This staff working paper was discussed at the Council's
March 2003 meeting.
It was prepared by staff solely to aid discussion, and does not represent
the official views of the Council or of the United States Government.
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.
_____________
- 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.
- 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.
- 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.
- 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.”
- Steven Rose, The Making of Memory:
From Molecules to Mind, p. 5-6.
- 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.
- 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?
- The concept of “memory IQ”
is discussed at the October 17, 2002 meeting of the President’s
Council on Bioethics.
- 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.
- 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.
- 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.
- See "Donepezil and flight simulator performance: Effects on retention of complex skills," Neurology 59 July 9, 2002.
- See James L. McGaugh, "Significance and Remembrance: The Role of Neuromodulatory Systems," Psychological Science, Vol. 1, No. 1, January 1990, p. 15-23.
- 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.
- Rose, op. cit., p. 3.
- See Langreth, "Viagra for the Brain,"
op. cit.
- Ibid.
- 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.
- 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.
- Schacter, Searching for Memory,
p. 215
- Larry Cahill et. al., "Beta-Adrenergic
activation and memory for emotional events," Nature,
Vol. 371, October 20, 1994, p. 702-704.
- 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.
- 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.
- 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.
- 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).
- 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.
- 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.
- George Orwell's 1984 offers just one literary account of how memory control might be central to social coercion.
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