Chemistry In The Holy Land

ASK ISRAELI SCIENTISTS in academia about their lives as researchers and they will likely paint a picture that in some ways resembles the lives of their counterparts in the U.S., Europe, and elsewhere but in other ways is quite distinct.

Like researchers abroad, Israeli academics in the chemical sciences must raise research funds, build and manage research groups, and publicize their findings under the scrutiny of peer review.

But unlike other countries that are widely known for scientific productivity, Israel is tiny. The country is smaller than the state of New Jersey and hosts a population of only some 6 million people. Furthermore, Israel is located in the Middle East, far from the Western countries with which it is aligned politically, socially, and academically. And it's surrounded by several hostile neighbors, some of which have declared publicly the desire to wipe the Jewish state off the map.

The odds of developing a successful chemical research program in such a place and under such circumstances might seem slim, and the task may be daunting. Yet Israeli chemists don't seem particularly fazed by the challenge. "Kacha zeh ba'aretz," they say in a matter-of-fact way. "That's just the way things are in Israel."

To get a firsthand look at the state of chemical research in Israel, C&EN visited some 30 research groups at three distinct types of academic institutions: Weizmann Institute of Science, in Rehovot, a leading private research institution; Technion—Israel Institute of Technology, in Haifa, an elite engineering and technical school; and Tel Aviv University (TAU), a large "full service" university. By drawing on interviews with scientists at those institutions, this profile aims to give a flavor of the kinds of research projects under way in Israel's academic chemistry laboratories and to open a window—just a crack—into the lives of the people who work there.

SITTING IN his office in the Weizmann Institute's original building, which dates back to the 1930s, organic chemistry professor Mordechai (Mudi) Sheves contemplates a question about the factors that make chemistry research in Israel unique from that in other countries. Sheves, who just finished serving a term as the dean of Weizmann's chemistry faculty, points to his colleagues' work in archaeology and solar energy as distinctive examples of chemical research tied specifically to the land, climate, and history of Israel. But for the most part, he says, "Israeli chemists focus on the same general areas of cutting-edge basic research as non-Israeli chemists." For example, Sheves' own area—molecular mechanisms that control retinal protein function—is studied in several countries.

For a unique-to-Israel angle, Sheves points instead to a fact of life for nearly every Israeli teenager: mandatory military service. As a result of that national requirement, which generally begins at age 18 and lasts three years for men and two for women, "Israelis tend to start their university education at an older age than American or European students," Sheves observes. It is typical, he says, for Israelis to begin their undergraduate studies at around age 21 and to graduate with a bachelor's degree at 24 or 25.

At that point, students can continue their education at an institution such as Weizmann, which offers only graduate degree programs, and spend roughly two years working toward a master's degree and another five years to complete a doctorate. Along the way, however, young Israeli researchers get called up for military reserve duty, which can keep them away from the lab for one month per year, sometimes longer. As a result, "by the time you get a Ph.D. in Israel," Sheves says, "you're likely to be around 32, which, by American standards, is quite old."

Precisely how an older student body and compulsory military service affect scientific research and productivity is an open-ended question. Perhaps serving in the army makes the average Israeli college student a little more worldly than his Western counterpart, Sheves suggests. "By the time you're done with the army, you have more experience in life," he says. That experience doesn't give Israelis a leg up in scientific know-how, Sheves explains, but it may lead them to be more independent and focus on goals and careers earlier in their education. Or the experience may cause less motivated students to decide against the lengthy time commitment required for an advanced degree in science and look instead for ways to join the workforce sooner.

Family life may also factor into the equation. Older students are more likely than younger ones to be married and have children. Those demands present additional challenges to young researchers. "In some ways, perhaps life is a little more difficult for students in Israel," Sheves summarizes. "But these are not problems that cannot be overcome. We manage."

At TAU, chemistry professor Aviv Amirav expresses a similar attitude. He notes that Israeli research groups, even the very successful ones, tend to be smaller than U.S. groups and therefore their output is correspondingly lower. Amirav's group, for example, which focuses on development of analytical instrumentation, typically includes about a half-dozen Ph.D. students, a senior scientist, and no postdocs. The team has commercialized a pulsed-flame photometric detector for gas chromatography and a novel sample introduction device. At present, the group is developing advanced gas chromatography-mass spectrometry techniques and instruments based on analyte-laden molecular beams.

"Our numbers are smaller than American groups because our financial resources are smaller," Amirav says. As a result, the number of laboratory developments and journal papers his group produces is limited. "Because of our size, I cannot make an impact by sheer volume," he notes. Small research groups and modest budgets are a challenge that Amirav and other Israeli scientists accept as a part of academic research in Israel. "It's not a complaint," Amirav states frankly. "It's a recognition of reality."

Moris S. Eisen is just as frank. "We're competing with less money and less manpower, and we're judged by the same rules of the scientific world as everyone else-publish or perish," he says. Eisen is no stranger to supersized chemistry research groups. As a postdoc, he worked with Northwestern University's Tobin J. Marks, an inorganic chemistry professor whose group has about 40 members. These days, Eisen is a professor of organometallic chemistry at Technion and director of its Institute of Catalysis Science & Technology.

As Eisen sees it, making the most of limited resources amounts to more than just a formula for success in academia; it's a route to national security. "If we want to be an economically independent country, we need to be strong in science and technology," he stresses. "Being strong means being a leader in your field." And to lead in science, "you have to find specific research areas in which you can make a real contribution." The breakthroughs don't have to come tomorrow or the day after, Eisen continues, "but you have to choose carefully to find a field with a bright prospect for success in the future."

In Eisen's case, the research is focused on designing organoactinide and other types of catalysts that are used for preparing advanced materials, often polymers. Recently, his group has been studying nonmetallocene amidinate polymerization catalysts and using them to synthesize elastic polypropylene (Organometallics 2006, 25, 2656). Eventually, the work may lead to a new recyclable material for automobile tires, he says. Eisen and coworkers also are developing a chemically active polymeric membrane that will serve as the heart of a purification system for patient-wearable dialysis equipment.

A HASTILY COMPILED list of topics under study by Israeli academics will resemble the lists compiled for U.S. and European scientists. But for all the similarities between the day-to-day activities in Israel's top research centers and those in the West, sometimes the differences stand out sharply. An extreme example was manifested in July and August 2006 when research at Technion ground to a halt as scientists fled repeatedly from the barrage of Hezbollah rockets to the safety of bomb shelters. Many of the locals headed south to distance themselves from the terrorists' positions in Lebanon. But some people, such as Technion's Alon Hoffman, a professor of physical chemistry, stayed on to relocate flammable and explosive chemicals and to keep an eye on his surface science lab (C&EN, Aug. 11, 2006, page 11).

Some Israeli scientists are free to move out of harm's way, but others aren't given a choice. Amit Sagi, a graduate student at TAU, responded to the call of reserve duty in Lebanon last summer. The interruption from graduate research was inevitable. But for Sagi it lasted longer than he anticipated: Shortly before Sagi's unit was scheduled to return from Lebanon, a land mine blew off part of his foot.

TAU's chemistry chairman, Shmuel Carmeli, also knows the pain of war all too well. A shrapnel-induced spinal cord injury suffered during the Yom Kippur War in 1973 robbed the organic chemist of the use of his legs.

Threats of terror and carnage aren't unique to Israel, but they are felt more strongly there than in many other countries, and their effects on research and life in general are visible. Eli Kolodney, a professor of physical chemistry at Technion, tells of a Chinese postdoc who left Kolodney's group and departed the country in fear after a rash of suicide bombings in Haifa.

"It's difficult to get good postdocs in Israel," Kolodney says, "because they are intimidated by the political turmoil. I can't blame them." In general, Israelis are encouraged to go abroad for postdoctoral research, so foreign postdocs are needed in Israel. Recruiting them, however, is a big challenge.

As with any field of science, the list of chemistry topics judged to have "bright prospects for success," as Eisen describes it, or deemed important to national security, changes over the years. In the 1930s, Chaim Weizmann, an organic chemist who would later become Israel's first president, directed what was then known as the Daniel Sieff Research Institute in scientific studies critical to the local citrus, dairy, silk, and tobacco industries. In the 1940s, with the outbreak of World War II and Israel's War of Independence, the research institute, which remained in the small town of Rehovot and was renamed in Weizmann's honor, focused on development of pharmaceuticals, including malaria drugs and painkillers. The institute also studied methods for producing chemicals essential for the war effort and the local population.

Nowadays, Rehovot retains its small-town charm, but research at Weizmann covers all the principal areas of chemistry, not just ones related to agriculture. Most of the research topics are not tied to the region, but some research projects still have an obvious Middle Eastern flavor due to their connection to antiquities or local climate.

In archaeology, chemistry professor Shimon Reich, a specialist in superconductivity, demonstrated a few years ago a new method for dating artifacts based on the magnetic properties of lead, a material widely used in Israel and elsewhere in antiquity. Reich and coworkers found that at cryogenic temperatures, lead becomes a superconductor, but the corrosion products formed from centuries of exposure to air and water-lead oxide and lead carbonate-do not superconduct. On the basis of magnetic measurements and comparison with artifacts that were determined via other techniques to be up to 2,500 years old, the group showed that the mass of lead corrosion products is directly proportional to an object's age (New J. Phys. 2003, 5, 99).

Another Weizmann research thrust with local significance is solar energy. Referring to a stadium-sized complex on the edge of campus, Jacob Karni, a professor of environmental sciences and energy research, describes the way 64 large, motorized mirrors reflect the abundant Israel sunlight to a 54-meter-high tower, where the concentrated solar energy drives various experiments.

"The whole field of solar energy is one of energy conversion—turning photons from the sun into something else, such as fuels that can be stored and transported," Karni says. Working along those lines, Karni and colleagues have developed solar-energy methods for preparing high-energy-value materials. Examples include separating hydrogen from water and making synthesis gas (CO and H₂) from methane and CO₂. The researchers have also demonstrated high-temperature solar methods for reducing zinc oxide to zinc, which can be reacted with water when and where fuel is needed to yield hydrogen, heat, and recyclable ZnO. The group is now studying similar reactions with boric oxide (B₂O₃), a high-energy-density material, as well as ways to prepare fuels from biomass.

While some Weizmann scientists ply their trade with huge solar reflectors, others, such as Roy Bar-Ziv, work with microscopic biochemical circuits. Bar-Ziv, a senior scientist in the department of materials and interfaces, is developing biochips that function as tiny artificial gene-expression machines for future use in medical diagnostics and biological analyses. A key challenge in that area is positioning the biomolecular components on the chips with micrometer-scale precision, he says.

To address that need, Bar-Ziv's group developed a biocompatible high-resolution lithography technique and demonstrated its ability to immobilize DNA molecules thousands of base pairs long on silica surfaces. The process is based on a new hybrid material that the researchers designed and synthesized. The group tested a chip prepared by the technique in a simple gene-expression experiment in which a protein synthesized at one location on a chip diffuses from that point to regulate the synthesis of another protein at a second location. The results of the study were just published (Small, DOI: 10.1002/smll.200600489).

Elsewhere at Weizmann, Daniella Goldfarb, a professor of chemical physics, leads a group that is developing theory, instrumentation, and methods for electron paramagnetic resonance (EPR) spectroscopy. One of the group's key advances is the design and construction of a high-magnetic-field spectrometer and its use in probing the structural and electronic properties of transition-metal sites in metalloenzymes. The instrument's high sensitivity and high resolution make it particularly well-suited to analyzing tiny single-crystal samples, Goldfarb notes.

In addition to bioinorganic systems, materials featuring nanometer&mdsh;sized pores?so-called mesoporous materials—also figure among the EPR group's research projects. Of particular interest is the mesoporous silica SBA-15. "The formation process in these materials is amazing," Goldfarb says. Her group monitored that process in detail through a combination of in situ microscopy and EPR methods. The study revealed details of the mechanism that guides the evolution of solution-phase microstructures from spheroidal micelles to the final hexagonal product (J. Am. Chem. Soc. 2006, 128, 3366).

Unlike the relative quiet of the Weizmann campus and the surrounding town of Rehovot, TAU is set in bustling, cosmopolitan Tel Aviv, the Mediterranean coast city that never sleeps. As with other major research schools, TAU is home to scientists whose work involves all the principal areas of chemistry.

At the intersection of organic chemistry and pharmaceutical science, TAU chemistry professor Doron Shabat is working on novel drug-delivery platforms. Based on highly branched dendrimers that can deliver a payload of drug molecules by falling apart on command, Shabat's molecular couriers are designed to ferry cancer-killing doses of medication directly to tumor tissue. By way of a video animation, Shabat explains that at the spot where the drug is needed, a tumor-specific enzyme cleaves a protecting group on the so-called self-immolative dendrimers and triggers release of the drug. Shabat's group recently synthesized a water-soluble system and confirmed its effectiveness in delivering four molecules of the anticancer agent camptothecin per dendrimer molecule (Bioconjugate Chem. 2006, 17, 1432).

Similar to other leading universities, TAU is home to a large number of scientists who endeavor to control and understand properties of matter at the nanometer scale. Many of those researchers carry out their work in the university's Center for Nanoscience & Nanotechnology. Ori Cheshnovsky, a professor of chemical physics and the center's general director, says the center was established to provide the intellectual framework and physical infrastructure conducive to the interdisciplinary research required in that field.

In one of the center's labs, Shachar Richter is devising methods for fabricating and testing molecular electronic devices for use as selective, sensitive biosensors. Recently, Richter's group came up with a procedure for preparing well-ordered self-assembling films of peptide nanotubes. A paper describing the method has just been accepted for publication in Advanced Materials. Now the plan is to make the nanotubes conductive by doping them with metal atoms so their response to analyte molecules can be measured electronically.

One of Richter's other projects, in the area of DNA-based sensors, is noteworthy because it pairs the Tel Aviv scientist with physicist Mukhles Sowwan of Al-Quds University, in the Palestinian Authority, and with a collaborator in Germany. A number of organizations sponsor such collaborations to help establish productive and peaceful ties between Israelis and Palestinians. In Richter's case, those goals are being achieved. "Mukhles is an optimistic person and a clever scientist," Richter says. He adds that, as a result of frequent visits, the two of them are forming a close friendship.

TAU's newest chemistry faculty member, Fernando Patolsky, is just setting up shop, but already he has big plans. Patolsky sees opportunities for success in advanced materials and nanobiotechnology.

One of Patolsky's goals is to develop synthesis methods based on new types of volatile chemical precursors that can be used to grow thin films and nanostructures of erbium sulfide and other lanthanide and actinide compounds. His aim is to use the materials to build efficient solar cells with enhanced light-collecting capabilities. Patolsky is also embarking on a project to develop large arrays of nanoscale detectors that can be used to carry out real-time chemical and biological profiling of cells. He proposes that cell "fingerprinting" methods of that type could lead to earlier and less invasive medical diagnoses than are available today.

Just a stone's throw from the synthesis labs, TAU's Eran Rabani investigates materials science and traditional chemical physics topics via theoretical and computational methods. One of the Rabani group's research thrusts has been dynamics of nanostructured materials. In that area, the group has studied self-assembly and crystallization in nanocrystals, as well as structure and transport phenomena in molecular junctions. Rabani and coworkers also investigate quantum effects in liquids; they developed a so-called quantum mode-coupling theory and have applied it successfully to investigate properties of liquid hydrogen, deuterium, and helium.

One hundred kilometers up the Mediterranean coast from Tel Aviv, at Technion, in Haifa, the situation is rather similar to TAU's: a top-notch university with scientists covering a broad range of topics in modern chemical research. In the area of solid-state chemistry, for example, Menahem Kaftory, dean of the chemistry faculty, studies structural changes in crystalline organic compounds that are induced by photochemical reactions. Just recently, Kaftory and graduate student Tali Lavy probed the effect of photodimerizing guest molecules (pyridone and methylpyridone) nestled within a crystalline inclusion compound. They found that the single-crystal-to-single-crystal transformation, which reduces the volume of the guests, decorates the host with a set of channels through which water molecules can diffuse (CrystEngComm 2007, 9, 123)

Another area of research at Technion is semiconductor nanocrystals. Chemistry professor Efrat Lifshitz synthesizes and explores the magneto-optical properties of cadmium sulfide, cadmium selenide, and other members of this family of materials, which are increasingly used in near-infrared lasers and in biological fluorescence tagging. A key advance from Lifshitz' group came from using colloidal chemistry methods to tailor the interface between the core and shell of two-component quantum dots, such as lead selenide/lead sulfide. Unlike other core-shell samples that feature a sharp interface between the two components, materials made in Lifshitz' lab include intervening alloy (mixed) layers, which enhance the nanocrystals' absorption and emission properties (Adv. Funct. Mater. 2005, 15, 1111).

On the surface, chemistry research in Israel is much the same as it is elsewhere in the subjects studied, the hustle to raise funds, and the drive to excel. But look a little deeper, and the difficulties associated with running a successful research program in the Holy Land stand out clearly.

Despite the daily challenges, however, life goes on and Israeli science flourishes. Perhaps it's determination or just a healthy dose of bravado, but somehow Israelis keep a stiff upper lip. "Kacha zeh ba'aretz," they say. "That's just the way things are in Israel."