The National Institutes of Health in Maryland keeps samples of the 1918 flu virus in a freezer at an undisclosed location. It’s not easy to get anywhere near that locked freezer, let alone inside it. First, you have to get onto the campus of the NIH, which requires identification, a reason to be admitted, and a PhD, preferably in one of the life sciences. Once you get through and find the building, a guard has to buzz you in via an airlocked entrance with double doors. Inside, you will pass through a metal detector and then be firmly guided toward a locker, where your cell phone, thumb drive, computer, pager, and camera must be deposited. Then, and only then, will you be escorted farther into the building.
Jeff Taubenberger makes this trip every day. He is the chief of the Viral Pathogenesis and Evolution Section, a laboratory within NIH. His unit houses a couple of dozen scientists, postdoctoral students, and fellows researching the influenza virus, who refer to it simply as “1918.” Their offices sit around the perimeter of a rectangle of sealed labs. In one of those labs, in a freezer, rests the 1918 virus, frozen and tamed. It took an epic effort to bring 1918 back from the dead. Scientists traveled to the ends of the earth, scavenging for stowaway viruses in buried corpses. Researchers hunted through dusty archives and painstakingly reconstructed genomes. If 1918 was purely a thing of the past, we couldn’t study it properly. We had to keep 1918 present. It was a difficult and dangerous proposition, and it started with a gimmick.
* * *
After completing medical school, Taubenberger began his career at the NIH, where he trained as a pathologist. In 1993, not long after getting his PhD for work that focused on stem cells and lymphoma, he was recruited by the Armed Forces Institute of Pathology (AFIP) at the Walter Reed Army Medical Center, a few miles away. There he was to set up a new department of molecular pathology, which would demystify diseases using DNA analysis. In the early 1990s new lab tricks and techniques allowed pathologists to analyze the DNA of tissues that had been biopsied and embedded in small paraffin cubes. This was a big deal because until then, it was only possible to analyze the DNA from frozen specimens, which involved costs and complications. In contrast, paraffin-embedded samples can be kept on a shelf in the lab. Taubenberger studied ways to handle these tissues, and hadn’t given a thought to flu. But then Congress got involved.
In 1994, with majorities in both the House and Senate, Republicans became locked in a series of nasty partisan battles with Democratic president Bill Clinton. In one of the many skirmishes over spending cuts, Congress toyed with the idea of abolishing the AFIP, where Taubenberger had recently been appointed the department head. As a result, he was under pressure to show Congress that the institute was worth keeping.
One way to do that was to demonstrate the scientific value of the tissue samples it contained. Taubenberger knew that the records of all its specimens were computerized and therefore searchable—all of them—going back nearly a hundred years. Perhaps, he thought, the institute might house an original tissue sample from a victim of the 1918 pandemic. If it did, the new techniques would allow him to sequence the genetic code of the virus. Now, that would be impressive—and surely enough to demonstrate the value of the institute in an era of cost-cutting.
He combed through specimens, using terms like “flu,” of course, and “gripe,” the Spanish word for “flu.” He found twenty-eight samples. Now he could apply the techniques of his molecular pathology lab. Usually, he would work to identify the genetic characteristics of a cancer in a living patient, which could then help doctors to identify a targeted therapy. This time, however, he wanted to reveal the genetic building blocks of a virus long dead.
To begin the process of uncovering the genetic code of 1918, Taubenberger needed to find the right kind of specimen. Like all flu viruses, 1918 reaches peak replication two days after infection. After about six days the virus stops multiplying, and it is no longer found in the lungs. This meant that tissue from a patient who had contracted the 1918 virus and died from a bacterial pneumonia several days later could not be used. Their tissue would not contain any viral particles; instead, it would be overrun with the bacteria that so often followed the viral infection.
So Taubenberger and his team had to find samples from patients who had died within a week of the initial symptoms. In one sample, tissue from each of the victim’s two lungs showed slightly different pathological changes. In one lung researchers found bacterial pneumonia, which was useless in this endeavor. But the other lung showed acute swelling of the walls of the tiny bronchi. This was enormously significant because this swelling is seen only in acute viral pneumonia, which meant Taubenberger had discovered a pathologist’s smoking gun: he knew that while most of the victims had died from the complications of the influenza virus, this victim had certainly died from lung damage caused directly by the virus. He named this victim “1918 case 1,” and this sample would be the key to identifying the genome of 1918. The sample belonged to Private Roscoe Vaughan.
On September 19, 1918, at Camp Jackson near Columbia, South Carolina, Private Vaughan came down with a fever and chills. One week later he died. After an autopsy, small specimens of his lung were preserved and set into wax, and then sent to the Army Medical Museum in Washington, D.C.—which later became a division of the AFIP. There they lay for almost eighty years, until Taubenberger and his team discovered them in 1994.
The next goal was to reconstruct the genes contained in the bits of virus in Roscoe’s single lung. But this reconstruction would require millions of copies of the virus, a number far higher than those found in the sample. So Taubenberger had to make copies of the few bits of the viral genes that were left, in the same way that you would photocopy a single sheet of paper. His lab was able to amplify the chains of some fragments of the genes that they found. One of these fragments was the gene that coded for HA, the influenza hemagglutinin that we first discussed in chapter 2. HA, remember, is a critical part of the weaponry of the influenza virus because it allows the particle to recognize the victim’s cell, like a radar acquiring its target. HA is more than just a radar, though. Once the virus particle locates and attaches to its target cell, HA then breaches the cell’s membrane, like an invading army storming a castle.
Taubenberger set to work with his genetic copier on pieces of the virus that were viable. When he had enough material to analyze, he identified the genetic code that built the hemagglutinin protein on the surface of the 1918 influenza virus and compared it with the genes of other influenza viruses. This piece of genetic detective work—routine today but groundbreaking when it was first performed more than twenty years ago—settled a long debate as to the provenance of 1918. The virus appeared most closely related to a kind of swine flu, although later work would show this strain also had some features in common with bird flu. The official name of the strain would be Influenza A/South Carolina/1/18 (H1N1), after the state from which the sample had originated.
Today, it would take about two weeks to sequence the entire genetic code of 1918, but in the 1990s it took five years for Taubenberger and his team of laboratory workers to identify the complete genome. Along the way, understanding the influenza virus became Taubenberger’s professional calling—an accidental by-product of an effort to save his lab from Newt Gingrich’s Congress. “It was a gimmick,” he said. “I had never taken a class in virology in my life.”
Taubenberger’s original research identified four fragments of the HA gene segment. Like all genes, they were built out of only four nucleotides, referred to by the letters A, G, C, and T. The building block of 1918, found in one of those fragments, opens like this:
AGTACTCGAAAAGAATGTGACCGTGACACAC
It was the sequence of these four letters, repeated thousands of times across only eight different genes, that turned 1918 into a killing machine. The 1918 influenza virus was composed of various parts, each with a particular role. Some enabled the virus to enter the lung cells; others directed the hijacked cells to reproduce the virus and then to release it, allowing it to infect more victims. When joined together, the virus became deadly.
Taubenberger, together with his lab team, had successfully discovered and then decoded the genetic makeup of the 1918 influenza virus. Later work would use new and faster techniques to verify their findings. But their efforts had been limited by the tiny amounts of raw lung material that they had. They needed more samples to confirm their work, but had exhausted their search among the dusty slides at the AFIP. Help would come from a most unexpected source: a Swedish pathologist who, decades earlier, had failed in his own attempt to find the virus.
* * *
In 1949, Johan Hultin came to the United States from Sweden as a visiting medical student. In his twenties and fascinated by influenza, he had taken advantage of a program at the medical school of Uppsala University that allowed its students to spend time abroad. Hultin had chosen to travel to the University of Iowa, both because of its reputation and because of the large community of Swedish immigrants who lived in the area. There he intended to study the reaction of the body to influenza.
In January 1950 Hultin had a chance meeting with Roger Hale, a leading virologist who was visiting from the Brookhaven National Laboratory. Hale, who knew that the Swede was interested in flu research, told Hultin that in order to advance the field he needed actual specimens of the 1918 virus. “We just don’t know what caused that flu,” Hale told him. “Somebody ought to go to the northern part of the world and try to find a victim of the 1918 flu pandemic buried in the permafrost. That victim is likely to have been frozen since 1918, and you could try to recover the virus.”
The conversation quickly moved on to other topics, but the remark made an impression on Hultin. He immediately asked his faculty adviser if he could change the topic of his PhD thesis. Now, instead of studying influenza in the lab, he wanted to get out and hunt for the virus itself. He would find a buried, preserved sample and then analyze it. And that could reveal what made the 1918 influenza virus so deadly.
Hultin was uniquely prepared to search the permafrost. He enjoyed traveling, and before joining the University of Iowa, he had worked in Fairbanks, Alaska, for a German paleontologist named Otto Geist, who gave him free board in return for help digging up mammoth tusks in the Arctic. Now Hultin wanted to return to Alaska, where the bodies of those who had died in the 1918 pandemic were buried in the permafrost. He wrote to Geist and asked if the paleontologist could introduce him to the local Inuit villages and missionaries who worked there. Perhaps Geist could ask those missionaries if they still had records of victims from the 1918 epidemic and where they had been buried. Hultin was only interested in bodies that had been buried in the permafrost, their lungs preserved with intact viruses frozen inside. He also applied for a $10,000 grant from his adoptive university to go find them. That’s about $100,000 in today’s money—a lot to invest in a visiting foreign student—but the university bought into the harebrained scheme.
Hultin met Geist in Alaska in 1951, and together they traveled to Fairbanks, and then another five hundred miles west to Nome, on the shore of the Bering Sea. Once there they discovered that a local river had changed its course, and during floods had melted the permafrost. There were no soft tissues left, no lungs had been preserved, and so there would be no virus to sample.
Hultin was undeterred. He hired a pilot to fly him to another site, this time farther north: the village of Wales, where almost half of the 400 residents had died in the 1918 epidemic. There was a mass grave, marked by a large cross, that contained the remains of the flu victims. But once again, he found that the permafrost had not been so perma. Hultin persuaded the pilot to fly him on to Brevig Mission, a tiny village on the shore of the Bering Sea, where 72 out of 80 residents died of 1918. But Brevig did not have a landing strip, so he touched down on the beach at a neighboring village, crossed the open water on a whaleboat, and then walked six miles through the soggy tundra.
His tenacious efforts paid off. In Brevig the permafrost was deep enough to have preserved the bodies buried there. In addition, Hultin found three survivors of the 1918 pandemic, whose support would be invaluable. He asked them to describe to the rest of the villagers what it had been like to live through the epidemic, and to witness the deaths of almost everyone during one horrendous week in November 1918. Hultin then explained to the villagers that obtaining a specimen of the virus could create a vaccine and prevent another outbreak. With their support, and that of the village council, he was given permission to proceed.
At first Hultin dug alone. He hacked through the topsoil with a pickax until he hit the permafrost. Using driftwood collected from the beach, he then started a small fire that melted the frozen layer. By the end of his second day he had reached a depth of four feet. There he uncovered the body of a girl, aged about twelve years. The body had been well preserved, and this encouraged him to dig even deeper to find better specimens. He was soon joined by his faculty adviser, a pathologist, and Otto Geist, the paleontologist. At a depth of six feet they found three other bodies. A postmortem exam of the lungs showed they were also preserved, and therefore likely to contain the 1918 virus.
In all they exhumed five bodies, dissected them, and took small cubed samples from their preserved lung tissues. In what seems today to be an insanely reckless move, they wore only gloves and surgical masks for protection. The specimens were transported back to Iowa on dry ice, where Hultin injected mixtures of them into the amniotic fluid of growing chick embryos, the ideal medium for the flu virus. Disappointingly, the virus did not reproduce, so Hultin moved on to live animals—mice, guinea pigs, and ferrets—but was unable to infect any of them with the flu.
It seemed the virus that had killed so many was no longer viable. It had been destroyed by time and the extremes of nature. Eventually Hultin ran out of tissue specimens, and there was nothing more to be done. The expedition ended as a scientific failure. Hultin never finished his PhD. Decades later, though, he’d get a shot at redemption.
* * *
For the next forty-six years, Johan Hultin’s expedition remained forgotten. He became a pathologist, settled into his career, and continued to travel with his wife. He rebuilt an ancient stone maze in Iceland and hiked in England and Turkey. “I’m going to settle down when I get old,” he told a reporter. “I have to do these things now. I’m afraid the warranty will run out.”
Hultin, always on the lookout for an adventure, found a new mission in 1997. It was a quest that completed the search for the influenza virus he had started nearly fifty years earlier. While retired and living in San Francisco, he read about Taubenberger’s work uncovering some of the genetic sequencing of 1918 from the dusty archives of the AFIP. Intrigued, Hultin wrote to Taubenberger and told him of his 1951 expedition and its disappointing outcome. He offered to fly back to Brevig and try to recover the flu virus a second time. Hultin would finance the mission on his own. It would be a one-man expedition to finish what he’d started.
Hultin had some competition. Around the same time, a thirty-two-year-old geographer at the University of Toronto named Kirsty Duncan was planning her own much larger and well-funded expedition. Duncan was initially interested in the relationship between the flu and the climate, but she also wanted to get her hands on a sample of the 1918 virus itself, to better understand what made it so deadly. She apparently hit upon the idea of an Alaskan expedition independently of Hultin, but was unable to narrow down her search to any known victims. Duncan turned her attention instead to the archipelago of Svalbard, which lies in the frigid sea between Norway and Greenland. Duncan discovered that seven miners had died from the flu in October 1918, soon after they had arrived for work at an outpost called Longyearbyen. If the permafrost had actually done its work, their bodies—along with the 1918 flu virus—would be preserved.
Duncan then put together an international team: the chief of the influenza branch at the CDC, a pediatrician and a geologist from Canada, an American virologist, and Dr. John Oxford from London. Oxford was a virologist with a long-held interest in the influenza virus and, you may recall, had a theory that the 1918 outbreak had originated in northern France.
Duncan was in the midst of preparations when Jeff Taubenberger and his colleagues published their paper that detailed the findings of Private Roscoe’s flu virus. Duncan and Taubenberger, unaware of each other’s work, met at a workshop in Atlanta that was convened to discuss Taubenberger’s reconstruction of the genetic code of the 1918 virus. Taubenberger offered to analyze any samples that Duncan obtained from the bodies of the miners in Svalbard.
But after the publication of Taubenberger’s paper, was Duncan’s plan still necessary? On the one hand, there was the cost, and the risk that exhuming bodies could expose the expedition—and the rest of the world—to infection. On the other hand, there were scientific concerns that the specimen of Roscoe Vaughan’s lung had somehow been altered by its long bath in formaldehyde. If that had happened, it would be critical to obtain additional samples of the virus and compare them to those in Taubenberger’s possession. Scientists at the CDC, which had once committed funds to support the expedition, now questioned its purpose. Citing a tight fiscal year, they withdrew from the project, taking their funding with them. Duncan’s team still had the support of the National Institutes of Health, and had secured a grant from the pharmaceutical giant Roche. They made the decision to proceed to Svalbard, buoyed by a federal grant for $150,000. There, they would use ground-penetrating radar to locate the bodies, and build a secure biohazard tent over the graves to minimize any risk.
Meanwhile, Johan Hultin, now seventy-two years old, returned to Alaska to dig once again. The village elders in Brevig Mission not only gave him permission to exhume the bodies but also provided four young men to assist him. They dug with pickaxes and shovels and eventually reached a depth of seven feet. And so it was that in August 1997, after three days of digging by hand, Hultin and the four villagers found the body of an obese woman whom he would name Lucy, out of respect for her and the contribution she might make to science. Hultin was photographed kneeling next to a small pile of Lucy’s remains, wearing waders and a pair of surgical gloves. Her body fat had insulated her organs when the permafrost occasionally thawed. As a result, her lungs were intact. Hultin removed them, hoping they would contain the 1918 virus, and mailed specimens to Taubenberger using three different carriers to minimize the risk that they would be lost. Within a week, the lab confirmed the presence of 1918 flu particles in them. With more lung tissue than ever to work with, Taubenberger’s lab could now rebuild the entire genetic code of the 1918 virus. The entire code.
Taubenberger announced the success of Johan Hultin’s second expedition in August 1998, just as Kirsty Duncan and her team left for Svalbard and the town of Longyearbyen. Kneeling on the ground and armed with shoe-box-sized ground-penetrating radar, they identified the likely area in which victims had been buried. They dug for eight days inside the biohazard tent before striking the lid of a coffin. The team’s elation was tempered by the coffin’s location in the upper layer of the permafrost, which meant that the body inside had likely thawed at some point. Out of respect for the dead, the team never publicly discussed the condition of the bodies, though the New York Times reported that they had been buried without clothes and were wrapped only in newspapers. Several samples of soft tissue were collected, but none was in a condition to provide viral particles. Duncan returned from Svalbard empty-handed, though she found renown later. In 2015 she became Canada’s minister of science in the cabinet of Prime Minister Justin Trudeau.
And the town of Longyearbyen also found later fame. In 2008 it was chosen to house the Global Seed Vault, where seeds from across the world are sent for safekeeping, in case of a global agricultural disaster. The vault is buried five hundred feet below the permafrost, can withstand bomb blasts, and contains more than a quarter of a million species of seeds. Once the site of so much death, Longyearbyen is now a monument to the living, to endurance, and to survival.
And so, thanks to Johan Hultin’s intervention, Taubenberger’s lab became the sole custodian of samples of the 1918 flu virus. But because each sample might yield only part of the genetic code of the 1918 influenza virus, still more were needed. The search widened, and researchers who had read Taubenberger’s original data hunted through their own specimens and slide collections. The Royal London Hospital, which had been founded in 1740, was certainly old enough to have treated patients in the 1918 epidemic. A search through its autopsy archives found two preserved samples of lung tissue as well as the clinical records of the patients to whom they belonged. These records put the preserved specimens into a clinical context that had been missing until now. They described when the patients became ill, how their illnesses progressed, and what the victims looked like as they succumbed to the virus. The records also ensured that the tissue specimens that had been found were taken from victims of the influenza virus itself, and not from a patient who had died due to a secondary bacterial infection.
When Taubenberger compared the genetic fingerprints across all the samples, he found something remarkable. Although they were separated by 7,500 miles (the distance from Brevig Mission to London) and by several months (the earliest sample came from September 1918 and the latest from February 1919), the genetic material of these viruses was 99 percent identical. This suggests that only a single strain of influenza was in circulation in the early stages of the 1918 outbreak, and that just one specific antiviral drug or vaccine might be effective during the most lethal wave of any future flu pandemic.
Today, Jeff Taubenberger continues to hunt for specimens of the 1918 virus that may be preserved in pathology collections around the world. So far he has been unsuccessful, but he retains his trademark optimism. After all, additional samples could further address the question of whether more than one flu strain circulated in 1918 and shed light on how the lethal virus evolved. But sequencing its genetic code cannot by itself help us understand why the 1918 virus was so lethal. It does not tell us how the virus worked when it infected or why it spread so quickly. To answer these questions, scientists would need to build a brand-new, fully functional copy of the extinct virus.
* * *
The resurrection of the 1918 virus took several years of collaboration between the Centers for Disease Control and Prevention, the Mount Sinai School of Medicine in New York, the Armed Forces Institute of Pathology in Maryland, and scientists from the U.S. Department of Agriculture. The actual building of the virus took place in Atlanta, in a CDC biosafety lab where scientists wore breathing hoods. Although the influenza virus was—and continues to be—easily spread between people, to cause illness it must be inhaled. A breathing hood was sufficient protection. In addition, it was thought that the scientists would have a degree of immunity to the 1918 virus, since its flu descendants had been circulating each fall and winter in the interim. At least, that is what they hoped. Just to be sure, those directly working with the virus took prophylactic doses of antiviral medications.
In 2005 the team announced that it had built several versions of the 1918 virus. The first was a fully working clone, with all eight of the original genes of the 1918 flu virus. It was capable of infecting test animals (and humans). The team also rebuilt versions of the virus that contained only one or three or five of the original eight genes, to use as controls. To test how lethal the virus was in mammals, the 1918 virus was sprayed into the noses of mice. Many died within three days. The lungs of these mice contained almost forty thousand times the amount of virus as the lungs of mice infected with the control version. If that wasn’t scary enough, the working eight-gene clone turned out to be at least one hundred times deadlier than the five-gene version. With a little more detective work, it became clear that the cause of this turbo-charged virulence was the gene that coded for hemagglutinin (HA), the critical protein that sits on the surface of the virus and attaches it to our cells.
Scientists now had at least a partial explanation of why the 1918 virus was so deadly, but there was still more to learn. One of the clinical features of the 1918 flu pandemic was a bloody, frothy cough that rapidly developed in the victims as the lining of the lungs was eaten away. From looking at specimens of the lungs from the infected mice, it was apparent that the resurrected 1918 virus was able to attract special white cells called neutrophils. These cells are recruited as part of the immune response to fight the virus, but when they go to war they produce a great amount of collateral damage to the healthy lung tissue itself, allowing a secondary bacterial pneumonia to develop. It had long been thought that some of the deaths in 1918 resulted from a “cytokine storm,” an overabundance of proteins that play an important role in our immune system. Now for the first time there was evidence that supported this theory.
There was another secret that the 1918 virus gave up in its resurrected state. One of the proteins that the virus manufactured was nearly identical to a protein made by bird flu viruses. This suggested that the 1918 virus did not arise as a result of reassortment, in which a few of its genes traded places with the genes of a bird flu strain. Instead the 1918 virus appeared to be a bird virus that somehow adapted to humans. It also seems to have spent some time in a mammalian host, although we still do not know which one. The 1918 virus traded a few genes with this mammal until it evolved into a perfect killer virus. It had just enough new proteins on its surface to be unrecognizable by our immune system. One of those proteins, HA from a bird virus, caused the body to mount an uncontrolled inflammatory response, destroying its own lung tissues in the process. And the virus generally didn’t kill its victims until several days after it infected the lungs, giving it time to replicate in its new victim and to be coughed out into the lungs of others.
When the resurrection was revealed in the October 2005 issue of Science, scientists were shocked and alarmed. Was the published paper too detailed in its description of the process? It is standard practice for scientists to share their experiments and results; this allows others to replicate and verify the original experiments, and it buoys the authors’ reputations. But wouldn’t information on how to resurrect the deadly virus be dangerous if it fell into the wrong hands?
The newly active 1918 virus rekindled a debate over “dual use” information. These new flu details could be used to create vaccines and treatments, prevent a repeat pandemic, and improve the health of our civilization. Or they could be used for nefarious purposes: hostile governments or terrorist groups could perhaps weaponize the flu. A great deal of scientific information is dual use, meaning it can be used for both good and evil. When physicists first split the atom in 1939, they realized nuclear energy could be used to either power a city (with a generating plant) or destroy it (with a bomb).
Before the re-creation of the pandemic influenza virus, there had been another dual-use controversy that began in 2002. Scientists from Stony Brook University announced that they had produced a polio virus from scratch by using a map of the virus that was available online and purchasing the chemical building blocks through a mail-order company. But could this information also allow a fanatic to build copies of polio without having access to a natural virus? What if terrorists used this methodology to build a highly contagious virus, like Ebola?
An attempt to resolve the dual-use question began in 2005, when the National Academies of Science appointed a committee to address it. After much deliberation and a report called Biotechnology Research in an Age of Terrorism, the committee recommended that the scientific community police itself. In an age of global information sharing, it made little sense to regulate papers published in the United States alone, because the authors would simply turn to a journal in another country with less stringent rules. To help scientists with their task of self-regulation, the committee also recommended the appointment of a National Science Advisory Board for Biosecurity (NSABB), which could provide advice and guidance.
Donald Kennedy, the editor of the journal that published the resurrection paper in 2005, had to grapple with the implications of having done so. Would the instructions on how to build the virus fall into the wrong hands and lead to a mass dispersal in a crowd at a football game, in a mall, or in the subway? Would the resurrection of 1918 lead to a repeat of 1918?
Before publishing, he sought advice from officials at the CDC and the NIH, all of whom supported publication. At the eleventh hour, Michael Leavitt, the secretary for the U.S. Department of Health and Human Services, insisted on getting approval from the NSABB. The paper went to press without the approval. Kennedy stuck by his decision, noting that the government “can’t order the nonpublication of a paper just because they consider the findings ‘sensitive.’ ”
Scientists are by definition a curious bunch, and now they had a sample of the 1918 virus to tinker with. What would happen if they added one kind of influenza gene or removed another? Would the virus become more or less deadly? Over the next several years the scientific community continued to study not only the 1918 virus but also several other pandemic flu viruses. For example, the H5N1 virus does not naturally have the ability to spread via droplets in humans, but it certainly could evolve that capability by the natural process of gene reassortment that happens in the wild. What would happen to the virus then? Would it become more deadly, as might be expected? Or would there be an unexpected genetic interaction within the virus that rendered it less dangerous?
There was only one way to find out. In 2012 an international group genetically modified the H5N1 virus and infected ferrets with it. It soon mutated and became airborne, but to everyone’s surprise, it also became less deadly. In another experiment, researchers at the University of Wisconsin took an avian flu virus that was similar to the 1918 influenza virus and tinkered with its genes just a little. When this virus was tested on mice, it proved to be more lethal than the original avian virus from which it originated.
All this tinkering was creating superviruses that did not exist outside the lab and that might be more easily transmissible between different species, or more virulent, or more resistant to any influenza vaccine. Most researchers were insistent that these “gain of function” studies were needed to better understand how the flu virus might evolve, but the federal government saw things differently. These experiments were a security risk.
In October 2014 the White House paused the federal funding of gain-of-function experiments to assess the risks and benefits. Many of the genetic experiments on the 1918 flu virus and its descendants came to a halt as the scientific community debated the wisdom of proceeding. Vaccine researcher Peter Hale thought the pause was an excellent idea. “The government has finally seen the light,” he said. “This is what we have all been waiting for and campaigning for. I shall sleep better tonight.”
Others thought that the pause was unnecessary and that it would stymie important research. It continued through January 2017, when the White House released new research guidelines. Any experiment that involved the creation of new viruses would need to be reviewed by an outside panel of experts and defended by the researcher. But these guidelines were not implemented, and so the ban on gain-of-function research remained in place. Then, in a move that surprised many, the government lifted the ban in December 2017. It released a brand-new set of rules to guide funding decisions that involved research on influenza, SARS, Ebola, and other dangerous viruses. These rules also covered research on viruses with a gain of function, and with their release the NIH promptly removed its ban on funding this kind of research.
Thanks to Johan Hultin and Jeff Taubenberger, we now know intimate details about the 1918 virus, including the sequences of its genetic building blocks. However, Taubenberger believes we still have far to go. He points out that we still don’t know why flu strains can affect some mammals but not others. We still don’t know if 1918 was a reassortment of an existing flu strain that turned suddenly lethal, or if it was a novel virus that appeared as if from nowhere. We still don’t know why 1918 was particularly lethal in young adults, the very group that is usually most resilient to these kinds of infections. We still don’t know what happened to the flu virus in the years after the 1918 pandemic—where it went and why it became less lethal. So many unknowns despite so much new information.
“I’ve been thinking heavily about the flu for twenty years,” said Taubenberger, the man who knows more about the flu than anyone, “and I know nothing.”