Yesterday news broke that a vaccine for cervical cancer might not be all it’s cracked up to be. Cervical cancer is caused by a virus known as human papillomavirus. It infects epithelial cells in the skin and other surface layers of the body, including the vagina and throat. On rare occasion it causes its host cells to start replicating madly, creating growths that sometimes progress into full-blown tumors. It’s a major menace: the American Cancer Society estimates that it causes 17 percent of all cancer cases–more than 1.8 million a year. Merck has designed a vaccine that turns out to be 98% effective against the types of virus that cause most cases of cancer. And yet, paradoxically enough, doctors found that when women were given the vaccine, it only had a 17% efficacy rate in preventing the lesion that can lead to cancer.
The coverage of the study was massive, but it seemed to me to keep away from the heart of the matter. Many reports zeroed in on the study’s finding that human papillomavirus may cause cancer in the throat through oral sex. Others took note that the paper came out just a couple days after Texas governor Rick Perry announced he would not veto a bill passed by the state legislature blocking his order that all girls in Texas get the vaccine. The move to block the order has been driven by several political groups, such as the Free Market Foundation and Texas Physicians Resource Council. They objected to the state taking over the decisions of parents, and also argued that there were too many questions about the new vaccines. It was possible that other vaccines to other strains of the virus would be more effective. A report in the Baptist Press claimed that the new study supported this claim.
Not having heard of these groups before, I checked out their web sites. When I visited the Free Market Foundation site, I had to smile. They not only fight against the Merck vaccine; they also fight against evolution. Their voters guide (pdf) includes on its list of make-or-break issues, “Present scientific evidence in our public schools supporting intelligent design, and not just evolution, and treat both theories as viable ones on the origin of life. You can catch their president, Kelly Shackelford, on a PBS show coming up about “Darwin versus Design.”
I smiled because I had just finishing reading some new papers with titles like “Multiple Evolutionary Mechanisms Drive Papillomavirus Diversification.” To understand why vaccinating against human papillomavirus is so tough, scientists study how it evolved over millions of years, just as it is evolving today. [More below the fold...]
Viruses sometimes mutate as they replicate inside host cells. Those mutations may be the result of sloppy copying of virus DNA, or of fragments of different strains of viruses recombining into new hybrids. Natural selection favors some of these mutants if they out compete other viruses, or if they can colonize some new niche. In recent years, scientists have been sequencing the genomes of about 150 different papillomaviruses and comparing them to figure out how they have evolved–and how some of them have evolved into cancer triggers. It’s a tough puzzle, because of the way viruses swap genes. All of the genes in a given papillomavirus may have different evolutionary history. In the study I referred to above, researchers in Europe searched for the stretches of DNA in the viruses that provide the clearest picture of their history.
The big debate going on in papillomavirus circles is how all the strains of the virus that infect humans ended up infecting humans. In 2006, for example, researchers at the University of California at Irvine found distinct differences between the strains, leading them to conclude that “all HPV types existed already when humans became a species. Consequently, humans had always suffered from lesions like anogenital cancer, genital warts and common warts.”
But the picture gets more complex when a team of European scientists looked at the papillomaviruses that infect other warm-blooded animals. (The viruses can sometimes cause cancer in them as well, and they are considered a serious threat to some endangered mammals.) The scientists compared how closely related virus strains were to how closely related their hosts were. If the virus’s evolution simply tracked that of its host, you’d expect their evolutionary trees to be mirror images. All human papillomaviruses should be more closely related to one another than any is to viruses in other animals, for example, and of those animal strains, the ones infecting chimpanzees should be closest. There are parts of the virus and host trees that mirror each other, indicating millions of years of coevolution. Some closely related branches of papillomavirus only infect whales and dolphins, for example, and no other species.
But there are also parts where the symmetry is shattered. Some human papillomaviruses all form a single tuft on the tree, but sprouting out of the middle of it is a strain that infects macaque monkeys. The virus leapt between hosts separated by over thirty million years of evolution. Many of these jumps occurred millions of years ago, after which the viruses evolved to adapt to their new hosts and then tracked their hosts’ evolution closely. But in other cases, the jumps were recent–perhaps even in the past few thousand years as humans and animals have spent more and more time in close contact.
As these viruses jump, mix, and evolve, they create a complex ecosystem inside every host. Even the skin of a perfectly healthy human or animal may be rife with different strains of papillomaviruses. Some viruses may do a better job of infecting cells than others, and come to dominate the virus ecosystem. Vaccines that wipe out one or two top cancer-causing viruses may just be making room for others. And unfortunately, the supply of potential sources of cancer–both in humans and in other animals–is practically bottomless. Not only is there a vast pool of these viruses already, but they can evolve rapidly, swapping genes that make them more of a risk to causing cancer.
It may seem strange that someone could simultaneously undermine teaching evolution and use the evolution of viruses to fight against a vaccine program. But this sort of disconnect is nothing new (paging Jeb Bush). Let’s just hope it doesn’t get in the way of more research of the sort I described here.
[For evolutionary tree-huggers, here's the key figure from the new paper. Click on it for a bigger view:]