  News Alert Update, Sheba Medical Center at
Tel Hashomer, Israel A new brain research center will be inaugurated next week at Sheba Medical Center. With the help of a $1 million donation from businessman Sammy Segol, the center will combine clinical work and research and is expected to place Sheba on the world map and consolidate its position in the forefront of the field. Haaretz For the past three years, Rahel Mussafia has watched with anguish as her husband Albert, a former commander of the Haifa police, descends into the oblivion of Alzheimer's. The incurable disease will be the focus of an ambitious new research center that is opening at Sheba Medical Center next month.
The pianist began to play and the sounds of "Over the Rainbow" filled the room. Albert Mussafia sat up in his chair and smiled like someone who has identified a long-loved song. His wife, Rahel, drew her face close to his and puckered her lips; he responded with a fleeting kiss, like a bird pecking at grass. "Do you love me?" she asked and caressed his hand. Albert did not reply. She tried again: "It's me, Rahel, your wife." But Albert stared a distant spot beyond her shoulder and started humming an unidentifiable tune. Rahel touched the rectangular gold pendant on her neck, which carries her husband's likeness, and said in despair, "What's going through his head? I'm dying to know what's going through his head. Does he know me? Does he care that I'm here? I have no idea. I have to know whether it makes him feel good for me to come to him. If there's any way to know what's going through his head, I'm willing to do all the tests there are." For the past three years Albert has been a patient in the Alzheimer's Center at Sheba Medical Center, Tel Hashomer, near Tel Aviv. For reasons that are not clear to the attending physicians, the incurable disease struck him at a very young age, when he was in his fifties, and since then his brain cells are being extinguished at a dizzying rate, like street lamps in a city where the power supply has been disrupted by a severe malfunction that no one knows how to repair. Just 10 years ago he was at the height of his powers and his name was mentioned as a possible candidate for commissioner of police after concluding his service with the rank of major general as commander of the Haifa District. However, then the lamps in his brain began to sputter and go out one after another, and by now darkness has descended on whole neighborhoods of his brain. What awaits him now is the final stage, when his brain will lose control of the motor skills, the senses and the ability to swallow. When that happens he will be moved one floor up, into the nursing ward of patients who are bed-fed. That will be the final station before total darkness blankets the city. But very rarely, Albert Mussafia's brain pulls off a surprise. A light that appeared to be forever extinguished flickers for a moment, and lights up a path that had been dark for many months. So it happened when Shlomo Aharonishki came to visit last year, wearing his police commissioner's uniform. To the wonder of all present, Albert Mussafia suddenly straightened up and saluted his former commander. "I couldn't believe what I was seeing," Rahel recalls. "I started to cry. That was the first time in a really long while that he showed any sign of being aware of his surroundings. Other police officers in uniform had visited him before that, but when Aharonishky came, Albert must have realized that here was a higher-ranking officer whom he had to salute. Who can fathom it?" Albert Mussafia is 68, with a handsome face and his hair combed back. Friends rarely come to visit any longer, and who can blame them? It's not easy to be around him and he doesn't recognize anyone anyway, so what's the point? His two sons from his first marriage visit him on weekends. Only Rahel, his wife for the past 17 years, comes every day and cares for him with admirable devotion. She combs, shaves and cleans him, makes sure he eats his afternoon sandwich, but above all she kisses and caresses him and wonders whether he is even aware of her presence. Growing forgetfulness Few people are more qualified than Prof. Anat Biegon to try to answer some of the questions that are bothering Rahel Mussafia. What happened to her husband's brain? Does he think, and if so, about what? Why did the disease afflict him, of all people, at such an early age? Why is his situation deteriorating so rapidly? Could anything have been done to prevent the outbreak of the disease? And the question that troubles her most: Is the great love that she is heaping on her husband helping him in any way? Dr. Biegon, a chemist and brain researcher, has been appointed to head the new brain research center that will be inaugurated at Sheba Medical Center on November 12. For the past two years she was a researcher at Brookhaven National Laboratory, a U.S. federal facility on Long Island. Before that she worked as a biochemist at the Imaging Center of the Lawrence Berkeley National Laboratory in California, and before that she was vice president for research and development at the Pharmos Corporation in the United States. At the beginning of this month, she arrived at the Alzheimer's Center of Sheba Medical Center and joined Rahel Mussafia on a visit to her husband. Rahel is very excited as the time for the meeting approaches. No, she doesn't expect great things. She knows that her husband's condition is irreversible and that no one can help him anymore. But the doubts continue to haunt her, the questions still distress her, and the faint hope that an expert on the order of Dr. Biegon will suddenly come up with an unexpected answer energizes her. After giving Albert his afternoon sandwich - he is also a diabetic and it is important for him to maintain a stable diet so that he does not suffer from sharp fluctuations of his sugar level - Rahel Mussafia describes for Anat Biegon the history of her husband's illness. At first normal memory-loss problems cropped up. Once he forgot the code that started the car, another time he forgot his ATM code. These are everyday, trivial events. Today, though, she realizes that they were ominous portents - the first lamps that burned out in Albert's head and heralded the larger electrical failures that lay ahead. But she wasn't suspicious then. After all, if every person who forgets his ATM code develops Alzheimer's anxiety, the imaging labs in the hospitals would collapse of overwork. Then less frequent phenomena appeared, which caused tension at home, especially when Albert began to make mistakes about places and times, and Rahel suspected he was lying to her and hiding things. But there was still no way to guess at the drama that was taking place among the nerve cells of his entorhinal cortex, an important memory center of the brain. There was no way to know that a protein called amyloid was starting to form in his brain and disrupt its activity. In the meantime, the nerve cells of Albert's hippocampus, another part of the brain connected to memory, were beginning to degenerate, affecting his short-term memory - and generating much anger over subjects that initially seemed nonsensical. For example, Albert was known among his friends for the superb pickles he made, but suddenly he began to become confused and changed the regular recipe he had followed for years. When Rahel remarked on this he grew upset and refused to talk to her about it. Today she understands that he felt that something bad was happening but didn't know what it was and that his anger was really directed at himself. He was angry at his brain for starting to betray him. "The human brain," Dr. Biegon explains, "has to explain to itself what is happening to it. It cannot accept the fact that it is being destroyed. It finds explanations for everything." Albert Mussafia's senses were not affected, but his problems quickly grew worse. After years of taking pride in his excellent memory - thanks to which he was able to speak in public without notes - he started to write himself little notes about things it was important for him to remember. His wife found the scraps of paper in his pockets and wondered about them, but didn't yet suspect anything. Since his family had perished in the Holocaust (he was born in Sarajevo) and he himself had survived thanks to Catholic nuns who adopted him, there was no known history of Alzheimer's in his family. As a result, the terrible word was not mentioned in the house, as it sometimes is in families where the disease has struck. Besides, Albert was still young enough so that not even the doctors thought in the direction of Alzheimer's. Nevertheless, his brain cells continued to die at a horrific rate and the external manifestations became odder and odder. When Rahel asked him what time it was and he looked at his watch and replied "Eighty," she thought he was making fun of her and became angry. But when tickets for driving through red lights began arriving at the house and Albert was unable to account for them, she realized that he was suffering from something far more serious than she had imagined. At the time, he was the police and Prisons Service ombudsman in the Public Security Ministry - not exactly the type that would be likely to drive through a red light on more than one occasion. After another round of visits to doctors, the dreaded word was spoken for the first time. Thus Albert Mussafia joined the 70,000 Israelis who suffer from Alzheimer's, almost all of whom were older than him. There are about a hundred of them at the Alzheimer's Center in Sheba, a unit that makes it possible for more affluent patients to finish their lives in a relatively dignified manner, for about NIS 13,000 a month. Patients whose families can't afford to pay such sums are trapped in their homes all over the country, spending their days gaping at the television screen and slowly dying, waiting for the systematic annihilation of their brain cells to put them and their families out of their misery. As Rahel Mussafia recounted in brief the history of her husband's deterioration, he sat by her side, humming to himself and occasionally smiling. "He is now in the stage of pleasant indifference," Biegon said. "The stage in which he got confused and didn't understand what was going on was the phase in which he suffered. The stage he is now in is the one in which the family suffers. His case is complex and shows that there is hardly a patient who exactly fits the definitions. One approach to Alzheimer's is to treat it like a mixture of symptoms. To get rid of the approach that says it is one disease that has one cause. In brain disease it is very rare for there to be one fomenter and a predictable course of progress. Every story is completely individual. I'm trying to school myself not to go after the miracle drug that will eradicate the disease, but rather to identify all the risk factors and to chip away at them." The soul is dead! There is probably no more thrilling field today than brain and central nervous system research. Three years ago the American writer Tom Wolfe - the man who has never missed a coming trend in the past 40 years - published "Hooking Up," a collection of essays. In the essay "Sorry, but Your Soul Just Died," he noted that he understood why students were flocking to the neurosciences. He himself would be ready to do the same. The brain, he wrote, confronts humanity with the two most fascinating riddles of the 21st century: "the riddle of the human mind and the riddle of what happens to the human mind when it comes to know itself absolutely." The American Society for Neuroscience was founded in 1970, with 1,100 members. When Wolfe published his book it had 26,000 members. Last Saturday Anat Biegon traveled to San Diego for the society's annual meeting. "35,000 neuroscientists!" she wrote me in an e-mail before departing. Many of the society's thousands of new members came from other fields of research - psychology, genetics, computer sciences, physics, mathematics - whatever can help the human mind explain the most sophisticated organ we know: the brain itself. Like many others of her generation, who came from other disciplines and now constitute the backbone of brain research, Biegon, who was born in Poland in 1954, did her doctorate in chemistry (at the Weizmann Institute in Rehovot, at the end of the 1970s). "Personally, I always thought the brain is the most interesting thing in the world," she says, "the only thing worth devoting a whole life to researching. We are the brain, the brain is us, and all the rest is meant to safeguard it. If more people are discovering this truth today, that makes me happy." The questions that occupy Biegon and her colleagues are naturally related to the functioning of the brain. Why did the cells in Albert Mussafia's brain suddenly start dying? Did the minor road accident in which he was involved once, in which his head smashed against the windshield of the car, set in motion a chain reaction that led, so many years later, to his situation today? Or was the tragedy inscribed in his genes at birth and only accelerated by the circumstances of his life? Could the outbreak of the disease have been prevented by a better diet? By closer control of the level of fat in his blood? By reducing the pressures to which he was subjected in his life? Would it have helped if he had taken aspirin and sipped red wine and tasked his brain with crossword puzzles and learning new languages? Is his diabetes connected with the deterioration of his brain? And what is the connection between all of this and the epileptic fits from which he has been suffering in recent years? These and many other questions will be addressed by Biegon's brain research institute, and we will come back to them later. The most dramatic development in brain research in recent times was the result of a technological breakthrough. New imaging instruments make it possible for physicians to observe the human brain in real time, as it goes about its tasks. The most advanced of these scans are F-MRI (functional magnetic resonance imaging), which shows the blood flow in the brain; MRS (magnetic resonance spectroscopy), which measures biochemical changes in the brain; and PET (positron emission tomography), which pinpoints activity in the brain. Scientists like Dr. Biegon, for whom three-dimensional imaging is part of their daily routine, will tell you that there is no single place in the brain where it is possible to see the consciousness or self-consciousness that we hold so dear. That is no more than an illusion generated by a cacophony of neurological systems that operate in superb coordination. An illusion! Thousands of years of preoccupation with "psyche," "mind," "soul," "self," "personality,' "spirit" and "human nature" - and not so much as a glint of any of them appears on the sophisticated FMRI or PET screen. So what's all the fuss about? Wolfe, too, in his essay, took the idea of the illusion of the soul a step farther. As Nietzsche declared in 1882 that "God is dead," meaning that in an age of rationalism and scientific research educated people no longer believe in the existence of God, Wolfe predicts that it will not be long before a new Nietzsche declares that "the soul is dead." As he puts it, quoting the future "new Nietzsche": "The soul, that last refuge of values, is dead, because educated people no longer believe it exists." Think of two of the most influential thinkers of the past two centuries - Karl Marx and Sigmund Freud. Both based their views on the assumption that human beings and their ideals are effectively shaped by their environment. From Marx's point of view, the most crucial factor influencing the shaping of consciousness was the social class into which one was born. Marx taught us that the ideals and the beliefs that prevail in society were no more than ideas that were implanted in the minds of the lower classes by the members of the upper classes in order to perpetuate their control of society. From Freud's point of view, the most crucial factor influencing the shaping of consciousness are the relations within the nuclear family. That is where the Oedipal drama takes place, what Wolfe calls "the unconscious sexual plot that was played out in the family early in the child's existence," which thrusts us into life equipped with a "personality" and a "character" which can only be understood by talking to a psychologist for several hundred shekels an hour. The collapse of the Iron Curtain on the one hand, and the development of countless popular chemical drugs to influence personality and character on the other hand, dealt a mortal blow to both theories and shook the popular belief in them to its foundations. That was the stage, Wolfe writes, at which neuroscience "surged in, as if into an intellectual vacuum." Suddenly the arena of social ideas began to teem with "scientific" theories. Here is the gene of homosexuality, exulted the liberals, who launched a struggle for equal rights; and here is fresh proof, in a live broadcast from the human brain, of innate differences between women and men, declared conservatives, who set out to undermine the demand of feminists for total equality; and here is an instrument that will be hooked up to your head and will test your IQ with marvelous precision within just 15 seconds, without anyone being able to allege "cultural bias" that accorded the ruling class a "cultural advantage." Thousands of future scientists who streamed to research labs may have thought they were embarking on an intellectual adventure, as they set out to map the last frontier, but without intending it they found themselves acting as the executioners of what we hold most precious: the human soul. Free will, you say? Forget it. Everything is predestined. IQ isn't everything Anat Biegon shows little enthusiasm, to put it mildly, for embarking on this track. "If Yeshayahu Leibowitz were still alive, I would suggest that you speak with him," she says. "It's not that I don't have opinions about some of these philosophical questions, it's just that I don't think my opinions about philosophical issues are any more important than someone else's. On a day-to-day basis I don't occupy myself with these questions. You can live a full life in the scientific world without engaging philosophical questions at all. I did not come to the brain from a philosophical discipline. I'm not familiar with its tools. I'm a scientist. When I finally manage to extract an answer, it is very precise. It entails a hypothesis that demands a thorough examination and proof. And I believe that the scientific method is like democracy: it's not perfect, but it's the best we've got. "I'm always surprised that people go into shock when they read that the IQ is actually genetically determined. Why should that be more surprising than the fact that tall people have tall children or that people with blue eyes have children with blue eyes? And why is it important, anyway? IQ isn't everything, you know. Let's take the most powerful person in the world, the president of the United States. I don't know what George Bush's IQ is, but if it's above 100, you could knock me down with a feather. But that didn't stop him from becoming the most important person in the world. There are other things in life besides IQ. People succeed in all kinds of fields because of a collection of abilities. "What I want to say is that there are people who got into brain research because they're interested in the philosophical questions - who are we. I belong to the group that got into brain research because I think the tax you have to pay society for letting you play at science for your whole life is to solve problems, to treat diseases. What truly interests me is how the human brain works, why it becomes ill and how to help it." The `brain' for brain research With this in mind, we return to the center for brain research that will be inaugurated on November 12 at Sheba Medical Center with the help of a $1 million donation from the businessman Sammy Segol (the new unit will be called the Segol Center). The initiative to establish the center was that of the hospital's director, Prof. Ze'ev Rothstein, who thinks that the combination of clinical work and researchers collaborating will place Sheba on the world map and consolidate its position in the forefront of development. Which brings us to the unavoidable ethical question: the possible danger that people who go to the hospital to be cured of an illness will become, without their knowledge, guinea pigs in research projects that are under way at the institution. Rothstein is quick to reassure: "We will not turn patients into guinea pigs. Absolutely not. If you are in the hospital and we want to perform an experiment on you, we can't do it without your consent. The laws and the rules about clinical experiments are very strict. Before you can publish the results of an experiment in the scientific press, you have to show that the experiment was approved by all the ethics boards and received the consent of all the patients who took part in it." To understand exactly how a hospital-based research center operates, I met at the end of last month with Dr. Biegon and with Prof. Michael Davidson, the director of the Psychiatry B ward at Sheba and an expert in Alzheimer's. Davidson was a leading force in getting the new center established. In a series of conversations and e-mail exchanges, they tried to outline their vision. It's not a simple matter, mainly because this is not a laboratory that will carry out any concrete research that can be described and illustrated, but a concept. They will have offices, no more, which will oversee all the different functions that already exist in the hospital, to transform them into something like the branches of a giant research laboratory. The idea is to establish a kind of "brain" that will channel the research activity that is in any case conducted in various departments of the hospital, with the aim of collecting the greatest possible amount of information that will ultimately help the researchers understand how the human brain works, why it falls ill and how it can be repaired. Biegon: "Sheba Medical Center has an impressive array of imaging instruments and 14 clinics and research labs that possess diverse capabilities. This rich infrastructure is a serious incentive to establish a research center within the hospital. The second factor, which is perhaps more important, is the human factor, which is the essence of a hospital but is absent from academic or private research centers. Patients and their range of illnesses, doctors and nurses - the combination of infrastructure and people will greatly facilitate the kind of research we want to conduct." Prof. Davidson explains that to decipher the totality of the approaches, factors and solutions to problems related to the brain, experts must cooperate and there must be mutual nourishment. "The question is where you want this type of research to be conducted. In the university? In an independent research institute? In a hospital? This is not clear, either. In some places it's done in universities. We - and we are not the only ones - think that a hospital is perhaps the most appropriate venue. For example, there is a leading cancer expert here who is engaged with genetics, because the field in which genetic research has developed the most is in cancer research, but he does not engage in neuroscience. And there is someone who deals with neuroscience but not with genetics, and there are experts in psychiatry and in radiology. And it turns out that cholesterol and fats in the blood are also connected to what happens in the brain, and there are also experts in cholesterol and lipids. "Why hasn't this been done in Israel until now? There were attempts that didn't succeed, maybe because the science wasn't ready. It's possible that it still hasn't advanced enough to make all the connections between the various disciplines. That is one possibility. Another is that ego problems will arise. For many years an attempt was made to do this, because it sounds so logical, but without success. Now we are hoping that Anat is so smart that she will be able to bring about the integration of all these experts." How does one start to advance an ambitious multidisciplinary, interdepartmental project of this scale? The first step, from Biegon's point of view, sounds amazingly simple. She went to the various departments in the hospital and asked the physicians not to throw out anything. "There are experts here who are working on the effect of fatty substances on the heart," she explains. "They kill the animal they are using for research and throw away its brain, because they are working on the heart and that's what interests them. All I need is for them not to dispose of the brain, because maybe the information they are collecting for their research on the heart will help me with my research on the brain. I go from department to department and ask people not to throw anything away. You wouldn't believe the incredible research that can be done in a hospital where people don't throw anything away, if you develop the physicians' awareness that every time they do medicine they are also doing research." So, drawing on a fusion of information, Davidson and Biegon hope to advance research on questions related to the brain, for example, to collect the MRI data in the hospital. "Let's say a pregnant woman goes to a radiologist for imaging of the fetus in the wake of the results of an ultrasound examination which showed that the fetus is suffering from enlarged lobes," Biegon says. "From my point of view, the imaging the radiologist does of the brain of the fetus inside his mother is like an atlas. But what does the radiologist do with the results? He writes his reply - there is or is not a problem, as the case may be - and as far as he is concerned that is the end of the story." Davidson: "And I want to know how the child in question, with the brain we have seen, develops, at what age he stands up, whether he reads earlier or not." Biegon: "When I sit with the radiologist, he very much wants to conduct a study. He doesn't understand that if he doesn't throw out anything, he has a terrific study at hand. As soon as you finish writing the reply to the specific question you were asked, start asking additional questions." This research effort and intellectual probe will not be able to help Albert Mussafia. He got on the train too early, traveled too fast, and now he is too close to the last stop. Paying one last, brief visit to the world of philosophy, we recall that Descartes said, "Cogito ergo sum" - "I think, therefore I exist." Does Albert Mussafia think? "Obviously, I haven't got a clue about what is going on in his head," Davidson replies. "I believe that frequent confusion means a mistaken interpretation of reality. Family members often look for meaning in a patient's mumblings, but I'm not convinced that controlled observation supports that effort. Still, I treat patients like him as though they understand everything. That is the only way that makes it possible for us to treat them with dignity and empathize with them." And that brings us back to the family's sense of helplessness. "What drives me crazy is that we will never know what he knows," Rahel Mussafia says toward the end of Dr. Biegon's visit to her husband. "`Never' is a big word," Biegon replied. "Maybe in another two months someone will come out with a new discovery." "Do you really believe that?" Rahel Mussafia asked with hope in her voice. "I hope," Biegon said. "We spend our whole life doing research
on the brain. If we didn't believe, we wouldn't do it." For more information, please contact: Lauri Novick, Executive Director, Friends of Sheba - Tel
Hashomer: New York
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