Original at: http://www.bioethics.gov/background/better_memories.html#endnote18

STAFF WORKING PAPER

“Better” Memories? The Promise and Perils of Pharmacological Interventions

This working paper seeks to provide background for considering the ethical questions raised by our growing biotechnical abilities to improve or alter human memory. The reasons for seeking such abilities are, at first glance, easy to understand. Because of the centrality of memory in all that we do and are, memory loss has far-reaching and potentially devastating consequences. Perhaps no disease elicits as much horror, sympathy, or biomedical urgency as Alzheimer’s Disease. We rightly shudder at the prospect of forgetting our own past or not recognizing our loved ones; of being forgotten by an ailing Alzheimer’s patient; or of having our own identity “die” to ourselves while we are still living. There is a massive research effort underway to understand Alzheimer’s Disease, and much public support for memory research in particular and brain research more generally is focused on curing this and other memory-destroying diseases.

But the human desire to “improve,” “control,” or “fix” our memory is not merely medical and therapeutic, and memory loss is not the only memory problem. Recognizing the desire of most people for quicker, sharper, and more reliable memories, many researchers are explicitly pursuing drugs or other pharmacological agents that might improve our “normal” capacity to remember; that might enhance the cognitive performance of both under-achievers (with below normal “memory IQs”) and over-achievers (who cannot bear simply to be “normal”); and that might prevent, halt, or reverse age-related memory decline.

In addition to efforts aimed at increasing our power to remember, the goal of producing “better memories” fosters pharmacological efforts aimed at decreasing the necessity of remembering bad things or at reducing the emotional sting of our worst memories. This new class of drugs has the great potential to help those who suffer from traumatic and life-disordering memories, increasing their chances of living, at least partially, a normal life. Yet these drugs also raise new possibilities for abuse and misuse. And even in their most welcome uses, they raise profound questions about the relationship between our subjective experience of memory and the true nature of what we remember.

Before we can begin to make sense of the new science of memory and the biotechnical powers it might set before us, we need to consider the human meaning of memory itself: in particular, we need to consider what memory is, what it would mean to improve it, and how it goes wrong.¹ The analysis that follows aims to provide a survey of some of the major issues and questions, not a comprehensive account. Some important matters are briefly noted without being fully considered, and other important issues are left out altogether. Yet we hope it provides sufficient background for considering the human significance of new pharmacological efforts to produce “better memories”: this includes interventions aimed at improving our capacity to remember new things, but especially interventions aimed at dulling or selectively blocking our most painful memories.

I. The Different Types of Memory

Any effort to understand “human memory,” let alone improve “it,” must confront a simple, if not always obvious, fact: Memory is not a singular phenomenon. Neither is it mediated by a single biological or psychological “system”: there are many types of remembering and forgetting.² We remember phone numbers we need only once and the phone numbers we use everyday; we remember the names of old classmates we barely knew and the experiences we shared with our oldest and closest friends; we remember the day we were mugged and the day we were married; we remember how to ride a bicycle and how to speak a foreign language; we remember the soldiers who died in World War II and the names and dates for tomorrow’s American History exam; we remember how to drive home from work and what we look like in the mirror. All of the above are surely acts of memory; but each of them involves different ways of remembering, and each of them has a different significance and meaning.

Human memory also looks different when viewed from various human perspectives: There is the vision of the novelist or artist, who attempts to capture descriptively and imaginatively the lived experience of memory; the vision of the philosopher or theologian, who seeks wisdom about the nature of memory and its relationship to human experience and the good life; the vision of the psychologist or clinician, who attempts to research, test, and discover how memory works and how to keep it intact; and the vision of the neuroscientist, who studies the workings of the brain itself: by dissecting and studying the brains of non-human animals, by conducting chemical tests on human patients, or by taking pictures of the human brain at work.³ Much of modern neuroscience has attempted to integrate the study of the “mind” and the “brain”; and at least one prominent neuroscientist sees the study of memory as the “Rosetta Stone”—that is, as a way to translate between the biological workings of the brain itself and the subjective experiences of those whose brain is at work or malfunctioning.

One of the goals of modern memory research is to organize and describe the different types of memory and “memory systems.” These include “short-term memory” and “long-term memory”; “explicit memory” and “implicit memory”; “eidetic memory” and “time-bound memory”; “voluntary memory” and “involuntary memory”; “semantic memory” and “episodic memory.” These models of memory are neither fixed nor mutually exclusive; and much of memory research is an effort to refine and perfect how we understand memory’s many faces. But building proper models of memory is, as philosopher Eva Brann argues, no easy task, relying as it must on metaphors and images:

The mechanism of memory itself is conceived of in terms of various models. It may be like a date-stamping machine that time-tags each perceptual event, or like a filing cabinet that is already predated and organized sequentially, or like a fading photograph that indicates time by waning vividness, or like an archaeological dig where dating inferences are made from context, or like a book with cross-references from which one can reconstruct the order of publication, that is, of perceptual occurrence. Sometimes neurophysiologically based systems are distinguished: “procedural memory” for motor skills, “semantic memory” for languages and facts, “working memory” for temporal order, “episodic memory” for personal experience. Often the memory is analyzed in terms of its structures and the depth as well as the capacity of their levels: immediate and fast-decaying sensory or “iconic” memory, short-term memory where all that is needed for present working purposes is stored, and long-term memory, our deep storage. These models are, of course and of necessity, figurative. Metaphors structure much of our experience in any case. But when we represent interiority we have practically no means except metaphor…⁴

And yet, as alluded to above, the goal of modern neuroscience over last few decades has been to move beyond metaphor by uncovering scientifically how these different types of memory correspond with the specific functions, sections, or activities of the brain itself. As Steven Rose describes in his book The Making of Memory: From Molecules to Mind:

Brain language has many dialects, spoken by many sorts of biologists—physiologists, biochemists, anatomists—and handles its claims to objectivity with confidence. Mind language can be—generally is—subjective, the language of everyday life, or of the poet or novelist. But in the hands of psychologists, it too aspires towards objectivity. One of the tasks of the new breed of neuroscientist… is to learn how to translate between the two objective languages of mind and brain. To help that translation we need a Rosetta stone, some inscription in which the two languages, the Greek of mind and the hieroglyphs of brain, can be read in parallel and the interpretation rules deciphered. Deciphering translation rules is not the same as reducing one language to the other. The Greek is never replaced by the Egyptian; the mind is never replaced by the brain. Instead, we have two distinct and legitimate languages, each describing the same unitary phenomena of the material world. The separate histories of these languages as they have developed over the past century have hitherto made them sometimes rivals, sometimes allies. But… the prospect of unity, of healing old divisions and of learning the translation rules, has never seemed brighter. ⁵

The first goal of modern memory research, in other words, is to give an objective or scientific account of subjective experience; it is to leave metaphor behind, or at least to verify in the brain which metaphors of the mind are true and which are false. But there is a second, more practical goal as well. Researchers seek to use our knowledge of how memory works—how the specific functions of the brain shape our lived experience of memory—to fix, alter, or manipulate its workings: specifically, to cure dreaded memory disorders, to improve the quality of everyday memory, or to achieve a more perfect control of what we remember and forget. Before moving to describe these potential new powers, it is worth considering both what a “better memory” might mean and the different ways that memory fails.

II. What is a “Better” Memory?

To speak about “better memory” is to imply some notion of “best” or “perfect” memory. But it is not easy to specify what having a “perfect” memory in fact means. Perhaps the most obvious reply is that an individual with a perfect memory would never forget anything; he would remember every fact, every face, every encounter, every piece of information, every transgression that he commits himself or suffers at the hands of others. But it does not take much reflection to see that such indiscriminate and perfect recall would be not a blessing but a curse. We would suffer like the Jorge Luis Borges character, “Funes, the Memorious,” who describes his “all-too-perfect” memory as “a garbage disposal”; or like the famous memory patient Shereshevskii, whose photographic memory prevented him from forming normal human relationships. Such total and indiscriminate recall may also make it more difficult to distinguish between big and small, important and trivial, needed and unnecessary, mere facts and their significance.

Perhaps a “perfect” memory means remembering only what we desire, or what we find desirable when we experience it. But this, too, does not seem quite right. For much that is most worth remembering is not by nature desirable; and much that seems undesirable when we first experience it only reveals its true significance, meaning, or value in our lives much later. To remember only what is desirable is to imagine ourselves as more autonomous than we really are—i.e., in full control of our memories—and thus to presume more wisdom than we really have at any given moment. It is also to diminish our horizons: Our memory would become little more than a sequence of seemingly desirable “presents,” with no way to relate past, present, and future into a maturing identity.

Perhaps a “perfect” memory means remembering things “as they really are” or “as they actually happen.” This seems closer to the truth—though giving an account of what this actually means is rather difficult. It is also only partially the truth. To remember things as they are offers no guidance about what is worth remembering. It provides no insight into the difference between simply cataloging events (the “brain” as camera) and discerning their meaning (the “mind” as photographer and editor). This dilemma raises further questions: Is memory more like an artistic vision (interpretive, creative, contingent) or a static reproduction of past events (objective, given, fixed)? Is the way we remember shaped more by the brain structure of our birth or by the experiences and character of our life? And to what extent do our experiences in-the-world alter the “memory hardware” of the brain itself?

In the end, there is probably no such thing as a “perfect” memory, just as there is no such thing as a perfect human life. To be imperfect beings means, among other things, having a memory that imperfectly renders many imperfect things. To be creatures of space and time means having a memory that is by nature incomplete. And to be mortal beings means having a memory that must ultimately fail. What we seek, in other words, is not a perfect memory but a good or excellent memory. We seek a memory that honestly helps account for the world as it is and human life as it is lived; a memory that recalls the facts we most need when we most need them; a memory that honors those who came before us and prepares those who will come after us; a memory that allows us to understand other people not simply for what they have done but for what they are, and thus a memory that works not simply chronologically but mosaically, and not simply historically but philosophically.

To remember well, in other words, is to remember at the “right pitch,” and it requires both a working instrument (the brain) and a learned capacity to remember with discernment (a well-ordered psyche). This means neither remembering too much, such as trivial facts, minor offenses, or the shames and horrors of life in such a way that we live only in the past; nor remembering too little, such as forgetting the defining moments of life, the information that allows for everyday functioning, or one’s own greatest sins and misdeeds. And it means remembering with neither too much emotion, so that we become so haunted by past terrors that our memories control us; nor too little emotion, so that we remember what is joyful, horrible, and inconsequential with the same monotone memory. It also requires an acceptance of the human fact that not all memory is chosen; sometimes memory simply happens to us—both for better and for worse.

III. The Ways Memory Fails

Those interested in bettering our memories take their bearings less from an idea of “excellent memory” than from the manifest facts of memory failure. We should therefore consider the different ways that memory “fails,” or fails to satisfy us; and describe those phenomena of remembering and forgetting that individuals experience as “memory problems.” But we must do so with caution. As Daniel Schacter has described, some of the apparent “vices” of memory are inextricably linked to its “virtues.” “Sometimes we forget the past and at other times we distort it; some disturbing memories haunt us for years,” he writes. But the “seven sins of memory,” as he calls them, are “byproducts of otherwise desirable and adaptive features of the human mind.” ⁶Put differently, to isolate (and seek to “cure”) memory’s individual failures risks distorting the way memory works as a whole. It risks disrupting memory’s “fragile power,” which allows us to weave past, present, and future together in a meaningful way. ⁷

Yet some problems of memory are not adaptive but destructive; life is often diminished, not improved, when memory fails; and many memory problems rightfully deserve our best effort to heal them. Consider the following six experiences of memory—all of them memory failures; each them humanly (and biologically) distinct.

Group A: Lost Memories

(1) Alzheimer’s Disease: A condition of declining and ultimately destroyed personal memory; a condition that begins with a self-conscious sense of what is happening and what is coming, and ends with the total loss of self-consciousness itself—or at least consciousness of the life one has lived, the people one has loved, the things one has done, and the world one has known. To cure this disease would mean restoring both a lost memory capacity and the possession of lost memories.

(2) Age-Related Decline (“Mild Cognitive Impairment”): This involves the decline of memory’s power from its peak; it involves the slowing down that comes with human aging, if more quickly or severely than normal. This decline often begins with the reduced ability to remember present names and facts, only to work its way forward, so to speak, by reducing the capacity to remember past experiences. This form of memory loss is described clinically as “Mild Cognitive Impairment,” and it has official status in the FDA as a treatable disease. Such treatments would involve a prevention of memory decline or restoration of lost memory capacity.

 

(3) Head Trauma: “Retrograde Amnesia”: A condition that results from a physical injury to the brain, resulting in the partial or total loss of one’s memory of the past. Such a trauma erases, for the subject, what has already happened; it shrouds the personal past in mystery, so that this past remains known only (partially) by others. It leaves intact the capacity to learn new things, and yet makes one a stranger to the world—thrown into a life and human relationships that one has no memory of forming. Curing this disease would mean restoring the possession of lost memories.

 

(4) Head Trauma: “Anterograde Amnesia”: A condition that results from a physical injury to the brain, resulting in the partial or total inability to remember new things, new events, or new experiences. The known past remains intact as memory, but one is unable to move beyond it. The “new” leaves as quickly as it comes, and our body ages without remembering the experience of being in the world as it ages. Curing this disease would mean restoring a lost memory capacity.

 

Group B: Weak Memories

(5) Low Memory IQ: To have a low “memory IQ”⁸ is not to experience a sudden or gradual loss of memory, but rather to be born with a lowered capacity to remember all along, or to be so adversely affected by various environmental factors at an early age that certain memory powers never develop. It is to be slow, not slowing down. Curing this disease, if it is a disease, would mean enhancing a limited memory capacity.

Group C: Bad Memories

(6) Experiential Trauma: “Post-Traumatic Stress Disorder”: A condition that results not from direct physical damage to the brain, but from the personal experience of something terrible and the haunting effect of how we remember it. To the extent that this phenomenon is understood neurologically—as a problem of the memory system—treating it would require transforming the way we encode and consolidate the memory of emotionally powerful experiences.

The purpose of describing these different memory problems is two-fold: First, it is to signal the distinct experiential and biological nature of different memory problems—slow and slowing down, damaged brains and haunted memories, losing the past and losing the capacity to remember what will happen to us in the future. Just as memory has many faces, so does the failure, destruction, and limitations of memory. The second (and hereafter more significant) purpose is to consider the connection between biotechnical efforts to heal these different memory problems and the prospect of biotechnical interventions that go “beyond therapy.”

In some of the above cases (Alzheimer’s, amnesia, age-related memory decline), the desire for a better memory involves the restoration of something lost, and thus the treatment of an existing affliction.⁹ In one case (low memory IQ), it involves the enhancement of a memory that is not “broken” but might have been better made in the first place. In the final case (post-traumatic stress disorder), it involves transforming the way a new memory is made—that is, by intervening after a traumatic experience has occurred to alter the way the experience is “encoded” into memory. It potentially involves treating a “disease” before it happens, and treating a disease that is caused not by a virus or physical trauma but an experience. And it involves intervening in the actual emotional content of our memories. This last case, as we shall see, may be the most profound—both because the technology is close at hand and because the questions it raises lay before us with great clarity the moral dilemmas that come with our expanding control over how we remember.

IV. Biotechnology and Better Memory

Our focus until now has been on examining the nature of memory itself: what it is, what it might mean to improve it, and the different ways that it fails. We now turn to consider the possibility of actually and actively improving human memory through pharmacology. So far, the effort to treat the major diseases of memory has achieved only limited biomedical success; the problem of memory, in its various guises, is apparently not easy to fix. But this does not mean that we are simply powerless when it comes to trying to better human memory. For while we may not yet be able to remedy un-chosen afflictions, we may soon be able to intervene in the workings of memory to achieve our own chosen effects. In what follows, we consider some of the scientific underpinnings and prospects of new biotechnical powers to alter the workings of human memory; we provide a narrative account of where the science stands and where it might be heading, not a comprehensive review of the scientific literature. We focus in particular on two kinds of “enhancements”: those that enhance our capacity to remember what is coming, and those that alter the way we remember what has already come. In both cases, we begin to explore the continuity and distinction between therapeutic interventions and interventions that go “beyond therapy.”

A. “Anterograde Enhancement”: Preparing for an Unknown Future

(1) While we have not yet cured Alzheimer’s disease, which is the focus of much memory research, our understanding of the underlying biology has increased, resulting in at least limited treatments that improve the memory capacity of some early-stage Alzheimer’s patients. For example, we have discovered that cholinergic cells are “among the first to die in Alzheimer’s patients and that cholinergic mechanisms may be involved in memory formation.” ¹⁰ This has led to therapeutic interventions with a class of drugs called acetylcholinesterase inhibitors, which inhibit the enzyme that destroys acetylcholine (a neurotransmitter that scientists believe is crucial to forming memories) when it is released. By inhibiting this enzyme, acetylcholine remains at the synapse for a longer period of time. This class of drugs has had a real but limited effect on improving memory in some patients; it can slow down or moderate the effects of the disease, but does not reverse the progressive destruction of the brain.

(2) But Alzheimer’s treatment is not the only use that has been made of acetylcholinesterase inhibitors, and curing disease is not the only ambition of many memory researchers, who see the prevention of typical age-related decline and the enhancement of everyday memory as a major new market and exciting new field. For example, a recent study tested the effect of donepezil, one of the major acetylcholinesterase inhibitors, on the performance of middle-aged pilots. As the American Academy of Neurology reports: “The study involved 18 pilots with an average age of 52. First, the pilots conducted seven practice flights on a flight simulator to train them to perform a complex series of instructions. Then half of them took the drug donepezil for 30 days and half took a placebo. They then took the flight simulator test twice more to see if they had retained the training. The pilots who had taken the drug retained the training better than those who had taken the placebo.”¹² There is also a large body of research, mostly in animals, demonstrating the effect of “opiate receptor antagonists” on memory formation by stimulating the hormones that are typically released in response to emotionally arousing experiences. This work, as we discuss below, is closely related to recent experiments aimed at dulling the emotional power of certain memories.¹³

(3) At the same time, the remarkable complexity of the brain in particular and the human body as a whole makes it very difficult to isolate the functions of memory from other physiological and neurological processes (perception, attention, arousal, etc.) with which it is interconnected. Many “non-memory drugs” or stimulants have a significant effect on memory; and many “memory drugs” have a significant effect on other bodily functions. So, for example, amphetamines, Ritalin, and dunking one’s hand in freezing water have a “positive effect” on the capacity to remember new information, at least over the short-term. But these drugs or experiences have their effect not so much by intervening directly in specific memory systems as they do by affecting other systems of the body that affect how the different memory systems function. They act not directly but indirectly. ¹⁴

(4) We should also not assume that bio-technical interventions that address or countervail the biological causes of specific memory diseases will improve the memory capacity of the “worried well,” or even prevent the onset of the given diseases themselves. As Stephen Rose explains: “The deficits in Alzheimer’s Disease and other conditions relate to specific biochemical or physiological lesions, and there is no a priori reason, irrespective of any ethical or other arguments, to suppose that, in the absence of pathology, pharmacological enhancement of such processes will necessarily enhance memory or cognition, which may already be ‘set’ at psychologically optimal levels.¹⁵” Moreover, even if such drugs or stimulants did improve certain types of memory—such as the speedy retention of new information for a limited period of time—there is little reason to assume that they will improve our memory as a whole, if we understand an excellent memory as remembering at the “right pitch” and with “proper discernment.” The cost of “speed” may be missing or misunderstanding what is most memorable; and of course the most powerful stimulants often have other undesirable side effects.

(5) Nevertheless, it is indeed possible that we will soon discover a drug that will enhance memory in the ways we desire: by enabling us to retain more new information with less effort, by allowing us to make richer connections between our remembered past and our soon-to-be-remembered future, or by refining the way we remember future experiences. These enhancements, we should note, all involve our capacity to remember experiences and information in the unknown future; they are all forward-looking. Surely there will be a great demand for such drugs if they were to be developed and proved effective, as the craze over lecithin, multivitamins, ginseng, gingko biloba, and a variety of other supplements and herbal extracts suggests.

(6) We also cannot ignore the profound significance of recent animal studies on the molecular and genetic “switches” that control memory. For example, in 1990, Eric Kandel discovered that blocking the molecule CREB (c-AMP, or cyclic adenosine monophosphate, Response Element Binding protein) in sea slug nerve cells blocked new long-term memory without affecting short-term memory.¹⁶ A few years later, Tim Tully and Jerry Yin genetically engineered fruit flies with the CREB molecule turned “on”; the resulting flies learned basic tasks in one try where for normal flies it often took ten tries or more. The hypothesis is that “CREB helps turn on the genes needed to produce new proteins that etch permanent connections between nerve cells,” and that it is “in these links that long-term memories are stored.¹⁷” Two companies—Memory Pharmaceuticals and Helicon Pharmaceuticals—have been formed to develop potential drugs based on this research. In 1999, Joe Tsien succeeded in genetically engineering mice that learn tasks much more readily. He inserted an additional NR2B gene into a mouse embryo, which caused over-expression of the mice’s NMDA receptor 2B: a biological mechanism “embedded in the outer wall of certain brain cells” and “long suspected to be one of the basic mechanisms of memory formation” because it allows the “brain to make an association between two events.¹⁸” Such work, of course, is all very preliminary; and its significance for producing biotechnologies that alter or enhance human memory is uncertain. So far, there seems to be no “silver pill” or “golden gene” for producing better memories with no countervailing biological cost.

B. “Retrograde Enhancement”: Altering Our Remembrance of Things Past

Perhaps closer at hand and more profound are capacities to alter the way we remember emotionally arousing experiences. Recent research on the formation of long-term memories has elaborated two crucial facts: First, there is a period of time after a new experience or new exposure to information during which bio-technical interventions in various memory systems can affect what kind of memories are formed. Second, emotionally arousing experiences activate particular memory systems. These two findings may seem like common sense: After all, the most memorable experiences are typically so complex or so dramatic that “encoding” them into memories cannot happen instantaneously; and precisely because different human experiences have a different meaning, we should expect our brain to encode them differently. And yet, by breaking memory formation down to its component parts—especially the different systems involved in encoding emotionally arousing and emotionally neutral experiences—we are gaining novel forms of control over how we remember.

The desire for such control is of course a very old one. In Shakespeare’s Macbeth, Macbeth begs his doctor to free Lady Macbeth from the haunting memory of her own guilty acts:

Doct. Not so sick, my lord,
As she is troubled with thick-coming fancies,
That keep her from her rest.
Macb. Cure her of that:
Canst thou not minister to a mind diseas’d,
Pluck from the memory a rooted sorrow,
Raze out the written troubles of the brain,
And with some sweet oblivious antidote
Cleanse the stuff’d bosom of that perilous stuff
Which weighs upon the heart?

Doct. Therein the patient
Must minister to himself.

Today, the doctor may soon have just the “sweet oblivious antidote” that Macbeth so desired: a class of drugs (beta-adrenergic blockers) that numb the emotional sting typically associated with our memory of intense (and intensely bad) experiences. Seeing how this new antidote was developed—and how it might be used—is a telling tale about the way biological science works and the way the biotechnological fruits of science set before us profound questions about the character of human life. This research also cuts to heart of memory itself, especially the prospect for controlling our remembrance of things past.

(1) By the early 1990s, a body of animal research had established that “newly acquired information can be modulated by drugs or hormones administered shortly after training,” focusing in particular on the effect of “opiate receptor agonists” (which impair memory) and “opiate receptor antagonists” (which enhance memory). Additional research in amnesia patients suggested that the amygdala, a “tiny almond-shaped” section of the brain near the hippocampus, “can help to influence or modulate explicit memory for emotionally significant events.” James McGaugh, Joseph LeDoux, and many others have done key work in this area,¹⁹ which is summarized by Schacter as follows:

This modulatory role of the amygdala is linked to its role in determining how various hormones affect memory. Studies of rats and other animals have shown that injecting a stress-related hormone such as epinephrine (which produces high arousal) immediately after an animal learns a task enhances subsequent memory for that task. This strongly implies that some of the beneficial effects of emotional arousal on memory are due to the release of stress-related hormones by a highly emotional experience. The amygdala plays a key role in this process. When the amygdala is damaged, injecting stress-related hormones no longer enhances memory. The amygdala, then, helps to regulate release of the stress-related hormones that underlie the memory-enhancing effects of emotional arousal. ²⁰

According to this view, our memory system has specific capacities, involving the amygdala, that match the intensity of an experience with the intensity of our memory of that experience. One adaptive benefit of such a system is that it enables both animals and human beings to attach fearful memories to fearful things, and so to avoid similar experiences in the future. The problem, however, is that the benefits of learning to avoid fearful experiences may be outweighed (or seem to some individuals to be outweighed) by the traumatic and life-disordering effect of the memories themselves. Some experiences for some people are simply too horrible to remember, or induce memories that are too horrible to live with.

(2) In 1994, Larry Cahill et. al. used the insights of this animal research to test whether the stress hormone system that modulated memory in human beings could be modified in such a way that the emotional power of certain experiences did not affect how we remember them. The study is summarized as follows:

Substantial evidence from animal studies suggests that enhanced memory associated with emotional arousal results from an activation of beta-adrenergic stress hormone systems during and after an emotional experience. To examine this implication in human subjects, we investigated the effect of the beta-adrenergic receptor antagonist propranolol hydrochloride on long-term memory for an emotionally arousing short story, or a closely matched but more emotionally neutral story. We report here that propranolol significantly impaired memory of the emotionally arousing story but did not affect memory of the emotionally neutral story. The impairing effect of propranolol on memory of the emotional story was not due either to reduced emotional responsiveness or to nonspecific sedative or attentional effects. The results support the hypothesis that enhanced memory associated with emotional experiences involves activation of the beta-adrenergic system.²¹

More specifically, subjects received either propranolol or a placebo one-hour before experiencing either the emotionally neutral or emotionally arousing version of a slide show. The four different test groups (propranolol/emotion, propranolol/neutral, placebo/emotion, placebo/neutral) were tested for their memory of the different stories one week later. Those taking propranolol and those taking the placebo did not differ in their memory of the neutral story; however, they differed significantly in their memory of the emotionally arousing story, but not in their “subjective emotional reactions to the story assessed immediately after story viewing.” In other words, propranolol had little to no effect on how individuals remember everyday or emotionally neutral information, but a significant effect on how they remembered emotionally powerful experiences—not on how they reacted to them in the moment, but how they remembered them once the moment had passed. The goal of this study, which moved the underlying research from animals to humans, was to increase our understanding of how we remember, and how we remember emotionally intense and emotionally neutral experiences in different ways. But it established the groundwork for research that aims at clinical (or non-clinical) applications of beta-blockers, and thus for the move from biological science to biotechnology.

(3) In 2002, Roger K. Pitman et. al. published a pilot study ²²describing the experimental use of propranolol administered to emergency room patients within 6 hours after a traumatic experience (mostly car accidents) and for an additional 10 days afterwards. The patients—both those taking the drug and those taking placebos—were tested for their psychological and physiological response to a re-telling (with related images) of the traumatic event. One month after the event, those taking propranolol showed measurably lower incidence of post-traumatic stress disorder (PTSD) symptoms than the control group; and three months later, while the PTSD symptoms of both groups had returned to comparable levels, the propranolol group showed measurably lower psycho-physiological response to “internal cues that symbolized or resembled the initial traumatic event.”

This study, while preliminary, raises a series of questions: How are we to judge an intervention in human memory so soon after an event, before the ultimate significance of the experience has fully revealed itself and before it is even possible to know whether the individuals will suffer from PTSD? Do such drugs “fix” a “broken” encoding system that attaches too much emotional power to a given memory? Or do they alter a well-working encoding system, one that matches the intensity of one’s memory to the intensity of the experience, so that the individual as a whole can better function? To what extent is the encoding system—and thus the incidence of PTSD—shaped by what is given genetically and to what extent by prior experience or condition of soul? And what lasting effect, if any, do such traumatic experiences have on the brain itself?²³

The prospect of such “memory numbing” drugs has already elicited considerable public interest in and concern about their potential uses in non-clinical settings: to prepare a soldier to kill (or kill again) on the battlefield; to dull the sting of one’s own shameful acts; to allow a criminal to numb the memory of his or her victims.²⁴ Some of these scenarios are perhaps far-fetched. But the significance of this potential new power—which allows us to separate the subjective experience of memory from the true nature of the experience that is remembered—cannot be underestimated. It surely returns us to the large ethical and anthropological questions with which we began—about the place of memory in shaping the character of human life and about the meaning of remembering things that we would rather forget.

V. Philosophical and Ethical Reflections

In this final section of the paper, we explore a few aspects of the possible human significance of new pharmacological powers to intervene in human memory. Most but not all of the issues are especially linked to the matter of memory blunting. Our mode is wisdom-seeking and reflective, preferring to raise questions rather than to presume answers. We are interested in how memory interventions might change human life as a whole, both for individuals and for society.

(1) The Experience of Memory and the Nature of What We Remember

The power to block or dull the emotional power of certain memories sets before us the “beyond therapy” dilemma in a very clear way. Clearly, some memories are so traumatic that they destroy the lives of those who suffer them. And clearly, many of us desire—at certain moments, if not always—to escape the sting of shameful, embarrassing, or painful memories. But we must consider not only how to draw the line between good and bad, medical and non-medical, uses of this power, but also the meaning of the power itself. For it seems to put truth (remembering events as they really happened and for what they are) in opposition to compassion or well-being (remembering events in a modified way, so that they seem less horrible than they really were). And it potentially gives us new powers of control over how and what we remember, and therefore who and what we are. (In reality, of course, such control is limited, since we cannot escape the memory of others.)

For example, these new powers might make us willing to do things we might not otherwise do, or allow us to do the things we desire without shame, hesitation, or remorse: either by changing our psyche before the act or by giving us the power (known in advance) to numb the sting or shame of the act after the fact. At the same time, the power to numb our memories might make us more “accepting” creatures, by altering our perception of the things we must accept. This forces us to consider the difference between forgiving and forgetting, or between forgiveness that requires soberly facing what needs to be forgiven and that which depends on chemically altering our perception of what needs to be forgiven.²⁵

Most profoundly, the power to numb the emotional significance of certain memories alters the inherent connection between how we perceive certain human phenomena and the phenomena themselves and their true nature. Imagine, for example, a witness to a horrible murder. Fearing that he will be haunted by the memory of this event, he immediately takes propranolol to make his memory of the murder “more tolerable.” But in doing so, does he risk coming to understand the murder itself as tolerable—that is, as an event that does not sting those who witness it? Does dulling our memory of terrible things make us more “whole” and more “at home in the world”? Or does the experience of terror—the experience of the un-chosen, the inexplicable, the tragic—remind us that we can never be fully whole in-this-world, especially if we are to take the reality of human evil seriously?

(2) Individual Good and Common Good

One can imagine cases where the good of the individual would be served by numbing the emotional impact of certain memories: for example, those with first-hand experience of the Holocaust.²⁶ And yet, would the good of society as a whole—or the good of history—be served by a mass numbing of memory? Do those who suffer evil have a duty to remember and bear witness, lest we forget the very horrors that haunt them? The examples of this dilemma need not be so dramatic: the memory of being embarrassed is a source of empathy for others who suffer embarrassment; the memory of loss is a source of empathy for others who experience loss. And yet, can we force those who have lived through a great trauma to endure its memory for the benefit of the rest of us? What kind of people would we be if we did not “want” to remember such things, if we sought simply to make the sting of the Holocaust go away? And yet, what kind of people are we, especially those who face such horrors first-hand, that we can endure such memories?

(3) Memory and Human Nature

Memory research raises large questions regarding human nature and human self-understanding. Among other things, it invites reflection on the relation between human beings and animals. Do animals remember in the same way that human beings remember, especially given that human beings have language and perceive the world through lenses colored by opinion and articulable beliefs?²⁷ Do animals experience the “seven sins of memory”—especially the sins that involve distorting our memory of the past (“bias”) in light of our present values and concerns? Or are these sins distinctly human phenomena? Is there an animal equivalent to the word/category test discussed by Dr. Schacter, or the memory process known as “semantic encoding”? Such an exploration of the differences between human beings and other animals might suggest that while there are important biological similarities between the animal brain and the human brain, the differences are perhaps most important. Are these differences explained best or simply in terms of how the different “memory systems” are put together? Or do we need other—perhaps richer—categories for understanding the distinctively human phenomenon of remembering and forgetting?

(4) Memory and Moral Responsibility

The new science of memory, by describing and seeking to understand memory as a “system,” raises questions about the difference between voluntary and involuntary action, and especially about the extent of our responsibility for what we remember and what we forget. For example, to what extent should a woman who forgets her child in a car be held “morally accountable” for her forgetting? Is forgetting an “action” or a “non-action”? Is it something we do or something that happens to us? Can we separate memory failure as a “systems failure” and memory failure as a failure of character (or the result of a disordered psyche)?

(5) Memory and Coercion

Finally, we can not be blind to the potentially coercive uses of drugs that alter how we remember and what we forget. Just as drugs that dull the emotional sting of certain memories might be desired by the victim to ease his trauma, they might be useful to the assailant to dull the victim’s sense of being wronged. Perhaps no one has a greater interest in blocking the painful memory of evil than the evil-doer. And while the use of chemical enhancements of our memory powers may be justifiable or necessary in certain extreme situations (e.g. military), we cannot ignore the potentially coercive nature of normalizing the use of such drugs in certain occupations. Nor can we forget the central place of manipulating memory in totalitarian societies, both real and imagined.²⁸

(6) Conclusion: The (Eternal) Puzzle of Memory

Perhaps Jane Austen captured the mysterious nature of memory and its human significance best: “If any one faculty of our nature may be called more wonderful than the rest, I do think it is memory. There seems something more speakingly incomprehensible in the powers, the failures, the inequalities of memory, than in any other of our intelligences. The memory is sometimes so retentive, so serviceable, so obedient—at others, so bewildered and so weak—and at others again, so tyrannical, so beyond control!—We are to be sure a miracle every way—but our powers of recollecting and of forgetting, do seem peculiarly past finding out.” Perhaps it is fitting, as we begin to evaluate the human significance of intervening in the workings of human memory, that we have more questions than answers, more dilemmas than solutions. It is an open question whether we will ever fully understand the nature of memory, a fact that should awaken at least some humility about our capacity to make memory “better.” And it is likely that we will be remembered, for better or for worse, by those who follow us, a fact that should inspire at least some sense of responsibility to use our new biotechnical powers wisely.
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1. A more complete analysis of the human meaning of human memory might begin by asking the following kinds of questions: What does it mean to be the creature that remembers and forgets, that studies and wonders about memory, and that seeks to manipulate and control the way we remember? How does human memory differ from the memory of other animals? Is memory decline actually “normal” for particular age groups? Are remembering and forgetting “activities we engage in” or “experiences that happen to us”? What would it mean to have a “perfect” memory? Why do we so often remember what we would like to forget, and forget what we would like to remember? To what extent is the way we remember shaped by our given genetic or neurological “equipment,” and to what extent by our choices, experiences, and upbringing? This paper will touch on many of these issues but adequately address none of them. Keeping them in mind, however, is crucial to considering the ways in which we might alter human memory that go “beyond therapy” and coming to some judgment about the significance or wisdom of doing so.
2. As Daniel Schacter explains: “[W]e have now come to believe that memory is not a single or unitary faculty of the mind, as was long assumed. Instead, it is composed of a variety of distinct and dissociable processes and systems. Each system depends on a particular constellation of networks in the brain that involve different neural structures, each of which plays a highly specialized role within the system. New breakthroughs in brain imaging allow us to see, for the first time, how these specific parts of the brain contribute to different memory processes.” See Schacter, Searching for Memory: The Brain, the Mind, and the Past, p. 5.
3. Of course, these different perspectives are not mutually exclusive, and much of the best writing about memory draws on all of them. But these perspectives are distinct enough in themselves to be worth noting.
4. Eva Brann, What, Then, is Time?, p. 170-171. Brann also describes additional memory distinctions—including the difference between “access to memory, the memory itself and the memories that it contains—the key, the container, and the contents.” And she notes: “There are multitudinous roads of remembrance, ways into memory: spontaneous remembrance, directed recollecting, musing reminiscence, reminding memoranda, directed recollecting, mindful recognition.”
5. Steven Rose, The Making of Memory: From Molecules to Mind, p. 5-6.
6. For a complete discussion, see Daniel Schacter, The Seven Sins of Memory: How the Mind Forgets and Remembers. Schacter describes these sins as: transience, absent-mindedness, blocking, misattribution, suggestibility, bias, and persistence.
7. For example: To what extent is the slowing down of memory that comes with growing old a “re-tuning” of memory that allows individuals to make sense of a long life? To what extent are the “memory vices” of old age inextricably linked to the “memory virtues” of coming to know what is most truly memorable or significant?
8. The concept of “memory IQ” is discussed at the October 17, 2002 meeting of the President’s Council on Bioethics.
9. Treatment of age-related memory decline might also involve not restoration but prevention: that is, taking drugs before the actual onset of age-related memory decline in an effort to prevent it. This raises important questions about treating diseases that may never arrive, or trying to preemptively stop diseases that might never come.
10. Steven Rose, “ ‘Smart Drugs’: Do They Work, Are They Ethical, Will They Be Legal?,” as included in the October 17-18, 2002 briefing book of the President’s Council on Bioethics, p. 6. The above discussion also draws on James McGaugh’s testimony before the President’s Council on Bioethics, October 17, 2002.
11. For a journalistic account of efforts to produce memory-enhancing drugs, see Stephen S. Hall, "Our Memories, Our Selves," New York Times Magazine, Feb. 15, 1998 and Robert Langreth, "Viagra for the Brain," Forbes, Feb. 4 2002.
12. See "Donepezil and flight simulator performance: Effects on retention of complex skills," Neurology 59 July 9, 2002.
13. See James L. McGaugh, "Significance and Remembrance: The Role of Neuromodulatory Systems," Psychological Science, Vol. 1, No. 1, January 1990, p. 15-23.
14. The above description draws heavily on Steven Rose, op. cit., p. 4-5. As Rose explains: "[M]emory formation requires, amongst other cerebral processes: perception, attention, arousal. All engage both peripheral (hormonal) and central mechanisms. Although the processes involved in recall are less well studied it may be assumed that it makes similar demands. Thus agents that affect any of these concomitant processes may also function to enhance (or inhibit) cognitive performance. Memory formation in simple learning tasks is affected by plasma steroid levels, by adrenaline and even by glucose. At least one agent claimed to function as a nootropic and once widely touted as a smart drug, piracetam, seems to act at least in part via modulation of peripheral steroid levels. Central processes too can affect performance by reducing anxiety, enhancing attention or increasing the salience of the experience to be learned and remembered. Amphetamines, methylphenidate (Ritalin) antidepressants and anxiolytics, probably act in this way. Other agents regularly cited as potential smart drugs, such as ACTH and vasopressin, may function similarly. Finally, there is evidence from animal studies that endogenous cerebral neuromodulators such as the neurosteroids (e.g., DHEA) and growth factors like BDNF will enhance long-term memory for weakly acquired stimuli." See original for complete list of citations.
15. Rose, op. cit., p. 3.
16. See Langreth, "Viagra for the Brain," op. cit.
17. Ibid.
18. Nicholas Wade, "Of Smart Mice and an Even Smarter Man," New York Times, Sept. 7, 1999. See also: Tsien, Joe Z. et al., "Genetic enhancement of learning and memory in mice," Nature 401, 63-69, September 2, 1999.
19. See, for example, J. E. LeDoux, "Emotion, Memory, and the Brain," Scientific American, 270, 32-39 (1994); James McGaugh, "Emotional Activation, neuromodulatory systems and memory," in Memory Distortion: How Minds, Brains, and Societies Reconstruct the Past, edited by Schacter et. al., p. 255-273, 1995; and James McGaugh, "Memory consolidation and the amygdala: a system perspective," Trends in Neuroscience, Vol. 25, No. 9, September 2002.
20. Schacter, Searching for Memory, p. 215
21. Larry Cahill et. al., "Beta-Adrenergic activation and memory for emotional events," Nature, Vol. 371, October 20, 1994, p. 702-704.
22. Roger K. Pitman et. al., "Pilot Study of Secondary Prevention of Posttraumatic Stress Disorder with Propranolol," Biological Psychiatry, 2002; 51: 189-142, p. 189-192.
23. For a discussion of the effect of traumatic experiences on the brain, see, for example, Amy F. T. Arnsten, "The biology of being frazzled: neurobiological research on response to stress," Science, June 12, 1998, and Robert Sapolsky, "Stress and Your Shrinking Brain: Post-Traumatic Stress Disorder's Effect on the Brain," Discover, March 1999.
24. See, for example, Ellen Goodman, "Matter Over Mind?," Washington Post, November 16, 2002, and Erik Baard, "The Guilt-Free Soldier," The Village Voice, January 28, 2003. It is interesting to note the dual appeal of such drugs to both the traumatized victim seeking escape from the horror of his or her experience and the traumatizing assailant looking to escape the inconvenience of his guilty memory.
25. It also forces us to consider the difference between an ethic of just retribution (which requires always remembering) and an ethic of forgiveness (which subordinates remembering the guilty act to the "rebirth" of the guilty).
26. This is not to suggest that drugs would be the only or even the best way to cope with monumental horror. Many survivors of the Holocaust, through a wide variety of other means, managed without actually forgetting to make a new life for themselves.
27. In addition to language as a distinguishing characteristic of human beings and human memory, we might also consider the following: man as the being who mourns those who die; man as the being who seeks to be remembered after death; man as the being who celebrates days of remembrance; man as the being who seeks to manipulate memory.
28. George Orwell's 1984 offers just one literary account of how memory control might be central to social coercion.