They do this by binding to messenger RNA molecules, preventing them from carrying out protein synthesis. RNA interference, as this process is called, provides the cell with a way of controlling the levels of hundreds of different proteins by turning genes off at the appropriate times.

“Now we understand that miRNAs are important in regulating the processes inside the cell, inside the organ, and inside the organism,” says Dr. Eran Hornstein of the Weizmann Institute of Science’s Department of Molecular Genetics. “When these components are malfunctioning, you end up with a disease.”

Dr. Hornstein and his team study how miRNAs regulate the activity of genes during the development of the pancreas, bone, and cartilage, and how malfunctions may contribute to diseases.

Before joining the Institute in 2006, Dr. Hornstein received his MD/PhD from the Hebrew University–Hadassah School of Medicine in Jerusalem. He started out with the goal of becoming a physician, but was ultimately drawn to basic science research and completed his postdoctoral studies in the Department of Genetics at Harvard Medical School.

While at Harvard, he helped provide some of the earliest evidence that miRNAs play a role in vertebrate development—specifically, in the development of limbs. The study of miRNAs is so new that at the time of Dr. Hornstein’s postdoctoral research, the first miRNA had been identified only a decade earlier.

Dr. Hornstein’s current investigations include studying the role of miRNAs in diabetes. “We know now that miRNAs are highly relevant to the regulation of insulin gene expression in beta cells that are key to controlling the body’s glucose levels. And we think we also have a clue about particular miRNAs that are highly relevant to the development of diabetes in mice,” he says.

Along with his colleagues, he is also looking at the role of miRNAs in amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease). ALS is a neurological disorder that affects motor neurons—the nerve cells in the brain and spinal cord that control muscle movements—causing muscle weakness and paralysis. “It’s a very devastating disease and the genetics of it are completely unknown, so we don’t yet know how to cure it,” says Dr. Hornstein. “But we have now developed a very nice model, in mice, to show that loss of miRNA activity may generate ALS.”

He believes this research could shed light on the role of miRNAs in other neurodegenerative conditions, such as Alzheimer’s disease. “It seems that miRNAs are extremely relevant to the functionality of neurons,” Dr. Hornstein says. He explains that mi-RNAs seem to work not at the cell nucleus, but at the periphery. Neurons sometimes need to regulate their functionality at a distance, very far away from the center of the cell. It now appears that regulatory RNAs—particularly miRNAs—might specialize in regulating cell functions at a distance from the center.

A better understanding of miRNAs, which are now thought to regulate more than a third of all human genes, could eventually be useful for the treatment of a wide range of illnesses ranging from osteoporosis to cancer. “Down the road, I hope the findings in my lab will come together with technologies that are being developed in order to generate new therapeutics for diseases,” says Dr. Hornstein.

It was during those early days of her research in the laboratory of microbiologist and Nobel laureate David Baltimore that she realized, she says, “that science is one of the most exciting things one can do—you can really pursue your dreams.”

Since then, Prof. Rotter, who is head of the Weizmann Institute’s Department of Molecular Cell Biology, has devoted her career to this gene, now known as the “guardian of the genome” because it protects us from developing cancer. She was one of the first to develop antibodies against p53, along with other genetic tools, laying the foundations for the study of its function.

In its normal form, p53 plays a pivotal role in protecting cells from becoming cancerous. “The p53 is a very smart gene,” says Prof. Rotter. It can sense when cells have damaged DNA (from exposure to ultraviolet radiation or chemicals, for example) and signal them to either repair that damage or undergo a process of self-destruction. When p53 is mutated, however, it loses this function; as a result, cells carrying damaged DNA can go on dividing and eventually transform into tumor cells. Mutant forms of p53 are found in more than 60 percent of human tumors.

Although p53 is possibly the most studied gene ever—thousands of papers on it have been published—Prof. Rotter finds that some basic questions have still only been partially answered: What is the function of p53 in the normal cell? How does mutant p53 contribute to cancer development? She believes that if we can understand exactly how p53 works, we can find ways to use it to stop the proliferation of cancer cells. Ultimately, her   goal is to come up with new kinds of therapies that she describes as “made just for you and your cancer.”

She has already made progress toward this goal through her research on the possibility of tailor-made chemotherapy. Prof. Rotter and her team conducted an  experiment in which they treated cancer cells with chemotherapy. Some of the cancers died, but others were very resistant to the chemo. The researchers evaluated the status of p53 in the cancers, and found that different types of mutant p53 exhibited different levels of resistance to the therapy.

Prof. Rotter thinks it may be possible, in the future, to increase the effectiveness of cancer therapy by evaluating the specific type of mutant p53 the patient is expressing and choosing a chemotherapy drug that is suited to it. Her team is now creating a library of chemotherapy drugs targeted to various mutant forms of p53.

Since 2000, Prof. Rotter has also directed the Weizmann Institute’s Women’s Health Research Center, which promotes basic research on gender-related physiology and diseases and has supported studies of cancer, fertility, and osteoporosis. For example, several of the research groups have examined the buildup and breakdown of bone mass and described a number of enzymes that affect the balance of bone accumulation or loss. Understanding how bone degradation is regulated may help in developing better treatments for osteoporosis.

Prof. Rotter is optimistic that basic research will continue to lead to better cancer treatments. For her part, she will continue to search for new kinds of therapies that could compensate for the malfunction of tumor suppressor genes.

Her ongoing goals include designing genetic methods for coping with cancer and making our genes stronger—possibly through inserting better genes, strengthening existing genes, or fighting the bad genes. “When we find a way to design this kind of tailormade therapy,” she says, “I think we will solve the problem of cancer.”

Made at room temperature - a first time achievement, the tubes exhibit unique electrical, optical and other properties, depending on their components, and as such, may form the basis for future nanosensors, catalysts and chemistry-on-a-chip systems.

The study, published in Angewandte Chemie, was performed by Prof. Israel Rubinstein, Dr. Alexander Vaskevich, postdoctoral associate Dr. Michal Lahav and doctoral student Tali Sehayek, all of the Institute’s Department of Materials and Interfaces.

“We were amazed when we discovered the beautifully formed tubes,” says Rubinstein. “The construction of nanotubes out of nanoparticles is unprecedented.

The new nanotube created at the WIS lacks the mechanical strength of carbon nanotubes. Its advantages lie instead in its use of nanoparticles as building blocks, which makes it possible to tailor the tube’s properties for diverse applications. The properties can be altered by choosing different types of nanoparticles or even a mixture, thus creating composite tubes. Moreover, the nanoparticle building blocks can serve as a scaffold for various add-ons, such as metallic, semiconducting or polymeric materials - thus further expanding the available properties.

The resulting tube is porous and has a high surface area, distinct optical properties and electrical conductivity. Collectively, the tubes’ unusual properties may enable the design of new catalysts as well as sensors capable of detecting diverse substances present in minuscule amounts.

A key feature of their success would be the ability, due to the tube’s room-temperature production, to add on biological molecules that would otherwise be destroyed by high production temperatures. These would then perform their natural function of recognizing other molecules in nature, in a key-fits-lock manner. Other tube applications might include lab-on-a-chip systems used in biotechnology, such as DNA chips that detect genetic mutations or evaluate drug performance. Yeda, the Institute's technology transfer arm, has filed a patent application for the tubes.

Nanotubes may soon join these preventive efforts. Prof. Daniel Wagner of the Institute’s Materials and Interfaces Department has found that the nanotubes (tiny, extremely tough tubes made of a web of carbon atoms) can be used to monitor mechanical stress in materials. His study, published in Applied Physics Letters, revealed that nanotubes offer a highly sensitive means of detecting material defects induced by stress, such as microscopic breaks or holes. Future applications based on this finding may use nanotubes as an early warning system of material fatigue in airplanes and other structures.

Recent research in Amsterdam’s laboratory has revealed that theophylline, a widely used asthma drug, makes ovarian and lung cancer cells more vulnerable to such common anticancer medications as cisplatin and gemcitabine HCl. Apparently, theophylline helps induce massive programmed death in the cancer cells. Therefore, by giving theophylline together with common cancer drugs, it may be possible to use the cancer drugs at lower concentrations and so minimize their harmful side effects. Clinical trials in which theophylline is administered to lung cancer patients in combination with cisplatin and gemcitabine HCl are under way at the Tel Aviv Sourasky Medical Center.

To do this, the scientists must surmount several fairly formidable obstacles: When fuel burns, the resulting chemical reaction releases energy; any method for reversing that process must restore the lost energy – and then some. The trick to creating a carbon-neutral cycle (one that takes as much carbon out of the atmosphere as it adds) is to not only add energy into the process but to employ renewable, non-polluting energy (such as sunlight) for that purpose. Ideally, the end product of this chemical reaction should be only the fuel and such substances as oxygen or water that won’t harm the environment.

Presently the scientists are following several avenues of inquiry into designing new catalysts – the materials facilitating chemical reactions – that will help turn CO₂ into such fuels as methanol, using the sun’s energy. The scientists are starting from scratch on this project: Few have attempted to recreate hydrocarbon fuels from CO₂ in any kind of continuous, sustainable manner, and none have succeeded. In fact, says Prof. Ronny Neumann, Head of the Institute’s Organic Chemistry Department, the team’s first step has been to review the scant literature on the subject and figure out where others went astray.

Although their task may seem daunting, the Institute team, all members of the Organic Chemistry Department, should be up to the challenge: Between them, Profs. Neumann and David Milstein have many years of experience in creating catalysts for a variety of industrial and scientific chemical reactions. Many of their catalysts have been designed with the aim of making these reactions safer for the environment – by working more efficiently and producing fewer polluting waste products. In fact, Milstein’s research was recently mentioned in Science magazine’s ”breakthroughs of the year” for its contribution to the field of green chemistry. Prof. Gershom (Jan) Martin's research focuses on catalysis from another angle: He develops computer simulations that reveal various potential catalyst molecules in atomic detail, a sort of ”drawing board” that allows the scientists to design and test different molecules on-screen in conjunction with lab experiments.

The scientists plan to explore several means of producing carbon-based fuel. Hydrocarbon molecules such as methanol are made of carbon atoms chemically bound to hydrogen. The chemical process to create the hydrocarbons must remove the oxygen from the CO₂ molecule and force the remaining carbon atoms to bond with hydrogen. This is a multistep procedure, and the scientists are researching various routes to the end product, which should be only hydrocarbon fuel and oxygen. The team also intends, in the future, to investigate the possibility of using CO₂ to produce hydrogen for fuel cells. In this case, only one oxygen atom will be split off from the CO₂ molecules, creating CO. In a separate reaction, the CO will undergo a chemical reaction with water (H₂O), producing hydrogen.

So far the scientists have seen some signs indicating they’re on a promising path, but Neumann cautions that the journey before them is likely to be quite a long one. Creating the technology to generate new fuels from the waste products of the old ones may require years of hard work and basic research. The research just beginning in the Weizmann Institute labs is a true investment in the future.

Weizmann Institute scientists have made seminal contributions to understanding the role of p53 in normal and cancerous cells. It is now known that p53 acts as the cell’s damage control and as a “guardian of the genome.” When genes are damaged by radiation, chemicals or other means, threatening to set the cell on a course toward malignant transformation, p53 senses the damage and its supply builds up. The p53 protein activates numerous genes that prevent tumors from forming; by so doing it either blocks the growth of damaged cells, allowing for the correction of DNA damage, or commands these cells to commit suicide. But if the cell has no healthy p53, the road to cancer remains open.

Prof. Moshe Oren of the Molecular Cell Biology Department, together with the Weizmann Institute’s Prof. Emeritus David Givol and Prof. Arnold Levine, then of Princeton University, was the first to clone p53 - in other words, to isolate the gene and determine the sequence of its genetic letters - in 1983. The p53 clone and its genetic sequence provided laboratories around the world with one of the most frequently used tools for studying cancer. Subsequently, Oren was the first to show that reactivation of p53 in cancer cells can prompt them to self-destruct, a principle that underlies the ongoing p53 gene therapy trials. Oren is now focusing on elucidating the biological processes that allow this gene to function as a tumor suppressor. Among the questions studied in his lab: How does p53 interact with other genes? How are the levels of p53 regulated in a cell? Usually, p53 is present in minute amounts, but its levels soar in response to DNA damage and other types of stress. Oren has discovered the role of a major regulator of p53 activity, called MDM2. He found that MDM2 is responsible for the elimination of p53, and he now seeks to clarify how exactly MDM2 achieves this. Oren predicts that interfering with MDM2 will strengthen p53, thereby boosting the natural anti-cancer defense mechanisms.

Prof. Varda Rotter of the Molecular Cell Biology Department was the first to develop antibodies against p53, laying the foundations for the study of this gene’s function. She also provided some of the earliest evidence that p53 is a tumor suppressor. At present, Rotter is working toward two major goals: to decipher the function of p53 in the normal cell and to clarify the behavior of mutant p53 in tumor cells. In particular, she seeks to understand how p53 can induce three different processes: blockage of growth, cell differentiation or cell death. She is working to clarify whether all three processes can occur in a single cell, or whether different cells respond differently to p53.

The state of a patient’s p53 may determine whether conventional cancer treatments are likely to be effective. Several years ago, oncologists made a surprising discovery: radiation therapy and some chemotherapies, rather than directly killing cells as had previously been thought, in fact work by activating p53, which in turn orders cells to self-destruct. Therefore, patients with intact copies of p53 are more likely to be helped by these treatments. In the absence of p53, the cancer is resistant to chemotherapy. Prof. Emeritus David Givol of the Molecular Cell Biology Department has conducted several studies exploring the effects of p53 on different chemotherapies. Givol is now using DNA chips to determine which other genes are activated by p53. He discovered new cell suicide genes that are turned on by p53 in response to DNA damage. If p53 is defective, alternative means may be used to activate such genes.

Cahen, together with colleagues from two other Israeli universities who share his concern, convinced the Batsheva de Rothschild Foundation to provide the bulk of the funding, which was supplemented by support from the Safed Foundation, the Institute’s AERI, Bar Ilan University and the Technion. They then selected 24 of the nation’s top students in the physical, life and engineering sciences who were in their final year of Ph.D. studies and invited them to spend five days with 20 Israeli and foreign senior experts in various aspects of alternative energy research – from the very basic to the very practical. (Weizmann Board of Governors member, Yehuda Bronicki, an industrialist, was one of the experts.) The conference, called ”Alternative, Sustainable Energy Options,” took place in a small hotel on an isolated Galilee hillside. Several of the students, most of whom were interested in the subject but had little or no alternative energy experience, admitted they thought the conference would be a ”pleasant week in a nice location.”

What they found was an intensive week of presentations by experts in everything from fundamentals to engineering, followed by small-group sessions on systematic, innovative thinking approaches that led to dynamic discussions and brainstorming, along with focused tutoring sessions in the senior scientists’ areas of expertise. The students themselves proposed the topics and led the discussions for the closing sessions of the conference.

Said one student: ”The seminar allowed us to form our own opinions about directions for fruitful avenues of research for possible new approaches to alternative energy.” The three conference organizers were optimistic: ”How large a new cadre of energy researchers will develop as a result of the meeting remains to be seen, but it seems very possible that its first seeds were planted on a beautiful, peaceful Galilee mountainside.”

One Weizmann Institute of Science research success story features the multiple sclerosis (MS) drugs Copaxone® and Rebif®. These two medicines—results of decades of hard work and experimentation by Weizmann scientists —are now frontline treatments for MS, but the beneficial effects of this research extend far beyond the medications themselves.

Production of these drugs has significantly contributed to the Israeli economy, helped establish and drive the country’s crucial biotechnology industry, and provided opportunities for new scientists to build thriving research careers.

THE COPAXONE® STORY
In the 1950s, the Weizmann Institute’s Prof. Ephraim Katzir (later the fourth president of the State ofIsrael) began researching proteins—the basic building blocks of all bio- logical systems. This work led to the design of synthetic models of proteins, called poly-amino acids.

Prof. Michael Sela, Katzir’s former research student, decided to test the influence of these synthetic molecules on the immune system. He theorized that giving mice certain poly-amino acids, or copolymers, might cause their immune systems to reproduce the symptoms of autoimmune diseases such as MS.

Along with Prof. Ruth Arnon and Dr. Dvora Teitelbaum, Sela synthesized several copolymers that mimic a component of myelin, the protective coating of nerves. Because the component was believed to trigger MS, the scientists hoped that their molecules could create a much-needed animal model for the study of MS; unfortunately, their experiment did not work.

Despite the initial failure, the scientists persisted. Their determination paid off when they stumbled on a surprising finding: Rather than causing MS symptoms, the copolymers were actually blocking an MS-like disease. Arnon says the results were “overwhelming ... at that early stage, we realized that this might eventually lead to a therapeutic agent.”

The team then conducted years of experiments with a molecule called copolymer-1, or Cop-1. Their studies ultimately led to the development of the drug Copaxone®, with clinical trials carried out by Teva—Israel’s largest pharmaceutical company—proving its efficacy in treating MS.

In 1996, Copaxone® became the first original Israeli drug to be approved by the U.S. Food and Drug Administration (FDA). Today, after more than a decade of active sales around the world, Copaxone® has made a major contribution to the Israeli economy and provided a significant boost to the country’s important biopharmaceutical industry.

But the story is still unfolding at Weizmann: Using molecular genetics, Prof. Doron Lancet recently identified a genetic basis for the positive effect of Copaxone® on many MS patients. These findings may help develop the field of personalized medicine. Prof. Michal Schwartz has used Copaxone® to stop the progressive loss of sight in animals with a glaucoma-like disease, suggesting that the drug may also aid people with glaucoma. The nature of basic research is that one never knows where the science will lead.

THE REBIF® STORY

Prof. Michel Revel was just a teenager when interferon—so named because interferes with viral activity—was discovered, and by the time he came to Weizmann in 1968, scientists still knew very little about the substance. It was difficult to produce, and no one had succeeded in generating it in large quantities. Looking for a challenge, Revel decided to explore exactly how interferon disrupts viral proteins ... and as soon as the mid-70s, the Weizmann team was known as a world leader in interferon research.

The team concentrated on a form of interferon called interferon beta. While other groups around the world were studying interferon alpha, Revel felt that the beta form might have a special role. However, interferon beta does not show up in blood when injected, and so scientists had predicted that it would never be developed as a drug. But Revel and company soon proved that injected interferon beta actually does leave evidence in the genes it activates—a finding that saved their research.

While Revel believed that interferon beta had unique potential, there was still no way to generate the large quantities needed—until the group used genetic engineering to produce interferon beta in animal cells. This technique has since become a mainstay of the biotech industry.

The team began to pursue medical applications in earnest. They learned that a researcher in the U.S., who thought MS might be caused by a virus, was treating patients with anti-viral interferon beta. The Weizmann group’s research had shown that interferon can influence immune activities even if no virus is present. They realized the virus theory was wrong, but that interferon beta might nonetheless prevent the symptoms of MS, and Revel convinced pharmaceutical giant Serono to conduct trials.

As a result, Rebif®, the interferon beta-based treatment for MS, entered the market in 1998. Produced for many years at Interpharm in Israel (in 2005, production moved to Switzerland), it made a major contribution to Israel’s economy and biotech sector. The impact of Revel’s research is huge: Today, interferon beta-based drugs for MS are a $4.6 billion industry, and are taken by three-quarters of MS sufferers.

Weizmann research continues on interferon beta, already leading to the discovery that a topical application can prevent recurrence of genital herpes symptoms. It also has shown promise for treating hepatitis C—a use for which Serono has recently completed clinical trials. The story of interferon and its wide-spread impacts is not yet over.

The normal function of blood vessels greatly depends on the dynamic properties of the endothelial cells that line the vessel. These cells are firmly attached to the underlying membrane as well as to their neighbors via specialized adhesions, which play a crucial role in regulating vessel formation (angiogenesis), stability and repair. When given a message by angiogenic factors, or following a pathological loss of cell-cell adhesion, endothelial cells extend flattened protrusions with motile properties, form new adhesions and migrate. This physiological response is essential for blood vessel maintenance.

This process can be simulated in the laboratory by an in vitro wound model, where cultured endothelial cells are allowed to migrate into and close a gap that has been artificially introduced into the endothelial layer. Under pathological conditions such as diabetes, the normal maintenance of blood vessels is severely disrupted, leading to increased fragility and malfunction of the vascular system.

Prof. Benjamin Geiger of the Molecular Cell Biology Department is investigating the mechanisms regulating endothelial adhesion and motility. Current studies in his laboratory address the mechanisms underlying these dynamic processes, in healthy and diseased vessels. A better understanding of the molecular mechanisms underlying the generation of new blood vessels and wound closure may point toward possible targets for drug development.

In related research, the work of Prof. Michal Neeman of the Biological Regulation Department may help address the necrotic wounds in the extremities, characteristic of diabetes. Neeman is working on the use of quantitative magnetic resonance imaging (MRI) methods for the analysis of vascular growth in limbs deprived of blood supply. Her objective is to generate criteria for testing the effi cacy of therapeutic approaches for blood vessel growth.

Working with bone marrow transplants for terminal leukemia patients, Prof. Yair Reisner of the Immunology Department has found a way to overcome residual immunity even in the case of transplants from unmatched donors. His method removes the main obstacles limiting the use of mismatched transplants – namely, graft failure and an adverse immunological reaction called graft-versus-host disease.

Normally, a donor and recipient are considered compatible when they are matched for all six immunological markers on their chromosomes – three inherited from the mother and three from the father. In Reisner’s method, developed in collaboration with Prof. Massimo Martelli of Italy’s Policlinico Monteluce, the donor and the recipient need to be matched for only three markers. Such a partial match is always found between parents and children, and there is a 75 percent chance of finding it between siblings.

To date, hundreds of patients throughout Europe have been treated using this approach, yielding significant success rates, as reported in the New England Journal of Medicine, Blood, and other publications. Following these encouraging results, Phase 1 clinical trials are currently under way in major centers in the United States, and the European Bone Marrow Transplantation Society has recently launched a formal prospective study in 35 centers throughout Europe.

A key element of this method is the use of extremely large doses of donor marrow that literally overwhelm the recipient’s rejection mechanism. The donated stem cells are “cleansed” to erase the characteristics contributing to rejection in mismatched transplants. But why does it work? How does bombarding the patient with a megadose of donor stem cells prevent transplant rejection?

A new study by Reisner and his team at the Weizmann Institute’s Department of Immunology provides insights into this riddle. They have shown that certain stem cells, using a “veto” mechanism, are capable of protecting themselves against attack by the body’s immune system. In addition to offering a possible explanation of how stem cells aid in preventing immune rejection, this finding may prove vital in targeting another longstanding research challenge – to lower the radiation dosages accompanying transplant therapies in a range of diseases, from advanced diabetes to leukemia.

Prof. Lubomirsky, a researcher in the cutting-edge field of nanoscience, brings a background in materials science to his investigations of ways to diversify our energy supply. For example, he discovered that, under certain conditions, a common ceramic material called cerium gadolinium oxide behaves more like rubber than like a regular ceramic. It adjusts to an externally imposed shape, but returns to its original form once released from its constraints. And unlike an average ceramic, it does not buckle when heated or crack when cooled. The ceramic’s ability to adapt to all temperatures could be useful in devices that undergo repetitive warming and cooling, such as fuel cells that convert chemical energy directly into electricity.

With regard to alternative energy, Prof. Lubomirsky is especially interested in solving a fundamental problem: how to convert a low-density energy source to one that is high density. Wind and solar power – currently the most promising forms of renewable energy – are very dilute compared to fossil fuels, which means that it may take a large surface area, many hours, and certain weather conditions to collect the energy at a practical rate. “As a society, we’ve never tried to switch from concentrated energy sources to dilute ones,” he says. “Ideally, we should try to harvest energy from the wind and sun and convert it to something we can use in the same ways we use fuel now.”
With the support of the Weizmann Institute’s Alternative Energy Research Initiative (AERI), Prof. Lubomirsky is working toward this goal. He is trying to develop a method of storing and transporting wind and solar power. One of the main reasons these cheap, non-polluting energy sources have not yet been used on large scales is that today’s technologies convert them to electricity or heat on the spot, and the power is then fed directly into the home or community where the equipment is sited and cannot be transmitted to faraway populations. Further complicating the situation is the fact that the best locations for exploiting these types of energy tend to be under- populated, such as deserts or the middle of an ocean.

One of Prof. Lubomirsky’s solutions is to use electricity generated from the wind or sun to power the production of chemical fuel, which is a moveable form of stored energy. He is interested in a chemical reaction that would split molecules of carbon dioxide (CO₂) to create carbon monoxide and oxygen. The carbon monoxide could then be easily transported to where it is needed, or converted by another simple chemical reaction into fuel for use in vehicles or power stations.

As splitting CO₂ molecules directly is extremely inefficient, Prof. Lubomirsky is developing an alternative process in which CO₂ is first converted into a cheap, reusable intermediate product such as soda (a common, naturally occurring mineral compound), and then split into oxygen and carbon monoxide by electrical current.

He hopes to develop a chemical process that is stable over time, non-polluting, and requires minimal maintenance. Because the gases CO₂ and carbon monoxide are easy to transport, plants for producing the carbon monoxide could be located in sparsely populated deserts. They could also be anchored in oceans, where steady, year-round winds provide a constant energy source.

Prof. Lubomirsky points out that searching for new ideas on how to use renewable energy sources and adapt them to our existing infrastructure is something that the Weizmann Institute, as a basic research institution, is uniquely positioned to do. And these ideas are essential, he says, because “we cannot solve our energy problems with the same logic we used to create them. Now we need new logic.”

In her studies in Kenya, Shahack-Gross used the geo-ethno-archaeological approach to identify ancient livestock enclosures. Accompanied by a Maasai tribe elder, she collected soil samples from his village and from a series of abandoned villages in which he had lived in the past. In this manner, she managed to create a “time axis” describing the breakdown of organic matter over 40 years. Under the guidance of Prof. Stephen Weiner of the Weizmann Institute’s Helen and Martin Kimmel Center for Archaeological Science, she developed a method for identifying livestock premises using a variety of soil analyses and microscopic tests, including an analysis of phytoliths – tiny silica particles present in many grasses, including animal feed, that end up in cattle dung. An analysis of phytoliths and additional minerals allows her to identify livestock enclosures long after organic matter – a more direct but less stable evidence of their presence – has disintegrated.

Shahack-Gross then joined a Kimmel Center team at the excavations in Tel Dor, where she got an opportunity to apply her method. Together with collaborators from Israel and Spain, she showed that the white-powdered surfaces in the excavated town were collections of phytoliths originating in the dung of livestock kept in enclosures within the city (and not from man-made plaster floors, as had been believed earlier). She also found evidence that animal dung had been used as fuel. These findings suggest that today’s clear-cut divide between agricultural and urban settlements came into being later than previously thought, providing new insights into the nature of the so-called “urban revolution” thought to have occurred in antiquity in the Mediterranean region.

Shahack-Gross, a senior lecturer in the Department of Land of Israel Studies and Archaeology at Bar-Ilan University, joined the Kimmel Center as a visiting scientist as part of a joint program initiated by Weiner. She uses a variety of analytical methods – infrared spectroscopy and oxygen and carbon isotope geochemistry, as well as microscopy – to identify the phytoliths and other materials in soil and ash samples. These methods allow her to gain new information about ancient societies, including the types of food consumed by their cattle. “Today hardly any archaeological excavations are conducted without backing from the natural sciences,” she says.

In another ethno-archaeological study, conducted with Prof. Israel Finkelstein of Tel Aviv University, she used analysis of materials, including phytoliths, to help solve a controversy over settlements created in the Negev Highlands during the Iron Age, corresponding to the Biblical period of Kings (circa 1,200 – 600 BCE). One opinion, based on the Bible, states that certain buildings are remains of fortresses built by King Solomon to protect his kingdom from Egypt and that they were destroyed by Pharaoh Sheshonq I during his northern campaign in the late tenth century BCE. Finkelstein, however, claimed that these buildings had been erected by cattle herders, but he relied on “circumstantial” evidence: The so-called “fortresses” were not located at strategic positions and did not have the uniform appearance of military structures.

Shahack-Gross collected numerous ash and soil samples from two sites near Sde Boker. Her analysis revealed traces of goat dung in the central courtyards of these fortresses. The sediments at the Negev Highlands sites were very low in phytoliths, reflecting a diet of wild plants and lichen. In addition, no phytoliths originating in domestic cereals – in other words, in agricultural crops – were found. These results, backed by analyses of sediments in contemporary Bedouin settlements in the Negev, suggest that the residents of the fortresses were indeed shepherds. And the hypothesis that the Iron Age settlements in the Negev Highlands were built as part of the Kingdom of Judea must be reconsidered.

The dating of plant remains using radioactive carbon, conducted in collaboration with Dr. Elisabetta Boaretto of Bar-Ilan University and the Weizmann Institute’s Kimmel Center, showed that these sites were set up in the late tenth century BCE and operated for about 100 years, until the end of the ninth century BCE. “Sheshonq’s campaign might have led to the creation rather than destruction of these settlements,” Shahack-Gross says. “Moreover, evidence suggests that these were seasonal settlements typical of nomadic herders.” In additional analyses, the scientists will try to determine whether these settlements were indeed seasonal and what they were like during the Iron Age.

Is it a qubit?

At the level of atomic and subatomic particles, things work very differently from the macro world of everyday objects. For instance, there's wave-particle duality: The basic bits of matter and light behave sometimes as discrete particles and sometimes as waves, which can be in many locations at once. And there's quantum superposition – particles existing simultaneously in more than one state at a time – which could, theoretically, provide a dramatic increase in computing power. An electronic computer bit can be in only one of two states (0 or 1), whereas a quantum bit (called a qubit) can exist simultaneously in both 0 and 1, in an infinite number of different superpositions. The challenge for scientists is to connect these fragile quantum states to the larger world without destroying them.

Several years ago, Prof. Ady Stern of the Condensed Matter Physics Department came up with a way to test a system to see whether it could be used as a special kind of qubit – a topological quantum bit. The system in question involves, on the one hand, electrons moving in a very cold two-dimensional plane, with a strong magnetic field applied at right angles to the plane and, on the other, quasiparticles. These "imaginary" particles – which have electrical charges of one-third, one-quarter or one-fifth of an electron – don't exist in nature, but they have been created and measured in the lab of Prof. Moty Heiblum of the Condensed Matter Physics Department.

Such a system must meet several criteria before it can be considered a possible qubit. The particles must be able to exchange places, and this exchange must leave a sort of trail that can be traced – that is, it must preserve information. In Stern's theoretical experiment, two parallel lines of current run through such a system with a separation "wall" containing quasiparticles between them. An odd number of quasiparticles should cause the electrons in the current to behave as particles, flowing in line through the material. But if they are separated by an even number, the electrons in the system should act as waves, producing interference patterns at the end of the current pathways.

In addition to the number of fractionally charged particles in a system, the fraction itself is relevant. The quasiparticles Heiblum measured in the 1990s had odd denominators, and these don't leave traces when they exchange places in the plane, making them unfit for storing information. Even-denominator fractions might be better for the purpose, but they're harder to produce. This past year, Heiblum and Stern, together with research student Merav Dolev and Drs. Vladimir Umansky and Diana Mahalu, all of the Condensed Matter Physics Department, succeeded in creating a nanoscopic device in which quasiparticles with one-quarter the charge of an electron were measured for the first time. They are now continuing their experiments to find out if quarter-charge quasiparticles are truly suitable candidates for quantum bits.

Can quantum errors be corrected?
Quantum "weirdness" – the strange reality that rules the world of ultra-tiny particles – presents some unique challenges. For instance, how can one perform calculations in a system in which the very act of measurement changes the basic configuration of that system?

Quantum superposition has been demonstrated in particles such as electrons, but it has never been observed in larger objects composed of many particles. The reason, scientists believe, is that in larger groups the particles interact with one another and with their environment, forcing the quantum superposition of the system into a single classical state. (Measurement is one form of interaction.) This transition is called decoherence. One could conceivably build a very simple quantum computer with only a few qubits, but how to create one that has millions?

Since joining the Weizmann Institute in 2007, Dr. Roee Ozeri and his students Nitzan Akerman, Yinnon Glickman, Shlomi Kotler, Yoni Dallal and Anna Keselman have been setting up a lab in the Physics of Complex Systems Department, and they have recently begun to conduct experiments that may one day help overcome the limitations. Ozeri is especially interested in error correction in quantum computing. Today's electronic computers compensate for possible errors by building in redundancy and using error-correction protocols. In analog quantum protocols, different kinds of error correction may help overcome decoherence and keep superpositions of many particle states "alive." Ozeri is also investigating ways of creating complex quantum logic gates – the basic operations of quantum computing – in which actions performed on one qubit can, under the right conditions, change the state of a second. Because quantum systems can't be measured directly without affecting the result, Ozeri must use roundabout methods that ascertain whether there are errors in the qubits' final state.

His experimental quantum system is based on ions – specifically, atoms of the element strontium that have undergone "laser surgery" to remove some of their electrons. Several of these ions are fired into a vacuum chamber, where they're trapped in an array of electrical fields, while another laser cools them to within a few millionths of a degree of absolute zero. Although Ozeri's experiments trap just a few ions at a time, he can examine the effects of decoherence by applying an electromagnetic field to create noise in the ions' environment. For "communicating" with the ions, he uses yet more lasers, which are precisely tuned to interact with various transitions between strontium ion states.

While the challenge of creating the basis of future computers is compelling, it is ultimately the questions of basic physics that Ozeri finds most fascinating: "We've been exploring the physics of the quantum world for around 100 years, and those of macro systems for much longer, but we still don't know much about the point at which one takes over from the other, how the transition happens or whether it's possible to push the limits and extend the quantum superposition principle into many-particle systems. This research might help provide answers to some of these very basic mysteries."

Do quantum codes communicate better?
Assuming quantum computers become a reality one day, what will they be used for? Will they be more efficient for every type of operation? For example, factoring large numbers – a process that could be used to break some encryption codes – is believed to take an impossibly long time on today's computers, but it could be done quite efficiently on a quantum computer. Prof. Ran Raz of the Computer Science and Applied Mathematics Department investigates whether communication between computers would be better with quantum methods. Quantum computers may be far in the future, but quantum communication has already been successfully demonstrated in experiments.

An example of a problem involving communication is a program for setting up a two-person meeting. The minimum number of bits needed to be communicated today to find a common free hour in each participant's network calendar equals the number of calendar slots that must be checked (n). But a quantum communication protocol could perform the same task using just the square root of (n) bits. Raz found that the difference for some other communication problems could be even greater: The improvement would be logarithmic. In other words, as the value of n rises, quantum communication protocols should quickly leave classic ones behind in the dust.

Bone and shell are composite materials in which the mineral component forms within a framework of soft macromolecules such as proteins. The framework is essentially a "mold" that directs the mineral formation. Bone grows continuously, layer by layer; but, unlike shell, it also undergoes constant remodeling. This makes it hard for scientists studying bone to distinguish new material from old, much less to trace the process by which bone is formed. Because of this difficulty, conflicting theories have arisen as to the mechanisms of bone formation. Many scientists thought that the minerals precipitate directly from a solution in the way that stalactites and stalagmites grow from elements dissolved in water. But findings published in the 1960s already hinted at the possibility that a different process was at work.

Ten years ago, research in a group headed by Profs. Lia Addadi and Stephen Weiner of the Institute's Structural Biology Department confirmed these earlier observations for shells. They showed that organisms first produce packets of amorphous material (unorganized material, as opposed to the ordered organization of crystal). These packets are transferred from the inside of cells to the building site – the spot where the mineralized tissue eventually forms. There, the packets undergo structural changes that turn them into a hard crystal. This observation triggered widespread interest in amorphous precursor mineral phases, and many different invertebrate mineralization processes were investigated.

Addadi and Weiner revealed this process in sea urchin spines, and their findings have been joined by a body of global research confirming that this method of construction is common to many different invertebrates that have shells, spines or other hard body structures. Addadi: "The original idea of precipitation from solution would require huge quantities of liquid to flow from inside the mollusk to the outside of its body. Transferring the materials in solid form – 'bricks and cement' – is a much more energy-efficient way of doing things."

While the issue has been more or less settled for the shells of invertebrates, the question of how vertebrate bones are formed remained unresolved. This is partly because of the difficulty inherent in attempting to observe a substance with no fixed location that exists for only a fleeting stage of growth. Recently, however, research student Julia Mahamid, together with Addadi and Weiner, found a biological system that enabled them to follow bone formation step by step and identify the processes taking place at each stage. This system is the fin of a small aquarium denizen called a zebrafish. The zebrafish fin bones, which continue to grow throughout the fish's lifetime, form a sort of fan. Each bony rib of the fan is composed of segments, and the segments nearest the fin's edge are always the newest. Thus the segments can be studied as a sort of timeline of bone formation. In addition, zebrafish, which live in relatively cold water, grow slowly, and the leisurely pace of their bone development enabled the scientists to get a good look at each stage.

Using both light microscopy and scanning electron microscopy, the scientists succeeded in observing abundant spherical parcels of amorphous mineral material in the newly formed fin bone. Their findings, which appeared in the Proceedings of the National Academy of Sciences (PNAS), USA, showed that about half the mineral makeup of the newer bone segments is amorphous – a fraction that dwindles in the segments farther away from the fin edge. Their observations suggest that the amorphous material does, indeed, turn to crystal over time.

These findings are shedding light on a number of scientific mysteries, giving scientists a unique perspective on how the hard substances in our body – bones and teeth – are formed. The scientists hope that a deeper understanding of these biological processes may, in the future, help researchers find cures for diseases involving faulty bone development or repair.

Last spring, a small research boat made an unusual trip – from one side to the other of the northwestern-most tip of the Red Sea. On this crossing (of the Gulf of Eilat or the Gulf of Aqaba, depending on one's map) were researchers from Jordan, Israel and the U.S. who had recently joined forces to study how water flows and mixes in the unique body of water that lies between Jordan and Israel.

Dr. Hezi Gildor of the Weizmann Institute's Environmental Sciences and Energy Research Department; Dr. Riyad Manasrah of the Marine Science Station in Aqaba, Jordan; Prof. Amatzia Genin of the Interuniversity Institute for Marine Sciences and the Hebrew University of Jerusalem, Eilat; and Dr. Stephen Monismith of Stanford University are conducting this research through the NATO Science for Peace and Security Program. Their efforts should greatly improve scientists' understanding of water currents and circulation. But the group has an immediate, practical goal as well: A detailed understanding of water movement in the Gulf can help the environmental agencies on both sides (which already cooperate to protect its unique ecology) plan a response to spills or prevent pollution from spreading.

Recent research by Gildor and Dr. Erick Fredj of the Jerusalem College of Technology has already revealed a surprise: Floating material such as oil might remain near the spill site for an extended period of time, rather than dispersing throughout the surface area of water. Using data collected from two on-shore high-frequency radar stations, Gildor created a computer map of the currents. He then added evenly spaced "particles" to a computer water-flow simulation to see where they would go. The calculation, which showed the particles moving with the currents over several days, revealed that some of the particles tended to move closer together, forming large clumps; at the same time, barriers created by the current separated particle clusters and prevented them from dispersing or mixing with other clusters. Large bodies of water don't normally lend themselves to experiments, but a set of aerial photos taken soon after a rare winter flood provided evidence for the accuracy of the model: The images show well-defined brown stains in the blue water – silt that had washed down from the nearby desert mountains into the Gulf and collected in the areas predicted in the model. In addition to the two radar stations on the Israeli side, a third is now set to go online on the Jordanian side, which will greatly increase the data available to the scientists.

"The Gulf of Eilat," says Gildor, "offers scientists an exceptional research opportunity. Although it is relatively small, it is also quite deep, and many types of ocean phenomena take place in its waters. Because of its limited size and the fact that it's almost entirely surrounded by land, detailed measurements can be obtained at a higher resolution than is possible in the open ocean. Also, there's the added advantage of being close to shore."

One such phenomenon is usually found only in places that are much harder to study, such as the waters off the Antarctic coast. Called a density current, it takes place when cold air from a nearby land mass cools the top layer of ocean, making it denser and heavier than the water below. This layer then sinks, creating a vertical current. Although density currents are confined to narrow belts of sea near land, they are important drivers of the global ocean currents that, in turn, affect global climate patterns. The Gulf of Eilat, although it is much closer to the equator than other areas that experience this phenomenon, has all the right conditions for density currents: On the one hand, the shallow strait at the entrance to the Red Sea prevents the deep, cold water of the outer ocean from flowing into the Gulf. On the other hand, the Gulf water is surrounded by desert, where atmospheric temperatures can drop to near freezing on winter nights, thus cooling the surface water. Gildor and his research team found that pulses of density current regularly occur off Eilat's shore in wintertime, and they used their observations to create a high-resolution computer model of these flows.

The Gulf is an invaluable natural laboratory – one that Gildor is turning into an important basis for improving ocean modeling – and collaboration between scientists on both sides is crucial to conducting research in its waters. Gildor: "There's no physical line down the middle of the Gulf, and its water doesn't recognize political borders. To really understand it, we need to be able to study this body of water as a whole."

Prof. Cahen explains that after the global crash in oil prices during the early- to mid-1980s, sup- port for research in alternative energy decreased drastically as well, resulting in what is now an extremely poor base on which to build new technologies. Meanwhile, the demand for energy is increasing worldwide, oil prices are unpredictable, and the burning of fossil fuels is causing pollution and releasing greenhouse gases that contribute to global warming. “We cannot afford another period of not-so-benign neglect,” he states.

To help provide this essential scientific ground- work and develop clean, efficient, affordable, and sustainable energy sources, the Weizmann Institute launched the Alternative Energy Research Initiative (AERI) in 2006. Prof. Cahen, the first scientific director of the AERI, has focused much of his own research on alternative energy. He is particularly interested in solar cells – devices that use the sun’s energy to generate electrical power – and his work includes studying how to  improve their performance and cost-effectiveness; for example, he and his colleagues recently showed how very inexpensive mirrors can help increase the utilization of sunlight by such cells.

Under Prof. Cahen’s guidance, the AERI provides support for innovative sustainable-energy research projects conducted by Weizmann scientists, with particular emphasis on work that is multidisciplinary, at an early stage, or that would otherwise be unlikely to compete successfully for funding.   

One such project is being carried out by scientists in two departments: Prof. Uri Pick of the Department of Biological Chemistry and Prof. Avihai Danon of the Department of Plant Sciences. Profs. Pick and Danon are investigating microalgae as a new source of biomass to generate biofuel. Some types of algae produce oil that can easily be converted to biodiesel. Algae have a number of advantages over other bio-fuel crops such as corn and sugarcane: it can be harvested year-round; it can be grown rapidly in saltwater or wastewater, without draining water resources; and it produces no waste byproducts.

Profs. Pick and Danon are studying the ways several strains of algae use sunlight and carbon dioxide (CO₂) to store energy and to grow, and are working to identify the genes that regulate the algal metabolism. Eventually they hope to create genetically engineered algae that can be grown in a controlled and sustainable way, and that can yield a liquid fuel source in much greater amounts than the best plant crops can produce.

Another AERI project is being conducted by Profs. Edward Bayer, Gideon Schreiber, and  Dan Tawfik of the Institute’s Department of Biological Chemistry, who are researching ways to break down cellulose – the main component of plant cell walls – so it can be used as a raw material for fuel. “When we have cellulose as fuel, we can also transport it and can even use it in fuel cells,” says Prof. Cahen.

Prof. Bayer has been conducting basic research on cellulose breakdown for more than 20 years and is one of the world’s foremost experts on the topic. He focuses on the cellulosome, a group of enzymes that degrades cellulose, and uses  genetic engineering to develop artificial cellulosomes that are more effective at breaking down, for example, manmade cellulose products such as paper. Now he is collaborating with Prof. Schreiber, an expert in designing and altering protein-protein interactions, and Prof. Tawfik, an expert in enzyme evolution, to design artificial cellulosomes with improved activity.

The most recent version of their artificial  cellulosome can turn a lab dish full of finely shredded paper into simple sugar syrup in about a day. These simple sugars are ideal for further conversion to liquid fuel, such as ethanol. In the future, the artificial cellulosome might be adapted to other cellulose-rich energy resources such as agricultural waste, and the scientists hope that liquid fuel will someday be made from recycled trash.

Another important goal of the AERI is to encourage young scientists to direct their careers to the pursuit of energy-related problems. Currently, says Prof. Cahen, few students are attracted to the field because of a dearth of funding and because relatively few top scientists pursue novel research in sustainable energy. To break this pattern, Prof. Cahen and his colleagues are making new outreach efforts, such as inviting top Israeli students to seminars. “We are planting the seeds and we hope that, in a few years, we can hire some of them as faculty,” he says.

The World Energy Council projects that worldwide energy demand will be at least double its present level by the middle of this century. The basic research conducted as part of the AERI is needed today, Prof. Cahen says, since “there’s typically a 15- to 20-year lag between a finding in the laboratory and its industrial success. Therefore, whatever we do now will be practical around 2025 or 2030, at the earliest.”

He stresses the importance of exploring many different approaches to sustainable energy. No single technology is likely to be able to supply all of the world’s future energy needs, and any solution will probably involve a mix of solar, biomass, wind, hydroelectric, nuclear, and other technologies. We need to work, Prof. Cahen says, “toward a strong, sustainable mosaic of many solutions, which, as a whole, will provide the solution.”  

The issue of understanding arose a number of years ago in the Science Teaching Department when several members were attempting to create a high school teaching unit on embryonic development – an especially complex subject that generally requires the mastery of a whole set of terms for key concepts and intricate processes. Clearly there was not enough time allotted in the curriculum to learn an entire scientific lexicon. Prof. Benjamin Geiger, then Dean of the Feinberg Graduate School (today Dean of the Faculty of Biology) proposed a new concept: Teach students how a developmental biologist thinks and works by having them read scientific research papers. Dr. Anat Yarden, whose background is in embryonic development, took up the idea.She developed a unique method of adapting scientific literature so that it could be read and understood by high school students.

The first textbook to come out of this initiative, The Secrets of Embryonic Development: Study through Research, contains adapted versions of three of the field’s groundbreaking articles along with background material, supplementary explanations, graphs and definitions. But the basic style and feel of the scientific papers were preserved, including the layout of the sections (abstract, introduction, methods, results and discussion) and the typical phrasing. In the process of creating the study materials, Yarden and her group found they had created a new genre of science writing, which they dubbed Adapted Primary Literature (APL). A second book followed the first: Gene Tamers: Studying Biotechnology through Research, and the books – used to teach matriculation-level biology – and the project behind them have begun to garner interest and spawn similar initiatives around the world.

Ultimately, Yarden would like to see APL used to teach areas of all the biology subjects studied for matriculation exams in high schools. As there is no shortage of exciting new scientific research, the articles could be continually updated, making the curriculum varied and pertinent. To help accomplish these goals, Yarden is bringing her method to those who teach science. Within the framework of the Caesarea Program – initiated this year at the Weizmann Institute to provide graduate education to outstanding high school teachers – she is starting a journal club. The club will encourage the teachers to read scientific articles, adapt them and use them in their classrooms. In this way, she hopes to extend the use of the method to more classrooms, as well as to broaden the subjects taught this way to include such fields as chemistry and physics.  

Collection Techniques
Natural sunlight is a dilute energy source: to produce a large amount of electricity, solar cells must be spread out over a very wide area. If today’s expensive photovoltaic units were replaced by optical concentrators that intensified sunlight by, say, a factor of 500, then the cell needed to produce the same amount of electricity would be 500 times smaller. The savings in silicon alone would go a long way toward making solar-produced energy economically attractive.

Focusing highly concentrated sunlight onto small solar cells, Prof. Amnon Yogev found that when filters are used to split sunlight into a number of spectral ranges, heating is reduced and efficiency of the photovoltaic unit is doubled. If the unused wavelengths are exploited for other uses, such as providing the energy for the “absorption cooling” that powers some refrigeration and air conditioning systems, the savings can be even greater.

Economic factors such as these hold the key to bringing solar energy to vast areas of the world that have no existing infrastructure for power generation and transmission based on fossil fuels. The investment necessary is modest: a 10-kilowatt photovoltaic unit could support the electric lighting, refrigeration, and communications infrastructure of an entire village. Anticipating the difficulties of maintaining solar installations in isolated areas, Institute scientists envisage building photovoltaic units complete with satellite communications networks, to allow maintenance reports to be transmitted automatically.

New Materials
Today most commercial solar cells are still made of silicon, which is stable but relatively expensive; however, several other materials are being developed for future use in photovoltaics. The goal: to produce solar cells that are both cheap and durable. The front-runners are thin-film technologies, in which a thin layer of a fine-grained photoelectronic material is deposited on an inexpensive large-area surface such as window glass.

Weizmann Institute research may speed up the application of one of the most advanced thin-film materials in solar cells. Cadmium telluride-based photovoltaics are already in the pilot stage of development and may soon be manufactured commercially on a large scale in the United States and Europe; but these cells tend to deteriorate over time. Because Institute scientists had in the past managed to solve major theoretical and practical problems related to photovoltaics, the U.S. Department of Energy asked them to address the deterioration of cadmium telluride-based units. The Institute team, headed by Profs. David Cahen and Gary Hodes of the Materials and Interfaces Department, revealed how these solar cells can be rendered more stable. Using chemical and physical investigation methods, the scientists showed, for example, that the cells must be used in a dry, preferably oxygen-free environment. The researchers are conducting further studies aimed at enhancing the stability of cadmium telluride cells and understanding the basic science underlying their performance. Such an understanding may help not only to develop better cells but also to overcome the psychological barriers - particularly, concerns over reliability - impeding the acceptance of experimental solar energy technologies.

In another project, Profs. Cahen and Hodes are investigating the mechanism of action of an innovative type of solar cell invented in the early 1990s in Switzerland. The dye-sensitized solar cell, or DSSC, is made of an organic material that is incorporated into a porous thin film consisting of microscopic semi-conductor particles held together like beads on a string. DSSC cells are radically different from other solar cells in several respects, and until recently it was unclear how exactly they generated electric power. Cahen and Hodes, in collaboration with colleagues in Israel and abroad, have suggested a mechanism that may account for the formation of photovoltage in these cells: apparently, the dye functions much like chlorophyll, the natural photosynthetic pigment in plants. The Institute researchers are currently striving to understand the mechanisms involved in the movement of electrons through DSSC cells.

Improving the Surface
The efficiency of silicon solar cells is limited by two major problems: surface recombination - the tendency of electrons to become trapped in the surface of the semiconductor; and light reflection from the surface of the solar cells, which can decrease the energy available for electricity production by 10-20 percent.

Prof. David Cahen and his colleagues are improving solar cell performance by eliminating the surface defects common to fine-grained semiconductor materials. This research involves analyzing the defects caused by minute amounts of impurities in the semi-conductor, then controlling those defects on the molecular level. Together with Prof. Avi Shanzer of the Organic Chemistry Department, Cahen has succeeded in improving semiconductor performance by grafting desirable properties onto organic molecules.

Prof. Shanzer is adapting models of chlorophyll, the substance that controls photosynthesis in plants, to improve the semiconductors used in photovoltaic cells. The technique involves dipping the semiconductor into a specially prepared solution containing porphyrins - the “backbone” of chlorophyll molecules. The porphyrin binds to the semiconductor surface, causing the semiconductor to absorb light more efficiently. This in turn induces a greater electric charge in the semiconductor. Developing his approach further, Shanzer’s group is working on synthesizing organic “wires” that would link light-harvesting groups such as porphyrins to a metal ion, creating molecular “antennae” to guide photons to the semiconductor surface. (For more on photosynthesis and solar energy, see p. 49.)

Ancient Heat Wave
It’s now official: the heating up of the Earth known as global warming has begun. The 1990s were the hottest decade on record, and according to an authoritative report issued by a United Nations-sponsored panel in January 2001, worldwide temperatures continue to climb. In the panel’s worst-case scenario, by the year 2100 these temperatures may rise by almost 6 degrees C. Are humans responsible for global warming? Science has yet to provide a definitive answer, but one thing is certain: if the warming trend continues, the ecological and economic consequences are likely to be catastrophic. Increasingly frequent natural disasters, agricultural damage due to rising sea levels, and consequent stress on health care and water management could cost the world more than 300 billion dollars. Therefore, understanding global warming and reining in its causes are matters of utmost urgency.

Prof. Aldo Shemesh seeks to shed light on current environmental debates by studying the climate that prevailed in various regions of the world in the ancient past. By examining ocean deposits, Shemesh is able to determine the climate fluctuations that occurred long before modern industry began releasing large quantities of greenhouse gases into the atmosphere. Shemesh derives his evidence from microscopic marine algae called diatoms, which make up marine sediments around the world. Diatoms have hints from past millennia hidden in their skeletons: to form their shells thousands of years ago, they absorbed carbon, nitrogen, and oxygen atoms from the environment. Depending on the climate, different varieties of these atoms, called isotopes, were fixed into the creatures’ shells. Now, by analyzing the isotopic composition of the remains, Shemesh’s group can peel back the layers of time and obtain glimpses into various aspects of the ancient environment - such as seawater temperature, the presence of ice, and the level of carbon dioxide (CO₂) in the atmosphere. For example, since the isotope Oxygen 18 tends to be enriched when the temperature is low, an alga shell with relatively high Oxygen 18 levels suggests a colder climate.

Using isotopic records of sediments from a high-altitude volcanic lake on Mt. Kenya, Shemesh reached the conclusion that a sudden warming of climate lasting several centuries took place in equatorial Africa some 2,000 years ago. The study revealed that the climate can warm up rapidly without any connection to human activity. Records obtained from lake sediments in the Swedish Lapland and on the Island of South Georgia also revealed climate variability caused by natural processes independent of human activity. Such research may enable scientists to distinguish between natural climate variability and global warming that results from man-made factors.

Another study has focused on the climate change that occurred during the coldest period of the last glacial age, some 20,000 years ago. By examining different ratios of certain carbon and nitrogen isotopes in diatoms in the Southern Ocean (the region surrounding Antarctica, including sectors of the Atlantic, Pacific, and Indian oceans), Shemesh was able to determine the level of CO₂ in the ocean water during the last ice age. He found that Antarctic surface water was a major source of CO₂ in the atmosphere. Since the Southern Ocean plays a major role in regulating the world’s CO₂ levels, these findings could help us understand the gas’s current status in the atmosphere. Shemesh is now developing new isotopic tools and studying marine records from different parts of the world in different time periods.

Vanishing Villain
Atmospheric levels of carbon dioxide (CO₂) stand today at an all-time high: whereas in the past 500,000 years they used to fluctuate between 180 and 280 parts per million, they have now hit 380 parts per million. This build-up is believed to be largely responsible for global warming: it exacerbates the greenhouse effect, which in turn heats up the Earth. However, in trying to determine how exactly CO₂ fits into the global warming puzzle, scientists run into a quandary: only half of the 7 billion tons of carbon spewed as CO₂ into the air each year accumulates in the atmosphere. The oceans appear to be responsible for dissolving about 1.5 billion tons, but what about the rest? Apparently, the remaining carbon is taken up by plants, but scientists do not yet fully understand the details of this uptake.

Along with researchers working on the problem around the world, environmental biologist Prof. Dan Yakir is determined to solve the CO₂ enigma. Understanding CO₂-related processes is essential for predicting climate change and for designing such environmental strategies as those aimed at controlling the levels of CO₂ and other so-called “greenhouse” gases in the atmosphere. Without knowing, for example, where a large portion of global CO₂ disappears to, it is impossible to tell exactly how this vanishing act affects the environment or whether it will continue indefinitely.

Prof. Yakir has designed a method for calculating the amount of CO₂ consumed by the world’s vegetation. The method is based on the analysis of different isotopes, versions of the same atom, in the atmosphere. Yakir found that plants prefer to absorb CO₂ that contains the light version of oxygen atoms, Oxygen 16, while the heavier version, the isotope Oxygen 18, tends to be left behind in the atmosphere. The ratio of the two oxygen isotopes in atmospheric CO₂ can therefore be used to calculate the extent of CO₂ consumption by plants and to follow its dynamics. However, various types of plants differ in the rate at which they consume CO₂. In recent studies, Yakir and his colleagues extended the isotope method to identify the contribution of different plant categories to CO₂ consumption. This approach is a valuable addition to the limited arsenal of tools available for the quantitative study of the biosphere’s response to changes in atmospheric CO₂ levels.

In addition to heading CO₂ studies at the Institute, Yakir coordinates the participation of several Israeli academic institutions in international networks aimed at understanding ecological processes involving carbon. In one such network, sponsored by the European Union, 30 research towers have been set up between Finland and Israel. The Israeli one, headed by Yakir, is considered the most special: its location in a transition zone between an arid and a semiarid climate ensures great sensitivity to perturbations in the environment. The 20-meter tower is located in the Yatir Forest, a plateau at the edge of the Negev desert planted with pine trees some 35 years ago. Research at the station has already yielded important findings. For example, it has revealed that high CO₂ content in the air seems to improve the efficiency with which forests growing on arid land use water: to absorb the same quantities of carbon, tree leaves lose less water than they would in a low-CO₂ environment. This revelation may make it possible to expand forests further into semiarid regions - an important prospect considering that forestation is a key carbon-reduction strategy under the Kyoto Protocol of the United Nations and one of the few means available for slowing down the potential climate change driven by the increase in such greenhouse gases as CO₂.

Rainwater “Archives”
Records of the Earth’s past and present climate are kept in an unlikely archive: rainwater. Every drop contains a wealth of information about the origins of rain and the climatic conditions under which it was formed. The information is “stored” in the isotopic composition of the rainwater: depending on the relative amounts of oxygen and hydrogen isotopes it contains, scientists can tell whether a particular drop comes from a lake or an ocean, whether it has traveled over deserts or lush forests, and how warm the air was when the drop originally condensed. This type of knowledge is crucial for understanding the water cycle and the global climate in general. On a worldwide scale, such knowledge is collected within the framework of a program called the Global Network for Isotopes in Precipitation, or GNIP.

Israeli researchers taking part in GNIP study the water cycle in the eastern Mediterranean area. Rainfall in this region is rather anomalous: Israel and its neighbors lie in a desert belt where hardly any rain would be expected at all, yet every winter they are blessed with significant amounts of precipitation, which replenish their groundwater reserves. Where does the rain come from, and why does it fall only in winter? It turns out that the region’s winter showers result from a geophysical upheaval: the Mediterranean Sea stays warm throughout the winter, and its evaporating water meets the dry, cold air arriving from Europe; the warm vapors, striving to rise above the cold air, create turbulence and cyclones that eventually lead to rainfall.

Isotopic studies of this and other local aspects of the water cycle were launched at the Weizmann Institute in the 1960s. Several Israeli academic institutions, including Weizmann, conduct isotopic studies as part of GNIP, and these national research efforts have been coordinated by the Institute’s Prof. Emeritus Joel Gat. The Mediterranean Sea, a large body of water encircled by land, is a perfect laboratory for studying air-sea interactions. A better understanding of the water cycle sheds light on both past and present climate, helps verify global climate models, and facilitates predictions in such vital areas as the relationship between climate change and rainfall.

World Oceans and Global Climate
One of the most dramatic climate phenomena affecting our planet is the appearance of a gigantic mass of warm water in the Pacific Ocean every few years. South American fishermen have named it “El Nino,” meaning “the child” in Spanish, since the event tends to occur around Christmas time. El Nino precipitates a variety of environmental disasters: it causes floods in South America, brings droughts to Australia, ignites forest fires in Indonesia, and decimates the Peruvian fishing industry. By predicting the irregular El Nino events, scientists may be able to help the world prepare for them and reduce their global damage.

Prof. Eli Tziperman studies the effects of oceans on the Earth’s climate. Using models and observations, he seeks to understand the behavior of oceans and such climate phenomena as El Nino.

El Nino is caused by oscillating deep ocean waves that travel back and forth along the equator in the Pacific. The waves alternately warm and cool the water at the surface of the ocean, which in turn affects the winds that caused the waves in the first place. These equatorial perturbations trigger changes in atmospheric temperature, pressure, and rain patterns around the world. Graduate student Eli Galanti and Prof. Tziperman are developing a sophisticated method that makes it possible to incorporate data gathered by research ships, satellites, and moored instruments into ocean models, in order to improve El Nino prediction. The Weizmann scientists have already used this method to understand how the mixing of deep ocean water with surface water affects El Nino’s dynamics.

Another study has focused on understanding the cyclical appearance of ice ages. Graduate student Hezi Gildor and Tziperman have proposed a new explanation as to why ice ages have occurred roughly every 100,000 years in the past million years, and why glaciers tended to cover the Earth slowly with the advent of each ice age, only to recede rapidly afterward. Their hypothesis is that sea ice, which can spread over the oceans in a matter of decades, may act as a “switch” that shifts the world’s climate into and out of an ice age. A better understanding of the cyclical mechanism that governs the occurrence of ice ages could improve the ability of scientists to predict climate changes.

Dust Is in the Air

Desert dust, ash spewed by volcanoes, smoke from burning forests, and soot from power plants are all potential sources of aerosols - minute particles suspended in the atmosphere. When sufficiently large, these particles may redden sunsets or fill the air with haze. But beyond their visual manifestations, aerosols can have a profound effect on the environment. They can affect the ozone layer, harm people’s health by lodging in their lungs, or alter the Earth’s climate; by scattering sunlight back into space they can reduce the amount of energy the planet absorbs, and by changing the properties of clouds they can modify rain patterns. Yet despite their importance, the exact role of aerosols in a variety of environmental processes is not fully understood.

Weizmann Institute physical chemist Prof. Yinon Rudich studies the relationship between the chemical composition of aerosols and the effect of these suspended particles on atmospheric systems. He and his team focus on organic aerosols and their interactions with atmospheric molecules ranging from water to ozone. Recent results, for example, revealed that water molecules can accumulate in cracks on the surface of organic aerosols. Other results explained how interaction with ozone changes the surface properties of aerosols. This research helps other atmospheric scientists to understand how aerosols behave and to clarify their impact on the environment.

Much of Rudich’s research focuses on one of the greatest uncertainties in climate research: the impact of aerosols on the properties of clouds. Working with colleagues from other Israeli academic institutions, Rudich found that clouds formed in an area affected by dust did not produce rain, while clouds formed at the same time and in the same region but outside the area influenced by dust did produce rain. The researchers concluded that dust particles coated by a soluble material serve as cloud-condensation nuclei around which water drops form. The presence of many cloud-condensation nuclei leads to the formation of clouds with large numbers of small drops of water, and in such clouds, the growth of drops by coalescence - which is essential for the production of rain - is blocked. Simply put, dust storms inhibit rain formation. These findings suggest that in arid regions such as central Africa, desert expansion may follow a vicious circle: poor land management - for example, exposure and disruption of topsoil for cattle grazing and agricultural cultivation - can increase the amount of dust blown into the air; more dust, in turn, reduces rainfall, exacerbating the drought conditions and contributing to desertification.

Early Achievements
Prof. Emeritus Joel Gat participated in a United Nations project to investigate the large-scale deforestation in the Amazon basin, which is likely to adversely affect the climate both locally and on a global scale. By gathering data on the stable hydrogen and oxygen isotopes in rain and river water and in atmospheric moisture, Gat quantified water balance estimates. On the basis of these data, researchers constructed theoretical models of water movement in the basin and evaluated the long-term effects of deforestation on the climate and hydrology of the region.

Ancient wood analysis performed by Prof. Dan Yakir may have yielded an explanation of the mysterious reference to agriculture in Masada in a first-century CE historic treatise. Masada, the last Jewish fortress to hold out against the Romans after Jerusalem was conquered in 70 CE, is situated near the Dead Sea, on the eastern margin of the Judean Desert, whose extremely arid climate cannot today support agriculture. An isotopic study of the tamarisk wood the Romans used to build a ramp to the fortress revealed that the climate in the region was cooler and more humid 2,000 years ago. This historic weather report could explain how the besieged Jews were able to farm in a region that is now a desert.

When cancer cells metastasize or tissues become damaged through inflammation, it’s likely that enzymes called matrix metalloproteinases (MMPs) are involved. This family of enzymes cuts through various bodily materials, including the tough collagen fibers that hold our tissues together.

One member of the family in particular – MMP-9 – is often produced by migrating cancer cells and in certain autoimmune diseases, and scientists have long believed that finding a way to inhibit its activities might be useful for treating these diseases. A team led by Prof. Irit Sagi of the Structural Biology Department in the Faculty of Chemistry has now employed an unconventional combination of techniques to reveal the structure of the entire MMP-9 protein. The team included Gabriel Rosenblum of the Structural Biology Department, Drs. Phillippe Van den Steen and Ghislain Opdenakker of the University of Leuven, Belgium, and Dr. Sidney Cohen of the Institute’s Chemical Research Support.

Their findings revealed a linker whose extreme flexibility and contortions “would impress even a swami yogi,” in the words of a scientific reviewer. The distinctive MMP-9 linker may turn out to be its Achilles’ heel: The team has already designed a molecule that binds directly to this domain to neutralize its activity, and Yeda, the business arm of the Weizmann Institute, has applied for a patent for this molecule. 

One Hundred Times Stronger
Natural interferon is widely used to treat a number of different cancers, but its effectiveness is rather modest. Weizmann Institute scientists have now succeeded in engineering a new version of interferon whose activity is 100 times stronger than that of the natural molecule.

Prof. Gideon Schreiber of the Institute’s Biological Chemistry Department was originally interested in a basic research question concerning interferons: How do these proteins produce two different kinds of effects inside the cell – either serving as the body’s first line of defense against viral infection or inducing programmed cell death, called apoptosis? Schreiber revealed that the different types of activity stem from the way interferon binds to its receptor. Moreover, his team identified the precise amino acids and structural features that affect the binding.

The scientists then created versions of interferon with different degrees of binding ability and different types of activity: They manipulated the interferon-receptor bond by replacing various amino acids in the interferon’s binding site and then testing the resulting interferon versions. Using this approach, they managed to create an interferon molecule, called YNS, that binds to cellular receptors much more strongly and, in a laboratory dish, is 100 times more effective than natural interferon at triggering the death of cancer cells. The scientists then found that the YNS molecule effectively eliminated human breast cancer cells in laboratory mice, while the natural interferon did not.

Yeda Research and Development Company, the Institute’s technology transfer arm, has patented the YNS molecule. If the new interferon proves sucessful at eliminating cancer cells in humans, it could be developed into an effective anti-cancer drug.

Deadly Repeats
Huntington’s disease is a genetic time bomb. Programmed in the genes, it appears at a predictable age in adulthood, causing a progressive decline in mental and neurological function, and finally death. There is, to date, no cure. Huntington’s, and a number of diseases like it, collectively known as trinucleotide repeat diseases, are caused by an unusual genetic mutation: A three-letter piece of gene code is repeated over and over in one gene. By the number of these DNA repeats, one can predict, like clockwork, both the age at which the disease will appear and how quickly it will progress. But what is the mechanism behind this remarkable precision?

Shai Kaplan in Prof. Ehud Shapiro’s lab in the Biological Chemistry, and Computer Science and Applied Mathematics Departments, realized the answer might lie in the buildup of mutations that occurs in our cells throughout our lives. The scientists realized that the longer the initial disease sequence, the greater the chance of additional mutations. In this manner, the genes carrying the disease code might accumulate more and more DNA repeats over time, until some critical threshold is crossed.

Shapiro, Kaplan and Dr. Shalev Itzkovitz of the Computer Science and Applied Mathematics Department have created a computer simulation that predicts, from the given number of genetic repeats, both the age of onset and the disease progression. The new disease model appears to fit all of the facts and to provide a good explanation for the onset and progression of all of the known trinucleotide repeat diseases. This explanation may, in the future, point researchers in the direction of a possible prevention or cure.

Ancient Throwback: New Technology
Today the management “posts” in the cell are occupied by proteins; but eons ago, when single-celled organisms were beginning to make their mark on Earth and life was simple, the living world might have been an “RNA world.” Recent findings suggest that RNA molecules, single strands of nucleic acids that are far less sophisticated than proteins, are capable of performing many of the cell’s main regulatory functions.

Riboswitches, discovered several years ago in bacteria, are segments of RNA that can bind to certain substances, thereby regulating the levels of these substances in the cell. Only one riboswitch has so far been found in higher organisms: The thiamin (vitamin B1) riboswitch regulates thiamin biosynthesis in numerous organisms that produce this vitamin – from the most ancient bacteria to highly developed plants. Dr. Asaph Aharoni and Samuel Bocobza of the Plant Sciences Department investigated this lone plant riboswitch. The scientists revealed the mechanism by which the riboswitch senses the presence of thiamin in the cell nucleus and makes sure the levels of this essential vitamin are neither too high nor too low by turning its production on or off as needed.

They may be ancient mechanisms, but riboswitches could be the basis of sophisticated future biotechnologies. Aharoni and Bocobza engineered reporter genes – genes that glow in fluorescent colors under the microscope when activated – that responded to thiamin levels as the riboswitches did. When inserted into plants, these reporters lit up whenever thiamin levels fell. This sort of reporter gene-riboswitch combination could pave the way to the design of live biosensors for all sorts of applications. 

Detection Goes Underground
Chemicals seeping in from toxic waste dumps, factories, gas stations, and other sources threaten underground water reservoirs. For example, one barrel of oil leaking slowly through the ground can pollute thousands of times its volume in freshwater. Considering that most of the world’s accessible freshwater is stored in underground aquifers, it is vitally important to safeguard these hidden reservoirs. Scientists usually rely on mathematical models to predict the movement of pollutants through layers of rock and soil. However, existing models are generally unreliable, largely because geological formations are extremely varied and complex.

Two professors in the Weizmann Institute’s Environmental Sciences and Energy Research Department - Brian Berkowitz, a hydrologist, and Harvey Scher, a physicist - are developing new mathematical models for predicting the movement of fluids and pollutants underground. On the basis of a theory previously used to model the passage of electrons through a disordered semiconductor, the scientists are seeking to discover how particles move through rock layers of different flow resistance. This research could help predict the consequences of leaks from nuclear waste canisters, evaluate the potential spread of contaminants from a new factory, or help engineers devise strategies for pollution containment.

Plotting the movement of pollutants through cracks or heterogeneous sediments is a tremendously uncertain business, data on the arrangement of the ground beneath the surface being generally limited and sketchy. Computer simulations help fill in the blanks, as does interdisciplinary collaboration among scientists. Using nuclear magnetic resonance imaging of fluid flow through rock fractures, and incorporating lab and field test data into their models, Berkowitz and Scher were able to predict not only how fluids move through cracks in the rock, but also how the cracks are dissolved and eroded as the fluid flows downward. The scientists have discovered that fluids flow especially quickly through such maze-like fissures and have developed models that reflect the risk of potentially catastrophic contamination.

In a separate project, Prof. Scher is studying the interface region known as the capillary fringe - a unique layer sandwiched between the rock formation that holds gases and water, and the stratum underneath that is saturated with water. He is developing models, based on theories describing the movement of a mixture of fluids through porous media, to describe the structure of the fringe and predict the transport of particles through this layer. An understanding of the capillary fringe will provide a better picture of how fluids move through the ground and how pollutants make their way into groundwater. Moreover, this research could clarify how bacteria residing underground may help degrade pollutants.

Seaside Modeling
Managing coastal aquifers is a crucial issue for seaside communities the world over. Near coastlines, seawater tends to seep into drinking water sources. Deep wells intended to pump freshwater from underground may gradually suck in salt water from the sea, endangering entire aquifers. And the problem is not limited to the coastline. Pockets of saltwater locked underground, away from the sea, may similarly endanger inland aquifers.

Prof. Brian Berkowitz is developing new quantitative models that specifically describe fluid flow and the movement of chemicals in rock formations near aquifers. This research may lead to improved management of freshwater resources along the coast or near underground sources of salinity. Such management is a particularly acute problem in Israel, a country prone to severe water shortages that derives about two-thirds of its water supply from groundwater - mainly the Coastal Aquifer, which extends some 130 kilometers along the Mediterranean, and the Yarkon-Taninim Aquifer, which runs parallel to the coastal one, under the Judean mountains. A sequence of drought years, as well as chronic overpumping, have already severely endangered the water quality in these underground reservoirs, and preventing their further deterioration is a matter of top national priority.

Averting the Metal Menace

Arsenic poisoning of drinking water has become a problem in many parts of the world, at times turning into a massive public health crisis, as occurred in Bangladesh in the 1990s. Chromium contamination has threatened water supplies in the United States; one famous case was featured in Erin Brockovich, a film in which the title character uncovers the poisoning of an entire town by a power company. These are examples of metal ion pollution, which has ravaged numerous communities around the world. Metal ions are among the deadliest water pollutants, harmful even in low quantities and tough to detect. Scientists are developing methods to detect the ions and remove them from water.

Laws against water pollution are only as good as the sensors that monitor compliance. New types of sensors for the real-time measurement of toxic metal levels in rivers and other fast-moving bodies of water are being investigated by Prof. Avi Shanzer of the Organic Chemistry Department and Prof. Israel Rubinstein of the Materials and Interfaces Department. The scientists have designed a gold electrode coated with a single layer of tightly packed metal-ion-binding molecules. When specific metal ions come into contact with the electrode, they bind to it, triggering an electrical response. Successfully tested in the laboratory with iron and copper, this metal sensor could in principle be developed into a device for detecting other toxic metals in water.

In a different approach, Prof. Shanzer is developing a method for removing metals from water. His team has demonstrated the possibility of synthesizing tailor-made organic molecules that bind to particular metal ions and has already successfully synthesized selective binders for copper, cobalt, nickel, lead, mercury, and cadmium. Currently available ion-exchange purification columns have a low capacity because they become plugged up by non-relevant metal ions; but columns based on Shanzer’s method - due to the high selectivity of his binders - are expected to have a high capacity. As a result, they should effectively remove even trace amounts of metal ions. The columns could be used, for example, to purify wells and aquifers that contain traces of poisonous ions.

A project launched by the late Prof. Abraham Warshawsky of the Organic Chemistry Department could help both detect and fight metal ion pollution. In Warshawsky’s method, water flows through a tube filled with synthetic beads that contain numerous holes. Inside the holes, two kinds of synthetic molecules, called ligands, are engaged in detection: one ligand is a collector molecule, designed to bind with a polluting metal; the other is a reporter molecule, which emits intense fluorescent light when bound to the metal. By manufacturing ligands that grab onto different ions, the scientists can make the system sensitive to a variety of pollutants. This work was conducted in Warshawsky’s lab by postdoctoral fellow Dr. Ying Wang, in collaboration with Dr. Gilad Haran of the Chemical Physics Department. The amount of light emitted by different pollutants is picked up by a photosensor, which indicates the chemicals in the water that have reached harmful levels. Metal-binding ligands may also be used to clean up pollution: if they hold on tightly to the polluting ions, they can be used to purify water in underground aquifers. This latter idea is being explored by Prof. Brian Berkowitz, who developed it originally with the late Prof. Warshawsky.

Early Achievements
Plants growing by the Dead Sea do not extract water from their immediate surroundings, which are excessively saline. Instead, they extract only winter flood water from the Judean hills, which occasionally reaches the area. This finding, by Prof. Dan Yakir, suggests that the plants are able to distinguish between salty water and non-salty flood water.

An ultrasensitive detector, developed in a collaborative study by three Weizmann Institute teams that began as a basic research project, has a wide variety of potential applications, ranging from sensing minute amounts of biomolecules to detecting pollutants in water or air. Profs. David Cahen, Ron Naaman, and Avi Shanzer of the Materials and Interfaces, Chemical Physics, and Organic Chemistry departments, respectively, led groups of researchers who succeeded in tracing the path of electrons moving from custom-made molecules to a semiconductor surface. This was accomplished by grafting a single layer of molecules onto a semiconductor, thereby creating an ultrasensitive detector for electron transfer. Cahen’s and Naaman’s groups are exploring new directions of research made possible by the innovative device, called MOCSER (MOlecular Controlled SEmiconductor Resistor), including its use as a sensor for chemicals in the brain, a detector for DNA mutations, and possibly as a DNA chip.

Deep inside the earth, there are underground pockets of groundwater similar to oil traps. The water in these geological traps, resembling a sealed bubble, has been stored underground for millions of years, safe from pollution. Prof. Emanuel Mazor, after studying underground water pockets in Australia and Israel, has reached the conclusion that they could serve as emergency reservoirs in a pollution event such as a nuclear catastrophe.

Scarcity of water in the Middle East and vulnerability of groundwater, Israel’s major water resource, to pollution have placed the country at risk of severe water shortages in the near future. Prof. Emanuel Mazor has drawn up a number of strategies for environmentally savvy water management. He has outlined a comprehensive approach: clean management of all enterprises, a nationwide campaign of water saving, special legislation, and the establishment of a research institute for water and environmental conservation.

Industrial plants, municipal waterworks, and private homes throughout the world use water-softening equipment to remove calcium from water (calcium minerals build up on pipe walls and restrict flow). However, the softening sometimes damages water quality or produces waste products, including tons of sodium-rich wastewater that pollutes underground aquifers. A new, environmentally friendly water softening method has been developed by Prof. Emeritus Ora Kedem. In her “cake filtration” approach, commercialized by an Israeli company, calcium minerals are filtered out without pollutants being released into the environment.

A new recruit to the Institute, Dr. Milko van der Boom of the Organic Chemistry Department, is working to create thin films with such desirable qualities as low weight and long-term thermostability. He is targeting an “all-organic” product, which he hopes will replace today’s inorganic materials. The rationale is simple. Organic films would be much easier to modify, offering far better, cheaper devices that could even be introduced into home appliances, revolutionizing the electronics industry.

The challenges of creating these films, however, are considerable - from effectively integrating organic molecules into thin films, to creating films that are thick enough to efficiently convey the light signal.

To address these challenges, Van der Boom and groups led by Prof. Tobin J. Marks and Prof. Pulak Dutta at Northwestern University have created a novel bottom-up growth method. The teams begin by producing custom-designed organic molecules, which they then integrate into the film, building it up layer by layer (each layer is only 2.5 nanometers thick).

They had to “trick” nature to do so, organizing the molecules in a novel arrangement in which the molecules are all aligned in one direction. “Nature prefers a random orientation,” says Van der Boom.

Another innovation is the introduction of polymers that help to organize the films, creating smoother materials. Using this approach, the teams have created highly organized films consisting of 100 layers - a marked improvement over the average 10-layer films achieved to date. The team has recently created the first prototype electro-optic modulators based on these films.

Roentgen had discovered X-rays. Within weeks, physicians were using these magical rays to see inside the human body and less than three months later, 14-year-old Eddie McCarthy of Massachusetts became the first person to have a broken bone set with their help. The new technology quickly found its way into scientific research, exploding into experimental significance following the 1912 development of X-ray crystallography, which offered a first-time look into the atomic-scale arrangement of crystals. Having exposed crystals to X-ray beams, the father-son team of Henry and Lawrence Bragg, found that the beams diffracted off the crystal’s atoms, and could be captured on film to disclose the crystal structure.

X-ray crystallography has since contributed to the discovery of DNA’s double-helix structure, drug development and far more. Today, sophisticated computational methods are applied to analyzing crystal diffraction patterns.

Crystal clear
Studies of how crystals form may weave together a web of unrelated fields, from those targeting semiconductor technologies, to studies of the origin of life, to the design of polymorphs - crystal formations of key importance in pharmacology.

The common denominator is size. To study these research challenges, Institute scientists apply X-rays to view as well as control the growth of crystals at the atomic level.

Profs. Meir Lahav and Leslie Leiserowitz of the Institute’s Materials and Interfaces Department pioneered the use of grazing incidence X-ray diffraction (GIXD) to analyze the structure of nanosized crystallites formed at the interface between air and water. The investigators are able to work out the exact structure of the crystals formed, according to the way the beam diffracts.

In their analyses, the team has yielded insights into a list of riddles, including how cholesterol crystals form in the body, causing heart disease and gallstones when in excess; the fundamental mechanisms of how water freezes; and the possible routes by which biological molecules such as proteins were first formed. The approach was developed in collaboration with a team of Danish physicists.

The team is currently studying how to control the design and growth of polymorphs - crystals that have different shapes despite being made from the same compound. Polymorphs are of keen interest to the pharmaceutical industry due to their potential influence on drug efficacy. For instance, penicillin crystallized into a form that easily dissolves in the body may be more potent than a penicillin drug packaged in a less soluble crystal. Polymorphs also feature prominently in the production of nanoscopic films used in semiconductors.

Oil from Algae
What are the best crops to grow for biofuels? Corn and sugarcane, presently converted to ethanol in Brazil and the USA, consume large amounts of petrochemicals and arable land in cultivation, and using them for fuel is already beginning to drive up the price of food. The contribution of soybean- and canola-based biodiesel in Europe to overall fuel consumption is small and cannot be extended. A better alternative, according to a number of scientists, may be lying under the nearest rock or floating on a stagnant pond: algae.

Algae have a number of advantages over other sources of biofuel. For one, they can be grown on marginal soil or in salt water, without draining water resources. For another, they grow rapidly and could be harvested regularly throughout the year. And there is no waste – no seeds, stems or roots to discard. Algae plantations placed near power plants would capture much of the emitted carbon dioxide to use as building blocks for biofuel, thus creating “green energy.”

Finally, some kinds of algae produce oil – up to 50% of their mass. This oil, says Prof. Avihai Danon of the Institute’s Plant Science Department, can be easily xtracted and converted to bio-diesel, which could be used in today’s diesel engines without significant investment. Algae could yield an estimated 30 times the oil output of the best crop plants, and could satisfy the fuel needs of the USA and other heavily industrialized countries around the world.

Danon and Prof. Uri Pick of the Biological Chemistry Department have begun a new project that aims to create strains of algae that will excel at generating oil for biofuel. Their first step is to understand how and when the algae produce the oil. Like green plants, algae get their energy from the sun and store it as sugars or oils. But there is a limit to how much energy one alga – a single-celled organism – can utilize. In fact, too much sunlight can overload the alga’s system, stimulating the production of free radicals that can harm or even kill the cell. This limit creates a trade-off between oil production and growth, and the cell must decide in which to invest its energy. The scientists suspect that it is in times of stress that the algae build up their stores of oil.

The researchers are working on several different strains of algae that grow in different conditions and have different traits. They are developing the tools to identify and compare the genes that regulate the algal metabolism, making decisions whether to stockpile oil or spread out, whether to take in additional sunlight or put up protective sunscreens. “Once we’ve identified the genes, we should be able to develop the means to control these processes in the algae ourselves,” says Danon, “and hopefully create algae that can be an excellent, environmentally friendly source of fuel.”

Recycled Fuel
While the debate rages over the ecological and economic value of using food crops to produce fuel, Weizmann Institute scientists are taking a different approach that could potentially solve two environmental problems with one stone – or at least one bacterial enzyme complex.

One of the obstacles to creating biofuels from organic substances such as agricultural waste is that they contain large amounts of tough materials – mainly cellulose – that do not break down easily. (Corn and sugarcane, on the other hand, are rich in starch and sugar that can easily be turned into ethanol.) Prof. Ed Bayer of the Biological Chemistry Department has been researching bacteria that chew up cellulose, converting it to sugar that they then feed on. In the 1980s Bayer, together with Prof. Raphael Lamed of Tel Aviv University, discovered how the bacteria’s cellulose-degrading machinery works. The cellulosome, as they dubbed this molecular machine, is a group of enzymes that work as a team to chop up the long chains of repeating sugar units in cellulose molecules into short sugars that can be dissolved in water.

About 50 percent of landfill material is cellulose, mostly in the form of paper, and it continues to pile up year after year. Breakdown is slow, partly due to landfill conditions and partly because the cellulose in such man-made products as paper turns out to be particularly hard for the bacterial cellulosome to digest. Bayer began tinkering with cellulosomes, adapting the bacterial machinery for turning plant cellulose into sugar into an effective tool for recycling paper. He and Lamed used genetic engineering techniques to create hundreds of different versions of the cellulosome, mixing and matching parts in their search for those that excelled at their new task. Prof. Gideon Schreiber, an expert in designing and altering protein-protein interactions, and Prof. Dan Tawfik, an expert in enzyme evolution, have joined the team to help design artificial cellulosomes with improved activity. The most recent version of the artificial cellulosome can potentially turn a lab dish full of finely shredded paper into simple sugar syrup in about a day.

Recently, this research has taken on new urgency. The simple sugars churned out in the process are ideal for conversion to ethanol, and the artificial cellulosome might be adapted to other cellulose-rich energy resources such as agricultural waste. Much research remains to be done before the process can be recreated efficiently on the industrial scale, Bayer cautions. Nonetheless, one day our cars may run on ethanol brewed from recycled trash.

Fuel of the Fittest
If algae and bacteria can be engineered to produce such bio-fuels as biodiesel and ethanol, might they also generate such futuristic energy resources as hydrogen? Hydrogen could be the cleanest fuel of all, as its combustion leaves behind only water. But most present-day methods of producing hydrogen still involve processing fossil fuels.

In an ambitious project, a consortium of scientists from France, Spain, Sweden, the UK, Portugal and Israel, including Prof. Dan Tawfik of the Biological Chemistry Department, are investigating the possibility of creating a bacterium that will produce hydrogen cleanly and economically. The researchers have started with a strain of cyanobacteria (often called blue-green algae, though they are not true algae). These photosynthetic, single-celled organisms have a long history of producing materials we need: They’re credited with releasing oxygen into the early atmosphere (paving the way for the evolution of oxygen-breathing animals), and with fixing nitrogen in soils so that plants such as rice can absorb it.

The researchers plan to use a cutting-edge approach to developing the new bacteria. Rather than adapting one or two existing genes, they aim to equip the cyanobacteria with a whole new set of biological components engineered for specific functions. The multidisciplinary team will use a slew of techniques to accomplish this, including one developed by Tawfik – directing the evolution of enzymes in cell culture to produce cellular components that are highly efficient at carrying out desirable tasks.

What is the difference between the experimental and theoretical fields? To understand, it helps to know that astrophysics examines how the universe – and the stars, galaxies, and other astronomical objects within it – works. Theoretical astrophysicists rely on the basic laws of nature to develop a physical understanding of the diverse phenomena that exist in the universe. Experimental astrophysicists collect information about the precise nature of these phenomena, providing their theoretical colleagues with the data to construct and test their models, as well as motivation for additional theoretical investigations to explain new and surprising observational results.

As an experimental astrophysicist, Dr. Gal-Yam has dedicated himself to the phenomena of supernovae. A supernova can be very basically defined as “a star that explodes,” says Dr. Gal-Yam; such an explosion, or supernova event, is observed as a tiny source of light that appears where none was visible before. Given the size of the universe, it is extremely difficult to find a new light source that represents an exploding star.

The key to finding supernovae is change. Most objects in the sky appear unchanged over a human lifetime. Take as an example Earth’s nearest star – its own sun. With a life expectancy of 10 billion years, it is highly unlikely that any changes in it will be observed. The same is true of most stars, and for this reason, much of astronomy is the study of things that do not change. However, this also means that if a scientist comes across a new source of light, chances are they have found something exciting.

Along with hunting for supernovae, Dr. Gal-Yam is trying to identify which stars exploded, and why. He points out that this is very difficult because scientists only know there was an explosion after the fact, and since there is no longer an actual star to study, it is hard to determine what kind of star it was.

“It turns out that there are all different kinds of stars that explode, as well as different types of explosions that have different physics,” he says, likening this research to asking what the shape of something was after it has been broken. But with a well-designed experiment – and a bit of luck – progress can be made in solving this  riddle. Advanced instruments such as the Hubble space telescope and giant land-based telescopes are helping in this quest.

There are two parts to experiencing a super- nova event: seeing the light of the explosion, and detecting miniscule, invisible particles called neutrinos. Dr. Gal-Yam says that “when we observe the light, we just see the envelope – we cannot see what is inside because the explosion is not transparent.”

However, it is known that the envelope contains neutrinos – and neutrinos teach scientists a lot about the physics of a supernova. Neutrinos are ejected from the core of an exploding star and can reach Earth, but only a few laboratories have equipment capable of detecting them. Such equipment includes large tanks of ultra-pure water. When neutrinos enter the water, they collide with other molecules; these collisions emit little sparks of light that can then be measured by researchers.

For scientists to know when to look for evidence of neutrinos in the water tanks, they must know that a supernova is going to occur. But how does one find such a tiny needle in the massive haystack of the universe?

One method is to continually watch the sky. The Weizmann Institute is taking part in a project that involves a network of powerful robotic telescopes spanning the Earth. Currently, there are seven worldwide, “watching very diligently, just waiting all the time for supernovae to happen,” says Dr. Gal-Yam.

The benefit of this network is that the telescopes provide constant observation: it is always night somewhere. The telescopes also take frequent photographs, allowing researchers to identify changes in a given section of sky. This scrutiny helps astronomers see stars as they blow up, providing the time of the event, among other valuable data – and alerting them to be on the lookout for neutrinos.

Because the amount of information produced by these photographs is so massive, researchers use sophisticated software to process the mountains of data in order to find the points of light that may represent supernovae. By examining “before” and “after” photos, astronomers can tell which star exploded, and then work backward to study that star and determine its properties. 

However, telescopes that are even more powerful than Hubble and other existing equipment are needed to gather clearer and greater data. To that end, Dr. Gal-Yam is collaborating with other institutions, including the California Institute of Technology (Caltech), on a new telescope, which will basically be a super-large, high-definition camera.

“The tools of my trade, so to speak, are these telescopes,” says Dr. Gal-Yam. It can be hit-or-miss work; nonetheless, “every night we look at the sky and compare photographs. A supernova might appear as a new dot in some galaxy, and then become brighter than the whole galaxy. And some of these provide keys to physical questions that have puzzled us for decades.”

Based on principles of active sensing that are widely adopted in the animal kingdom, the multinational team is developing innovative touch technologies, including a “whiskered” robotic rat. The whiskered robot will be able to quickly locate, identify, and capture moving objects. “The use of touch in the design of artificial intelligence systems has been largely overlooked, until now,” says Prof. Ehud Ahissar of the Weizmann Institute of Science’s Neurobiology Department, whose research team is one of the groups participating in the multinational project.

“In nocturnal creatures, or those that inhabit poorly lit places, the use of touch is widely preferred to vision as a primary means of learning and receiving physical information about their surrounding environment.” One such animal that employs this method is the rat. Several groups of the international consortium are investigating the ways in which rats use their bristly whiskers to explore their environment, and how their brains process such information. “If we succeed in understanding what makes an animal’s sense of touch so efficient, we will be able to develop robots imitating this feature, and put them to effective use.”

What is the whisker’s “secret”? Why is the sense of touch through a rat’s whiskers much more efficient than that of the average person’s fingertips? The consortium’s teams have provided some insights into these questions. One explanation concerns the way in which the sensory system works: Whiskers actively sweep back and forth repetitively, accumulating information about the surrounding environment. The sensing begins in the neurons at the whiskers’ bases, which then fire signals off to the brain. Moreover, experiments have shown that the way in which a rat uses its whiskers is context-dependent. The seemingly simple act of feeling out a three-dimensional object, for example, requires three different types of code, each encoding a different dimension — the horizontal, the vertical, and the radial (distance from the whisker base). The horizontal plane, for instance, is encoded in the precise timing of neural signals relative to the whisking motion. The vertical, i.e., the object height, is encoded by the vertical spacing of the whiskers, which are arranged grid-like on either side of the snout. The radial plane, on the other hand, is encoded in the number of times the neurons fire: The closer an object is to the rat’s snout, the higher the number of neuron-signaling spikes.

The consortium’s research also suggest that the signals travel from the whiskers through parallel pathways that function within parallel closed feedback loops, constantly monitoring the signals they receive and changing their responses accordingly. The researchers believe that it is the complex interactions between the feedback loops that are responsible for the rich and accurate control of movement, but at the same time, it poses an engineering challenge when trying to build artificial systems based on this concept.

“In order to investigate the role of feedback loops further,” says Prof. David Golomb of Ben Gurion University, Israel, whose research team is one of the groups participating in the multinational project, “consortium members will implement theoretical methods and calculations from theoretical physics and applied mathematics in order to develop and research models that describe the complicated neural processes that control active sensing.” The models are based on experimental observations, and are expected to be tested by experimental consortium teams.

Ahissar: “The aim of this research is to help gain a better understanding of the brain, on the one hand, and to advance technology on the other. That is to say, researchers can use robots as an experimental tool, by building a brain-like system, step-by-step, gaining insights into the workings of the brain’s inside components. With regard to technological applications, we suggest that it is the multiple closed feedback loops that are the key features giving biological systems an advantage over robotic systems. Therefore, implementing this biological knowledge will hopefully allow robotics researchers to build machines that are more efficient, which can be used in rescue missions, as well as search missions under conditions of restricted visibility.”

The BIOTACT project, which is funded primarily by the EC Seventh Research Framework Programme, includes participation by scientists from universities, research institutes, and high-tech companies from Britain, Israel, Switzerland, Italy, France, Germany, and the U.S.

Children and adults alike enjoyed a fascinating evening of guided tours of the Institute’s Clore Garden of Science, the Joseph H. and Belle R. Braun Center for Submicron Research, the laboratories of the Koffler Accelerator, and the Jean Goldwurm 3-D Visualization Theater.

At the Clore Garden of Science, visitors were treated to a demonstration, with audience participation, of “Vacuum Power,” a recreation of the famous Magdeburg experiments. The first such experiment took place in the late 1600s at Magdeburg, Germany, at the instigation of Otto von Guericke, a scientist, politician, and inventor who helped prove the physics of vacuums. For centuries now, people have enjoyed taking up the challenge to fight the power of the vacuum, carrying out their own versions of the Madgeburg experiment – which involves trying to pull apart two hemispheres held together by vacuum power – such as at Researchers’ Night.

Science café
Scientists and research students from the Institute came out of their labs to meet the public. These meetings took place not just on campus, but also in coffee shops in nearby cities. In this setting, called “Science Café,” the scientists and students talked informally with café patrons, giving the community a taste of the burning questions facing the researchers in their day-to-day work at the cutting edge of science.

The response to these casual encounters was overwhelmingly positive, and several coffee shops reported capacity crowds.

Draw Me a Scientist
“Israel is, without a doubt, part of the family of nations of Europe,” said Gianmatteo Arena, Head of the Operations Section of the EU Delegation to the State of Israel (and acting Science Counselor of the Delegation).

Arena was visibly moved as he spoke at the opening ceremony of the exhibition of children’s artwork, “Draw Me a Scientist,” which took place during Researchers’ Night at the Jeanne and Joseph Nissim Pavilion at the Clore Garden of Science. The opening was the culmination of an Israel-wide children’s drawing competition undertaken by the Weizmann Institute in which children were invited to show in their drawings what they imagined a scientist to look like. From the many hundreds of drawings sent in to the contest, 32 were chosen to hang in the exhibition, and four were awarded prizes.

Institute Vice President for Resource Development Prof. Israel Bar-Joseph, who awarded certificates to the winners, said in his speech that “Science and art start off from the same point: from an idea, or from imagination. Only farther on do the two separate: Science deals with facts, in an attempt to understand the world in which we live. Art, on the other hand, offers us an interpretation of our world. When these children set out to draw a scientist from their imaginations, as they see us, we were asking them in effect to give us a mirror. This exhibit, over and above its aesthetic and artistic aspects, is really a kind of social experiment from which we can learn how children see us scientists. And for this valuable insight, we sincerely thank you.”

Prof. Bar-Joseph then read to the children, parents, and invited guests the words that Noa Kahana, age 11, had attached to the picture she sent: “My picture is called ‘constant activity’ and it shows a woman scientist who is excited to discover thousands of things at once. She is tired and exhausted, but encouraged by the fact that in a little while she will succeed in discovering what she wants.”

Also taking part in the opening ceremony were Dr. Yoav Rozen, Director General of the Ministry of Science, Culture and Sport; and David Wizel, Project Officer of the  Directorate-General for Research, Strategy and Policy Aspects of the European Com- mission, who came especially from Brussels to attend the opening.

Prof. Doron Lancet of the Department of Molecular Genetics at the Weizmann Institute of Science is one of Israel’s most prominent genome researchers. The head of the Crown Human Genome Center, Prof. Lancet has directed research on DNA chips, disease genes, and genes responsible for smell and taste, and is currently working to develop a computational model for the origin of life on earth. Because the Weizmann Institute was Israel’s liaison to the international Human Genome Project, Prof. Lancet and his colleagues have unusually intimate knowledge of the field of genomics and its implications.

What are some of these implications? Prof. Lancet sees the genome revolution as leading to a “new tomorrow.” In the first part of this revolution, says Prof. Lancet, science concerned itself with discovering smaller and smaller bits of living organisms – from the body to cells to genes, and finally down to the level of DNA. “Now we are going in the opposite direction,” he says. “We are trying to understand how DNA makes us.”

Prof. Lancet compares the human genome to an encyclopedia: the volumes are the chromosomes, the pages are the genes, and the letters are the chemical components that make up the alphabet of the genomic code. Unlike a print encyclopedia, however, genetic material can reproduce itself. This reproduction happens when the two strands of the DNA molecule pull apart, acting as mirror-image templates for what will become two new, identical, double-stranded molecules of DNA. During this process of replication, errors (mutations) can be introduced into the sequence of chemical units (or nucleotide bases) that compose the two complementary DNA strands.

Scientists are trying to determine which of these errors might lead to particular diseases. Given that there are approximately three billion base pairs in the human genome, this would seem to be a daunting task. Luckily, scientists now have at their disposal some powerful tools and technologies, including what Prof. Lancet calls the “workhorses of genomics”: polymerase chain reaction (PCR) machines, which amplify DNA, and automated fluorescence-based DNA sequencers, which read the chemical language of DNA automatically.

As the current medical paradigm of mass treatment of patients shifts towards individualized medicine tailored to each person, it will become increasingly important for doctors and researchers to be able to identify specific genetic patterns that lead to disease. Many disease mutations are already well known, particularly those responsible for the so-called single-gene diseases. These diseases, such as Fragile X syndrome, cystic fibrosis, Tay-Sachs disease, or Gaucher disease, result from a mutation in a single gene.

Far more common — and more complicated to comprehend and diagnose — are multiple-gene diseases, which include high blood pressure, heart disease, osteoporosis, Alzheimer’s disease, schizophrenia, asthma, and cancer. These diseases, Prof. Lancet says, result from “combinations of small DNA changes, none of which can be honestly called a mutation.” None of these changes causes harm by itself, but they do have the potential to cause harm in combination.

The small changes that lead to multiple-gene diseases are called single nucleotide polymorphisms, or SNPs (pronounced “snips”). SNPs can combine in many ways, leading to a bell-curve distribution of disease severity within a population. Using schizophrenia as an example, Prof. Lancet points out that one percent of all humans have the disease, which can cause delusions, hallucinations, and incoherence, but that there are “several types of schizophrenia, with no one characteristic to them all.” Research at the Weizmann Institute has already identified a link between schizophrenia and SNPs within a gene known as AHI1, which could be a step toward new treatments for this devastating illness.

Just as there is variation in how genetic factors can contribute to disease, there is also variation in how a person’s genetic profile can influence his or her reaction to a drug. Like multiple-gene diseases, drug reactions are also distributed along a bell curve in populations. The promise in teasing apart an individual’s SNPs and genetic drug profile, says Prof. Lancet, lies in a new field called pharmacogenetics.

Pharmacogenetics would allow doctors to look at a person’s genetic profile to decide what medication that person will receive, in what dose, and potentially even in combination with other drugs, in a personalized cocktail.

Whether it is the search for more SNPs contributing to disease, or the creation of portable databases of individual DNA profiles, the future of medicine is contained in each person’s encyclopedia of genetic information — that’s Prof. Lancet’s vision for the “new tomorrow” and the dawn of individualized medicine. “Ten years from now, you might walk around with a card that says exactly what genome you have, and based on that, your medications and treatment will be prescribed,” he says.

Dunaliella bardawil, a single-celled alga so resistant to salt and sunlight that it can even survive in the hostile environment of the Dead Sea, is turning out to be a very versatile little creature.

It was Weizmann Institute scientists ? the late Prof. Mordhay Avron and his co-worker Dr. Ami Ben-Amotz ? who studied Dunaliella and learned to exploit the hardy alga's ability to produce vast quantities of beta-carotene, a natural pigment and source of Vitamin A. The Weizmann findings became the basis of a thriving export industry. Nature Beta Technologies, an algae-growing enterprise in Eilat owned by the Japanese company Nikken Sohonsha, produces beta-carotene-rich Dunaliella powder and other products that are sold as health food in Japan. And now two research teams headed by Profs. Ada Zamir and Uri Pick of the Biochemistry Department are exploring methods to boost and expand the alga's productivity in order to further increase its commercial value.

But beta-carotene is just one of the assets of this lowly plant. According to the scientists, Dunaliella?s unique survival strategies could make this alga a rich source of other high-value biochemical items. Furthermore, they believe that Dunaliella has the potential to become a vehicle for creating "smart" genetically engineered substances for biotechnology industries. Because its high-salt environment is nearly sterile, mass production of the alga and its potential products holds little risk of contamination. Once the method is perfected, Dunaliella could serve as an economical natural "factory" for an unlimited number of genetically engineered products, including vaccines, drugs and hormones.

As a first step in mining the alga for useful biochemicals, the Weizmann researchers have isolated an enzyme and a transport protein in Dunaliella that are capable of carrying out a variety of biochemical processes under high salt and temperature conditions.

The alga research is being done within the framework of the Magnet Consortium, a program of Israel's Industry and Trade Ministry aimed at building partnerships between Israel's scientific research institutes and high-tech industries.

The Magnet Algae Consortium is made up of the Weizmann Institute of Science and Nature Beta Technologies (the Eilat-based company) collaborating on Dunaliella, and Israel's Oceanographic and Limnological Research Institute, working together with a kibbutz and a chemical firm on a related alga project.

"We are all investigating basic issues regarding the biology of algae," says Prof. Zamir. "But belonging to the Consortium has made the scientists more aware of the practical economic implications of our work, so that what we do has two aspects ? basic and applied."

An additional, surprising role for dust was identified in the 1990s: As torrential rains in the Amazon region continuously wash minerals out of the soil, they are replaced by new minerals carried in dust blown over 5,000 km across the Atlantic Ocean from the largest desert in the world – the Sahara. Scientists believe that without a steady supply of vital minerals, the Amazon region would become a wet, but largely lifeless, desert.

In winter, seasonal winds lift dust into the air in the Sahel, the southern part of the Sahara, and carry it to the rainforest in South America. How much dust is expelled from the Sahara and how much of it reaches the Amazon rainforest? What turns particular desert regions into good sources of dust? These questions lie at the basis of research led by Dr. Ilan Koren of the Weizmann Institute’s Environmental Sciences and Energy Research Department. In a study conducted with the late Dr. Yoram Kaufman of NASA and other colleagues from Israel, the United Kingdom, the United States and Brazil, and published in Environmental Research Letters, the scientists focused on a particular desert region considered the largest source of dust in the world – the Bodele Valley, covering a 20,000-sq-km area in northern Chad.

Koren’s goal was to quantify, for the first time, the Bodele Valley’s contribution to the Amazon rainforest. An additional goal was to try to explain what turns this small valley into a leading “exporter” of dust. He and his colleagues combined the data collected by two different types of satellite sensors: One made it possible to cover a wide area and evaluate the extent of dust clouds and their movement; the other supplied precise optical information about the dust’s properties. In addition, satellite photographs taken at regular intervals allowed the scientists to evaluate the speed and direction of the winds and calculate the size of the dust “shipments.” Additional measurements at two spots above the Atlantic helped evaluate the amount of dust that is “lost” on the way to South America.

Analyses of the findings produced unexpected results: The Bodele Valley, which accounts for about 0.2% of the Sahara’s area, is responsible for 56% of the dust reaching the Amazon rainforest. Moreover, the total amount of dust arriving in South America from the Sahara each year is about 50 million tons – a much higher figure than the previously estimated 13 million tons and one that matches the amount thought to be needed to sustain the rainforest.

Why does the Bodele Valley supply such a significant amount of Amazon dust? “I looked at the satellite photos, and the answer was staring me in the eye,” says Koren, referring to Bodele’s unique geological shape. It is flanked on both sides by enormous basalt mountain ridges, with a narrow opening in the northeast. Winds that “drain” into the valley focus on this funnel-like opening, creating a large wind tunnel that directs the surface winds toward the dust source and accelerates them.

Though dust may not be a profitable export item, understanding its long-distance movement is a matter of global importance.

At first glance, cancer and Alzheimer’s disease appear to have little in common. Cancer is a group of over a hundred diseases in which cells grow out of control and spread throughout the body. Alzheimer’s is a progressive neurodegenerative disease caused by the abnormal buildup of protein in the brain. The common link between the diseases is the role played by enzymes called proteases, which cut long strands of protein into fragments. Cancer cells secrete proteases that dissolve collagen, creating holes in the surrounding cell matrix that enable the cancer cells to bulldoze their way through tissue and into other cells. In Alzheimer’s disease, insoluble fragments of a protein snipped from a larger protein by proteases accumulate in the brain, interfering with cognitive function and memory.

The proteases involved in both cancer and Alzheimer’s disease utilize a zinc ion to execute their harmful activity. Because little information on how this works was available, Weizmann scientists decided to find out. They developed a method that enables the process to be seen in real time – that is, as it is actually taking place.

“We used high-intensity monochromatic x-rays to study the environment around a metal ion during protease activity,” Prof. Irit Sagi explained to an audience of supporters of the American Committee for the Weizmann Institute of Science (ACWIS). “This allowed us to make molecular movies showing how a metal atom is activated inside a protease by water and other key protein residues. Our tools can be used to characterize the reaction elements that drive an increase in the rate of a chemical reaction in individual Alzheimer’s and cancer enzymes.”

Up to this point, scientists studying the workings of ultra-microscopic forms had to rely on the scientific equivalents of still photos, something like trying to fathom the concept of driving by looking at a photograph of a car. The resolution of Prof. Sagi’s animated “video clips” of enzyme molecules at work is so fi ne that the scientists are able to see the movements of individual atoms within the molecule.

The challenge facing the Weizmann team was to capture, step-by-step, the complex process (the whole of which takes place in a tiny fraction of a second) that an enzyme molecule goes through as it performs its work. Their pioneering method, published in Nature Structural Biology, was hailed as the first of its kind, and a potentially important tool for biophysicists. 

To obtain the “live action” footage, Prof. Sagi and her team use a technique akin to stop-action photography, but on an infi nitely smaller scale. They literally freeze the process at certain stages, using advanced methods of chemical analysis to determine the exact molecular layout at each stage. The most diffi cult part, says Prof. Sagi, was figuring out the correct time frames that would allow them to see each phase of enzyme activity clearly. She compares it to attempting to capture on film the swirling of syrup being mixed into cake batter — one has to gauge the points at which individual stages of the process will be most visible.

Building an animated sequence from individual frames, the scientists are granted a rare peek into the intricate dance of life on the molecular level. “This method,” says Prof. Sagi, “represents more than a major breakthrough in the techniques used to understand enzyme activity. It changes the whole paradigm of drug formulation. Now we can precisely identify which parts of the molecule are the active regions [those which directly perform tasks], and the exact permutations of these molecular segments throughout the whole process. New, synthetic drugs can be designed to target specific actions or critical confi gurations.”

Prof. Sagi’s team is doing just that for one enzyme family known to play a role in cancer metastasis. Matrix metalloproteinases (MMPs) assist the cancer cells’ escape and entry into new tissues by breaking down the structural proteins that keep cells in place, a skill normally needed to clear out tissue in preparation for growth or repair.

The ability to visualize complex processes inside a molecule also paves the way for developing drugs that selectively stop the activity of metal ions — in this case, zinc — inside proteases. Prof. Sagi of the Weizmann Institute’s Department of Structural Biology is working with the pharmaceutical company Novartis to translate this research into drug design. More than just a pipe dream, the information derived from these “molecular movies” has already been put to good use.

“We recently designed an antibody to block the activity of proteases by constraining the zinc-protein dynamics required for effi cient enzyme activity, thereby minimizing uncontrolled collagen dissolving in cancer,” says Prof. Sagi.

“Within five to ten years, we must provide a large-scale practical approach for renewable energy production, storage, and transport. Within 20 to 25 years, we must develop a non-proliferating source of nuclear energy using abundant material, generating low-hazard byproducts,” says Prof. Jacob Karni of the Weizmann Institute’s Department of Environmental Science and Energy Research.

Karni and his team feel the renewable energy development phase of this goal can be achieved largely by using energy from the sun as an alternative to burning fossil fuels such as oil, gas, and coal. Solar energy is the only renewable resource available in large enough quantities to replace a significant portion of the energy now supplied by fossil fuels, and therefore must be exploited worldwide on a large scale.

“Sufficient solar energy is available in many countries [and] on all continents except Antarctica. It can be turned into electricity, heat, or clean fuels that can be used or stored and transported,” says Prof. Karni. “The effort takes a multidisciplinary group, and the Weizmann Institute has the capability to bring the necessary disciplines together.”

Weizmann’s solar research laboratory, established in 1987, is the only such facility in the world located on an academic campus. The laboratory has six solar workstations, each capable of housing between one and three experiments. The results of one extensive project led to the development of a solar-thermal demonstration plant, which was installed in Nanjing, China, and began operation in November 2005. The plant implements state-of-the-art technology to convert sunlight to electricity.

The Weizmann Institute has taken a leading role in the development of practical alternative energy technologies. Regretfully, this effort is severely hindered by shrinking government support for alternative energy research.

“Research is defocused and underfunded. The problem cannot be solved this way. It is clear that we simply cannot rely on government funding,” explains Prof. Karni. “Conventional government policies say that fossil fuel consumption cannot be reduced in the next 25 years, so we need to increase efficiency. Driving hybrid cars, increasing production efficiency, reducing waste in the consumption of fuels and electricity, implementing stricter regulations, and using solar panels can help alleviate the problem to some extent, but they will not solve it,” he emphasized.

Western governments have taken baby steps to  encourage alternative energy sources, but Prof. Karni feels their efforts are a “talk tough, do little” approach.

“The Kyoto Protocol calls for a reduction in CO₂ emissions by a minimum of 5 percent below 1990 levels by 2012. This will be impossible to accomplish globally when more than half the world is expected to use 2 to 5 times more energy from fossil fuels without emission restrictions,” Prof. Karni says. “We might be able to develop enough nuclear energy to provide 20 percent to 30 percent of the world’s energy requirements by 2030 to 2040, but it is not likely to happen unless we develop and implement methods to better deal with the storage of spent nuclear fuel, proliferation, safety, and security issues,” he explains.

Fossil fuels are a concern not only because recovering them is becoming increasingly costly and polluting, but because burning them produces carbon emissions. 1.5 billion people live in countries where the consumption of electricity tripled from 1990 to 2003. Another 2 billion live in countries where electric consumption doubled during the same time period. Carbon emissions in these fast-growing countries are rising quickly.

“Their governments and industries are not concerned about pollution, because they are in a losing race to supply the need of fast-expanding economies, but the world may pay a terrible price,” says Prof. Karni. He continues: “There is increasingly convincing evidence that warming from fossil fuel—the greenhouse effect—has already become a dominant factor in climate change. The mean surface temperature of the earth is higher today than at any time in the last millennium, causing large-scale melting of arctic ice. Since 1979, the size of the summer polar ice cap near the North Pole has shrunk more than 20 percent. The world gets rid of heat through storms, which have increased in number and intensified in strength.”

Solar energy can solve the world’s immediate and future energy needs, but the development of this resource requires funding.

“The cheapest level is the initial conceptual-level research, but no one wants to fund it,” says Prof. Karni. “The second development level is demonstration, like we have in China, then commercialization. It’s all within our grasp.” 

When Prof. Ada Yonath of the Weizmann Institute of Science was recovering from a concussion suffered while riding her bike, she read an article about hibernating polar bears, which led her to consider the physical processes that enable and support a dormant state. It occurred to her that in order for the bears to go in and out of hibernation, it was possible that ribosomes were packed in an orderly manner – an idea that went against then-current thinking. And she wondered, “Why do they do this?”

More than 20 years later, Prof. Yonath won the 2009 Nobel Prize in Chemistry for her work deciphering the structure of ribosomes.

She began with the realization that in order to investigate ribosomes, they first needed to be crystallized. Often called the cell’s protein factories, ribosomes are composed of a large number of protein molecules loosely bound to giant chains of nucleic acids. Ribosomes are also notoriously unstable and tend to disintegrate, and crystallization should allow them to be imaged and their action studied. At the time – the 1970s – most scientists thought this was impossible.

“Top teams around the world, such as those at UCLA and MIT in the United States and the Medical Research Council in England, had been trying to crystallize ribosomes since the 1960s – with no success. I thought, this is such a delightful group of ‘unsuccessful’ people – they were all Nobel Prize winners – I would like to be among them,” Prof. Yonath recalled.

“People called me a dreamer,” she said, but she believed in her unconventional idea and pressed onward. Fortunately, she was conducting her studies at the Weizmann Institute of Science, where curiosity-driven research is actively encouraged.

Prof. Yonath needed strong ribosomes for her crystallization experiments, which led her to use ribosomal material from hardy bacterial strains isolated from the Dead Sea. These tough, thermophilic (heat-loving) and halophilic (salt-loving) bacteria proved ideal candidates. “After all, they’ve been around almost unchanged for five million years,” she explained.

In order to get the stable ribosomes she needed, she pioneered a new approach that involved exposing ribosome crystals to cryo-temperature during x-ray measurement. This method, called cryo-crystallography, is now a standard research procedure in structural biology. Prof. Yonath and her team made a staggering 25,000 attempts before they succeeded in creating the first ribosome crystals in 1980.

Over the next 20 years, using a sophisticated technique called x-ray crystallography, Prof. Yonath and her colleagues would continue to refine their studies. In 2000, teams at Weizmann and the Max Planck Institute in Hamburg, Germany – both headed by Prof. Yonath – solved, for the first time, the complete spatial structure of both subunits of a bacterial ribosome. Science magazine counted this achievement among the ten most important scientific developments of that year.

Later, Prof. Yonath’s team discovered the mechanism of action of five antibiotic drugs: they identified exactly how each of the antibiotics binds to the bacterial ribosome, shutting off protein production. Proteins are the cell’s primary component and the basis of all enzymatic reactions; thus, blocking their production kills the bacterium.

Prof. Yonath has said that her goal is to “to try to understand the principles of life from the inside by unraveling the detailed structure of ribosomes.” But why are ribosomes so important?

They are essential to life, and solving the ribosome’s structure gives scientists unprecedented insight into how the genetic code is translated into proteins. Upon receiving genetically encoded instructions from the cell nucleus, the ribosomal factory churns out proteins. Understanding protein biosynthesis is therefore the gateway to grasping life itself – including what happens when things go wrong and disease results.

The science done by Prof. Yonath and her co-winners of the Nobel Prize in Chemistry, Thomas Steitz of Yale University and Venkatraman Ramakrishnan of the Medical Research Council Laboratory of Molecular Biology in Cambridge, could lead to benefits such as more advanced and effective antibiotics and better ways to fight the pathogenic protein biosynthesis characterizing cancer cells. The three scientists separately used x-ray crystallography to reveal the atomic structure and inner workings of the ribosome.

This discovery will hopefully also help in the struggle against antibiotic-resistant bacteria, a problem that has already proven fatal to many and that is recognized as one of the most central medical challenges of the 21st century.

Prof. Yonath is the first woman in the world since 1964 to become a chemistry laureate, and only the fourth in history. She is also Israel’s first woman laureate. However, while she admires and respects the female laureates before her, she does not feel her gender is important: it is all about the research. “I am a scientist, not male or female,” she said. “A scientist.”

For more information on Prof. Ada Yonath, please visit:  http://www.weizmann.ac.il/YonathNobel/

Prof. Varda Rotter, head of the Institute’s Department of Molecular Cell Biology, studies p53, a gene that suppresses tumor growth and may one day open doors to the development of new cancer treatment drugs. “There is really a strong feeling that a critical breakthrough in preventing cancer and designing future therapies will occur once it is understood how this gene works,” said Prof. Rotter.

With the mapping of the human genome, knowledge of p53 is expanding: both biology and genetics as a whole have, in the past six years, undergone a major revolution. Prof. Rotter went on to explain that p53 is a very important gene and one of the major tumor suppressors in our genome.

She elaborated that the human genome is comprised of some 30,000 genes, which are present in each individual human cell. The beauty of biology is that each healthy cell can only “read” a certain part of the genome. For example, our skin cells can interpret the information needed to produce melanin and protect us from the sun, while ovarian cells will read enough information to know to secrete hormones in a coordinated way at a given time.

While healthy cells carry out their intended functions, researchers are asking themselves how cancer cells differ. For molecular biologists, understanding the unique features of the cancer cell is critical for recognizing the enemy.

A cancer cell, while similar to a normal cell, not only reads and translates genes at the wrong time and place, but also contains mutated genes, Prof. Rotter stated. Contributing to malignancy are oncogenes, which under certain conditions turn a normal cell into a cancerous one. “There is no simple answer as to why we carry oncogenes,” she said.

There about 150 oncogenes, all of which are supposed to be silent, explained Prof. Rotter, but certain incidents or accidents provoke the cells to start growing or multiplying in an uncontrolled way. In contrast, healthy cells know how to grow and reproduce themselves to a certain degree and then stop.

At least 300 mechanisms can awaken oncogenes, said Prof. Rotter. The most common is the occurrence of a genetic mutation which, although not necessarily inherited, can be passed down from parent to child. Environmental factors, such as exposure to too much ultraviolet light or x-rays, can also awaken an oncogene. Once a mutation in a dormant oncogene occurs and becomes functional, it cannot be turned off.

“Our cells knew about the problem of oncogene ‘awakening’ long before it was discovered by us,” she said. Healthy cells, having this knowledge, contain tumor suppressor genes such as p53 that fight oncogenes by scanning for genetic mistakes and signaling cells to repair the damage or stop replicating, and thus helping to prevent uncontrolled proliferation. Genes such as p53 also initiate cell death: a healthy cell knows when to die, noted Prof. Rotter. 

Researchers have found that many cancer cells do not contain healthy tumor suppressor genes. These genes are instead mutated and cannot execute their functions. They do not know how to sense damaged DNA or how to put repair or cell death into motion, she said.

“Some people are born with less-than- perfect tumor suppressor genes –that’s the concept of genetic predisposition to cancer,” said Prof. Rotter. “A parent can have a mutation in the p53 gene and can transmit it to his or her children.”

While p53’s role as a single gene is important, knowing how it interacts with the rest of the genome is crucial to understanding cancer development, Prof. Rotter said. “Cancer growth is not mediated by a single gene. Rather, it involves a multitude of genes,” she added.

To better understand how p53 prevents cancer, Prof. Rotter and her colleagues developed a system that makes it possible to change the status of the tumor suppressor gene in a controlled way at specific and defined stages of cancer development. They then analyzed how other genes expressed themselves at given time points in relation to p53 status using “gene chips,” which are small glass slides containing microscopic strips of DNA. One chip provides a printout of activity levels of about 10,000 genes, allowing researchers to observe which genes are involved at a given time point in the cancer’s development.

A group of physicists from the Weizmann Institute have developed computational tools in order to help the researchers make sense of the genes’ activity on these chips. These tools have enabled Prof. Rotter and her colleagues to identify ten clusters of genes that are altered in the course of cancer development. They found one group to be negatively regulated by p53 – a discovery that would have been impossible without the new computational tools, explained Prof. Rotter. “It’s like putting a new lens in your glasses and being able to see everything in an additional dimension,” she said. 

Understanding how a network of genes is affected by p53 may lead to the development of therapies that target these entire genetic pathways rather than just one specific gene. “We hope to one day develop therapies that will target specific networks of genes,” Prof. Rotter said. “Continued research of p53 and defining its role in preventing cancer growth is a fantastic challenge.”

Prof. Yehiam Prior of the Institute’s Department of Chemical Physics is researching the detection of trace explosives with lasers and developing an innovative method to protect computer conversations from eavesdroppers.

Finding a needle in a haystack
The detection of materials employed in explosives is generally done by moving suspect particles from a given location, such as a person’s clothing, to a detector for analysis. For example, “puff machines,” which are installed in many airports, blow a puff of air across a traveler’s clothes and skin and into a machine. If the traveler has had any contact with a number of “red flag” substances, such molecules will be detected and identified.

Puff machines may be adequate for airport security purposes, but contact detection has limitations, says Prof. Prior.

“Puff machines identify molecules by their mass and the way in which they shatter into their fragments. This is fine for common explosives such as TNT, but it does not work for complex objects such as anthrax. Some compounds may be too similar to other compounds to make a distinction by weight only,” he explains.

Prof. Prior’s laboratory is also working on an innovative method that employs laser light to identify trace explosives. The technique is based on the principle that the reflection of light shined on molecules provides a unique “optical fingerprint” that computers can be trained to identify. Thanks to the special properties of lasers, detection can be done from afar, negating the need to bring a suspect molecule to a machine.

A fascinating aspect of this technology is that pulses of laser light can be shortened and manipulated to selectively excite individual bonds within a molecule before that molecule has a chance to redistribute its excitation within all degrees of freedom. The pulses are so short that they must be measured in “femtoseconds” – one millionth of a billionth of a second.

Using selective excitation by these ultrashort pulses, methods are being developed to identify minute amounts of a material – for example, 10 drops of a hazardous substance in a large lake.

When fully developed, one may envisage a remote sensing laser-based machine that will routinely and nonintrusively monitor crowds and identify people who have been in contact with hazardous substances.

Making computer communication more secure
The word “eavesdropping” conjures up images of listening in on a private telephone conversation from an extension phone in another room. But eavesdropping can easily be done on computer conversations: the message is simply diverted to another computer, read, and sent on its way without the user’s knowledge.

Weizmann scientists are striving to make communication more secure by preventing a message from being read without the knowledge of the intended recipient. One method is to scramble the message so that it is difficult to decipher without knowing the code.

In a good example of Weizmann’s complementary research, Prof. Prior is taking a different approach to this problem. In order to make it impossible to surreptitiously intercept a communication, he has tapped the principles of quantum mechanics by invoking the power of photons, which are massless particles. Single photons can be copied by a computer, but if they are prepared as entangled pairs, any manipulation of one of them can be undeniably traced.

“Photon-tapping is not possible if photon pairs are used, because the connection between the two photons is such that when one is detected the other one, which might be miles away, will tell the difference. Therefore, any conniving listener will leave a clear sign of the intrusion,” explains Prof. Prior.

These are just two examples of projects that will be tackled in the Nancy and Stephen Grand Research Center for Sensors and Security, which is being established at the Institute with a $5 million grant from Nancy and Stephen Grand. The interdisciplinary center will enable Weizmann physicists, chemists, and biologists to work together on useful technologies that make the world a safer place.

“In the next few years, we want to build on our significant strengths and establish several new research groups in these and related fields. This will enable us to develop new methods to win the confrontation between the bad guys and us,” says Prof. Prior.

The machine is a particle accelerator. It’s nestled in a 27-km-long tunnel, dug some 100 meters beneath the border between France and Switzerland, near Geneva. This accelerator is a part of CERN, the European particle physics laboratory. CERN is a world giant in the field of physics: Its scientists came up with, among other things, the computer languages and protocols that became the basis of the World Wide Web, and it has an effect on the European economy similar to that of the American space program in the U.S. Yet for all its accomplishments, the scientists at CERN, with all their complex machinery, haven’t managed to track down this one missing particle. Their best hope yet lies with the new accelerator being built, called the Large Hadron Collider (LHC), which will be able to accelerate bundles of protons to 99.999998% of the speed of light. These bundles will be aimed straight at each other, causing collisions that will release so much energy, the protons themselves will explode. For less than the blink of an eye, conditions similar to those that existed in the universe in the first fraction of a second after the big bang will be present in the accelerator.

At that first moment, the universe was simple, hot and very energetic. As the seconds ticked by, space expanded, and that energy began to dissipate. The universe cooled, becoming more complex as it did so, until it reached the level of complexity we know today. Inside the collider, the scientists will try to recreate those simpler, primordial conditions – a cosmos in which all particles were simply “different faces” of a small number of elementary particles, and the four fundamental forces that act between those particles were but expressions of a single force. As a first step in reconstructing that primal force, scientists have managed to join two of those forces: the electromagnetic force and the weak nuclear force. (The other two are the strong nuclear force and gravity.) But the existence of this “electro-weak” force presupposes the existence of a particle called a “Higgs” – named after the Scottish physicist Peter Higgs who, along with Robert Brout and Francois Englert, first predicted it. The only fly in the ointment is that since its prediction over 40 years ago, no Higgs particle has yet been detected.

A number of Weizmann Institute physicists have joined in the effort to find the missing Higgs particle. They’re a somewhat multigenerational scientific family – Prof. Giora Mikenberg, who heads the Israeli team, is the teacher and mentor of Prof. Ehud Duchovni, who taught Prof. Eilam Gross. Also working with these three are Dr. Vladimir Smakhtin, Dr. Daniel Lellouch and Dr. Lorne Levinson, all of the Particle Physics Department and the Nella and Leon Benoziyo Center for High Energy Physics.

High-Speed Collisions
Inside the accelerator, powerful, head-on collisions take place continuously between the protons, resulting in highly energetic particles that wink in and out of existence in a tiny fraction of a second. To obtain proof of their existence, one must identify the traces they leave behind. Thus a number of particle detectors have been created, each designed to trap a different kind of particle. The Weizmann team led by Mikenberg has developed a special detector, constructed at the Institute and other places around the world, which will contribute to detecting the elusive Higgs. “Elusive” may be an understatement: The chances of being able to find a Higgs particle in a single collision are about the same as those of coming up with a specific cell from a specific leaf on a specific plant by plucking one cell at random from all of the plants on the whole planet.

The LHC, equipped with superconducting magnets that work at temperatures of less than 2 degrees above absolute zero (absolute zero is -273° C), will produce something like a billion collisions per second. If protons were people, the collision rate would entail every person on the planet running into every other person on the planet every six seconds. Calculating and analyzing the data from all of these collisions will be akin to listening in on all of the planet’s telephone conversations at once, assuming the entire population is talking simultaneously on 20 phones apiece.

Hidden Dimensions and Black Holes
In addition to the Higgs particle, the LHC might, at some time in the future, produce millions of very tiny black holes. This surprising idea arises indirectly from string theory, which posits that the particles we know are simply manifestations of one “fundamental constituent,” called a string, and all the forces acting in nature are nothing more than different aspects of one single primeval force. Reality, as suggested by this theory, contains at least eleven dimensions, but seven of them are “curled up” and shrunk so small they can’t be observed.

Another recent model has suggested that the gravitational force can propagate in the additional dimensions, and that the size of the curvature of some of these additional dimensions might not be so small. Under these assumptions gravitational force becomes very strong at short distances, in particular for very energetic (massive) particles. Close to particle collision sites, this can lead to an enormous concentration of gravitational power in a small area. If this happens, a black hole might form. In fact, if calculations are correct, black holes could be created in the LHC at a rate of up to one per second. There’s no need to worry though: The physics of black holes dictates that the smaller the black hole, the higher its temperature. Such tiny black holes will be so hot they’ll vaporize almost as soon as they come into existence.   

An Israeli-Pakistani team at the “Atlas” experimental station

Prof. Ehud Duchovni
Ehud was born in Israel in 1953. In his youth he was an Israeli swimming and target-shooting champion. He served in an elite army unit and was later a target of a terrorist attack. He was awarded a medal for bravery by the Israeli Police, and the Verdienstkreuz am Band by the German President, for his actions in this attack. Later, while on reserve duty, he was wounded in the back. Duchovni is married to Noga and is the father of Inbal, Eynat, Gilead and Avner.

Prof. Giora Mikenberg

He was born Jorge Mikenberg in Buenos Aires, Argentina, in 1947. When he was just 16, he left his family in South America, changed his name to Giora, and set out for Israel to live on a kibbutz. In Israel, with encouragement from Prof. Yehuda Shadmi, he began to study physics, eventually ending up at the Weizmann Institute of Science. In the army, he served under Sergeant Ehud Duchovni, who would become his pupil. At CERN, Giora is known as George. 

Prof. Eilam Gross
Prof. Eilam Gross was born in Tel Aviv. After completing his army service in an elite communications unit, he left for New York to study music. There he came across a cult book, The Tao of Physics, which prompted him to come back to Israel and study physics at the Hebrew University of Jerusalem. His master’s thesis at the Weizmann Institute was written on string theory, after which he “deserted” theortical work for experimental high-energy physics and the team of Prof. Mikenberg. Today, between mathematical formulas and charting particle trajectories, he continues to work on his music, and he dreams of staging a performance that will combine music with insights gained from particle physics. He is the father of two daughters, Nuphar (20) and Yaara (15).

Prof. Adi Kimchi, Head of the Molecular Genetics Department, and research student Sharon Reef recently identified a novel protein that tells the cancerous cell to choose the self-eating method of suicide. In research that was published in the journal Molecular Cell, Kimchi and Reef discovered that this new protein is actually a shortened version of a previously known protein that usually causes apoptosis. These two proteins are in fact encoded by the same gene, even though each instructs the cancerous cell to commit suicide in a different way. The scientists proved that the shorter version of the protein, due to the missing segment, carries out its activity in an area of the cell completely different from that used by the longer protein. Consequently, autophagy is
triggered instead of apoptosis.

The process of autophagy is based on the concept of “recycling bins”: double-membraned sac-like structures that actively develop in the cells. Especially during times of starvation, when food is lacking, these bins are able to recycle some of the cell’s contents, providing it with extra food and energy. But under certain circumstances, the recycling bins work in overdrive mode, resulting in self-eating to the point of death. The question arose: Is the observed autophagy – that triggered by the novel protein – a survival mechanism or its opposite, an agent of self-destruction?

To answer the question, Kimchi and Reef, together with Einat Zalckvar and Shani Bialik of the Molecular Genetics Department and Prof. Moshe Oren and Ohad Shifman of the Molecular Cell Biology Department, silenced two genes that are known to be necessary for assembling the sac-like autophagic “recycling bins.” They discovered that reducing the occurrence of autophagy via gene silencing increased the survival of cells and thus concluded that the formation of the membrane-bound sacs in this case spells total degradation for the cells’ contents.

But why have two different suicide mechanisms developed in cells? Kimchi suggests that the autophagy track is a sort of back-up plan, in case the cancer cell fails – for a variety of possible reasons – to sacrifice itself by apoptosis. By employing a back-up plan, the cell continues to ensure the prevention of the spread of cancer. Now the scientists plan to check if their understanding is correct, or whether autophagy is an independent process, unrelated to the cell's  earlier failed attempts to commit apoptosis.   

Eating Machines
Anyone who’s had the experience of putting machinery back together and having a part left over knows that some parts are more essential than others. Prof. Zvulun Elazar of the Biological Chemistry Department has used this principle to identify, for the first time, two sites on a particular yeast protein that are indispensable for protein recognition. Without these recognition sites, the process of assembling the “recycling bins” needed for cellular self-eating can’t take place.

For the protein to carry out its activity, a specific, complementary protein needs to recognize and “plug” into one of its “sockets” – an action that initiates a cascade of events. By removing various socket-like structures one at a time from the protein and seeing how this affected the overall working of the autophagic machine, Elazar and his research team were able to isolate the specific site the second protein must recognize and hook up to. When this site was missing, that protein remained unplugged, leaving the cellular recycling machinery idle. They also found a second site on the protein that appears to be necessary for autophagic activity, although how it works needs to be studied further.

Autophagy in mammalian cells has significant associations with neurodegenerative diseases, heart disease, cancer, program-med cell death, and bacterial and viral infections. Because the autophagic recycling system found in yeast is similar to that in mammals, this research could provide crucial insight for further studies into the malfunctioning of cellular machinery and its consequences.

This research, which was published in EMBO Reports, was conducted with Ph.D. students Nira Amar of the Biological Chemistry Department and Gila Lustig of the Biological Regulation Department, in collaboration with Dr. Yoshinobu Ichimura and Prof.Yoshinori Ohsumi of the National Institute for Basic Biology, Japan.

The brain is made up of a network of neurons that “talk” to each other via synapses – specialized junctions that act like electric wires, explains Prof. Schwartz. Originally, scientists widely accepted that no new nerves are formed after the birth of an individual.

However, over the last few decades, researchers have found that certain brain regions are able to renew their neurons throughout life, including the olfactory region, spinal cord, eyes, and a certain region in the adult brain – the hippocampus – believed to be the area responsible for our cognitive ability, learning, and memory functions.

“The mechanisms which allow the formation of these new neurons in the adult brain are not fully understood,” says Prof. Schwartz. “Research is still in its infancy.”

However, about ten years ago, Prof. Schwartz and her colleagues found evidence to support their suggestion that cells normally involved in immune responses can promote the healing of damaged neurons in the central nervous system (CNS). Prior to that time, the scientific community thought immune cells should be kept away from the brain, because they were perceived as a threat to the organ’s delicate networks. “Our discovery therefore ran against the dogma,” she said.

The researchers asked themselves what kind of immune cells are needed to generate this healing and found that the answer seemed to be T cells (a type of white blood cell produced in the bone marrow and which are part of the body’s immune defense system) that recognize self-proteins in the brain.

Originally, researchers hypothesized that the thymus deletes all T cells that recognize the body’s own proteins, as they could ultimately cause autoimmune disease. Over the years, however, scientists have found the presence of autoimmune cells in healthy individuals and the debate has been whether they are an outcome of a failure of deletion or a purposeful selection.

Prof. Schwartz and her colleagues suggest that, based on their evidence, autoimmune cells are needed in everyday life to fight off enemies arising within the body, such as toxic substances generated by damaged nerve tissues. But the level of these autoimmune cells must be controlled; if they are not, they can cause autoimmune disease, she explains.

Prof. Schwartz and her colleagues first observed the presence of autoimmune cells in the CNS of animals recovering from optic nerve injury in the 1990s. Shortly thereafter, they found that animals receiving a vaccination of T cells experienced a better recovery from spinal cord injury than animals that did not receive vaccinations.

In their latest research, published in Nature Neuroscience, Prof. Schwartz and her colleagues showed that these autoimmune T cells may also be key players in the body’s maintenance of a normal, healthy brain, enabling the brain regions to form new nerve cells, maintaining the person’s cognitive capacity.

They already knew from earlier research conducted by other groups that rats kept in an enriched environment with mental stimulation, socialization, opportunities for physical activity, and proper nourishment, exhibited increased formation of new neurons close to the hippocampus region, when immune cells were present in the brain.

Therefore, to test their theory, Schwartz and colleagues repeated the experiment using genetically engineered mice that lacked T cells. Significantly fewer neurons were formed in those mice, even though they lived in an enriched environment.

They then used engineered mice possessing all of the other important immune cells except for the T cells that recognize brain-specific antigens. They found impairment of brain-cell renewal, confirming that the missing T cells appear to be an essential requirement for this process, and can be partially restored by replenishment of the immune-cell pool.

In another set of experiments, the researchers found that mice possessing the relevant CNS-specific T cells performed better in some memory tasks than mice lacking CNS-specific T cells, suggesting that the presence of these T cells in mice plays a role in maintaining learning and memory abilities in adulthood.

Based in part on this research, Prof. Schwartz speculates that as people age and the effectiveness of their immune systems declines, safely boosting autoimmunity via a vaccine using a weak self-antigen may be a way to preserve neurogenesis.

In animal models, this approach is already being tested for the neurodegenerative diseases Alzheimer’s, Parkinson’s, and glaucoma. It may help boost a weak autoimmune response to these diseases and slow down chronic neurodegeneration, explains Prof. Schwartz. Such a vaccine may be used in combination with stem cell therapy to create a synergistic effect, she added.

Prof. Schwartz anticipates that this research will lead to many different ways to prevent brain senescence, development of dementia, and halt the progress of neurodegenerative diseases. “The bottom line is that we all hope that this research will translate into a healthy brain and a healthy immune system,” she says.

Prof. Zvi Livneh and his team of Weizmann Institute scientists in the Department of Biological Chemistry have pinpointed an enzyme that plays a role in protecting individuals against lung cancer. Genetic differences in the activity of this enzyme may help explain why some get cancer and others don’t. The scientists hope the finding will be used to assess a smoker’s risk for lung cancer, making it easier to persuade high-risk smokers to kick the habit.
 

How cancer occurs
When we are young and growing, many of our body’s cells multiply constantly. After we reach maturity, cells begin to multiply for replacement only, rather than growth; they are programmed to know when to stop. Cancer occurs when cells lose their “brakes” and multiply in an uncontrolled fashion.

“Cancer means a genetic change (mutation) has occurred. You must control mutations to prevent cancer or slow its progression. This requires an understanding of what makes a normal cell suddenly transform into a cancer cell,” Prof. Livneh told an audience in Florida.

Human DNA is comprised of information bits that are chemically coded T,C,G, and A. DNA is formed in two long strands that are twisted together in a double helix pattern. When a cell multiplies, the DNA strands separate, and each strand then makes a copy to form a new double helix. The replication process is highly accurate, but not perfect: each cell averages 1 “typo” in 10 billion letters. These mistakes are greatly increased by external DNA-damaging agents, such as sun, tobacco smoke, or food additives, or internal processes, such as waste products left over from the body’s own metabolic processes.

“There is no way to avoid damage. It’s a part of normal life,” said Prof. Livneh.

When DNA damage is extensive, a cell might choose to commit suicide. Cells, however, prefer to continue replicating. To this end, sophisticated DNA repair mechanisms in the cell recognize damage, cut short segments out of the strand, and replace the damaged bits. Countless instances of damage are caught and repaired daily. Yet some escape proper repair. The replaced segment might contain mismatched letters, for example. If the mutation is passed on unrepaired, it can eventually lead to cancer. Five to 20 mutations must accumulate in a single cell before it begins to divide in an out-of-control fashion.

Finding a way to measure DNA repair
“Cancer can be caused by the excessive actions of DNA- damaging agents such as tobacco smoke or other external factors, the reduced ability to respond to this damage with DNA repair mechanisms or, more likely, a combination of both,” said Prof. Livneh. “We know this because as our ability to repair DNA decreases, cancer risk rises.”

Prof. Livneh and his colleagues have identifi ed an enzyme, known as OGG1, which plays a central role in repairing a type of DNA damage that can lead to lung cancer and head and neck cancers.

High levels of OGG1 are desirable – nonsmokers have an average OGG1 level of 7. Smokers with an OGG1 level of 4 have 124 times the risk of lung cancer than nonsmokers with normal OGG1 levels. (A high level, of course, is not a 100 percent guarantee that cancer will not develop, nor does it protect against other effects of smoking such as hypertension.)

The goal

Applying this information to medicine requires only the development of a simple blood test for OGG1 levels. “The test could be used to screen smokers. It might be a convincing tool to warn those most at risk to stop smoking. If you have low OGG1 levels, you should reduce your exposure to tobacco, ultraviolet radiation, and other carcinogens,” said Prof. Livneh. “It would also open the door to developing drugs to strengthen OGG1 levels.”

While knowing the role of OGG1 cannot, at present, prevent cancer or stop mutations from occurring, it might help those at risk postpone the development of cancer until it becomes irrelevant. “Since the incidence of cancer increases with age, if you reduce the rate at which mutations accumulate, you can delay the age at which cancer appears. Who cares if you get cancer when you are 120?” Prof. Livneh said.

While the topic of neuroscience could be perceived as daunting, the half-day seminar, which featured four prominent scientists, attracted about 150 people to the Helen & Martin Kimmel Center for University Life at NYU. This large turnout is perhaps because, as Prof. Ilan Chet, President of the Weizmann Institute of Science (WIS), Israel, indicated in his welcoming remarks, brain research is one of the areas of science that attracts the most interest from the public. We all want to know who we are, and what makes us “us,” both as a species and as individuals.

Prof. Yadin Dudai, head of the Weizmann Institute’s Department of Neurobiology, performs globally recognized neuroscience work, particularly with respect to the processes and mechanisms of learning and memory. In his presentation entitled “The Hidden Life of Memories,” Prof. Dudai led the audience through the lifespan of a memory, or, as he prefers to call it, “the biography of an item in our memory.”

When we encounter a stimulus (such as observing a face or a building), it takes about a fraction of a second to register that stimulus. If you record that information for slightly longer – two or three seconds – it becomes short-term memory, which lasts for a few minutes.

Next is the vital stage called “consolidation.” This is the phase in which short-term memory becomes stabilized as long-term memory. This can take from a few minutes to a few weeks, and involves interaction between the cortex and the hippocampus brain regions. If something goes wrong in this interaction, the memory remains short-term.

Once a memory is long-term and stable, how do we actually “remember”? Typically it is through exposure to a stimulus (for example, smelling and tasting hot chocolate), which then triggers “associative recall” so that the stimulus calls up an existing long-term memory (ice-skating with your sister and drinking hot chocolate to get warm).

Each item in our memory has a distinct biography, including properties such as content and age (how old the memory is). But no matter what the memory is about, the lifespan of a memory can be described in terms of phases. These phases are crucial, as Prof. Dudai’s research shows that at these points we may be able to modify or erase a long-term memory.

First, the memory must be called up. When a long-term memory is retrieved, it shifts from the inactive, stable state to the active, unstable state (in other words, it is again short-term), after which the memory may then be reconsolidated. This has clinical promise for persons who live with harmful memories. Interference with damaging, long-term memories may be performed in a number of ways, including electroconvulsive therapy or medicines. This research could help people who suffer from severe, debilitating problems of memory, such as post-traumatic stress disorder (PTSD).

In this work on amelioration of traumatic memories, Prof. Dudai is collaborating with NYU’s Prof. Joseph LeDoux, who is a University Professor, the Henry and Lucy Moses Professor of Science, and a member of the Center for Neural Science and the Department of Psychology.

Prof. LeDoux, whose lecture was entitled “The Emotional Brain: Friend and Foe,” focuses on a topic long ignored by neuroscientists: emotion. By studying emotion and memory, Prof. LeDoux has learned that when we retrieve memories, we call up the last, most recent version of the memory; this is new and evolving research, as it was previously generally accepted that the original memory was the first to be retrieved. This research has implications for issues such as the reliability of eyewitness testimony and other situations where accurate memory is critical.

Another aspect of his research is the many effects of fear on the emotional brain and the problems (such as anxiety, depression, panic, obsessive-compulsive disorder, and other syndromes, such as PTSD) that may result.

Intangibles such as emotions have long been considered unmeasurable; however, thanks to new techniques in human brain imaging, these can now be studied empirically. The WIS/NYU collaboration involves core research in brain imaging and is providing extraordinary results, as David Heeger, Professor of Psychology and Neural Science at NYU, discussed in his presentation “Brain Imaging: A New Window into the Human Mind.”

Brain imaging by functional magnetic resonance imaging (fMRI) is similar to the MRIs performed for routine medical examinations. The difference between an fMRI and a standard MRI is that the fMRI has the ability to observe both the structures of the brain and also which structures participate in specific functions; for example, the part of the brain that responds to a given type of stimulation, whether it is physical, verbal, visual, or memory-related.

However, multiple parts of the visual cortex respond to optic stimulation. There are two locations in the brain that process motion, but they do it in different ways, enabling the brain to make inferences about motion and space.

Dr. Heeger stated that when the back of the brain – the visual cortex – is viewed via fMRI during a visual experience, the image shows a sweeping change across the cortex, proving that there is an actual physical change in the brain as a result of perception.

Such physical change as a result of perception is clearly demonstrated by the work of Prof. Rafael Malach and his group at the Weizmann Institute’s Neurobiology Department, whose research using “natural” brain conditions has drawn worldwide attention. His presentation, “Watching Brains Watching Movies: Studying the Human Brain under Free, Natural Conditions,” drew a great deal of interest from the audience, who were encouraged to challenge their own powers of perception.

Scientists, says Prof. Malach, are tempted to treat human psychology and the human mind as an engineering problem, because it is “very convenient” to believe that you have total control over the research and examine the brain as discrete parts.

His intuition, however, is that while this is indeed a powerful approach, it cannot provide the full picture since our minds work in creative, original, spontaneous ways that cannot always be considered in machinelike terms.

His solution? To study the brain under more naturalistic conditions. Prof. Malach thought films would be a good way to simulate natural vision: movies are streaming, are multidimensional, contain auditory stimulation, have emotional aspects, and are much more like our natural vision than the traditional stimulus/response studies.

Together with the Weizmann Institute’s Dr. Uri Hasson, who is now at NYU, and other students in his group, they performed an experiment that was both scientific and fun – they showed people 30 minutes of the classic Western, “The Good, The Bad and the Ugly.” All the subjects had to do was lie in an fMRI machine and enjoy the movie while Prof. Malach and his team performed scans to see what happens when the brain is engaged and taking in many stimuli.

The researchers were surprised by the results, which showed that people’s visual systems are remarkably similar when receiving the same sensory stimuli. In fact, the readouts from each of the participants were so alike that by observing a map of brain activity of one individual watching the movie, it is possible to tell, with a great degree of confidence, what all the other brains will do when watching the same movie. This phenomenon, called “intersubject synchronization,” extends across a variety of factors, including gender lines.

While our experience of a movie is of a continuous stream, fMRI shows that the activity in our brain is actually more like an orchestra – different areas rise and fall in response to cues, and each area is responding to a different scene or aspect of the movie.

These free-viewing studies also have great potential for use as diagnostic tools to find brain abnormalities. For example, could movies diagnose or reveal what goes on in the autistic brain? Again, Prof. Malach showed intriguing preliminary results from a study in collaboration with Uri Hasson and Prof. Marlene Behrmann. The brains of autistic persons showed a drastic reduction in the “synchronization” effect of the movies.

However, the autistic brain was not quiet and inexpressive – rather, it appeared to be engaged in spontaneous action, which the fMRI displayed in washes of color representing vast waves of activity. The mystery is that this change was generated from inside the autistic brain, not from outside stimulation such as the movie.

It is not yet understood why this happens, but Prof. Malach’s further studies could shed light on this effect. Very little of this activity is seen in the “normal” brain. Such research is a promising tool with great potential to reveal brain deficits in people not only with autism, but with conditions such as retardation and dyslexia.

The WIS/NYU partnership is taking this and other research even further, into issues of time, narrative, consciousness, and diagnostic tools. This exploration of the inner workings of the brain will enable us to not only understand the basic ways in which our minds work, but will bring us closer to alleviating the suffering caused when something goes wrong, resulting in disorders such as Alzheimer’s disease, autism, and schizophrenia. New knowledge can lead to new therapies. The scientists allied in the WIS/NYU collaboration in neuroscience are truly using science for the benefit of humanity.

Prof. Scherz and his colleagues hope that this vascular targeting photodynamic treatment (VTP) can be used as a first-line therapy for prostate cancer. If this is accomplished, patients could avoid surgery or radiation, which can cause side effects that negatively impact sexual function and quality of life. In the Phase II studies, which are sponsored by Steba Biotech of France, the treatment destroyed cancerous tissue and spared vital organs, such as the urethra, in men with prostate cancer who had not benefited from prior radiation therapy. VTP took an average of 20 minutes and did not cause significant side effects. Approximately 50% of the patients appear disease free at one year after a single treatment.

One advantage that this treatment has over other forms of photodynamic therapy (PDT) is that the chlorophyll-containing drug clears the system within hours, rather than days. This helps to reduce side effects to the skin, such as sunburn, and should allow for multiple treatments within a short period of time, explains Prof. Scherz. Additionally, one optic fiber is able to treat a tumor up to 3 to 4 centimeters in diameter, which is larger than tumors treatable by conventional PDT.

Researchers also plan to treat about 30 patients in a clinical trial in England. These men are not undergoing any treatment for prostate cancer, other than watchful waiting to make sure the disease doesn’t spread. They want to avoid surgical removal of the prostate and receive the bacteriochlorophyll-based PDT. Prof. Scherz hopes that this form of PDT for prostate cancer will be available in the United States, England, France, Canada, and Israel in the near future. In the meantime, he and his colleagues are evaluating how this treatment might help treat breast, liver, pancreatic, kidney, and brain cancers. “The therapy will have to undergo modification for each type of cancer,” he explains.
Prof. Scherz points out that the strides in his research would not have been possible outside of the special habitat of the Weizmann Institute. The congregation of different disciplines within a supportive multidisciplinary infrastructure allowed for the rapid development and implementation of the project.

To better benefit from the PDT modality, researchers have to understand the ways some molecules, when excited by light, transfer energy to create radicals.(Radicals are entities that are able to destroy larger chemical entities, such as proteins or membrane lipids.) Then researchers must decipher the impact of such processes on the tumor tissue and normal blood tissues and, finally, define the treatment targets – cells, blood vessels, interstitial tissue.

Prof. Scherz explains, “We then asked ourselves – first, how can we make PDT with the new reagents and, second, how can we make this general modality most effective?” They arrived at the idea of targeting the tumor vessels with molecules that will not leave the blood vessels, but will clear rapidly from the treated patients. Chlorophylls of photosynthetic bacteria appeared to be the best choice, as nature adapted them for efficient light harvesting and radical production at near-infrared, where light penetrates deeply into animal tissues.

Creating a team that could meet on a daily basis to answer such questions was crucial, and the readiness of researchers and students at the Weizmann Institute to enter such multidisciplinary efforts made it easy. Profs. Scherz and Salomon succeeded in gathering students with experience in chemistry, as well as staff scientists and colleagues in biology and physics. The Institute’s technology transfer arm, Yeda Research and Development, provided the critical connection to the pharmaceutical industry, and Steba Biotech undertook the development of Tookad, the first candidate in the modified-chlorophyll series.

Prof. Scherz concludes, “The Weizmann Institute helps to bring ideas forward and helps those ideas become realized.”

Taking advantage of recent advances in DNA technology, the researchers are working to fi nd out what goes wrong, at the molecular level, when colon cancer develops — what are the defects in genes, or in the “expression” of those genes, that allow abnormal cells to grow out of control?

Speaking at an American Committee for the Weizmann Institute of Science (ACWIS) forum in New York, Prof. Eytan Domany of the Weizmann Institute’s Department of Physics of Complex Systems, likened DNA — that familiar double-stranded carrier of genes inside every cell of the body — to a cookbook. Each gene is like a single recipe for a dish which is akin to a protein, whose chemical formula is “written” on the gene. The gene is expressed when the corresponding protein is actually produced.

As Prof. Domany noted, there are many opportunities for errors in this cookbook, just like a misprinted ingredient in one of the recipes. In cooking, the result is a ruined meal; in the body, the result is a fl awed protein, leading possibly to cancer.

To try to discover where the recipes are going wrong in colon cancer, Prof. Domany and his colleagues have begun with tissue samples from 144 individuals — including samples of colon cancer, colon growths called polyps that can become cancerous, and normal colon tissue. The job of creating an initial “profi le” of gene expression for each of these individuals goes to Dr. Daniel A. Notterman, a professor of pediatrics and molecular genetics at the University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School.

To do this, Dr. Notterman focuses on the amount of messenger RNA (mRNA) in the cells of each tissue sample. mRNA is the molecule that takes the instructions from a gene in the cell’s nucleus and carries the information to the cell’s protein-making machinery, which in turn churns out the appropriate protein. Sticking with the culinary analogy, mRNA is a photocopy of the recipe, sent to the cook.

Proteins are the workhorses that actually carry out all the functions in the body. When a gene acquires a defect, the result may be an abnormal protein or protein levels within a cell that are too high or too low — that is, a problem in the way the gene is being expressed. Cancer arises when such cells continue to grow and spread unchecked.

For technical reasons, it’s easier to study a gene’s expression by looking at RNA levels in the cells of a tissue sample rather than by studying proteins, Dr. Notterman explained at the briefi ng. Using a DNA “chip” that allows the simultaneous analysis of thousands of RNA molecules over a matter of hours, his lab was able to create expression profiles for the roughly 30,000 genes in each of the 144 tissue samples.

Those data, in the form of what looks like a sea of numbers, then go to Prof. Domany, whose job is to find meaningful patterns in the “noise” — pulling out the relative handful of “candidate” genes most likely to play essential roles in colon cancer. To begin to make sense of the numbers, Prof. Domany color-codes the data, with different shades of color representing the expression levels of the thousands of genes in each patient.

The aim, as Prof. Domany explained, is to separate the patients into groups based on similarities in their gene expression profi les. “We take a picture that looks very random and reorganize it so that we can reveal the structure,” he said. What his lab has come up with so far is roughly 200 genes that are altered at the level of RNA and appear key in colon cancer progression.

That list of genes then moves on to Dr. Francis Barany of the Weill Medical College of Cornell University, who tries to uncover the changes in DNA — the master cookbook — that contribute to colon cancer. “The problem is, how do you distinguish the really important cancer-specifi c defect from the ‘bystander’ defect,” said Dr. Barany. The foundation of this research project, he explained, is that “candidate genes that are consistently altered at the DNA level are likely to be cancer-specific.”

Cancer-gene research, Dr. Barany noted, generally focuses on three types of genes: oncogenes, which promote cancer growth; tumor suppressor genes, which act like the name implies; and genome integrity genes, which act like the body’s “mechanic.” Among the problems that can arise are mutations in the structure of the DNA, as well as so-called “epigenetic” changes, which refer to alterations in the way genes are expressed in the absence of structural defects in the gene.

The future of cancer treatment, Dr. Barany said, is to move away from “blanket treatments” that try to slow down cancer cells — and harm healthy cells in the process — toward targeted drugs aimed at specifi c gene defects in cancer. The ultimate hope is to be able to test a patient for the specifi c molecular characteristics of his or her tumor, and then choose the right treatment from an arsenal of targeted drugs.

Reaching that goal will, of course, take a continuing effort to identify the genetic culprits in cancer. As Prof. Domany noted, colon cancer, on the molecular level, varies widely from person to person, and much work remains in untan- gling the genetic underpinnings. The collaboration he and his colleagues have undertaken is currently in the early, data acquisition and “data mining” phase of what is expected to be a 5- to 10-year effort.

A new international research project aims to improve this situation by setting out to write a "Cell Operations Manual" and a "Cell Repair Manual." This project is part of an ambitious initiative of the National Institutes of Health (NIH) in the U.S. called the "Roadmap for Medical Research." The brainchild of NIH director Elias Zerhouni, the Roadmap was set up to fund innovative biomedical research in a number of areas, with no less a goal than that of transforming medical science. In the futuristic area of nanomedicine, four groups were awarded grants totaling $43 million over five years. Prof. Benjamin Geiger, Dean of Biology and researcher in the Molecular Cell Biology Department at the Weizmann Institute of Science, is a member of one of these four groups, the NanoMedicine Center for Mechanical Biology. Each member of the group, which includes biologists, materials scientists, physicists and theoreticians from the U.S., Israel and Switzerland, will bring his or her own research experience to bear on fundamental questions concerning the mechanics of life on the incredibly tiny scales of cells and molecules.

Scale, in fact, is one of the more tangled puzzles the scientists plan to address. How do cells, around 40 microns across (a micron is a millionth of a meter), self-organize to become organisms that are meters in size? At the other end of the scale, single molecules, the information-bearing units of the cell, are in the nanometer range - just thousandths of the cell's size. If cells were the size of people, their sense organs would be little bigger than grains of sand. How does communication between a cell and its parts take place across this range?

Communication is another subject the scientists will tackle. Cells are continually subjected to mechanical forces, whether the pumping force of blood or the structural force of bones, tissues and neighboring cells. Endowed with sophisticated means of sensing these forces, they are able to convert their "readout" on the nature of the force into biochemical signals that then inform the cell's actions. But how exactly does this happen? Many diseases - including metastasis, in which cancer cells stop clinging to their neighbors and move away - might be tied to the cells' failure to properly sense and interpret forces. In addition, bioengineers attempting to grow tissues from various stem cells have found that cells need the proper mechanical cues in their environment to know how to develop into specific cell types.

From nanomaterials and nanoelectronics to molecular biology, the world of the ultra-small has its own physical laws, which very often differ from those of the everyday world. By incorporating knowledge from varied fields, the research group intends to develop new approaches to understanding the mechanics of the cell. As their work progresses, the scientists hope to gain insight into many of the major health issues facing us today: wound healing, hypertension and cardiovascular diseases, osteoporosis, nerve regeneration,immune responses and cancer. The "instruction manuals" they're planning will then become works-in-progress that can be applied to maintaining the machinery of life in good working order.

Surface Patterns
For a number of years Prof. Geiger, a molecular cell biologist, and Prof. Joachim Spatz of the University of Heidelberg, a materials scientist, have been working together to try to figure out how the cell "reads" and responds to the information in its environment. Spatz and his group in Heidelberg create materials with surfaces that mimic collagen, one of the body's support materials. They simulate different conditions by controlling various properties of these materials, such as their surface topography or relative hardness, and they also produce nanopatterned surfaces with minuscule areas of differing properties. Onto this carefully designed surface they anchor assorted molecules using gold nanoparticles.

These molecules are positioned so as to create tiny islands on which only one receptor (a cellular "antenna" through which cells connect to the world outside their walls) can gain a foothold at a time. "With these materials, we see exactly which molecules the receptors recognize and interact with," says Geiger. In recent studies, the scientists have discovered that the placement of the binding molecules affects the ability of the cell receptors to work together either to keep the cell stuck to the surface or to help it move. The method has the added advantage of providing a relatively large surface - a centimeter or so square (several football fields to a cell) - to work with.

Numerous plants in nature are capable of recruiting bodyguards via a chain process, which involves a slew of enzymes and culminates in the plant releasing a mixture of volatile organic materials, among them substances called terpenoids. Terpenoid-producing plants include corn, apple trees, beans, cucumbers, cotton and strawberries. They attract a wide variety of predator insects, such as ladybugs, which devour aphids, and parasitic wasps, which lay their eggs in the larvae of harmful bugs.

The pathway of terpenoid production and release is extremely complex, making it possible for the plants to generate different terpenoids to attract assorted insects for all sorts of purposes - from pollination to the repulsion of harmful bugs. But what happens when terpenoid production is ineffective and does not sufficiently protect the plant? Can the pathway be corrected to adjust the time, place and quantity of terpenoid release? Such a correction would significantly improve the plants’ ability to protect themselves against their enemies. The scientists studied this possibility in a model research plant called Arabidopsis thaliana, the first plant to have its entire genome mapped and deciphered.

In attempts to jump-start the terpenoid release system, scientists around the world have tried equipping the cells of different plants with a gene that codes for a unique enzyme responsible for terpenoid production. These experiments, however, failed to produce the desired results because the enzyme "chose" to work in a particular area of the plant cells that was lacking in sufficient raw materials to make terpenoids. To overcome this difficulty, Dr. Aharoni decided to insert into the Arabidopsis plant a single strawberry gene to which he attached a "routing" genetic segment. This segment directed the enzyme to a part of the cell that was rich in the required raw materials - a strategy that allowed the enzyme to step up terpenoid production.

The engineered plant released large quantities - 25 times more than the natural plant - of a signaling chemical that recruits predator mites. At this stage, the scientists decided to test the effectiveness of the method. Predator mites were allowed to roam freely and choose between a genetically engineered and a regular plant. The result: On average, 388 mites rushed to the engineered plant, while only 191 flew over to the regular plant. These results were recently published in the journal Science.

Unlike natural plants, which produce terpenoids only on demand, the engineered plant releases the signaling chemical continuously, so that it cries "Wolf!" even when it’s not being attacked. This never-ending alert could conceivably create a problem, as predator mites have occasionally been known to become disappointed and lose their "trust" in the help-recruiting signals. To prevent this undesirable situation, the scientists are currently striving to engineer plants in which it will be possible to control when the signaling substances are released. 

A synchrotron is a large, ring-shaped pipe in which electrons are accelerated to near-light speeds. As they whiz through the pipe, the electrons emit radiation, such as X rays. In research stations situated around the facility, scientists perform experiments using this radiation. Although the synchrotron is a sort of particle accelerator, such as those used in nuclear physics research, many scientists employ it as a giant microscope that allows them to observe things at the scale of molecules and atoms. SESAME will have five different beam lines, making it valuable for research in nanotechnology, atomic medicine, spectroscopy, atomic and molecular physics, archaeology, environmental science and more.

Structural biologists, for instance, rely on synchrotrons to unravel the three-dimensional structures of proteins - an essential step in understanding how they work as well as in creating new and better drugs. To solve a protein’s three-dimensional structure, scientists crystallize the protein and then bombard it with strong X-ray radiation. As the rays bounce off the crystal, they create a pattern that, after analysis, yields the structure of the protein molecule.

With a capacity of 2.5 GeV (2.5 billion electron volts) and an accelerator ring circumference of 125 meters, the synchrotron is mid-sized - smaller than the three giant synchrotrons in the U.S., Japan and France - but it will have boosters to up that capacity if needed.

The idea of a Middle Eastern synchrotron was first suggested by Prof. Herman Winick of the Stanford Linear Accelerator in Palo Alto, California. Winick recently received the New York Academy of Sciences Heinz R. Pagels Human Rights Award, in part for his work on SESAME. A number of Israeli scientists, including the Weizmann Institute’s Profs. Irit Sagi and Joel Sussman of the Structural Biology Department, have been actively involved in the project. Instead of flying five hours to Grenoble each time he or one of his colleagues wants to carry out an experiment, says Sussman, "I thought it would be good, when possible, to drive a few hours and be able to return home that evening or the next day."

The final green light for the project came in 1997, with the decision to close down the BESSY-1 accelerator in Germany. Rather than junk the old accelerator, it was agreed to fix it, upgrading the facility to meet the demands of modern, cutting-edge science; and thus the German government donated it to the Middle East project. Jordan was chosen as a "good place in the middle," and construction commenced in 1998. If all goes well, SESAME will begin operating in 2009.

Just as scientific cooperation between Germany and Israel in the 1960s helped pave the way to full political and economic ties, those involved in SESAME hope that their example can spur other types of regional cooperation. Already, the project is an exemplary model of cross-cultural participation. For instance, the synchrotron’s Italian technical director, Dr. Gaetano Vignola, works with a skilled team of Jordanians, Palestinians, Iranians, Moroccans and Turks. The head of the SESAME council is Prof. Herwig Schopper from Switzerland, and the scientific director, Prof. Khaled Toukan, is also Jordan’s Minister of Higher Education and Scientific Research. The Weizmann Institute’s Prof. Sagi is a member of the project’s international steering committee.

Participation in workshops has already led to the creation of a regional scientific network and an exchange program for students and young scientists that exposes promising Arab researchers to global science. Israel’s participation and investment in the project are seen in a positive light by the other partners. Chaim Weizmann, the first President of the State of Israel and of the Weizmann Institute, had a vision over 50 years ago that science could play an important role in bringing peace to the region. SESAME may help to prove him right.

Dr. Ami Shalit admits that his job has its unconventional aspects. As the director and academic secretary of the Feinberg Graduate School, Dr. Shalit explains that a critical aspect of his role at the academic arm of the Weizmann Institute of Science (WIS) is “to swim in the students’ veins, understanding what their needs are.”

It is an extraordinary job description for any administrator, and Dr. Shalit’s degree of involvement with the Feinberg Graduate School’s students is all the more remarkable considering the depth and variety of students. In an effort to fulfi ll its mission of educating future scientific leaders, the school grants all of its nearly one thousand master’s and Ph.D. students full tuition remission and stipends. This policy allows the graduate students to focus their complete attention on the scientifi c achievements for which the Weizmann Institute is known.

As Paul Berkman, a member of the the American Committee for the Weizmann Institute of Science’s (ACWIS’s) Board of Directors, explained during a recent event in New York, students at the Feinberg Graduate School are currently on the cutting edge of scientific research in diverse fi elds, including nanotechnology, the search for new energy sources, agriculture, cures for cancer, and the search for treatments for everything from Alzheimer’s disease to the fl u. Mr. Berkman welcomed the New York audience with a presentation titled “Responsibility for the Future: Educating Scientists.” The program featured comments from Dr. David J. Haas, a former postdoctoral fellow at the Institute who has enjoyed a successful career in technology and business, and who is today an active supporter of ACWIS.

The Feinberg Graduate School was founded in 1958 to function in conjunction with WIS. In 2000, Dr. Shalit, a distinguished linguistic researcher, assumed responsibility for its day-to-day operations. He is familiar with the needs of students from around the world, having received his undergraduate education at New York University and his graduate training at the University of Toronto in Canada and the University of Cape Town in South Africa.

Admission to the Feinberg Graduate School is highly competitive. Of about 800 applicants to the Master of Science program each year, only 150 are admitted. New doctoral admissions are limited to 165 annually. Currently, 275 M.Sc. and 685 Ph.D. students are in attendance, creating an intimate atmosphere in which scientists and students regularly communicate across disciplines. One distinguishing feature Dr. Shalit points out is the even gender ratio. Nearly half the students in both degree programs are women, which is unusual for postgraduate science programs. Although more female students are studying the life and chemical sciences, their numbers are surging in physics and mathematics.

Though not designed to foster relationships among students, the graduate programs have yielded many marriages between students. Dr. Shalit was impressed by the dedication of a female M.Sc. student from France who, shortly after entering the program, married a fellow student. By the time she graduated—on schedule with her class—she and her husband already had two children. Being able to support students’ rigorous scientific research while they pursue other life goals is clearly a point of pride for the Feinberg Graduate School’s administrators.

According to Dr. Shalit, the most remarkable aspect of life at the Feinberg Graduate School is students’ direct involvement with groundbreaking research. At any given time scientists at the Institute are engaged in at least 1,200 research projects, every one of which involves graduate student participation. Many students help to develop key patents, while others publish papers in prominent scientific journals.

For example, Dr. Raz Zarivach of the Feinberg Graduate School worked closely with Prof. Ada Yonath of the Department of Structural Biology and incumbent of the Martin S. and Helen Kimmel Chair. Fueled by the desire to elucidate the structure of the ribosome, Prof. Yonath conducted research that yielded striking results, and led to the U.S. National Institutes of Health naming the year 2000 the “Year of the Ribosome.” Dr. Zarivach provided a breakthrough when he discovered a tool for discerning how the ribosome “factory” works. His contribution has paved the way for understanding how disease-causing bacteria develop resistance to antibiotics. This may allow the pharmaceutical industry to develop new drugs designed to prevent that resistance.

Another doctoral student, Yaakov Benenson, assisted Dr. Ehud Shapiro of the Department of Computer Science and Applied Mathematics and the Department of Biological Chemistry, incumbent of the Harry Weinrebe Professorial Chair, in creating the world’s smallest biological computing device. For his crucial contributions, Benenson was included on the 2004 list of the world’s 100 Top Young Innovators by MIT’s Technology Review.

In a study conducted under the guidance of Prof. David Cahen of the Materials and Interfaces Department, who is the incumbent of the Rowland and Sylvia Schaefer Chair in Energy Research, doctoral student Iris Visoly-Fisher was able to investigate how defective solar cells outperform so-called high-quality solar cells. Solar power may very well be the force that transforms the energy industry and reduces human dependence on depleted oil resources; Visoly-Fisher has made an enormous contribution with her discovery that, contrary to previous assumptions, solar cells’ effi ciency actually increases with grain-boundary defects.

Though the importance of the scientifi c research conducted by graduate students at Feinberg is clear, where the support will come from is less so. According to Dr. Shalit, the downward trend of support from the Israeli government has stretched the school’s resources. The school has a charter granted by the Board of Regents of the State of New York, making it eligible for American Schools and Hospitals Abroad (ASHA) grants. ASHA uses the Feinberg Graduate School as an exemplary model of higher education, and it has been the recipient of multiple grants, but this is no guarantee for the future.

According to Dr. David Haas, who was a postdoctoral fellow at the Weizmann Institute in the late 1960s, it is precisely because the Feinberg Graduate School’s students have ample resources available to them that they are able to produce the quality of research they deliver. Students who are “articulate, enthusiastic and well-trained” are able to produce “remarkable, published results with no worries about the necessary resources and equipment,” he said. Funds are also necessary for graduate students to participate in the larger scientifi c community through travel to conferences, where they present their work, network, and establish collaborations. Both Dr. Shalit and Dr. Haas emphasized the importance of involving graduate students in the global scientifi c community—not simply for their own benefit, but for the benefit for humanity.

Though its scientific research has enormous ramifi cations around the world, the Feinberg Graduate School is an intimate, serene haven. “Every day,” remarked Dr. Shalit, “I go to work with a song in my heart.”

Polytechnic is the second oldest private engineering and science institution in the U.S., and its Planning Committee helped establish WIS by expanding the Daniel Sieff Research Institute. The Planning Committee was created at the end of World War II under the chairmanship of Prof. Herman Mark, often called the “father of polymer science” and a close associate of Dr. Chaim Weizmann, who was known as, among other things, the “father of industrial fermentation.” In fact, as Prof. Mark states in his memoir, Dr. Weizmann personally asked him to serve ashead of the Planning Committee. Another of the committee members was Ephraim Katzir, then Prof. Mark’s post-doctoral student, who would later become a Weizmann Institute professor and Israel’s fourth president.

The Planning Committee, established in 1945, and the Weizmann Institute, established in 1949 (the Sieff Institute was established in 1934), were conceived during a time of war and continued to support one another during the periods of confl ict and peace that followed.

Even during Israel’s War of Independence, when equipment intended for WIS could not be shipped to Israel because of security reasons, the two institutions remained in contact. Polytechnic directly supported WIS during the war by storing this equipment until it could be safely transported. The university even went so far as to set up a temporary laboratory for Dr. Weizmann  and other Sieff Institute scientists.

Speaking at the gathering that honored this long- term partnership, Prof. Harold Kaufman, director of Polytechnic’s extension program in Israel, said that in addition to Prof. Katzir, more than one thousand Israelis were educated at Polytechnic University. As a result of this cross-education, the largest concentration of Polytechnic alumni outside the United States is in Israel.

One of the goals of the Planning Committee was to attract young, promising scientists to the then- new Weizmann Institute. This goal remains important to both institutions; Prof. Kaufman stated that the university continues to contribute to educating future leaders of science and technology in Israel through its Master of Science program at WIS, which focuses on science and high-tech management. A number of students have pursued this program in parallel with their graduate studies at the Institute.

In addition to Prof. Kaufman’s speech, the event included a videotaped address by Polytechnic University president Prof. David Chang; remarks by Weizmann Institute president Ilan Chet, and Dr. Uzia Galil, founder and former CEO of Elron Electronic Industries; screening of a video entitled “Inspiration & Innovation: 150 Years of Discovery & Invention at Polytechnic University”; and a luncheon.

Three keynote lectures were delivered by Polytechnic alumni. Prof. Israel (Izzy) Borovich of Tel Aviv University’s Faculty of Management and president of Arkia Israeli Airlines and Knafaim-Arkia Holdings, who shortly after the event was appointed chairman of El Al, spoke about his move from academia to the world of business.

Amos Raviv, deputy chairman of the Israel Port and Railways Authority, provided advice to new alumni of Polytechnic’s Israel extension who intend to pursue doctoral studies.

David Rubin, chairman of the board of Starling Advanced Communications and CEO of Tech Capital and the TIX Group, spoke about his transition from the world of business to public service, referring to his tenure as Israel’s economic attaché to North Africa. He also addressed the enormous positive impact on his career of his own studies in the US, and stressed the importance of global education for a global economy.

How many teenagers love studying science or reading scientific papers and texts? Probably very few, since most youngsters find subjects like chemistry and physics daunting, even intimidating. A Weizmann Institute educational program that fosters skills for tackling scientific topics in secondary school students is currently being introduced in England.

Entitled "Learning Skills for Science," it teaches youngsters how to find their way through the vast ocean of scientific knowledge. "If you throw non-swimmers into deep water, only a lucky few will figure out how to stay afloat - most will drown. But if you first teach these people how to swim, they will all survive!" says Dr. Zahava Scherz of the Institute’s Science Teaching Department.

"Learning Skills for Science" provides youngsters with challenging yet fun tasks designed to teach them how to find, critically evaluate and present information in order to increase their scientific knowledge. For example, they learn how to take notes in a lecture, evaluate the reliability of a website, interpret data in a diagram or table, prepare a presentation and make good judgments about the quality of an article on the basis of a quick reading. In this last activity, students are taught browsing skills that help them answer questions about a six-page scientific article after reading it for only five minutes.

Scherz originally developed the program in the late 1990s with Dr. Ornit Spektor-Levy, at the time a Ph.D. student, as part of the MATMON science education project headed by the Weizmann Institute’s Prof. Bat-Sheva Eylon and sponsored by the Israel Ministry of Education, Culture and Sport. The program has now been expanded, updated and adapted to the needs of the British education system, with the support of a grant awarded to Eylon and Scherz by the Gatsby Science Enhancement Programme (SEP), one of the Sainsbury Family Charitable Trusts. The learning and teaching materials have been published in collaboration with the prestigious Nuffield Curriculum Centre, which has supported the development of innovative science curricula in the United Kingdom for more than 40 years.

According to Sally Johnson, project manager for SEP, "Learning Skills for Science" fits well with the new approach to teaching science in British high schools - particularly the "Twenty First Century Science" syllabus - which seeks to increase public understanding of science by getting children involved in how science and scientists work. New courses along these lines currently introduced in British high schools stress skills as well as content in science education, and "Learning Skills for Science" is seen as a helpful preparation for students following the new curriculum. Johnson adds that "teachers who are going through the 'Learning Skills for Science' training have greeted the program with enthusiasm."

Scherz and Spektor-Levy have conducted a number of workshops at the University of London and elsewhere in England over the past two years, both for teachers and for trainers of the teachers in the program. About 100 teachers are presently being trained, and in June-July 2006, at the end of the current school year, the program will enter a further pilot stage in which it will be taught to ninth-graders in 75 schools throughout England. After the pilot has been evaluated, the organizers hope to distribute the program more widely in the United Kingdom. Considerable interest has also been expressed by science teaching experts in other countries, such as India, Ireland, the Netherlands and South Africa.

Summing up the objectives of the program, Scherz says: "Today, people have access to knowledge not just through their teachers but through a variety of other sources. The 'Learning Skills for Science' program offers school students a way to develop the skills for life-long independent learning."

Prof. Bat-Sheva Eylon's research is supported by the Gerald and Daphna Cramer Family Foundation. Prof. Eylon is the incumbent of the Chief Justice Bora Laskin Professorial Chair of Science Teaching.

Innovation for Teachers
The collaboration with the British education system is further fostered through an additional grant, awarded by SEP to Profs. Bat-Sheva Eylon and Avi Hofstein of the Institute’s Science Teaching Department. This project, carried out with King’s College, London, is aimed at designing innovative programs for the continuing professional development of science teachers.

Field Study

Three years ago the management of the "Nirim" youth village in northern Israel turned to the Weizmann Institute's Prof. Nir Orion for assistance. Founded by ex-naval commandos wishing to contribute to society, "Nirim" enrolls boys and girls who have dropped out of school; one of its goals is to help its students graduate from high school with a full matriculation certificate, which requires passing several exams, including an extended in-depth exam in one subject. The village's management hoped that a special outdoor teaching program in the earth sciences developed by Orion and his team in the Institute's Science Teaching Department would enable the boys and girls to meet the in-depth examination requirement.

Inspired by the challenge, Orion and his team have been putting in dozens of work days at "Nirim" on a volunteer basis over the past three years. The results weren't long in coming. Barely six months after the new program had been introduced, one group of students passed a field matriculation exam in the earth sciences with an average of 94.5; and after two years, all the students passed all the matriculation exams in this subject with flying colors.

The secret of the program's success lies in its relevance to the "real" world, as some youngsters drop out of school because they find classroom study boring and irrelevant to their lives. The program involves at least 12 field trips throughout Israel and focuses on environmental concepts pertinent to daily living. Says Orion: "This approach is amazingly simple and incredibly effective. All it requires is that the learning take place through a concrete interaction with the real world outside the classroom."

Type 2 diabetes is a complex disorder characterized by the body’s inability to utilize sugar efficiently. Two stages of the disease have been identified: In the first, “silent” stage, the body’s cells lose their ability to respond properly to the crucial hormone, insulin, responsible for moving sugar from the blood into cells. If sugar remains in the bloodstream, the insulin-producing beta cells in the pancreas compensate by stepping up production. Eventually this leads to beta cell exhaustion, reduced insulin output and the appearance of full-blown diabetes.

Elevated fat in the bloodstream appears to accelerate both stages of the disease. Exactly how does this happen? Beta cells are attuned to changes in blood sugar levels, responding to after-meal surges with a sharp increase in insulin production. But a recently discovered protein, a receptor on the surface of the beta cell called GPR40, responds not to sugar, but to fatty acids. When fat is present in addition to sugar, the GPR40 receptor causes an even higher spike in insulin output. If beta cells are frequently overstimulated and overworked, persistently elevated insulin levels may hasten the onset of the disease.

To investigate GPR40’s role, Prof. Michael Walker and students Nir Rubins and Reut Bartoov-Shifman of the Weizmann Institute’s Biological Chemistry Department teamed up with Prof. Helena Edlund and postdoctoral fellow Dr. Per Steneberg of the University of Umea in Sweden. Together, they developed two types of lab mice with modified GPR40 activity. In the first, the scientists used a technique known as gene knockout to prevent production of the GPR40 receptor. In the second type, overactive GPR40 genes created a surfeit of fat-signaling receptors that tricked the beta cells into sensing high fatty acid levels, even on a normal diet.

Throughout the trial, the GPR40 knockout mice remained healthy, apparently suffering no adverse effects from the deletion of the receptor, even when the fat content of their diet was raised substantially. In contrast, normal mice on a high-fat diet displayed typical symptoms of the first stage of diabetes. But strikingly, in the animals with extra GPR40 receptors, the disease progression was swift: They soon began to exhibit the classic symptoms of full-blown diabetes, including failure of the beta cells to produce adequate amounts of insulin.

Walker: “Our results establish GPR40 as an important link between obesity and diabetes. This gives us a new tool to combat the diabetes epidemic: It might be possible in the future to treat the condition using drugs that block the action of this receptor.”

When friends of the Weizmann Institute - and of Israel - ask me for some good news from our region, I have no difficulty in responding. The irrepressible energy and boundless ingenuity of Israeli inventors and entrepreneurs are there for all to see, but to none are they more evident than to those of us immersed in science and research.

Israel is home today to about 500 communications technology companies, 200 in medical instrumen-tation, 100 in fabless circuit design plus a number of circuit production giants, and 50 in digital printing and imaging. It has become a veritable superpower in data security, with some major companies in the field and about 80 start-ups. There are hundreds of companies developing an impressive range of programming applications - for trading in foreign currency options, for Internet applications and a great deal more. In my own field of plant science, the long tradition of Israeli innovation is being carried forward by a growing number of biotechnology companies devoted to advanced crop improvement and the production of plant-derived products. In drug design and development, Teva Pharmaceuticals leads as a major player in the world arena and is Israel's largest and most successful commercial company ever. All this, and more, in a country of less than 6 million people!

What drives this phenomenal technological dynamism and entrepreneurship? Of the many reasons I could cite, one is most relevant to our endeavor: the strength of Israeli scientific education and technological training, in which the Weizmann Institute of Science plays such a dominant role - through its emphasis upon basic research (the root of its multivaried achievements since its earliest days), its practical inventions, its science education programs and its network of graduates throughout Israel.

Clearly, the cultivation of our only abundant natural resource, our brain power, is critical to our economic and social well-being. At the Weizmann Institute we also believe that this cultivation is of value in itself, beyond its immediate utilitarian impact. We believe that knowledge and its pursuit are the crowning achievements of every society, and should always be a priority.

Put in this perspective of aspirations and achievements, the past year has been a good one for the Weizmann Institute. Let me touch on some highlights.

Following his earlier astounding development of the world’s smallest biological computer consisting of DNA, the material of genes, Prof. Ehud Shapiro took a dramatic step into futuristic medicine by showing how this molecular device, of which about a trillion can fit in a drop of water, might one day function as a tiny medical kit. Made entirely of biological molecules, this computer was successfully programmed to identify - in a test tube - changes in the balance of molecules in the body that indicate the presence of certain cancers, to diagnose the type of cancer, and to react by producing a drug molecule to fight the cancerous cells. It may well take decades before this concept of “a doctor inside the cell” can be converted to a system operating inside the human body, but its potential is thrilling. This research was supported, among other sources, by the M.D. Moross Institute for Cancer Research.

Having obtained FDA clearance last year, Prof. Hadassa Degani's work in magnetic resonance imaging (MRI) for the non-invasive diagnosis of breast and prostate cancer is now being developed commercially for clinical use. Recently, she directed her attention to an entirely different application - kidney function. Standard MRI scanners found in hospitals and clinics work by imaging water molecules in the body, but in water-logged kidneys, the image may not distinguish between different functional parts. By scanning sodium ions rather than water, Prof. Degani's method may enable tomorrow’s doctors to pinpoint exactly where a problem lies, reveal a disease before symptoms occur, or evaluate how a drug affects a patient. Prof. Degani’s work was supported by the Willner Family Center for Vascular Biology and other generous donors.

Prof. Yair Reisner's breakthrough research in inducing porcine stem cells to grow new kidney tissue in a mouse stands to benefit from Prof. Degani's innovation, which could greatly facilitate the difficult task of assessing how well such kidneys are, in fact, functioning. Other aspects of Prof. Reisner's pioneering work, namely in bone marrow transplantation, are featured in this Annual Report. Again, both Prof. Degani's and Prof. Reisner's research benefited from the support of the M.D. Moross Institute for Cancer Research. Prof. Reisner also received major support from the Gabrielle Rich Center for Transplantation Biology Research and other generous donors.

It is a pleasure to acknowledge here, with thanks, the generous gift of the Skirball Foundation of Los Angeles for its challenge grant of $1.5m toward the purchase of a new MRI machine for Prof. Degani and half a dozen additional research groups. The new equipment will give a great boost to a significant segment of our biomedical researchers. We have received a number of matching gifts, most notably from Mrs. Rita Markus of New York, Mr. Hans Rausing of the UK and the Harry M. Ringel Foundation of California. We are still looking for additional donors to come forward with funds that will help meet the Skirball Foundation's challenge.

Further clinical progress in cancer therapy was achieved by the team of Profs. Avigdor Scherz and Yoram Salomon, who conduct (Phase I/II) clinical trials for prostate cancer in collaboration with Steba Biotech (France). They have developed a novel substance for use in photodynamic therapy (PDT), which effectively destroys tumors by destroying the blood vessels that supply them with oxygen and nutrients. The work is presently carried out in medical centers in Canada, England, France and Israel.

In neuroscience, sophisticated use of MRI techniques is yielding insights into the mechanisms of perception and visual experience. Prof. Rafael Malach showed volunteers a segment of a movie while they were undergoing brain scans with functional MRI equipment. Interestingly, the brain scans revealed that in viewing a movie, the various regions of the brain each actively view different movies. Each area is activated by a specific kind of visual cue, and therefore only picks up on those bits that “speak” directly to its specialized preference. For instance, a region known to be involved with face recognition lit up only when close-ups appeared on the screen, whereas scenery elicited a response from the part of the brain that helps us navigate in three-dimensional space. The scientists noted a third area that seemed to be activated when delicate hand motions were performed; this area, they think may be part of a network of brain regions used to understand the actions and intentions of others. Thus the unified percept we experience is, in fact, the coordinated result of a tremendous “jam session” played out by our different, highly specialized brain regions.

Also in Neurobiology, Prof. Amiram Grinvald - widely regarded as a world leader in functional optical imaging and, as such, of having exercised a tremendous impact on brain research - was awarded the prestigious Dan David Prize for 2004. Prof. Grinvald's method of intrinsic optical imaging on the molecular level makes it possible to visualize electrical activity in the living brain. This technique is currently advancing clinical applications in neurosurgery operating rooms in the US, Europe and Japan. Both Prof. Grinvald and Prof. Malach are supported by the Murray H. and Meyer Grodetsky Center for Research of Higher Brain Functions.

Another possible future application of Institute research in neurosurgery comes from an entirely different direction. Prof. Elisha Moses of the Physics of Complex Systems Department, postdoctoral fellow Dr. Stephan Thiberge, and Institute graduate Dr. Ory Zik have devised a method to view samples of biological materials under the beam of the scanning electron microscope (SEM) in their natural, untreated (i.e. “wet”) state. The SEM's superb ability to distinguish the delicate structure of a living cell could thus be utilized, for example, in making a quick decision during brain surgery as to the borders between a malignant tumor and healthy tissue, or between a malignant and a benign growth.

Since the discovery was made, Dr. Zik, in cooperation with Yeda, the Institute's business arm, has founded a company, called QuantomiX, based on this technology. The findings of the team were published this year in the Proceedings of the National Academy of Sciences (PNAS) USA. This is just one fine example of the Institute's leadership in advanced imaging and microscopy techniques, a field that is of vast importance for science, medicine and industry. I urge the Institute's friends to support our efforts in this sophisticated - and costly - endeavor through such projects as the proposed Electron Microscopy Center or the Bioimaging and Diagnostics Center.

Gratifying acknowledgement of our work in nerve regeneration was recently received from the Christopher Reeve Paralysis Foundation (CRPF), which awarded its first grant in Israel to Dr. Michael Fainzilber. “The Weizmann Institute, as I saw first-hand when I visited Israel last year,” said Christopher Reeve, “has established pre-eminence in the field of paralysis research.” Applying a unique peptide, Dr. Fainzilber will identify changes in genes that are activated very early in the regenerative process, in order to modulate injury-induced changes. The data generated using this innovative model has the potential to identify new molecules important for regenerative growth in patients with nerve injuries.

In the coming year, our work in neuroscience will be significantly enhanced by a major gift from Mrs. Nella Benoziyo toward the establishment of a new research center dedicated to neurological diseases. This is in addition to the existing Nella and Leon Benoziyo Center for Neurosciences, from which Prof. Malach's work has benefited, and the Y. Leon Benoziyo Institute for Molecular Medicine, which has supported Dr. Fainzilber's research. In appreciation of this magnanimity, the brain research building has now been named the Nella and Leon Benoziyo Building for Brain Research.

Basic science is the heart and core of our work, and is particularly characteristic of young scientists in the early stages of their careers. This issue of the Annual Report features outstanding work in structural biology by two young scientists, Dr. Deborah Fass and Prof. Gideon Schreiber. Dr. Fass, whose work was recently featured in the prestigious journal Cell, is applying X-ray technology to study newly-discovered enzymes taking part in protein folding - the fateful process by which “newborn” proteins fold into precise three-dimensional structures to become functional. Proteins are also a central theme in the work of Prof. Schreiber, who is applying both theoretical and experimental techniques to examine how cells “talk” to one another. Amongst his findings, Prof. Schreiber has achieved valuable insights into how interferons, proteins serving as the body’s first line of defense, convey their messages into the cell.

We are eager to promote this vigorous activity in structural proteomics. Elucidation of the 3-D structure of proteins - so critical for understanding their function in health and disease - is an enormously complex process. When Sir John Kendrew and Sir Max Perutz received the Nobel Prize in 1962 for the first solving of a protein’s 3-D structure, they had spent over 20 years on the task. Though some aspects of the process have since become more efficient, scientists may still spend months, sometimes years, in similar efforts.

Having received initial support for a pilot project in this area from Israel's Ministry of Science, the European Union, and a visionary private Israeli donor - Board member Yossi Hollander - we now seek to establish an endowed research institute that will serve Israeli science as a whole. The institute will serve researchers from the Weizmann Institute as well as from other scientific research institutes and the biotech industry in their attempts to elucidate the structure of proteins involved in disease. Their findings might prove essential to future applications in drug design, diagnostic tests, biosensors, agrochemicals and more.

Providing a boost to the efforts of all such research-ers is an outstanding new facility for visualizing proteins three-dimensionally, in their enormously complex structure and internal movement: The Jean Goldwurm Scientific 3-D Visualization Theater in the Wix Auditorium building.

Prof. Israel Rubinstein of the Faculty of Chemistry has demonstrated how minuscule particles of gold, silver and other materials can serve as building blocks of tiny cylinder-shaped structures called nanotubes (a nanometer is one millionth of a millimeter). Characterized by unique electrical and optical properties, these nanotubes can be tailored for diverse applications, such as future nanosensors, catalysts and chemistry-on-a-chip systems. This work was supported, among other sources, by the Clore Center for Biological Physics.

Our efforts in nanoscience received an important boost this past year through the magnanimous gift of Helen and Martin Kimmel of New York establishing the new Helen and Martin Kimmel Center for Nanoscale Science. Additional notable support ($2.9m) for nanoscience, in particular for the renewal of equipment in the Braun Submicron Center, but also for research in the Faculty of Chemistry, has been assured by the TELEM (acronym for National Science Infrastructures) Committee of the Israel Academy of Science. More than two years ago, the Wolfson Foundation had committed a large seed gift toward this fund, to be matched by the Israel Academy of Sciences and Humanities and five institutions of higher learning, including the Weizmann Institute, with the aim of making a significant investment in Israeli nanotechnology. We continue to seek donor assistance in this mega-project for advancing the Institute's world-class nano-electronics research.

The Physics Faculty celebrated its 50th anniversary this year with a rich record of achievements. This Annual Report features the work of two young theoreticians, Profs. Micha Berkooz and Ofer Aharony, who both work in the most fundamental area of string theory. This generation of young scientists is propelling us toward more focused efforts in particle astrophysics, where we hope to attract additional talent and establish a dedicated research center. The Physics faculty also has a strong tradition of commitment to science education - we are proud that this year’s EMET Prize is being awarded to Prof. Haim Harari for his outstanding leadership in this area.

I mention with pride that Prof. David Harel, Dean of the Faculty of Mathematics and Computer Science, received this year's Israel Prize for his work in several diverse areas of computer science, including the invention of languages and methods for developing complex systems and his widely-acclaimed expository writing. The citation described him as “one of the leading computer scientists in Israel and in the world.” Prof. Adi Shamir, co-inventor of the famous RSA encryption system, and his student Eran Tromer have been busy listening to computers. They are working on a system that could enable certain kinds of encryption techniques for securing classified information to be cracked by analyzing the faint sounds produced by tantalum capacitators on the motherboard. Additional achievements in mathematics and computer science are highlighted later in this Annual Report.

Young scientists
Of the six scientists featured in this report, you will note that four belong to the young generation of recently-tenured professors. This young face of the Institute is a genuine emerging trend, following a few years of difficulty in recruiting a sufficient number of young scientists, due mainly to the political and economic situation. It is heartwarming to witness young people's eagerness to join the Institute.

One of our most important tools for the successful recruitment and absorption of young scientists is our ability to provide them with equipment for their research needs. Such equipment costs may run into the hundreds of thousands, in some cases, even millions, of dollars. The Institute's major source of equipment funding, the Israel Science Foundation, has drastically reduced its support in the past few years, as part of the overall cut in government allocations to research and education. Our dream is to establish a large endowed fund that will enable us to respond effectively and quickly to such needs.

Recruitment of young scientists, particularly women, could be further boosted with greater attention on our part to the work/family balance. Specifically, we would like to expand the recently-established childcare facility, which has proven highly successful but is unable to meet the demand by Institute staff and scientists. We are seeking a donor gift for this project.

Major issues resolved
I am pleased to report that three of the four issues that have been hanging menacingly over our future during the past few years have been satisfactorily resolved. Of grave concern, primarily to our sister universities in Israel, has been the Ministry of Education's requirement to change the governance of Israel's institutions of higher learning. We have successfully convinced the Ministry that the Weizmann Institute's structure was already largely in line with the new requirements, principally, the unification of responsibilities for the organization's fiscal and academic functions. Thus, we have not been called upon to change our governance structure.

This year, it was officially confirmed that we would not be subjected to any tax liability for our income stemming from Yeda royalties. The State Comptroller General had for some time been questioning the fact that this income was not taxed. After a lengthy process of presentations and clarifications to the State Comptroller and the income tax authorities, the Institute succeeded, with the invaluable aid of our Board Member Moshe Gavish, in making a compelling case for its position, resulting in confirmation by the tax authorities of the accepted position that a not-for-profit organization like the Institute should continue to maintain this tax exemption. Needless to say, the individual scientists who receive royalty income do pay taxes on it.

A third major issue that was resolved this year was our six-year-long disagreement with the State Comptroller on reporting procedures for external grants. Having now obtained the Comptroller's agreement to a reporting procedure that takes into account the inherently fluid nature of cash flow from external grants, our scientists can continue to compete for international grants with a reasonable degree of flexibility. Regrettably, the dispute with the Municipality of Rehovot regarding tax payment is still pending, notwithstanding the considerable progress we have made.

Financial situation
The Israeli government has continued to impose cuts on the national budget. For us, this meant that in 2003/4 the government’s share in our operating budget fell to 36 percent, necessitating a further reduction in expenses from the previous year’s budget. Even though governmental cuts were announced twice in mid-year, we continue to maintain a balanced budget, thanks largely to the discipline and cooperation of the Institute's scientific and administrative staff. My warm thanks also go to the Institute's loyal friends, who have continued to give generously to the President's Contingency Fund - a resource the importance of which I cannot exaggerate. Part of the shortfall in government support was also made up for by an increased injection of funds ($15m, or 8.5 percent of our budget) from Yeda's royalty income. All this has enabled us to maintain an acceptable level of support for research and infrastructure and, most importantly, not to be forced to reduce our support for new scientists and graduate students.

The Institute's income from Yeda is based primarily on three products: two drugs for multiple sclerosis (Copaxone® and Rebif®) and the satellite television encryption card. In keeping with the Institute's far-sighted policy, this highly volatile income - the dependability of which is entirely outside our control - was not used to increase expenditures. Rather, as indicated above, it partially offset the shortfall in the operating budget created by the government's drastic cuts in support of basic research. The rest was put toward future-oriented purposes: the development and maintenance of our infrastructure, facilities and equipment, and the enlargement of our endowment.

Yeda's earnings testify to the talent and enterprise of Institute scientists. Given that all three products listed above have a manufacturing base in Israel, they also point to the coming of age of Israeli industrial, financial and business capabilities. We can be proud that with only 250 principal investigators, we lead all Israeli institutions of higher education in technology transfer, and that even on a global scale, our successes are remarkable. It is also most gratifying that the basic research behind Rebif® was recognized this year by the award of the EMET Prize to Prof. Michel Revel.

External research-funding sources constitute 25.6 percent of the budget, a figure that has remained steady in the past year. But steady-state in this case is by no means trivial news. If we bear in mind that major Israeli funding entities, such as the Israel Science Foundation and the various government ministries, have severely reduced their support in the past two years, it is clear that the continued high level of external support sources can only be ascribed to increased funding from abroad. Grants from the NIH have been increasing steadily and today reach $1.8m, and grants from the European Union, where we have done better than any other Israeli institution of higher learning, have reached $6m.

I would like to mention here an $8.5m competitive grant awarded by the Flight Attendants Medical Research Institute (FAMRI) of the US to a Weizmann Institute team working with the Chaim Sheba Medical Center on the harmful effects of passive smoking.

Our success in obtaining such large external grants may be partially attributed to the leverage afforded by philanthropic sources, notably in this case, the M.D. Moross Institute for Cancer Research. This success in the highly competitive world science arena can surely be taken as an objective indicator of the high quality of Weizmann Institute researchers. This quality was again reaffirmed this year by the comparative study of the “impact factor” of scientific publications: Israel ranks third, after the US and Switzerland, in its number of scientists cited (in relation to the country's population). Of the 37 Israeli scientists most often quoted by others (out of 250 worldwide), 11 - nearly one third - are at the Weizmann Institute.

As to ongoing (not endowed) donation income, we have been experiencing a declining trend in the past five years, from a high of close to $24m in 2000/1 to an estimated $17m in 2003/4. This is partly due to the fact that during the Jubilee Campaign, we oncentrated our efforts on increasing our endowment, as opposed to raising consumable funds. Thus, both the endowment itself has grown, currently standing at close to $600m, and the annual yield it provides to the Institute has risen, from about $18m five years ago, to close to $29m today. W-GEM, the Institute's arm for the professional management of its investment portfolio, has yielded excellent results in the past year.

Campus infrastructure and development
We are moving forward with our plans for constructing a major new transgenic plant growth facility, which should give a significant boost to our research in plant science. This project is still seeking donor support and I would like to take a moment to make the case for it once again.

Making a Mark
Eleven of the world’s 250 most quoted scientists are at the Weizmann Institute:

-Prof. Moshe Oren

-Prof. Oded Goldriech

-Prof. Benny Geiger

-Prof. Ehud Dochovni

-Prof. David Harel

-Prof. Ilan Chet

-Prof. Irun Cohen

-Prof. Giora Mikenberg

-Prof. David Peleg

-Prof. Amir Pnueli

-Prof. Itamar Procaccia

We are justly proud that Israel has been a powerhouse of agricultural development - surely one of the most amazing features of Israel's rebirth in its arid land. We are witnessing exciting new trends in this field. Since the 1980s, it has become clear that it makes little sense for us to engage in intensive agriculture, where (fortunately) we no longer can or wish to compete with the low wages that prevail in less developed countries; nor do we have the large land and water reserves required. Instead, Israelis have identified the enormous potential of advanced agricultural research - a kilogram of seeds sells for 1,000 times more than a kilogram of fruit - and are developing new crop seeds with high added value, such as resistance to disease, adaptability to various climate conditions, increased yields, improved nutritional value, etc. Being myself in the field of plant biological control, I can personally affirm that such characteristics have enormous impact globally in protecting the environment (fewer pesticides, fewer fertilizers) and in their potential for feeding a hungry world.

Most of this research in Israel is carried out by academic institutions, rather than by industry, and there can be no doubt that Israel's innovativeness in plant science owes much to this fact. We must give the Institute’s plant researchers the advanced high-tech facility that their talents and efforts so fully merit.

We are also finalizing plans for a new facility for pre-clinical research, scheduled for construction in the northern campus area recently acquired from the Jewish Agency. This is an enormously costly project, for which we are seeking donor support. Our major existing facility was built in the 1960s and is now obsolete beyond our ability to refurbish it. Inter-national standards of ethics - to which the Institute adheres strictly - and the technical capabilities for housing, treating and monitoring of mice and rats undergoing pre-clinical experiments have improved dramatically since then. In addition, there are many new research projects today in cancer, genetics and immunology that require upgraded facilities.

The clean-up and refurbishment of the Arnold Meyer Building is progressing well, and should be completed by mid-2005.

In May 2004, we had the pleasure of dedicating “Oasis,” a lovely water sculpture given to us by our former graduate student, Dr. Barton Rubenstein of Washington, DC. In November 2004, we will dedicate three new campus installations: the Ruthie and Samy Cohn Student Residence, the Joe Weinstein and Major Max L. Shulman EcoSphere in the Clore Garden of Science, and the Jean Goldwurm Scientific 3-D Visualization Theater.

The campus and the community

This year, with abatement in the fury of suicide bombings inside Israel, we saw an increase in the number of visitors from abroad, as well as an increase in the number of scientific gatherings held on campus. In May alone, we held ten conferences with international participation, including one in honor of former Institute President Prof. Michael Sela's 80th birthday.

Educational activities for young people are as dynamic as ever. The annual Shalhevet Freier Physics Tournament, where youngsters must figure out how to crack safes, had a record number of participants, including, for the first time, two teams from Canadian schools. Our Science Mobile traveled extensively this year to schools and centers in peripheral areas, partly thanks to the Rehovot-based Israeli division of Applied Materials, Inc., which not only gave financial support but also actively involved its management and staff. Our most public event, the Science Festival held during the Passover holiday, attracted some 15,000 participants.

We have initiated a number of appealing lectures for wider Institute audiences: the Helen and Martin Kimmel Center for Archaeological Sciences had standing-room-only attendance at its series on the civilizations of the eastern Mediterranean; Prof. Itamar Procaccia of the Chemistry Faculty offered an illuminating talk on Zen and the Arts of East Asia, featuring a number of scrolls from his own collection; and the Faculties of Biology and Biochemistry began a series of noon lectures “Biology at Eye Level,” where Institute scientists present their work to the campus community.

On June 10, 2004, the Feinberg Graduate School celebrated its largest ever graduation ceremony: 117 Ph.D. and 146 M.Sc. degrees were conferred. At this year's ceremony, the keynote speaker was Mr. Benny Landa, founder and former chairman of Indigo, a world leader in digital color printing. Benny and Patsy Landa are enthusiastic supporters of education in Israel, with a particularly attentive eye for students whose economic background has made higher education a difficult goal to reach. Earlier this year, we opened the Ruthie and Samy Cohn Student Residence to help relieve the demand for on-campus student housing for singles and couples. The school continues to attract the best students in Israel in Mathematics, Computer Sciences, Physics, Chemistry and Biology. The large number of applications and their exceptionally high quality led us to increase the size of the M.Sc. class entering in October 2004.

Under the banner “Administrative Excellence in the Service of Scientific Excellence,” we have launched an organizational development program for Institute personnel. Initially, we are focusing on enhancing management skills. This effort goes hand-in-hand with our implementation of an ERP (Enterprise Resource Planning) program. Together, we expect these initiatives to significantly increase the effectiveness and efficiency of our administration.

The Global Partnership Campaign
For the past year, we have been preparing to launch the Global Partnership Campaign, perhaps our most important fundraising initiative since the Jubilee Campaign. The Global Partnership Campaign is intended to bring together our lay leadership, our administration, our committees and our scientific community for the purpose of ensuring the excellence of scientific research and education conducted at the Institute. We have put together a dynamic Campaign leadership group under the gracious and talented team of Gershon Kekst, Global Chair, and Bob Drake, Executive Chair, and will be sharing the Campaign's goals with our Governors during our meetings on campus in November. Under the banner “Partners through Time,” we will discuss how each of us can make a difference in ensuring the future of the Weizmann legacy.

Thanks
For their friendly cooperation, good counsel and steady support, I thank Stu Eizenstat, Chair of the Board of Governors, Abraham Ben-Naftali, Chair of the Executive Council, Deputy Chairs of the Board, Chairs and members of the Board committees, and the entire Board membership; Prof. Michael Kirson, Chair of the Scientific Council, the Institute Vice Presidents, Deans of the Faculties and Department Heads.

I am particularly grateful to the Weizmann Institute family of scientific, technical and administrative staff, who have given me their generous support and friendship.

I am indebted to our supporting committees at home and overseas, who work unflaggingly for the Institute's welfare throughout the year - the devoted lay leaders, the outstanding Executive Directors, and all the enthusiastic members of their professional staffs.

I thank all of our friends in Israel and abroad for their interest, devotion and generosity over the past year. May the Institute's scientific and humanitarian achievements continue to fuel our aspirations and efforts in the year ahead.

“Like all good science — particularly at Weizmann — our work is curiosity driven,” he said recently, during a visit to the national ACWIS office. “For example, you have an oil spill — the oil seeps into the groundwater and starts to spread. The engineering approach is to drill holes and pump out the contaminated water — but six months later the contamination is back.” To solve the problem, he said, “You have to go back and determine how the oil behaves, how it travels, and what you can do with it. How does the oil interact with the water?”

Prof. Berkowitz has developed a highly accurate model of groundwater movement that can provide information to develop sound environmental policy. The ability to predict the flow of water and pollutants is critical for effective management and remediation of groundwater resources, and for protection against accidental exposure of radioactive and toxic wastes, as in the proposed use of Yucca Mountain in Nevada for underground repositories for radioactive and toxic wastes.

Prof. Berkowitz began his career in applied math, receiving a degree in petroleum engineering. While studying music in Israel (he is a passionate bassoon player), he happened to meet a chemical engineer. When he revealed his interest in the flow dynamics of oil, the man mentioned that he knew a world-renowned Israeli hydrologist. Reasoning that the only difference between water and oil was density and viscosity, he jumped into hydrology with both feet and has made quite a splash.

The biggest project in his lab is challenging assumptions about water and pollutant movement underground. The model in use is, quite simply, wrong, Prof. Berkowitz said. “We know it has an enormous error, and we’ve developed a new theory that seems to describe beautifully what’s going on.” His lab is developing the theory with computer software that models it, and encouraging others to adopt the theory by placing free software online.

He is also working on another legacy: last year, his parents were tragically killed in a car accident. He has taken on his late father’s work of a revolutionary way of processing oil and coal, which could have a profound impact on the coal and oil industry. “I taught myself hydrocarbon chemistry and developed a set up to test my father’s ideas — all those years it never occurred to us to work together, even though what we did was so related.”

How does he keep up with it all? “I don’t sleep much,” he said.

For people suffering from fatal diseases, such as leukemia or kidney failure, the scarcity of available transplants is often the cause of feelings of hopelessness. Thousands of people in the U.S. alone languish on waiting lists, tied to dialysis tubing, hoping for the transplant that may save their lives.

But if there were a way to make transplants immediately and widely available to all who need them, suddenly, it would be something everyone could afford, and something that would be accessible to all.

This is what Prof. Yair Reisner is trying to achieve. Having recently garnered international attention for growing functional kidneys in mice out of human stem cells, Prof. Reisner has long been finding ways to foil the human immune system into accepting transplants that it would otherwise reject.

Prof. Reisner began his long career by researching alternatives to bone marrow transplants. Since bone marrow harbors immune cells, bone marrow transplants are exceptionally tricky. Not only can the immune system attack the foreign marrow — known as graft rejection — but in some cases, immune cells in the marrow actually attack the patient, causing a sometimes-fatal condition called Graft Versus Host Disease (GVHD). Four out of 10 patients needing a marrow transplant cannot find a matching donor, putting them at risk for either never receiving a transplant, facing devastating complications, or GVHD from a poorly matched donor.

Prof. Reisner tackled this problem by using a hormone to mobilize the patient’s bone marrow cells, instead of the traditional method of attempting to kill them with radiation. He then used a special filter to remove every last one of the cells to prepare the patient for the new marrow. By following this procedure with a “megadose” transplant that infuses up to a liter of donated marrow — a quantity large enough to overcome the body’s rejection mechanism — he substantially reduced the rejection rate of transplants. Not only did the patients go into remission, but further studies show that they continue to do well. This method saved the lives of leukemia patients and “bubble” children and is now in clinical trials in Europe. At a recent lecture at ACWIS headquarters, Prof. Reisner was pleased to report on clinical success. “Now we have experience to show the patients survived. The rest is up to the clinicians.”

Not satisfied with that major advance, Prof. Reisner continues to pursue his interest in circumventing the human immune system to allow it to accept transplants. His latest achievement is growing tiny, functional kidneys in mice out of human stem cells. The trick to growing the kidneys is timing. Implant too early and the implanted cells grow into a mass of mixed tissue cells; too late, and the body rejects the kidney. Prof. Reisner and his team discovered a window of opportunity during which the transplant can occur. The cells already know how to become kidney cells, but are not so developed that the body will recognize and reject them.

If organs could be grown on demand from stem cells, rejection would be a thing of the past, and transplants could be done quickly, safely, and less expensively than now. Over 50,000 people in the U.S. are on the kidney transplant waiting list, and more than 2,000 die annually waiting for a match. Prof. Reisner hopes that eventually organs can be grown to supplement damaged or diseased organs, such as a pancreas that would produce insulin for diabetics. The procedure he developed is now in the pre-clinical study stage. If all goes well, new treatments may ensue in the near future.

For many schoolchildren, Ilan Ramon was proof that becoming an astronaut was an attainable dream, even for an Israeli. A year ago, many young eyes were glued to the TV screen as he shared his thoughts and emotions on board the Columbia. It is not surprising, then, that schoolchildren featured prominently in the nationwide events commemorating his passing.

About 100 junior high schools participated in a space competition that was held via the Internet in his honor. The contest, initiated by Israel’s Ministry of Education, was carried out by the National Teacher Center for Science and Technology, which is run by the Weizmann Institute’s Science Teaching Department at the Davidson Institute for Science Education. Fourteen finalists were challenged to plan either a space colony or a habitat on Mars, while dealing with scientific issues such as creating an artificial atmosphere or a self-sustaining ecosystem. The winners were announced in a science education conference commemorating Ramon, in the presence of his father and brother.

The six students in the winning group, who had suggested two original models for a space colony, were surprised to learn, as they went on stage to shake the hand of Ilan Ramon’s father, that the first prize was a trip to a summer space camp in Turkey. “The students were motivated by their interest in the subject. They did not know that there would be a prize for the winners – and nor did we, early on,” says Dr. Zahava Scherz, director of the National Teacher Center for Science and Technology. The endeavor was voluntary, and the prizes contributed by El Al, Young@Science at the Weizmann Institute and Israel’s Space Agency.

“Even the flower arrangements for the ceremony were given to us free of charge when the florist heard what they were for,” says Scherz. “The competition would have been impossible had we not been located at the Weizmann Institute, where we received active help and advice from numerous scientific and educational experts and enjoyed the continuous involvement of the Institute’s extracurricular science education unit, Young@Science.”

In the days before the ceremony, the students met American astronaut Terry W. Virts, who, arriving to attend the memorial services, expressed a wish to meet students interested in space science. In addition, some students traveled to the Knesset to present their projects before the Knesset Education Committee.

“The students demonstrated a high level of learning,” says Scherz. “They have shown that they are capable of dealing with advanced scientific material and are willing to dedicate hours after school for that purpose.”

Roars of applause mingled with tears as Ilan Ramon’s father, visibly moved, said to the schoolchildren, “Unfortunately, Ilan is not here – but if he were, you can all be sure that he would have heartily applauded you.” And again, as a boy from the Arab city of Nazareth pronounced at the end of his school’s presentation: “Ilan Ramon, we will all continue in your footsteps. May his memory be cherished.”

How many people can say that their job is directly related to those long, glorious days of childhood, when the only responsibility you had was to be home in time for dinner? Dr. Einat Aharonov is one of the lucky ones. Throughout her youth, she enjoyed long hikes, and contemplating the forces that shaped the mountains, rocks, and land that she loved.

"As a child, I was fascinated by how mountains were once under the sea and that you could find seashells on mountain sides," she says. "I wanted to understand the large forces of nature that could do that."

Now, as a researcher at the Weizmann Institute of Science, she studies these forces, devising ways to compress events that take eons in geological time so that they can be studied in her lab. Her interests are in the forces that move the Earth, from the slowly shifting tectonic plates that make up the Earth's crust to the physics of granular motion that describe the motion of massive landslides. The only problem? The phenomena are difficult to capture in the controlled settings of a research lab. Studying these events within a human lifetime - using manageable pressures and temperatures - requires computer models, analog materials such as salt or silicone, and most of all, innovation.

In one of her current projects, Dr. Aharonov and one of her doctoral students are looking at how massive landslides occur using computer models and boxes filled with fine sand. "The computer can simulate collections of grains, which can flow like fluid yet behave like solids at the same time," she says. Her research has shown that large-scale landslides are a result of the way particles move, conserving their kinetic energy through a bouncing motion. When this happens in nature - a phenomenon Dr. Aharonov dubs "spontaneous subchronization" - it can amplify a relatively small triggering event and cause devastatingly large landslides to flow unexpectedly across large distances. Dr. Aharonov and her student are in the process of writing a scientific report on this research, which she has shown in two-dimensional models. Her student is working on establishing a model to test the work in three dimensions. But there are still more dimensions to her research. Dr. Aharonov is also looking into the forces that work on tectonic plates. Rather than watching the plates themselves, which drift only inches a year, Prof. Yossi Mart of Haifa University and Dr. Aharonov have partnered with a laboratory in Sweden. Together they are using centrifuges to artificially enhance gravity and speed up geological time - at least in the lab - to see how the giant interlocking pieces of the Earth's crust move in relation to each other.

"We're trying to understand the physical processes that take place at the point where oceans meet continents," she says. Dr. Aharonov does not just study how the Earth is moved, but how it is formed. Her team is also looking at how rocks are formed and how they dissolve over time, again using special techniques and materials to speed up the process in the lab.

Since joining the Weizmann Institute in 2000, Dr. Aharonov has had an opportunity to be a force of her own, aiding in the development of a relatively new department at the Institute: the Environmental Sciences and Energy Research Department, a growing group of dedicated researchers who investigate everything from atmospheric chemistry and ocean and climate dynamics to solar energy. "It is very exciting to be a part of building this new department and these new studies," she says.

Dr. Aharonov hopes that enhanced understanding of the geophysical processes she is studying may facilitate engineering measures to better prepare us for the next time the Earth suddenly fails beneath us - as it inevitably will.

Thanks to technology developed in Prof. Hadassa Degani's laboratory, that relief may be had without the invasive, painful procedures that have accompanied cancer diagnosis methods until now. Prof. Degani discussed her breakthrough diagnostic method in a talk at MIT sponsored by ACWIS New England.

Prof. Degani's MRI-based method may someday be an alternative to mammography, presently the most widely available tool for breast cancer diagnosis. "The truth is mammography is not accurate. If the breast tissue is dense, as is the case for younger women, then mammography can miss malignant tumors. It also can't always differentiate between malignant and benign tumors. Too often pieces of a tumor must be removed for further testing. In 65 to 80 percent of cases these biopsies are unnecessary, because the tumors are benign," Prof. Degani said.

Prof. Degani uses MRI as a non-invasive way to differentiate between benign and malignant tumors at very early stages, sometimes even when tumors are undetectable by other methods. Unlike mammography, which uses X-rays to take a snapshot from two to three angles, MRI gives a three dimensional image of the whole breast at high resolution. MRI also provides high contrast in soft tissues, thereby generating the clearest and most detailed images.

A doctor can then use a computer to manipulate the image and look at "slices" of breast tissue from any angle or direction to pinpoint a tumor. Besides providing physical information about size and location of a tumor, MRI can also give information about location of blood vessels, blood flow, and density of cells in tissue.

To test for breast cancer, a patient is injected with a liquid that circulates in the blood and shows up on a MRI image. For the most accurate measurements, MRI images are taken at three time points: one before injection and two after injection of the fluid. As the fluid flows into breast tissue, it will move differently through cancerous cells than through normal tissue. "If you find tissue with densely packed cells and a lot of leaky blood vessels, then it indicates cancer," Prof. Degani explained. A computer takes the information from the MRI readings and analyzes it and then color-codes the image for easier interpretation.

Prostate Cancer
In theory, this MRI technique should be applicable to many types of cancer and other diseases. She and her colleagues have already successfully extended the technology to diagnose prostate cancer. Until recently, the only way to confirm a suspicion for prostate cancer has been to do biopsies on tissues that are taken from up to eight different places. But merely by optimizing the time points when the three MRI images were taken, the researchers were able to identify malignant tumors and predict the type of treatment necessary.

"Literally, we are trying to improve early detection and diagnosis of malignancy and thereby help extend the life of patients around the world. Thanks to our many collaborations, we have images coming to our labs in Israel from clinical trials in such diverse areas as Chicago and Vienna. I hope someday this will be a widely used diagnostic tool," Prof. Degani concluded.

Update:
Prof. Degani's method, known as 3TP (Three Time Point), has received FDA clearance for use in the detection of breast and prostate cancer. The 3TP technology is being licensed worldwide by 3TP LLC of New York, a privately held company.

Prof. Michal Schwartz, working in the Weizmann Institute's Neurobiology Department, came up with a novel idea. She suggested that toxic substances triggered by the initial damage are responsible for the ongoing nerve degeneration. These substances spill out of the damaged nerve cells and adversely affect healthy neighboring cells. Schwartz suggested activating the immune system – known to defend the body against external invaders such as bacteria – to combat the body's own toxic substances. She showed that in complete contrast to the generally accepted concept of autoimmunity (i.e., activity against the self) as inherently  harmful, it can serve as a defense mechanism against damaging self-compounds. Autoimmune disease results when control of this mechanism breaks down.

On the basis of these findings, Schwartz developed a method of boosting this defense mechanism without risking autoimmune disease. She showed that using Copaxone* (a drug that induces a “beneficial” autoimmune response) as a vaccine protects the optic nerve from neuronal degeneration.

This innovative procedure will soon undergo clinical trials. In the  past her approach resulted in a therapy for spinal cord injuries now being tested in clinical trials.

A team of researchers led by Prof. Irun Cohen of the Weizmann Institute of Science has developed a vaccine that halts the progression of Type I (juvenile or insulin-dependent) diabetes. The vaccine functions by blocking the destruction of insulin-secreting pancreatic cells.

Diabetes is a chronic disease associated with elevated blood sugar levels, in which the body does not produce or improperly uses insulin - a hormone needed to convert sugar, starches and other foods into energy. Recent data show that between 120 and 140 million people suffer from diabetes worldwide. Type I diabetes usually results from an autoimmune disorder in which the immune system mistakenly attacks the body's own insulin-producing pancreatic cells, reducing and ultimately eliminating all insulin production. All Type I diabetes patients eventually must receive insulin injections to compensate for their loss of natural insulin production.

For the past several years researchers at the Weizmann Institute's Department of Immunology led by Cohen have been studying the mechanism by which the immune system destroys the insulin-producing pancreatic cells. Working with mice, the scientists discovered that a particular protein called HSP60 was closely linked to this destructive process.

The protein acts like an antigen, prompting the immune cells to attack. Further investigation by Cohen, Dr. Dana Elias (first a graduate student and then a postdoctoral fellow at the Institute), and other students and colleagues revealed that injecting sick mice with p277, a small peptide fragment of the HSP60 protein, shut down the immune response, preventing the progression of Type I diabetes. This led Peptor Ltd., a biopharmaceutical company based in Rehovot, Israel, to develop the experimental drug DiaPep277, designed to prevent or treat Type I diabetes.

A combined clinical study performed recently by researchers at Hadassah-Hebrew University Medical School, Peptor Ltd., and Cohen proved that DiaPep277 is successful in arresting the progression of Type I diabetes in newly diagnosed patients. The research findings were published in the Lancet.

The study involved 35 patients newly diagnosed with Type I diabetes. Eighteen patients received injections of DiaPep277 - at the beginning of the study, after one month, and after six months; 17 patients received three injections of an inert substance (a placebo). Patients in the treatment group (those receiving DiaPep277) showed a delay or even a cessation in the attack by the immune system upon their pancreatic insulin-producing cells. These results were evident in the level of the body's own insulin production and a decreased need for insulin injections. The researchers were able to trace the mechanism of this improvement to changes in the patients' immune lymphocytes called T-cells. In contrast, patients receiving the placebo showed a significant decline in their natural insulin production and a persistent rise in the need for insulin injections. No significant side effects as a result of injecting DiaPep277 were found.

'The idea of using p277 stemmed from the discovery that the immune system has different options to choose from in responding to an antigen,' says Cohen. 'It can act to destroy the antigen or alternatively protect it from being destroyed. In the latter case it protects the antigen, thereby indirectly preventing damage to the pancreatic cells. The peptide essentially acts to 'reeducate' the immune cells, switching off their destructive activity.'

The scientists participating in this study are: Prof. Itamar Raz and Dr. Muriel Metzger of Hadassah-Hebrew University Medical School; Dr. Dana Elias (now VP R&D at Peptor Ltd.); and Drs. Ann Avron and Merana Tamir, also of Peptor Ltd.

Prevention rather than replacement
Back in 1920 Dr. Federick Banting and Charles Best of the University of Toronto made a discovery that would change the course of medical history. They had succeeded in obtaining a pancreatic extract which proved to have potent anti-diabetic characteristics when tested on dogs. Within two years their team would isolate and purify the extract's key ingredient, a hormone known as insulin, and the first human trial would begin, extending the life of Leonard Thomson, a fourteen year-old-boy who lay dying in hospital, for an additional 13 years.
Today extensive research efforts have yielded dramatically improved high-quality insulin as well as better delivery methods. Nevertheless insulin is not a cure, it merely helps to maintain blood sugar levels in check. A cure would be to stop the autoimmune destruction, sparing the insulin-producing beta cells. In contrast to the replacement therapy offered by insulin, the vaccine currently in development by Prof. Cohen's team has been shown to prevent the destruction of pancreatic cells.

Another turn, another groan of the engine, and the large van has already passed the village's first houses, circled the main square, driven along a street flanked by two torrential streams of water, and reached the community center. Nazam Siran, head of the center's activities is waiting at the entrance. 'I knew you wouldn't disappoint us,' he says, breaking into a broad smile beneath his large mustache. 'After your success here last year, I simply knew you would make it again, despite the storm.'

Rather appropriately, the first lecture the youths hear this morning has to do with thunder and lightning. The wide windows provide a perfect view as the storms plays out its fury. Later, they watch and participate in the process of glass-making under Nutman's direction.

The Madanoa van is equipped with science education exhibits and teaching aids that can be transported and set up in classrooms and school courtyards as well as in community centers. Some of Madanoa's teaching items are simplified versions of exhibits found in the Clore Garden of Science, the Weizmann Institute's award-winning outdoor science museum. The approach is simple: to make it possible to touch, feel, and try out natural and physical phenomena, making learning effective and fun.

First created in 1994, the goal of Madanoa is to offer this unique learning experience in relatively remote places, where the teachers and students can't pay regular visits to large city museums, universities, or research centers. Madanoa's instructors also work in the Weizmann Institute's Youth Activities Section and in the Clore Garden of Science. Thus, for example, when instructor Hila Dotan explains to Mrar youngsters about climatic phenomena such as wind and lightning, she uses models that she's brought along to make the various concepts easier to understand.
After the lecture, students Sahar and Reja share their impressions: 'It was really interesting. This is a lecture from life, unlike our usual classes, which are based on books. It's fun to understand what's happening right where you are - the mystery behind thunder, lightning, rain and other powerful forces of nature.'

The synthetic molecule has a structure similar to the soccerball-like clusters of carbon atoms called fullerenes, or buckyballs, named after R. Buckminster Fuller, architect of the geodesic dome. Fullerenes were discovered in the last decade when a U.S.-British team of scientists noted that, under certain conditions, carbon atoms will cluster together to form a stable, hollow sphere. The discovery won the researchers the 1996 Nobel Prize in Chemistry.

Initially, it was believed that only carbon, or molecules containing carbon, exhibit this behavior. But in 1992, Tenne and his Institute colleagues succeeded in producing inorganic fullerene-like molecules from tungsten disulfide. Since then, several other inorganic buckyball compounds have been synthesized at the Institute and elsewhere. To Tenne, the properties of the new, inert molecules seemed to have great potential for the development of a new generation of solid lubricants.

Why solid? Liquid lubricants, it turns out, are not appropriate for all environments. They freeze in the extreme cold of outer space and lose their effectiveness in a heated engine and in heavy-load transmission systems. Currently available solid lubricants, even ones made of tungsten or molybdenum disulfides, have drawbacks too.

"Existing solid lubricants contain crystallites, which are shaped like flat platelets and have chemically reactive edges," says Tenne. "In working conditions, they stick to machinery parts and undergo chemical reactions that lead them to decompose and rub off." The parts are then subject to grinding, substantially shortening the lifespan of the machinery.

The Weizmann tungsten disulfide buckyballs get "around" this problem. Being round and inert, they have no edges where the chemical reactions that make other lubricants stick can take place. Since machine parts just roll over them, they make reliable chemical ball-bearings. They wear better, too, because they are made up of many layers, like an onion. If the top layer wears off, the underlying layer continues the lubricating action. These balls are also larger than the carbon fullerenes, thus keeping the metal parts further separated and giving more bounce to resist mechanical pressure.

Tenne's next challenge was to produce the new material in the laboratory and test it under conditions simulating those prevailing in industry. The results that rolled in proved that this was definitely the right stuff. The new lubricant outperformed all existing solid lubricants, including normal tungsten disulfide and molybdenum disulfide. The synthetic buckyballs caused half the friction and only one-sixth as much wear.

The potential market for this new substance is tremendous. The automobile industry faces ever stricter environmental regulations that require it to reduce pollution and make engines and transmission systems more efficient. In general, earthbound enterprises are looking for ways to conserve resources and cut costs by making machinery last longer. In microelectronics, where minuscule transistors are produced under sterile conditions, solid lubricants are preferred over liquid ones because they cause no contamination of the electric circuitry. And in space, where commercial projects are proliferating, more and more equipment that can function in extreme temperatures will be required.

Currently, the Weizmann Institute laboratory can synthesize about a gram a day of inorganic buckyballs. To get this enterprise moving, it will be necessary to scale up the synthesis to at least a couple of hundred grams daily, a matter for smart engineering. Then a homogenous and stable emulsion of the solid particles in oil and cooling fluids must be formulated. And finally, extensive field tests have to be carried out to ascertain the stability of the lubricant in various environments. Yeda Research and Development Co. Ltd., the Institute?s technology transfer arm, has filed patent applications for the new material. Interest in it is being expressed by industrial companies around the world.

Tenne's team was made up of doctoral students Yishay Feldman and Moshe Homyonfer, Dr. Sidney Cohen of the Institute?s Chemical Services Unit and Dr. Lev Rapoport and other researchers from the Center for Technological Education in Holon.

According to one theory, memory loss and other cognitive deficits in Alzheimer patients result from degeneration of the nerve cells that release the message-carrying chemical, acetylcholine. The acetylcholine shortage that ensues is compounded by the action of AChE, the enzyme that breaks down acetylcholine in the body. Two Alzheimer drugs approved by the U.S. Food and Drug Administration, tacrine (Cognex) and E2020 (Aricept), work by inhibiting AChE.

A Qian Ceng Ta extract has recently captured the attention of researchers and physicians in China and the West because it too inhibits this brain enzyme, although it differs markedly in chemical structure from both tacrine and E2020. The extract is currently under investigation in China and elsewhere as a possible Alzheimer drug.

What the new Weizmann Institute study has shown is precisely how a chemical purified from this extract, called Huperzine A (HupA), blocks the enzyme. Using a method known as X-ray crystallography, the scientists solved the 3-D structure of the complex formed by HupA and the enzyme and found a strikingly good fit between the two: HupA slides smoothly into the active site of AChE where acetylcholine is broken down, and latches onto this site via a very large number of subtle chemical links. This binding closes off the enzyme's "cutting" machinery and keeps acetylcholine out of danger.

"It is as if this natural substance were ingeniously designed to fit into the exact spot in AChE where it will do the most good," says crystallographer Prof. Joel Sussman, one of the authors of the study.

"The good fit also means that HupA could be a potent drug even when used in small quantities, so that the risk of side effects would be minimal," according to fellow author, neurochemist Prof. Israel Silman. In any case, these risks are relatively small because HupA is believed to have low toxicity.

The research was carried out by graduate student Mia Raves together with crystallographer Dr. Michal Harel and Profs. Sussman and Silman, all of the Weizmann Institute. It involved close collaboration with Prof. Alan Kozikowski, a medicinal chemist at Georgetown University in Washington, D.C., who was the first to synthesize HupA in a test tube, and Dr. Yuan-Ping Pang, a chemist at the Mayo Clinic in Jacksonville, Florida, who had made theoretical predictions of the HupA-AChE interaction.

Heading in the opposite direction were two Moroccan physicists, Prof. El Hassane Saidi of the Mohammed V University in Rabat and Prof. Mohammed Saber of the Moulay Ismail University in Meknes. Among the first Moroccan scientists to visit Israel, they came to the Institute at the invitation of Weizmann physicists whom they met at a scientific meeting in Dahab, Egypt. "I wish more people in the Arab world knew what Israel is really like," commented Saber. "I'm sure that would benefit relations between our countries."

Israel-born Shapiro, now on leave of absence from the Institute's Applied Mathematics and Computer Science Department, has made a hit with his Virtual Places software, which allows interaction on the World Wide Web part of the Internet. The program enables users to meet at any Web site, explore different sites together and discuss their findings, via computer.

At the Institute, Shapiro's major focus was programming languages and, particularly, logic programming, and he spent a decade participating in Japan's Fifth Generation Project to advance artificial intelligence. Virtual Places arose from that research.

Shapiro was quick to realize the potential of the Internet, the global computer network that has mushroomed exponentially this decade. In late 1993, he took official leave and obtained a license from Yeda Research & Development Co. ? which is responsible for the commercialization of Weizmann Institute research ? to set up a company, Ubique. In March last year, he launched Virtual Places at a computer trade fair. America Online, the giant computer services company, was impressed and offered to buy Ubique. Shapiro sold the company in September 1995, and now serves as Ubique's president, reporting to America Online executives. Ubique's Vice President, Avner Shafrir, and the development staff remain in Rehovot.

In April this year, America Online officially launched Virtual Places for open testing on the Web.