Gr-isms

It seems like every day Greta gets up in the morning, finds a coin laying around, and announces to the world in her excited voice "Iss my lucky day!" I'm thinking about putting a penny next to her bed every night so her lucky streak will never end.

July 9 - She walks up to me as I'm studying for the law exam, and she says, "Tan you help me?" all exasperated with her arms hanging down. "I tan' t find Lena." So I asked her if she'd checked upstairs, maybe in Daniel's room. With her attitude she said, "I did! It's daok ... bwack ... daok pitch up dere!" stumbling over her words. Then she gave me a big smile and said, "Yizzy teached me dat." Lizzy is definitely her best "cousin buddy" and she's learning things like ' pitch black' from her.

Greta-isms

The other day as Lena and Greta were watching Dora in the other room, I heard them talking to the TV (which is just what Dora wants them to do), and Greta must have answered correctly because Lena yells out, "Mei Mei! that's great! how did you know that?!" Without pause Greta says, "I just knowed it ... wid my powuhs" So matter-of-fact, as if her having powers was so obvious.

More recently, Greta was

Drugs from Mother-Nature

This is likely an incomplete list, but is definitely a starting point for the sake of record-keeping. For me, drug development can be more interesting than the actual drug itself, especially when the development started from a biological source. And maybe after a quick review, you too will appreciate what scientists have accomplished with a little help from the Earth, and you'll have the heart to say thanks to your "Nature" mother next time you use one of these (or something in the same drug class) --

1. Captopril - Brazilian viper venom
2. Exenatide - Gila monster saliva
3. Lovastatin - Aspergillus fungus (also found in oyster mushrooms and red yeast rice)
4. Quinine - Cinchona bark
5. Aspirin - Willow bark and Meadowsweet herb (salicylic acid)
6. Paclitaxel - Yew tree bark

Expecting Excellence

So I was looking at an article today about a teacher (Natalie Munroe) who had supposedly stepped over the line and blogged about her experiences in teaching a high-school English class. Her blog's title is "Where are we going & why are we in this handbasket". The news articles and the comments I read were so nasty that I had to try and find the actual source material. As it turns out, the saying "nothing is as bad as it seems" seems to fit here. She didn't just curse all throughout, and there's no reason to doubt her sincerity and honesty. She seems genuinely interested in teaching and getting through to her students so I say - give her a break. You'll see that from her other blogs - especially the one on "honor". We all know kids many times fit these descriptions, and no names are ever mentioned, so laugh it off and leave it alone. Here's the actual entry that the kids and parents at CB East were so up-in-arms about:

--Also, as the kids get worse and worse, I find that the canned comments don't accurately express my true sentiments about them. So now I pretty much choose "Cooperative in Class" for every kid (or, in some instances, will speak in other codes. For instance, if they talk a lot, I'll put "is easily distracted" or "talks persistently"; if it's a kid that has no personality, I'll put "ability to work independently"). For some kids, though, my scornful feelings reach such fever pitch that I have a hard time even putting "cooperative in class" and have, sadly, had some kids for which none of the comments fit. (Again, this was NOT me. It couldn't have been. I was a delight!!)

Thus, for this blog, I will list the comments I'd like to see added to the canned comment list, as an accurate reflection of what we really want to say to these parents. Here they are, in no particular order:

* Concerned your kid is automaton, as she just sits there emotionless for an entire 90 minutes, staring into the abyss, never volunteering to speak or do anything.

* Seems smarter than she actually is.

* Has a massive chip on her shoulder.

* Too smart for her own good and refuses to play the school 'game' such that she'll never live up to her true potential here.

* Has no business being in Honors.

* A complete and utter jerk in all ways. Although academically ok, your child has no other redeeming qualities.

* Lazy.

* Shy isn't cute in 11th grade; it's annoying. Must learn to advocate for himself instead of having Mommy do it.

* One of the few students I can abide this semester!

* Two words come to mind: brown AND nose.

* Dunderhead.

* Complainer.

* Gimme an A. I. R. H. E. A. D. What's that spell? Your kid!

* There is such a thing as too loud in oral presentations. We shouldn't need earplugs.

* Att-i-tude!

* Nowhere near as good as her sibling. Are you sure they're related?

* I won't even remember her name next semester if I see her in the hall.

* Asked too many questions and took too long to ask them. The bell means it's time to leave!

* Has no business being in Academic.

* Rat-like.

* Lazy asshole.

* Just as bad as his sibling. Don't you know how to raise kids?

* Sneaky, complaining, jerkoff.

* Frightfully dim.

* Dresses like a street walker.

* Whiny, simpering grade-grubber with an unrealistically high perception of own ability level.

* One of the most annoying students I've had the displeasure of being locked in a room with for an extended time.

* Rude, beligerent, argumentative fuck.

* Tactless.

* Weirdest kid I've ever met.

* Am concerned that your kid is going to come in one day and open fire on the school. (Wish I was kidding.)

* I didn't realize one person could have this many problems.

* Your daughter is royalty. (The Queen of Drama)

* Liar and cheater.

* Unable to think for himself.

* I hear the trash company is hiring...

* Utterly loathsome in all imaginable ways.

* I called out sick a couple of days just to avoid your son.

* There's no other way to say this: I hate your kid.

These comments, I think, would serve me well when filling out the cards. Only, I don't think parents want to hear these truths.

Thus, the old addage... if you don't have anything nice to say...

...say "cooperative in class."

Propranolol in PTSD

I remembered this article from a couple years ago. Intriguing how the mind is able to pack away emotion and memory, and then when recalled can alter the original content because of some inexpensive, centrally-acting beta-blocker. Here it is, from July-August 2009:


Rita Magil was driving down a Montreal boulevard one sunny morning in 2002 when a car came blasting through a red light straight toward her. “I slammed the brakes, but I knew it was too late,” she says. “I thought I was going to die.” The oncoming car smashed into hers, pushing her off the road and into a building with large cement pillars in front. A pillar tore through the car, stopping only about a foot from her face. She was trapped in the crumpled vehicle, but to her shock, she was still alive.

The accident left Magil with two broken ribs and a broken collarbone. It also left her with post-traumatic stress disorder (PTSD) and a desperate wish to forget. Long after her bones healed, Magil was plagued by the memory of the cement barriers looming toward her. “I would be doing regular things—cooking something, shopping, whatever—and the image would just come into my mind from nowhere,” she says. Her heart would pound; she would start to sweat and feel jumpy all over. It felt visceral and real, like something that was happening at that very moment.

Most people who survive accidents or attacks never develop PTSD. But for some, the event forges a memory that is pathologically potent, erupting into consciousness again and again. “PTSD really can be characterized as a disorder of memory,” says McGill University psychologist Alain Brunet, who studies and treats psychological trauma. “It’s about what you wish to forget and what you cannot forget.” This kind of memory is not misty and water­colored. It is relentless.

More than a year after her accident, Magil saw Brunet’s ad for an experimental treatment for PTSD, and she volunteered. She took a low dose of a common blood-pressure drug, propranolol, that reduces activity in the amygdala, a part of the brain that processes emotions. Then she listened to a taped re-creation of her car accident. She had relived that day in her mind a thousand times. The difference this time was that the drug broke the link between her factual memory and her emotional memory. Propranolol blocks the action of adrenaline, so it prevented her from tensing up and getting anxious. By having Magil think about the accident while the drug was in her body, Brunet hoped to permanently change how she remembered the crash. It worked. She did not forget the accident but was actively able to reshape her memory of the event, stripping away the terror while leaving the facts behind.

Brunet’s experiment emerges from one of the most exciting and controversial recent findings in neuroscience: that we alter our memories just by remembering them. Karim Nader of McGill—the scientist who made this discovery—hopes it means that people with PTSD can cure themselves by editing their memories. Altering remembered thoughts might also liberate people imprisoned by anxiety, obsessive-compulsive disorder, even addiction. “There is no such thing as a pharmacological cure in psychiatry,” Brunet says. “But we may be on the verge of changing that.”

These recent insights into memory are part of a larger about-face in neuroscience research. Until recently, long-term memories were thought to be physically etched into our brain, permanent and unchanging. Now it is becoming clear that memories are surprisingly vulnerable and highly dynamic. In the lab they can be flicked on or dimmed with a simple dose of drugs. “For a hundred years, people thought memory was wired into the brain,” Nader says. “Instead, we find it can be rewired—you can add false information to it, make it stronger, make it weaker, and possibly even make it disappear.” Nader and Brunet are not the only ones to make this observation. Other scientists probing different parts of the brain’s memory machinery are similarly finding that memory is inherently flexible.

Someday this new science of memory could cure PTSD and other mental traumas. Already it corrodes our trust in what we know and how we know it. It pokes holes in eyewitness testimony, in memoirs, in our most intimate records of truth. Every time we remember, it seems, we add new details, shade the facts, prune and tweak. Without realizing it, we continually rewrite the stories of our lives. Memory, it turns out, has a surprising amount in common with imagination, conjuring worlds that never existed until they were forged by our minds.

On the Trail of the Memory Meme
Neuroscientists have long viewed memory as a kind of neural architecture, a literal physical reshaping of the microstructure of the brain. In the 19th century, the pioneering neuroanatomist Santiago Ramón y Cajal theorized that information was processed in our heads each time an electrical impulse traveled across a synapse, the gap between one nerve cell and the next. Memories were made or altered, he proposed, when structures near the synapse changed.

More than a century later, the textbook description of episodic memory (conscious knowledge of an event) is a more sophisticated version of that same basic idea. Memory formation requires an elaborate chemical choreography of more than a hundred proteins, but the upshot is that sensory information, coded as electrical pulses, zips through neural networks of the brain. The impulses cause glutamate (one of the brain’s main neurotransmitters) to pop out of one nerve cell and travel across the synapse to activate the next by binding to its receptors, chemically active signaling stations on the cell surface. Ultimately the electrical and chemical signals reach the centers of memory, the almond-size amyg­dala and the banana-shaped hippocampus, adjacent structures buried on either side of the brain.

Neuroscientists believe that memory forms when neurons in these key brain structures are simultaneously activated by glutamate and an electrical pulse, a result of everyday sensory experience. The experience triggers a biochemical riot, causing a specialized glutamate receptor, called NMDA, to spring open and allow calcium ions to flood the cells. The ions stimulate dozens of enzymes that reshape the cells by opening up additional receptors and by prompting the formation of more synapses and new protrusions that contain still more receptors and synapses. In aggregate, these changes make neurons more sensitive to each other and put the anatomical scaffold of a memory in place.

Enacting all these changes takes time, and for up to a few hours the memory is like wet concrete—solidifying but not quite set, still open to interference. Once the process is over, though, the memory is said to be “consolidated.” In the textbook description, neuroscientists talk of memory the way geoscientists describe mountains—built through a dynamic process, but once established almost impossible to reshape quickly except by extraordinary means. By the late 1990s, this explanation of memory was so widely accepted by neuroscientists that its major author, Columbia University neuroscientist Eric Kandel, was awarded the Nobel Prize. It seemed that the most important questions about memory had been answered.

No wonder, then, that Nader—at the time a young postdoc studying the neurobiology of fear at New York University—was electrified when he attended one of Kandel’s lectures. “It was so beautiful and so convincing,” Nader says. But he began to wonder: What actually happens when we recall the past? Does the very act of remembering undo what happened? Does a memory have to go through the consolidation process again? Nader asked his adviser, the noted fear researcher Joseph LeDoux, if he could study these questions. LeDoux says his initial response was “Don’t waste our time and money,” but Nader talked him into it, little suspecting just how far this line of research would go.

Meanwhile, doubts about the standard theory of memory were piling up in the world outside the neuroscience lab. In the early 1990s many people began reporting what seemed to be long-buried memories of childhood sexual abuse. These traumatic recollections frequently surfaced with the help of recovered-memory therapy techniques like hypnosis and guided imagery, in which patients are encouraged to visualize terrible experiences. Cognitive scientists suspected that some of these memories were bogus, the unwitting product of suggestion by the therapist. In support of this view, psychologist Elizabeth Loftus, then of the University of Washington, proved how easy it is to implant a false memory, especially one that is plausible. In a famous experiment, she gave volunteers a booklet narrating three true stories of events from their own childhood along with an invented tale that described their getting lost in the mall at age 5. When prompted later to write down all they could remember about the events, 25 percent were sure that all four events had actually happened to them.

Spurred on by the controversy over recovered memory, other cognitive scientists found that false memory is a normal phenomenon. David Rubin, who studies autobiographical memory at Duke University, observed that adult twins often disagree over who experienced something in childhood. Each might believe, for example, that he was the one to get pushed off his bike by a neighbor at age 8. Apparently, even the most basic facts about a past event (such as who experienced it) could be lost.

Even harrowing memories—the so-called flashbulb memories that feel as if they have been permanently seared into the brain—are not as accurate as we think. Less than a year after a cargo plane crashed into an Amsterdam apartment building in 1992, 55 percent of the Dutch population said they had watched the plane hit the building on TV. Many of them recalled specifics of the crash, such as the angle of descent, and could report whether or not the plane was on fire before it hit. But the event had not been caught on video. The “memory” shared by the majority was a hallucination, a convincing fiction pieced together out of descriptions and pictures of the event.

By the late 1990s, hundreds of psychology experiments suggested that the description of memory as a neurally encoded recapitulation of the past was so oversimplified as to completely miss the point. Instead of being a perfect movie of the past, psychologists found, memory is more like a shifting collage, a narrative spun out of scraps and constructed anew whenever recollection takes place. The science of memory was conflicted, with the neurobiological and psychological versions at odds. If a memory is wired into brain cells—a literal engraving of information—then why is it so easy to alter many years after the fact? It took an outsider to connect the dots.

Rewriting the Past
In the hierarchy of memory science, Karim Nader hardly ranked—a lowly postdoc, only 33 years old, and not even a memory researcher. But in 1999, inspired by Kandel’s talk, he set out to satisfy his big questions about how we recall and forget through a simple experiment. Nader tweaked a standard method used in fear research, in which rats are trained to associate a tone with an electric shock to the foot. The animals quickly learn that the sound is bad news. If they hear it weeks later, they freeze in fear. It is an easy way for the experimenter to know that they remember what took place.

Nader trained some rats, then played the tone again 14 days later, prompting them to remember. He also simultaneously injected them with a protein-synthesis inhibitor, which prevents new memory from forming by prohibiting alteration at the synapses. According to the standard model of memory, the chemical should have no effect since the memory of the tone has already consolidated. In reality, the treated rats’ memory disappeared. When Nader sounded the tone again later, the animals did not freeze. LeDoux was won over by this simple but powerful demonstration. In 2000 Nader’s paper on reconsolidation sparked a commotion in the world of memory research. He showed that reactivating a memory destabilizes it, putting it back into a flexible, vulnerable state.

Immediately reconsolidation became a fighting word. The gossip Nader heard terrified him; some of the biggest bigwigs of memory research thought he had made a ludicrous mistake. “I had no idea how much of a backlash there was going to be,” he says. Even so, Nader kept at his experiments, and in the fall of 2001, he was scheduled to present his research at a huge Society for Neuroscience meeting. It would be his moment of truth, his one chance to persuade the field to take his finding seriously. “I knew the old guard was saying, ‘This sucks; it’s all crap,’?” he says. “I knew if I didn’t hit a grand slam, this thing was dead.” The talk drew an overflow crowd of more than a thousand, including the legend himself, Eric Kandel. (“I really wanted to die,” Nader says.)

That day, by addressing the major criticisms of his research, Nader managed to convince his colleagues that memory reconsolidation was at least worth a serious look. Various labs took on the challenge, soon repeating his findings and discovering that many types of memory in many different species reconsolidate. Other groups began teasing out the reconsolidation process molecule by molecule. Nader’s group found that the NMDA glutamate receptor—which solidifies memory—also is involved in destabilizing it. A group led by Sue-Hyun Lee at Seoul National University demonstrated that proteins must be actively dismantled to destabilize a memory, more evidence that the old memory is actually changed as it is recalled.

Brain researchers are still grappling with the implications of this idea, trying to figure out exactly how malleable memory really is. “People are willing to say we have to go back to the drawing board,” says LeDoux, whose group has also continued to study reconsolidation. At the 2008 Society for Neuroscience meeting in Washington, D.C., 43 presentations focused on reconsolidation, and Nader was besieged by students and young researchers eager to talk.

With this new understanding of memory has come the even more startling possibility of new ways to control it: The era of memory treatment has arrived. For Rita Magil, who got just two doses of propranolol over the course of a single day, the results were encouraging. Her heart rate and muscle tension eased while the drug was in her body. She sensed the difference too. “I felt more detached from it,” she says. “I felt that I was relating a narrative rather than describing something right in front of me right now.” After the study was over, the flashbacks returned, though with less intensity. For her, the only real cure was time.

Six-session treatments with a total of 12 doses of propranolol have shown better results. Collaborating with Harvard psychiatrist Roger Pitman, who was the first to try propranolol for post-traumatic stress, the McGill group has treated about 45 PTSD patients, ranging from soldiers to rape victims. Most had been suffering for years. But after the longer treatment, their symptoms declined by half and stayed that way even six months afterward. They still remember what happened, but it is less disturbing. “They say: ‘I’m not thinking about it as much. It just doesn’t bother me as much anymore,’?” Brunet says. As a group, they are considered to be in remission.

The researchers must still prove that the improvement will last. If it does, it could offer rare hope to millions of people with PTSD, a disorder from which only a third completely recover.

Brunet hopes that similar treatments can address other psychiatric problems, too. Anxiety, acquired phobias, and addiction are increasingly described as disorders of emotional memory. An overly powerful fear memory, for example, can crystallize into a phobia, in which a relatively safe experience like flying in a plane is inextricably linked to a feeling of extreme danger. No matter how the phobic person tries, his emotional memory refuses to update itself to incorporate reassuring information. A treatment that restores his emotional memory to a flexible state could help him cope.

Addiction is another kind of pathological remembering, but in this case the memory is pleasurable. Just as adrenaline sears emotional memories into the brain with the help of the amygdala, drugs of abuse enlist the amygdala and the brain’s reward centers to forge unforgettable memories of pleasure. Anything connected to the bliss reawakens the memory, in the form of craving. “When you see someone with a beer and a smoke and you get a craving, you are suffering from reminiscence, from an emotional memory,” Brunet says. Adapting experimental methods of forgetting to addiction might make it easier to quit.

The Reconsolidated Life
While neuroscientists were skeptical of Nader’s findings, cognitive scientists were immediately fascinated that memory might be constantly revamped. It certainly seemed to explain their observations: The home run you hit in Little League? Your first kiss? As you replay these memories, you reawaken and reconsolidate them hundreds of times. Each time, you replace the original with a slightly modified version. Eventually you are not really remembering what happened; you are remembering your story about it. “Reconsolidation suggests that when you use a memory, the one you had originally is no longer valid or maybe no longer accessible,” LeDoux says. “If you take it to the extreme, your memory is only as good as your last memory. The fewer times you use it, the more pristine it is. The more you use it, the more you change it.” We’ve all had the experience of repeating a dramatic story so many times that the events seem dead, as if they came from a novel rather than real life. This might be reconsolidation at work.

Reconsolidation research has helped foster a growing sense that the flexibility of memory might be functional—an advantage rather than a bug in the brain. Reconsolidation might be how we update our store of knowledge, by making old memories malleable in response to new information. “When you encounter a familiar experience, you are remembering the original memory at the same time, and ?the new experience somehow gets blended in,” says Jonathan Lee of the University of Birmingham in England, who recently found evidence for this effect in animals. “That is essentially what reconsolidation is.” The evident purpose of episodic memory, after all, is to store facts in the hope of anticipating what might happen next. From the perspective of survival, constructive memory is an asset. It allows you to pull together scraps of information to simulate the future on the fly.

“The brain knows there is a future,” says neuroscientist Yadin Dudai, head of the department of neurobiology at the Weizmann Institute of Science in Israel, who collaborates with Nader and LeDoux. Facing something new, we want to link the novel information with memories to better interpret the situation. If the side effect is a few mistakes, that is probably a small price to pay. “Having a memory that is too accurate is not always good,” he says.

Put another way, memory and imagination are two sides of the same coin. Like memory, imagination allows you to put yourself in a time and place other than the one we actually occupy. This isn’t just a clever analogy: In recent neuroimaging studies, Harvard psychologist Daniel Schacter has shown that remembering and imagining mobilize many of the same brain circuits. “When people are instructed to imagine events that might happen in their personal future and then to remember actual events in the past, we find extensive and very striking overlap in areas of brain activation,” he says. Other researchers have found that people with severe amnesia lose their ability to imagine. Without memory, they can barely picture the future at all.

The Spotless Mind
Reconsolidation modifies old memories, but other new research points the way toward erasing them wholesale. One technique for blanking out the past, developed by Joe Tsien at the Medical College of Georgia, flows from his studies of memory formation. When calcium floods a neuron as a memory is formed, it turns on an enzyme called CaMKII (calcium/calmodulin-dependent protein kinase). Among many other things, the enzyme responds to signals from NMDA receptors, leading to more receptor activity and stronger signaling throughout the network of cells.

You would think, therefore, that the more CaMKII, the more robust a memory would be. But in experiments with mice, Tsien has found there is a limit. If he drives CaMKII above the normal limit while the animal is actively remembering an experience, the memory simply vaporizes, as the connections between the cells suddenly weaken. The effect happens within minutes, and it is permanent and selective, affecting the recalled memory while leaving the others unchanged. Indeed, when Tsien trained a mouse to fear both an unfamiliar cage and a particular tone, then pumped up CaMKII while the mouse was in the cage, it forgot the cage-fear memory but not the tone-fear memory. “At the time the memory was retrieved, it disappeared,” he says. “It erases the memory being recalled. It is feasible that by manipulating specific molecules, we can selectively alter memories in the brain.”

Todd Sacktor, a professor of physiology, pharmacology, and neurology at the State University of New York Downstate Medical Center in Brooklyn, has found a blunter but more powerful technique that can eradicate whole categories of memory. He studies protein kinase M-zeta (PKMzeta), which is involved in memory maintenance. As calcium rushes into a memory neuron, PKMzeta is synthesized, linking up with spare glutamate receptors and dragging them to the synapse, where memory construction occurs. With more receptors at the synapse, signals are boosted and amplified and the memory persists.

When Sacktor deactivated PKMzeta with a compound called zeta-inhibitory peptide (ZIP), he got a spectacular response: total amnesia for one type of memory. Rats that had learned a day or a month before to avoid part of a platform that was rigged with electric shock forgot everything they knew about the location generating the jolt. “You inhibit the PKMzeta and those glutamate receptors float away very, very fast,” he says. “As a result, the memory is lost—very, very fast.”

Certain types of memory are encoded in different brain areas, and depending on where Sacktor injects the inhibitor in his animals, he can zap away different categories of memory. In the hippocampus, he erases memory for spatial locations like the platform; in the amygdala, fear memories; in the insular cortex, memories of nauseating taste. Very rarely, Sacktor says, neurosurgeons remove nerve clusters to help disturbed psychiatric patients who do not respond to any other treatment. His research may eventually provide a way to erase memory without causing damage.

The implications are staggering. If stored memories were inscribed in the brain, it is hard to imagine how flipping one chemical switch could erase them so quickly. “It really is a paradigm shift in how people think about long-term memories,” Sacktor says. In the old view, erasure should cause permanent brain damage as the synapses are ripped apart. Instead, Sacktor’s rats’ brains remain intact. Once the ZIP treatment wears off, the animals behave and even learn normally again. “It’s like wiping a hard disk,” he says.

ZIP is nowhere near ready for human use. First, the compound would have to be made activity-dependent in order to target specific memories. You would also have to find a way to get it to the right spot in the brain without using a needle. People are clamoring to be test subjects anyway. When Sacktor’s study first came out in 2006, people, especially rape survivors, tracked him down, imploring him to eradicate their painful memories. “They were suffering,” he says. “They couldn’t work or have relationships. Some of them wanted everything erased.” They didn’t care that it would also vaporize all they had ever known.

Benevolent Forgetting
If you feel that you’ve heard this story before, there’s a reason. Moviemakers love the idea of erasing memory, and they work a consistent theme: If you try to undo the past, you pay the price. Nader’s research supposedly inspired the 2004 movie Eternal Sunshine of the Spotless Mind, in which Jim Carrey and Kate Winslet both pay to have memories of their painful love affair obliterated. Needless to say, it makes them both miserable. But not as miserable as Arnold Schwarzenegger’s character in Total Recall, from 1990, in which he learns that his real memories have been erased, that his life is a fake, and that his faux wife, played by Sharon Stone, is trying to kill him.

You don’t have to be a rape survivor or a soldier to have memories you would rather forget. For most people, though, unpleasant memories also serve as a guide. Indeed, some fear the consequences of undermining appropriately bad memories—say, allowing a murderer to forget what he did. Members of the President’s Council on Bioethics warn that altering the memory of a violent crime could unleash moral havoc by lifting the repercussions of malice. “Perhaps no one has a greater interest in blocking the painful memory of evil than the evildoer,” their report cautions.

Beyond all this, memory is the essence of who we are. Eternal Sunshine of the Spotless Mind is difficult to watch as Carrey’s character flails around in confusion and loss. His fear and desperation may be a realistic portrayal of what it would be like to erase your memory: basically, a waking nightmare. Memory is how you know who you are, how you point yourself toward a destination. We already know that people with Alzheimer’s disease do not feel liberated. They feel utterly lost.

Thankfully, Nader and Brunet’s studies suggest much more benevolent possibilities. If he had received reconsolidation therapy, Carrey’s character would not have forgotten Winslet’s. He simply wouldn’t care that much about her anymore. He would be able to look at his failed relationship as if through the wrong end of a telescope. What is on the other side is still visible, but it is tiny and far away.

That is basically what all these scientists hope to do. Nader, Brunet, and Pitman are now expanding their PTSD study with a new, $6.7 million grant from the U.S. Army, looking for drugs that go beyond propranolol. They are increasingly convinced that reconsolidation will prove to be a powerful and practical way to ease traumatic memories. Sacktor also believes that some version of the techniques they apply in the lab will eventually be used to help people. Most recently, LeDoux’s lab has figured out a way to trigger reconsolidation without drugs to weaken memory, simply by carefully timing the sessions of remembering. “The protocol is ridiculously simple,” LeDoux says.

None of these researchers are looking to create brain-zapped, amoral zombies—or even amnesiacs. They are just trying to take control of the messy, fragile biological process of remembering and rewriting and give it a nudge in the right direction. Brunet’s patients remember everything that happened, but they feel a little less tortured by their own pathological powers of recollection. “We’re turning traumatic memories into regular bad memories,” Brunet says. “That’s all we want to do.”

And here's a similar article from Smithsonian:

Jan. 17, 1961: Eisenhower's Farewell Address

By Dwight D. Eisenhower

Good evening, my fellow Americans.

First, I should like to express my gratitude to the radio and television networks for the opportunities they have given me over the years to bring reports and messages to our nation. My special thanks go to them for the opportunity of addressing you this evening.

Three days from now, after half a century in the service of our country, I shall lay down the responsibilities of office as, in traditional and solemn ceremony, the authority of the presidency is vested in my successor. This evening, I come to you with a message of leave-taking and farewell and to share a few final thoughts with you, my countrymen.

Like every other citizen, I wish the new president, and all who will labor with him, Godspeed. I pray that the coming years will be blessed with peace and prosperity for all.

Our people expect their president and the Congress to find essential agreement on issues of great moment, the wise resolution of which will better shape the future of the nation. My own relations with the Congress, which began on a remote and tenuous basis when, long ago, a member of the Senate appointed me to West Point, have since ranged to the intimate during the war and immediate postwar period and finally to the mutually inter-dependent during these past eight years. In this final relationship, the Congress and the administration have, on most vital issues, co-operated well, to serve the national good, rather than mere partisanship, and so have assured that the business of the nation should go forward. So, my official relationship with the Congress ends in a feeling—on my part—of gratitude that we have been able to do so much together.

We now stand ten years past the midpoint of a century that has witnessed four major wars among great nations. Three of these involved our own country. Despite these holocausts, America is today the strongest, the most influential, and most productive nation in the world. Understandably proud of this pre-eminence, we yet realize that America’s leadership and prestige depend, not merely upon our unmatched material progress, riches, and military strength, but on how we use our power in the interests of world peace and human betterment.

Throughout America’s adventure in free government, our basic purposes have been to keep the peace, to foster progress in human achievement, and to enhance liberty, dignity, and integrity among peoples and among nations. To strive for less would be unworthy of a free and religious people. Any failure traceable to arrogance, or our lack of comprehension or readiness to sacrifice, would inflict upon us grievous hurt, both at home and abroad.

Progress toward these noble goals is persistently threatened by the conflict now engulfing the world. It commands our whole attention, absorbs our very beings. We face a hostile ideology global in scope, atheistic in character, ruthless in purpose, and insidious in method. Unhappily, the danger it poses promises to be of indefinite duration. To meet it successfully, there is called for, not so much the emotional and transitory sacrifices of crisis, but rather those which enable us to carry forward steadily, surely, and without complaint the burdens of a prolonged and complex struggle—with liberty the stake. Only thus shall we remain, despite every provocation, on our charted course toward permanent peace and human betterment.

Crises there will continue to be. In meeting them, whether foreign or domestic, great or small, there is a recurring temptation to feel that some spectacular and costly action could become the miraculous solution to all current difficulties. A huge increase in newer elements of our defenses; development of unrealistic programs to cure every ill in agriculture; a dramatic expansion in basic and applied research—these and many other possibilities, each possibly promising in itself, may be suggested as the only way to the road we wish to travel.

But each proposal must be weighed in the light of a broader consideration: the need to maintain balance in and among national programs, balance between the private and the public economy, balance between the cost and hoped for advantages, balance between the clearly necessary and the comfortably desirable, balance between our essential requirements as a nation and the duties imposed by the nation upon the individual, balance between actions of the moment and the national welfare of the future. Good judgment seeks balance and progress. Lack of it eventually finds imbalance and frustration. The record of many decades stands as proof that our people and their government have, in the main, understood these truths and have responded to them well, in the face of threat and stress.

But threats, new in kind or degree, constantly arise. Of these, I mention two only.

A vital element in keeping the peace is our military establishment. Our arms must be mighty, ready for instant action, so that no potential aggressor may be tempted to risk his own destruction. Our military organization today bears little relation to that known of any of my predecessors in peacetime, or, indeed, by the fighting men of World War II or Korea.

Until the latest of our world conflicts, the United States had no armaments industry. American makers of plowshares could, with time and as required, make swords as well. But we can no longer risk emergency improvisation of national defense. We have been compelled to create a permanent armaments industry of vast proportions. Added to this, three and a half million men and women are directly engaged in the defense establishment. We annually spend on military security alone more than the net income of all United States corporations.

Now this conjunction of an immense military establishment and a large arms industry is new in the American experience. The total influence—economic, political, even spiritual—is felt in every city, every statehouse, every office of the federal government. We recognize the imperative need for this development. Yet we must not fail to comprehend its grave implications. Our toil, resources, and livelihood are all involved. So is the very structure of our society.

In the councils of government, we must guard against the acquisition of unwarranted influence, whether sought or unsought, by the military-industrial complex. The potential for the disastrous rise of misplaced power exists and will persist. We must never let the weight of this combination endanger our liberties or democratic processes. We should take nothing for granted. Only an alert and knowledgeable citizenry can compel the proper meshing of the huge industrial and military machinery of defense with our peaceful methods and goals, so that security and liberty may prosper together.

Akin to and largely responsible for the sweeping changes in our industrial-military posture has been the technological revolution during recent decades. In this revolution, research has become central; it also becomes more formalized, complex, and costly. A steadily increasing share is conducted for, by, or at the direction of the federal government.

Today, the solitary inventor, tinkering in his shop, has been overshadowed by task forces of scientists in laboratories and testing fields. In the same fashion, the free university, historically the fountainhead of free ideas and scientific discovery, has experienced a revolution in the conduct of research. Partly because of the huge costs involved, a government contract becomes virtually a substitute for intellectual curiosity. For every old blackboard there are now hundreds of new electronic computers. The prospect of domination of the nation’s scholars by federal employment, project allocations, and the power of money is ever present—and is gravely to be regarded.

Yet in holding scientific research and discovery in respect, as we should, we must also be alert to the equal and opposite danger that public policy could itself become the captive of a scientific-technological elite.

It is the task of statesmanship to mold, to balance, and to integrate these and other forces, new and old, within the principles of our democratic system—ever aiming toward the supreme goals of our free society.

Another factor in maintaining balance involves the element of time. As we peer into society’s future, we—you and I, and our government—must avoid the impulse to live only for today, plundering for our own ease and convenience the precious resources of tomorrow. We cannot mortgage the material assets of our grandchildren without risking the loss also of their political and spiritual heritage. We want democracy to survive for all generations to come, not to become the insolvent phantom of tomorrow.

During the long lane of the history yet to be written, America knows that this world of ours, ever growing smaller, must avoid becoming a community of dreadful fear and hate, and be instead a proud confederation of mutual trust and respect. Such a confederation must be one of equals. The weakest must come to the conference table with the same confidence as do we, protected as we are by our moral, economic, and military strength. That table, though scarred by many past frustrations, cannot be abandoned for the certain agony of the battlefield.

Disarmament, with mutual honor and confidence, is a continuing imperative. Together we must learn how to compose differences, not with arms, but with intellect and decent purpose. Because this need is so sharp and apparent, I confess that I lay down my official responsibilities in this field with a definite sense of disappointment. As one who has witnessed the horror and the lingering sadness of war, as one who knows that another war could utterly destroy this civilization which has been so slowly and painfully built over thousands of years, I wish I could say tonight that a lasting peace is in sight.

Happily, I can say that war has been avoided. Steady progress toward our ultimate goal has been made. But so much remains to be done. As a private citizen, I shall never cease to do what little I can to help the world advance along that road.

So, in this, my last good night to you as your president, I thank you for the many opportunities you have given me for public service in war and in peace. I trust in that service you find some things worthy. As for the rest of it, I know you will find ways to improve performance in the future.

You and I, my fellow citizens, need to be strong in our faith that all nations, under God, will reach the goal of peace with justice. May we be ever unswerving in devotion to principle, confident but humble with power, diligent in pursuit of the nation’s great goals.

To all the peoples of the world, I once more give expression to America’s prayerful and continuing aspiration: we pray that peoples of all faiths, all races, all nations, may have their great human needs satisfied; that those now denied opportunity shall come to enjoy it to the full; that all who yearn for freedom may experience its spiritual blessings; that those who have freedom will understand, also, its heavy responsibilities; that all who are insensitive to the needs of others will learn charity; that the scourges of poverty, disease, and ignorance will be made to disappear from the earth; and that, in the goodness of time, all peoples will come to live together in a peace guaranteed by the binding force of mutual respect and love.

Now, on Friday noon, I am to become a private citizen. I am proud to do so. I look forward to it.

Thank you, and good night.

Dwight D. Eisenhower (1890-1969) was the 34th president of the United States.