Three breakthrough Israeli scientists you never heard of

By ETTAY NEVO
June 10, 2017 10:31

A geneticist who saved the citrus industry from collapse, a researcher involved in the development of a drug worth billions of dollars but who gave it all up for her husband’s career.




Jerusalem market

Fruits and vegtables in a Jerusalem market. (photo credit:REUTERS)

Almost since the beginning of Zionism, the citrus industry was one of the most important symbols of agriculture in Israel and one of the country’s economic anchors. For example, in the 1930s about 75% of exports from the Land of Israel were citrus fruits, mainly oranges and grapefruits. Over the years, the glory diminished due to economic and social changes, and in the 1970s the citrus industry found itself in a deep crisis. One of those responsible for its successful revamp was geneticist Aliza Vardi.

Born in 1935, Vardi grew up in Rishon Lezion. During her military service she was a draftswoman and continued working in the field in the aerospace industry. She decided to fulfill her love of sciences and studied biology at the Hebrew University. She specialized in genetics and her doctorate, under the supervision of Prof. Daniel Zohari, focused on genetics, and the evolution of wheat crops. She continued her training in the field at Cambridge University in the UK, and after returning in 1972, went to work at the Volcani Center in Beit Dagan, which today is known as the agricultural research organization.

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In 1973, Vardi was appointed head of citrus enhancement projects at the Volcani Center. With the deepening citrus crisis, the institute realized it needed to shift its focus to innovation, and in the 1980s it was Vardi who was in charge of developing new citrus varieties. One of the challenges researchers faced was developing varieties of seedless fruit, which were popular in Europe.

“To produce seedless fruit, we need to create mutations in the young plant, then we need to select the right varieties, grow them and see if they develop into seedless fruit,” explains Dr. Nir Carmi, who is head of citrus enhancement and development of new varieties at the agricultural research organization.

“Citrus development is very time-consuming and requires a lot of patience. Aliza Vardi had the patience and the ability for this painstaking work. With tenacity, intuition and scientific vision she chose the right varieties.”

Vardi continued the work of Prof. Pinkas Spiegel, who headed the enhancement team before her, and focused mainly on developing varieties of clementines and mandarins. Among other things, it led to the development of new strains Nova (marketed overseas as Suntina), Ora, Shani, Merav, Rishon and Moore. The star of the new developments was clementine strain “Or,” which is characterized by sweet, tasty fruit that is very easy to peel and contains almost no seeds. Not to mention the fact that it ripens later than other varieties of clementines, so even in April, when the citrus season is essentially over, you can still pick and sell Or clementines.

The development of Or was completed in the early 1990s and seemed to be a total failure. Although the clementines were tasty, the fruits were not particularly attractive in appearance and the trees’ yield was too low to be economically worthwhile for the farmers. The solution to the problem was relatively simple – an incision in the bark, which left more sugars at the top to achieve a greater output of larger-sized fruit.

In the 1990s only a few farmers were breeding the Or strain, but by the beginning of the 2000s, encouraged by the Ministry of Agriculture, many other breeders got on board and there was a big leap in growth. Today Or orchards are spread over more than 20 hectares and the sweet clementines are exported to many countries, especially in Western Europe, but also North America, Russia and even Japan.

In 2014, export earnings for Or reached NIS 350 million a year – more than a third of total citrus export revenue from Israel.

“IF NOT for Or, the Israeli citrus industry would have been doomed. Or saved the citrus industry and a large part of it is credited to Vardi,” says Carmi. “There were those that harassed her and disagreed with her pursuing this species, but she did not give up, and she suffered a lot because of this. It was not easy to introduce the breed, but she insisted and in the end she was recognized as being right all along.”

Vardi contributed to many improvements in the mutagenesis process that created varieties with the most desired features.

“She used existing techniques and integrated new ones,” says Carmi. “She also discovered the inheritance mechanism for seedlessness, which in her time was very difficult to explore and develop.

Nevertheless, she managed to find out that there is probably a single gene responsible for it, and using the technology we have today, we continue her work to efficiently develop new varieties that are free of seeds.”

In 1998 Vardi was appointed director of enhancement and genetics for fruit trees. She retired in 2001, shortly before the huge success of Or. She won a prize for outstanding researcher awarded by the Plant Council, and in 2011 she received the Kent award for breakthrough agricultural research. She died of cancer in 2014.

“Aliza was a remarkable woman. It was a pleasure to work with her,” her colleagues wrote in her eulogy. “Even in her last decade as a retiree, she was interested and happy to help give advice from her vast experience.”

Carmi says she deserved more recognition than she received. “I would have been thrilled if she had received the Israel Prize. She made a tremendous contribution to the citrus industry.”

Even without the prize, her colleagues have shown her respect on her contribution to the development of many varieties of citrus, by naming a strain of grapefruit “Aliza” after her – a hybrid of pomelo and the Ora mandarins, which produce sweet fruit the size of a grapefruit. They have no seeds and are easy to peel, not to mention very tasty.

Moreover, “Aliza” is safe to eat for those who are taking drugs to lower cholesterol levels. Pomelo and grapefruit contain furanocoumarins, which disrupt the activity of the enzyme responsible for breaking down these drugs. Without breaking these drugs down, their increased level can be toxic for the patient.

“Vardi began developing this strain and I have continued her work,” says Carmi, “so we decided to name it after her. Maybe this will be the grapefruit of the future.”

Developing the drug, without the glory

Copaxone appears on any list of the most important Israeli inventions. This drug inhibits the progression of multiple sclerosis and has been marketed in dozens of countries worldwide, earning billions of dollars for Teva Pharmaceutical Industries, which held exclusive rights to it for many years.

In 1996, the US Food and Drug Administration approved the drug for marketing, based on a patent recorded more than two decades earlier by three scientists from the Weizmann Institute. Two senior scientists, Prof. Michael Sela and Prof. Ruth Arnon, were prominent figures, having won prestigious prizes including the Wolf Prize, the Rothschild Prize and the Israel Prize. However, the third party remained in the shadows, not sharing the glory and limelight of the other two.

DVORA SAVITSKY was born in Tel Aviv in 1941 to parents who immigrated from Poland in the 1930s. She grew up in Tel Aviv, and in high school began to take an interest in science, veering towards biology. During her military service she met Chaim Teitelbaum, who later became a senior IDF officer, and they married in 1962. Dvora Teitelbaum studied biology at Tel Aviv University and in 1966 completed her master’s degree.

She then moved to the Weizmann Institute and began her doctorate under the supervision of Prof. Ruth Arnon at the Department of Immunology.

The group was studying immune responses, among other things searching for ways to induce in laboratory animals the disease known as experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis, in which the immune system attacks myelin. Myelin is the lipid layer that covers nerve fibers and allows them to conduct electrical signals.

“Our research proved we could produce an immune response against substances such as fatty myelin sheath,” says Arnon.

“Later, when we identified a specific protein in cerebrospinal fluid that caused the diseased model and saw that it was very basic, we decided to try to produce small and short artificial proteins that would have the same effect, so we could then examine how they do it, and whether the level of acidity or basicity indeed affects the development of the disease. We added Prof. Michael Sela as a co-adviser, since he specialized in producing these short proteins.”

Teitelbaum was in charge of the development of these protein-like polymers to induce EAE in laboratory animals.

For more than a year she tested different materials and tried to see how they bind to lipids, but all development efforts were in vain; the injected materials did not cause the disease. This led her and her advisers to propose another concept – if these artificial proteins do not cause disease, they might be able to compete with the proteins that do.

This approach proved to be much more effective. Soon they identified a group of several short proteins that have become known as copolymers, which indeed were effective against EAE. One of these substances, copolymer-1, was also very effective in preventing the disease if injected before the causative protein was introduced, as well as suppressing the disease if injected into an animal already suffering the symptoms.

This material was termed Copaxone and was later purchased by Teva.

In 1974 Teitelbaum completed her doctorate, by which time the researchers managed to patent the material equally among the three of them: Sela, Arnon and Teitelbaum.

“Her doctoral dissertation was the basis for the development of Copaxone, so she was registered to the patent equally,” says Arnon. “She gave an enormous contribution to the Copaxone project, in her PhD dissertation and in the years that followed. It was her project.”

AFTER COMPLETING her doctorate, Teitelbaum gave up post-doctoral training.

“Raising children was very important to her, and most of the burden fell on her because our father served for long periods away from home,” says Teitelbaum’s daughter, Sagit Shiran.

“His military career prevented her from traveling overseas, as most scientists do at that stage of their career.”

Teitelbaum stayed at the Weizmann Institute and continued to work on Copaxone as a research fellow in the Department of Immunology. When Teva began to develop Copaxone as a drug, she served as consultant to the company and assisted them in planning and conducting research and experiments.

“The fact that she gave up on doing a post-doc may have been good,” Arnon says. “In such circumstances she would have moved on to study a different topic, but this way she remained a partner in developing the drug.”

Eventually, in 1980, Teitelbaum went for a year of post-doctoral training at Tufts University in Massachusetts, but it was too late to embark on an independent academic career. Though she had passed the ranking status of staff scientist, she could not become a group leader or guide research students, so reaching the rank of professor was not open for her. She continued to work on the Copaxone project and its related studies almost until her death from cancer in 2008. After her death her children established in their parents’ memory at the Weizmann Institute a research fund that supports cooperation between the institute and hospitals.

“She was a smart woman, but very humble, and never interested in standing out,” says Shiran.

“She loved her work and was a scientist by nature. The scientific way of thinking accompanied her in everything she did, even if it was planning a trip abroad, or inviting guests for dinner.”

Arnon agreed. “She was a first-rate scientist.She had science in her spirit and in her soul. Moreover, she was kind and everyone loved her, both at Weizmann and Teva. She knew how to push and promote things, but always pleasantly, and achieved way more than others.

Her husband used to say she was a Dvora [Hebrew for bee] but just from the sweet honey aspect, without the sting.”

Working with Einstein and kibbutz chores

Children who grew up in Kibbutz Mishmar Ha’emek in the 1960s and 1970s, had no idea the lovely woman working in the factory and the post office and playing the piano also had a significant role in the work of Nobel Prize laureates. In all of her modesty, none of that mattered. Only when asked, she happily agreed to teach mathematics to the kibbutz children.

Bruria Kaufman was born in New York in 1918. When she was a child, her family immigrated to Israel, settling first in Tel Aviv and then Jerusalem. From young age she excelled in science – especially mathematics – as well as music, becoming an accomplished pianist. Her father, Yehuda Even Shmuel Kaufman, a scholar in Jewish studies known for his translation of Yehuda Halevi’s The Kuzari into Hebrew, was sometimes nicknamed the “culture minister” of the budding state. Bruria’s brother Samuel Kaufman, was killed in 1947 during his Palmah service, and to this day he is remembered for his loving relationship with Zohara Leviatov, a fighter who also died then. Their love story has been immortalized in a famous book by Dvora Omer, To Love Until Death, and the play Zohara’s Shmulik.

Kaufman studied mathematics at the Hebrew University, graduating in 1938.

She returned to the US and continued advanced studies in mathematics at Columbia University. In 1941, she married the linguist Zellig Harris. The marriage blossomed over the years as an on-off relationship across both the US and Israel.

In 1947, she completed a PhD in mathematics and became a research associate at the Institute for Advanced Study at Princeton University. Her studies mostly involved mathematical solutions to complex physics problems. She wrote several papers with physicist Lars Onsager, who received a Nobel prize in chemistry in 1968. Among other things, she took part in the work to find simplified mathematical equations for the Ising model – a complex system of formulas that describe the behavior of magnetic materials and explain phenomena like phase transitions.

KAUFMAN WORKED at Princeton with renowned mathematician John von Neumann, one of the founding fathers of game theory, computer science and the atom bomb. She worked with him on investigating the Mössbauer effect, which involves the emission of gamma rays from solid material. In 1950, she became the mathematical assistant to the renowned physicist Albert Einstein, a role she continued until Einstein’s death in 1955. During these years they wrote two papers together and co-wrote a book about the meaning of relativity.

Following Einstein’s death, Kaufman spent time arranging his notes and research, and in 1957 joined her husband at the University of Pennsylvania, where she participated in mathematical research in the field of linguistics. In 1960, the couple immigrated to Israel, settling in Kibbutz Mishmar Ha’emek.

Kaufman was a professor of mathematics at the Weizmann Institute, and in 1972 moved to the University of Haifa.

In 1965, when the Hebrew University received Einstein’s estate, Kaufman was a member in the team that published his scientific writings.

All along their scientific work, Kaufman and her partner Harris were enthusiastically dedicated to the socialist movement and devoted to kibbutz labor. Zellig worked in the orchards and Bruria did shiftwork on the production line at the Tama factory that produces plastic tableware. She also taught mathematics to the children of the kibbutz, and loved playing piano and singing at kibbutz events.

“Story has it, with definite roots in reality, that they would travel for a few weeks for lectures in the United States, and return in time for their shifts in the kibbutz dining room,” as reported by one of their fellow kibbutz members to the kibbutz movement’s paper The Green Time.

In the 1980s, when their only child grew up, the couple left the kibbutz and returned to the US, mainly due to Harris’ academic career. Kaufman served as a visiting professor at Columbia and the University of Arizona, where she eventually moved after her husband’s death in 1992. Four years later she married Nobel laureate physicist Willis Lamb, a colleague from their days at Columbia, but the marriage did not last. Kaufman’s final years were spent in a nursing home in Kiryat Tivon until her death in 2010 at age 92.

■ This article was written under the auspices of the Davidson Institute of Science Education.


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