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What's new at the RAT institute
by Dawn Walton
April 04, 2005
With the shelving of drugs such as Celebrex, scientists are keen to know how
medication affects behaviour. That's where a much-reviled rodent comes in. DAWN
WALTON visits a Canadian expert known as the 'rat whisperer'
LETHBRIDGE, ALTA. -- In a brightly lit laboratory, rats are placed one by one
into a pool and clocked to see how long each takes to swim to a dry platform. In
another, food rewards are used to test the memories of rats being put through
their paces in a maze.
Down the hall, a student researcher pushes a trolley of rats back to their cages
after observing their behaviour when placed in a cramped space for varying
Ask her to explain the rodents' reactions to confinement and she passes on the
question. "Ask the rat whisperer," the budding scientist replies.
Here, at the Canadian Centre for Behavioural Neuroscience at the University of
Lethbridge, that means talking to Ian Whishaw.
The soft-spoken professor of psychology and neuroscience has been studying rat
behaviour for almost 40 years and, in the course of it, has built a reputation
as the guy who can get into the head of a rat and explain what it means to the
rest of us.
His research has influenced an array of scientific experimentation and even
turned a long-held theory upside down.
"I discovered that rats use their hands to pick things up," Prof. Whishaw says
as he gives a visitor a tour through a labyrinth of labs at the centre.
He sounds neither boastful nor aware that, to the scientific neophyte, this
ah-ha moment seems meaningless. Then, using his right hand, he reaches out to
demonstrate how rats extend their forelegs and move each digit independently to
grab food with their paws before bringing it to their mouths.
"The paw use in the rat trashed the theory that only primates and humans used
their hands," Prof. Whishaw explains. ". . . It took a whole line of
evolutionary thinking and modified it based on the observation of one animal."
But this kind of revelation isn't just esoteric theory best left for the ivory
tower and those hard-wired for scientific thinking. Discovering how rats use
their paws, for example, could influence how people suffering from brain
injuries or Parkinson's disease are treated to increase mobility, Prof. Whishaw
Rats are actually a boon to science despite their roots as a much-maligned
rodent known for heralding plagues, decimating crops and outnumbering -- even
attacking -- urbanites. (In fact, rats are so reviled in Alberta that they were
declared an official pest 55 years ago as the province moved swiftly to
eradicate them -- except in approved laboratories.)
Yet for years, behavioural research trailblazers such as Prof. Whishaw have been
dismissed as kind of kooky and sort of irrelevant. The serious scientists would
be mapping out genes or developing drugs. Few of them really thought about how
things such as biology and chemistry affected behaviour.
Indeed, medications, including arthritis drugs Vioxx and Celebrex, have recently
been pulled off the shelves because of serious side effects and what Prof.
Whishaw describes as a lack of understanding of how drugs influence behaviour.
"Now, people are coming from other disciplines saying, 'How in the hell do you
study behaviour?' " Prof. Whishaw says. "So there's a market for it, a huge
market for it. It has become important and I think, in most circles, very
respected. Literally everybody now has a huge investment in this."
To feed that growing appetite, Prof. Whishaw and colleague Bryan Kolb have put
together what they hope will be the definitive textbook on the lowly rodent: The
Behavior of the Laboratory Rat: A Handbook with Tests (Oxford University Press).
But their text is hardly a handbook. At 504 pages, it is the bible for rat
researchers, with dozens of experts contributing chapters on fear, pain, taste,
sex and stress, along with a variety of models and tests for rat behaviour.
Rats have been the unconventional focus of books in the past.
Writer Robert Sullivan spent a year following rodents around New York and
recently produced Rats (Bloomsbury), in which he notes charming aspects of rat
behaviour such as a voracious appetite for sex (20 times a day) and a propensity
to propagate litters of about 10 pups every 21 days.
Almost 30 years ago, D. Brian Plummer unleashed Tales of a Rat-Hunting Man
(Boydell & Brewer Inc.). It included details not for the squeamish about how to
kill rats using ferrets and terriers. In Britain, according to Mr. Plummer, the
rat is an "unheralded game animal."
But the last serious scientific book on the animal was The Rat: A Study in
Behavior (University of Chicago Press), written by S. Anthony Barnett in 1963.
During the Second World War, Dr. Barnett advised the British government on how
to exterminate the food-gobbling and disease-carrying animals from the trenches.
He found himself always outsmarted by the rodents.
Before his death in 2003, Dr. Barnett penned a chapter in the Whishaw-Kolb book
about rat ecology and the book is dedicated to him as the sort of father of
modern-day rat research.
Norway rats (Rattus norvegicus), also known as brown rats, although they tend to
be grey or black, were first brought into labs about 100 years ago. Scientists
were interested in learning about nutrition and the human digestive system.
Psychologists started thinking about the human sleep-waking cycle and memory.
Around the same time, a debate was emerging about conditioning versus thinking.
The rat seemed to be the ideal mechanisms to help us better understand
Although mice tend to be used more widely in research -- largely because
manipulating the genes of a mouse has been easier than those of the rat -- rats
are in many cases still the research model of choice.
Rat biology is similar to that of humans. Unlike mice, they are large enough to
manipulate in various testing apparatus and perform surgeries on. But mostly,
they are clever, like us.
They have the gift of being able to adapt to any environment, Prof. Whishaw
"It's just that they can cope," he says. "It's a colony-dwelling animal so it's
more social. A mouse tends to live just in a family unit. . . . A lot of the
ways it [the rat] thinks and the ways it learns are really related to that
social background and that makes them like us in a lot of respects."
Rats are currently being used to find out if stress has a role in triggering
Parkinson's disease or makes the symptoms worse for those who already have it.
The study of strokes in people was furthered after Prof. Whishaw performed an
MRI on what he thought was a dumb rat and discovered that it actually had had a
Head-start programs in schools may not exist but for the study of the behaviour
of young rats in enriched environments.
But rats haven't always been so well regarded or treated by researchers.
A few years ago, a member of People for the Ethical Treatment of Animals (PETA)
used a hidden camera in a University of North Carolina research facility and
taped a researcher cutting open the skulls of young wriggling rats to remove
their brains. Normally and under regulations, the animals would be numbed with
ice, the researcher acknowledges on the tape. This kind of shortcut is "illegal,
but it's easier," he says.
The same video showed live rodents that weren't properly euthanized being thrown
alive into garbage bins.
In 1989, a research project at the University of Florida came to an end after a
researcher failed to follow approved guidelines for breaking the legs of rats in
the course of his nutrition research.
Leg-breaking was used to determine the impact of anabolic agents on
stress-induced malnutrition. The researcher was given the okay from regulatory
officials to break the animals' fibulas, but he broke their femurs.
But attitudes and the treatment of lab rats have changed as we become more aware
of the complexity of the rodents' behaviour and have more respect for the
animals, Prof. Whishaw says.
"There was a time when people thought animals were the equivalent of machines
and humans were different because they had a soul. It would be hard to find a
person in that category any more. We now realize that animals are much more
complicated than that. They are much more like us than less like us," he says.
The controversy over the use of animals in research is evident at the University
of Lethbridge, where tacked on the door of one lab is a poster of
animal-research protesters with a caption reading, "Thanks to animal research,
they'll be able to protest 20.8 years longer."
The poster, by the Washington-based Foundation for Biomedical Research, which
advocates the humane use of animals in research, has suggested that animal
research has extended the average human life expectancy by 20.8 years.
However, the use of rats -- indeed all animals -- in labs by universities and
industry is shrinking, both because of tough regulatory regimes, which increase
the cost of care, as well as advances in computer modelling.
According to the Canadian Council on Animal Care, 289,542 rats were used for
scientific purposes in 2001 compared with 594,678 in 1975.
But scientists say there is no way to eliminate them or other animals completely
Prof. Whishaw looks over a cartoon in a recent issue of The New Yorker that
includes two caged lab rats talking to one another. One rat says, "What if these
guys in white coats who bring us food are, like, studying us and we're part of
some kind of big experiment?"
Prof. Whishaw smiles. The cartoonist is on to something. It's funny because it's