The women that come to see Deane Aikins, a clinical psychologist at Wayne State University, in Detroit, are searching for a way to leave their traumas behind them. Veterans in their late 20s and 30s, they served in Iraq and Afghanistan. Technically, they’d been in non-combat positions, but that didn’t eliminate the dangers of warfare. Mortars and rockets were an ever-present threat on their bases, and they learned to sleep lightly so as not to miss alarms signaling late-night attacks.

Some of the women drove convoys of supplies across the desert. It was a job that involved worrying about whether a bump in the road was an improvised explosive device, or if civilians in their path were strategic human roadblocks.

On top of all that, some of the women had been sexually assaulted by their military colleagues. After one woman was raped, she helped her drunk assailant sneak back into his barracks because she worried that if they were caught, she’d be disciplined or lose her job.

These traumas followed the women home. Today, far from the battlefield, they find themselves struggling with vivid flashbacks and nightmares, tucking their guns under their pillows at night. Some have turned to alcohol to manage their symptoms; others have developed exhausting routines to avoid any people or places that might trigger painful memories and cause them to re-live their experiences in excruciating detail.

Despite their sometimes debilitating symptoms, the women, who have all been diagnosed with post-traumatic stress disorder (PTSD), are working hard to carry out the tasks of day-to-day living. “They’re trying to get a job or go back to school,” says Aikins. “They’re just trying to get on with their lives.” Aikins is hoping to help the veterans do just that, using what may seem like an unlikely remedy: a cheap, generic pill commonly prescribed for high blood pressure. The drug, a beta blocker called propranolol, has gained attention for its potential to dial down traumatic memories, making them less emotionally upsetting when they’re recalled.

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When these recollections come, the sympathetic nervous system kicks into overdrive; hearts pound, palms sweat, and breathing quickens.

However, promising studies have also stirred controversy, with some bioethicists warning that memory-dulling drugs could have profound, unintended consequences for our psyches and our society. The debate is raising tricky questions about what—and who—memory is for. The European Union’s highest court recently ruled that, at least when it comes to the Internet, we all have the “right to be forgotten” for things no longer relevant. Do we also have the right to forget?





When they’re being formed, memories are fragile. At the neurological level, learning occurs when the connections, or synapses, between two or more neurons grow stronger. This synaptic strengthening involves a cascade of cellular and molecular processes as neurons turn genes on and off, synthesizing new proteins. These changes can take hours and are susceptible to disruption. (That’s why someone with a concussion, for instance, may not remember anything from several hours before the injury.) Over time, however, this flurry of neuronal activity appears to transform transient, short-term memories into stable, long-term ones in a process known as memory consolidation.

During a stressful or frightening event, the body releases a flood of “fight or flight” hormones, including epinephrine in the blood and norepinephrine in the brain. The rush of norepinephrine causes the amygdala, a brain region involved in the processing of emotion, to send signals to parts of the brain that consolidate memories. “What the amygdala does is to say, ‘Make a better, strong memory of whatever happened,’” says James McGaugh, a neuroscientist at the University of California, Irvine.

As a result, emotionally arousing experiences get stamped more firmly into our brains than routine events, such as a weekly trip to the grocery store. Although vivid memories of stressful events can provide important lessons for the future, in a small number of cases these memories become intrusive and disabling, resulting in PTSD. In this disorder, even innocuous environmental stimuli—the sound of a car backfiring, a glimpse of a neighbor who looks vaguely like an assailant—can trigger traumatic memories, as well as the overwhelming fear that accompanied the initial trauma. And when these recollections come, the sympathetic nervous system kicks into overdrive; hearts pound, palms sweat, and breathing quickens, even though the danger has long passed. “It’s this incredibly debilitating sympathetic surge,” Aikins says. Some 7.7 million American adults suffer from PTSD, according to the National Institute of Mental Health.

Two decades ago, scientists began to wonder if they could weaken traumatic memories by suppressing the hormonal rush that accompanies their formation. They turned to propranolol, which was already on the market as a treatment for hypertension and blocks the activity of hormones like epinephrine and norepinephrine. Psychological studies with the drug helped to reveal how stress hormones and the “emotional” amygdala influence memory consolidation. In 1994, McGaugh and Larry Cahill, also a neuroscientist at the University of California, Irvine, reported that healthy subjects who received a dose of propranolol before they heard an upsetting story later recalled fewer details about that story than those who took a placebo. Next, in 2002, neuroscientists reported that emergency room patients who took propranolol within 6 hours of a traumatic event were less likely to experience the heightened emotions and arousal associated with PTSD one month later, compared with people who took placebos.1

The hitch was that in order to interfere with memory consolidation, propranolol needed to be given within hours of a trauma, long before doctors knew whether someone would go on to develop PTSD. But around the same time, studies began to show that memories can once again become fragile when they are recalled. “There’s new encoding happening so that you’re not only playing back the memory, but you’re also updating it,” says Stephen Maren, a neuroscientist at Texas A&M University. “It’s sort of opening this window of opportunity to manipulate the memory, to erase the memory, to dampen it.” After recall, the brain must then reconsolidate the new version of the memory, which requires cellular changes similar to those involved in the initial consolidation.

Perhaps, researchers hypothesized, propranolol could weaken emotional memories if PTSD patients took the drug after they conjured up the details of a painful experience. By blocking the effects of norepinephrine and epinephrine upon recall, propranolol might dampen down activity in the amygdala and disrupt reconsolidation.

Initial tests of this idea have been promising. In these experiments, patients with PTSD are typically given propranolol either shortly before or after describing their traumas in detail. In a 2011 report on three trials, researchers reported that after six propranolol-recall treatment sessions, patients showed a significant decrease in PTSD symptoms.2 Larger clinical trials are now underway, including Aikins’s study, in which female veterans with PTSD will receive either propranolol or a placebo after thinking about their wartime experiences. Four weeks later, Aikins will measure the veterans’ physiological responsiveness and their PTSD symptoms, looking for signs of improvement.

It’s still unclear exactly how propranolol works, but the evidence so far suggests that the drug is not erasing people’s recollections of the facts, but just muting their emotional and physiological responses. In a study of healthy volunteers, subjects who received uncomfortable electric shocks after viewing certain slides were perfectly capable of recalling which images foretold a shock after they’d taken propranolol. But they did not become fearful when they saw the images again, unlike control subjects who took a placebo.3 Propranolol appeared to alter the emotional content of the memory, while sparing fact-based recall.

However, scientists don’t yet know how the drug will alter remembrances of real-world traumas. Although some studies of healthy subjects have found that people given propranolol remember fewer details about a fictional story, researchers theorize that the drug largely spares the facts that comprise declarative memory, particularly when the memory is a powerfully negative one. Anecdotally, Alain Brunet, a psychologist at McGill University, says that forgetfulness has not been a problem among the trauma victims who have participated in his propranolol studies. Patients still remember their traumas—they just seem less distressed by them. Some people with PTSD turn to alcohol or illegal drugs to calm themselves down and ease the pain of their memories; propranolol could provide a safer, more targeted way to do a similar thing.





Vasily Vereshchagin (1842–1904)

From the start, the notion of memory dampening made bioethicists uneasy. Some worried pharmaceutical companies might “medicalize” ordinary bad memories, such as break-ups or workplace embarrassments. Others pointed out that there’s a reason that dangerous events typically prompt such strong emotion—and are engraved so deeply in our minds: They help us remember to avoid similar situations in the future.

Some of the strongest objections came from the President’s Council on Bioethics, created by President George W. Bush, which critiqued “memory-blunting” from seemingly every angle in a 2003 report.4 They suggested that the technology might alter people’s sense of identity and make “shameful acts seem less shameful or terrible acts less terrible.” A criminal could exploit them to ease his own conscience after harming another person. Or, the Council wrote, we might be tempted to start giving these compounds to soldiers to numb the emotion they feel when they kill other human beings in combat.

Finally, the Council argued that memory-blunting should not necessarily be a personal choice, writing: “Strange to say, our own memory is not merely our own; it is part of the fabric of the society in which we live.” To make its point, the Council invoked the Holocaust. Though survivors themselves might benefit from dampening their recollections, the Council suggested society needs them to bear witness, “lest we all forget the very horrors that haunt them.”

To many clinicians, and even other ethicists, the Council’s abstract concerns rang a bit hollow compared to patients—who exist in the here and now—whose suffering could potentially be eased by these compounds. “These are extremely theoretical arguments, and they’re interesting, but when we start talking about PTSD it’s almost irresponsible,” says Stuart Youngner, a bioethicist at Case Western Reserve University. “I thought that the examples that they gave were so outlandish and dystopian and [showed] very little consideration of the suffering of people with PTSD.”

As for the Council’s worry that the drug might be used to absolve people of their guilt over harming others, some psychologists countered that any drug can be misused, and such concerns do not justify abandoning a promising therapy. Further, many of the Council’s fears do not seem to align with scientific reality, researchers said. “Accounts suggesting that propranolol wipes memory are totally exaggerated and unduly alarming,” Brunet says. “This is not what propranolol does.”



Researchers are currently exploring other substances that may be useful for cordoning off the emotional content of a memory. In June, scientists at Emory University discovered that a compound, called osanetant, disrupts the consolidation of fear memories.5 Mice given the drug, which interferes with a gene expressed by certain neurons in the amygdala, were still able to learn the connection between a sound and an electric foot shock, but they displayed less fear when they heard the sound.

As far as a drug that can annihilate specific memories with pinpoint precision is concerned—that still exists only in Hollywood. The techniques and compounds that have shown promise so far seem to exert their effects primarily on the emotional and physiological components of memory, and fear memories in particular.

Even so, they bring us into new territory, and it’s little wonder that the approach has been met with controversy. “Anytime we have the potential to develop a new kind of control over our bodies it makes us uneasy,” says Adam Kolber, a law professor at Brooklyn Law School in New York. He acknowledges that there may indeed be cases in which the drugs pit what’s good for an individual against what’s good for society. For instance, emotionally muting the memory of a violent assault may make it more difficult for victims to persuasively testify against a perpetrator in front of a jury.

However, Kolber adds, that’s no reason to abandon the treatments. He predicts that concerns over memory-dampening technology will eventually fade away, particularly if the therapies end up relieving suffering. “Memory just always seems like something that’s given to us, that we can’t really do anything about,” he says. “It almost feels like it’s not ours to control.” Soon, it will be.





Emily Anthes is a Brooklyn-based science journalist and author of the book Frankenstein’s Cat: Cuddling Up to Biotech’s Brave New Beasts.





References

1. Pitman, R., Sanders, M., Zusman, R., et al. Pilot Study of Secondary Prevention of Posttraumatic Stress Disorder with Propranolol. Biological Psychiatry 51, 189-142 (2002).

2. Brunet, A., Poundja, J., Tremblay, J., et al. Trauma reactivation under the influence of propranolol decreases posttraumatic stress symptoms and disorder: 3 open-label trials. Journal of Clinical Psychopharmacology 31, 547-550 (2011).

3. Kindt, M., Soeter, M., and Vervliet, B. Beyond extinction: erasing human fear responses and preventing the return of fear. Nature Neuroscience 12, 256-258 (2009).

4. President’s Council on Bioethics. Beyond therapy: Biotechnology and the pursuit of happiness (2003).

5. Andero, R., Dias, B., and Ressler, K. A Role for Tac2, NkB, and Nk3 Receptor in Normal and Dysregulated Fear Memory Consolidation. Neuron epub ahead of print (2014).