Luis Federico Leloir of Argentina received the Nobel Prize in Chemist in 1970 “for his discovery of sugar nucleotides and their role in the biosynthesis of carbohydrates.”
As he described it himself in an autobiographical essay “Far Away and Long Ago,” Luis Federico Leloir was born at roughly the same time as the scientific field (biochemistry) to which he would devote his life. Leloir’s life also began in the shadow of tragedy. His father, Federico Augusto Leloir Bernal, had become very ill, so Luis’ parents left Buenos Aires for Paris, France, in search of a cure. Unfortunately, the illness was terminal, and Federico died one week before his son Luis Federico Leloir Aguirre was born near the Arc de Triomphe on September 6, 1906.
Leloir and his mother, Hortensia Mercedes Aguirre Herrera de Leloir, returned to Buenos Aires in 1908 to live on the family estate near San Clemente del Tuyú. Luis’ grandparents had immigrated to Argentina from the Basque region in southwestern France/ northeastern Spain and purchased enough land to build up an agricultural enterprise based on grain and cattle, the “rural activities” that allowed Luis to graduate and devote himself to research rather than worry about a stable salary by earning a living.
In his childhood home, there were many books on a variety of subjects related to natural phenomena, which complemented his natural curiosity and interest in the animal life he saw in the countryside around him. His schooling, however, did not lead him directly to biochemistry. His early years were spent at private schools such as Escuela General San Martín and the Colegio Lacordaire, followed by a few months at Beaumont College in England and the Ecole Polytechnique in Paris. As these did not satisfy him, however, he returned to Argentina, obtained Argentine citizenship (as he had been born in France), and enrolled in the Department of Medicine at the Universidad de Buenos Aires to get a doctorate. After passing the anatomy exam on the fourth try, he received his degree in 1932 and began his two-year residency in the Hospital de Clínicas, with a medical internship at the Ramos Mejía hospital.
During his residency, Leloir realized that, at the time, there were not enough effective treatments for his patients, so he decided to direct his efforts towards medical research rather than treating patients. At the time, Dr. Bernardo Houssay was the most prominent researcher in Argentina. Through family connections, Leloir met Houssay in 1933 and the two became closely inked, collaborating on research projects until Houssay died in 1971. Leloir credited Houssay with having the greatest influence on his career. Houssay became Leloir’s doctoral adviser, supervising his thesis work in the role of the adrenal glands in carbohydrate metabolism while serving as a research assistant at the Instituto de Fisiología (Institute of Physiology) at the Universidad de Buenos Aires. As this work required more knowledge about chemistry than Leloir had learned for his medical degree, he continued to take courses at the Facultad de Ciencias (Faculty of Sciences). With Houssay’s help performing adrenalectomies on dogs, Leloir completed his thesis work, which won the Annual Prize of the Faculty for best thesis in 1934.
After Leloir completed his doctoral thesis, Houssay advised him to gain some work experience abroad. To better grasp biochemistry, in 1936-1937 Leloir went to work in the Biochemical Laboratory in Cambridge, England, with the Nobel Prize winner Sir Frederick Gowland Hopkins, considered the father of English biochemistry. While in Cambridge, Leloir also worked with Malcolm Dixon on enzymology, looking at the effects of cyanide and phosphate on succinic dehydrogenase. His time in England introduced Leloir to the international scientific community and exposed him to international scientific practices such as the methods involved in selecting the fundamental problem to study. He also learned solid work habits and how to work in small spaces.
When he returned to the Instituto de Fisiología in Buenos Aires in 1937, Leloir brought with him enzymes to study. He teamed up with Juan M. Muñoz, who provided a small distillation apparatus that could be used to reliably measure ethanol in their work on ethanol metabolism. Although this equipment was not ideal, the research team used “lo que tiene a mano” (what one has at hand). This ability to innovate was extremely necessary when they started to study the metabolism of alcohol and formation of fatty acids in the liver. The tissue samples used in the experiments had to be kept cold so liver homogenates would remain active. As refrigerated centrifuges were too expensive, Leloir and Muñoz covered their regular centrifuge with inner tubes filled with a mixture of water, ice, and salt. By using a substance thus extracted from liver cells, they showed that oxidation of fatty acids was due to the enzymes found in the cells and not intact cells themselves, which had previously been believed. Leloir and Muñoz also worked with Eduard Braun Menendez on the effect an enzyme found in the kidneys could have on a transient or temporary increase in blood pressure.
In 1943, at the age of 37, Leloir married Amelia Zuberbühler, whom he had first met in 1941 at a friend’s wedding. The two shared a love of the fine arts, outside of Leloir’s devotion to science. Unfortunately, this life milestone coincided with a coup d’etat that replaced the civilian government with a military junta that included Juan Perón. As the new government was more sympathetic with the Axis powers, Houssay, Leloir, and other scientists promoted the return to democracy, the constitution, and solidarity with the American hemisphere in support of the Allied forces. This activism caused Houssay to lose his position at the Universidad de Buenos Aires. Although he decided to remain in Argentina, Leloir moved to the United States with Amelia. There he continued his training in biochemistry, first with Carl and Gerty Cori at Washington University in St. Louis, Missouri, then with David Green at Columbia University in New York City, where he worked on the purification of aminotransferases. Another important aspect of science that Leloir learned from working with Green is that groups of researchers can apply for grants to fund salaries, equipment, and supplies if they have a space somewhere set aside for them to perform their experiments.
Although Houssay no longer had a government position at the Universidad de Buenos Aires, he was able to raise sufficient private funding to open the Instituto de Biología y Medicina Experimental (Institute of Biology and Experimental Medicine) in 1944. In 1945, Leloir returned to Argentina and renewed his collaboration with Houssay at this new research institute. Around the same time, a textile industrialist, Jaime Campomar, approached Houssay with the idea of establishing a new research institute to focus on biochemistry. Houssay recommended that Leloir be the director. The Instituto de Investigaciones Bioquímicas del la Fundación Campomar (Biochemical Research Institute of the Campomar Foundation) was inaugurated in 1947 in a small house next to Houssay’s institute in Buenos Aires.
Leloir preferred working with others rather than alone and had assembled a research team, including Carlos Cardini, Alejandro Paladini, Enrico Cabib, Ranwell Caputto, and Raúl Trucco. This group began work on the biosynthesis of saccharides, a relatively new field at the time. Their initial research looked at the formation of lactose but when those efforts were not successful they shifted their focus to the degradation of lactose and galactose utilization. Leloir and his team used enzymatic tests and paper chromatography to identify the substances separated and purified in their experiments. This allowed them to detect nucleotides involved in storing sugar during the biosynthesis of carbohydrates. Because of the work that the Instituto Campomar did to identify the sugar nucleotides that are fundamental to the metabolism of carbohydrates, Leloir was awarded the Premio de la Sociedad Científica Argentina (Argentine Scientific Society Prize). The research team’s efforts expanded to include glycoproteins and the mechanisms of galactose metabolism, which led to their discovery of the cause of galactosemia, a disorder related to lactose intolerance.
In 1957, Jaime Campomar died, depriving the Instituto Campomar of its annual funding. Finding support from the United States National Institutes of Health (US NIH) and other organizations, Leloir and his team continued their work measuring the activating action on galactose transformation using yeast extracts and detecting biosynthesis of sucrose using wheat germ enzymes. In addition, they found that liver extracts could catalyze the formation of glycogen and worked to clarify how glycogen is synthesized and degraded. This gave new impetus to their work on the regulation of glycogen metabolism. Different types of glucose are bound together to form glycogen in times of plenty; glycogen then is degraded back to glucose as fuel in liver cells in times of scarcity.
After Perón was ousted from power in 1955, the new government started to support the sciences. By 1958, several new scientific institutions were being established, such as the Consejo Nacional de Investigaciones Científicas y Técnicas (National Council for Scientific and Technical Research — CONICET). At the same time, Argentine universities regained their autonomy. The Facultad de Ciencias Exactas y Naturales (Faculty of Exact and Natural Sciences) of the Universidad de Buenos Aires became associated with the Instituto Campomar when the Argentine government converted a larger building, which had been a school for nuns, into the new site for Leloir’s institute, that of Houssay, and the new Instituto de Investigaciones Bioquímicas (Institute for Biochemical Research) established by the Facultad itself. As Leloir was the head of this new institute as well as being the director of the Instituto Campomar, he also served as a professor at the Facultad. In this way, the two institutes and that headed by Houssay collaborated with each other, sharing space, equipment, and researchers. Leloir and his team thus had a greater number of sources of support, including US NIH, CONICET, the Facultad, the Rockefeller Foundation, and the Science and Technology section of the Ministerio de Economia.
With such support, Leloir’s team expanded their research beyond glycogen to the formation of starch in plants. They found that the glycoprotein (UDP-Glc) that worked well as a precursor for glycogen did not work well for starch but that another glycoprotein (ADP-Glc) did.
In 1970, Leloir was awarded the Nobel Prize in Chemistry “for his discovery of sugar nucleotides and their role in the biosynthesis of carbohydrates.” He donated his prize money to the Fundación Campomar to support research. In addition to this honor and being the head of both the Fundación Instituto Campomar and the Instituto de Investigaciones Bioquímicas, Leloir at various times was a professor and head of the department of biochemistry at the Facultad de Ciencias Exactas y Naturales of the Universidad de Buenos Aires, a member of the Board of Directors of CONICET, president of the Asociacíon Argentina para el Progreso de Ciencia (Argentine Association for the Advancement of Sciences), and a founding member of the Third World Academy of Sciences, which was established in 1983. Also in 1983, Leloir wrote a short autobiography, “Long ago and Far Away,” which was published in the Annual Review of Biochemistry (Annual Review 52: 1-15 at http://www.annualreview.org). In that year, the Instituto Campomar moved into a new building that was constructed on land donated by the mayor of Buenos Aires to be a center for biochemical research. Leloir devoted the rest of his career to that institute.
In 1987, after returning home from a day of work at the laboratory, Leloir died of a heart attack. The institute to which he devoted so many years of his life was renamed the Fundacíon Instituto Leloir which continues to conduct research in a variety of medical fields.
According to Armando Parodi (in his article “Luis Federico Leloir, or How to Do Good Science in a Hostile Environment, in IUBMB Life, 9 May 2012, Vol 64, #6, pp. 567-572), Leloir gave some valuable advise to other scientists who were at the beginning of their careers, by comparing his career in science with how he learned to play polo as a young man:
“One thing I have always tried to avoid is working on subjects that have already drawn other researchers’ interest. Young scientists tend to become fascinated with subjects that are in fashion and decide to focus their work on them. By the time they become experts, those subjects themselves may already be running out of fashion, or what is worse, they may have become the subject of fierce competition. This whole situation reminds me of the times when I played polo in my youth. The older, more experienced players would always advise me not to ride after the ball itself, for once one reached it, it was already too late. The wise thing to do, they kept telling me, was to ride straight to where one thought the ball will end up. There is a slight time difference between both tactics, and in sport strategy is truly learnt only by experience. When dealing with science, I guess the right strategy is to follow the results from experiments rather than those from literature.”
Sources: http://www.nobelprize.com “Luis Leloir — Biographical”
en.wikipedia.org/wiki/Luis_Federico_Leloir
Leloir, Luis (1983). “Far Away and Long Ago.” Annual Review of Biochemistry, Vol. 52: 1-16. https://doi.org/10.1146/annurev.bi.52.070183000245
http://www.britannica.com/biography/Luis-Federico-Leloir
http://www.thefamouspeople.com “Luis Federico Leloir”
http://www.biografiasyvidas.com “Luis Federico Leloir”
http://www.esearch.sc4.edu Hispanic and Latinx Scientists
Parodi, Armando J. “Luis Federico Leloir, or how to do good science in a hostile environment.” 9 May 2012. iubmb.onlinelibrary.wiley.com. IUBMB Life 64:6, pp. 567-572.
Saavedra, Gabriela (21 March 2021). http://www.serargentino.com “Luis Federico Leloir: un genio modesto”
Lorenzano, Cesar (2015). Luis Federico Leloir: Historia de una Investigacion Nobel. http://www.academia.edu
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