When antibiotics first came to market barely 70 years ago, they were clear evidence of modern medicine’s power. These days, they are equally potent evidence of its limitations. Experts warn that we’re entering a “post-antibiotic era” full of microbes that eat our puny drugs for breakfast while fomenting new infections that are as untreatable as infections were centuries ago.
The story of antibiotic-resistant infections is nuanced and complicated — not necessarily the easiest or happiest reading, but vitally important. All drugs are double-edged swords, after all; antibiotics happen to be especially two-faced, with benefits and risks intertwined so closely that using them courts disasters large and small — and so, of course, does not using them. Welcome to the Faustian Rubik’s cube in medicine cabinets all over the world — and to help you solve it, here’s a reality-based, up-to-date “bugs and drugs” reading list.
The science behind antibiotic-resistant infections is straightforward enough: Microbes exposed to antibiotics can and will develop defenses against them. We’ve used huge quantities of antibiotics, and have created correspondingly huge populations of drug-resistant organisms. For a clear picture of the complex microbial world our drugs have interfered with, no recent book has yet surpassed Ed Yong’s 2016 “I Contain Multitudes,” which the reviewer Jonathan Weiner called “a terrific story” in these pages. Yong is a science journalist less interested in human pathogens (the tiny fraction of microbes that cause human disease) than in all the friendly bacteria out there. Zillions live in the soil and oceans, and zillions more compose the human microbiome — the bacteria lining the human intestine, skin and mouth.
These bacteria are so plentiful and so essential to our well-being that in Yong’s vision there is really no such thing as bacterial and human, no “us” and “them”: We are all an indivisible unit. And, weirdly but symmetrically enough, the same applies to microbes — the bugs have their own little resident bugs to make them themselves. Think matryoshka doll microbiomes — “bugs within bugs within bugs,” on down the line.
Yong writes: “Every one of us is a zoo in our own right. A multispecies collective. An entire world.” So it’s no surprise that tossing a few grams of killer antibiotic into that nested universe causes a far-reaching nuclear holocaust.
On the other hand, when you’re dying of a treatable infection, do you really care?
For a reminder of what great drugs antibiotics can be, William Rosen’s 2017 “Miracle Cure” is a reasonable place to start. Rosen writes from a traditional vantage point, casting the bugs as enemies and drugs as weapons in the war against them. Familiar figures from the dawn of microbiology are all here: Pasteur, Koch, Ehrlich, Alexander Fleming and his famous petri dish full of penicillin. Less well known is Gerhard Domagk, the German chemist whose dogged benchwork in the 1930s created the first sulfa drugs. Domagk’s 6-year-old daughter would probably have died of a strep infection had she not been treated with sulfa, one of the first in a parade of unprecedented medical resurrections.
Rosen does a nice job of detailing the labor and staggering expense behind industrial antibiotic development. Once a drug is discovered, generally through a plodding process of trial and error, it must be purified, repeatedly tested in animals and humans, then manufactured in bulk. We’ve come a long way from the days when virtually all the world’s penicillin hailed from a moldy cantaloupe purchased at a market in Peoria, Ill. But the most striking details of Rosen’s account are those confirming that antibiotic resistance was forecast long ago. Alexander Fleming saw it coming in 1945; by January 1959, a cover story in The Saturday Review was blasting doctors for “taking the miracle out of miracle drugs” by overusing them.
Did doctors listen? No, they did not (and neither did farmers gleefully incorporating antibiotics into animal feed to fatten poultry and cattle for market). It was antibiotics for one and all.
The medical fallout from this overuse is cogently detailed in Martin Blaser’s 2014 ”Missing Microbes.” A professor of medicine, Blaser reports on a surprisingly wide swath of human illness. There are the now-familiar drug-resistant infections with the tenacious skin pathogen MRSA and the infamous intestinal “C. diff.” Both used to cause problems only in sick, hospitalized patients; now they’ve exploded into the community, affecting even healthy people with no personal history of antibiotic use.
Blaser also details the still-unfolding links between antibiotics and diseases that are not infections. Depleting the body’s friendly bacteria may precipitate asthma and other allergic diseases, and may elevate risk for some autoimmune diseases. Some evidence supports including diabetes and even autism on the list. Just like cattle, young mice can be fattened with antibiotics in their chow. Researchers now wonder if the same applies to pudgy young humans unnecessarily dosed up for every viral infection they acquire.
Looking to the future, what is to be done? We can escalate the war on bugs: Most of the roughly 100 antibiotics on the market are quite venerable, and many experts (including Blaser, ironically enough) are calling for the urgent development of newer, stronger agents.
Inevitably, though, resistance will disarm even the newest and strongest. So we must also learn to pick our battles. Good evidence suggests that the less we use antibiotics, the more useful they will become. In the meantime we must cast around for scientifically valid alternatives.
That’s what Steffanie Strathdee did. Strathdee and her husband, Tom Patterson, both scientists, were on a vacation in Egypt in 2015 when Patterson suddenly collapsed. By the time he was airlifted first to Frankfurt, then home to San Diego, doctors had diagnosed a giant abdominal infection caused by a strain of drug-resistant bacteria so commonly seen in the Middle East that military medics call it “Iraqibacter.”
No antibiotics were effective against this infection, and neither were any antibiotic combinations. As Patterson got sicker and sicker, weeks turning to months in the I.C.U., Strathdee finally headed for the internet.
There, as she writes in this year’s “The Perfect Predator” (Hachette, $28), she discovered a growing body of literature on phage therapy. Phages are viruses that kill bacteria without directly affecting human cells. They can be cumbersome to use for treatment, and American scientists are late to the phage game: It was in Stalinist Georgia that much of the early research was done. One attractive feature of these agents, though, is that each one is targeted to very specific bacteria, so that, at least in theory, the right phages can annihilate an Iraqibacter without harming any of the body’s other microbes.
Spoiler alert, but it’s right there on the book’s cover: Patterson, who wrote the book with Strathdee, was saved by a concoction of phages urgently assembled by a nationwide network of researchers and clinicians. Had he not been so sick, and had Strathdee not been so persistent, it seems unlikely Patterson’s doctors would have signed onto the effort. Still, use of phages in cases like Patterson’s is becoming more common, and they can sound welcome notes of hope and success in an otherwise bleak story.
But, alas, phages are by no means the end of that story. Bacteria quickly develop resistance to them too.
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I CONTAIN MULTITUDES: The Microbes Within Us and a Grander View of Life, by Ed Yong. Welcome to Microbes 101. Yong explores the territory with humor and boundless curiosity.
MIRACLE CURE: The Creation of Antibiotics and the Birth of Modern Medicine, by William Rosen. To wrap your mind around where antibiotics are now, it’s helpful to know where they came from. Meet all the great scientists and their immensely grateful patients here.
MISSING MICROBES: How the Overuse of Antibiotics is Fueling our Modern Plagues, by Martin J. Blaser. For a step-by-step indictment of our addiction to antibiotics, look no further than Blaser’s methodical overview.
THE PERFECT PREDATOR: A Scientist’s Race to Save Her Husband From a Deadly Superbug, by Steffanie Strathdee. When antibiotics fail, treatment with viruses called phages can sometimes work. Learn all about them in this memoir that reads like a thriller.
