Kharin
Archon
Posts: 407
Reputation: 8.42
Rate Kharin
In heaven all the interesting people are missing.
  
|
 |
Forgetfulness of things past
« on: 2004-04-29 05:42:23 » |
 |
Are scientists on the brink of learning how to erase memories, asks Steven Rose
http://www.guardian.co.uk/life/feature/story/0,13026,1205160,00.html
Thursday April 29, 2004
The Guardian
The great dread of our age is the insidious onset of Alzheimer's disease, the inexorable loss of the very memories that constitute our individuality, our personhood. Big pharmaceutical companies are investing massively in drugs which might retard or even prevent the decline and preserve the failing memory. Yet, suppose our memories are painful, bringing back painful experiences. Might it be possible to erase them, wipe them out as cleanly as pressing the delete button on a computer?
This is the central scientific premise to the new film from the writer of Being John Malkovich and Adaptation, Charlie Kaufman - Eternal Sunshine of the Spotless Mind. The central characters in Kaufman's film aren't exactly blameless vestals, but are recoiling from their unhappy love affair, and so each in turn visits a lab (Lacuna Inc) where neurotechnicians endeavour to wipe out recollection of their troubled relationship. The wordy title is a line from a poem by Alexander Pope; the previous lines run: "How happy is the blameless vestal's lot! The world forgetting, by the world forgot".
The film plays neatly with the enigmatic nature of memory, and the impossibility of separating the continuous stream of our recollections into "files" that can be tidily dissected and removed. Kaufman's interest in the quirks of the human mind has run through some of his previous films (especially Being John Malkovich), and this is the latest in film-makers' current interest in memory and its brain mechanisms. Think of Memento, a Christopher Nolan film in which the central character is unable to form short-term memories as a result of brain damage.
Whether the film-makers knew it or not, their scenario plays into some very current science indeed, and a major debate among neuroscientists. Some even seriously claim they could erase the unpleasant memories of a soldier in battle or a passenger in a train crash.
Memories fascinate scientists, perhaps because they are created in such a complicated fashion. Our senses are continually bombarded with information, some novel, some a repeat of previous experience. Much is ignored, some is remembered for a few minutes only (short-term memory), and a proportion of that is retained more permanently (long-term memory). Within the brain, short-term memories are "held" in the form of transient increases in neurotransmission between nerve cells, notably in a region known as the hippocampus.
But translating short- into longer-term memory involves more permanent structural changes in the connections (synapses) between the nerve cells. This process involves a cascade of biochemical mechanisms, triggered by the initial increases in neurotransmission resulting eventually in the creation of new proteins. These move to the synapse, modifying its structure. My own lab has spent several decades unravelling the details of this cascade in young chickens. There are good reasons to believe that similar molecular processes operate in humans.
Because a sequence of biochemical steps is required to reshape the synapses in the hours after an important event or experience, it is possible to use drugs or inhibitors to disrupt the process. Indeed it is through the use of such specific drugs that many of the steps have been explained.
Say you find out your partner is having an affair. Would it be possible to excise the moment of discovery from your brain? Disrupting neurotransmission in the minutes after the experience, or blocking protein synthesis in the hours that follow does prevent long-term memory being formed, and the result is amnesia of that event. However, blocking protein synthesis outside this critical period leaves memory unimpaired. So the conventional wisdom, at least since the 1960s, has been that once a memory is "fixed" biochemically, it is permanent and cannot be erased.
There have always been some anomalies that have sat uncomfortably with this assumption - for instance, memories don't stay in the hippocampus; it seems that after some days or weeks they are transferred to the cerebral cortex. But the community of memory researchers has mostly tried to ignore such inconvenient data.
Until recently, that is. Four years ago, Karim Nader and his colleagues in New York showed that if an animal was taught a particular task, and then days later was reminded of it by being put in the same context, the memory became labile once more - that means it could be disrupted by protein synthesis inhibitors. It was as if the reminder not only reactivated the old memory, but resulted in an entirely new memory being formed on top of it. Of course, we can intuitively recognise this; when we recall a past event, we are not recalling the event per se, but our memory of it from the last time we recalled it. This is why our autobiographical memories are being reshaped as we go through life.
Nader's report has triggered a minor research industry, focusing on the exact details of the reactivation process and the cellular mechanisms involved - for instance, my own lab has shown that in some crucial ways the biochemical pathways involved differ from those during initial learning, engaging different brain regions and different types of protein. However, it has also raised in some people's minds the serious question of whether it might indeed prove possible to erase unwanted memories in humans. Perhaps in a wish to make headlines, attract grant funds or the interest of biotech companies, they have suggested that such erasure might prove useful in treating one of those newly labelled conditions so beloved of modern psychiatrist: post-traumatic stress disorder.
It seems these days that in the immediate aftermath of any horrific murder or other disaster, grief counsellors are blue-lighted in to treat survivors, relatives and shocked bystanders. Soldiers returning from battle, police and emergency workers, even those recovering from a messy divorce, are being diagnosed with PTSD, whose symptoms are described as recurrent and intrusive distressing recollections of the event, including images, thoughts, perceptions or dreams, acting or feeling as if the traumatic event were recurring. So might it not prove possible to erase the unwanted memory? All that would be necessary, if the animal experiments are right, would be to re-evoke it - perhaps by revisiting the scene - and then inject some biochemical blocker and it would be gone for good. So enthusiastic have some advocates become that even the US President's Bioethics Council has been obliged to consider the possibility.
In Kaufman's film, Lacuna Inc technicians perform the erasure by placing an imaging helmet on the potential erasee's head, locating the site at which the memory is stored, and then zapping it with some type of focused energy source. There are indeed techniques of transcranial brain stimulation being developed, largely funded by the US military, in which focused pulsed magnetic fields are directed at specific brain regions and which temporarily disrupt mental processes. These might serve Lacuna Inc's purposes, but are unlikely to be effective if only because in practice there are unlikely to be specific "sites" for specific memories - rather they are stored, if at all, in the form of distributed networks of synapses. In the film, the attempt at erasure runs into difficulties because other memories get entangled with those they are aiming at, and this is likely to be the consequence of any such attempt based on disrupting the brain's electrical communication systems. This is why the PTSD snake oil salespeople are thinking chemically, of a drug that disrupts neurotransmission across a wide region of the brain.
The trouble is that any such treatment is likely to be pretty toxic and the side-effects more serious than the PTSD they are trying to cure. However, I'd hazard a guess that if the Lacuna Inc name - lacuna means gap or space - is not yet formally registered as a company, it won't be long before some enterprising neurobiotechnologists adopt it and make themselves a tidy living. There are several US companies in the memory drug business, mainly searching for agents that will enhance memory, but their publicists have already been quick to point out that erasure is the flip side of enhancement, and that if they can achieve the one, a quick toss of the pharmacological coin will come up with its opposite.
But I suspect that even leaving the ethical issues to one side, a non-toxic drug is unlikely to have the desired effect. The animal experiments are run in controlled conditions in which both the initial learning experience and its recall are precisely managed by the experimenter. Just how to reactivate the terrors of the multiple experiences of the survivors of a train crash, still less the richness, pain and pleasure of a love affair gone awry beggars imagination. And because the memories concerned are vastly more complex than those involved in a rat anticipating an electric shock, they are going to engage many more neural processes.
To achieve the vestal virgin's happily spotless mind will take more than pharmacology. It may even need such old-fashioned techniques as talking through the problem. Some years ago I ran an experiment which showed that for mildly depressed people psychotherapy could achieve the same effects on the body's biochemistry as could taking a standard anti-depressant drug. The brain/mind is after all a profoundly social organ, and memories are more than mere molecules.
This is why in the film, human attraction triumphs over erased memories and the ex-lovers, meeting again, fall once more for each other, and start over - wiser only in their knowing that they may well fail again.
Hollywood obsession
Hollywood is obsessed with memory, or the loss of it. And although forgetfulness can take different forms, film-makers tend to fixate on just one: retrograde amnesia.
This is when you forget information you already had stored, such as who you are and why you're being scooped out of the Mediterranean by strange fishermen, like Jason Bourne in The Bourne Identity. Or what you're doing posing as a famous psychiatrist about to take charge of the mental asylum: Gregory Peck in Alfred Hitchcock's Spellbound.
As a fictional device, this kind of amnesia offers huge scope for invention. It can also catch out unwary scriptwriters who haven't done their homework, says Sergio Della Sala, an expert in memory disorders at Edinburgh University.
One film he gives full marks for scientific accuracy is Amateur, in which Isabelle Huppert plays an ex-nun and writer of pornography who befriends Thomas, an amnesiac. When Thomas lights up a cigarette she expresses surprise, because although he can remember nothing about his past he can remember how to smoke. "That's accurate," says Della Sala. "People with amnesia do not forget procedures. They can still ride a bike."
Retrograde amnesia is very rare. But there is another kind of forgetfulness that crops up in real life as often as the Gregory Peck variety does in the movies: anterograde amnesia. This is a core symptom of Alzheimer's disease, the most common of dementias, and people who suffer from it have difficulty learning new things. They get stuck in a rut of what they already know.
Anterograde amnesia is not that sexy. It doesn't allow you to slap a new identity on a person and until a few years ago it didn't sell scripts. Then, in 2000, came the film Memento. Guy Pearce plays Leonard, an insurance investigator who, following a blow to the head, is unable to remember anything that happens to him. Since he is looking for his wife's killer, it's important that he logs each new lead. So he compensates for his condition by taking snaps with a Polaroid camera, annotating them, and tattooing important facts on his body.
Della Sala says the scriptwriters force Leonard to repeat a howler: "He keeps saying he has a short term memory problem, but that's wrong, he has anterograde amnesia." In other words, it's not that he loses memories, it's that he can't form them in the first place.
Finding Nemo, on the other hand, is top of Della Sala's amnesia class. In this Walt Disney/Pixar cartoon about fish, the amnesiac Dory is advised to swim through a trench rather than over it, to avoid danger. When she arrives at the trench she says she feels compelled to swim through it, but doesn't know why. "They did their homework," says Della Sala. "She remembers the emotion linked to some particular event, but not the event itself, which is exactly what people with amnesia do."
Laura Spinney
|
Author
Logged
