Sweet forgetting: a pill to ease painful memories
ANNE MCILROY
From Saturday's Globe and Mail
For three years, Rita Magil relived the scene in her nightmares and in daytime flashbacks.
?I could see two cement pillars that my car was being propelled towards,? she says. ?I remember going towards them, being unable to stop the car, powerless and totally out of control, and watching my death coming.?
In July, 2002, Ms. Magil was cruising down Sherbrooke Street in Montreal when another vehicle smashed into her white Fiero, pushing it over the sidewalk toward the pillars that mark the front entrance of the Imperial West apartments, near Kensington Avenue.
In the months and years that followed, the memory left her stressed and shaken when it surfaced, unbidden, day and night.
As her physical wounds healed, the occupational therapist tried to get on with life. She bought another car, forced herself to drive by the intersection where the accident happened and tried not to be overly cautious behind the wheel. But the crash continued to haunt her.
Then, last year, she saw a newspaper ad seeking volunteers for an experiment on post-traumatic stress syndrome.
The experiment, run by McGill University researcher Alain Brunet at the Douglas Hospital, aimed to replicate a revolutionary finding made in animal studies ? that memories of traumatic events can be altered with the use of drugs.
The idea is controversial, because our memories make us who we are. Ethicists worry that one day criminals will be able to pop a pill and remove the shame or guilt from their memories, or even the details of a murder or rape. There is concern that dictators might be able to create drones, with no memories of their pasts.
We have come to accept the notion that we can tinker with mood or personality through pharmaceuticals, and we know that drugs such as alcohol can wipe out the memory of a bender. But the notion of deliberately altering a specific memory seems more disturbing.
Dr. Brunet and his colleagues stress that they aren't trying to erase or even edit traumatic memories. They want to dampen their emotional component, so people will be able to recall what happened without constantly reliving the associated panic, humiliation or pain.
Their theory is that the emotional memory of an incident ? what Ms. Magil was feeling as she faced death ? is stored in a different part of the brain than the details of flying over the curb toward the pillars, wiggling her toes to see if she was paralyzed, hearing the other driver shrieking, ?Is she dead, is she dead??
Dr. Brunet knew the experiment was a long shot. It is one thing to give rats a drug that makes them forget they have been given an electric shock. It's quite another to pharmaceutically tamper with human subjects' long-term recall.
?We were skeptical when we began,? he says.
People remember emotional events, whether terrifying or joyful, more vividly than everyday experiences. Your wedding day will stand out more than the dinner you ate in front of the television a few years into your marriage.
It seems that the stress hormones the body produces during emotionally charged events help imprint memories in a particularly powerful way.
Think about it from an evolutionary perspective: If you retain a strong memory of the terror of being bitten by a snake, you are more likely to take evasive action the next time you see something slithering through the grass.
Even hearing about a traumatic event seems to improve memory. In California, researchers James McGaugh and Larry Cahill showed one group of volunteers slides that were accompanied by a dramatic story about a boy being hit by a car and nearly losing his leg. A second group saw the same images, but were told a less sensational tale.
The group that heard the more gripping narrative were better at remembering the details of the pictures they had been shown.
In a follow-up experiment, volunteers who listened to the more emotional story were given a beta blocker called propranolol, which lowers blood pressure by reducing the effects of the stress hormone adrenaline.
This time, the volunteers told the story about the boy weren't any better at remembering the details of the slides than the other group. The beta blocker appeared to dampen the memory-heightening effect of adrenaline.
This led Harvard University researcher Roger Pitman to try propranolol on people brought to the emergency ward of a Boston Hospital after traumatic experiences such as being stabbed, knocked over by a bike courier or hit by a car.
In the days after a life-threatening event, most people relive it repeatedly. When they think of it, the heart beat increases. They start to sweat, or feel paralyzed; they are preparing to fight or to flee, just as they were during the original incident.
Over time, for most people, this effect lessens and eventually disappears. But not for the estimated 10 to 30 per cent who go on to develop post-traumatic stress disorder.
Dr. Pitman thought giving propranolol to people soon after a traumatic experience might help. And a preliminary experiment found that the beta blocker indeed offered a protective effect against post-traumatic stress disorder.
Dr. Brunet, a clinical psychiatrist, did a similar experiment in co-operation with a French colleague and got similar results: The drug appeared to interfere with what researchers call memory consolidation ? in which fresh memories are transferred from the hippocampus to long-term storage in the vault of the cerebral cortex.
It would be a different task to dampen memories that were already in storage. Both Dr. Brunet and Dr. Pitman were curious to test if propranolol could do it.
For years, researchers had believed that long-term memories were immutable. Then Dr. Brunet's colleague at McGill, Karim Nader, did experiments in rats that suggested that old memories can be changed, perhaps even erased.
Believing that new brain proteins are essential for storing or restoring memories, Dr. Nader injected an antibiotic that blocks the production of protein directly into the brains of rats (something you could never do in humans).
The process seemingly was able to make the rats forget that they had been given an electric shock. They no longer responded to cues they had been conditioned to take as signs they were about to be zapped ? either a musical tone or the sight of a box where the mild current was previously administered.
Dr. Nader's experiments offered evidence that when an event is recalled from memory, it becomes more fragile, more open to editing. This process is called reconsolidation, and scientists now believe it may exist to allow us to update our memories, to add information that we have learned over time.
After his work with rats was published in the prestigious journal Nature, other scientists doubted that a similar experiment would work in humans.
But Dr. Brunet was intrigued by Dr. Nader's results, and at the suggestion of Dr. Pitman, the two designed an experiment and began advertising for volunteers suffering from post-traumatic stress disorder. Ms. Magil called and was accepted into the study, along with 18 other people who had experienced traumatic events in the past. On average, the incidents took place 10 years ago.
The next step was difficult, for the researchers as well as the subjects. Dr. Brunet asked each of them to write an account of their own personal horror. Some had been raped, others had been abused as children. Some, like Ms. Magil, had been in serious car accidents.
?It is always hard,? he says. ?You try to do it in a gentle way.?
Ms. Magil was crying as she wrote out her story; she found it hard to keep her hand steady. Then Dr. Brunet gave her a pill.
She didn't know if it was propranolol or a placebo ? half the participants were given the real thing, which has been used for 25 years to lower blood pressure, while the other half were given a sugar pill.
One week later, Ms. Magil was back at the Douglas Hospital to hear her ?trauma script? ? a taped account of her accident, based on what she had written, but narrated by a member of the scientific team. As she listened, researchers used electrodes to measure signs of stress ? heart rate, sweat, muscle tension in her face. She was asked to imagine the accident as vividly as possible, as if it was recurring.
?It is a sunny summer day, July 2002. Around noon,? the voice on the tape said. ?You are driving you car eastward on Sherbrooke when suddenly you get hit by a car. Your car is pushed to the other side of the street. Your heart races, your chest feels constricted. You see the white concrete pillar of an apartment, and your unavoidable approach and ultimate impact. You say to yourself, ?I am dying.' You panic about having a spinal injury. Help seems to be taking forever.?
It was the scene from her nightmares and flashbacks. But this time, she didn't react. ?I wasn't anxious,? she says.
She told the researchers that maybe she was the wrong person for the experiment ? maybe she didn't have post-traumatic stress disorder after all. They told her not to worry.
She had, in fact, been given the beta blocker. And it had worked. The nightmares and the flashbacks were banished. She could summon the memory of the accident without being overwhelmed.
?I felt that I had control over the emotion. It wasn't spontaneous. It didn't come over me, unsolicited.?
Today, she can sit happily near the corner of Sherbrooke and Kensington, beside one of those pillars that loomed so menacingly in her memory, blowing flowers in the wind for a photographer.
?I have no emotional reaction,? she says, ?Although I am surprised to see that the pillars are so small, so non-threatening.?
Dr. Nader believes that his Nature article on reconsolidating memories may have inspired the 2004 movie The Eternal Sunshine of the Spotless Mind, in which the characters played by Jim Carrey and Kate Winslet hire technicians to wipe their tumultuous love affair out of their heads.
Some researchers worry this work eventually will turn Hollywood fantasy into reality: What if criminals could delete their offences from their memory banks? Worse, what if victims ? anxious to get over trauma ? erased the details essential for a conviction?
Nobel Prize winner Eric Kandel, who studies memory at Columbia University in New York, has warned that drugs could be used to wipe away guilt and remorse.
A report from the President's Council on Bioethics in the U.S. has expressed similar concerns: ?Changing the content of our memories, or altering their emotional tonalities, however desirable to alleviate guilty or painful consciousness, could subtly reshape who we are.?
Would you be a worse person if you didn't remember the remorse you felt over doing wrong? How would people learn from mistakes, including in relationships, if they couldn't remember how they felt?
Empathy might even be at risk: If you couldn't recall, for example, the pain of being fired, would you be able to put yourself in the place of a friend who had lost her job ? much less the plights of strangers covered in the news?
It's conventional wisdom to think that people are stronger for working through traumatic events and coming to terms with what happened, even if it requires therapy, taking other drugs, like antidepressants, or the passage of time.
But Dr. Nader says the goal of the research is not to create spotless minds. ?I think those issues are largely misplaced,? he says.
Rather, the aim is specifically to help people with post-traumatic stress disorder from being overwhelmed by their memories.
?We are not getting rid of any memories ? we just want to tone them down a bit.?
He is doubtful that the technology ever will become so advanced that people will be able to pick and choose what they want to forget.
If Dr. Brunet's theory is correct, what the beta blocker did for Ms. Magil was to turn down the intensity of the emotional memory stored in an almond-shaped part of her brain known as the amygdala, which scientists believe plays a key role in processing emotional information.
Memories stored there aren't verbal or linear, Dr. Brunet says. And they are triggered, rather then summoned.
?A person without an amygdala would be like Spock,? he says.
And Ms. Magil is nowhere near becoming the Vulcan character on Star Trek, who felt no emotions. ?I'm not apathetic,? she says.
She still recalls the details of the accident, and how she felt. She remembers being grateful to the rescuers who cut her out of the crumpled car. She hasn't forgotten the pain from her broken ribs and collar bone, of feeling lucky to be alive. She is still angry at the woman in the other vehicle, who never phoned to see if she had lived or died.
This is what the researchers were hoping for. They wanted to transform overwhelming, traumatic memories into ?normal, horrible memories,? Dr. Nader says.
Not all of the participants in the study improved as much as Ms. Magil. But their physical responses to their ?trauma script? were less elevated than the control group, and those who had taken the drug reported an average reduction of nearly 20 per cent in symptoms afterward.
The sample in this experiment was too small to conclude that propranolol was a success. But Dr. Brunet has begun a second, much larger study, with a longer follow-up period.
And what about side effects? Dr. Brunet says there was a remote possibility that Ms. Magil and the others might inadvertently alter emotional memories of happy events.
But while he understands the concerns critics raise over the science of forgetting, he says such fears won't stop him from working with people whose lives have been compromised by their memories ? in ways healthy people may find difficult to understand.
?You can't think of all the risks,? he says. ?I'm sure there are people who will find uses that are not in people's best interests.?
Ms. Magil, for one, is convinced that propranolol was in her best interest.
?I talk about the accident. There is no memory erasure. The only difference is I have no emotional distress when I talk about it or think about it.?
Her mind may not be bathed in eternal sunshine, but a terrible storm has passed.
Anne McIlroy is The Globe and Mail's science reporter.
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