Bitter Pill

Front page Washington Post headline

Antibiotics may be even less help. We live in a global, just-in-time economy, which allows manufacturers worldwide to streamline their production to precisely meet demand, thereby reducing inventory warehousing costs and waste. The problem is that a single glitch in the supply chain can almost instantly dry up supply. Thus, even now, we have a shortage of seven major antibiotics and three pediatric chemotherapy drugs. During a crisis in which we shut down our borders, globalized supply chains will be shattered and vital goods like pharmaceuticals in general will be in short supply or unavailable.⁵⁰⁷

Antibiotics only work against bacteria. Although they can be effective in treating secondary bacterial infections, they are useless against viral pneumonia. Antibiotics were useful during the 1957 and 1968 pandemics because these were essentially just bad flu seasons when more people than expected came down with the flu due to the novelty of the bird-human hybrid viruses. 1918 was different: Many people were killed by their own immune systems in the cytokine firestorm sparked by the virus.⁵⁰⁸ Antibiotics may not have been much help in 1918,⁵⁰⁹ and we may face the same situation with H5N1.⁵¹⁰

In the 1960s, though, a breakthrough was made. A new class of drugs—antiviral drugs—hit the market, drugs that could actually block influenza viruses from entering cells.⁵¹¹ The medical community breathed a collective sigh of relief. The CDC’s report of the 1997 Hong Kong outbreak confidently declared, for example, “Two antiviral drugs, amantadine and rimantadine, inhibit replication of virtually all naturally occurring human and animal strains of influenza type A [influenza strains with pandemic potential] and therefore can be useful for prophylaxis and treatment of influenza A infections.”⁵¹²

Devastating news broke in June 2005. For years, Chinese chicken farmers had been slipping those very drugs into their chickens’ water supply to prevent economic losses from bird flu. Because of this practice, the emerging H5N1 became resistant to these potentially life-saving drugs. “Bird Flu Drug Rendered Useless,” headlined The Washington Post’s exposé.⁵¹³ The scientific community’s fears had been realized.⁵¹⁴ “In essence,” one expert wrote, “this finding means that a whole class of antiviral drugs has been lost as treatment for this virus.”⁵¹⁵

China learned it from us. The use of amantadine in the water supply of commercial poultry as prophylaxis against avian influenza was pioneered in the United States after the 1983 outbreak in Pennsylvania.⁵¹⁶ Even then it was shown that drug-resistant mutants arose within nine days of application.⁵¹⁷ Although Europe has banned the use of antibiotics of human importance in farm animals for non-treatment purposes since 1998, producers in the United States continue to legally spike farm animal feed with more than a dozen antibiotics. In fact, the Union of Concerned Scientists estimates that fully 70% of antimicrobials used in the United States are fed to farm animals for non-therapeutic purposes. U.S. poultry eat more than 10 million pounds of antibiotics a year, more than a 300% rise since the 1980s.⁵¹⁸ With few, if any, new classes of antibiotics in clinical development,⁵¹⁹ an expert on antibiotic resistance at the Institute for Agriculture and Trade Policy warned that “we’re sacrificing a future where antibiotics will work for treating sick people by squandering them today for animals that are not sick at all.”⁵²⁰

Thankfully, in 1999, a new class of antivirals came onto the market, notably oseltamivir (brand name Tamiflu®).⁵²¹ Unfortunately, there is not enough to go around. Historically, it has been made in one plant, from one plant. One factory in Switzerland has made the entire world reserve of the drug from star anise, a plant in limited global supply. “It’s not just about having a magic bullet,” Osterholm cautioned, “it’s whether you can make it and find enough guns from which to shoot it.”⁵²² The current U.S. stockpile covers less than 1% of the population,⁵²³ and there is a long waiting list for new orders.⁵²⁴

The Chinese poultry industry’s actions have created, as one world’s authority on bird flu put it, a “very, very dangerous” situation.⁵²⁵ “We are living in a brave new world where we only have one drug,” another expert told the G7+ Global Health Security Action Group.⁵²⁶ While Tamiflu is relatively unavailable, expensive, and hard to make, amantadine, as described by National Institutes of Health director Anthony Fauci, is a “very cheap drug, a widely available drug, a drug of which there are ample supplies.”⁵²⁷ Amantadine costs as little as $10 a pound;⁵²⁸ Tamiflu, because it’s still under patent, costs closer to $10 a pill.⁵²⁹ Even if there were enough Tamiflu, most developing nations could not afford it.⁵³⁰

Tamiflu is also a relatively unstable compound, expiring after just a few years, which makes it difficult to stockpile. Amantadine, on the other hand, is adamantine; it’s sticking around. Researchers took amantadine that had already been sitting on the shelf for literally decades, then boiled it for a few hours. It still retained full antiviral activity.⁵³¹ “Thus,” the researchers concluded, “amantadine and rimantadine could be synthesized in large quantities and stored for at least one generation without loss of activity in preparation for the next influenza A pandemic in humans.”⁵³² Not anymore, though, thanks to global poultry industry practices.⁵³³ Amantadine was no panacea—it had rare but serious side effects, and resistance may well have developed with human use as well⁵³⁴ —but it may have been our best bet,⁵³⁵ a bet we’ve now gambled away.