The Forgetting Pill Erases Painful Memories Forever

Jeffrey Mitchell, a volunteer firefighter in the suburbs of Baltimore, came across the accident by chance: A car had smashed into a pickup truck loaded with metal pipes. Mitchell tried to help, but he saw at once that he was too late.

The car had rear-ended the truck at high speed, sending a pipe through the windshield and into the chest of the passenger—a young bride returning home from her wedding. There was blood everywhere, staining her white dress crimson.

Mitchell couldn’t get the dead woman out of his mind; the tableau was stuck before his eyes. He tried to tough it out, but after months of suffering, he couldn’t take it anymore. He finally told his brother, a fellow firefighter, about it.

Pushing to remember a traumatic event soon after it occurs doesn’t unburden us—it reinforces the fear and stress.
Miraculously, that worked. No more trauma; Mitchell felt free. This dramatic recovery, along with the experiences of fellow first responders, led Mitchell to do some research into recovery from trauma. He eventually concluded that he had stumbled upon a powerful treatment. In 1983, nearly a decade after the car accident, Mitchell wrote an influential paper in the Journal of Emergency Medical Services that transformed his experience into a seven-step practice, which he called critical incident stress debriefing, or CISD. The central idea: People who survive a painful event should express their feelings soon after so the memory isn’t “sealed over” and repressed, which could lead to post-traumatic stress disorder.

In recent years, CISD has become exceedingly popular, used by the US Department of Defense, the Federal Emergency Management Agency, the Israeli army, the United Nations, and the American Red Cross. Each year, more than 30,000 people are trained in the technique. (After the September 11 attacks, 2,000 facilitators descended on New York City.)

Even though PTSD is triggered by a stressful incident, it is really a disease of memory. The problem isn’t the trauma—it’s that the trauma can’t be forgotten. Most memories, and their associated emotions, fade with time. But PTSD memories remain horribly intense, bleeding into the present and ruining the future. So, in theory, the act of sharing those memories is an act of forgetting them.

A typical CISD session lasts about three hours and involves a trained facilitator who encourages people involved to describe the event from their perspective in as much detail as possible. Facilitators are trained to probe deeply and directly, asking questions such as, what was the worst part of the incident for you personally? The underlying assumption is that a way to ease a traumatic memory is to express it.

The problem is, CISD rarely helps—and recent studies show it often makes things worse. In one, burn victims were randomly assigned to receive either CISD or no treatment at all. A year later, those who went through a debriefing were more anxious and depressed and nearly three times as likely to suffer from PTSD. Another trial showed CISD was ineffective at preventing post-traumatic stress in victims of violent crime, and a US Army study of 952 Kosovo peacekeepers found that debriefing did not hasten recovery and led to more alcohol abuse. Psychologists have begun to recommend that the practice be discontinued for disaster survivors. (Mitchell now says that he doesn’t think CISD necessarily helps post-traumatic stress at all, but his early papers on the subject seem clear on the link.)

Mitchell was right about one thing, though. Traumatic, persistent memories are indeed a case of recall gone awry. But as a treatment, CISD misapprehends how memory works. It suggests that the way to get rid of a bad memory, or at a minimum denude it of its negative emotional connotations, is to talk it out. That’s where Mitchell went wrong. It wasn’t his fault, really; this mistaken notion has been around for thousands of years. Since the time of the ancient Greeks, people have imagined memories to be a stable form of information that persists reliably. The metaphors for this persistence have changed over time—Plato compared our recollections to impressions in a wax tablet, and the idea of a biological hard drive is popular today—but the basic model has not. Once a memory is formed, we assume that it will stay the same. This, in fact, is why we trust our recollections. They feel like indelible portraits of the past.

None of this is true. In the past decade, scientists have come to realize that our memories are not inert packets of data and they don’t remain constant. Even though every memory feels like an honest representation, that sense of authenticity is the biggest lie of all.

When CISD fails, it fails because, as scientists have recently learned, the very act of remembering changes the memory itself. New research is showing that every time we recall an event, the structure of that memory in the brain is altered in light of the present moment, warped by our current feelings and knowledge. That’s why pushing to remember a traumatic event so soon after it occurs doesn’t unburden us; it reinforces the fear and stress that are part of the recollection.

This new model of memory isn’t just a theory—neuroscientists actually have a molecular explanation of how and why memories change. In fact, their definition of memory has broadened to encompass not only the cliché cinematic scenes from childhood but also the persisting mental loops of illnesses like PTSD and addiction—and even pain disorders like neuropathy. Unlike most brain research, the field of memory has actually developed simpler explanations. Whenever the brain wants to retain something, it relies on just a handful of chemicals. Even more startling, an equally small family of compounds could turn out to be a universal eraser of history, a pill that we could take whenever we wanted to forget anything.

And researchers have found one of these compounds.

In the very near future, the act of remembering will become a choice.

Every memory begins as a changed set of connections among cells in the brain. If you happen to remember this moment—the content of this sentence—it’s because a network of neurons has been altered, woven more tightly together within a vast electrical fabric. This linkage is literal: For a memory to exist, these scattered cells must become more sensitive to the activity of the others, so that if one cell fires, the rest of the circuit lights up as well. Scientists refer to this process as long-term potentiation, and it involves an intricate cascade of gene activations and protein synthesis that makes it easier for these neurons to pass along their electrical excitement. Sometimes this requires the addition of new receptors at the dendritic end of a neuron, or an increase in the release of the chemical neurotransmitters that nerve cells use to communicate. Neurons will actually sprout new ion channels along their length, allowing them to generate more voltage. Collectively this creation of long-term potentiation is called the consolidation phase, when the circuit of cells representing a memory is first linked together. Regardless of the molecular details, it’s clear that even minor memories require major work. The past has to be wired into your hardware.

That understanding of how memories are created emerged in the 1970s. But what happens after a memory is formed, when we attempt to access it, was much less well understood. In the late 1990s, Karim Nader, a young neuroscientist studying emotional response at New York University, realized that no one knew. “My big advantage was that I wasn’t trained in memory,” Nader says. “I was very naive about the subject. Even though the field wasn’t that interested in the mechanisms of recall, it struck me as a mystery worth pursuing.”

He began with the simplest question he could think of. While it was clear that new proteins were needed for the making of memories—proteins are cellular bricks and mortar, the basis of any new biological construction—were additional proteins made when those memories were recalled? Nader hypothesized that they were, and he realized that he could test his notion by temporarily blocking protein synthesis in a brain and looking to see if that altered recall. “This is the kind of question you ask when you don’t know how else to approach the subject,” Nader says. “But I had to do something, so why not this?”

His boss, the famed neuroscientist Joseph LeDoux, couldn’t have been more discouraging. “I told Karim he was wasting his time,” LeDoux says. “I didn’t think the experiment would work.” To LeDoux, the reason was obvious: Even if Nader blocked protein synthesis during recall, the original circuitry would still be intact, so the memory should be too. If Nader could induce amnesia, it would be temporary. Once the block was removed, the recall would return as strong as ever. And so LeDoux and Nader made a bet: If Nader failed to permanently erase a set of fear memories in four lab animals, he had to buy LeDoux a bottle of tequila. If it worked, drinks were on LeDoux. “I honestly assumed I’d be spending a bunch of money on alcohol,” Nader says. “Everyone else knew a lot more about the neuroscience of memory. And they all told me it would never work.”

He taught several dozen rats to associate a loud noise with a mild but painful electric shock. It terrified them—whenever the sound played, the rats froze in fear, anticipating the shock. After reinforcing this memory for several weeks, Nader hit the rats with the noise once again, but this time he then injected their brains with a chemical that inhibited protein synthesis. Then he played the sound again. “I couldn’t believe what happened,” Nader says. “The fear memory was gone. The rats had forgotten everything.” The absence of fear persisted even after the injection wore off.

The secret was the timing: If new proteins couldn’t be created during the act of remembering, then the original memory ceased to exist. The erasure was also exceedingly specific. The rats could still learn new associations, and they remained scared of other sounds associated with a shock but that hadn’t been played during the protein block. They forgot only what they’d been forced to remember while under the influence of the protein inhibitor.

The disappearance of the fear memory suggested that every time we think about the past we are delicately transforming its cellular representation in the brain, changing its underlying neural circuitry. It was a stunning discovery: Memories are not formed and then pristinely maintained, as neuroscientists thought; they are formed and then rebuilt every time they’re accessed. “The brain isn’t interested in having a perfect set of memories about the past,” LeDoux says. “Instead, memory comes with a natural updating mechanism, which is how we make sure that the information taking up valuable space inside our head is still useful. That might make our memories less accurate, but it probably also makes them more relevant to the future.”

After collecting his tequila, Nader hit the library in an attempt to make sense of his bizarre observations. “I couldn’t believe that no one had ever done this experiment before,” he says. “I thought, there’s no way I’m this lucky.” Nader was right. He had unknowingly replicated a 44-year-old experiment performed by a Rutgers psychologist named Donald Lewis, in which rats had been trained to be afraid of a sound—associating it, again, with an electric shock—and then had those memories erased by a separate electroconvulsive shock. Lewis had discovered what came to be called memory reconsolidation, the brain’s practice of re-creating memories over and over again.

But by the mid-1970s, neuroscientists had largely stopped investigating reconsolidation. Other researchers failed to replicate several of Lewis’ original experiments, so the phenomenon was dismissed as an experimental error. “These guys had discovered it all way before me,” Nader says. “But they had been left out of all the textbooks.”

Nader was convinced that Lewis’ work had been rejected unjustly. But no one wanted to hear it. “Man, it was brutal,” Nader says. “I couldn’t get published anywhere.” He was shunned at conferences and accused in journal articles of “forgetting the lessons of the past.” By 2001, just a few years after his experimental triumph, he was on the verge of leaving the field. He thought of Thomas Kuhn, the philosopher of science who famously observed that overturning paradigms is always a fearsome task. “Why put up with this shit?” Nader says. “I finally understood what Kuhn was talking about. I’d run straight into a very stubborn paradigm.”

But Nader was so angry at his scientific opponents that he refused to let them win, and by 2005 other researchers had started to take his side. Multiple papers demonstrated that the act of recall required some kind of protein synthesis—that it was, at the molecular level, nearly identical to the initial creation of a long-term recollection.

To be more specific: I can recall vividly the party for my eighth birthday. I can almost taste the Baskin-Robbins ice cream cake and summon the thrill of tearing wrapping paper off boxes of Legos. This memory is embedded deep in my brain as a circuit of connected cells that I will likely have forever. Yet the science of reconsolidation suggests that the memory is less stable and trustworthy than it appears. Whenever I remember the party, I re-create the memory and alter its map of neural connections. Some details are reinforced—my current hunger makes me focus on the ice cream—while others get erased, like the face of a friend whose name I can no longer conjure. The memory is less like a movie, a permanent emulsion of chemicals on celluloid, and more like a play—subtly different each time it’s performed. In my brain, a network of cells is constantly being reconsolidated, rewritten, remade. That two-letter prefix changes everything.

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