The new drug law that President Kennedy signed on October 10, 1962, codified a profound change in attitude. With infectious diseases all but finished, the drugs of the future would target human chemistry. A horrified world had just discovered that one such drug, which effectively relieved morning sickness and helped people fall asleep, also halted the growth of a baby’s limbs in the womb. Before, when microbes were the enemy, drugs got the benefit of the doubt. After the 1962 Thalidomide amendments, the unknown cure was officially more dangerous than the known disease. Very strong evidence would be necessary to establish otherwise.

The 1962 drug-law amendments gave decisive weight to human tests and clinical outcomes: a drug would not be deemed “effective” without clinical trials in which human patients started out sick and finished up healthy. Progressing in little steps from that seemingly sensible starting point, the FDA has since reached the point of worrying more about drugs evolving into sugar pills than about currently innocuous germs evolving into plagues.

The FDA has long required that clinical tests demonstrate that a new antibiotic is as good as or better than one already on the shelf, and it wants these trials to be extremely thorough and convincing. It worries that with too few patients tested, statistical anomalies might allow an inferior antibiotic to win its license, and the new one might then become the benchmark for a third even worse one, and so on until the industry slouches its way down to licensed sugar pills. The agency calls this scenario “biocreep.” It’s just the sort of logical but overly theoretical concern that sneaks into government offices where the paramount objective is to avoid mistakes. But nowadays, “no mistakes” means no new drugs licensed until the germs start killing lots of people again. Most serious infectious diseases are rare, and it’s unethical to test a new drug on seriously ill patients when there’s an old, licensed alternative in easy reach. This makes it all but impossible to assemble enough sick-but-not-too-sick patients for statistically meaningful clinical tests.

For example, the FDA recently had to decide whether to approve the use of Cubicin against a vicious germ that infects heart valves. Dubbed the “Darth Vader” bacterium, it is stealthy, difficult to kill, and almost always fatal if untreated. The FDA’s staff wasn’t convinced that enough patients had been tested to establish that the drug was better than the already existing alternatives—and argued that if it was too weak, the germ might evolve into something beyond Darth, resistant to everything. On the other hand, doctors were already using Cubicin off-label—prescribing it in ways never officially vetted or approved by the drug company or the regulator—but in low doses, thus possibly creating an even greater beyond-Darth risk. In the end, the chief of the FDA’s anti-infectives division overruled a staff recommendation and granted the license. But every such decision is a fight, and all the legal, political, and institutional cards are now stacked against quick, bold action.

A letter coauthored by a doctor at Harvard’s medical school and published in Clinical Infectious Diseases in 2002 bluntly linked the FDA’s approach to “the end of antibiotics.” “For nearly two decades,” it began, “antibacterial research has been the ‘Cinderella’ area in the pharmaceutical industry.” Increasingly stringent demands for proof efficacy, framed in ways that seem “innocent and technical,” the authors argued, have thrown the industry “into a panic.” They have “wreaked irreparable damage to our ability to provide a reliable pipeline of new antibiotics for treatment of serious infections.” And they probably helped propel Lilly and Bristol-Myers Squibb out of antibacterial research and development.

Most fundamentally, the FDA has no mandate—none at all— to prepare us for war against the next cholera. Its mandate is to make sure that we don’t lose the battle against the next Thalidomide. “Safe” and “effective,” the two key standards set out in the 1962 drug law, have intelligible meaning only with a germ to fight and infected patients to fight it in. The agency, in other words, actually needs thriving germs to supply enough really sick patients to provide FDA-caliber evidence to validate the drug that will wipe out the germs. Epidemics that lurk in the future, waiting for germs still under construction, can’t be officially considered at all. But those germs—the ones that don’t yet exist, the ones still evolving, by chance or with human help in a terrorist’s lab—should worry us most.

Today’s public health guardians have made things even harder for vaccines than for antibiotics. Gene-splicing and other bioengineering tools make it far easier today than ever before to build safe corpses, cousins, or fragments of horrible microbes. But many vaccines that could quite easily be developed haven’t been, and probably won’t be, because no drug company will take them to market.

Political support for the FDA depends on the public perception that it’s solving problems. When widely administered, as it must be, a vaccine wipes out the disease that it targets. The disease can thus be eclipsed in the public’s mind by the vaccine’s side effects, however rare or even imaginary. The more effective the vaccine at the outset, the more likely it will be condemned as unsafe at the end. Moreover, the FDA has an acknowledged policy of being extra cautious in licensing any product that healthy people will use, especially children. Nothing could better suit the germs. Healthy children with undeveloped immune systems are their favorite targets.

Judges and juries have even more trouble balancing the interests of the individual who claims that a vaccine has injured him against those of the rest of the disease-free community. New legal standards formulated in the 1950s and ’60s made it much easier to sue vaccine manufacturers, and relaxed rules of evidence soon made junk-science allegations much more common than legitimate ones. When liability claims spiraled to the point where they threatened to cut off the supply of some vaccines entirely, Congress set up an alternative compensation system for children (though not for adults) actually injured by their immunizations, and imposed a broad-based vaccine tax to fund it.

But it was too little, too late. Enveloped in bureaucracy, the germ-killing segment of the drug industry has lost much of its flexibility, resilience, and reserve capacity—and has become painfully slow in developing what new science makes possible. Short-term economics and federal law have converged to create a systematic bias in favor of the germicidal drug invented and licensed decades ago. The principal fiscal concern is who should pay how much for the new, patented drug, or whether the old, cheaper generic might not do as well. The principal regulatory concern centers on the risks of the new drug, not the perils of the new germ. Insurers are cost averse: wherever they can, they favor cheap drugs with expired patents. The FDA is risk averse: when in doubt, it sticks with the old and says no to the new.

Research labs do continue to come up with new vaccines, but that decade-long process is now routinely followed by a second decade (at least) before a commercial product makes it to market. No one doubts that the extra time helps ensure that the vaccine eventually injected into millions of arms is safer and more effective than it might otherwise be. But the whole effort is long and costly, and the likely profits waiting at the end, many manufacturers have concluded, are very modest by comparison. In 1957, five important vaccines were being supplied by 26 companies. By 2004, just four companies were supplying 12. Mergers accounted for some of the attrition, but most of it resulted from companies getting out of the business. More than half of the vaccines routinely given to young children in 2005 came from just one manufacturer; four others had only two suppliers.

Having surrendered on all other social aspects of infectious disease, the health authorities now focus principally on socializing costs. Capping profits is the politically inevitable corollary. The federal government now buys over half of all vaccines used in the United States, and by taking on that role, it has effectively taken control of prices.

After the anthrax mail attacks in late 2001, federal authorities made it clear that if push came to shove, they would rescind patents, too. Just two years earlier, at the government’s specific request, Bayer had asked the FDA to approve and label Cipro for use against inhalational anthrax. The agency granted the license—the first ever for a drug for use in responding to a deliberate biological attack—in a matter of months, basing its approval not on human trials but on the antibiotic’s effectiveness in inhibiting anthrax in rhesus monkeys. Then came the 2001 mail terror. Demand for Cipro soared—and prices collapsed. Yes, collapsed.

It was politically unthinkable for Bayer to raise the retail price in pharmacies, and federal authorities immediately demanded huge discounts on the pills that they wanted to stockpile. The Canadian government initiated its price negotiations by announcing that it would ignore Bayer’s Canadian patent and order a million tablets of a generic version of the drug from another company.

A couple of years later, Congress passed the 2004 BioShield law. It is intended to create a federal stockpile of bioterror vaccines, and to that end, it empowers the Pentagon to bypass certain aspects of the 1962 drug laws. Those provisions have already been invoked once, to cut off litigation against military use of the anthrax vaccine. The federal government also offered almost $1 billion of BioShield cash for the development of a new anthrax vaccine and the provision of 75 million doses. But established drug companies just weren’t interested. The contract went to VaxGen, a tiny startup that had never brought a licensed drug to market and that proposed to supply a bioengineered vaccine that the army had already developed. VaxGen failed to deliver, and last December, the government canceled the contract.

A decades-old alternative with various problems continues to be provided by BioPort, whose declared mission is to develop products for use against infectious diseases “with significant unmet or underserved medical needs” and, most notably, “potential weapons of bioterrorism.” That would mean anthrax, botulism, Ebola, and smallpox, among other killers. BioPort employs about 450 people.

So what would a watchmaker have done—not a blind one, but one with keen eyes and an excellent loupe—if called upon to design a microbe that could thrive among people fortified by fistfuls of vaccines and backed up by dozens of potent antibiotics? Nature got there, without the loupe.

Humans had spent a painstaking century developing vaccines. So nature designed an “immunodeficiency” virus—an all-purpose anti-vaccine, so tiny, quiet, slow, methodical, and gentle that it spread unnoticed for decades, and so innocuous that it never quite gets around to killing you at all. It leaves that to the old guard—the bacteria, protozoa, and viruses that invade when your immune system shuts down, and feast on your brain, lungs, blood, liver, heart, bone marrow, guts, skin, and the surface of your eyes. In its final stages, AIDS is truly horrible.

When the blind watchmaker has been pulling such stunts for 4 billion years, it’s reckless to suppose that HIV was its last or worst. Quite the contrary: our casual willingness to tolerate a septic underclass, so long as it remains insular and out of sight, is certain to hasten the rise of much more and much worse. People as negligent with pills as they are with germs have already helped spawn drug-resistant forms of tuberculosis, by taking enough medicine to kill weaker strains, while leaving hardy mutants alive to take over the business. HIV patients who don’t strictly follow the complex, unpleasant drug regimen used to suppress the virus become human petri dishes, in which microbes multiply and evolve to resist the stew of antibiotics prescribed as a last resort.

The new infectious diseases are already very good at this sort of adaptation—they have evolved to be as nimble as we are now institutionally stolid, as flexible as we are rigid. The influenza virus evolves exceptionally fast, using pigs as its genetic mixing bowl. HIV mutates constantly—one drug-resistant strain of the virus now apparently depends for its survival on a chemical constituent of the drug widely prescribed to stop its advance. Stubbornly persistent pelvic infections are on the rise, along with drug-resistant gonorrhea and even syphilis. A certain staph bacterium responsible for the most common infection acquired in hospitals has developed ways to pass the gene that produces a lethal toxin from one strain to the next and also to certain viruses that can spread it further still.

It’s because the threat is so grave that one must avoid the temptation to propose a simpleminded checklist of reforms to shoehorn somewhere into the middle of the next 1,000-page revision of the federal drug laws and FDA regulations. Germs are terrorists: they let the dead past bury its dead, they are always changing, and the ones you know aren’t the ones that will kill you. If we somehow revive a tough, germ-fearing culture, the risk-averse drug regulators, penny-pinching insurers, overreaching judges, clueless juries, and preening, industry-bashing congressional committees will fall into line. If we don’t, no tinkering will make much difference.

What we need is quite simple. We need many people to be much more frightened than they currently are. And we need a robust, flexible, innovative portfolio of drug companies to sink a lot of new capital into highly speculative ventures, almost all of which will lose money, with just one or two ending up embraced by regulators, eagerly paid for by insurers, vindicated every time by judges and juries, lauded by nonconformist preachers, and so spectacularly profitable for investors that they crowd in to fund more.

If we can’t drum up concern by other means, some dreadful germ will materialize and do the job for us. Nobody knows which one; that’s why we so desperately need the right popular culture and vigorous private enterprise. If the germs in the tattoo parlors today were both virulent and untreatable with current medicine, you wouldn’t be reading this, at least not in the heart of any big city. You’d be heading for the country.

That’s what the rich did when epidemics struck in Dickens’s day. They knew what they were fleeing—the urban pathologies described in Our Mutual Friend in 1864 were as familiar to Londoners as the Thames. And familiar not just to the boatmen who made a living fishing human corpses out of the river but also to the middle class, decimated by a violent cholera outbreak in Soho at the end of August 1854; to the entrepreneurs who made fortunes collecting and sorting mountains of trash; to members of Parliament, who, in June 1858, had to evacuate the House of Commons to escape the pestilential stench of the river; and to Queen Victoria, who lost her husband to another waterborne disease, typhoid fever, in 1861. Small wonder that cholera was a great agency for social change. In the time of cholera, the bacterium itself loved everyone.

Anthrax prefers goats; it finds its way into human bodies only very occasionally, through open wounds. The spores can be inhaled, too, but ordinarily they clump together and don’t spread well through the air. They become mass killers only when people painstakingly coat them with other materials and take special efforts to disperse them. The spores that struck 11 Americans (and killed five) in Washington, D.C., and New York in late 2001 weren’t dispersed through the Potomac or Hudson Rivers; they arrived by U.S. mail. A few pounds, suitably prepared and dispersed in the New York subway, could kill 100,000 people. If cholera is a social disease, weaponized anthrax defines the antisocial bottom of contagion—it’s a microbe that infects humans only with the help of sociopaths.

But we live in an age of sociopaths, and there remains much that we don’t know about germs. Viruses and prions may play a far larger role in genetic malfunctions than we yet fully understand. HIV and influenza demonstrate the boundless viral capacity to mutate and evolve. And while anthrax could never make it on its own in New York, murderous people are scheming to give it help. One way or another, germs will contrive to horrify us again, in some very nasty way. A society’s only real defense is to stay horrified, well ahead of the curve.

This article originally appeared in City Journal