The enclosure is glass-walled. Through the glass door a long tube resembling a telescope is visible. A sign on the wall identifies the apparatus as a molecular beam epitaxy machine.

This futuristic setting is in fact the "clean room" at the Weizmann Institute's Joseph H. and Belle R. Braun Center for Submicron Research, where physicists are growing crystals of gallium arsenide.

The Institute team, headed by Prof. Mordehai Heiblum, and including Dr. Vladimir Umansky and doctoral student Rafael de-Picciotto, recently succeeded in growing the world's purest crystal of gallium arsenide, the semiconductor that is gradually replacing silicon, the mainstay of the microelectronics industry, in a variety of applications. For example, the main component of a cellular phone and the laser element in a compact disc player are made of gallium arsenide. This semiconductor is proving to be more efficient in carrying more and faster electronic signals, and it holds up better in outer space, where communications equipment is subjected to very low temperatures and high dosages of radiation.

Purity in semiconductors can be tested in two ways: the number of foreign, or non-gallium arsenide atoms the crystal contains, and the speed at which an electron can pass through it. The Institute team's crystal has only one foreign atom per five billion gallium arsenide atoms. This is the equivalent of a single cube of sugar in a five-story apartment house on a 300-square-meter lot.

As for speed, the new crystal beat the world record set by Bell Laboratories in 1989. Their material logged 11.7 million centimeters per second. Under the same conditions, electrons zoom through the Weizmann Institute crystal at 14.4 million centimeters per second. That's a speed of 518,400 km (324,000 miles) an hour.

What's the significance of these numbers? First, there are the commercial possibilities that producing a pure gallium arsenide crystal may bring. With fewer impurities, electrons will move faster, and this, in turn, will make a device work more quickly and more efficiently. Purity is also essential for manufacturing miniature electronic devices that behave in a predictable and uniform manner, a crucial factor for the electronics industry.

This research also has important implications for mesoscopic physics, the study of the behavior of electrons in very small devices.

Using this molecular "radar," the scientists have mapped the exact progress of an intercellular messenger that plays a key role in embryonic development.

The achievement, featured recently on the cover of Science, is expected to prove valuable in gaining a better understanding of how signals are transferred inside a cell and how the signaling process goes awry in diseases such as cancer. It could also help resolve the mystery of how cells in an embryo manage to form the different types of tissues and organs of a human or animal body.

"Previously, in studying message transmission inside the cells of a developing organism, we scientists were rather like people at an airport watching the planes take off and land," says research team leader Prof. Ben-Zion Shilo, head of the Institute's Molecular Genetics Department.

"We could make some intelligent inferences about where the planes were going or where they had come from, but we couldn't see the course a plane was following.

"Our new method gives us an ability equivalent to that of an air traffic controller, who looks at the dots on the radar screen and can thus follow the movements of each plane step by step," Shilo says. "Suddenly we can look at processes in a cell or an embryo as they are happening and we don't have to infer things from the consequences any more."

Shilo conducted the study with Dr. Rony Seger of the Biological Regulation Department and with doctoral student Limor Gabay of the Molecular Genetics Department.

The starting point for the study was the knowledge that many messages inside cells are passed on by means of phosphate atoms.

When a molecular messenger, such as a hormone, attaches itself to a receptor on the cell membrane, it sets off a chain reaction inside the cell in which one molecule activates the next, through the addition of phosphate atoms, a process known as phosphorylation.

To track the activated, phosphate-containing molecules, the team developed antibodies that react only with molecules phosphorylated in a particular fashion. Since these antibodies can be easily traced, the system allowed the scientists actually to observe phosphorylation --  the pathway of signal transmission -- in real time.

Shilo and his team worked with Drosophila fruit flies. These insects are used commonly in scientific research because they share many genetic and molecular characteristics with higher animals, develop rapidly, and are easy to study. The researchers focused on a hormone-like messenger called epidermal growth factor (EGF), which becomes active during embryonic development and ensures the formation of a proper body pattern.

Using the new method, they followed the signal transmitted by EGF from the point at which EGF attaches to its receptor on the cell membrane up to the time it delivers the message to the genes in the cell nucleus. They were able to see precisely when and where the signal is passed on within individual cells, and also to observe which cells within an embryo are affected by EGF at different stages of embryonic development.

 

 

A bone marrow transplant is a last-ditch effort undertaken only after all other means of combating the leukemia have been tried. That's because it is inherently fraught with danger. Patients may die from the radiation or the chemotherapy used to kill off the cancer and to disarm their own immune system so that it doesn't attack the transplant. They may succumb to infections during the period after their immune system has been knocked out and before the new marrow takes root. In cases of partially matched marrow, there is the danger of graft-versus-host disease, in which the foreign white cells attack the patient's own tissue. Or the transplant may fail because residual white cells in the patients system simply overcome the transplanted ones before they can confer healthy immunity.

A potential solution to these life-threatening problems is emerging from the work of Prof. Yair Reisner of the Institute's Immunology Department. A decade ago, Reisner, then working at the Memorial Sloan-Kettering Cancer Center and using a technique he developed with Weizmann Institute's Prof. Nathan Sharon, helped solve the problem of conferring immunity on 'bubble children.' These youngsters are born without immune systems and cannot survive outside the protective confines of large plastic bubbles. Before transplanting the bone marrow, Reisner first treated it with lectin, a soybean derivative. The lectin neutralized aggressive white cells in the donor marrow that can cause graft-versus-host disease. Once cleansed of these cells, marrow stem cells could be implanted in the young patients with no fear of rejection, since the children had no immune systems to act against the transplanted tissue. The donated stem cells proliferated, creating the immunity that had been lacking.

Recently, Reisner developed this technique further so that it can be applied to leukemia patients. First, donated stem cells are cleansed with the soybean lectin to erase the characteristics that are the source of trouble in mismatched tissue. This makes it possible to use marrow from non-matching donors. Then, the number of stem cells taken from the donor is greatly increased so that the sheer volume of implanted cells overwhelms any resistance mounted by residual white cells in the recipient.

To increase the quantity of stem cells, Reisner, working with Prof. Massimo Martelli of Italy's Perugia University, decided to try an approach used originally to isolate stem cells from cancer patients. It consists of treating the donor with hormone injections for a week prior to harvesting. This releases large numbers of stem cells into the bloodstream. In a procedure called leukapheresis, blood is then taken and passed through a machine that extracts the stem cells. The rest of the blood is then returned to the donor. The extracted stem cells are cleansed of white blood cells and readied for transplant.

Since 1993, some 100 patients have been treated in Perugia with the Institute-derived method. The current survival rate is almost 50 percent, similar to that obtained with perfectly matched transplants. The donor marrow comes from one of the patients relatives. Since the tissue need be only partially matched, a suitable donor can nearly always be found among family members. Several hospitals in Israel, Germany and the United States have begun to introduce the new method.

Reisner is now pursuing research to reduce the amount of radiation that bone marrow transplant candidates receive in preparation for the procedure, a factor that has limited its use to cancer patients. If successful, his research may make bone marrow transplants a viable treatment option for people with such disorders as thalassemia, sickle-cell anemia and Gaucher's disease. Reisner's work may also allow physicians to transplant organs and tissues other than bone marrow from mismatched donors.

Prof. Reisner will soon be appointed to the Henry H. Drake Professorial Chair in Immunology. This research was funded in part by Rowland Schaefer, Miami, Florida; the Pauline Fried Estate, Los Angeles, California; the Concern Foundation, Los Angeles, California; and the Israel Academy of Sciences and Humanities. Research facilities: Mr. and Mrs. Sanford Diller, Los Angeles, California.