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."

1968. Profs. Ruth Arnon and Michael Sela and Dr. Dvora Teitelbaum synthesize several molecules, known as copolymers, that mimic a component of myelin, the protective coating of nerves. Because this component is believed to trigger multiple sclerosis, the scientists hope that their molecules can help create an animal model for the study of MS. However, the copolymers fail to produce an MS-like disease in laboratory animals.

1971. Despite the initial failure, the scientists persist in their study of the molecules' properties and stumble on a surprising finding: rather than causing MS symptoms, the copolymers actually block an MS-like disease.

 

1972-74. Patent applications for copolymer-1, dubbed Cop 1, are submitted in Israel and several other countries. Meanwhile, the scientists show that while suppressing the symptoms of the MS-like animal disease, called EAE, Cop 1 does not depress the entire immune system indiscriminately. They also show that it works in several species of laboratory animals.

 

 

1977. The first clinical trial is conducted at the Hadassah-Hebrew University Medical Center in Jerusalem, in collaboration with Dr. Oded Abramsky, a former Ph.D. student of Arnon's, who at the time was Head of Neurology and then served as Dean of the Medical School at Hadassah. Four MS patients in the terminal stages of the disease receive Cop 1 and show no major side effects.

 

 

1978-81. The Weizmann Institute scientists embark on the formidable task of convincing clinicians to perform larger-scale clinical trials. Two physicians respond to their call: Dr. Helmut J. Bauer of the University of Gottingen, Germany, and Dr. Murray B. Bornstein of the Albert Einstein College of Medicine in New York.

 

 

1980-85. Preliminary results both in Gottingen and in New York are encouraging, and Bornstein decided to extend the evaluation of Cop 1 to a rigorous double-blind study. Fifty patients are recruited for the study, a complicated process involving the interviewing of several hundred people.

 

 

1987. The results of the double-blind trial are published in the New England Journal of Medicine. Cop 1 is found to reduce the number of attacks in patients with relapsing-remitting MS while having minimal side effects.

 

 

1987. Cop 1 is licensed to Teva Pharmaceutical Industries Ltd., Israel. Commercial development of the drug is launched.

 

 

1987. Meanwhile, the scientists continue to pursue research aimed at clarifying Cop 1's mechanism of action.

 

 

1994. Weizmann Institute scientists are invited to the presentation of the results of an extensive trial conducted by Teva at 11 medical centers throughout the United States.

 

 

June 14, 1995. The file on Cop 1 is submitted by Teva to the U.S. Food and Drug Administration.

 

 

December 23, 1996. Copaxone® is approved by the FDA for use in patients with MS.

Sometimes, however, a "bully" cell is born or moves into the area, where it ignores other inhabitants and its surroundings, moves around and reproduces uncaringly. That "bully" is a tumor cell, and it can ruin the neighborhood.

Profs. Benjamin Geiger and Avri Ben-Ze'ev of the Molecular Cell Biology Department are studying how cells manage to maintain good neighborliness through communication and how this process goes awry in tumor cells.

Cell communication takes place when cells adhere to their surrounding substance, the matrix, and to their neighboring cells. This adhesion anchors cells in one place and enables them to link up to form tissues and organs and to exchange signals that control their behavior. Molecules known as junctional proteins, found in and just under the cell membrane, join cells with the matrix and with their neighbors, and carry adhesion signals to the cell interior.

Tumor cells are known to be associated with poor adhesiveness, and Geiger and Ben-Ze'ev believe this contributes to cancer in two ways. First, while normal cells receive signals to stop reproducing when they reach a certain density, the lack of adhesion to the matrix and to other cells that is characteristic of tumor cells means these cells do not receive such signals.

"Normal cells don't like overcrowding," says Geiger. "Once cell density reaches a certain optimal level in a normal tissue or organ, specific signals induce growth arrest. Tumor cells usually don't respond to crowding in this way; they keep reproducing, one on top of the other."

Second, the reduced adhesion of cells within a tumor means they are freer to migrate and spread, or metastasize, leading to secondary cancers.

The Institute scientists have made several discoveries that throw light on adhesion-related cell signaling and its connection with cancer. Two decades ago, Geiger identified the first junctional protein, vinculin. Around the same time, Ben-Ze'ev demonstrated that adhesion to the right matrix is essential for normal cell functioning, and that cells denied this adhesion show marked changes in gene expression, the process by which a particular gene produces its protein. Uncontrolled growth, the hallmark of cancer, can proceed in the absence of adhesion.

More recently, Ben-Ze'ev and Geiger found that in tumor cells some junctional proteins, such as vinculin, actinin and plakoglobin, are present in reduced amounts or are absent altogether. When they genetically manipulated human kidney cancer cells to contain these proteins, tumor growth was inhibited.

"This suggests that a reduction in junctional proteins is probably an essential step for tumor formation," says Ben-Ze'ev.

This research also produced an unexpected finding. In their engineered tumor cells, Ben-Ze'ev and Geiger noticed that plakoglobin was not located in its usual place under the membrane, but had made its way to the cell nucleus and was apparently suppressing tumor growth from there. This led to their realization that in normal cells plakoglobin is present also in the nucleus, albeit in minute amounts, as well as under the membrane. The scientists suggest that this "dual nationality" for a molecule such as plakoglobin might be a previously unknown means to control cell growth -- the molecule not only affects cell adhesion and signaling from its usual place under the membrane but probably also acts on genes involved in regulating cell growth, affecting their expression. While the mechanism by which the protein enters the nucleus, and exactly what it does there, are still under study, this finding may shed further light on the development of tumor cells.

The scientists also believe that their research has the potential for helping in the design of a future cancer therapy that would aim to halt tumor growth by improving cellular adhesion and communication.

A radically new approach to controlling chemical reactions, based on the use of laser light, is under study at the Center of Excellence headed by Weizmann Institute Prof. Moshe Shapiro.

Known as coherent control, the approach was pioneered by Weizmann Institute Prof. Shapiro and University of Toronto Prof. Paul Brumer over a decade ago. These days, this laser method is arousing great interest -- in large part because of its potential applications for industrial chemistry, paving the way for the more efficient manufacture of a variety of products, from pharmaceutical drugs to superfast optical switches.

The desire to use laser beams to break chemical bonds between molecules is not new. But previous attempts largely failed to meet the challenge of breaking a single bond without affecting others.

Coherent control, the Shapiro-Brumer approach, has addressed the problem by using a laser beam to excite the wavelike aspects of molecules. Inside the molecules, as in a stormy sea, two waves that meet crest to crest will produce an even bigger, deeper wave. Conversely, when the waves meet crest to trough, they extinguish each other. Shapiro and Brumer exploited these effects in order to direct chemical reactions so as to break specific molecular bonds, thereby producing the desired reaction products.

In an experiment reported earlier this year in the scientific literature, Shapiro, Brumer and their colleagues at the Weizmann Institute and University of Toronto demonstrated for the first time that it is also possible to use laser light to control the quantity of materials produced in a chemical reaction. By varying the wavelengths of the laser beams, they were able to increase the yield of one product produced in the reaction, while decreasing that of another.

Shapiro cautions, however, that there are numerous obstacles to overcome before coherent control can be used for large-scale industrial technology. But if these limitations are overcome the technique could, for instance, revolutionize the pharmaceutical industry by providing a fast and efficient method for producing righthanded or lefthanded forms of compound. Like our hands, molecules often exist in two mirror forms, or enantiomers, one of which is biologically active and the other either inactive or harmful. Today pharmaceutical companies expend considerable time and money to produce the correct form of these molecules for drugs.

Coherent control may also lead to novel technologies, such as improved optical switches for semiconductor devices that are many times faster than existing ones, as well as lasers that emit supershort bursts of light that are a tenth the length of ones now in use.

This new Center of Excellence includes four research groups, two of them at the Weizmann Institute -- one headed by Shapiro and the other by Prof. David Tannor, another pioneer of coherent control who recently joined the Institute from the University of Notre Dame. The other two teams are led by scientists from the Hebrew University of Jerusalem. Shapiro and Tannor are members of the Chemical Physics Department .