Forgotten Breakthrough Women Scientists

The researcher who saved the citrus industry

Since early in the history 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. But over the years, economic and social changes led to the citrus industry’s diminished glory, which found itself in a deep crisis in the 1970s. One of those responsible for its revitalization was geneticist Aliza Vardi.

Born in 1935, Vardi grew up in Rishon LeZion. A draftswoman during her military service, she continued her work in the aerospace industry until finally deciding to pursue her love of science as a biology student at the Hebrew University. She specialized in genetics and her doctorate, under the supervision of Prof. Daniel Zohari, focused on the genetics and evolution of wheat. She continued her training at Cambridge University in the UK, and returned to Israel in 1972 to work at the Volcani Center, today’s Agricultural Research Organization.

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

“To produce seedless fruit, we need to generate mutations in the young plant, then select the right varieties, grow them and see if they develop into seedless fruit,” explains Dr. Nir Carmi, who is the current head of citrus enhancement and development of new varieties at the Agricultural Research Organization. “Citrus development is highly time-consuming and requires considerable 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. Pinchas Spiegel, her predecessor at the head of the research team, focusing mainly on developing clementine and mandarin varieties. This led, among other things, to the development of new cultivars Nova (marketed overseas as Suntina), Ora, Shani, Merav, Rishon, and Moore. The star of the new developments was the “Or” clementine, which was characterized by sweet, tasty, easy-to-peel fruit with almost no seeds, which notably ripens later than other varieties, so that as late as April, when the citrus season is essentially over, Or clementines can still be picked and sold.

Preventing the collapse of the citrus industry: Or – a sweet, easy-to-peel, no-seeds clementine | Photograph: Agricultural Research Organization

The development of “Or” had been completed in the early 1990s, a seemingly total failure. While tasty, the fruits were not particularly attractive in appearance and the trees’ yield was too low to be economically worth the farmers’ investment. The solution was relatively simple: An incision made in the bark of the tree left more sugars at the top to achieve a greater output of larger sized fruit.

In the 1990s, only a few farmers were growing the Or strain, but by the early 2000s, with the encouragement of  the Ministry of Agriculture, many growers got on board, resulting in a large leap in growth. Today, Or is grown over 12,000 acres and the sweet clementines are exported to many countries, especially in Western Europe, but also North America, Russia, and even Japan. In 2014, Or’s annual export earnings reached NIS 350 million – more than one-third of the total revenue from Israel’s citrus export.

Worthy of the Israel Prize

“If not for Or, the Israeli citrus industry would be doomed. Or saved it – and a large part of it is credited to Vardi,” says Carmi. “There were those who disagreed and went against her pursuit of this species, but she did not give up, and she suffered considerably because of this. It was not easy to introduce the cultivar, 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 had been very difficult to explore and develop. But she found out that there is probably a single gene responsible for this trait, and, using the technology available to us today, we continue her work to efficiently develop new varieties that are devoid of seeds.”

In 1998, Vardi was appointed Director of Enhancement and Genetics for Fruit Trees, retiring in 2001, shortly before Or’s huge success. She won a prize for outstanding researcher awarded by the Plant Council, and in 2011 was awarded the Kent award for breakthrough agricultural research. She passed away in 2014 after losing her battle to cancer.

“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 and advise from her vast experience,” Carmi even went on to say she deserved greater recognition than she received. “I would have been thrilled if she had received the Israel Prize. Hers was a tremendous contribution to the citrus industry, and it may very well be a missed opportunity that she did not receive the prize.”

Even without the prize, her contribution to the development of many varieties of citrus won her the respect of her colleagues, who paid tribute by naming a strain of grapefruit after her – “Aliza” is a hybrid of pomelo and the Ora mandarins, which produce sweet fruit, the size of a grapefruit. They are seedless, peel easily – and are very tasty. Moreover, “Aliza” is safe for those people who take medications to lower their 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 levels can be toxic for the patient. “Vardi began developing this strain and I continued her work,” says Carmi, “so we decided to name it for her. Perhaps this is the grapefruit of the future.”

Developing the drug, not the career

Any list of the most leading Israeli inventions definitely features Copaxone. This blockbuster drug inhibits the progression of multiple sclerosis and has been marketed in dozens of countries worldwide, earning billions of dollars for Teva Pharmaceuticals, which, for many years, held its exclusive manufacturing rights.

In 1996, the U.S. Food and Drug Administration approved marketing of the drug, based on a patent registered more than two decades earlier by three Weizmann Institute scientists. Two of them were Profs. Michael Sela and Ruth Arnon, prominent figures who have won numerous prestigious prizes, including the Wolf Prize, the Rothschild Prize, and the Israel Prize. But the third scientist, Dvora Teitelbaum, remained somewhat in the shadows, not sharing the glory and limelight.

Born Dvora Savitsky in Tel Aviv in 1941, her parents had emigrated from Poland in the 1930s. She began taking an interest in science in high school, veering towards biology. During her military service she met Chaim Teitelbaum, who would later become a senior IDF officer, and they married in 1962. Dvora studied biology at Tel Aviv University and, in 1966, completed her master's degree. She then undertook PhD studies at the Weizmann Institute under the supervision of Prof. Ruth Arnon in the Department of Immunology.

The research group had been studying immune responses and, amongst other things, was searching for ways to induce the disease known as EAE (Experimental Autoimmune Encephalomyelitis) in laboratory animals. EAE served as a model for multiple sclerosis, in which the immune system attacks myelin – the lipid layer that insulates nerve fibers and enables them to conduct electrical signals.

“Our research proved we could produce an immune response against substances such as the fatty myelin sheath,” says Arnon. “Later, we identified a specific protein in cerebrospinal fluid that caused the disease model, and found out that it was very basic; we decided to try and produce small and short artificial proteins that would cause the same effect. This would enable us to examine how they do it, and whether the level of acidity or basicity indeed affects the development of the disease. So we added Prof. Michael Sela as a co-advisor, since he specialized in producing these short proteins.”

Teitelbaum was responsible for the development of these protein-like polymers to induce EAE in laboratory animals. For over a year, she tested different compounds, in an attempt to see how they bind to lipids. But the development efforts failed – and the injected materials did not cause the disease. This led her and her advisors to propose another concept – if these artificial proteins do not cause disease, they may 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 proved effective against EAE. One of these, 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 would be termed Copaxone and was later purchased by Teva. Teitelbaum completed her doctorate in 1974, 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 made an enormous contribution to the Copaxone project, in her PhD dissertation and in the years that followed. It was her project.”

A first-rate scientist whose PhD was the basis for developing Copaxone. Dvora Teitelbaum | Photograph courtesy of the family 

Army versus professorship

After completing her doctorate, Teitelbaum opted not to pursue 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.”

She 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 it 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, she did one year of post-doctoral training at Tufts University in the United States in 1980, but it was too late to embark on an independent academic career. Though she had moved from the engineering ranking to that of staff scientists, it did not enable her to lead her own research group, mentor students, or achieve the rank of professor. She continued to work on the development of Copaxone and its related studies almost until her death from cancer in 2008. Her children established a research fund at the Weizmann Institute in their parents’ memory, in support of collaborations between the Institute scientists and hospitals.

“She was a smart woman, but also very humble, and was 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 with these words. “She was a first-rate scientist. She had science in her spirit and soul. Moreover, she was kind and everyone loved her, both at the Institute and at Teva. She knew how to push and promote things, but always pleasantly, and achieved considerably 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.”

Articles with Einstein and Kibbutz chores

Children who grew up in Kibbutz Mishmar HaEmek in the 1960s and 1970s had no idea that one kibbutz member, a lovely woman working in the factory and the post office and playing the piano – had also played a part in the work of Nobel Prize laureates. She, on her part, did not make a big deal out of it, and only when asked, she happily agreed to teach the Kibbutz children mathematics.

Bruria Kaufman was born in New York in 1918, and immigrated to Israel with her family as a child, settling first in Tel Aviv and then Jerusalem. From a young age, she excelled in science – especially mathematics – as well as music, and became an accomplished pianist. Her father, Yehuda Even Shmuel Kaufman, was an important scholar of Jewish studies, sometimes nicknamed the “Culture Minister” of the budding state, and known for his translation of the The Kuzari to Hebrew. Bruria’s brother, Shmuel Kaufman, was killed in 1947 during in his service in the Palmach, and to this day he is remembered for his loving relationship with Zohara Levitov, a fighter and pilot who was also killed during her service. Their love story was immortalized in a famous book by Devorah 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 United States and continued on to advanced studies in mathematics at Columbia University. In 1941, she married the linguist Zellig Harris, who, like her, grew up in both the United States and Israel. She completed a PhD in mathematics in 1947 and became a research associate at the Institute for Advanced Study in Princeton University. Her studies mostly involved mathematical solutions to complex physics problems. She wrote several papers with physicist Lars Onsager, who later received a Nobel Prize in Chemistry in 1968. And she also 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.

Publishing papers with Nobel Prize laureates and working factory shifts in the kibbutz. Bruria Kaufman | Source: Wikipedia

Relativity and Socialism

Kaufman worked at Princeton with renowned mathematician John von Neumann, one of the founding fathers of game theory, computer science and the atomic bomb. With him, she investigated the Mossbauer effect, which involves with the emission of gamma rays from solid material. In 1950, she became the mathematical assistant to Albert Einstein, a role she continued until Einstein's death in 1955. During these years, she contributed to the theory of general relativity; they wrote two papers together on the mathematical aspects of this important theory, and co-wrote a book about the meaning of relativity.

After 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 HaEmek. 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 of the team that published his scientific writings.

All along their scientific work, Kaufman and 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, which produces plastic tableware. She also taught mathematics at the kibbutz, and loved playing the piano and singing at kibbutz events. “Story has it, with definite roots in reality, that when travelling to the U.S. for a few weeks of lectures, they would cut their visit short in order to return in time for their kibbutz dining room shifts,” reported one of their fellow Kibbutz members to the kibbutz movement’s paper The Green Time.

In the 1980s, after their only daughter grew up, the couple left the kibbutz and returned to the United States, 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 her days in Colombia, but the marriage did not last. Kaufman’s final years of life were spent in a nursing home in Kiryat Tivon, until her death in 2010 at the age of 92.