAs on the epithelial cells, invade those cells, and voila, a weekend of vomiting and diarrhea.

As sensible as that scenario sounded, though, there was one big problem: when scientists would run experiments, the viruses didn’t show any interest in infecting epithelial cells. Nor did the viruses seem to stay around on the surface of the intestines. Karst and her colleagues infected mice with a mouse version of norovirus, they found that it somehow burrowed deep inside the intestinal lining.

Buried deep in the lining of our gut, there are pouches of immune cells that protect us from intestinal infections. As food slides down through the intestines, the epithelial cells pick out suspicious-looking proteins and deliver them into those pouches. Cells known as B cells can then make antibodies that attack dangerous pathogens.

The deep dive that the noroviruses were taking raised the possibility that they were infecting B cells in the gut. Karst and her colleagues got even more interested in B cells when they ran another experiment on mice. The scientists were hoping to better understand how a norovirus infection may protect a mouse for future infections. As part of their experiment, they reared mice that couldn’t make B cells.

You might expect that the mice would become less able to withstand norovirus infections, since they couldn’t make antibodies. But the opposite was true: without B cells, the mice became more resistant.

Pondering all these pieces of evidence, Karst and her colleagues suspected that maybe B cells–not epithelial cells–really were the target of noroviruses.

The scientists tested out the idea on mouse noroviruses. When they mixed mouse noroviruses in a dish with mouse B cells, the viruses could indeed invade the cells, as the scientists predicted. But when they tried to infect epithelial cells, on the other hand, the viruses failed to invade.

The scientists couldn’t be sure that what was true for mice was true for humans. But testing their idea on human noroviruses would be a lot harder, since Karst and her colleagues didn’t have an endless supply of pure noroviruses.

Instead, the scientists had to collect stool samples from sick patients. They diluted the virus-laden stool and mixed it with human B cells. Just as they had hoped, the viruses infected the B cells.

There was, however, a fascinating catch. If the scientists put the stool through very fine filters–fine enough to exclude bacteria–the noroviruses could no longer infect the B cells.

This failure suggested that resident gut bacteria–or at least one species of bacteria–were helping the noroviruses.

It would have been absurd for Karst and her colleagues to test out every species of gut bacteria to see which one was aiding the noroviruses. Our guts contains many hundreds of species. Fortunately, previous research by other scientists allowed Karst and her colleagues to avoid this brute-force approach.

It turns out that blood type cells and epithelial cells are not the only cells to produce blood-type molecules. Certain species of bacteria have HBGAs, too. It’s not clear why they have the same molecules as we do. But whatever the reason, noroviruses can grab onto bacterial HBGAs as well as they can onto our own.

Diagram by Stephanie Karst
Diagram by Stephanie Karst

Karst and her colleagues picked out one of the species that other scientists had shown could bind noroviruses. It’s a common kind of bacteria called Enterobacter cloacae. The scientists added Enterobacter cloacae to filtered stool samples that contained human noroviruses. And then they combined this mixture with human B cells. Now they could get human noroviruses to infect B cells.

This experiment doesn’t reveal precisely how Enterobacter cloacae help noroviruses get into B cells. It’s possible that the bacteria ferry them into the hidden pouches where B cells lurk. It’s also possible that when the viruses latch onto the bacteria, the connection triggers a change in their surface molecules, making it possible for them to infect the cells. Karst hopes to get some answers with more research.

But this new results may offer an explanation for why people’s blood types make them more or less vulnerable to noroviruses. Let’s say you’re type B. Your immune system learns to recognize type B HBGAs as harmless, because they’re part of your own body. It’s possible that if you’re colonized by bacteria that have type B HBGAs, too, your body will tolerate them as well.

But if you get infected with bacteria that carry type A HBGAs, your immune system may make antibodies and attack them as foreign. That’s the likely reason that getting a tranfusion with the wrong blood type can be so dangerous. If you are Type B, for example, you have lots of antibodies to Type A HBGAs. So your body will attack Type A blood as foreign.

The new study from Karst and her colleagues may also explain why noroviruses seem to care about your blood type. Your blood type may determine the kinds of bacteria that can survive in the gut–and thus the kinds of bacteria that noroviruses can latch onto and use to get into B cells.

It would be great to say that this discovery immediately points to a sure-fire cure for the noroviruses blues. It doesn’t, alas. Karst and her colleagues were able to block norovirus infection in mice by using antibiotics to wipe out their gut bacteria. Without bacteria to help, the virus couldn’t get into B cells. But that’s the sort of cure that’s worse than the disease. The microbiome performs lots of important tasks, including helping with digestion and creating a kind of ecological barrier that prevents nasty pathogens from invading. Take it away, and you could get very sick–much sicker than you’d be with a norovirus infection.

Nevertheless, this discovery is still important, because it explains why previous attempts to raise noroviruses have failed. The viruses were provided with the wrong target and didn’t get the help they needed to hit it. Now, Karst hopes, she and her colleagues can finally develop a recipe to brew up lots and lots of human noroviruses for research on vaccines and antivirals.

And that’s the only sense in which the phrase “lots of lots of noroviruses” can make us happy.

Flu and Ebola: How Viruses Get Around

A couple viruses are waving hello to the United States right now. Flu season is about to kick off, while people have been diagnosed with Ebola not just in Texas, but in New York. But there are some important differences between the two viruses that I explore in an article in today’s New York Times. Most importantly: there’s no evidence that Ebola spreads through the air like the flu.

Ebola’s Past and Future

I have a story in the news section of today’s New York Times on the past and future of Ebola. There is so much anxiety and curiosity about the virus that it seemed like an opportune time to check in with a bunch of evolutionary biologists who study Ebola–as well as other viruses. In my piece, I make two basic points: 1) the scientists I’ve spoken to don’t think that the virus currently spreading around West Africa (and beyond) is some freakish mutant, and 2) it’s very unlikely that during this outbreak it will transform into some fundamentally different–and more dangerous–pathogen.

Reporting a story like this is a bit like dipping a bucket into a burbling fountain. There’s just too much to capture in a single article–especially a standard 1000-word newspaper piece. Fortunately, the Internet provides us with infinite overflow space.

So here I’d like to just expand on a couple of the more compressed points in my story. And I’ll extend an invitation to you, dear reader, to use the comment section below to post any questions my story raises in your mind. I’ll do my journalistic best to answer them in updates to this post. (I’ll also note any revisions I have to make to the post to correct any errors I’ve made.)

1. Ebola is 20 million years old? How do you know? Viruses are terrible at leaving fossils, but they can leave their imprint on their hosts.

Every now and then, a virus will insert some of its DNA into its host’s genome, and that viral DNA gets passed down their descendants for millions of years.

Our own DNA is riddled with viral DNA, which makes up at least 8 percent of the human genome. Most of it has mutated into useless baggage, but some has been transformed into useful genes (useful to us, that is). I’ve written here about how virus proteins are essential for our placentas to develop.

The presence of the same virus at the same spot in two different host species can give a clue to its age. That’s because the virus must have infected the common ancestor of the two species.

In recent years, scientists have been finding DNA from the lineage of viruses that includes Ebola (called filoviruses) in mammal genomes. Last month, they published an especially interesting study on this fossil virus material. They found the same viral DNA at the same spot in two species of rodents–hamsters and voles. And this DNA is more similar to Ebolavirus than to its closet relative, Marburg virus. Hamsters and voles share a common ancestor that lives roughly 20 million years ago, and so that means that Ebola viruses had split off from Marburg virus relatives at least that long ago.

There’s even some evidence that some of this Ebolavirus DNA is performing some useful jobs in its mammal hosts. It would be fascinating to learn more how this deadly virus has been domesticated.

2. Hasn’t Ebola gone airborne already? There’s been some suggestive evidence in the past, but scientists have questioned whether transmissions that seemed like they were airborne were just the result of short-range droplets–not long-range aerosols. Here is a report from July in which Canadian researchers tested out a bunch of nasty viruses for how easily they could be transmitted by air between monkeys. “In the current study,” they write, “two NHPs [non-human primates] were lethally infected with EBOV [Ebola virus], and no EBOV virus or antibodies to EBOV GP [a virus surface protein] were detected in the neighbouring uninfected NHPs for up to 28 days after the challenge date.” Here is a lengthy blog post from Heather Lander on this study and previous ones. And here is virologist Vincent Racaniello with more thoughts on the issue.

3. Mike Lewinski asks:

What is the likelihood that ebola might adapt to transmission by tick or mosquito? I know that it evolved to infect mammals and there’s no evidence it can infect insects now. Is infection of the insect cells a necessary prerequisite to transmission by insect?

As you’ve noted elsewhere, ticks are veritable “swiss army knife of disease vectors” and carry several different viruses such as Powassan virus which killed a woman here in Maine a year ago. Are any of those closely related to ebola?

My hunch is that this is another wolves with wings scenario.

One team of scientists have reported that they could get Ebola to replicate in mosquitoes, but another team failed to when they replicated the experiment. “This virus does not replicate in arthropods [mosquitoes and ticks] tested to date,” they concluded. In a new review on Ebola and related viruses, another pair of scientists stated, “The role of vectors [such as mosquitoes] is unlikely, but not known.”



Forecasting the Future of Flu

Influenza strikes every year, but every flu season is rife with uncertainty. In other words, it’s a lot like the weather–important to our lives, and hard to predict. For my new “Matter” column for the New York Times, I take a look at how flu researchers are borrowing the tools of weather forecasting to look into the future–with increasing accuracy. Check it out.

The Future of Fighting the Flu: My Feature in The Atlantic

A few weeks ago I went to my local drug story a got a flu vaccine. So far <knock on lab bench> I’ve had a pretty healthy flu season. But there’s a fair chance I may get the flu anyway this winter, because flu vaccine effectiveness is modest compared to vaccines for many other diseases. What’s more, I’ll need to head back next year to the store to get another shot. That’s because flu vaccines today are still based in some fundamental ways–in their production in chicken eggs and in the molecules they target on viruses–on World War II-era science.

I’ve written an article for the December issue of the Atlantic about how we got into this strange situation, and how scientists are trying to bring our fight against flu into the twenty-first century. Check it out.

MERS At One: The Deadly Virus Drizzle

We have the dubious privilege of observing a new disease in the midst of being born. The disease could go on to spread around the world, stall out as a minor, local blight, or disappear altogether. Scientists have been observing its emergence for a year now, and while they know more than they did in 2012, they still can’t predict quite what will happen. Part of their uncertainty stems from the fact that they still don’t know much about its past.

The disease I speak of is Middle Eastern Respiratory Syndrome–MERS for short. Last fall, doctors began recognizing this pneumonia-like disease in people who either lived in or passed through Saudi Arabia. Virologists soon isolated a virus common to them all, which they named MERS-CoV. Now, a year after its discovery, people are still getting infected with MERS, and many of the infected are dying. The World Health Organization reported on Friday that, from September 2012 to date, they’ve been notified of 130 people with laboratory-confirmed MERS-CoV infections, the vast majority of whom are in Saudi Arabia. Out of those 130 people, 58 have died.

Some scientists are scrambling to test out MERS vaccines and anti-viral drugs that can fight the pathogen. Others are acting as the virus’s historians, trying to figure out where it came from. Back in March, I wrote about the preliminary investigations into the origins of MERS. Now, six months later, researchers have looked at some of the viruses from newer cases, using powerful methods for statistically comparing the genes in the viruses. They’ve carried out the biggest genetic study of MERS so far.

The new study, from a team of Saudi and British scientists, appears in the journal The Lancet. (It’s free if you register. Or get it free without registering here.) The researchers isolated genetic material from viruses taken from 21 people sick with MERS. Many of them had become ill during a hospital outbreak in May 2013 in eastern Saudi Arabia. The scientists sequenced the full genome of 13 of the viruses, and got a third or more of the genetic material of the other eight. They compared the viruses to one another, as well as to other viruses that have been found earlier.

The differences between virus genes can tell scientists how the viruses spread to their victims. Each time a virus replicates inside a host, there’s a chance that its genes will mutate. Its descendants will inherit that mutation, and as more mutations stack up, they can create a fingerprint-like identifier for different lineages.

Reading these viral fingerprints isn’t easy, however, in part because viruses mutate fast. It’s possible for the same mutation to arise in two different lineages, or for a second mutation to reverse an earlier one, erasing a virus’s genealogical tracks. Scientists take on this challenge with statistics. Based on what they know about how viruses mutate–which mutations are more common and which less, for example–they can calculate the most likely evolutionary tree to explain the genetic diversity in a group of viruses.

Scientists can then overlay other kinds of information on this tree to probe the virus’s history. They can estimate how long ago the viruses all split from a common ancestor by adding up their mutations and comparing that figure to the rate at which the viruses mutate.

They can also trace the spread by looking at the geography of infection, noting where different lineages of the virus infected people. It’s even possible in some cases to get clues about how an outbreak spreads from person to person by tracking the mutations carried the viruses in each patient. (In January described this new method in this feature for Wired about a deadly bacterial outbreak.)

What’s striking about the new results is the difference between different groups of the MERS viruses. The scientists found that the viruses fell into distinct genetic clusters, suggesting that they’ve been diverging from other clusters for a long time. One virus isolated from a patient from Riyadh on October 23, 2012 was on a separate branch from another virus isolated from another Riyadh patient a week later. That suggests that two virus strains were circulating in the city at that time.

That’s not to say that all of the viruses were distantly related to each other. Some of the viruses in the May 2013 hospital outbreak were very similar, genetically speaking–so similar, in fact, that the scientists could track their spread from one patient to another. Nevertheless, even in the hospital outbreak, some of the viruses were distantly related to the others.

When the scientists looked at all the genetic diversity of the viruses in their study, they concluded that their common ancestor emerged in July 2011, over a year before MERS was identified. There are a couple possible scenarios in which MERS viruses could have evolved this way.

Hypothetically, MERS might have leaped from an animal to a human over two years ago and then spread from one person to another, splitting into genetically distinct branches. The researchers find this unlikely. If that were true, you’d expect that doctors would have encountered a lot more sick people along the virus’s path.

The alternative is that the virus has been jumping again and again from animals. They’ve been circulating in some animal host for the past couple years, splitting into different lineages. Those different lineages have independently infected humans. Once the viruses cross over, people may bring them to cities, such as Riyadh, and from there to other parts of the country. Along the way they sometimes spread the virus to other people–especially in hospitals, where the virus encounters sick people with weakened immune systems.

Back in March, I noted that MERS closely resembles viruses in bats on other continents. Researchers at Columbia University identified short fragments of MERS virus in Saudi bats, but a number of virologists find the results far from conclusive. Even if MERS did get its start in bats (which happened with other human diseases like SARS and Nipah virus), people may not be getting sick from direct contact with them. One possibility scientists are investigating is that camels or other livestock have picked up MERS from bats, and are now passing it on to people.

These results got me wondering. Should we feel comforted by these results, or freaked out, or warily mindful? We might take comfort from the fact that all of the people sick with MERS do not seem to form a single human-to-human chain of infection. Instead, they form many chains, most of which may have few human links. That pattern might mean that MERS is lousy at spreading among people and a poor candidate for a new scourge.

On the other hand, perhaps we should feel a chill up our spines when we consider that MERS is peppering our species boundary, implying that there’s a big supply of the viruses in close contact with us in some unknown species, and one of them may manage to get through and evolve into a fast-spreading human scourge.

Hoping for a little clarity, I got in touch with Andrew Rambaut of the University of Edinburgh, one of the co-authors of the new paper. Rambaut has studied a number of these boundary-crossing viruses, including influenza, SARS, and HIV.

To Rambaut, success for a cross-over virus is largely a matter of luck. “It is down to a virus with the right properties getting into an adequately connected network to allow sustained transmission,” he told me.

HIV, for example, probably infected a lot of people in rural west central Africa over many years without reaching sustained transmission. Only when it happened to get from the bush into the city of Kinshasa in the mid-1900s did it take off. SARS, likewise, exploded once it got into the urban regions of southern China.

The research Rambaut and his colleagues have carried out on MERS shows that the virus is indeed mutating. But even in the hospital outbreaks, they haven’t seen any clear evidence that those mutations are favored by natural selection for spreading among humans. And Rambaut sees little opportunity for MERS to undergo that transformation.

“Natural selection requires time and numbers,” says Rambaut. “It can’t pull a rabbit out of a hat.”

In other words, a virus needs a big population and many generations for natural selection to allow a mutation to rise to dominance. Rambaut estimates that MERS has infected hundreds of people at most. If one virus inside a person gains a mutation that increases its spread among humans, the odds that it will be the one that gets the chance to infect another human is tiny.

For now, in Rambaut’s view, MERS is a virus that relies on chronically ill people to spread. In hospitals, it can find lots of new hosts, and so it can sustain its population. Outside of hospitals, it fares poorly and will be unlikely to do better.

Of course, Rambaut warns that this conclusion is based on what he calls “wildly inadequate information.” This recent article by Helen Branswell provides an excellent survey of what scientists have learned after a year of studying MERS, and it’s a small fraction of what was learned after a year of studying SARS. Basic epidemiology has yet to be carried out on MERS, according to Branswell’s sources, and we don’t even know what animals are hosting the virus yet. The latest study on the history of MERS brings it into sharper focus, but a lot of blurriness remains.


Where Plagues Come From: Making A Catalog of the World’s Viruses

In 1999, a new disease came to light–a brutal fever that sometimes led to fatal encephalitis. After the first outbreak in Malaysia, scientists traced the cause of the disease to a virus called Nipah. Although it was new to medicine, Nipah virus didn’t come out of thin air. It had replicated for generations inside Indian Flying Foxes, a common species of fruit bat in southeast Asia. The virus spilled over into humans, thanks to the fondness both species have for date palms. Now Nipah virus can spread from person to person.

This scenario sounds like it came from the pitch meeting for last year’s creepfest Contagion. Unfortunately, it’s all quite well documented. So is the emergence of many other viral diseases. (Check out David Quammen’s book Spillover for a sweeping view of these new diseases.)

In my Matter column this week in the New York Times, I take a look at a new way to battle these emerging diseases: by figuring out how many viruses there are in mammals that might spill over in the future. Scientists have taken the first step to such a virus catalog with a suitable species: the Indian Flying Fox. And unfortunately, it’s chockful of mammal viruses, most of which are new to science. Here’s the full story. (Also check out fellow Phenom Ed Yong’s report on the study for The Scientist.)

The Renewed Hope for Virus-Repaired Genes: My New Story for Wired

Since the mid-1900s, medical researchers have dreamed of fixing genetic disorders by supplying people with working versions of genes. By the late 1990s, that dream–known as gene therapy–seemed very, very close. Scientists were developing engineered viruses that would infect patients with DNA that would allow their bodies to make the proteins they needed to survive.

But then, in 1999, a young man who had volunteered for a trial died. The whole field of gene therapy went into a tailspin. Only in recent years has it recovered.

I’ve written a story for Wired about that turnaround, focusing on the career of the scientist who oversaw that fateful 1999 trial, James Wilson. For the past fourteen years Wilson been hunting for better viruses for gene therapy, and his viruses are now involved in some of the most promising research for treating diseases ranging from hemophilia to blindness. To find out more about Wilson and gene therapy, check out “The Fall and Rise of Gene Therapy.”

Gigantic Giant Viruses and the Endless Viral Frontier

Pandoravirus. Photo by Chantal Abergel and Jean-Michel Claverie
Pandoravirus. Photo by Chantal Abergel and Jean-Michel Claverie

In my column this week for the New York Times, I write about the discovery of record-breaking viruses called pandoraviruses. They’re 1000 times bigger than a flu virus and have almost 200 times as many genes–over 2500. That’s twice as many genes as the previous giant-virus record holder, which I blogged about in 2011.

These giant viruses are important to our understanding of what the difference is–if any–between viruses and the rest of life. But they’re also part of a bigger story, one that inspired the title of my recent book A Planet of Viruses. Viruses are the most common life form on Earth, they are by far the most genetically diverse, and we have barely started to explore the viral frontier.

That frontier includes giant viruses–and tiny ones, too. Just last week, for example, Jessica Labonte and Curtis Suttle of the University of British Columbia published a survey of another group of viruses called single-stranded DNA viruses. Their ranks include parvoviruses, which cause an infection sometimes known as the Fifth Disease. If you’ve gotten it, like I did a few years ago, you know that feeling it provides you that someone has been using your body as a punching bag for hours.

The ranks of single stranded DNA viruses include many other pathogens of plants and animals, plus others that infect bacteria. They are exquisitely small, with as few as three genes.

Labonte and Suttle searched through sequenced of DNA that have been trawled up from sea water at a few sites around the world. They found a lot of single-stranded DNA virus genes, which they compared to the seven known families of the viruses. They realized they have probably discovered 129 new families.

Just another week on the viral frontier…