IT'S SMALL, chocolate-covered, not quite the size of a ping-pong ball When you come into the lab, you are given a carefully chosen ball of this sort. A technician whirls it into a milk shake, and you drink up.
Two hours later, you take a memory test: Can you recall a list of 14 words better than you could the week before?
Sometimes the chocolate ball contains high doses of lecithin, a natural substance found in egg yolks and some other foods and now viewed with particular interest by brain researchers.
At other time, the ball contains a placebo, a mix of chemicals designed to look and taste just like the lecthin, so that each person's memory can be tested under both conditions, without anyone's knowing which is which until the code is broken at the end of the test.
In Bethesda, Md., Cambridge, Mass., New York and a few other cities around the world, healthy volunters of various ages are now participating in such experiments. So far, the results have been mildly encouraging. Lecithin is the latest hope of a generation of researchers who have tried hundreds of drugs, subjected thousands of rats, mice, monkeys, fish and squid to outlandish operations and tests and studied millions of brain slides in vain efforts to discover why any living creature remembers anything.
Scientists still don't understand how memories are made -- let alone how memories are stored or retrieved. Memory remains a sort of miracle, a magical transformation of electricity and chemistry into the private record which makes each person what he is. But researchers now have some promising leads both to the maintenace and to the sharpening of memory; and for the first time, they are working with large numbers of human subjects.
The stakes are high. Who wouldn't want the opportunity to improve his memory at will? Students cramming for an exam, speechmakers or actors preparing for their performances, artists who want to recall the details of a compostion, executives who have to remember figures and all others who wish they could remember names or places better would love to be able to take a safe memory pill.
Yet their needs are trivial compared to those of millions of people over the age of 45 or 50 who notice their memories beginning to erode, and especially to the urgent needs of many aged persons who have serious memory problems.
"It worries me," says a vigorous lawyer in his mid-50s. "I've noticed that recently I've had to grope for the names of people and for specific details -- I never had to grope before. I always had an excellent memory."
The volunteers in some of the lecithin studies are just like this lawyer -- healthy, middle-aged men and women who have intellectually demanding jobs and realize that their memory isn't as good as it used to be. Others are college students, In Bethesda, a group of students has been taking part in such studies at the National Institute of Mental Health in exchange for a salary, college credit and the opportunity to work with outstanding researchers. In Cambridge, lecithin has been tried on healthy aged people, as well as on victims of Alzheimer's disease, which causes memory loss and which has provided scientists with some clues to the brain changes involved in memory defects.
Lecithin in used in these experimentsbecause researchers have found that it increases the brain's supply of an essential chemical called acetylcholine, which seems involved in memory. Unlike choline, another substance which increases acetylcholine, lecithin has the advantage of not producing a decidedly unplesant, fishy smell in people who take it.
When the NIMH research group gave choline to some volunteers two years age, recalls Dr. J. Christian Gillin, a psychiatrist who has been running a series of memory studies in Bethesda together with psychologist Hebert Weingartner and psychiatrist Natraj Sitaram, a nurse once came running in to ask what had happened to one of the students. "He smells like dead fish," she complained. The odor of choline being converted to other chemicals in the gut was so distinctive that both volunteers and experimenters knew right away what had been used.
A single does of choline did, however, produce a mild improvement in the the 10 volunteers' memories. For example, they required fewer trials to recall a list of unrelated words -- particularly the kind of abstract words with low imagery which they had had the most difficully remembering without the choline.
The choline work had begun in 1975, when Dr. Richard Wurtman of the Massachusetts Institute of Technology and a graduate student, Edith Cohen, reported that taking choline increased brain levels of acetylcholine. In 1978, Wurtman and his colleagues showed that lecithin, the natural source on choline in human and animals, was even more effective than choline itself, since the lecithin did not get broken down in the intestine, as choline does, and therefore produced proportionately larger increases of acetylcholine in the brain.
This report led to the present wave of research on lecithin, generally with doses of 20 to 40 grams of a particularly potent kind of lecithin, each dose being equivalent to the lecithin in about 25 eggs. This lecithin is especially purified and certainly should not be confused with the lecithin available in health food stores, which contains less than 20 percent of its active constituent, phosphatidylcholine.
"It's a whole new view of the brain," says Dr. Wurtman, summing up eight years of experimentation on the effect of nutrition on brain function. "Our lab found that the brain's ability to make certain neurotransmitters, such as acetylcholine, depends on the amount of various nutrients circulating in the blood. This means that the brain is not above it all, as many people thought, but is intimately affected by what we eat." Therefore, he points out, "Memory may be affected by what we had for breakfast."
Neurotransmitters are the chemicals through which the brain's billions of nerve cells, or neurons, communicate with each other at lightning speed. More than a dozen neurotransmitters have been indentified so far. Memory undoubtedly involves several of them, but at present, much interest centers on acetylcholine because it has been definitely linked with at least some aspects of memory.
For example, drugs which block acetylcholine, such as scopolamine, have devasting effects on the memory of normal volunteers. By contrast, drugs such as arecoline, which mimic the action of acetylcholine, improve the ability to recall word lists. And people who suffered from severe memory defects as a result of Alzheimer's disease have been found, at autopsy, to have dramatic decreases in the number of brain neurons which produce acetylcholine in their brains, especially in an area of the brain called the hippocampus.
Though the idea that biochemistry is involved in memory is now taken for granted, it only won acceptance in the 1960s. Until then, memory was believed to depend entirely on electrical activity. Electrical circuits in the brain were supposed to lay down lasting paterns, or engrams, which stored memories in various parts of the brain.
A noted Harvard neuropsychologist, Karl Lashley, spent a lifetime looking for such engrams in the brains of animals after they had learned specific skills, but he failed to find any physical trace of their learning and finally concluded, tongue in cheek, that "learning just is not possible at all."
The electrical theory fizzled when it was shown that animals retained their memories despite the worst that scientists could inflict on them -- freezing, electroconvulsive shock, anesthesia or other miseries which also disrupted the electrical activity of the animals' brains. Clearly memory had to have a chemical component to enable it to survive such treatment. It soon appeared that only older memories were invulnerable, however. New skills, which rats or fish had learned minutes earlier, could be wiped out by electroconvulsive shock, or even by chemicals which prevented the formation of new protein.
This led scientists to conclude that there must be several kinds, or stages, of memory; long-term memory, short-term memory and probably several others in between. New information must be registered in some-fashion, then retained for various lengths of time and finally retrieved. But to this day, nobody knows how these processes occur, or how they relate to one another. Nor, for that matter, do scientists understand how anybody forgets information, once it had been registered in the brain. When researchers discuss these questions, they often bring up the tragic case of a man known to all medical students through his initials, H. M. As the result of a brain operation, H. M., who is now in his mid-50s, lost the ability to make new memories in 1953. At the time of operation, he was only 26 years old. He had suffered from epilepsy for years, but his attacks had become increasingly frequent and severe, and although he was taking nearly toxic doses of drugs, he had had to quit his job with an electric motor company. Nothing seemed to help him.
Finally, a neurosurgeon suggested cutting out parts of his temporal lobe (the area around his ears and temples) to relieve him of the attacks. Operations of this kind had been done before, but because H. M.'s case was so severe, the surgeon cut unusually far into his brain, removing a small structure, the hippocampus, from each side. No one knew then what functions the hippocampus served. Now -- too late for H. M. -- it has become clear that this three-centimeter structure, which is shaped like a sea horse, holds the key to all new memories.
Something the hippocampus does is crucial to forming a permanent record of events. Having lost it, H. M. lives permanently in the past. He cannot recognize his next-door neighbor, because his parents moved to his present house shortly after his operation. He does not recognize his doctors. Unlike some victims of amnesia, he remembers his background very clearly. However, everything new vanishes from his mind so quickly -- within minutes -- that his own life since 1953 remains a total blank.
While researchers agree that the hippocampus plays a crucial role in memory, they differ in the interpretation of it. Some believe that short-term memories must be "consolidated" through a chemical process in order to become permanent memories and that this process depends on the hippocampus. H. M. would then be unable to consolidate what he had learned. Other researchers question whether H. M. can, in fact, learn anything without a hippocampus, even for a short time; perhaps the hippocampus is essential to registering or encoding memory traces in the proper way.
H. M. represents an extreme case, but many old people also forget what they have read in the morning's newspaper, though they remember the past very vividly. The big difference, of course, is that H. M. lost large portions of his brain, while, through aging, people lose only some brain cells. Therefore, there is good reason to hope that drugs which make their remaining brain cells work more efficiently may help older people regain their lost ability. This is the rationale behind much of the work with lecithin.
If the current research with memory drugs proves fruitful, millions of active and otherwise healthy people who have only slight problems with their memory my benefit immensely. At the same time, persons with serious memory defects may be helped a little.
In addition to lecithin, a dozen drugs are now being tested for their effects on memory; derivatives of vasopressin, a hormone which plays a role in water retention, are given by nasal spray and have produced small memory increases in some volunteers. Piracetam, a curious drug whcih has been marketed in Europe since the early 1970s specifically for the improvement of memory, is said to have helped some English students who were studying for an exam. Several vasodilators, which improve celebral circulation, several stimulants and a totally new compound, PRL-8-53, which is said to affect not just one, but three, of the brain's neurotransmitters, are among those being tested.
It's a sort of horse race, and most on the research teams involved are working with more than a single drug. After studying choline and starting work on piracetam, for instance, Millhauser Laboratories at N. Y. U. Medical Center is now planning studies of lecithin and vasopressin.
At Creighton University in Omaha, Neb., Nikolaus R. Hansl, a 'neruopharmacologist, has been trying PRL-8-53 on college students and some professors. He reports that when these volunteers were asked to recall a list of words one day after hearing it, their recall was 32.5 percent better after taking the drug than after the placebo, an unusually high increase. The volunteers' serial memory (their recall of words in the correct order ) increased even more -- by 42.7 percent.
Suprisingly, those who remembered least well without the drug improved the most. This was particularly true of people over the age of 30, whose memory of the word list one day after hearing it improved by as much as 108 percent when they had taken the drug.
At NIMH, Weingartner points out that with lecithin, too, the slow learners benefit most, though the increases in memory that are attributed to this substance seldom go beyond 15 percent. "We won't develop super learners this way," he says, "but we may be correcting some memory deficits." NIMH groups are studying lecithin, vasopressin and some other substances. According to Weingartner, not one of these drugs is yet ready for use, however. Too little is known about their effects, especially over the long run.
On the other hand, "there is a lot of activity now, and the research is becoming increasingly sophisticated," he says. "It's no longer enough just to say, 'Aha, I got a response!' Now we are asking what system in the brain is affected. We want to know how various drugs mimic or model pathological states, and how other drugs reverse them. Then we will have a matrix, and it will be much like solving a set of differential equations."
In many ways, then, researchers are zeroing in on chemicals that could help to keep one's memory sharp. "Memory pills" which would prevent some of the memory losses of middle age no longer seems so remote; after all, they may turn out to be just food supplements, much like vitamins. If so, soon we may all be taking them, perhaps in the form of chocolate balls.