Until the nineteen-forties, whooping cough—the hundred-day hack that causes victims to gasp for air, vomit, pass out, or worse—was as common as it was ghastly. But then, as with so many other childhood plagues, American kids began to receive regular immunizations, and deaths from the disease dropped dramatically. For decades, the number of cases in this country dropped to about five thousand per year.
Now, however, whooping cough is resurgent: just under fifty thousand people caught it in 2012. This is mainly because protection from the current shots wanes over time. But, as the bug circulates, it is also morphing. Last February, researchers identified mutant strains of the bacteria in eleven patients in Philadelphia. These mutants, it turns out, appear to be the dominant form of the bug in this country. Whooping cough has evolved in a way that vaccine-preventable diseases rarely do.
Researchers at the Centers for Disease Control and Prevention, who have analyzed samples dating back to 1935, say that these mutants first appeared in 1994, in what seems to have been a sporadic case in a single individual in North Carolina (though no one identified it as such at the time). These particular variants, which are missing a key surface protein, didn’t turn up again until 2010, and then only rarely. Since then, however, they seem to have multiplied madly, appearing in roughly sixty per cent of isolates, or samples, in 2012. In Vermont, they are found in more than ninety per cent.
This is raising eyebrows. Unnervingly, C.D.C. scientists speculate that the current vaccine may be helping to drive the bugs’ evolution. “The fact that this happened so quickly, to the proportions we’re seeing now, clearly suggests some selective pressures …. Vaccine pressure is probably one of them,” Lucia Pawloski, a whooping-cough expert at the C.D.C., told me. Think of mice that are hard for cats to see; they might proliferate if cats were introduced to their environment and started eating all the easy-to-see mice. Similarly, bugs that might be less “visible” to the immune system could spread in response to the vaccine.
The mutants do not seem to make people sicker than the old bugs. Nor does the new data undermine the importance of getting vaccinated. Individuals are far better off getting the shots than not. Still, other diseases, such as measles, rubella, and polio, have also been longtime targets of immunization, yet they haven’t adapted. Why is whooping cough evolving this way, and why, after decades of immunization, is it doing so now?
Early on, the whooping-cough vaccine was considered an unambiguous success story_._ Over time, though, scientists—as well as crusading vaccine skeptics—raised concerns about the shots’ side effects, which could include high fever and, occasionally, seizures. In the late nineteen-nineties, the U.S. switched to a new formulation, made not from dead, whole cells of bacteria (as the original had been) but from selected components of the bug that would trigger an immune response more safely. Unfortunately, though, the effectiveness of the updated vaccine waned far faster than the old version had, and faster than researchers had expected. This is probably the main reason that whooping cough has surged recently in older children: those who received the newer vaccine as babies became vulnerable again as the doses that they received between ages four and six, and the boosters that they received between eleven and twelve, wore off. (Parents who refuse to vaccinate their children undoubtedly make the problem worse.)
Higher levels of circulating disease, including among people who had received the shots, meant that the bacteria may have had, in essence, a chance to sniff around. The current formulation, called the acellular vaccine, trains the immune system to recognize three to five components of the bacteria. One of these is a protein, pertactin, that the bacteria use to adhere to the respiratory tract. The mutants that gained an edge—and now dominate—are those that no longer produce pertactin. In other words, they can hide from one component of the body’s defenses. (Fortunately, the immune system still recognizes other parts of the bug, thanks to the rest of the vaccine, which is why the shots are not ineffective, even against the mutants.) At the same time, the bacteria may be circulating even more than surveillance would suggest. As researchers at the Food and Drug Administration reported in the fall, baboons that received the acellular shots could still transmit the disease, to some degree, even if they did not get sick. If this applies to people, it would imply still another opportunity for the bugs to evolve. (It would also make it even more critical for children and adults to get immunized, because they may be at greater risk from asymptomatic carriers than was previously understood.)
Scientists are still trying to figure out how much the mutations matter clinically, and how effective the vaccine remains against them. What’s remarkable, though, is how unusual any vaccine-related adaptation is when it comes to traditional childhood afflictions. The shots against measles, rubella, and polio have protected decades of children, with no fundamental changes. The flu evolves, but probably not mainly because of immunization, said Stanley Plotkin, an emeritus professor of pediatrics at the University of Pennsylvania. Meanwhile, different types of Streptococcus pneumoniae bacteria, which can cause ear infections and meningitis, have spread recently, perhaps because the vaccine targeted their competition. Researchers, in response, have updated the shots. But these are exceptions.
Measles hasn’t avoided natural selection, of course. More than twenty strains are known to exist, yet our shots protect against all of them, Samuel Katz, a pediatrician and vaccinologist affiliated with Duke, said. He and others helped to create the original vaccine in the late fifties and early sixties, using a strain isolated from a Massachusetts schoolboy. Given what was known at the time, it seemed like “purely good fortune” that they were able to create a lasting formulation, Katz told me. Somehow, measles shots stimulate a strong defense against parts of the pathogen that are critical to its existence. The virus can evolve in some ways, but it hasn’t circumvented the vaccine.
Another notable example is smallpox, which was essentially eliminated by immunization. Despite intense vaccine pressure, “natural selection failed, thank goodness,” Andrew Read, an evolutionary biologist at Penn State University, said. It isn’t clear why the elements of smallpox, polio, and measles that the immune system targets haven’t mutated. It must have something to do with their function. Perhaps they play an indispensible role in reproduction. But these are hard points to prove because researchers can’t generate variants or observe naturally occurring ones. “You can tell all sorts of stories, but it’s really hard to study the evolution of something that doesn’t evolve,” Read told me.
As it turns out, the childhood vaccines that confer long-lasting protection to kids also seem to be evolution-proof. Children who get shots against measles, rubella, and polio are unlikely to get these diseases, even years down the road. In essence, the vaccine mimics the extraordinary long-term protection conferred by getting sick, without all the misery. Those who suffer through whooping-cough infections, by contrast, tend not to gain lifelong protection, and neither do those vaccinated against the disease. This was true with the old whole-cell shots, and is even truer with the acellular version. (Other factors, related to whether the pathogen enters the bloodstream and how strongly it stimulates the immune system, also play a role in how long protection lasts, according to Paul Offit, the chief of the division of infectious diseases at the Children’s Hospital of Philadelphia.) Researchers are already working on an updated whooping-cough vaccine that they hope will provide longer-lasting immunity. (Returning to the old vaccine, with its harsher side effects, seems neither politically possible nor appealing.) At the same time, it’s worth appreciating the lives already saved by whooping-cough shots—as well as by the many other vaccines that have been passed down now, like heirlooms, for generations.
Amanda Schaffer last wrote for Elements about whether our bones influence our minds.
Illustration by Matthew Hollister.