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Why our flu vaccines can’t keep up

It’s evolution—and, as a century-old experiment on sparrows showed, it can happen overnight.


This winter’s flu season is one of the worst in a decade; it started particularly early, and by January, Boston Mayor Thomas M. Menino had declared a public health emergency. Nationwide, there have been large numbers of hospitalizations and deaths, particularly among those over 65. Our only protection, aside from hand-washing and shunning social interaction, is the flu vaccine.

Still, as we have all heard by now, this season’s flu vaccine is only 62 percent effective (an average of the protection against each of the major strains prevalent this year). While that’s far better than crossing your fingers and hoping for the best, the risk of getting sick even when vaccinated is much greater than with vaccines for diseases such as polio. Why is it so hard to develop and maintain a highly protective vaccine for flu? The reason is, in a word, evolution.

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It might be hard to imagine evolution working quickly enough to touch our day-to-day lives, and when the theory was still young, the speed of evolution was an open question in science. A key experiment that helped answer the question was carried out right in New England, during another blustery winter over a century ago.

In 1898, the region was experiencing record-setting bad weather. Rather than bemoan the cold temperatures, an extravagantly mustached scientist named Hermon Bumpus, an assistant professor of comparative zoology at Brown University, decided to profit from misfortune in the name of science.

After a brutal early February storm, Bumpus was brought 136 dead or stunned house sparrows. (His paper is curiously mute about the source—was he well known to friends and neighbors for an interest in dying birds?) Once Bumpus saw that about half the birds recovered after they were warmed, while the others died, he knew he had a potential gold mine of information on his hands. Darwin’s theory of evolution by natural selection, then still just a few decades old, predicted that certain individuals would survive and reproduce while others failed. If this process had just happened with the sparrows, then the survivors might show characteristics that the others did not.

So Bumpus methodically measured the size of bills, wings, legs, and other body parts in the survivors and those not so fortunate, and then compared the two groups. They differed substantially. Unusually large or unusually small birds fared worse than those clustered around the average size of the group, and Bumpus postulated that stabilizing selection, a kind of natural selection that winnows out the extremes and favors those in the middle, had been at work. Through the pattern of death and survival, the genes in the population had changed in relative frequency. In other words, evolution had occurred.

Bumpus had confirmed that evolution happened in the wild; his study is still used by biology classes today in calculating the action of evolution. But he had also shown that it could, literally, occur overnight. What is required is a strong selective agent, like the storm, and the variation to ensure that at least some individuals survive to reproduce. Since Bumpus’s time, and ever more readily in the last two decades, scientists have confirmed so-called contemporary evolution—genetic change in a population within 100 generations or fewer—in scores of species.

Today, the most common modern-day equivalent of the Providence blizzard is human activity. Trophy hunters can change a population of sheep or deer by shooting the rams with the largest horns or antlers; similarly, fishing seems to have to have altered the life schedules of salmon and other commercially important fish by removing specimens that grow to a large size before they have a chance to reproduce. Keep picking off those slow-maturing larger individuals, and soon the average salmon is smaller and precocious, a process called fishery-induced evolution. Where viruses like influenza are concerned, meanwhile, the strong selective agent is the human immune response—which can be bolstered by vaccines.

Vaccines work because they stimulate the immune system in much the way that an actual pathogen would, but in a more muted fashion, so that when the real thing comes along, our system can recognize and defeat the invader before it takes hold. Some pathogens are extremely vulnerable to such an approach, which accounts for the disappearance of smallpox from the world. Others, including HIV and flu, are not so easily conquered—likely because these viruses produce genetic mutations, the raw material for evolution, with extraordinarily frustrating rapidity.

Why is it so hard to foresee what changes in the flu genes will happen next and design a vaccine accordingly? For the same reason that Bumpus needed to actually measure those sparrows. Bumpus knew that the survivors would have some traits that allowed them to withstand the cold, but many such traits exist. Neither he nor the birds could know in advance which characteristics would have been the smart ones to bear, because the variation itself is produced at random. Selection will produce better adapted individuals, but the paths to that adaptation are often innumerable.

Similarly, we know that the flu virus will change in response to selection, but the precise direction it will take is difficult to predict, because evolution itself is never goal-oriented. The sparrows weren’t trying to get to a particular point, and neither is the flu. All scientists can do is study the genetic variation that exists in the viruses from a given year, and try to determine which mutations are statistically more likely to occur the next time.

Scientists don’t fully understand why some viruses, like polio, seem to be evolutionarily conserved, as it’s termed, while others change like chameleons. But the distinction means that to conquer the flu, we need to proceed on two fronts. First, of course, broad vaccine coverage is essential: The more vaccinated people, the greater our herd immunity and the better the protection for vulnerable individuals. But second, because the flu virus is such an evolutionary quick-change artist, we need to redouble our efforts to make better vaccines. An average efficacy of 62 percent instead of, say, 90 or 95 percent, is not because the scientists developing the vaccine aren’t as clever as Jonas Salk. It’s because flu is different, evolutionarily, from polio. And that means that we can’t just concentrate on getting everyone vaccinated. We need to do more research into rapid evolution.

Indeed, a recent report from the University of Minnesota’s Center for Infectious Disease Research and Policy decried the focus on getting more widespread coverage with the currently less-than-perfect vaccines, rather than on improving the efficacy of the vaccines themselves. The lead author of the report, Dr. Michael Osterholm, said in an accompanying release, “We found a general perception that we don’t need a better flu vaccine, we just need to make more of it faster.” But the more basic research on viruses that will lead to improved vaccines is crucial, since the flu, like humanity and those sparrows, keeps on evolving.

Marlene Zuk is a professor in the department of ecology, evolution, and behavior at the University of Minnesota. Her book “Paleofantasy: What Evolution Really Tells Us about Sex, Diet, and How We Live” is forthcoming in March.
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