In the Darwin bicentennial, new insights into fossils, genes, birdsong, and cancer.
The latest issue of Nature to land in my mailbox-the May 28th one-was not a tribute to Darwin in honor of his 200th birthday and the 150th of The Origin of Species; Nature has been there, done that. But it might as well have been another celebration for him, since without even trying it delivered four items of Darwinian news, all with direct or indirect relevance to us humans.
One is about a fossil named Darwinius, affectionately known as Ida. It’s an amazingly complete skeleton of a cat-size 47-million-year-old primate which its discoverers claim is one of our direct ancestors. Whether that is true or not (it probably isn’t), the hype around the announcement was fascinating. Not only was it called “the missing link,” “the Holy Grail,” and “the eighth wonder of the world,” but it found its way into Google’s logo on its home page for a while. It says a lot about us that we could get so excited about a bunch of old bones, just because of their place in Darwin’s theory. Ida seemed like an Adam or Eve we could believe in.
Another piece of news was about birdsong. A young woman named Olga Feher and her colleagues at my alma mater (the City University of New York) raised some zebra finch males with no chance to hear their fathers sing. That, we know, produces some very abnormal noises when those boy-chicks grow up and try to pipe like kings of the hill. But here’s the news: take one of those males, give females no choice but to breed with him, and his sons will sing more normally than he does. His grandsons will do even better, and his great-grandsons approximate the normal wild song-which none of these fellows has ever heard. Some sort of collective cultural evolution puts the song right again. It’s hard to avoid a comparison with the transition from pidgins to creoles, where a first generation of colonized people speak a crude, broken version of the colonizers’ language, but their children create a unique but more fully developed version. It’s a strange kind of evolution, combining the power of genes with cultural change.
The third was the cover story-probably the first time a supermodel graced the cover of Nature. Cute as anything, but (sorry) it’s a “biomedical supermodel,” a monkey called a marmoset, and it’s a super model organism for medical research. The news is that it became the first monkey to have its genes manipulated and to pass its new genes on to its offspring. This is big. So far, most gene-manipulation experiments have been done in mice, known as knock-in, knockout, and knockdown models depending on whether genes are added, removed, or temporarily turned off. They’ve produced many findings relevant to human disease. But as Darwin knew, marmosets are much closer cousins to us than mice, and the possibilities they offer to medical science are that much greater.
Finally, an essay in the issue talked about a new Darwinian perspective on cancer, one that may lead to surprising solutions. I’ve written before here about my frustration with medical science’s failures in treating cancer. The only common cancers we’ve succeeded with are the ones we figured out how to prevent, and only a few uncommon ones have become highly treatable. Why? The answer, again, is Darwinian.
Cancers act like viruses, bacteria, or parasites-only more so. These organisms evolve in the face of our treatments, but we can cure most of them in most individuals, because they’re different enough from us biologically so that we can find agents that kill them without hurting ourselves too much. As a species, we’ll always be involved in an arms race with each of them, but we can stay ahead.
With cancer it’s different. Tumors are too much like the rest of us-they are us-and so our best weapons against them are deadly to us too. We have to play softball, which allows them to evolve resistance within each stricken individual.
Robert Gatenby and his colleagues at the Moffitt Cancer Center in Tampa suggest we might try playing even softer ball. Instead of the analogy of the magic bullet that kills all tumor cells the way we kill some bacteria, we might try to reach a standoff with the tumor, allowing it to hang around without killing the patient and without evolving intractable resistance. Their mathematical models and experiments show that the no-holds-barred approach may kill the victim faster than the fight-to-a-standoff approach. Mice with tumors lived longer when the chemotherapy was adjusted to keep the tumor volume stable instead of wiping it out-except for the resistant cells, which in usual chemo come back with a vengeance.
The idea for this approach, as well as the models, came from evolutionary ecology, and it works well for some invasive pests, like the diamondback moth that threatens vegetable crops. It couldn’t be eradicated because it evolved resistance to all known pesticides. But it can be held to a level that is compatible with economically sustainable crop yields.
Gatenby doesn’t want cancer researchers to give up searching for cures. But in the meantime, he says, “instead of focusing exclusively on a glorious victory, they should address the possible benefits of an uneasy stalemate . . . in battles against cancer, magic bullets may not exist and evolution dictates the rules of engagement.” To Darwin’s younger contemporary Louis Pasteur, we owe our understanding of how microbes cause disease; two centuries after they were born, we find ourselves stumped at a species level by some microbes and at an individual level by almost all cancers. In the always-uphill battle against disease, Darwin’s ideas are coming to the fore.