Credit: Joe Kloc
Natural selection is stingy in its edits. It takes only three letters to go from “Hamlet” to “ham” and hardly more differences in DNA nucleotides to span the distance back between rodent and Rodin. The entire diversity of mammals reflects a modest tinkering with the original mammal plan. We share 99 percent of our genes with chimps, but we also share 95 percent of our genes with pigs and rats. And so most of the story of humans, our biology and deep history, is told equally well by the body of any mammal — even a lowly rat. Especially a rat.
We imagine the rat as despicable, disease ridden, grotesque. In tandem with fleas and plague, rats nearly did us in. But they may also have saved us. It is from the rat that we have learned most of what we know about ourselves. Look into a lab rat’s black eyes and you will find, if not your sister, an increasingly good mirror. Rats have immune systems like our immune systems. They have brains like our brains, fat like our fat. They have no language. They don’t dream about the stars. But otherwise we are the same. And so we poke them to learn about ourselves. We have long known that rats are like us. What is new is the realization that our similarities to each other are greater each year. More and more, I am a laboratory rat, and so are you.
Our stories and the stories of rats were long divergent. Our most common shared ancestor lived more than 70 million years ago. From there, the lineage that would become the Norway rat — the species that is used in labs and that is also most common in cities — and the one that would become humans went different ways. You know our story. As for the Norway rats, they evolved somewhere in Asia in ancient history (“Norway” having apparently been bestowed on the rat by the Swedish). Eventually, they found us, our scraps, and our throwaways. They came to our doorsteps and stayed and prospered. As we spread, they spread, from Asia to Europe, from Europe to Americas and then beyond. They spread like and with us (the best evidence of the routes that Pacific islanders took from island to island comes from what we know about the genetics of rats introduced with those humans). As they spread, they carried disease. They also ousted other species and races and came to be generalists, living off what could be had. On islands, they ate flightless birds. In cities, they ate what we left them. They found the scraps of civilization and tended to them with their delicate pink hands.
But times have changed. Few of us still live a self-sufficient life, gathering from the land. We have built cities and industrial agriculture. The wild rat lives a life that echoes our past but is removed from our present. One can still find wild rats (sometimes in great abundance), but most rats escaped that hardscrabble life at the same time we did. They became domesticated. In the midst of the industrial revolution, we brought Norway rats into the lab. We built them apartments, like smaller versions of our own. We fed them, like we fed ourselves, on sugars and without end. We let them grow fat, just as we grew fat. We stripped them of their parasites and doused them with antibiotics, just as we did to ourselves. Wild rats in their varied wild habitats live divergent lives, but lab rats (like, some would argue, humans in cities), have a shared experience of life.
In some ways, the way we care for rats is more advanced, at least technically, than the way we care for our own. In the lab, rat parasites are nearly absent; babies are often born via C-section to prevent transmission of any parasites that might be present. Newborns are moved to sterile environments, by hand, one at a time. Born red-pink with blood and life, they are cared for from that day on. And attempts at even better care continue — all, of course, to the ultimate end of making the rats more useful, though that does not matter to them. While wild rats have become a study in our past, lab rats have become a vision of our future. We test our drugs first on them and then, if they work, use the drugs on them and only later on ourselves. We make discoveries in them and only later prove them to be the case for ourselves. A recent study concluded that rats that are afraid of novelty die sooner. Upon hearing this, one knows the rub: that when we get around to testing it, the same will be true of us. The rats are always a step ahead of us.
That our rats precede us into the future, whether as guinea pig or vanguard, is not a new insight. What’s remarkable is that the basic biology of the lab rats has changed as we have gone on studying and raising them. There are ways in which the lab rats are, despite being parasite free and spoon fed, less healthy than their ancestors. And because we are like them, there are ways in which that realization applies to us.
William Parker is an assistant professor of experimental surgery at Duke Medical Center. Over the past few years he has been collecting wild rats not far from his office in Durham, North Carolina. Duke Medical Center is a serious, high-profile sort of place, and collecting wild rats is, at this point in history, just a wee bit taboo. But Parker went out and found rat colonies, living among boxes and urban realities. He gave them food, to get them used to taking food and then, slowly, he put out traps. He could be seen for a while, moving along darkened streets, carrying his quarry — their bald tails dangling — one in each arm. He took them back to the lab and there, among the civilized, domesticated, rats, studied them. He examined their immune systems. He predicted that the wild rats, because they are exposed to a slew of parasites (like our wild ancestors), would have fewer problems associated with autoimmune diseases and that they would be, despite their plagues of pathogens, more healthy. The lab rats, Parker hypothesized, like us, had immune systems with “basically nothing to do.” The wild rats had immune systems primed by and focused on the worms of the wild world.
Parker has begun comparing wild and lab rat immune systems and it is clear they are different. Some antibodies, particularly IgE, are far more abundant in wild rats than in lab rats. A separate study has shown the same is true in the comparison between wolves and domestic dogs. One’s first reaction to noticing that the immune systems of lab rats behave differently from those of wild (and natural) rats might be to say that we should stop studying lab rats. Domestication has rendered them strange and no longer representative of a wild mammal. Fortunately, our own lifestyles have rendered us strange, too. The “strange” response of the lab rats more closely resembles that of our immune system than do the wilder responses of wild rats, wolves, or for that matter any of the other mammals that have been studied to date.
The lives of lab rats and wild rats differ in many ways, and so there are many factors that might explain the differences in their immune systems. But the feature that stands out most is that lab rats have no parasites and, for quite a few generations, no history of parasites. In addition (and here both I and the researchers themselves struggle to find the right words), the wild rat immune system seems more “balanced” than that of the lab rats. Anecdotally, it appears as though mammal immune systems are tuned up with parasites in mind. When parasites are absent, the tuning is wrong. The immunological orchestra is too far off-key, far enough in fact that it attacks pollen (hence allergies) and even the body itself (in the case of autoimmune diseases).
As for Bill Parker, he continues to collect and study wild rats. He, like others, has begun to believe that “we will have to get back to our stone-age roots if we want a solution to our immune problems, since we have a stone-age immune system.” Parker likes the idea that we might be able to domesticate some of our parasites, in the way we domesticated the rat. We could give ourselves a dose of tapeworm to busy the bored immune system, but we would want the tapeworm (like the lab rat) to be docile and harmless, and so it needs to be “tamed.” That we might house a domesticated animal is, for Parker, the “answer in the gloom of it all,” but it is also a sign that regardless of where you buy your latte, your body, like that of a lab rat, misses what it has left behind.
For now, more is unknown than known about the causes of differences in the immune systems of wild and lab rats (or humans without or with modern medical care). But the broader truth is that we and rats have changed almost in lockstep as our lifestyles have changed. Rats have become our window into who we are and how to keep ourselves healthy. They have gone from following us from village to village to leading us into our own futures. Looking at the Norway rat and urban rats more generally in the wild, we seem to see aspects of our past. But it is in looking at laboratory rats that we see where we are and where we are going. The rats depend on us, whether in the urban wilds or in labs, for food and shelter. We depend on them to understand ourselves. None of this seems likely to change. In simple terms, the Norway rat is a predator (and an ecologically damaging, disease-carrying, invasive predator at that). But in a broader sense, we and the rat are mutualists. We live better because the Norway rat lives on. It lives better too, at least in a Darwinian sense, as we carry forward its genes, cage to cage, one delicate C-section at a time.
Jared Diamond has called humans the third chimpanzee, but we are much more like the second rat. Neither the chimpanzee nor the rat shares our hopes or fears, but the rat, as it looks out, dark-eyed, from its cage, shares our fate. — Rob Dunn is an assistant professor in the department of biology at North Carolina State University. He is the author of Every Living Thing.
Originally published April 6, 2009