The "wow" reverberated through the third-floor laboratories of the Hunterian Building here one morning in November 1978.
Dr. Michael Kuhar looked through his microscope and saw what looked like the Milky Way -- millions of white dots on a black field.
The dots were Valium, radioactive bits of it, on a slice of human brain. Each dot marked a spot on a single brain cell that was particularly sensitive to the benzodiazepines, Valium's chemical family.
Scientists had learned four years ago that certain parts of the brain were especially sensitive to the Valium family, but that November morning was the first time anyone had located these cells and photographed them.
The discovery several years ago that parts of certain brain cells are sensitive to certain drugs carried brain research a quantum leap forward. It suggested that there may be chemical and genetic explanations for drug addiction in addition to the standard psychological and social theories.
The work of Kuhar and his student associate, Scott Young, at Johns Hopkins University Medical School has shown what parts of the brain Valium affects and provides some clues as to how it works.
"It (the work) gives you an understanding of how one drug can affect different parts of the brain. You have a totally different view of what happens in the person's head, a radically different view," Kuhar said.
"It was particularly interesting to work with Valium," he said, because Valium controls anxiety, and anxiety is "a really sophisticated process."
"To have a drug that acts on such a complex process is very exciting, and if you can find out where that drug works in the brain, you can perhaps . . . learn something about anxiety," which involves awareness, muscle tension and other stress reactions.
Some researchers had believed that Valium works on the brain's limbic system, which helps control emotions and emotional reactions, such as sweaty palms, a fast heartbeat and a dry mouth.
The Kuhar-Young studies confirmed that there were millions of Valium sensitive cells -- or receptors -- in the limbic system, but only in certain parts of it.
Because scientists are learning more about how and where such a drug works, they may be able to change such drugs to produce specific effects. The work of Kuhar and Young, for example, could lead to a refinement of Valium into two different drugs: one would work purely to control anxiety, without causing drowsiness or relaxing muscles, the other might work to relax muscles without tranquilizing the mind.
Additionally, Kuhar said, researchers will now try to see if the body produces its own kind of Valium.
When scientists discovered a few years ago brain cells that were sensitive to opiates such as morphine and heroin, they found that the brain produces its own opium-like substance -- endorphin -- that causes the opiate receptors to trigger bodily responses such as euphoria or numbness.
Researchers theorize that because there are receptors for Valium, the body probably produces a sort of natural Valium of its own that attaches to the Valium receptor cells and triggers processes that control stress.
This theory, researchers say, may explain why some people are more anxious than others. Those who can control anxiety without the use of drugs may have enough "natural" Valium, while those with a shortage of the substance or a shortage of receptors, may need help from tranquilizers.