Look no further than the coronavirus pandemic to see an immediate and high-profile example of the evolutionary battle between microbes and humans and the antimicrobial resistance it breeds.
Even as medicines and vaccines are developed to defeat Covid-19, new viral variants that resist treatment are evolving and spreading. We have seen dramatic examples of this as an antibody therapy, one of the first-line treatments developed for the coronavirus, has been supplemented and modified to deal with reduced effectiveness against variants in Britain, South Africa, and the United States. Some vaccine makers are preparing booster shots with increased effectiveness against variants.
Yet Covid-19 is just one instance of the perpetual arms race between infectious diseases and our limited arsenal to manage them.
To stay ahead of superbugs — not just viruses but bacteria, parasites, and fungi that are resistant to existing treatments — the world needs continued development of new antimicrobial drugs. Because market forces tend to divert the private sector away from this area, the federal government should create incentives to develop these drugs.
Successful examples of such incentives emerged in the development of coronavirus vaccines, where rapid progress was stimulated by substantial financial commitments from the U.S. and U.K. governments and resulted in the development of revolutionary new vaccines, resulting in their citizens becoming the earliest and most highly vaccinated among the larger countries in the world.
Antimicrobial resistance happens with all infectious pathogens and represents a major challenge to the ability to treat infectious disease. More than 2.8 million drug-resistant infections occurred in 2019 in the U.S. alone, where antimicrobial resistance killed more than 35,000 people. Some have argued that this is a substantial underestimate and that antimicrobial resistance may be the third leading cause of death in the United States. Worldwide, the numbers are even more staggering.
Even for those who survive drug resistant infections, the potential consequences can be severe.
Here’s one example: A co-worker of ours, Gajus Worthington, nicked his finger while bringing firewood into his house in New Mexico. Not long afterward, he was in the emergency room with a swollen hand the size of a baseball mitt and red streaks snaking up his arm. The infection was spreading quickly and wasn’t responding to first-line antibiotics. His doctors were considering amputating his arm. Worthington didn’t know if he would become delirious from fever or enter septic shock, so he wrote parting letters to his 5- and 7-year-old sons. Fortunately, a last-line antibiotic stopped the infection. But it is sobering to realize that microbes found in a relatively innocuous place such as a home woodpile may soon be untreatable.
Given the limited supply of new antimicrobials and increasing rates of antimicrobial resistance, doctors tend to prescribe new drugs only after exhausting older ones. While this keeps the new drug as a last resort backup in the arsenal, its developers don’t sell enough to stay afloat and can’t afford to keep the drugs on the market. This has doomed several recent antibiotic companies even though the FDA approved their new drugs. A spectacular example is Achaogen, which declared bankruptcy less than 10 months after Food and Drug Administration approval of its lead molecule, which took 15 years and $1 billion to develop.
An innovative way to stabilize the antimicrobial marketplace is a subscription model. In this approach, the government enters into contracts with antimicrobial developers that are valued based on the public health importance of the drug. It’s time to bring this approach, which is already being explored in the United Kingdom, to the United States.
The PASTEUR Act (H.R. 8920 and S. 4760), a bipartisan bill cosponsored by Sens. Michael Bennet (D-Colo.) and Todd Young (R-Ind.) and Reps. Mike Doyle (D-Pa.) and Drew Ferguson (R-Ga.), would implement a version of this model.
Under the PASTEUR Act, the federal government would create market incentives for the development of lifesaving antimicrobial drugs. Developers would be paid contractually agreed-upon amounts annually, for a duration ranging from five years up to the antimicrobial’s patent life. The subscription contract eligibility and value would be based on the clinical need and novelty of the drug.
Specifically, such contracts would promote the development of antimicrobials against the most threatening superbugs identified by the Centers for Disease Control and Prevention, including Candida auris, a fungus, and bacteria such as carbapenem-resistant Acinetobacter and Clostridioides difficile. Additionally, PASTEUR contracts would incentivize the development of antimicrobials with novel mechanisms of action and novel structure, creating a powerful arsenal against superbugs, which currently have limited treatment options.
Under this model, patients covered by federal insurance programs like Medicare or Medicaid would have access to these drugs at no additional cost to the government. It is important to note that this is not a giveaway to big pharmaceutical companies because 95% of antimicrobials are developed by small companies.
This approach would position the U.S. as a leader in pandemic preparedness and in the development of drugs with global health importance. House Speaker Nancy Pelosi and Senate Majority Leader Chuck Schumer should help pass the PASTEUR Act, and the Biden administration should favor antimicrobial resistance in its pandemic preparedness strategy.
President Biden’s infrastructure plan earmarks $10 billion for pandemic response, but antimicrobial resistance is never mentioned in it. If we can see the value in maintaining infrastructure — the president is proposing to spend $115 billion modernizing American roads and bridges — we should be doing the same for health care.
Antimicrobial resistance threatens many scientific and medical innovations that scientists like us are working to develop across the spectrum of health care needs. Procedures as diverse as hip replacement surgery, cesarean section, and some cancer treatments depend on preventing infection. And as Worthington, who is the chief operating officer of the Chan Zuckerberg Biohub, points out, of the nicks and scratches people will get from every day activities, “some fraction will become lethal and another will lead to amputations.”
Addressing antimicrobial resistance right now will allow scientists and engineers like us to work on unsolved medical problems that society faces instead of damage control for the microbial crisis that, left untreated, would bring us back to the time before antimicrobials became available in the 1940s when infectious diseases — not cancer and heart disease — were the primary cause of death.
These drugs are needed to sustain modern medicine as we know it. If the U.S. does not take action now, the superbugs may win.
Sevahn Vorperian is a doctoral candidate in chemical engineering at Stanford University. Stephen Quake is a professor of bioengineering and professor of applied physics at Stanford University and co-president of the Chan Zuckerberg Biohub.
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