by Tim Folger
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, allow ing 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."
JOHN COLAPINTO Brain Games
FROM The New Yorker
ONE MORNING IN JANUARY, a tall, gray-haired man whom I will call Arthur Jamieson arrived at the Mandler Hall psychology building at the University of California, San Diego, in La Jolla. Jamieson is seventy years old and lives in the Midwest. He is a physician and an amateur cellist and has been married for forty-seven years. He also suffers from a rare and bewildering condition called apotemnophilia, the compulsion to have a perfectly healthy limb amputated—in his case, the right leg, at midthigh. He had come to La Jolla not to be cured of his desire (like most people with the syndrome, he believed that relief would come only with the removal of the limb) but to gain insight into its cause. To that end, he had scheduled a meeting with Dr. Vilayanur S. Ramachandran, an Indian-born behavioral neurologist who is the director of the Center for Brain and Cognition at UCSD and who has a reputation among his peers for being able to solve some of the most mystifying riddles of neuroscience.
Ramachandran, who is fifty-seven, has held prestigious fellowships at All Souls College in Oxford and at the Royal Institution in London. His 1998 book, Phantoms in the Brain, about rare neurological disorders, was adapted as a miniseries on BBC television, and the Indian government recently accorded him the title Padma Bhushan, the country's third-highest civilian honor. But it is the awe that he inspires in his scientific colleagues that best illuminates his position in neuroscience, where the originality of his thinking and the simple elegance of his experiments give him a unique status. "Ramachandran is a latter-day Marco Polo, journeying the silk road of science to strange and exotic Cathays of the mind," Richard Dawkins once wrote. Eric Kandel, the Columbia University neuroscientist whose work on the physiological basis of learning and memory earned him a Nobel Prize in 2000, invoked two pioneering brain scientists to describe Ramachandran's contribution to the field: "He is a continuation of a tradition in neurology that goes back to the nineteenth century, to giants like Broca and Wernicke, who gave us, from studying clinical material, enormous insights into the functioning of the human mind."
Ramachandran, who has dark skin, curly black hair, and a mustache, cultivates a slightly rebellious image, often wearing dark polo shirts and a black leather jacket. However, when he meets with patients he tends to dress more conservatively. The day that he met with Jamieson, he was wearing a wool blazer and a tie. He greeted Jamieson in his office, whose décor reflects Ramachandran's many interests outside neurology: Darwinian evolution, plate tectonics, Indian art, Victorian medicine, paleontology, optical illusions. A four-foot stone sculpture of the god Shiva stood behind his desk. On one wall, there was a 300-million-year-old fossil of a mesosaur, a freshwater reptile found only in South America and Africa (and which, as Ramachandran likes to explain, is a central piece of evidence in the theory of continental drift). On a side table was an array of antique scientific items: a brass Gilbert telescope, a hand-cranked electrical machine for curing "nervous diseases," a box of glass tubes containing Victorian homeopathic medicines. Another table held what appeared to be a smoothly sanded wooden sculpture of a woman's pelvis. Ramachandran often tells visitors that the object is a Henry Moore before revealing, with a booming laugh, that it is actually a specimen of the world's largest seed, from the coco-de-mer palm.
Ramachandran listened closely as Jamieson talked about his condition. In a specialty that today relies chiefly on the power of multi-million-dollar imaging machines to peer deep inside the brain, Ramachandran is known for his low-tech method, which often involves little more than interviews with patients and a few hands-on tests—an approach that he traces to his medical education in India, in the 1970s, when expensive diagnostic machines were scarce. "The lack of technology actually forces you to be ingenious," he told me. "You have to rely on your clinical acumen. You have to use your Sherlock Holmes-like deductive abilities to figure things out."
Ramachandran suspected that apotemnophilia was a neurological disorder and not, as Freudians have theorized, a psychological syndrome associated with repressed sexual desires. After interviewing several apotemnophiliacs—Jamieson is the fifth person with the disorder whom he has studied—Ramachandran was struck by the fact that all of them said they became aware of the compulsion in early childhood, that it centered on a particular limb (or limbs), that they could draw a line at the ex
act spot where they wanted the amputation to occur, and that they attached little or no erotic significance to the condition. Furthermore, none rejected the limb as "not belonging" to them, as some stroke victims do in the case of a paralyzed arm or leg, and as Ramachandran had predicted they might. Instead, they said that the limb over-belonged to them: it felt intrusive. "If you talk to independent apotemnophiliacs, they say the same bloody things," Ramachandran told me. "'The line for cutting is here.' 'It started in early childhood.' 'It's over-present.' They're not crazy."
Jamieson, who was born and raised in New York City, first remembers having an unusual relationship with his right leg when, at around the age of seven, he was waiting for a bus. He found himself thinking that if he stuck out his leg it would be crushed and severed by the bus. "What came to me was not 'No, I don't want to do that' but 'How would I ever explain this?'" he told Ramachandran. In recounting his childhood memories, he said, "One of the things that's astonishing to me is how clear these recollections are."
"These things are very salient," Ramachandran said in a resonant baritone, which carries a British-inflected Indian accent. "It's interesting to contrast these very clear-cut descriptions with these vague, Freudian notions about this whole phenomenon—that it's primarily connected with sexual stuff."
"Yeah," Jamieson said with disgust. "I've got no desire to cozy up to anyone with a stump. It's psychobabble."
Asked where he would make the cut line for the amputation, Jamieson unhesitatingly drew an index finger across the middle of his right thigh. As to whether he felt that his leg didn't "belong" to him, Jamieson was emphatic. "Somehow, for me, that just doesn't compute, that kind of language," he said. "I have always been fascinated by amputation and wished that I had one. Why? Who the hell knows?"
***
Ramachandran is one of a dozen or so scientists and doctors who, in the past thirty years, have revolutionized the field of neurology by overturning a paradigm that dates back more than a hundred years: that of the brain as an organ with discrete modules (for vision, touch, pain, language, memory, and so on) that are fixed early in life and immutable. Neurological syndromes, such as paralysis from stroke, forms of mental illness, and the perception of pain in an amputated limb (a phenomenon known as phantom-limb pain), were considered largely untreatable. But Ramachandran and other researchers have shown that the brain is what scientists call "plastic"—it can reorganize itself. Not only are different regions of the brain engaged in ongoing communication with one another, with the body, and with the surrounding world; these relationships can be manipulated in ways that can reverse damage or dysfunction previously believed to be permanent. Ramachandran's work with patients at UCSD has led to one of the most effective treatments for chronic phantom-limb pain and to a new therapy for paralysis resulting from a stroke. (In both instances, his treatment involves only a five-dollar household mirror.) It has also provided suggestive insights into the physiological cause of such mystifying syndromes as autism.
Until the mid-1990s, Ramachandran's specialty was visual perception, but he had been interested in brain science since his days as a medical student in India. He made the switch to neurology in midcareer. "A scientist with that kind of creativity—it's rare," says Michael Merzenich, a neuroscientist at the University of California, San Francisco, whose experiments with monkeys in the 1980s provided much of the groundwork for understanding brain plasticity. "It's usually not allowed, in some sense. You're not supposed to be a butterfly like that."
Little about Ramachandran's scientific career has been conventional. He was born in Tamil Nadu, in southern India, to a Hindu family of the Brahman caste. His grandfather, Alladi Krishnaswamy Iyer, was the attorney general of Madras and a framer of India's constitution. Ramachandran's father was a diplomat in the United Nations. However, science ran in the family. His mother had a master's degree in mathematics; one uncle was a professor of optics at the University of Sydney; another was an expert in theoretical physics and relativity.
At around the age of nine, Ramachandran began collecting fossils and seashells and became fascinated by taxonomy and evolution. He wrote to a conchologist at the American Museum of Natural History. "Here's this little kid from India sending him sketches of shells and asking, 'Are these new species?'" Ramachandran said. "And he is writing back saying, 'A, B, C, and D are well-known species; E is very rare and has not been reported from your locality and is very interesting.' So for a while I was the only conchologist in India!" Ramachandran continues to collect fossils and has gone on digs in South Dakota, where he has found specimens of trilobites and a 30-million-year-old oreodon, a sheeplike creature. His most notable find, however, was not in the field but at the annual Tucson Gem and Mineral Show, in 2004, when he noticed on a table, amid heaps of bones and rocks, a skull that he thought could be a new species of ankylosaur, a herbivorous dinosaur from the Jurassic and Cretaceous periods. Ramachandran's friend Cliff Miles, a paleontologist, was with him and suggested that Ramachandran buy the fossil so that it could be studied and described. In January of this year, Miles and his brother Clark, also a paleontologist, announced the discovery of a new species of ankylosaur from the Upper Cretaceous period: Minotaurasaurus ramachandrani.
In his early teens, Ramachandran began conducting experiments in chemistry and biology in a makeshift laboratory under the staircase in the family's house in Bangkok, where his father was stationed. He also read books on the history of science and was struck by the role of intuition and play in many important discoveries: Galileo adapting a child's spyglass and discovering the moons of Jupiter, which led him to challenge the geocentric model of the universe; Faraday tinkering with a magnet and coil and discovering electromagnetism. Ramachandran often recounts these anecdotes to his students. "These stories are inspirational and fun," he told me. "But they're also telling you about how to do science."
Ramachandran's father discouraged him from pursuing a career as a researcher. "My father was intensely pragmatic," Ramachandran said. "He told me, 'Forget about chemistry and biology and all that. I know it's fun, but you're not going to make a living out of this.'" He urged his son to become a doctor, and Ramachandran duly enrolled at Stanley Medical College, in Madras. But he continued to read British and American science journals, and in his sec ond year, he devised an experiment that was inspired in part by conversations he had had as a child with his uncle the optics professor. The experiment addressed a question debated by experts since the time of Hermann von Helmholtz, in the late nineteenth century, about how the brain harmonizes the two slightly different images seen by each eye. For years, scientists believed that when the eyes are given conflicting information—for instance, a green image in front of one eye and a red one in front of the other—the brain accepts input from one retina at a time. Ramachandran, using an old-fashioned stereoscope and volunteers from his medical-school class, found that, when presented with a pattern that was colored differently for each eye, his test subjects continued to see in three dimensions. He concluded that a neural channel was still active in the "shut-down" eye—even though his subjects were consciously seeing only one eye's color at a time. "This suggests that concepts of retinal rivalry need drastic revision," Ramachandran wrote in a report of the experiment.
He sent the report to Nature in December 1971, a few months after his twentieth birthday. "To my astonishment, it was published without revision," Ramachandran told me. Soon he published a more ambitious paper, "The Role of Contours in Stereopsis," which explored ideas about visual processing that became influential decades later. Ramachandran also wrote to one of the foremost vision scientists at the time, Dr. William Rushton, a professor of physiology at Trinity College, Cambridge, describing several original experiments that he was eager to try. The letter was passed to Oliver Braddick, a psychology lecturer who worked on vision. "The letter was obviously the product of a very fertile young mind," Braddick, who is now a professor of experimental psychology at Oxford, told me. "Perhaps a little kind of
spinning off in all directions. But he had all these great ideas."
Braddick and another researcher, Fergus Campbell, invited Ramachandran to visit Cambridge for a month, at the university's expense, to conduct experiments. The results of one experiment, on which Braddick collaborated, were published as "Orientation-Specific Learning in Stereopsis," in the journal Perception. "Maybe fifteen years later, various people started publishing in this area of how specific developments of perceptual skills could be highly related," Braddick told me.
Ramachandran returned to Madras to complete his medical degree, and in the fall of 1974 he enrolled at Trinity College to begin a Ph.D. in visual perception. "I thought they'd all be like Faraday and the great Renaissance scientists," he said of the researchers he met in England. "Ninety percent of them are like Indian scientists, or scientists here, for that matter, or anywhere—it's a nine-to-five job. They're not moved by the great romantic spirit of science, and they're not great Renaissance people. So I was a bit disillusioned. Then I ran into Richard Gregory soon after I arrived, and I said, 'Well, at least there's some of them here!'"
Gregory was a professor of neuropsy chol ogy at the University of Bristol, the author of several best-selling books about science, and an expert in visual perception who had a special interest in optical illusions. Typical of his approach was a demonstration involving a Charlie Chaplin mask on a rotating axle, in which he shows how the brain uses prior knowledge of shape, shading, and other light effects to make sense of visual information and assemble a coherent representation of the world. Gregory's playful style irritated some of his colleagues, but Ramachandran found it electrifying. "He came to Cambridge to give a lecture," Ramachandran recalls. "He was like a magician! He is truly one of the five most amazing men I have met in my life."