The final frontier

New world-class Hebrew U. brain sciences center promises to keep Israel in vanguard of this vital field.

By JUDY SIEGEL-ITZKOVICH
brain skull skeleton health 248 88 (photo credit: extension.missouri.edu)
brain skull skeleton health 248 88
(photo credit: extension.missouri.edu)
During most of human history, the heart was considered the most important part of the body, while the brain took a back seat. Thanks to 17th-century French philosopher, scientist and mathematician René Descartes, who (mistakenly) viewed the brain's pineal gland as the seat of the soul and the place in which all human thoughts are formed, what is in the human head has superceded what beats in the human chest. However, longer life expectancy has brought a growing prevalence of central nervous system (CNS) diseases from Parkinson's to Alzheimer's. Today's cardiologists understand cardiovascular diseases much better than they did just 50 years ago, and new medical technologies have been developed to treat them. But the same cannot be said of many brain diseases. As a result, then-US president George H.W. Bush declared 19901999 "The Decade of the Brain" to increase public awareness of CNS disorders and increase funding for research through the US National Institutes of Health. The brain is one of the few remaining "great frontiers" in medical research. As part of the worldwide effort to discover the causes of CNS diseases and how to delay and treat them, Swiss philanthropist Lily Safra, president of the Edmond J. Safra Foundation, has joined with the Hebrew University to establish one of the world's six largest brain research centers. The Edmond J. and Lily Safra Center for Brain Sciences (ELSC) has already opened on the Edmond J. Safra Givat Ram campus in the capital, and a large building will eventually be constructed to house it. The foundation donated $50 million (the largest gift of its kind ever made for the establishment of an Israeli research center), and an additional $80 million is being sought for the project, which was announced during the university's board of governors meetings attended by Safra in early June. The decision to invest in a center for brain sciences is based on the findings of an international monitoring committee whose members include two Nobel laureates - Prof. Bert Sakmann of Heidelberg and Prof. Richard Axel of New York. Brain diseases are devastating not only to the victims and their families but also to the health system and the economy, as expensive caregivers are often needed. "In another 15 years or so, we as a society won't have the financial capacity to support all the health problems of the ageing population, and so we must quickly find solutions," said ELSC acting director Prof. Eilon Vaadia. "Brain research should be a key issue in modern society." HU PRESIDENT Prof. Menachem Magidor said that thanks to the foundation, the university would be able to help solve one of the key scientific questions of the 21st century - how the human brain works - by discovering new medical approaches for treating neurological disorders and applying new technologies that imitate the brain's activity. The new center will pursue different fields: Genes, molecules and nerve cells in the brain; the structure and function of local neuronal circuits; electrical activity and the communication between brain areas, with the aim of understanding how senses, movement and thoughts are created; cognitive processes and aspects of human brain function; and theoretical fields, building models of the nervous system. Three symposia on brain research were held at the university during the week of the board of governors' meetings. The first one on the Mount Scopus campus was attended by hundreds of scientists, students, board of governors members and other laymen. Magidor, who concluded his last term as president and was replaced by (former MK) Prof. Menahem Ben-Sasson, said that "understanding the human brain is the most challenging, fascinating and complex subject in human research. "Just knowing more is very important, but brain research also has many applications, especially in medicine. Brain diseases cause a lot of suffering. The CNS is one of the most complicated natural systems in the world," said Magidor, a distinguished mathematician. "Research needs a multidisciplinary approach - but at the Hebrew University we are used to doing this and thinking out of the box." The outgoing president concluded that a few years ago, as part of a university review, a top advisory committee that included Sakmann produced a report "that no university administration can afford to ignore. It said that students in the field are very promising, and that resources must be provided to create one of the world's greatest brain research centers. The Edmond J. Safra foundation generously made a major contribution, and here we are." VAADIA, WHO teaches at the Hebrew University-Hadassah Medical School, explained that "our brains are collections of billions of cells that know how to interact with each other. Every human is an individual with passions, an ego and desires that must act together. We want to find new ways to study the brain and increase our understanding of these phenomena. We hope to bring about a revolution by working together - just like brain cells - and creating new technologies. We want to educate the next generation and connect people. We don't want to be isolated in an ivory tower." The acting ELSC director said the center will work on brain networks and connectivity; cellular mechanisms that are the building blocks of brain function, neuronal circuits and human behavior. "We want to go from basic science to brain repair, to restore normal brain functioning in people aged 60 and 70 for example. There are new three-dimensional techniques such as connectomics to check on every brain cell - identify and track it using different colors. We want to understand the brain's hardware and how it creates behavior. In the new center, we will put great stress on the future, and recruit young faculty members, thus creating fruitful interaction with veteran staffers. There will be a state-of-the art building for the ELSC, so we can do science under optimal conditions, hold public lectures, issue publications and cooperate with the Bloomfield Science Museum nearby." Sakmann, one of the world's leaders in brain research who won the Nobel Prize in Physiology or Medicine with Prof. Erwin Neher in 1991 and received an honorary doctorate from the HU, delivered a very technical lecture on brain anatomy and functions. Until now, he said, "most of what we know about the brain has been in two dimensions. But now we have begun to reconstruct the structure of each neuron in 3-D, all individually, as each is different. We will watch the cells' electrical activity in 3-D, and even see the electrical stimulation. Brain anatomy is a crucial subject. We want to understand how many active cells drive a behavior, what is the contribution of different cell types, and the degree of syncrhonization between cells during behavior. I hope you at the ELSC will discover these things, and I hope to collaborate," Sakmann said. Alzheimer's disease, which is becoming a world epidemic, is a "frontier brain disease in mouse models," he noted. "We are learning how plaques in the brain affect the network. New plaques made of amyloid-beta protein can form in the brain within 24 hours, and damage from substances emerging from these tangles can occur quickly." HU EMERITUS Prof. Marta Weinstock-Rosin, who helped develop the drug Exelon for alleviating Alzheimer's, said this most common form of dementia affects about 5% of those over 65, and more than a quarter of those over 85. She and colleagues discovered in the 1980s that cognitive deficits were associated with a reduction in the release of the neurotransnitter acetylcholine. They realized that the dementia ensued because not enough of the neurotransmitter reached the next neuron. The team synthesized rivastigmine, the active ingredient in Exelon, and improved memory, attention and cognitive function in a significant number of patients - but not all of them - for up to two years. RETIRED COLUMBIA University Prof. Gerald Fischbach discussed genetics and autism. "This disease involves aloneness, the preservation of sameness, language delays and a lack of understanding of others' beliefs," he said, but the definition of autism has grown, and ranges from the milder Asperger's Syndrome to full retardation." One in 150 births - more boys than girls - will be diagnosed at around two or three as autistic, said Fischbach, who is now at the Simons Foundation to direct basic research into the disease. Autism "is genetic. If there is one identical twin, the other is over 90 percent more likely to have it than a non-twin. But people with autism usually don't marry, so it is not passed on. We believe there are new mutations in the parents' sperm and egg cells. A landmark study of 300,000 Israel Defense Forces soldiers found that men who become fathers after 40 are 40% more likely to father an autistic child." There has been enormous progress in understanding autism in the past decade, even in the past three years, said Fischbach, but there is plenty more to know. "The old model of one person working in one lab is obsolete. Science is in desperate need of research money. I was glad to head the committee that recommended the establishment of a brain research center here. The great universities like this one will be judged on how each contributes in the next decades to understanding the human brain."