Business October 2011

Resistance Is Futile

We won’t stop the rising tide of infections until we develop a new business model to fight them.
Julian Stratenschulte/EPA/Corbis

On Christmas Eve 1947, George Orwell was admitted to a Scottish hospital with a case of galloping consumption. Orwell had first been diagnosed with tuberculosis almost 10 years earlier, but nonetheless, in what a biographer called “one of the many ill-judged decisions in a life littered with misjudgements,” he had recently moved to a remote and primitive Scottish cottage, where he began work on Nineteen Eighty-Four. There, he developed the night sweats, fever, and weight loss that are hallmarks of active TB. By the time he was admitted to the hospital, Mycobacterium tuberculosis had husked nearly 30 pounds off his already slender frame.

When I was younger and more romantic, I imagined that tuberculosis made you a good writer. After all, so many great ones, from Keats to Chekhov to all three Brontës, seemed to have died of it. Indeed, in 19th-century Europe, the “White Plague” may have caused as many as a quarter of all deaths. Though that proportion had fallen by Orwell’s time, writers from Camus to Bukowski were still contracting tuberculosis, as were millions of their less famous countrymen. Only antibiotics finally conquered the disease.

Victory arrived just barely too late for Orwell. His friends actually managed to obtain a supply of streptomycin, the brand-new anti-TB drug, from America, but it caused such a violent reaction that every morning when he woke, blood from the ulcers in his mouth had glued his lips shut. It had to be soaked off before he could speak. After several weeks, his doctors had to give up. A less powerful new drug called PAS, which he tried in 1949, didn’t make him so sick, but apparently didn’t much bother the tuberculosis bacilli, either. In January of 1950, an artery burst in his lungs, and at the age of 46, George Orwell drowned in his own blood.

It seems a medieval end for a very modern man. But we are not as far from TB as we like to think. It remains endemic in the developing world and is coming back in richer countries, thanks to travel and immigration, but also to a phenomenon that Alexander Fleming, the discoverer of penicillin, warned of in the 1940s: antibiotic resistance.

“What people might not know about resistance,” says Eric Utt, a former antibiotic researcher now working in Pfizer’s science public-policy division, “is that the resistant organisms are already there. This is why we find bacteria that are resistant to new antibiotics, even before those drugs reach the market.” They’re often the loners in the corner with the mutation that just happens to confer immunity to some super-drug. When we bombard their competition with lethal weapons, they get the place to themselves, and eventually, they take over. After generations of this, the super-drug loses its effectiveness.

Worse, other drugs lose their effectiveness, because many bacteria that are resistant to one drug will also resist other drugs in the same class. We are now learning that bacteria trade genes with each other promiscuously, even between different species, so that resistance developed by one strain of bacteria can be acquired by another. The more we use these drugs, the faster they begin to fail.

By 2004, more than 50 percent of staph infections were caused by methicillin-resistant Staphylococcus aureus (MRSA), up from 2 percent in 1987; some are also resistant to vancomycin, a common backup antibiotic. Other disease organisms show similar patterns: pneumococcus, E. coli, and, yes, M. tuberculosis now come in multidrug-resistant or extremely drug-resistant varieties. In 2001, the Food and Drug Administration warned:

Unless antibiotic resistance problems are detected as they emerge, and actions are taken to contain them, the world could be faced with previously treatable diseases that have again become untreatable, as in the days before antibiotics were developed.

We are not quite on the brink of some dystopian Victorian future. But every year, the prognosis for infectious-disease patients gets a bit grimmer. Ramanan Laxminarayan, an economist at the Center for Disease Dynamics, Economics & Policy, says that even extremely drug-resistant TB “can be treated with a couple of drugs. They’re just extremely toxic, and they’re not something you’d want to take”—think blood-sealed lips. And more-powerful drugs tend to cost more than the old drugs. “Right now the cost is in the hundreds of dollars, but the next step will be thousands of dollars,” Laxminarayan says. “In developed countries, it’s manifested in slightly higher average prices of antibiotics. In poorer countries, it manifests as more people sick and dying of resistant infections.”

Even in the rich world, death from infection still looms; MRSA alone kills thousands every year. And firms are not developing antibiotics as fast as they used to. According to the Infectious Diseases Society of America (IDSA), between 1983 and 1987, the FDA approved 16 new antibacterial drugs for use in humans; from 2003 to 2007, it approved six.

Whom to blame for all of this depends on whom you ask. Patients, physicians, hospitals, drug companies, and even regulators have all taken their turn in the dock. But to an economist, when it’s everyone’s fault, it’s really no one’s fault: what we’re witnessing is not a personal failure, but a market failure.

Almost no one develops something like MRSA in his or her own body. Resistance arises over generations of treatment, usually in hospitals with lots of patients. Though resistance is ultimately inevitable, we can slow its emergence considerably. However, doing so requires strict compliance with tedious and often expensive protocols. Each slip contributes only slightly to the problem, so there’s a high temptation to free-ride: Just this once, I’ll skip washing my hands between patients, or Just today, I’ll skip taking the last of the pills that upset my tummy. Anyone who lived in a group house in college knows how this story turns out.

Markets and property rights give people incentives to avert the tragedy of the commons, and have yielded a steady stream of life-saving drugs and medical innovations. But antibiotics are different from most of the other drugs we use. As Kevin Outterson, a professor of health law and bioethics at Boston University, points out, 100 million people could be taking Lipitor and it would remain just as effective as the day it was first invented. Unless we discover something even better, patients could still be taking Lipitor 1,000 years from now. But antibiotics like penicillin inevitably begin to lose effectiveness.

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Megan McArdle is a columnist at Bloomberg View and a former senior editor at The Atlantic. Her new book is The Up Side of Down.

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