I hurriedly write about Santiago Grisolía on the same day of his death in Valencia at the age of 99 years and 8 months. I am not doing it because of my friendship and collaboration with him for almost 50 years, but because he has been a Spanish scientist of international stature, charismatic and with strong public projection for at least half a century, and even more in the medical and research field. Also because his passage through life has improved it for us, and not just for a few, having had an important and positive social impact.

Grisolia was trained as a researcher, first in Valencia, with the excellent professor of Physiology D. José García Blanco (disciple of Juan Negrín, who was president of the Republic during the civil war). Then he was trained in the United States with Severo Ochoa in New York and with P. P. Cohen in Wisconsin. He made momentous discoveries on the forefront of scientific research at the time of his training, the study of enzymes (biological catalysts) and metabolism (conversions of substances in the body). In Wisconsin, he placed on solid biochemical ground how urea is manufactured by our body, actually demonstrating the existence of the urea cycle, until then a plausible hypothesis formulated by Hans Krebs (later a Nobel Prize winner for this cycle and for the energy-producing cycle called Krebs cycle). In this process, Grisolía discovered enzymes that are targets of rare diseases, the so-called urea cycle diseases. These successes led the University of Kansas to offer Grisolía the creation of the first biochemical research laboratory at the Kansas University Medical Center in Kansas City, the Mac Ilwaine Laboratory. There he developed his activity for the next 20 years, until 1976, creating and directing until 1973 the Department of Biochemistry, and then as Sam E. Roberts Distinguished Professor of Biochemistry, a true personal chair and highest academic degree of said university.

During his stay in Kansas, Grisolia did an extraordinary job in enzymology, then at the scientific forefront, laid the foundations for a form of treatment for sickle cell anemia, and trained many biochemists from all over the world in his department, with a large group of trained Spaniards, among whose last batch I count myself. During this period, his interest on Spain led him to multiple initiatives of regeneration and promotion of scientific and university modernity in our country, many of them in collaboration with the Nobel Laureate Severo Ochoa. I shall highlight: 1) Their contribution to the successful creation of the Spanish Society of Biochemistry and Molecular Biology (1961-1963). 2) Their contribution as advisors to the White Paper that based the General Law of Education of Villar Palasí. This law drastically modernized the Spanish universities, making the public system able to serve much broader social layers. 3) His participation in the organization of a great symposium in honor of Ochoa, then a Nobel laureate; this placed the most modern molecular biological research on the front pages of all the media. 4) The organization at the University of Valencia of a great congress on the Urea Cycle presided over by Krebs himself, with all the discoverers of said cycle, with an extraordinary Dalí poster, and which crystallized in an excellent book still of reference on said cycle (The Urea Cycle, 1976, Wiley. Grisolía, Báguena & Mayor, eds).

However, the true Spanish adventure of Santiago Grisolia began when he accepted the direction of the Institute of Cytological Research of the Caja de Ahorros y Monte de Piedad de Valencia. This biomedical research center of Valencia was owned by a foundation belonging to a savings bank. It was created by the doctor-researcher Gerónimo Forteza, who died in 1975, being succeeded by Grisolía (see https://metode.es/revistas-metode/article-revistes/la-bioquimica-en-valencia-desde-la-guerra-civil.html). He left in Kansas City almost all his previous life, as well as an excellent position with extraordinary research capabilities, for a private institute, well endowed for what was usual in Spain, but with a future considered very uncertain. The challenge was important. Grisolía set out to enhance the institute's existing capacities by introducing a strong biochemical component. Some of us were lucky enough to collaborate in this endeavor, the results of which were spectacular, despite using quite modest means, resulting in a true benchmark center of excellence for biomedicine in Valencia for many years, and in the training of a large number of scientists who have populated universities and research centers around the world. In it, for example, we prepared the carbamylglutamate used for the first time in a patient with a rare congenital disease (acetylglutamate synthase deficiency), today a specific commercial drug for the practically curative treatment of this disease, and also very effective in other congenital errors such as organic acidurias. Also in it, at the initiative of Grisolía and under the auspices of the Real Patronato para la Prevención de la Subnormalidad, was mass neonatal screening for congenital diseases started in Valencia in Valencia, in 1980-81. Santiago Grisolía not only directed said Institute, precursor of the current Príncipe Felipe Research Center, and in part, also, of the Valencia Biomedicine Institute of the CSIC (see https://metode.es/revistas-metode/article- magazines/la-bioquimica-en-valencia-desde-la-guerra-civil.html), but Grisolía also developed his work as a scientific researcher there until he left the center's management back in the 90s of the last century.

Grisolía has also been an extraordinary promoter and advocate of science in civil society until the last moment of his life, since he firmly believed in the supreme value of science as a social transformer. First, he created and led the Valencian Foundation for Advanced Studies, convincing members of the Valencian business sector to finance it through patronage, generating within that Foundation numerous debate and discussion meetings not only on scientific problems, but also on citizen issues and of social interests. With the Valencia meetings on the human genome, organized by him under the auspices of UNESCO, he promoted the development of genomics and the sequencing of the human genome. The most relevant international actors involved participated in these meetings, as well as the most advanced Spanish and especially Valencian geneticists, which was undoubtedly a key factor in the fact that Valencia is an important Spanish hub of genetic and genomic companies.

He also obtained public and private support that led him to the creation of the famous Rei Jaume I Awards, for whose management he created the Rey Jaime I Awards Foundation (of which he was now Honorary President). These awards were first only for Science but later also for Medicine, Economy, Environment, New Technologies, Architecture and Entrepreneurship, very well endowed, with irreproachable international juries that include a large number of Nobel Prize winners. He contributed to the creation of the architecturally exceptional and for its contents, the Principe Felipe Science Museum of Valencia, whose Council of Experts he has chaired until his death. He was also the driving force behind the creation of the Príncipe Felipe Research Center, a modern continuation of the Valencia Cytological Research Institute, but much larger.

It is worth mentioning a political-social function that Grisolía has performed with great skill, practically since the Government of the Generalitat Valenciana obtained its first powers. This is the Presidency of the Consell Valencià de Cultura (CVC) of the Generalitat Valenciana (https://elsfurs.gva.es/es/la-comunitat-valenciana/las-institucións/consell-valencia-de-cultura), a body created in the Statute for the preservation and promotion of culture and the cultural legacy of the Valencian Community. Grisolía has been its first and only president until the very day of his death. He has led from that position very important activities, particularly the preservation of monuments, the mediation in the debate on the language of the Community, and in so many other matters in which the CVC seeks to achieve a universal consensus of preservation and empowerment, also conserving the memory with an excellent publication policy.

In summary, Santiago Grisolia has been an exceptional person, committed and proactive. He had the trade and passion of a scientist of international stature and recognition (International Union of Biochemistry and Molecular Biology medal 2012; Prince of Asturias Award). He was creative, hard-working and had an exceptional capacity for conciliation, largely based on the high degree of trust in him from his interlocutors, which allowed him a transversal and non-sectarian access in the societies in which he has lived. His transformative commitment and his enduring and relentless effort, right to the end, should be lasting examples and cause for thanks. I wish we were able to generate many people like him in our society. We will miss him.

Vicente Rubio Zamora
Ad Honorem Research Professor
Institute of Biomedicine of Valencia of the Higher Spanish Council for Scientific Research (IBV-CSIC)