As long as the brain is a mystery, the universe will also be a mystery.
--Santiago Ramon y Cajal, early 1900s
We can think differently about the mind now. It is not a mystical thing but something that can be understood.
--Dr. David Hubel, 1979
It is the business of science to unravel mysteries, but rarely have the clues come so fast and furiously. During the past decade -- barely a blink of the eye in the history of scientific research -- scientists have unlocked the doors to understanding the body's most complicated and baffling organ: the brain.
What Shakespeare called "the soul's frail dwelling-house" is today the subject of more attention and sheer excitement than any other biological science except the genetics of the human cell.
The information spilling from scores of laboratories across the world has caused even traditionally cautious scientists to herald "the birth of a new era" and "a revolution in neuroscience."
What has so excited them is not one discovery but many, in fields as diverse as biochemistry and computer technology. It is as if a small trail painstakingly carved through a jungle over the course of centuries had been, within the space of 10 years, turned into a superhighway.
Neuroscientists are exploring the neural pathways of the brain with chemicals and electrodes, seeking and often finding the keys that unlock human emotions. Through the magic of computers, researchers have devised ways to watch the brain at work. Surgeons have started to test the barriers to brain transplants -- and are finding promise in their ability to implant bits of tissue into the brains of laboratory animals.
A decade ago most scientists said that complete understanding of the brain -- and therefore of man's mind -- seemed impossible. But psychologists, psychiatrists and other doctors already are beginning to use their new scientific tools to enhance learning, manage emotions and alleviate mental and physical illness.
As with many great advances, the burgeoning body of knowledge is open to controversy. The many misgivings about genetic engineering, expressed by eminent scientists as well as theologians, have their counterparts in the science of the brain.
Advances in understanding the brain's chemistry, for example, one day may permit man to shape his own intellect -- to improve "cognitive" or learning ability or to sharpen memory. But the same knowledge, applied in another way, might be used to cripple the mind, or destroy it.
The advances in the labs also are shaking the foundations of thought about the psyche. For example, it now appears virtually certain that problems in the brain's chemical functions, rather than purely psychological or emotional upset, underlie much mental illness.
"It's very humane to be able to tell patients, 'There's a disorder in your biochemistry,' " said Dr. Frederick Goodwin, scientific director of the National Institute of Mental Health, the government agency that is playing a leading role in this new science. "It's very relieving psychologically for patients not to feel responsible for every shift in their mood."
There is still interplay, of course, between psyche and cells, but the new chemical discoveries are lending new meaning to ancient views of the brain.
Hippocrates suggested 2,400 years ago that "Not only our pleasure, our joy and our laughter but also our sorrow, pain, grief and tears arise from the brain, and the brain alone. With it we think and understand, see and hear, and we discriminate between the ugly and the beautiful, between what is pleasant and what is unpleasant and between good and evil."
His contemporary, Plato, agreed, but thought the brain governed only ideas, not sensation. Plato's influential student, Aristotle, disagreed strenuously. Much like the ancient Egyptians, Hebrews, Hindus and Chinese, he thought the heart was the seat of intelligence and emotion.
This series of five articles was reported and written by Philip J. Hilts, Cristine Russell and Victor Cohn, and edited by Cass Peterson.
The Dark Ages meant centuries of darkness about the whole body, with the dominant church discouraging dissection or any attempts to link body and "soul." In 1543, however, a Flemish physician, Andreas Vesalias, boldly dissected "the heads of executed criminals . . . still warm," he explained, and clearly established that the brain and nerves are the site of our mental and sensory processes.
Not until the early 1900s did Spain's great Santiago Ramon y Cajal show that each nerve cell of the brain and spinal cord is a distinct body with a central nucleus and two kinds of antennae: long, cable-like axons that transmit information and arrays of short, thread-like dendrites that receive it.
There gradually emerged the modern view of the brain, made of somewhere between 10 billion and 100 billion of Ramon y Cajal's neurons, or nerve cells, held together by 10 times that many glue-like connecting cells.
We must still say an imprecise "10 billion to 100 billion" nerve cells. They are "packed together so intimately," their branches intertwined in such dense thickets, writes Dr. David Hubel, that "when all the cells in a region are stained, one sees . . . only a dense and useless mass."
Even now, with their far more precise knowledge of the anatomy of the brain, scientists must grapple in an imprecise world in trying to explaining how it functions.
To Dr. Roger Sperry of the California Institute of Technology, the brain is divided by nature and function into separate halves: "two separate selves." A deep cleft or valley divides the brain's upper layers, the cerebrum and the "thinking" cortex, into two halves, or hemispheres, linked by bright, glistening bands and connections.
Sperry's work indicates that the left brain (in right-handed persons) houses speech and analytical skills such as reading, writing, arithmetic and logic. The right brain is the site of space and pattern perception -- recognition of faces, for example -- and artistic appreciation.
The localization is not complete. There is much sharing and crossover. But when Sperry won an award for his contributions (preceding a 1981 Nobel prize) he said, "The pleasure and honor that my right brain feels is more than my left brain can express."
Other scientists have borrowed from the disciplines of philosophy and sociology to form their theories of brain function. To scientist-philosopher Dr. Paul MacLean of the National Institute of Mental Health, we have not just a two-halved but also a three-stage brain: reptilian, mammalian and human.
In a description that is as much sociological as biological, he sees the brain stem and lowest brain structures as our "R-complex" ("R" for reptilian) brain, a brain much like a lizard's, an animal that is entirely selfish and bound by narrow, repetitive instinct, a creature that does not even feed and nurture its young.
MacLean says he believes our next higher "mammalian brain" is the limbic system, a part of the brain controlling memory and emotions. Higher animals nourish and shelter their young, and it is this area, MacLean says, that gave mammals this caring behavior vital for the survival of a more slowly maturing, yet higher species.
Finally came our "third" brain, the neocortex, the brain of higher intellect, "the mother of invention and father of abstract thought."
To some scientists, MacLean's brain is a useful concept to understand much human behavior, such as the fierce mammalian love of mother for child. Or the obsessive, lizard-like stalking of his prey by an Arthur Bremer or John Hinckley, the attackers of George C. Wallace and Ronald Reagan.
MacLean admits, "I have a route by which I come to work which is pretty reptilian. I just favor that way because it seems more comfortable."
There is also emerging a new view of a "unified brain," an organ highly interdependent and interacting, rather than just a set of autonomous, evolutionary-bound parts.
Like MacLean, Dr. Vernon Mountcastle of Johns Hopkins University has been a student of the brain for more than four decades. He studies carefully wired monkeys as they perform task after task, while a computer records the activities of single brain cells and cell pathways.
"It's true that particular areas of the brain are especially important in certain emotions and so on," he says. "But the idea of a hierarchy, the idea of local areas giving 'commands' -- no. We're finding that the brain is much more of a unit, that it's far more integrative than hierarchical. We're finding that in movement, or if you experience a pain, many areas are active in parallel. It is a very interconnected system."
The connections, oddly, are the gaps -- or synapses -- between the neurons. These tiny, fluid-filled spaces are the meeting places of the nerve cells' long, interconnecting axons, and it is at these key junctions or crossroads that our view of the brain takes its newest form.
Across those synaptic gaps, surges of electricity and sudden spurts of powerful chemicals trigger simultaneous responses in many parts of the brain, from the top of the cortex to the tip of the brain stem. A thought, a response to pain, a command to a finger to move -- each is an electrical signal or set of signals traveling at 200 mph from appropriate neurons along their elongated axons to appropriate synapses. There each signal must leap across the synapse with the aid of a vital chemical called a neurotransmitter.
"Brain cells talk to each other. That's the key event," Johns Hopkins' Dr. Solomon Snyder explains. "When a nerve impulse gets to a nerve ending it triggers release of a neurotransmitter. The transmitter diffuses to adjacent neurons. It excites them, makes them fire, or inhibits them, turns them off.
"All information-processing in the brain consists of neurons communicating in this way. Any given neuron will receive inputs from up to 1,000, others, maybe more. It will send out signals to as many as 10,000. And that's the brain -- at least 10 billion neurons talking to each other."
Snyder is one of a new breed of neuroscientists who in the last decade have increased the number of known neurotransmitters from two firmly established ones (norepinephrine and acetylcholine) to perhaps 40 strong candidates. He says he thinks there are probably hundreds.
Their existence, and their role in normal and abnormal brain activity, including mental illness, is one of the signal discoveries of the last decade. It is one reason why scientists like NIMH's Goodwin say, "Our view of the brain has changed drastically. Instead of looking at it as a set of parts or wiring or an amorphous soup, we are beginning to see it as a set of systems with 50 billion to 100 billion elements, each communicating."
The father of psychiatry, Sigmund Freud, began his career as a neurologist, not an explorer of the mind. As late as 1925, in one of his great leaps of imagination, he called neuroses "conditions arising from an excess or a relative lack of certain highly active substances, whether produced outside the body or introduced into it . . . . In short, . . . disturbances of the chemistry of the body," though "for the present" he saw no way to find these "hypothetical substances."
Now neuroscientists are at last integrating Freud's imagined chemistry with behavior. Links between abnormal chemistry and abnormal behavior have been found in serious depression, manic-depressive illness, schizophrenia and anxiety. New evidence may link altered chemistry to much aggression, violence, sociopathic or criminal behavior and suicide.
Some mental disorders are plainly genetic, but there are indications that the abnormal genes "express themselves" at the synapses, where they act through disordered chemistry.
Within a few years, Snyder says, drug companies will begin releasing new agents they are testing: molecules specifically designed to correct or inhibit normal neurochemistry.
"All psychotropic drugs work at the neurotransmitter level," he says. "So we now have a way to screen, evaluate and design drugs and eliminate undesirable side effects. Every one of these neurotransmitters we are finding may spawn a new class of drugs."
No one expects a day when all mental illness will be cured by a chemical. The best current thinking is that in most such illness, just as in most infection, there must be two elements: a physical agent, perhaps a faulty neurotransmitter, and a receptive environment, a patient weakened by fatigue or corrosive emotion.
No one thinks the brain will quickly give up all its secrets, certainly not in this century. But what was once thought impossible -- a mystery beyond man's abilities to solve -- has come tantalizingly within his reach.
NEXT: The brain's chemistry