Blanks for the memories:
Someday you may be able to take a pill to forget painful
Scott LaFee, (c) San Diego
Union Tribune Feb. 11, 2004
There's a scene in Shakespeare's "Macbeth"
where the protagonist implores a doctor to treat Lady Macbeth,
who is wracked by memories of past bad acts.
"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?"
The doctor, of course, can
offer no real salvation. Lady Macbeth is condemned to live with
her bad memories. Recalling our past is a part of the human
condition. But what if that reality changed? What if people –
400 years after Shakespeare asked – could take a pill to
purposefully dim – perhaps erase – our most painful and unwanted
The notion has long been a
favorite of fiction writers, from Shakespeare to fantasists like
the late Philip K. Dick, but serious people – scientists and
scholars – now believe it might be possible.
"The burgeoning field of
neuroscience is providing new, more specific, and safer agents
to help us combat all sorts of psychic distress," wrote the
authors of "Beyond
Therapy," a recently released report by the President's
Council on Bioethics.
"Soon, doctors may have just
the 'sweet oblivious antidote' that Macbeth so desired: drugs
that numb the emotional sting typically associated with our
intensely bad memories."
The authors do not think this
is necessarily a good thing.
Think it with feelings
Memory isn't a single entity.
There are different kinds and types.
Short-term memory lasts just a
few seconds. It's the ability to recall a phone number long
enough to dial it. Capacity is limited. It's no coincidence that
phone numbers are just seven numbers long. That's the working
limit for most people's short-term memory.
Long-term memories come in two
broad categories. Explicit memories are general knowledge, facts
of life, conscious recollections, the sort of stuff most people
think of as memory.
Implicit memories are
perceptual abilities, motor skills, conditioned or instinctive
responses that operate outside of consciousness, such as
instantly recognizing an object or knowing how to ride a bike.
Researchers focus on long-term
memory because it is the primary driver of behavior. Much about
how long-term memories are formed or function is fuzzy or
unknown, but some fundamentals are well-understood.
To wit: Strong emotions make
Most daily events are quickly
forgotten. They are memories writ in pencil, never made
permanent. But some events provoke an emotional response. In
these moments of joy or sadness, terror or surprise, the body is
flooded with stress hormones released by the adrenal glands,
which are located above the kidneys. This is part of the ancient
"fight or flight" response. Hormones like adrenaline wash over
the amygdala – an almond-shaped portion of the brain that
processes emotion, most notably fear. Adrenaline tells the
amygdala that what's happening at that moment is worth
remembering, that this is a memory to be writ in neurological
Here's where many
neuroscientists think there's an opportunity to act, to perhaps
dilute a potentially traumatic memory before it dries hard and
"We've learned that if you can
prevent the system from working, give a drug that blocks the
action of stress hormones (upon the amygdala and brain), then
you may be able to prevent the influence of making stronger
memories," said James L. McGaugh, director of UC Irvine's Center
for the Neurobiology of Learning and Memory and author of
"Memory & Emotion: The Making of Lasting Memories."
Memory-altering drug research
is currently focused on propranolol, one of several so-called
beta blockers widely used to reduce blood pressure, treat
abnormal heart rhythms and prevent migraines. The brand name for
propranolol is Inderal. Other beta blocker brand names are
Inderide, Innopran XL, Betachron E-R, Kerlone, Lopressor,
Tenormin, Toprol XL, Visken and Zebeta.
Beta blockers work by
"blocking" the stimulative influence of stress hormones –
specifically adrenaline – upon the body, relaxing blood vessels
and slowing nerve impulses inside the heart.
propranolol also blocks the effect of adrenaline upon areas of
the brain involved in memory formation, including the amygdala.
It seems to disconnect emotion from memory.
In a study conducted by Larry
Cahill, a neurobiologist at UC Irvine, McGaugh and others in the
late 1990s, test subjects were told an emotionally neutral,
comparatively boring story illustrated by 12 slides. A second
group of subjects was then shown the same 12 slides. The related
story, however, was much more emotional, involving a severely
When later asked what they
remembered seeing in the pictures, subjects in the second group
recalled much greater detail about the story than the first
group did about theirs.
Cahill and McGaugh then
presented the second, emotionally upsetting story with slides to
a third group of volunteers who were given a standard dose of
propranolol or endurol (another beta blocker). Their memories,
when tested three weeks later, were "just like that of subjects
who had received the boring story," said McGaugh.
Subjects remembered the story,
but without any emotional depth.
Such findings suggest an
obvious potential therapeutic benefit: If people who have just
experienced a traumatic event could be given a memory-dampening
drug like propranolol, they might avoid suffering later psychic
damage, such as post-traumatic stress disorder or PTSD.
Roughly 5 million Americans
between the ages of 18 and 54 suffer from PTSD at any given
time. Almost 8 percent of Americans will experience PTSD at some
point in their lives, women twice as likely as men. Clearly,
McGaugh and others said, there are times when blocking the
formation of traumatic memories would be beneficial.
"Let me give you an example
from the 1978 PSA (plane) crash in San Diego where they made the
horrible mistake of sending out desk people and baggage handlers
to clean up body parts after the crash. Later, there was a
follow-up report that said a very high percentage of those
people were never able to work again. They had been permanently
disabled because of the trauma.
"Now, that's PTSD to the nth
degree, that would be a case in which something like (a
memory-blunting drug) would be of value."
Two subsequent studies
reinforce the potential efficacy of using beta blockers to blunt
memory. In a 2002 pilot study, Roger Pitman, a professor of
psychiatry at Harvard University, recruited 31 people from the
emergency room of Massachusetts General Hospital who had just
been involved in a traumatic event, typically an automobile
Some of the study volunteers
were treated with propranolol for 10 days after the trauma; some
received a placebo. Evaluated one month later, none of the
subjects treated with propranolol had a stressful physical
reaction to re-creations of their traumatic event, while six of
the 14 subjects treated with a placebo did.
A similar 2003 study, conducted
at two French hospitals, produced analogous results. Larger
studies are being planned.
A need to remember
Despite its therapeutic
potential, some people are wary of memory-altering drugs. Chief
among them: the President's Council on Bioethics, an advisory
group of doctors and scholars formed in 2001.
In its report, the council
worries that dampening painful memories – or in the future,
erasing them altogether – may disconnect people from reality or
their true selves.
"The use of memory-blunters at
the time of traumatic events could interfere with the normal
psychic work and adaptive value of emotionally charged memory,"
the council wrote. "A primary function of the brain's special
way of encoding memories for emotional experiences would seem to
be to make us remember important events longer and more vividly
than trivial events."
In other words, emotional
memories, however painful, serve a purpose. We remember memories
linked to emotions longer and better because they help us learn,
adapt, survive. Early hominids needed to know and remember that
lions were dangerous. Modern children burn their fingers on a
match and learn that fire hurts. We all learn to avoid bad
things by remembering bad experiences.
Council members fret that
dampening traumatic memories with beta blockers may
short-circuit "the normal process of recovery," that in some way
it may diminish our character or our personal development.
Blocking emotional memories,
the council asserted, risks "falsifying our perception and
understanding of the world. It risks making shameful acts seem
less shameful, or terrible acts less terrible, than they really
"It's the morning-after pill
for just about anything that produces regret, remorse, pain, or
guilt," said Dr. Leon Kass, who chaired the President's Council,
to the Village Voice last year. (Kass noted he was speaking as
an individual, not on behalf of the council.)
The council expressed a host of
concerns and troubling scenarios.
For example, the council
posited, what if somebody committed an act of violence and then
took propranolol to dull the emotional impact. Would they come
to think of violence as more tolerable than it really is?
Would rape victims, having
taken memory-altering drugs to ease their trauma, forget key
details vital to the prosecution of their attackers?
More broadly, is there a social
obligation for people to remember the past events for the
communal good, such as victims of the Holocaust?
"The impulse is to help people
to not fall apart. You don't want to condemn that," said Kass.
"But that you would treat these things with equanimity, the
horrible things of the world, so that they don't disturb you ...
you'd cease to be a human being."
Such talk dismays researchers
like McGaugh. Partly because they believe it overstates current
scientific realities; partly because it seems a moot point.
Society, suggests McGaugh, decided decades ago that the benefits
of certain drugs outweighed any memory-altering side effects.
"We made that decision with the
advent and use of psychoactive drugs. Valium is a
memory-impairing drug, but I don't hear people raising memory
issues about it."
More to the point, the
influence of propranolol seems to be limited to new, emotional
memories – and only if taken during or shortly after a traumatic
"The (memory-dampening) effects
(of beta blockers) are rather weak," said Larry Squire, a
neurobiologist at UCSD and the Veterans' Administration Medical
Center in La Jolla. "And no one can imagine possibly tinkering
with memory that represents our personal identities, memories of
childhood, our connections to people and the past. Those are
transformed over time. They're hard-wired in our brains and
can't be fooled with."
But some researchers aren't so
sure. In animal studies, neuroscientists like Joseph Ledoux at
New York University say they have found evidence that there is a
window of opportunity to alter a memory each time it is
Specifically, lab rats were
trained to expect an electric shock when they heard a particular
tone. The rats soon froze in fear whenever they heard the tone,
even if no shock followed. Then the NYU researchers backed off,
allowing the rats' brains to consolidate the memory, to embed it
long-term. Days later, they played the tone again, eliciting the
fearful response. But this time, some of the rats were given a
drug that prevented the amygdala from making proteins necessary
for memory storage. These rats stopped being fearful of the
tone, apparently forgetting their earlier emotional response to
Other studies, blocking protein
production in the hippocampus of crabs and chicks, produced
Karim Nader, an assistant
professor of psychology at Montreal's McGill University who
participated in the NYU rat research, believes there may be a
human corollary to these animal studies and a potential
opportunity to influence deeper, older memories when they are
recalled, and then laid back down.
But the idea is highly
controversial, with many skeptics.
"It's likely that any effects
are reversible, temporary," said Squire. "You may be able to
bring up a memory, weaken it, but eventually the memory comes
back. The effect is more like interference than real change."
"I simply do not believe the
(NYU) research is valid," added McGaugh. "Human studies have
shown no such effect. They show human memory doesn't work that
Fact and fiction
McGaugh and similarly minded
researchers doubt science will ever be able to probe an
individual's mind, precisely plucking and altering specific
memories like they do in movies. The brains of real people are
far too complex. Memories aren't single molecules or neurons,
but intricate patterns of biochemical and electrical energy
occurring in various parts of the brain and different levels of
Take, for example, new findings
from Michael Anderson and John Gabrieli, psychology professors
at the University of Oregon and Stanford, respectively. Last
month, they reported identifying the brain mechanism that allows
humans to voluntarily block unwanted memories.
"Often in life we encounter
reminders of things we'd rather not think about," Anderson said.
"We have all had that experience at some point – the experience
of seeing something that reminds us of an unwanted memory,
leading us to wince briefly – but just as quickly to put the
recollection out of mind. How do human beings do this?"
Anderson and Gabrieli
discovered that when people consciously determine not to think
about something they do not want to remember, their ability to
recall that memory gradually weakens. Call it motivated
The effect, said McGaugh, is
not unlike what propranolol does biochemically and it fits
neatly into what's known about how PTSD can progressively worsen
with each recurrence of the traumatic memory.
How Anderson and Gabrieli's
work can be exploited therapeutically, if at all, remains to be
Currently, the pursuit of
memory-altering drugs is limited, both in terms of the numbers
of researchers involved and in what they are trying to do or
learn. Prospects of a pill-to-forget hitting the market anytime
soon are nil.
But even the existence of that
prospect raises profound questions that demand answers, said Dr.
William B. Hurlbut, a consulting professor in biology at
Stanford University and a member of the President's Council on
"The pattern of our personality
is like a Persian rug," Hurlbut said. "It is built one knot at a
time, each woven into the others. There's a continuity to self,
a sense that who we are is based upon solid, reliable
experience. We build our whole interpretation and understanding
of the world based upon that experience or on the accuracy of
"If you disrupt those memories,
remove continuity, what you have is an erosion of personhood."
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