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IF A JAZ DISK can hold two gigabytes of retrievable data, can someone please explain why I can't recall my own Visa number? Perhaps the most amazing thing of all about the information revolution is that, somehow, a few decades of computer engineering appear to have outmatched a billion years of nervous system natural selection. Next to the total recall of a Pentium III, our own fuzzy and forgetful brains don't seem so impressive any more.
With such formidable powers of recollection sitting on our desktops, it's no wonder that the allure of "smart drugs" and "memory pills" -- now popping up all over the news and on the Net -- has grown almost irresistible in recent years. Who wouldn't pay handsomely for a pill to help us keep up with a faster-paced world? In 1995, the famous Cold Spring Harbor Laboratory created a fruit fly with an apparent photographic memory; now the Lab has partnered with Hoffman-La Roche to see what they can do for the human mind (and consumer economy). In Switzerland, Albert Hoffman, the Sandoz chemist who invented LSD a few decades back, has created a popular (if unproven) antioxidant called Hydergine. Scientists aren't calling this "the decade of the brain" for nothing; powerful new scanning technologies and increased funding for research on pressing diseases like Alzheimer's are fueling astounding advances in neurological understanding. We're finally getting to know something about our own thinking machines. Can real brain boosters be far away?
A solid answer to that question will most likely depend much more on our own evolving understanding of the brain than the doings of any creative chemist. In fact, the best way to help understand the prospects of what many are trumpeting as the emerging memory revolution is probably to revisit the last great memory revolution.
IN THE MID-1960s, a series of exhilarating discoveries concerning the molecular basis of human memory threatened to revolutionize not just academic biology, but the very fabric of human society. The first revelation came in a 1962 Journal of Neuropsychiatry article, "Memory Transfer Through Cannibalism in Planaria," by the University of Michigan's James McConnell. McConnell reported that he had trained a group of flatworms to respond to light in a non-instinctive way; he then killed these worms, chopped them up, and fed them to untrained flatworms. After eating their brethren, the untrained worms proceeded to behave as if they had been trained -- they had somehow acquired the "memory" of the trained worms by eating them. It was the unexpected apotheosis of the old yarn, "you are what you eat."
Out of this a thousand research grants were borne, some of which yielded tantalizing results. Three years after McConnell's initial study, four California scientists reported in the journal Science that when RNA from the brains of trained rats was injected into the guts of untrained rats, the untrained rats exhibited the learned behavior of the trained rats. These experiments apparently showed that specific, concrete personal memories were embedded as information in RNA protein structures in the same way that genetic information is embedded in DNA, and that these memories were transferable from brain to brain. A later experiment by Baylor University's Georges Ungar was the most vivid yet: brain cells from rats that had been trained to fear the dark were transferred to untrained mice (ordinarily, neither mice nor rats fear the dark), who suddenly took on this new fear. Ungar even isolated a peptide comprised of 15 amino acids that evidently contained the newly-created fear-of-the-dark memory. He called it scotophobin.
These studies together suggested a radical breakthrough in our understanding of mind: memory as a distinct informational molecule that could be created organically in one brain, isolated, and then transferred to another brain -- even to the brain of another species! Had this cold fusion of an idea been validated -- rather than methodically disassembled -- not long after Ungar's paper was published in Nature in 1972, ours would be a very different world today. Contemporary fantasies/fears of genetic editing would be a distant back seat to the daily reality of memory swaps, consciousness transfers, and neurochemical behavioral enhancements, making Prozac seem like baby aspirin. The rapid decoding of a hidden science of memory molecules might well have spawned a new type of biochemical computer that could register, react to and -- "15 amino acids? No problem" -- even create memory molecules of their own. Laptops (or cars or stuffed animals) could be afraid of the dark or partial to jazz or concerned about child abuse. Memories could be bottled and sold as easily as perfume.
Alas, that world did not (and cannot) emerge. The memory transfer experiments, while entertaining and even seductive -- DNA pioneer Francis Crick was among the many prestigious scientists on board for a while -- were all badly flawed both in theory and practice. After a decade or so, the entire notion, and burgeoning industry, of memory molecules crumbled into dust. It is now one particularly humiliating memory that many neuroscientists would just as soon not retain.
WHAT HAS GROWN UP out of that rubble over the last 30 years is a very different understanding of memory not as a substance but as a system. Think symphony orchestra or urban metropolis or ant colony. We now know that memory, like consciousness itself, isn't a thing that can be isolated or extracted, but a living process, a vast and dynamic interaction of neuronal synapses in what Harvard's Daniel Schacter elegantly terms "a temporary constellation of activity" simultaneously involving several different regions of the brain.
The molecular basis for these synaptic constellations that can be re-ignited again and again (though never in precisely the same configuration) is a biochemical process called Long-term Potentiation (LTP) which ramps up the affinity between specific neurons after a significant connection is made. That is, after a notable experience (listening for the first time to track two of Keith Jarrett's "Changeless," for example, or catching a glimpse outside my window of a man in a red t-shirt standing on the roof of a 12-story building) causes a unique set of neurons to fire in conjunction with one another, those connections become chemically more sensitive to one another, so that they can more easily trigger each other again, leaving a permanent physical trace of that original sensation. Neurologists call these long-term memory traces "engrams." Think trails of dominos, with new trails and inter-connections between trails constantly being created. The dramatic extent to which this soft-wiring takes place in our brains (integrated, of course, with an enormous amount of modular hard-wiring) is what makes us such creatures of experience, as compared with other more predominantly hard-wired animals.
By their very nature, memory constellations overlap with and trigger one another. Any common free-association experiment is a vivid illustration of this interdependence: for me, at this moment, the word "cat" prompts... a thought of Brownfoot, my loyal white-footed feline friend when I was a boy... the garage roof she used to gracefully leap down from... the 1971 T-top Corvette my dad used to drive... the tragicomic episode in which mom wrecked two of dad's Corvettes in one month's time... a general feeling of malaise associated with my parent's divorce (many years later). This instant montage of memories is neither chronological nor predictable, even by me. If someone were to prompt me with "cat" tomorrow, it might not even be my own cat that I think of; depending on my mood or other recent experiences, it could be that I will think of the cat that my daughter was calling out for yesterday on Seventh Avenue. Or it could be that Brownfoot will come to mind, but that from there I will involuntarily shift to a memory of how I was her pretend dentist, and then I might think of my own current dentist and how I'm way overdue for a cleaning. That guilty feeling might then trigger... you get the idea. The domino pathways linking engrams can be built on temporal, intellectual or aesthetic associations, and when the mind really wanders, during daydreams or at night before sleep sets in, it's amazing what sort of involuntary memory leaps one makes, from impressions that often have no logical or logistical relationship but which share a texture or smell or emotional fragment. Further, every time a memory is recalled, new trails are made. Taken together, this interconnected universe of constellations in each of us forms the core of who we are.
OVERLAP, IN OTHER WORDS, is not only built into the biology of memory; it is the very basis of memory -- and identity. New perceptions are analyzed and memory traces laid down exclusively on a foundation of old memories, and old memories can only be recalled in conjunction with the particulars of present consciousness. Think of a single painting being created over the course of a lifetime on one (giant) canvas. A new brushstroke of Jarrett crosses over and bleeds into past brushstrokes of Jarrett albums, of other piano music I've heard, other jazz albums, jazz shows, relevant conversations, places I've been when listening to these albums, and so on. Neither the new stroke nor any of the old strokes are truly distinct from anything else. The painting is forever changed by this new experience, and so are any old memories I try to recall. Whether I like it or not, my past is informed by my present.
Scores of experiments confirm the vulnerability and malleability of old memories, and horror stories of False Memory Syndrome are by now well known. Part of the romantic attraction of the idea of distinct memory molecules was that it connoted the ability to replay old memories as they were originally recorded. But the biology of memory constellations dictates that there is no such thing as pure memory, no freedom from taint. Recall is never replay.
But why? Why would millions of years of evolution produce a machine so otherwise sophisticated but with an apparent built-in fuzziness, a tendency to regularly forget, repress and distort information and experience?
The answer, it turns out, is that fuzziness is not a severe limitation but a highly advanced feature. As a matter of engineering, the brain does not have any physical limitations in the amount of information it can theoretically hold. One remarkable man from Russia inadvertently proved this point early in this century. He also proved that forgetting is not a failure but an active metabolic process, a flushing out of data in the pursuit of knowledge and meaning.
In the 1920s, S., as he is known in the psychological literature, was a twenty-something newspaper reporter in Moscow who got into some trouble with his editor one day for not taking notes at a staff meeting. In the midst of his reprimand, he surprised his boss by repeating everything that had been said in the meeting, word for word. This was no trouble at all for S., who, it emerged upon closer examination, apparently remembered every detail of sight and sound that he had come into contact with in his entire life. To him, it seemed perfectly normal that he forgot nothing.
For the rest of his life S. was tested vigorously. No one could find any real limit to his capacity to recall details. As an illustration, not only could he perfectly recall tables like this one full of random data after looking at them for just a few minutes --
6 6 8 0 5 4 3 2 1 6 8 4 7 9 3 5 4 2 3 7 3 8 9 1 1 0 0 2 3 4 5 1 2 7 6 8 1 9 2 6 2 9 6 7 5 5 2 0 x 0 1 x
-- and not only could he recall these tables in any way requested (i.e., forwards, backwards, upside down, diagonal, etc.), but after years of memorizing thousands of such tables, he could also reproduce any particular one of them, without warning, whether it was an hour after he had first seen it, or 20 years. The man remembered everything.
And yet he understood almost nothing. S. was plagued by an inability to make meaning out of what he saw. Unless one pointed the obvious pattern out to him, for example, this table appeared just as bereft of order and meaning as any other:
1 2 3 4 2 3 4 5 3 4 5 6 4 5 6 7
"If I had been given the letters of the alphabet arranged in a similar order," he remarked after being questioned about this particular table, "I wouldn't have noticed their arrangement." He was also unable to make sense out of poetry or prose, to understand much about the law, or even to remember people's faces. "They're so changeable," he complained to his chronicler, the great Russian psychologist A.R. Luria. "A person's expression depends on his mood and on the circumstances under which you happen to meet him. People's faces are constantly changing; it's the different shades of expression that confuse me and make it so hard to remember faces."
LURIA ALSO NOTED that S. came across as generally disorganized, dull-witted and without much of a sense of purpose or direction in life. This astounding man, then, was not so much gifted with the ability to remember everything as he was cursed with the inability to forget detail and form more general impressions. He was, metaphorically speaking, a memory molecule maker, rather than a constellationist. He recorded only information, and was bereft of the essential ability to draw meaning out of events. His disability demonstrates compellingly that the qualities which make details hazy and can make memories unreliable and confusing are the same qualities which enable us to prioritize information, recognize and retain patterns. The brain, to invoke the old cliche, eliminates most of the trees it comes across in order to make sense of, and remember, the forests. We understand so much precisely because we forget so much.
Still want that memory pill? If so, the first round of "nootropics," untested and unproven, are now available (Piracetum, Hydergine, Centrophenoxine and Vasopressin are all available in one venue or another, though none have been approved as intelligence or memory boosters by the FDA). And you can bet that pharmaceutical companies are going to be promising us the memory moon over the next decade or so. But if you follow the lesson of S., you'll be very wary of anything that seeks to alter the balance that natural selection has refined for us over the eons. If the story of S. isn't enough to convince you, perhaps the wisdom of British neurologist Steven Rose will help. "Because the brain is such a finely equilibrated and dynamic system, with great capacity for self-adjustment and control," he writes in The Making of Memory, "the effect of disrupting its biochemistry by flooding it, via a pill, with some drug which affects protein synthesis, or particular neurotransmitters or neuro-modulators, is more likely to be the equivalent of trying to retune a radio or reprogram a computer by jamming a screwdriver into its circuit boards."
I've seen the gruesome guts of a hi-fi after some kid (me) blasted it with tools from the basement. I think I'll settle for the brain that evolution gave me.
David Shenk's collection of essays, The End of Patience, will be published in September. The Forgetting, a book he is writing about Alzheimer's disease, will be published sometime in the next millennium.
What will the future of neuroscience be? Share your thoughts on the New Brain in the FEED Loop.