The really smart rats are at Johns Hopkins.
Oh sure, NIMH (pronounced N-I-M-H), the National Institute of Mental Health, has lots of rats, and many of them are getting the kind of chemical brain enhancement that could suggest the rats in the new movie "The Secret of NIMH" (pronounced Nimm). The fictional "NIMH" is also the National Institute of Mental Health, only the rats don't know it. Neither do a lot of people who see the movie.
And some of the real NIMH rats are doing their smart things at Hopkins, in Baltimore, where a behavioral scientist is putting the clever little rodents through paces that bemuse the scientists quite enough, never mind that they--the rats--don't know how to read. Yet.
"The Secret of NIMH," based on the Newbery Award-winning book "Mrs. Frisby and the Rats of NIMH" by Robert C. O'Brien, is the animated film about rats and mice injected with a chemical that increases their intelligence and lengthens their lives. The "NIMH" scientists who do the injecting are klutzy enough not to notice that the rodents have learned how to read and, reading the instructions on their cages, open the doors and split from the lab. Off to assorted anthropomorphic adventures and eventual independent living for rats.
The book, which was published in 1971, did have some of its roots in genuine rat research at NIMH, but in experiments that did not involve injections. No one could have known even a decade ago that today's NIMH scientists really would be injecting rats with substances designed to make them smarter. "NIMH" was another instance in which science fiction, even in a child's story, anticipated science fact.
And so now we get to the real secret of the real NIMH.
Today's rats of NIMH are not street rats, which are naturally clever and wily creatures. They are inbred white rats that are probably, say the scientists, less intelligent than normal because of all that inbreeding.
But the scientists are making them smarter.
It is all part of the exploding brain research going on in psychobiological laboratories all over the world.
Much of it is being done at NIMH on the campus of the National Institutes of Health in Bethesda. It is also being done at Johns Hopkins Medical Center in Baltimore.
In the past few years, scientists have discovered that the brain and the way it regulates the body are infinitely complex, both electrically and chemically. They have identified sets of chemical substances in brain cells that act as messengers, regulating not just the automatic functions, like heartbeat and blood pressure, but other things never before believed to be physiological--things like behavior or mood. Or memory and intelligence.
"We are," says Dr. Frederick Goodwin, scientific director of NIMH, "beginning investigations into a very new and in a sense very mysterious area . . . and to understand the abnormal, which is our ultimate goal, we need to understand more about the range of the normal. It's impossible to limit your questions to a single function, because one thing increasingly clear about the central nervous system is the enormous inter-connectedness and complexity."
The newly identified substances, strings of amino acids called neuropeptides or neurotransmitters, act on certain specially designated cells--like a key in a lock--to stimulate or inhibit a seemingly endless string of functions and behaviors.
About 40 neurotransmitters have been identified so far, although scientists believe there are many more. And of these, two or three seem to have functions related to learning and memory enhancement. In short, smarts.
For example, those smart rats at Johns Hopkins were injected with a substance called Alpha-MSH. Dr. Gail Handelmann runs the rats through a radial maze and tries to confound them. So far, the injected rats outsmart her every time: They learn their way through the maze with visual cues, like lights, because Alpha-MSH comes from the part of the brain related to vision. If she uses sound cues, like bells or whistles, the injected rats do no better than those without Alpha-MSH.
Dr. Thomas O'Donohue, who is married to Handelmann, has done much of the NIMH research on Alpha-MSH, which is contained in the same neuron as the natural pain-killing substance Beta-endorphin, another neurotransmitter.
Alpha-MSH, notes O'Donohue, is the substance in chameleons that triggers the change of color, when different kinds of light are perceived by its brain--a clue perhaps to the original purpose of the substance along the evolutionary trail.
Other NIMH researchers are working with vasopressin, a substance used both in rats of NIMH and recently in some tests with people. In rats, and under certain circumstances in people, it enhances memory. It also seems to be related to mood--people with medical depression have less vasopressin in their spinal fluid than others. Very preliminary studies indicate that it may eventually be useful in treating memory loss associated with depression, but not in cases where there has been cellular damage, as in senile dementia.
None of this was happening in the late '60s, when "Mrs. Frisby and the Rats of NIMH" was written. Instead, it was the work of veteran NIMH scientist Dr. John Calhoun that apparently inspired the author. Calhoun, who believes he was the prototype for the book's Dr. Schultz, is assigned to the NIMH animal facility in Poolesville, in upper Montgomery County.
More than a decade ago Calhoun was conducting "cultural, not chemical" experiments with Norway rats--a breed of street rat--demonstrating the breakdown of societal, familial and physiological functions under the stresses of overpopulation. He and others have extrapolated his work to the human experience in urban centers, overcrowded prisons and ghettos. Calhoun believes he remembers the late O'Brien, the book's author, visiting the facility in the late '60s or early '70s. In fact, Calhoun believes that Mrs. Frisby's name came from the blue Frisbee he kept hanging on his door "to help when things got too stressful for us." (For some reason, Mrs. Frisby became Mrs. Brisby in the film.)
If Poolesville is the locale of the lab in the movie, of course, that means that Thorn Valley is somewhere upcounty in Montgomery, somewhere near Sugarloaf Mountain. Thorn Valley is where the fictional rats of "NIMH" end up.
They and Mrs. Frisby-Brisby's late lamented husband, Jonathan (a mouse), were the rodents supposedly injected with smarts chemicals in the mysterious laboratory called "Nimm" by the animals.
In the story, some of their exploits do seem to reflect some of the rat-cultural happenings in Calhoun's overcrowded rat population--leadership rivalries, for example. But Calhoun's rats weren't injected with anything. They were just crowded.
The real NIMH scientists are rather tickled with the book and the film, although they feel that the fictional "NIMH" laboratory is gratuitously depicted as cruel in its animated incarnation.
The NIMH scientists who do deal with today's rats of NIMH are scrupulously humane. Said research scientist O'Donohue, "After all, most scientists go into research and biology because they're fascinated by the beauty of life and hate to see anything done that is bad or cruel to an animal."
Moreover, the real NIMH scientists don't want people (or rats) to think that bottled smarts are just around the corner. All this research doesn't mean that there will be folks with super-memories or, indeed, super-brains. Only that some human ills may be better treated sometime in the future.
As for the rats, well that's another story . . . Was that a mushroom cloud somebody saw over Sugarloaf?