Cristina Arruti (1944-2018): the culture at the center

The unpleasant situation of having to leave the country, convulsed by the period that preceded and followed the coup d'état and the military intervention of the University, meant for Cristina the bitterness of leaving her beloved laboratory, but also an opportunity to complete her training abroad. It was in Paris, where she had previously made brief visits to the embryology laboratories of Étienne Wolff and Louis Gallien, that she reached what I am sure she considered the best stage of her career, in the Gerontological Research Unit of the INSERM (“la Unité "), directed by Yves Courtois. Her previous training, as well as the vast culture of literature related to the effects of hormones on isolated tissues, led her to become interested in the functional relationship between the retina and the lens. Two organs of the eye that do not touch, but that during embryonic development grow in a coordinated manner, always remaining aligned to achieve the desired final effect: forming a perfect dark camera capable of generating clear images. A germ of an idea had been born in Cristina's head, and legend has it that she simply told Courtois to leave her alone for a while, that she was going to do a series of experiments and would inform him when she had results.

The director of the Unité, an affable and very patient man, accepted, although his perplexity at such a proposal is imaginable. The results that eventually arrived and were published in the journal Experimental Cell Research in 1978 were simply spectacular: the retina contains a soluble factor with the ability to violently modify the behavior of lens epithelial cells in culture, causing them to go from being epithelial to mesenchymal, and greatly increasing their proliferative capacity. This work began a long and prolific relationship between Cristina and the members of the Unité and led her to obtain in 1979 the valuable title of Doctorat d'État ès Sciences, at the University of Paris V René Descartes. Valuable in general terms, for its prestige, but also in personal terms, since it was her only university degree (having had to abandon her degree studies in Uruguay before finishing them). Growth factors, neurotrophins and cytokines were a huge mass of pressurized magma that erupted in the 1970s, following the earthquake of molecular biology. Suddenly, the scientific literature was invaded by hundreds of reports of new “growth factor” type activities. Cristina's discovery was of utmost importance, it was the “basic fibroblast growth factor” (bFGF, currently FGF2), but it was not the only one at that time. There was even a Nobel Prize, awarded in 1986 to the great Italian researcher Rita Levi Montalcini for the discovery of NGF (“nerve growth factor”), and to the US researcher Stanley Cohen for the discovery of EGF (“epidermal growth factor”). But not for the FGF.

In any case, the positive impact was important for Cristina, and for our country. Eventually she returned, restored the old Tissue Culture Laboratory and formed a group of collaborators that was consolidated since the late 1970s. She returned with her hands full: an important European Union project made it possible to purchase laboratory materials, reagents and, above all, equipment that was scarce in Uruguay. When I arrived at the laboratory more than ten years and several projects later, it was at its peak: several graduate students, visiting researchers, two technicians, top-notch equipment, apparently limitless access to reagents. “The factor” was omnipresent, although other research topics were soon added, especially related to the theses of the new students. For example, her interest in the lens as a target of FGF led her to study some special characteristics of cell differentiation in this organ. Here it is worth highlighting what was part of Alicia De María's doctoral work, involving the identification and characterization of the enzyme DNase I (the same one that is secreted by the pancreas during digestion) in the necessary nuclear degradation process that fibers of the lens undergo for the sake of transparency. I was fortunate to be another of her students, and to share Cristina's encounter with another protein that would fascinate her in the second half of her scientific career: MARCKS. We found it completely by chance, using antibodies to find molecules distributed in a peculiar way in the embryonic retina of the chicken, and it took us three years to identify it and stop calling it “3C3 antigen.” Our initial reaction included some disappointment, because this was a protein that had been known for over 15 years (as would be expected in the second half of the 1990s). Disappointment that soon turned into excitement, when we discovered that what we were studying was a form modified by phosphorylation, unique to neurons, of this molecule related to the cytoskeleton and cell membrane. We also soon discovered that many details of this protein expression, modifications and interactions were rather well characterized, without really understanding its function. A total of thirteen publications and six completed postgraduate theses have resulted to date (2019) from this line of research. In each and every one of the enterprises described, Cristina showed her eternal passion for solving mysteries. Curiosity was her driving force, an innocent curiosity similar to that of small children, with the seemingly simple ambition of increasing human knowledge.

Culture is only useful when it is shared, which can be done in many ways. Cristina had grown up in a home of teachers, so it was natural for her to extend her knowledge and ideas to others through formal teaching. From 1964 (when she was barely 19 years old) and until 1975, she was a Secondary School Teacher of Natural History and Biology, and between 1973 and 1975, a Cytology Teacher at the Artigas Teachers Institute (IPA). It was in this decade that she surely acquired the pedagogical tools that she continued to deploy and perfect throughout her life. Since 1970, she also held various teaching positions at the University of the Republic, both in the Faculty of Medicine and in the Faculty of Humanities and Sciences (continuing in the Faculty of Sciences). In 1986, she accepted the position of Full Professor of Cell Biology, a full-time position that she maintained until retiring in 2015. It was in these almost 30 years that she imposed in our country a very particular stile on the teaching of the discipline at a basic undergraduate level, always respecting the premise of academic freedom for participating teachers, but with clear lines in terms of promoting discussion and practical activities, with the greatest possible access of students to experimental manipulations. She also created the Developmental Biology course in the late 1980s, essentially based on experimental modules and initially aimed at graduate students, but then with some variants over time, incorporated into the undergraduate courses of the Faculty of Sciences.

The teaching and training of qualified human resources at the postgraduate level, with a strong inclination to the generation of new researchers, was a constant concern of Cristina. For this reason, she was, along with several other fellow citizens, a pioneer and a great champion of the Basic Sciences Development Program (PEDECIBA), which had as its main objective, since its inception in the mid-1980s, to tend towards a continuous growth of the mass of scientific researchers in our country. The numbers are surprising, when it is evident that with minimal funding throughout most of its history, PEDECIBA completely changed the face of science in Uruguay, as well as increased its insertion into global academia. More than 30 years later, the process is still underway and even today, with such important changes in the last decade in terms of how research is funded in our country, PEDECIBA is still as valid and necessary as it was at the beginning. Clearly, an innovative and visionary idea from those researchers who, many of them returning after long periods abroad, converged on Uruguay with the desire to turn it into a modern and prosperous country. Shortly after, she would embark with other professors of the University in the project of creating the current Faculty of Sciences, crystallized in 1990 as a split of the old Faculty of Humanities and Sciences, and completed in 1998 with the move of the entire Faculty from the old Tristán Narvaja Street premises to the new building in Malvín Norte.

After so many decades in the Faculty of Medicine, the Tissue Culture Laboratory also moved to this new building in 1999, integrating and still remaining in the current Cell Biology Section, as part of Cristina's commitment to dedicate herself one hundred percent to teaching and research in the Faculty of Sciences. This did not mean, however, that she forgot her interest in teaching at all levels, and she always worried about being able to interact in some way with basic education, whether visiting schools, receiving school teachers in the laboratory or participating in commissions. I want to highlight in particular what was her last activity at this level, which she organized after retiring from her position as Full Professor. Concerned about updating teaching content at the secondary level, particularly in the area of ​​Cell Biology, she sought to influence where she could have a broader impact: in the “training of trainers.” Thus, together with members of the IPA, especially highlighting her former graduate student Virginia Pellegrino, she designed and carried out a course-workshop in 2016 in which she involved several teachers from the Faculty of Sciences, aimed at IPA teachers and other training centers. The idea of ​​the workshop, which was very successful, was to transmit not only knowledge but also modern but simple enough experimental tolos, so that they could be used by these teachers when training the next secondary education teachers.

In tribute to this scientific career and her contributions to the training of human resources, the Faculty of Sciences awarded Cristina Arruti the title of Professor Emeritus in 2017, a year before she physically left us, on November 29, 2018. An immense legacy, distributed among all his students and in the academic institutions with which she interacted, in addition to the most measurable production in the form of articles in international magazines and book chapters, remained. It was a clear example of a generation that will not be repeated, who lived many revolutions in all fields of human existence, locally and globally. Some had, like her, the privilege of not only surviving them by adapting, but also of being protagonists and drivers of the changes that have helped us grow, obtaining the achievements that we all recognize in modern society. Always with culture at the center.

Flavio Zolessi, august 2019