If you could erase the worst memory of your life, would you? Scientists are working on a pill for that
If you could erase the
worst memory of your life, would you? Scientists are working on a pill for that
Researchers are working on ways to edit memories — to
make the intolerable bearable — by, say, blocking the synaptic changes needed
for a memory to solidify
SHARON KIRKEY October 31, 2019 2:25 PM EDT
The 60 souls that signed on for Dr. Alain Brunet’s memory
manipulation study were united by something they would rather not remember. The
trauma of betrayal.
For some, it was infidelity and for others, a brutal,
unanticipated abandonment. “It was like, ‘I’m leaving you. Goodbye,” the McGill
University associate professor of psychiatry says.
In cold, clinical terms, his patients were suffering from
an “adjustment disorder” due to the termination (not of their choosing) of a
romantic relationship. The goal of Brunet and other researchers is to help
people like this — the scorned, the betrayed, the traumatized — lose their
total recall. To deliberately forget.
Over four to six sessions, volunteers read aloud from a
typed script they had composed themselves — a first-person account of their
breakup, with as many emotional details as possible — while under the influence
of propranolol, a common and inexpensive blood pressure pill. The idea was to
purposely reactivate the memory and bring the experience and the stinging
emotions it aroused to life again. “How did you feel about that?” they were
asked. How do you feel right now? And, most importantly: Has your memory
changed since last week?
The investigators had hypothesized that four to six
sessions of memory reactivation under propranolol would be sufficient to
dramatically blunt the memories associated with their “attachment injury.”
Decrease the strength of the memory, Brunet says, and you decrease the strength
of the pain.
The study is now complete, and Brunet is hesitant to
discuss the results, which have been submitted to a journal for peer review and
publication. However, the participants “just couldn’t believe that we could do
so much in such a small amount of time,” he confides.
“They were able to turn the page. That’s what they would
tell us — ‘I feel like I’ve turned the page. I’m no longer obsessed by this
person, or this relationship.’”
Brunet insists he isn’t interested in deleting or
scrubbing painful memories out entirely. The idea of memory erasure, of finding
the cellular imprint of a specific, discreet memory in the brain, of isolating
and inactivating the brain cells behind that memory, unnerves him. ‘It’s not
going to come from my lab,” he says, although others are certainly working on it.
Memories are part of who we are, what forms our identity, what makes us
authentic, “and as long as only one choice exists right now, and it’s toning
down a memory, we feel on very solid and comfortable ground,” ethically
speaking, Brunet says.
“However, if one day you had two options — I can tone
down your memory, or I can remove it altogether, from your head, from your mind
— what would you choose?”
The choice might soon be yours.
“If you could erase the memory of the worst day of your
life, would you,” Elizabeth Phelps and Stefan Hofmann write in the journal,
Nature. “How about your memory of a person who has caused you pain?”
What was once purely science fiction is moving ever
closer to clinical reality. Researchers are working on techniques and drugs
that might enable us to edit our memories or at least seriously dull their
impact — to make the intolerable bearable — by, say, swallowing a pill to block
the synaptic changes needed for a memory to solidify. A pill that could be
taken hours, even months or years after the event.
Much of the work is based on the theory of memory
reconsolidation – the belief that the mere conscious act of recalling or
conjuring a memory makes it vulnerable to tinkering or meddling. When a memory
is evoked, a reconsolidation window opens for a brief period of time (two to
five hours, according to Brunet), during which time the memory returns to a
state of “lability.” It becomes pliable, like Play-Doh. It also becomes
susceptible to modification, before “reconsolidating” or re-storage. The
thought is that propranolol interferes with proteins in the brain needed to
lock down the memory again.
A similar line of thinking holds that a memory isn’t an
exact impression of the original event, an Iphone video of the past, says Boston
University neuroscientist Steve Ramirez. Rather it’s more like Plato’s wax
tablet. Press a signet ring into the wax and it leaves an imprint, but the wax
can melt when we recall the memory, form again and then melt all over again.
“Memory is dynamic,” Ramirez says. It isn’t static. Memories can also be
updated with new information when they’re recalled, like hitting “save as”
every time you go into a Word file.
But the idea that memories can be edited, softened or
dialled down, is more than a little discomfiting to some, and not just for what
it means for eyewitness testimony. “We’re not reliable narrators when it comes
to some details, and sometimes even entire scenarios,” Ramirez says. More
profoundly, without good and bad memories it’s hard to imagine how we would
know how to behave, says Dr. Judy Illes, professor of neurology and Canada
Research Chair in neuroethics at the University of British Columbia.
Learning doesn’t occur without memory. How do we learn
from a bad relationship, if we can’t remember it? “And so now, if we pre-select
what memories stick and don’t stick, it almost starts to be like the eugenics
of memory,” Illes says. “We ought to think carefully about that.”
She has absolutely no qualms about using memory
manipulation for people suffering desperately from post-traumatic stress
disorder, people whose burden of suffering from horrifying experiences exceeds
any moral argument against using it.
“To me, a PTSD that is profound and debilitating is like
a disease of any other and, to the extent that we can have an intervention that
treats it, we should vigorously pursue it.”
Even the heartbroken recruited for Brunet’s study were
experiencing symptoms congruent with PTSD. We’re geared to form attachments, he
says, and not so much to detach.
But memory manipulation has a slippery slope. Would it
bleed into not-so-disabling disorders? If someone misbehaves at a cocktail
party and would really sooner forget what happened, is that an appropriate use?
Isn’t it good to be embarrassed by your past behaviour, to keep you from doing
it again? What about war fighters, asks Illes. “If we had a drug that can
mitigate a bad memory, could we possibly use it in advance of an act to
actually prevent a memory from forming, and therefore enable people to fight
less fearfully, and more fiercely, because there’s no consolidation of the acts
of crime, or acts of war?”
The pull of moral responsibility — “one’s future
‘oughtness’” — is grounded in our life story, writes bioethicist Dr. Peter
DePergola in the Journal of Cognition and Neuroethics. Using blood pressure
pills or some other intervention like, say, transcranial direct current
stimulation, to deaden or blast away memories of trauma “ultimately undermines
one’s ability to seek, identify and act on the good,” DePergola argues.
And how do you manipulate a bad memory, without risking
happy, shiny, positive ones? What does a memory even look like in the brain?
Can we visualize it? Can we see what happens when positive and negative
memories form? And where would all the bad memories go? Saved in glass bottles
in the Ministry of Magic?
We can’t go into the brain and erase memories in an
Eternal-Sunshine-of-the-Spotless-Mind kind of way, Ramirez says, at least not
yet. We can’t touch or poke a memory. However, scientists are starting to get
unprecedented glimpses into the physical structure of memory in the brain. The
goal is to identify the brain cells a particular memory gloms onto, and
artificially manipulate those cells.
The challenge is that human memories aren’t localized to
one specific location in the brain. There’s no spot X you can point to, and
say, Aha! There it is. Rather, they’re scattered throughout the organ. The
sights and sounds and smells and emotions of a memory are going to recruit
different corners of the brain that are involved in processing the sights and
sounds and smells and emotions, Ramirez says.
“Right now, there are a lot of memories that are asleep
in your brain. If I asked you, ‘what did you do last night?’, that memory just
woke up. How did that happen? You just did that effortlessly in, like, 500
milliseconds. And yet we don’t know how that process works.”
However, we know that it does happen, and scientists have
some pretty good indications of what happens physically when we recall a
memory, and what it means for that memory to become awake again.
American-Canadian neurosurgeon Wilder Penfield was one of
the first to hint at where to look. When Penfield stimulated cells in the
hippocampus of people who were undergoing surgery for epilepsy in the 1940s
with mild jolts of electricity, specific episodic
memories — memories of actual experiences — suddenly
popped into their minds. “It was like, ‘I have no idea why, but I’m randomly
remembering my 16th birthday and I was walking my cat,’’” Ramirez said on a
National Geographic podcast earlier this year.
In experiments that helped open the floodgates, Ramirez
and other scientists at MIT reported that they could identify — in mice — the
cells that make up part of an engram, the coding for a specific memory, and
reactive those same cells using a technology called optogenetics.
Briefly, here’s what they did: Viruses were inserted into
the brain cells of genetically modified mice that made the cells glow green in
response to light. Next, the researchers isolated cells in the hippocampus of a
mouse as the rodents were forming a specific memory — in this case, the memory
of receiving a mild electric foot shock while exploring a box.
A day later, the mouse was placed in a different box —
different smells, different floor, meaning there should be no reason for them
to be fearful. But when those memory cells were activated with a laser, the
mouse froze in fear.
More recently, in a paper published earlier this year,
Ramirez and co-author Briana Chen mapped out which cells in the hippocampus
were being activated when male mice made new memories of positive (meeting a
female mouse) and negative (those mild electric foot zaps again) experiences.
They were able to trigger the memories again later, using laser light to
activate the memory cells. When memory cells in the bottom part of the
hippocampus were stimulated, it seemed to dial up the negative memories. But
stimulating memory cells in the top part of the hippocampus seemed to dial them
down.
The goal, says Ramirez, is to artificially activate
positive memories to overwrite the bad ones — in a sense, using the brain as a
drug. “In depression, there is a bias toward negative thinking,” Ramirez says.
We’ve been using drugs like Xanax and Prozac for decades, but we haven’t really
advanced all that much since the 1970s, Ramirez says. “Maybe we need to tackle
these kinds of disorders from all angles.”
Ten years ago, Sheena Josselyn’s lab was the first to
offer fairly convincing evidence that we can erase a specific fear memory in
mice, without erasing every one of the rodent’s fears. The University of
Toronto neuroscientist used a toxin to destroy a handful of neurons housing the
memory “It wasn’t like a huge legion. If you take out the entire brain, the
mouse doesn’t remember a darn thing.”
That’s obviously not technically, or ethically ideal in
humans. No one is talking about ablating neurons in people, or injecting
viruses into human brain cells to make them glow green. “But it does tell us
that in order to manipulate a memory in people we don’t have to give an entire,
systemic thing,” Josselyn says. Rather, we could go in and just hit the target
neurons using some kind of smart bomb.
Mice aren’t humans, and efforts to translate the results
from animal experiments to healthy humans have been mixed, Phelps and Hoffman
note in their Nature article. Still, whether it’s beta-blockers like
propranolol, or ecstasy or ketamine or other drugs being tested that might
block the synthesis of proteins required to lock down a memory after it’s been
retrieved, Ramirez and others believe we could tackle the emotional “oomph,”
the psychological sting, of a traumatic memory, while leaving the
autobiographic experience — the actual, conscious recollection of the event —
intact. No, you may not be able to “erase the memory of the venomous, evil
snake that is my ex,” as one Redditor asked Ramirez. There isn’t a memory
anti-venom. With memory manipulation, people would still remember the breakup,
and the person, but the toxic, gut-twisting emotions associated with it would
melt, like ice cream in the sun. And, just as doctors shouldn’t hand out
anti-depressants to the entire population of Boston, Ramirez says memory
manipulation should be reserved for those suffering crippling anxiety,
depression or other symptoms.
Betrayal and abandonment themselves are “no small stuff,”
adds Brunet. “This is the material Greek tragedies are made of.” People can
become hyper vigilant, he says. They have intrusive thoughts. Everything around
them reminds them of the former relationship. “It affects negatively your world
views, your self esteem and the trust you can place in other people,” Brunet
says.
However, a memory buster is challenging, Illes, of UBC
says, because it interferes with our experience as humans.
Our brains are hardwired to remember emotionally charged
events. “Do you remember where you were on 9/11? Do you remember five
supermarkets ago?” Illes asks.
Our memories are so closely interrelated and
interconnected, she adds, that you can’t just pull one brick out without the
integrity of the entire wall being affected.
“Go back to your dating question,” Illes says as a
thought experiment. “We have a bad relationship. Unless two people are on an
isolated island and don’t interact with other humans, your bad relationship has
other people in there. And, so, how do you remove all the memories associated
with all the complexities that we have on a daily basis?”
Memories give us a sense of consciousness, she says, of
who we are and what we know to be right and wrong and moral and immoral.
A prescient 2003 report from the U.S. President’s Council
on Bioethics asked whether the then-emerging field of memory-alteration would
mean abandoning our own truthful identities.
“Armed with new powers to ease the suffering of bad
memories, we might come to see all psychic pain as unnecessary and in the
process come to pursue a happiness that is less than human,” the authors wrote,
“an unmindful happiness, unchanged by time and events, unmoved by life’s
vicissitudes.”
Steve Ramirez was running in the Boston marathon in 2013
when two crude pressure cooker bombs detonated 12 seconds apart near the finish
line, killing three and injuring several hundred more. The sights, the sounds,
the smells — “they helped carve a very deep corner into my personality,” he
says.
“It exposed a darker aspect of humanity, but I wouldn’t
really find any personal gain in not knowing that corner, either.”
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