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TODD SACKTOR USED TO TELL a story about the day he chose science as his field. The year would have been 1966. The memory is a snapshot: He is sitting on the floor of his grandmother’s Bronx high-rise apartment overlooking the Hudson River. He is reading a newly purchased book called Understanding the Brain by the Nobel laureate John Eccles. It’s a happy day for the nine-year-old in what was sometimes a tumultuous childhood – the family drove from Baltimore to see his beloved “granny,” for Thanksgiving, perhaps, though he can’t be sure of that detail. Sacktor devours Eccles’ illustrations, clear descriptions and grand tone – the book claims the human brain is “the most complexly organized matter in the universe.” He closes its pages with missionary zeal to take Eccles’ title seriously – he will understand the brain. In 1990, his first year at SUNY Downstate Medical Center in the gritty East Flatbush district of Brooklyn, Sacktor made what many believe was a major discovery to do just that. He discovered an enzyme in the brain called PKMzeta, which he suspected – and has since demonstrated – keeps a long-term memory persisting in the brain, even when the mind is not consciously engaging it. What that 9-year-old child could not have known, what even Sacktor the adult did not realize at first, was a basic truth about science – claiming a novel discovery places you
squarely in the professional desert. For the next 16 years, his peers largely ignored his work while he published in lesser journals and gave unheralded talks. Still, Sacktor single-mindedly pursued the purpose of the enzyme’s existence, certain he was onto a big discovery. Then five years ago a team of neuroscientists, led by Sacktor, ran a series of tests on rats’ memories that revolved around the enzyme. Their finding, named a “Top Ten Breakthrough of 2006” by Science, was simple, fascinating and disturbing – keep PKMzeta from doing its job for just a few hours and memories that could have lasted a lifetime are forgotten forever without any damage to the brain. Two months ago, a Science report written by a team at the Weizmann Institute showed that an “overexpression” of PKMzeta enhanced memory retention of rats. Deep in the recesses of the Society for Neuroscience website is a snapshot of Sacktor from 2008. The society has just awarded him the Research Award for Innovation in Neuroscience, which comes with a $25,000 prize. In his black suit and black tie, Sacktor, a 52-year-old, smallish, wispy-haired man with sharp features, peers down at the camera from the podium, his mouth smiling but closed, his round face nearly expressionless. His eyes tell the story. They are not wide, thankful eyes of other neuroscientists pictured on the website from previous award ceremonies, but the dark and cool, half-closed eyes of someone who just proved his point. On a bright Thursday afternoon shedding harsh light on Sacktor’s dingy Downstate laboratory, Research Assistant Professor Panayiotis Tsokas walks in with a cage holding two large black and white rats, brought in pairs to relieve their stress of being moved. One rat will live to see another day. Tsokas picks up the other. He places the rat in the bottom portion of a Culligan bottle cut in half, originally intended for a water cooler but now filled with an anesthetic gas. He places a tin lid on top and weights the lid with the cover of an old steel oxygen bottle. The rat pushes its nose against the plastic, looking out to the lab filled with chemical bottles, arcane machinery and posters of Albert Einstein. It takes three steps and falls to his side, relaxes gently until its breathing becomes barely perceptible. Tsokas prepares a tiny guillotine by the lab sink. Meanwhile, sitting in his office, Sacktor stirs a test tube-shaped stainless steel tea infuser in a mug of hot water. His Society for Neuroscience plaque hangs near the door, neither hidden nor highlighted. As the leader of his lab, Sacktor never touches the experiments. His job is to think – to ask new questions and examine results. He says what Tsokas is about to do requires such precision and speed that it takes about nine months to master. The goal is to harvest the rat’s hippocampus, a section of the brain essential to most kinds of memories. Sacktor is not finished making his point about PKMzeta, the memory molecule. Knowing what retains memory might give scientists the clues needed to track specific
memories forming in the brain – that’s what Sacktor is after these days. It also will further prove his theory, sink his discovery deeper into the realm of accepted wisdom about memory. Tsokas, an associate professor at Downstate, pulls out the unconscious rat, slides its head beneath the hovering blade and with one firm press of the guillotine gate beheads the animal. Now it’s a race. He grabs scissors to split the scalp and skull, then a scalpel to carefully but quickly extract the brain, which begins to decay almost immediately after death. Tsokas has minutes to extract the hippocampus before that happens. He runs down the lab hall, brain in a small container, to a walk-in freezer where he expertly extracts the gelatinous membrane, smaller than a baby pea. While dissecting, Tsokas talks about Sacktor. “He’s very open to ideas, he’s ready to try whatever you think might work.” He divides the hippocampus into thin sections with a miniature round-blade slicer, then races back to the lab, where he sets the hippocampus slices into a solution that mimics spinal fluid. Because he acted fast enough, the hippocampus will perform as if it were functioning in the brain for about a day. The slices will be studied with a process called Long Term Potentiation, which delivers shocks to the hippocampus to study how the brain’s neural pathways respond. These shocks, many scientists believe, are roughly analogous to experiences that become memories. When shocked, PKMzeta proliferates and takes on a life of its own. “I wish we didn’t have to kill animals,” Tsokas says over the morbid scene in the sink, “but it’s going to help someone someday.” + Basic neuroscience does not necessarily search for cures to a disease, but rather for answers about the fundamental nature of the brain. This is Sacktor's job. Basic neuroscientists believe their work in the murky depths of neural networks will someday surface as important to everyday life, but oftentimes they don’t know exactly how. April 6, 2009 was one of those rare days when Sacktor watched his work emerge in the real world. He sat in the kitchen of his Yonkers turn-of-the-century shingle house reading the Monday New York Times with more than a passing interest – his name was on the front page above the fold, under the article, “So You Just Want to Forget? Science is Working on an Eraser.” The article reported how Sacktor’s team was able to erase a living rat’s memory without damaging the brain. “The discovery of such an apparently critical memory molecule,” Times writer Benedict Carey wrote of Sacktor’s work, “and its many potential uses, are part of the buzz surrounding a field that, in just the past few years, has made the seemingly impossible suddenly probable: neuroscience, the study of the brain.”
“Oh great,” Bette Sacktor, Todd’s wife of 21 years, joked when she learned of the front-page treatment, “now you’re going to be even more intolerable to live with.” Living with Sacktor means living with his quest and with his near-obsession for a microscopic protein. It means living with his monumental confidence about being right, even when close colleagues had their doubts. “It always seemed a silly thing, intellectually, to imagine there would be one molecule that would be crucial for memory,” says André Fenton, a former SUNY Downstate colleague now at NYU. + Sacktor’s search may have appeared quixotic, but he is no Don Quixote. He is too self-aware – he admits to being arrogant, stubborn and lazy, which are deficits, he says, overcome by being smarter than most people. He is also too informal for Spanish knight analogies – his regular uniform consists of oxford shirt, chinos and Ecco shoes. Years in Yonkers have bent his accent towards New York over his native Baltimore – the rising octave of his voice as he finishes a thought invokes comedian over neurosurgeon, as if he’s saying, “but seriously folks” instead of “when you electrically stimulate the synapses.” He seems too relaxed to appear a crusader – he gets in the office late most days, plays squash at the gym as part of his workday, and avoids doing too many experiments at once. Most importantly, he is not delusional like Quixote. Interviews with leading neuroscientists revealed a general consensus that discovering PKMzeta has placed Sacktor among the most important brain researchers of his generation. “Yeah, I think I am,” Sacktor agrees. His research may eventually mean editing our memory bank, erasing traumatic memories and enhancing important ones, although that is many years away. It could also mean finding a cure for addictions and persistent pain, which turn out to work very much like memory. It could have serious implications for the study of dementia, such as Alzheimer’s. But at this stage, his research still stirs up controversy. Sacktor not only claims the enzyme he discovered is necessary for memory storage, he claims it is sufficient, meaning all of the other 100-plus molecules nearby are just pawns in PKMzeta’s game. “It’s still a new finding in scientific terms,” says University of California – Irvine professor James McGaugh, a pioneering neuroscientist who has studied memory since the 1950s who’s dubious about the sufficiency claim. “What needs to happen next is that young scientists take up the findings and test them, build on them, make new discoveries based on his work. Once his name is not on every paper about PKMzeta, then you will know it has become established.”
Some scientists are not ready to concede Sacktor’s discovery is primed for canonization. “One of the real pitfalls of doing science is that your tools may not be as good as you think they are,” says John Lisman, a neuroscientist at Brandeis University. Lisman believes he has found a different molecule that maintains longterm memory. “One kind of tool people have is drugs, another tool is genetic modification. So far, all of his work has relied on the pharmacological approach. That is a major hole in his research.” Sacktor says a genetic test is underway. A mouse has been genetically mutated so it won’t produce the memory molecule, which means it should not be able to retain long-term memories. Even before those tests are complete, McGaugh, who called himself an objective observer, says, “it appears he has answered a question that long perplexed scientists. How do humans remember something long-term without actively keeping the memory in mind? He may have filled in a blank.” Filling in a blank is the best any one scientist could hope to do. That’s what wins Nobel Prizes and changes textbooks. Sacktor says none of that matters to him anymore. + “What matters is that PKMzeta is remembered,” he says at his kitchen table in his modest home in southern Westchester County. He says a major literary agent has approached him, but “I’m too lazy to write a book.” He could entice pharmaceutical companies to use his discoveries, but he says any riches gained from his intellectual property are not necessary. “I'm in my fifties and there are fewer and fewer things I want to buy,” he says. “I drive a Toyota Highlander, it’s a good car. Why would I want to be in a BMW?” Driving that Highlander through Yonkers one Sunday evening, Sacktor talks about his hero Albert Einstein, specifically about the physicist’s ability to focus on the essential questions of a problem. Sacktor has taken that lesson to the microscopic level. “I love PKMzeta,” says Sacktor and he’s not using “love” loosely. After all, he guards PKMzeta’s Wikipedia page, making sure no one misrepresents it. When he hears the memory molecule called “strange,” he says he prefers the term “atypical.” He freely gives out the antibody that makes it possible to see the enzyme and provides other scientists with generous intellectual input to assist their research, which is why his name appears on almost every paper about PKMzeta.
“He’s incredibly generous with his time,” says Maria Eugenia Velez, a PhD candidate in physiology at the University of Puerto Rico, who in her research has found that the memory molecule plays a similar role in creating addictions as it does in creating memories. Sacktor has agreed to sit on Velez’s dissertation review panel, “which is a real honor for me. I know he does it because he cares about PKMzeta.” Sacktor can make an argument that the enzyme he discovered is fundamental to the human experience. During a visit to his office, Sacktor takes me through a mental test regarding the issue of consciousness, how any person has an individual identity. He sits relaxed in his ergonomic desk chair while I sit on a couch that looks out towards two unwashed windows. On the window sill to my right stands a small golem, a Jewish religious symbol that a friend brought back from Prague. Next to it is a Krishna statue, which another friend brought back from India. They are nothing but art to Sacktor who says, “Whenever I find myself in a state of magical thinking, I ask, ‘What’s the mechanism for that.’ So if I want the Yankees to win the World Series, does that desire have any effect on the outcome? Of course not, there’s no mechanism.’ At first he’s reluctant to allow the discussion about consciousness to go on the record because, “this is so goofy. But you might find it interesting.” Sacktor begins a Socratic dialectic that mirrors the plot of the movie Freaky Friday, starting with the premise that he and I switched brains, keeping all other body parts. “So would you be where I am sitting and would I be where you are sitting?” he asks. I answered yes, though I am now in his body I remain myself. Then, he continued – imagine we switched only the cerebral cortex and hippocampus, the knowledge centers of the brain. Would I still be me but in Sacktor’s body? Again, I answered yes. “I would agree with that,” Sacktor says. “We might get more emotional about some things, some aspects of our character might change. But we’d say, ‘That's weird, I'm not myself.’ So now, neurosurgery has gotten thousands of years advanced and we could simply switch the PKMzeta locations. We place PKMzeta in your brain in the exact same places as they are in my brain and vice versa, so now what? In fact, we could do this experiment today: Erase the PKMzeta from your mind…” and I cease to be me. “You're a zombie,” Sacktor says. I ask, when I get back out in the world, with a blank slate, would I make similar decisions as before, would my tendencies be the same?
“I would guess that, yeah,” Sacktor replies, “your tendencies would be the same, but maybe not a whole lot more than identical twins’ tendencies are the same.” Therefore, PKMzeta is necessary for consciousness, for the details needed for me to be me. “But it’s not sufficient for consciousness. You also need ongoing experiences for that.” Sacktor was reluctant to have that exercise printed because it extends the discussion beyond what science knows about the brain. Neuroscience is a humbling subject, memory especially. For instance, Sacktor discovered a few years ago that his childhood memory about reading Eccles book in his grandmother’s apartment could not possibly be accurate. Sacktor found his copy of Eccles’ book at his childhood home in Baltimore. Understanding the Brain was published in 1973, at least three years after his grandmother left the Bronx to be closer to his mother. How could Sacktor’s memory be that vivid, that important, and still be wrong? How well can we trust our memories? “No one knows,” he says. “Memories are not perfect, obviously, but it is the best we’ve got.” + His father Bertram and mother June both grew up in the Bronx, but they moved to Baltimore where Bertram, a biochemist, worked at the Edgewood Arsenal. He eventually moved to the National Institute of Aging, where he was chief of the biological chemistry lab. Sacktor was born in Baltimore, the second child. His first memory is of his older sister April when he was less than three years old. They were in the downstairs den at their home. “And I asked her, could you read me this book?” he remembers. “And she said, ‘No, go ask mother.’ So I feel bad I can’t read, I feel bad that she yelled at me and I remember walking glumly up the stairs to find my mom.” It is his only memory of her. Before Sacktor turned three, April died of leukemia. The death was devastating, Sacktor says – Bertram stayed away from home more often and June fell into a depression that almost led her to suicide. “She couldn’t live with the loss,” Sacktor says, “but what kept her going was me.” The birth of Ned, about three years later, made life better for the family, but it was never an easy childhood for Todd. “I hated school,” Sacktor says of his time at Gillman, an all-boys school in Baltimore that prepared students for prestigious colleges. “I was a fat, smart and shy kid. No redeeming social value for a boy.” There were problems at home too.
Sacktor was close to his mother, who died in 2008 from Parkinson’s disease, but he says his relationship with his father was contentious. “Contentious seems like too strong of a word,” says Ned, a professor of neurology at Johns Hopkins University who admits his relationship with Bertram was easier. “I think they had their arguments, but like all fathers and sons do.” Sacktor disagrees. “It was more than that,” he says. “It was very serious.” The disagreements began with typical topics – cleaning the room, talking back – but they ended, Sacktor says, in screaming matches and two fistfights. Digging into the specifics of those fights yields little. “I can’t remember a specific time,” Sacktor says, uncharacteristically tightening his jaw. “It happened a lot.” Sitting in his home one afternoon, I wonder out loud if Bertram’s demands on Todd made it possible for him to withstand the rigors of science, especially breakthrough science. He shakes his head. Did that tension propel him to go beyond his father in science? “Probably,” Sacktor says, as if divested from the subject. + Sacktor studied biology at Harvard, taking courses to prepare himself for medical school. He wanted to pursue the neurology of memory because, “psychiatry wasn’t hard enough.” It took him time to find his place, says Harvard roommate Steve Greenberg, now director of clinical research at the pharmaceutical company Merck. “We didn’t fit in the pre-med mold,” says Greenberg. “We had a lot of interests outside of medicine and biology, both of us were very curious and wanted to explore and discuss a number of fields. In fact, the house we finally lived in had a reputation for people who were artsy, not scientists.” Sacktor calls himself a mediocre student at Harvard, something Greenberg says is “a little self-effacing.” Sacktor’s GPA was 3.3, “and that’s mediocre,” he says, “but remember, I’m lazy and I was lazy at Harvard.” After graduation he was accepted at Albert Einstein Medical School, in the Bronx, which didn’t thrill him. “It started a series of events where I thought the worst thing in the world was happening to me and it turned out to be the best,” Sacktor says. After earning his MD, he interned at Montefiore Medical Center, followed by a residency at the Neurological Institute at Columbia University Medical Center, “my sixth choice for a residency. When I complained to my advisor at Einstein about not getting into my first five choices, she said, ‘You are such an idiot.’” Some of the best research on memory in the country happened at Columbia. Molecular biologist Jimmy Schwartz was there studying memory of the Aplysia, a sea snail with a conveniently simple and large neural network, his advisor told Sacktor,
“‘and he’s smarter than you.’ That piqued my interest, because I like being around people smarter than me, that means you’re going to learn.” Sacktor primarily did hospital rounds at the Neurological Institute the first two years, but his third year was spent in Schwartz’s lab, away from patients and alone with molecules. Schwartz believed memory maintenance could be boiled down to a simple molecular mechanism, but it was no easy matter to find the important one. A Harvard study pinpoints 117 molecules involved in the memory formation process. Given the years it takes to thoroughly study one molecule, trying to find the key enzyme was treacherous for a career – there might be one, maybe two chances at finding it. So most neuroscientists left the research behind. But there was one clue, another Schwartz idea – the molecule would have to be selfsustaining some way, an organic Energizer bunny. Fortunately for Sacktor, the relationship with his father Bertram greatly improved after he left home for college. Not only was the reconciliation emotionally gratifying, it proved to be professionally important. “They didn’t have the tension of living together every day,” says Bette, a practicing psychologist. “And they also had so many interests in common, they could always talk about science.” One day in 1985 they were discussing Sacktor’s work when Bertram suggested to Todd that he look at a group of molecules called PKC, which happened to include PKMzeta, though no one knew that at the time. “He thought they looked interesting,” Sacktor says. “There was a lot of fog around the field right then and everyone was looking for anything to clear the fog.” Sacktor set to work on investigating the enzymes, looking for clues that one might be self-sustaining and populous during memory maintenance. Bertram never got to see the results. On July 8, 1988, Sacktor received a phone call from a doctor in Maine, near Acadia National Park. The doctor told him his father had a heart attack while running. “I remember asking him if he was okay,” Sacktor says. “And he said, ‘No, he died.’” Bertram was 66. At the time, Sacktor was seeing a psychiatrist, who asked the usual introductory question the next week, “How was your week?” Sacktor added to a short list that his father died. “He was shocked, because obviously my father was a major piece of my therapy,” Sacktor says, trying to illustrate the continued ambivalence of his relationship with his father.
But Bette says, “I think Todd is very glad he and his dad had a good relationship when Bert died.” Sacktor left Columbia in 1990 with Bob Wong, a Columbia researcher who accepted the chairmanship of the pharmacology department at Downstate. “I felt like it might not be a good move,” Sacktor says, “but I liked Bob, and again, it turns out it was the best thing that could have happened to me. My father told me there were two important things for a young researcher – hard money, meaning I didn’t have to raise funds for my salary, and a chairman who likes you.” Sacktor didn’t unlock the mystery of the PKC molecules until he got to Downstate, where he had his own lab for the first time. He switched from studying sea snails to the hippocampus of rats. He studied eight PKC strains – alpha through theta – looking for any one that increased rapidly when the hippocampus slice was shocked. That’s where PKMzeta made itself known. “We ran four tests before we were sure,” says Sacktor, who kept seeing the memory molecule proliferate after the hippocampus slice was shocked. “But once I saw the same results all four times, I knew we had something.” + PKM stands for Protein Kinase M. Kinase is an enzyme that transfers negatively charged phosphate groups from a high-powered donor molecule to other molecules such as carbohydrates, amino acids and nucleotides – causing the molecule to change its function. In PKM, protein is the target of the kinase, which explains the first word of its name. “M” stands for magnesium ATP, the molecular source of the energy. Most protein kinases have a natural modifier – usually another molecule that tells it to work or stop. PKMzeta heeds no master, Sacktor says, “they’re like a husband, they just do what they want to do.” That bit of information matched Schwartz’s theory that the molecule would have to be self-sufficient. In his research, Sacktor developed a metaphor for the enzyme’s role near the synapse, where long-term memories are stored, comparing it to a sheep dog. The memory molecule likes to work in packs and as a group they do one thing obsessively – they herd AMPA receptors, membrane proteins that are key to receiving neural signals. After herding the receptors to the site of connection between nerve cells, the memory molecules stand guard to keep AMPA receptors in place. This herding and guarding sustains the memory through continual chemical reaction. How the molecules stay at the right synapse to perpetuate a particular memory is still a mystery, but it seems it has something to do with the "dogs'" obsession with the AMPA receptors.
The best way to prove Sacktor’s case was to erase the memory in a living animal by stopping the PKMzeta from doing its work. That’s when he asked Fenton, the behaviorist who thought Sacktor was being “silly,” to help. Yadin Dudai and Reut Shema at Weizmann Institute in Rehovot, Israel also got involved. Fenton taught rats to avoid a shock, Dudai taught rats to avoid food that they associated with nausea and Sacktor taught rats to find a reward. Then the rats were injected with a drug called ZIP, which temporarily blocks the memory molecule’s obsession with AMPA receptors. After two hours with this drug in their system, the rats completely forgot what they learned. What proved their brains were not simply damaged was the fact that the rats could be retrained to remember what they had forgotten. And they never forgot the rules of the game – they knew to stay away from shocks and nauseating food associations or to go find the reward. They just forgot what exactly they should avoid and what to seek. “What we've learned is that PKMzeta stores the kinds of information that allow animals to have precise memories of their experiences,” Fenton says, “precise association, the specifics of the information, not the general concepts.” Fenton is now a believer. “I thought it was silly, but I was wrong.” “There is more coming,” Dudai says, referring primarily to the study published in Science that showed adding more PKMzeta in the mammalian brain strengthens memories. “More evidence that the theory is right and more implications about what it might mean.” For Sacktor, one goal of tracking the memory molecules is to figure out how the packs are able to retain memories over long periods of time – one individual molecule lives about two weeks. Another long-term result of Sacktor’s current research may be the ability to find specific memories in the brain. “We’re not sure how a memory works across the neural network,” cautions the UC Irvine neuroscientist McGaugh. “It appears that different aspects of a memory are stored in different parts of the brain.” So the emotional aspects of memory might be stored in one place, while the spatial information of the place it happened is placed in another. By some unknown mechanism, the different areas are brought together in recollection. Sacktor doesn’t expect to answer how that happens in his lifetime. “That’s for the next generation of scientists to look at,” Sacktor says, “but they won’t have to work to find the mechanism for memory storage. They already know it’s PKMzeta.” + Science is more than a profession – it is a subculture. An uneasy balance of competition and collaboration is the natural state. Scientists are already professional skeptics and getting their grants funded and their work recognized
drives them to not only pursue their own hypotheses, but also cast harsh light onto competing theories. Sacktor’s desert experience is not that special, says his Harvard roommate Greenberg, “it’s the rule rather than the exception.” “The reality is there are two ways for a theory to get traction,” says Jerry Yin, a neuroscientist at the University of Wisconsin – Madison. “Either your experiments and data are so compelling that people can’t ignore them or you speak very loudly. Todd’s success comes from the first one.” During the 1990s, John Lisman held the spotlight Sacktor now enjoys. Lisman still is not convinced PKMzeta is necessary for memory storage. The molecule Lisman discovered, CAM Kinase II is also self-sufficient. It is plentiful too, accounting for between 2 and 4 percent of the brain’s molecular make-up. PKMzeta makes up just .02 percent of the brain’s chemistry. CAM Kinase II has also been proven to be essential during the initial processing of memory, called induction. All this made Lisman’s theory appear more compelling than Sacktor’s. But Lisman admits there have been no physiological tests – analogous to Sacktor’s rat experiments – that show CAM Kinase II is essential to long-term memory in live animals. Yin, who studies memory in fruit flies, first heard Sacktor at a conference in 1998. Impressed with the findings, Yin decided to try the first behavioral tests of PKMzeta on fruit flies. After several modifications, Yin showed that not only do fruit flies forget what they learned without PKMzeta, they also remember longer with higher amounts of the enzyme in their system. Yin’s results began to turn the tide toward Sacktor. The subsequent rat experiments created a tidal wave for the Downstate team. Talking to Lisman today gives a sense of what Sacktor must have felt like 10 years ago. Lisman says he is having trouble getting grants for his research now, because so much of the scientific community has grown enamored with Sacktor’s answer. “I wish it was more of a debate, we’ve never debated,” says Lisman. “What I like about Todd’s work is he has been really involved in convincing people that his theory is right.” “I would love a debate, anytime,” Sacktor says, a gamesome smile on his face. “Because I have the data.” Yin says that Sacktor’s data is increasingly indisputable, although he does not agree with all of the conclusions. “I think it is very hard to dispute that PKMzeta is necessary for maintaining long-term memories,” says Yin. “I don’t think it’s going to prove sufficient. I think other molecules will also prove important and even vital.”
Sacktor agrees, “it’s possible” that Yin’s critique is accurate, but sufficient is an ambiguous word in biology. What they know now is that all other molecules appear to be supportive parts in a system. PKMzeta is the leader that drives the system and no other molecule known today is needed or sufficient for that. He noted Yin’s own research, where adding only PKMzeta improved memory, as a good argument for sufficiency. Sacktor’s department chairman Bob Wong is well aware of Sacktor’s competitive streak. They play squash nearly every working day and Sacktor wins the majority of matches. Wong watched his colleague struggle through years of being ignored and Sacktor admits he grew depressed over the indifference from colleagues. But Wong says Sacktor did the only thing he could – keep doing experiments and persevere. “There’s an old saying in science about breakthrough discoveries,” Wong says. “First they ignore it, then they get mad about it. Then they act like they knew it all along. Right now, we’re between phase two and three.” Will Sacktor’s perseverance prove valuable for humanity? Not everyone thinks so. Elie Wiesel, the Nobel laureate and survivor of the Nazi death camp in Auschwitz, wrote an editorial in the New York Daily News questioning the ethical ramifications of Sacktor’s research. “I am somewhat hesitant,” Wiesel wrote, “to trust the proposed therapeutic means to use forgetting as a tool for healing. Once forgetting has begun, where and when should it stop?” Sacktor, also Jewish, replied to the Daily News, which never published his letter. Sacktor regrets that decision, he says, because he’s afraid people will misunderstand the point of all those hippocampus slices, all those amnesiac rats relearning lessons they once knew. It is in the letter that Sacktor reveals something deeper than a love for an enzyme, or even for winning the game. The point was not to erase memories, he wrote, but instead “the search for knowledge and the faith that that knowledge will bring benefit to mankind.”
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