51 THE COMING PANDEMIC

In 2015, there was no mainstream media reporting that seven of the top ten selling medications in America were orphan drugs. Although high prescription prices were frequently discussed, the complex reasons behind the price-gouging were something only covered in industry publications and by patient advocacy groups. One of the pharmaceutical stories that dominated the year’s media coverage was antibiotic resistance. A study commissioned by the U.K. delivered sobering news. At least fifty thousand people died annually in the U.S. and Europe from antimicrobial-resistant infections.1 Upward of 50 percent of bloodstream infections were the result of drug-resistant strains.2 Not only was the use of antibiotics up (rose by 40 percent from 2000 to 2010), but the ease of international travel translated into superbugs spreading to every country. The report predicted that by 2050, 10 million people would die annually from drug-resistant bacteria, more than from cancer.3 If governments did not address it as a major health crisis, modern health care that relied heavily on antibiotics would “be undermined” and could lead to “a return to the dark age of medicine.” The WHO later emphasized that: “A post-antibiotic era [is one] in which common infections and minor injuries… can once again kill.”4

In March, President Obama urged Congress to double the budget to fight antibiotic-resistant bacteria. Doctors write a quarter billion antibiotic prescriptions annually to Americans.5 That is twice the rate of Europeans and the CDC says that a third of those dispensed are “unnecessary.”6 In May, the United Nations and the World Health Organization unanimously adopted plans to develop better tools to spot cases of resistance and to commit enough funding to develop new antibiotics.7

Sally Davies, the U.K.’s chief medical officer, concluded that the threat posed by antibiotic-resistant bacteria was as great as terrorism. She had overseen a government report that concluded superbugs were the top public health emergency. “We may be a bit late,” she told The New York Times. “If you look at the trajectories of rising antimicrobial-resistance, increasing use of antibiotics and a lack of new antibiotics, this could be a catastrophe.”8

Since that warning, a series of sobering reports in medical journals exposed the extent to which antimicrobial-resistant infections have spread and wreaked havoc. In 2017, the same year that the CDC announced the death of the Nevada woman who was a victim of a resistant strain that did not respond to any antibiotics, superbugs infected 3,000,000 Americans and killed more than 24,000. Worldwide, an estimated 700,000 died.9

It took the CDC three years to develop a system to identify superbugs.10 When five hundred CDC workers fanned out across the country in 2018 to collect random samples, the results were not good. There were 221 instances in which so-called nightmare bacteria—germs with already high levels of resistance—had developed “unusual” and “novel” antibiotic-resistant genes. CDC researchers worry that upward of a quarter of those might spread their resistance to other germs. If that happens, antibiotic resistance will not just be an evolutionary question of how long it takes germs to survive when faced with new drugs. Instead, superbugs might convert otherwise vulnerable bacteria into dangerous clones.11

The CDC and FDA are also worried about the widespread use of antibiotics in the food chain.12 A remarkable 80 percent of antibiotics manufactured in the U.S. are not dispensed to patients but used by livestock farmers. The drugs have been used since the 1950s to spur faster growth in cows, pigs, and chickens and are a cheap substitute for hygiene in overcrowded and unsanitary conditions. The Obama administration addressed that in 2015 by having the FDA set stricter reporting requirements from pharma companies that make the drugs for animals. That only clarified the size of the problem. In 2017, farmers gave 141,000 tons of antibiotics to food animals. That was when the U.N. released the first of two studies concluding the widespread use of antibiotics in livestock had created a “rise of AMR [antimicrobial resistance] in zoonotic pathogens, including to last-resort drugs.… [It] is an important challenge for human medicine because it can lead to untreatable infections.”13 The FDA responded finally in 2017 by banning all antibiotics used on livestock for “growth promotion and feed efficiency.”14 Tremendous lobbying by the farming and food industries allowed them to keep using the drugs for “health maintenance.”

An equally worrying development is the agricultural use of antibiotics. Florida’s $7.2 billion citrus industry has been fighting “citrus greening disease,” a bacterial infection that arrived in 2005 and makes fruit too bitter for commercial use. It is spread by a flying insect originally from China. Efforts to control it with pesticides had mixed success. In 2016, the Environmental Protection Agency under the Obama administration approved the limited spraying of two vintage antibiotics, streptomycin and oxytetracycline. The FDA and CDC objected, fearing the widespread use of those antimicrobials could fuel drug resistance. In Europe and Brazil, they are banned for agricultural use.

In May 2019, under the Trump administration, the EPA approved an expansion of the use of those two antibiotics to three quarters of a million acres in Texas, California, and other citrus-producing states. Once again, it was over strenuous protests from the FDA and CDC. Under the current guidelines, while Americans will consume about 15,000 pounds of those drugs annually, some 650,000 pounds will be sprayed on citrus crops.15 The objections from the two regulatory agencies with oversight on health were straightforward. It is not even clear after three years of use in Florida that the drugs stop the citrus greening disease. Studies showed that pathogenic bacteria in soil became resistant to them over time. That is most likely with streptomycin, which stays active in dirt for weeks.16 The drugs spread to people through groundwater and accelerate human resistance.17

The EPA stuck to its position. It cited studies from pesticide manufacturers who claimed the antibiotics would be “quickly dissipated in the environment.”18 While the EPA eventually agreed there was a “medium” risk from the expanded use of the drugs, it did not ban them since it concluded there was no conclusive research on “whether a massive increase in spraying would affect the bacteria that infect humans.”19 In response to the concerns from federal health regulators, the EPA said it would implement additional monitoring of the spraying and also require new approvals every seven years.

The CDC released an alarming report in November 2019 in which it concluded that drug-resistant germs presented a much greater “public health threat” than it had previously forecast. Its latest analysis revealed that, on average, every eleven seconds someone in the U.S. is infected by a superbug, and every fifteen minutes, someone dies.20

“No one knows where it [the next pandemic] will come from,” says Karen Bush, a biology professor who had worked for nearly forty years in antibacterial development at a succession of large pharma companies. “Only when it arrives can we look back and identify what sparked it.” Some of her colleagues worry about avian or swine flu that might morph into more deadly strains in humans. Cross-species transmissions have been the cause of every major epidemic from the bubonic plague (rats and fleas) to the l918 influenza (birds), malaria (mosquitoes), and HIV/AIDS (primates). Scientists have identified eighty-four diseases that pass from animals to humans. The one about which they are most concerned is the one that has not yet jumped species. “We won’t know that until it happens,” says Bush. Reports in 2019 that an African swine fever had killed 150 million of China’s 440 million pigs attracted considerable attention from epidemiologists and infectious disease experts. A story about its devastation in Bloomberg noted, “The good news is it can’t infect humans. The bad news is that nobody knows when it will stop spreading.”21

Exacerbating fears over the growth of supergerms is that few pharmaceutical companies are developing new antibiotics. “In 1980, there were thirty-six U.S. and European companies in the antibiotic business,” notes Bush. “Today there are fewer than six.”22

In 1968, Smith Kline had introduced Proloprim, a combination sulfonamide and synthetic antimicrobial agent. It took thirty-one years before there was a new class of antibiotics, oxazolidinones.23 Every antibiotic used to fight infectious bacteria in the interim was a chemically similar me-too clone of an earlier drug. In the last decade, the FDA approved only nine new antibiotics.24 In contrast, explosive advances in nanotechnology, stem cells, and deciphering the microbiome have led to almost a hundred new anti-cancer drugs over the same period.25 Those are credited with survival rates having doubled since the 1970s.26

“Innovation, especially in the antibacterial area, is certainly not what it used to be,” says Barry Eisenstein, the senior vice president in charge of Scientific Affairs at Cubist.27 “Part of this problem is that anti-infectives can be notoriously difficult to make,” says Mike Skoien, a former marketing executive in charge of Merck’s anti-infective program.

There is less profit too. “The cost of production is much higher and the return almost always lower,” says Skoien.28 Some highly anticipated biotech antibiotic startups filed for bankruptcy in 2019 while others that were in desperate need of cash had difficulty finding investors. “Antibiotic treatment used to be seven days, and is now five or less,” notes Eisenstein. “On the other hand, drugs that treat high cholesterol, hypertension, diabetes, depression, and other chronic conditions yield much bigger profits for the long-term bottom line.”29

“The problem is that we cured most patients and did it too quickly and cheaply,” says Steven Projan, head of infectious diseases at Astra Zeneca’s MedImmune.30

“Without a renaissance in antibiotic development,” says Eisenstein, “the very preservation of society as we know it will be at risk.”31

The prediction of a coming pandemic, unstoppable because the pharmaceutical industry has put profits over its duty to develop drugs for the public good, is no wild-eyed conspiracy theory heavy on drama and light on evidence. “It is not a question of if,” warns Professor Bush, “it is a question of when.”32