The End of a Panacea

The coevolution between parasites and hosts has not faded into history’s fog. It continues every day, and we humans are a subject of one of the newest experiments in host‑parasite coevolution. We are trying to artificially improve our defense against bacteria with antibiotics, and it’s becoming abundantly clear that we’re in danger of losing this arms race.

When Selman Waksmann and his fellow scientists first discovered antibiotics, many people thought the war against infectious diseases was as good as won. But some researchers warned from the beginning that evolution might wipe away the miracles. Sir Alexander Fleming, the British microbiologist who discovered penicillin in 1928, was one of them. He ran an experiment in which he exposed bacteria to low levels of penicillin and gradually increased the exposure. In each successive generation, more and more of the bacteria could withstand the effects of the drug, and before long his petri dishes were swarming with bacteria that regular prescriptions of penicillin could not harm.

During World War II the American military closely guarded its stocks of penicillin, releasing only a few doses to civilian doctors whose patients were desperately ill. But after the war, pharmaceutical companies began selling the drug, even inventing a pill to take the place of injections. Fleming worried that doctors would prescribe it indiscriminately and, worst of all, people would be able to buy penicillin and take it on their own:

The greatest possibility of evil in self‑medication is the use of too‑small doses, so that, instead of clearing up the infection, the microbes are educated to resist penicillin and a host of penicillin‑fast organisms is bred out which can be passed on to other individuals and perhaps from there to others until they reach someone who gets a septicemia or a pneumonia which penicillin cannot save.

In such a case the thoughtless person playing with penicillin treatment is morally responsible for the death of the man who finally succumbs to infection with the penicillin‑resistant organism. I hope this evil can be averted.

Bacteria, microbiologists would later discover, are even more adept at coevolution than insects, able to alter their genetic makeup with staggering speed. Because they can divide several times an hour, bacteria can mutate quickly, stumbling across new formulas for resisting antibiotics. These mutations may create proteins that can destroy the drugs; some resistant bacteria are equipped with pumps in their membranes that can squirt the antibiotics out as quickly as they flow in. Normally, these mutants would not be favored by natural selection. But when faced with antibiotics, their offspring become successful.

Unlike insects, bacteria can acquire resistance genes not just from their parents but from the bacteria that surround them. Independent loops of DNA can shuttle from one microbe to another; they can slurp up the genes of dead bacteria and integrate some of them into their own DNA. Antibiotic‑resistant bacteria can thus pass on their resistance genes not only to their descendants but to different species altogether.

A twenty‑first‑century Russian prison is a perfect laboratory for microbial evolution. Crime has soared since the fall of the Soviet Union, and the Russian courts are sending more and more people to prison–a million currently are jailed. But the prisons are in no shape to receive them. The prisoners receive a few cents’ worth of food each day, leaving them malnourished and primed for infection. Then dozens of them are crammed into cells the size of living rooms. Those who are sick with tuberculosis can easily infect their prison mates with their coughs, letting the germs shuttle quickly from host to host, multiplying and mutating as they go.

Mycobacterium is a particularly tenacious bug, which can be destroyed only with a long course of antibiotics that usually lasts for months. If a patient doesn’t take the full prescription of pills, the bacteria may be able to survive long enough for resistant strains to multiply. Russian prisons rarely provide a full course of antibiotics for their prisoners or make sure that they finish it. In their famished, undermedicated bodies, resistant bacteria spread easily.

When a person falls ill with resistant TB, doctors have to resort to much more expensive drugs, which can cost thousands of dollars. With so little money to spend on medicine, Russian prisons have no choice but to let new forms fester. The prison doctors have no illusions about curing their patients: they know that most of their patients will still be infectious when they are released from jail. The prisoners then carry resistant tuberculosis back to their hometowns to infect more people. By releasing sick prisoners back into the population at large, the government quintupled the tuberculosis rate in Russia between 1990 and 1996. It is now the leading contributor to increased mortality among young Russian men.

“All the strains that are in the Russian prisons will eventually come to our doorstep,” says Barry Kreisworth, an epidemiologist with the Public Health Research Institute in New York City. In fact, Kreisworth has already detected some of the strains that evolved at the Tomsk Prison in immigrants arriving in New York City.

The Public Health Research Institute and other organizations are now trying to stop the spread of resistant tuberculosis in Russia and elsewhere by providing aggressive treatment with the most powerful antibiotics available. They hope to destroy resistant strains before they get a chance to evolve into new forms. The stakes are high in this gamble. If the bacteria continue to evolve, an unstoppable form of TB may emerge, one that is resistant to every known antibiotic.

The antibiotic crisis is out of hand not just in Russia but across the world. New strains of E. coli, Streptococcus, and other bacteria that can resist almost all antibiotics are emerging. Gonorrhea, once a harmless nuisance, has evolved into a life‑threatening disease: in Southeast Asia, 98 percent of gonorrhea is now resistant to penicillin. In London doctors have isolated a remarkable strain of Enterococcus bacteria that has evolved to the point where it actually depends on the antibiotic vancomycin for its survival.

After 20 years of complacency, pharmaceutical companies are only now working on new antibiotics. It will take years until this next generation of drugs is ready; once they hit the market, no one knows how long they will stay effective against bacteria. In the meantime, we may face a frightening reversal of medical history. The risk of infection with unstoppable superbugs may make surgery as dangerous as it was during the Civil War.

Experts on antibiotic resistance are calling for global action. One way to cut down on the threat of resistant bacteria may be to stop encouraging their evolution. Antibiotics were introduced to the world as a panacea in the 1940s, and we still imagine that they can cure all things. As a result, they are prescribed far more often than they really need to be. (Many people, for example, think that antibiotics can kill viruses, when in fact they can only attack bacteria.) As a result, more than 25 million pounds of antibiotics are prescribed each year in the United States alone, of which a third to half is either inappropriately prescribed or just unnecessary.

Doctors need to do a better job of prescribing drugs, but patients have a duty to take their full courses of antibiotics so that the bacteria infecting them can’t get a chance to breed resistance. Consumers have to resist the lure of antibiotic soaps and sprays, which encourage resistant bacteria to evolve. Meanwhile, the flow of cheaply made antibiotics sold over the counter in developing countries has to stop.

A number of scientists are also worried about the 20 million pounds of antibiotics that U.S. farmers feed to their livestock. Cows, chickens, and other animals are given antibiotics not to cure a particular outbreak but to keep them from getting sick in the first place. Farmers also find that antibiotics–for reasons still unknown–make animals grow faster. By pumping animals full of antibiotics, farmers are breeding resistant strains of Salmonella and other bacteria that can then attack people. In 1994 the FDA approved the use of antibiotics called quinolones in chickens, to prevent infections by intestinal bacteria called Campylobacter jejuni. Since then, quinoloneresistant Campylobacter cultures in humans have risen from percent to 17 percent.

Bacteria are enjoying a strange new age. Never before in their long history have such a combination of molecules been used against them, and in such spectacular quantities. Genes for antibiotic resistance, once a burden, are now the secret to success. For our own survival, we have to bring this peculiar era to an end.