Indiana University Research & Creative Activity

On the Human Condition

Volume XXVIII Number 2
Spring 2006

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prairie vole
NPS photo by J. Hemphill

monk parakeet
Monk parakeet
Photo © Kathleen Carr

junco nestlings
Junco nestlings
Photo courtesy IU Department of Biology

The Scientists and the Supermodels

by Kelly L. Phillips

Tour any major animal research lab in the world, and you'll see mice. It's inevitable. There are literally millions of them. And their infestation of science is lasting--they have been considered a scientist's most valuable biological research model for more than a century.

Mice, along with rats and birds, make up nearly 85 percent of species studied in labs. They're perfect for a research environment: quick to reproduce, easy to care for, and generally unruffled by manhandling. Because they are such a popular mammalian medical model, it was a no-brainer to choose mice--alongside humans and chimpanzees--as one of the first mammals to have its entire genome sequence published. In 2005, they were joined by rats, opossums, and dogs.

Because of their broad research presence and highly deciphered genetic code, we know a lot about mice. And due to all of the human functions, diseases, and behaviors mice have modeled, they may know just as much about us. In the lab, mice act as mammal models for, well, everything. They're the closest we've got to a scientific supermodel.

But despite all our knowledge, the connections between humans and our furry white counterparts go only so far. In 2005 alone, scientists cured model mice of the West Nile virus and Severe Acute Respiratory Syndrome (SARS). We've prevented mice from developing Parkinson's disease, Type 1 diabetes, and even baldness.

Clearly our track record for curing these same problems in humans isn't quite up to speed.

Finding a true supermodel to accurately test a human condition is a tough, multifaceted challenge. In many cases, mice don't cut it--we're just too different. Even primates, our closest genetic and physiological matches, aren't perfect. Discovering an undisputable link between what works for an animal and what works for a human is nearly impossible in scientific research.

So the scientific literature is packed with unusual models, chosen to demonstrate a particular brain structure, neural pattern, behavior, etc. Crabs and lobsters have been some of the influential models of muscle activity. Marine invertebrates and electric eels have taught us some of the most basic principles of neural function. And songbirds have been one of the most studied models of vocal learning.

There's much to learn from going beyond the mouse, as the 19 core members of Indiana University's Center for the Integrative Study of Animal Behavior (CISAB) know well. Some of their research applies to humans, and some might, someday. But one thing is certain--as the work coming out of IU's animal behavior center shows, animal models are highly significant and useful in understanding humans, our shared evolutionary history, and our world.

Modeling Immunity, Energy, and Stress

Take the work of biologist Gregory Demas, one of the core members of the CISAB. His latest animal research, a study modeled by Siberian hamsters and prairie voles, was the first to show that loss of body fat leads to decreased levels of infection-fighting antibodies and an overall impairment of the immune system.

Demas used a liposuction-like procedure called a lipectomy to remove fat tissue from the animals, then exposed them to an antigen that induces a strong immune response without causing sickness. With the stress of the missing fat, his test animals lost much of their humoral (meaning, related to body fluids) immune protection--in other words, they lost their normal ability to fight off infections. The study adds weight to the idea that the immune system requires a great deal of energy to function optimally.

So if a human lost weight rapidly, could his or her immune system be affected? Possibly, says Demas. Liposuction is a common human cosmetic procedure, and it's possible that his hamsters could be modeling a body stressor that humans also experience.

"I don't think anyone's really looked into what happens with your health after liposuction," he says. "I've had some people contact me as a result of this study and say that they've gotten sick after some sort of liposuction procedure, but they're all anecdotal accounts. I wouldn't call it a direct connection, but it's definitely an intriguing one."

Demas also argues that hamsters are a great model system for humans in several respects. Hamsters share the so-called "stress hormone" cortisol, secreted by the adrenal glands, with humans. Rats and mice don't. Plus, unlike mice, hamsters have not been artificially bred for similarity over years and years, making hamsters a more naturalistic model, he says.

The connections between body fat, energy, and immune function are the focus in Demas's lab now, as well as links between the brain and the immune system. "We know an important link exists between the brain and the immune system, so we're trying to get a better understanding of it," he says. Modeling that particular system, a project that could shed light on how human brains work to find off sickness, is a plan Demas has in mind for the future.

Modeling Vocal Development

Biologist Roderick Suthers, another member of the CISAB, and his students study the physiology of song production in songbirds and parrots. For songbirds, as for humans, there are critical periods when juveniles must hear adult vocalizations and later, their own attempts to mimic those adult vocalizations, if the child or young bird is to develop normal speech or song. This trait makes birds an excellent subject in which to study vocal learning. True vocal learning is a skill shared by few mammals--for example, humans, certain birds (such as songbirds, parrots, and some hummingbirds), dolphins, and whales--so studying these animals can certainly provide clues human learning.

"In trying to use animals to understand basic scientific questions, you really have a choice between picking a very simple animal system in which it's possible to study the function of all the different parts, or looking for animals where key mechanisms are highly developed and may be easier to identify and study," says Suthers, a professor of physiology and neuroscience.

Simple forms of learning in some marine mollusks, for example, involve a circuit containing only a few nerve cells, so the contribution each cell makes to learning can be worked out. Vocal learning in songbirds, on the other hand, involves many thousands of nerve cells in the brain, organized into clusters specialized to perform different aspects of song learning and production. Simple or highly specialized, each of these systems has different advantages (and limitations) for understanding the biological mechanisms of learning, and both deserve "supermodel" status.

Suthers's own work concentrates on song production--how birds use their vocal system to generate complex sounds for acoustic communication. Recently, his team has shown that songbirds continually adjust the shape of their vocal tract to efficiently transmit the dominant frequency of their song. Interestingly, other scientists have recently shown that human sopranos use the same technique to amplify their high notes so they can be heard above the orchestra.

Uncovering another parallel between bird song and human speech, Suthers's group has also found recently that parrots can change the sound frequencies emphasized in their vocalizations by making very small changes in the position of their tongues. Tongue movements play an important role in the production of human speech, and it may be that a parrot's use of tongue movements contributes to its ability to mimic human speech.

Modeling Sex, Aggression, and Selection

Evolutionary biologist Ellen Ketterson, also a member of the CISAB, has focused on birds throughout her career as well. Rather than study sound, Ketterson's research focuses on hormones and the roles they play in behavior. For the past 15 years, her research has centered around the monogamous dark-eyed junco male and the effects of increasing its levels of testosterone, the hormone responsible for male sex characteristics. Ketterson's team increased the amount of testosterone in a select group of males to equal that of a polygynous, or multiple-mating, species. They found that testosterone-treated juncos became secretly polygynous, sang more, had larger home ranges, and were generally more attractive to females.

Ketterson's lab is widely known for this research with junco males. Her attention has now switched to the effects of testosterone levels in females, a study that, like her last, may take 10 years to amass the amount of data she'd like. Her lab is looking at sexual and aggressive behaviors, parental behavior toward nestlings, and overall fitness (the ability to reproduce) in the females they've treated with testosterone.

Birds, humans, and all species share this important hormone. But are juncos particularly good models for demonstrating the potential effects of excess testosterone in human males?

Not really, says Ketterson. Besides, she adds, she leaves the job of making those connections to anthropologists. Drawing this clear distinction underscores how she conducts herself as a scientist.

"I'm a biologist, not a psychologist," says Ketterson. "I'm not trying to help humans in their relationships. I'm studying birds in their natural environment to understand why they have evolved the mating systems they have and also to predict how they might respond to environmental changes. Am I interested in human connections? You bet. But it's not what I do."

Us and Them

Ketterson's strong stance hints at one of the greatest dangers of using animal models to study human scientific questions: the possibility of anthropomorphism, or assigning human characteristics, behaviors, and motivations to animals. Anthropomorphizing animal subjects can lead to questionable data, false or exaggerated conclusions, and ultimately, just plain bad science. Yet more than any other researchers, scientists who work with animals are constantly asked whether their work says anything conclusive about people. And it's easy to see why we're so interested, Suthers points out. "Everybody is a little egocentric and anthropocentric; we're all interested in ourselves, our species, and our welfare," he says.

But it's ethically and scientifically tricky for a scientist to insinuate links between humans and systems modeled by animals and still remain objective, says Ketterson. So she doesn't do it. Period.

"My work is dedicated to basic research. I'm trying to learn how complicated behavior evolves," she says. "I leave the rest up to others, like anthropologists who are trained in the nuances and the complexities."

Ketterson's published work would never explicitly say, for instance, that observations of male juncos mating more often under the influence of heightened testosterone levels means that human males with high testosterone levels would act similarly. But that doesn't mean her work hasn't raised the question. In a 2005 study, biological anthropologist Peter Gray of the University of Nevada compared the testosterone levels of bachelors, married fathers, and married yet childless men in Bejing, China. He found that bachelors had the highest levels of testosterone, while married fathers had the lowest--which suggests that testosterone levels differ according to mating and parenting efforts. Gray's results for humans are highly similar to Ketterson's for birds--and Gray and Ketterson have even communicated about that fact. Gray told her that some of the questions he posed in his own work were directly influenced by her studies, Ketterson says.

Nonetheless, regardless of direct links to human health or behavior, basic biological research is clearly important and worthwhile. "Questioning is a basic aspect of our humanity; curiosity and exploratory behavior are among our most important attributes," says Suthers. "We can't predict what discoveries may come from basic research, but we know that understanding life on earth is important for our survival."

Who, or what, might be science's next top model? Will there ever be one being we can use to demonstrate, test, and ultimately solve the questions we still have about our human bodies, behaviors, and brains? So far, that model just doesn't exist. "The truth of the matter is, there is no perfect animal model when it comes to extrapolating to a human," Demas says.

It may be true, but that's hardly slowed down the hunt. Meanwhile, mice--our favorite furry supermodel--keep multiplying.

Kelly L. Phillips is a freelance science writer living in New York City.