Horse of Wands: NICOLÁS ACHÚCARRO and PÍO DEL RÍO-HORTEGA, the incredible riders of the “third element”

Nicolás Achúcarro Lund (1880-1918) and Pío del Río-Hortega (1882–1945) are two monuments of Spanish neuroscience who have nothing to envy of the figure of their teacher Cajal in terms of research, scientific illustration, international recognition and creation of a neuroscientific school is concerned. However, it is very likely that these names will not sound familiar to you if you are not neuroscientists, nor Valladolid, nor Basque 😞. With our Horse of Wands we want to contribute to the luster of this incredible pair of neuroscience horsemen insufficiently recognized in Spain.

In this entry you will be surprised by Nicolás Achúcarro who multiplied his stays in European countries during his medical studies at the beginning of the 20th century, long before the idea of the European Union germinated and Erasmus student exchange programs became popular! ! A Nicolás Achúcarro who was invited by two very prominent neuropathologists and neuropsychiatrists of the time, Franz Nissl (1860-1919) and Alois Alzheimer (1864-1915) to write an article in one of the six volumes of his magnum opus «Encyclopedia of histology and histopathology of the cerebral cortex. And as Don Gregorio Marañón already stressed in 1918 (El Liberal, April 25, 1918), it was not common for internationally recognized scientists to invite a young Spaniard to write in a work of such magnitude and scope [1]. Also exceptional was Alzheimer’s recommendation to the director of St. Elizabeth’s Hospital in Washington D.C. (USA) For a Spanish neuropathologist of only 28 years to direct the new histopathology laboratory of the old Federal Psychiatric Hospital, a position that from 1910 to 1912 was assumed by another of his brilliant Spanish disciples: Gonzalo Rodríguez Lafora (1886 -1971).

We owe Nicolás Achúcarro, thanks to the tannin and ammoniacal silver method that bears his last name (1911), the research into “rod cells” (stäbchenzellen, cells that Franz Nissl had described in 1898 in the brains of paralyzed people). brain) that laid the foundations for the studies of microglia that Pío del Río-Hortega would continue with such success. And this is part of Achúcarro’s greatness: that he knew how to sense the genius of his disciple Pius and, even going so far as to hide from her that the money from his scholarship was actually a part of his salary, he He managed to transmit all his science to her.

Histologist, pathologist and psychiatrist, Achúcarro inaugurated the histopathology section at the Escuela de Cajal and was also the initiator of the Spanish neuropsychiatric school, thanks to the fact that he knew how to open the knowledge of Spanish neurologists to international advances in the field and train them in good techniques. histological. We owe Nicolás Achúcarro the first descriptions of gliopathies (diseases caused by malfunctioning glial cells), at a time when it was believed that only neuron disorders caused diseases.

“Exceptional Spaniard, barely known in Spain, he stood out for his strong originality” Gregorio Marañón (El Liberal, April 25, 1918)

“Let me say that Nicolás Achúcarro seemed to me to be one of the ten or twelve Spaniards of the highest intellectual quality… Achúcarro’s smile was gone, and with it an enormous capital of accumulated science and an eminent power of thought.” Ortega y Gasset (in his obituary article in El Sol, April 26, 1918) [2]

Achúcarro was the “most brilliant companion, […] fraternal friend” and who “would have been the most worthy successor of the great master Cajal […] discoverer of very interesting facts in the histopathology of the nervous centers and inventor of technical resources very valuable» Francisco Tello (admission speech at the Royal National Academy of Medicine, January 14, 1923)[3]

Pío del Río-Hortega collected the histological legacy of his teacher Nicolás (the metallic impregnations to stain neuroglial cells, contributing his own silver carbonate method) and, immersed in the splendor of the Cajalian school, headed the section of histopathology, achieved international recognition comparable to that of Maestro Cajal. For Fernando de Castro he should be a hero for all of Spanish science, because the two types of cells of nervous tissue that were already known at the time, the neurons (our suit of Pentacles) and the astrocytes (our suit of Cups), Del Río-Hortega added the description of the other two main types of nerve cells: oligodendrocytes (our suit of Wands) and microglia (our suit of Swords).

On the national stage, Pío del Río-Hortega’s research took off with his arrival at the Laboratory of Normal and Pathological Histology of Achúcarro, where between 1915 and 1918 he published twenty scientific articles. After the death of his teacher Achúcarro, Pío del Río-Hortega assumed direction of the laboratory, but after a confrontation with Cajal he found himself expelled from the building where he shared space with the Biological Research Laboratory. At the head of his own laboratory created by the Board of Expansion of Studies in the Student Residence (curiously with the endorsement of Cajal) he continued his brilliant neurohistological research. Deprived of publishing in the prestigious magazine Trabajos del Laboratorio de Investigaciones Bilógicas directed by Cajal, he ended up founding a magazine that was published between 1918 and 1934 under the name Trabajos del Laboratorio de Histopathología. Cajal would recognize his mistake years later and both would resume the friendship they had. Río-Hortega, at the end of his life, would say that at Cajal’s side he felt “stimulated and depressed, he experienced joys and bitterness, he enjoyed the deepest emotions” and he confessed that his life was “full of Cajal” and that his memory “had become embedded in [his] brain” [4].

On an international scale, Pío del Río-Hortega was one of the most important neuroscientists of the 1920s and the disciple of Cajal who achieved the greatest international recognition. Among his achievements is having created a school of national and foreign disciples, among whom Wilder Penfield (called the topographer of the brain and the magician of epilepsy), Dorothy Russell and Amanda Pellegrino de Iraldi stand out.

Few of us know that he was an honorary doctor from the Universities of Yale (1912), Montevideo (1925), Oxford (1937), Paris (1939) and the University of La Plata (1941); He received the French Legion of Honor, and was twice a candidate for the Nobel Prize in Medicine or Physiology, in 1929 and 1937, for his revolutionary contributions to knowledge: in 1919, he published his work on microglia in four parts (initially called “cells of Hortega») and describes another cell variety that he will call oligodendroglia, of neuroectodermal origin. In 1921 he described the mesodermal origin of microglia and their phagocytic functions in different pathological processes. As with Cajal’s postulates, electron microscopy and immunohistochemical techniques will confirm, some decades later, the validity of his discoveries.

Like his teacher Achúcarro, Del Río-Hortega completed his histological facet with the study of pathologies of the nervous system. In 1928 he began working at the National Cancer Institute (which he directed from 1931), where he developed fruitful work alongside Severo Ochoa and, in 1930, founded the Spanish Archives of Oncology. As a histopathologist, another of the great contributions of the great Pío del Río-Hortega to science was the first histogenetic classification of tumors of the nervous system (1932), a classification in force until the recent arrival of new monoclonal markers.

Fleeing the Spanish Civil War first (he was a convinced republican) and the Second World War later, he had no choice but to flee to continue developing his research outside of Spain, in Paris (with the neurosurgeon Clovis Vincent in 1936), Oxford ( where Hugh Cairns built a replica of the Madrid laboratory for him to work between 1938 and 1940) and, finally, exiled in Argentina since 1940.

He remained in Argentina until his death, directing a laboratory built for him by the Spanish Cultural Institution of Buenos Aires (baptized “Ramón y Cajal” in homage to his teacher), where he continued researching (including the satellite cells that surround the neurons of the sensory ganglia of the peripheral nervous system in oligodendroglia) and working on tumors of the nervous system. He died on June 1, 1945 in Buenos Aires, but in 1986 his mortal remains returned to his native land, where Severo Ochoa received them to deposit them in the Pantheon. No. of Illustrious Men of Valladolid. Achúcarro and Del Río-Hortega, two scientists whose brilliance illness or wars have dulled, but perhaps we can give them back by making them known in our environment and giving them the recognition they deserve.

Have you been curious and want to know more?

SOURCES CITED

NICOLAS ACHÚCARRO LUND:

[1] EZPELETA, D., MORALES, F., GIMÉNEZ-ROLDÁN, S. (2019). Nicolás Achúcarro and the histopathology of rabies: a historical invitation from Nissl and Alzheimer. Neurosciences and History 2019; 7(4): 122-136  https://nah.sen.es/vmfiles/vol7/NAHV7N42019122_136ES.pdf

[2] LAÍN ENTRALGO, P. (1962). Life and significance of Nicolás Achúcarro. Digital edition from Medicamenta, no. 375 (1962), pp. 36-40, in the Miguel de Cervantes Virtual Library (2018) https://www.cervantesvirtual.com/nd/ark:/59851/bmc0924985

[3] Neuroscience Blog, José Ramón Alonso. Achúcarro  https://jralonso.es/2014/08/11/achucarro/

Achúcarro Basque Center for Neuroscience. About Nicolás Achúcarro Lund https://www.achucarro.org/es/about-nicolas-achucarro

Spanish Society of Neuroscience (SENC): “Meet the neuroscientists who have made history” Nicolás Achúcarro Lund: https://www.senc.es/wp-content/uploads/2017/11/biografia-Nicola%CC%81s- Achucarro.pdf

DÍAZ-RUBIO GARCÍA, Manuel. Royal Academy of History: Electronic Biographical Dictionary (DB-e), entry Nicolás Achúcarro Lund https://dbe.rah.es/biografias/4970/nicolas-achucarro-lund?msclkid=a7b87a52be6b11ec9e26a3f03cfc95bb

CAMPOS MUÑOZ, A. (2018). Nicolás Achúcarro. His life and his legacy one hundred years after his death. RANM ANNALS [Internet]. Royal National Academy of Medicine of Spain; An RANM 2018 · 135(02):125-131. DOI: http://dx.doi.org/10.32440/ar.2018.135.02.rev02

A Hombros de Gigantes (RNE), Series about Santiago Ramón y Cajal, his school and his legacy. Podcast of 02/28/2021 (LISTEN MINUTES 43:09 to 51:46): Manuel Seara interviews Fernando de Castro Soubriet, who tells us about the brilliant career of Nicolás Achúcarro Lund, which was cut short by Hodgkin’s lymphoma at the age of 38 https: //www.rtve.es/alacarta/audios/a-hombros-de-gigantes/hombros-gigantes-esperanza-optimismo-despues-ano-coronavirus-dia-mundial-enfermedades-raras-arn-otras-moleculas-origen- life-nicolas-achucarro-brilliant-career-truncated-28-02-21/5804787/

PIO DEL RÍO-HORTEGA:

[4] Neuroscience Blog, José Ramón Alonso. Don Pío, the glia and the war. https://jralonso.es/2014/04/12/don-pio-la-glia-y-la-guerra/

Royal Academy of History: Electronic Biographical Dictionary (DB-e), entry Pío del Río-Hortega https://dbe.rah.es/biografias/4344/pio-del-rio-hortega?msclkid=0297a593bea011ec92c171f7da455749

CAMPOS MUÑOZ, A. (2018). Rio-Hortega. The forging of a histologist (I). RANM ANNALS [Internet]. Royal National Academy of Medicine of Spain; An RANM 2018 · 135(03):222-229. DOI: http://dx.doi.org/10.32440/ar.2018.135.02.rev01

NOMBELA C., FERNÁNDEZ-EGEA E., GINÉ E., WORBE Y., DEL RÍO-HORTEGA BERECIARTU J. and DE CASTRO F. (2021) Women Neuroscientist Disciples of Pío del Río-Hortega: the Cajal School Spreads in Europe and South America. Front. Neuroanat.15:666938. https://www.frontiersin.org/articles/10.3389/fnana.2021.666938/full

Mini-report Pío del Río-Hortega, doctor and researcher. Television Castilla y León, 3.10.2013 https://www.youtube.com/watch?v=pGcau94a6FI

A Hombros de Gigantes (RNE), Series about Santiago Ramón y Cajal, his school and his legacy. Podcast from 4-4-2021 (LISTEN MINUTES 40:15 to 49:20) Manuel Seara interviews Fernando de Castro Soubriet, who tells us about the great Pío del Río-Hortega https://www.rtve.es/alacarta/audios /a-shoulders-of-giants/giant-shoulders-wormholes-internet-polluting-odderon-advances-mundo-rna-pio-del-rio-hortega-exhibition-origins-alicante-04-04-21/5832541 /

Obsolete Technology Blog, by Alejandro POLANCO MASA. Entry Pío del Río Hortega, explorer of nervous tissue, May 27, 2015 https://alpoma.net/tecob/?p=11383

A Hombros de Gigantes (RNE), Series about Santiago Ramón y Cajal, his school and his legacy. Podcast from 02/13/2022 (LISTEN MINUTES 33:30 to 44:40): Manuel Seara interviews Fernando de Castro Soubriet, who tells us about the national and international disciples of the Pío del Río-Hortega school https://www. rtve.es/play/audios/a-hombros-de-gigantes/hombros-gigantes-three-paraplegics-achieve-walking-thanks-to-electrical-implant-13-02-22/6367248/?msclkid=d588cb9cbb7911ec970ffb521f37deb3

PÉREZ CERDÁ, Fernando, SÁNCHEZ-GÓMEZ, María Victoria and MATUTE, Carlos (2015). Pío del Río Hortega and the discovery of the oligodendrocytes. Frontiers in Neuroanatomy, vol. 9      DOI=10.3389/fnana.2015.00092      https://www.frontiersin.org/articles/10.3389/fnana.2015.00092/full

The Pío del Río-Hortega Archive https://archivoprh.sen.es/ is a legacy probably compiled by Felisa del Río-Hortega (sister of Don Pío), which currently belongs to Dr. Juan del Río-Hortega Bereciartu. It has signed an agreement with the Spanish Society of Neurology to digitize it, so as to contribute to promoting research, conservation, donation and historical heritage of the SEN and neurology in Spain. Likewise, at the end of 2017, UNESCO included the Santiago Ramón y Cajal Archives and the Spanish Neurohistological School (which includes the Pío del Río-Hortega Archive) in its World Heritage Memory of the World program for archives and documentary collections. You can read more about the importance of this declaration in this article by Fernando de Castro and Juan del Río-Hortega Bereciartu https://theconversation.com/cajal-y-su-escuela-neurologica-when-la-ciencia-es-patrimonio -of-humanity-and-we-don’t-see-it-142740

OTHER INTERESTING SOURCES:

YouTube Channel Friends of the Museum of Natural Sciences. Series of lectures on the exhibition of Santiago Ramón y Cajal at the MNCN: If ever a scientist was a school, it was Cajal: the Spanish Neurological School. In just three decades, Cajal trained a series of disciples who, following in his footsteps, shone with their own light. His brother Pedro Ramón y Cajal, Francisco Tello, Domingo Sánchez, Nicolás Achúcarro, Pío del Río-Hortega, Gonzalo R. Lafora, Fernando de Castro and Rafael Lorente de Nó illuminated fundamental discoveries. Fernando de Castro Soubriet delves into the trajectories and contributions of what we know as the Spanish Neurological School, January 28, 2022 https://youtu.be/4wwbi4IvbrM?t=1187

TREMBLAY M.-È., LECOURS C., SAMSON L., SÁNCHEZ-ZAFRA V. and SIERRA A. (2015) From the Cajal alumni Achúcarro and Río-Hortega to the rediscovery of never-resting microglia. Front. Neuroanat. 9:45. doi:10.3389/fnana.2015.00045

BALCELLS, M (2014). Gonzalo Rodríguez Lafora (1886-1971). Neurosciences and History 2014; 2(4):176-180  https://nah.sen.es/vmfiles/abstract/NAHV2N42014176_180EN.pdf

BBVA Open Mind / Science Series, Great Characters. Entry Cajal, much more than a Nobel, October 18, 2015. https://www.bbvaopenmind.com/ciencia/grandes-personajes/cajal-mucho-mas-que-un-nobel/