text: If vaccines are the nuclear bomb in the fight against COVID-19, antivirals are the infantry. Unfortunately, though, viral illnesses are notoriously harder to treat than bacterial infections. In fact, after the discovery of penicillin in 1945, it took nearly another forty years for the first antiviral drug to be licensed. As noted earlier, pathogenic bacteria are largely free-living, single-celled organisms. That means antibiotics can target bacteria cells within the body while leaving our own cells unharmed. Viruses, on the other hand, are gifted hijackers that use our own cells to replicate themselves. Because of this, it's difficult to stop their reproduction without harming the host. While certain antibiotics can treat a wide variety of bacterial infections, antivirals are usually limited to a single virus, or a virus group. The first licensed antiviral, aciclovir, was introduced in the 1970s and treated herpesvirus infections, including cold sores and chickenpox. Like a virus, aciclovir is tricky, camouflaging itself as a nucleoside, the building block of DNA. Essentially, it terminates viral DNA replication and spares uninfected host cells. The crew of HIV antiviral drugs, taken together, is another example of a working, established drug therapy. The flu can also be treated with antivirals that inhibit the virus and block its entry into host cells. And, as Canada registered record-breaking case counts and the U.S. watched its own case count climb unabated in October, the latter country approved the first COVID-19 drug. Remdesivir is an antiviral that can cut recovery times by five days. It was a big breakthrough, but it wasn't the only one.
  
  Throughout the end of 2019 and early 2020, immunologist Eleanor Fish was, as usual, travelling abroad. At each conference or academic institution, she shared the same message. "The twentieth century was the century of bacteria, and then along came antibiotics," she told me. "The twenty-first century is going to be one of viral infections." So, she'd asked the gathered experts, how are we going to handle this? How are we going to prepare ourselves? Closer to home, the U of T professor and scientist at the Toronto General Hospital Research Institute would share another, additional warning: Canada is a lightning rod for viral outbreaks. Our wonderfully diverse population means that people will arrive at our border from all around the world. They will cross it, in both directions, by plane, boat, train, car, and some of them, sometimes, will bring a virus with them. It doesn't matter where the outbreak originates, added Fish. When it stops moving, the chances are it will end up here, where it will spread. Because of all this, she thinks it is a lost cause to keep developing pathogen-specific antivirals. "You're always playing catch-up," she explained. A virus will travel, mutate, adapt, develop resistant strains—all of it often outpacing human speed. As an example, she pointed to Tamiflu, or oseltamivir, which many countries, including Canada, stockpiled in 2009 to fight the H1N1 swine flu pandemic. Canada recorded its first case on April 26, 2009, and its first aseltamivir-resistant case scant weeks later on July 21, 2009. It is not inconceivable that remdesivir could meet a similar fate. Which is why Fish argues it's time to stop making pathogen-specific drugs and try something else: interferons.
  
  Interferons are a set of proteins that already occur naturally within our bodies. Our immune system cells secrete them in response to viruses and other threats. Discovered in 1957, interferons can be grouped into several classes that, together, help regulate the body's immune system response. They can, as the name suggests, interfere with viral proliferation, enhance innate or acquired immune system responses, and also respond to cancerous growth. When it comes to viruses like SARS-CoV-2, an infected cell may release interferons, stimulating nearby cells into entering an antiviral state. In other words, interferons won't kill a virus directly, but they will trigger a defence response in other cells, preventing the virus from replicating within them. This will, in turn, stem infection—sort of like turning each healthy cell into a battle fortress. Their use as a pharmaceutical product is not new. Since the 1980s, they've already been used to treat everything from Ebola to multiple sclerosis, to varying, and not always remarkable, effect. Fish herself has been studying their applications for decades. She has long believed that they do have a "wow factor" but that scientists have also missed interferons' true calling: as the perfect first responders in a global pandemic.
  
  In December 2019, as news of the emerging novel coronavirus trickled out of Wuhan, Fish contacted colleagues in China who immediately set up an exploratory study using interferons to treat virus patients at a hospital in Wuhan. She was glad, but not exactly surprised, to discover the interferon treatment worked. Between January 16 and February 20, doctors administered interferon treatment to a total of seventy-seven people at the Union Hospital, Tongji Medical College at the Huazhong University of Science and Technology. The patients presented with a moderate case of COVID-19, and although they had been admitted into the intensive care unit, they did not require supplemental oxygen; it was early on into their possible disease progression. Researchers defined viral clearance as two consecutive negative tests at least twenty-four hours apart. Results were significant. Interferon treatment had accelerated viral clearance by approximately seven days. That's even faster than remdesivir, noted Fish. The treatment also reduced inflammatory markers of the disease. "Interferons are a no-brainer," she added.
  
  Fish and her colleagues' study was published in May 2020 in Frontiers in Immunology. The publication had an oddly dual outcome: she became incredibly busy and optimistic, and also incredibly frustrated. When we spoke months later in early August, she joked that when she "allows" her iPhone to give her notifications, she will receive constant emails and calls from around the globe, from 7:30 a.m. until 11 p.m. She has helped researchers worldwide map out clinical trials, craft journal publications, edit research papers, and learn about interferon treatment. She has been asked, and has sometimes agreed, to join the scientific advisory boards of several pharmaceutical companies. She's given dozens of media interviews, everywhere. In short, she's made herself available around the clock. But even as she's seen interest in interferons explode, she's also seen a blanket of apathy.
  
  If interferons were on, say, a dating app for antivirals, they'd have a lot going for them to make a person swipe right: they're already FDA approved, they have three decades of clinical experience, and they can work on a wide number of viruses—all of which also makes them an economically sound choice. Unfortunately, they have also not been very effective in their main use to date, which is against chronic virus infections. In that context, they work just "okay" and can have side effects that are "really quite unpleasant," said Fish. (It may be worth noting here that Fish is British by birth, and has the exact dry humour you might expect from a British scientist.) She knows that's why, even in the face of increasingly positive evidence, some scientists have been hesitant to throw them at another challenge. Luckily, that reticence had already started to shift when we spoke, thanks in large part to her persistence. Early on in the pandemic, she had, for example, shared her findings with the United States' Dr. Anthony Fauci, who, as Fish put it, "passed it on to his team, where it died a nice death." She noted, though, that it had since been resurrected, and that a randomized control trial was finally underway, too, which would only add to the growing body of evidence. And Fish thought fondly of her colleagues around the world who emailed her with their own disbelief as researchers scrambled to develop an antiviral, overlooking the one that already existed, and worked.
  
  "Until there are organizations independent of Eleanor Fish who say, 'Yes, this looks promising,'" she noted, "This is going to be an uphill battle that continues." Still, Fish is used to proving people wrong. In 2014, she ran an interferon trial in Guinea to treat Ebola; the virus has more than a 60 per cent fatality rate in the country. Despite established protocol and recommendations, she refused to make it a randomized control trial; she believed the interferons would work and did not want to "randomize people to death." In the end, she convinced everybody there was enough historical data to provide an accurate contrast between those who received the treatment and those who didn't. And that contrast was stark: 67 per cent of the interferon-treated patients were still alive three weeks after infection, while only 19 per cent of those who received the standard care survived at day twenty-one. The study was so successful, she's now helping local health authorities develop an interferon clinic. Beneath all the frustration, COVID-19 offers a chance to prove naysayers wrong again. In the process, Fish won't only be helping us make it more safely through this pandemic—she'll be showing us how to better survive the next one.