The scientific roots of José A. Campos-Ortega, a German neurobiologist born in Spain

Authors

  • Roberto Marco

    Corresponding author
    1. Departamento de Bioquímica de la Universidad Autónoma de Madrid, Instituto de Investigaciones Biomédicas “Alberto Sols,” UAM-CSIC, Madrid Spain
    • Departamento de Bioquímica de la Universidad Autónoma de Madrid, Instituto de Investigaciones Biomédicas “Alberto Sols,” UAM-CSIC, C/Arzobipo Morcillo, 4, Madrid 28029, Spain
    Search for more papers by this author

Abstract

In this review article, we shall focus our attention on the initial steps in the research career of José A. Campos-Ortega and the studies he undertook. Particular emphasis will be placed on how these early experiences shaped his personality and his future scientific contributions. Developmental Dynamics 235:855–860, 2006. © 2006 Wiley-Liss, Inc.

THE VALENCIAN PERIOD (1940–1966)

José A. Campos-Ortega was born in Valencia (Spain) in August 1940, almost a year and a half after the Spanish Civil War had ended. This was a period in which most of the Spanish population that remained in the country was embarking on a long journey through the desert. The majority of Spanish intellectuals had fought on the side of the losers, the democratically elected Republican Government, and they were removed from their official positions in the Universities or in other Institutions by Franco's regime. Due to the political constraints imposed on them, many were forced to emigrate while others were summarily executed. Despite the existence of some isolated oasis, the intellectual conditions in which Campos-Ortega grew were far from optimal. He pursued his secondary education in a religious school run by the Dominicans, one of the orders that had recovered control of primary and secondary education, reversing the educative reforms that had been initiated by the Republican regime before the civil war. During this initial period of his life, José decided to follow the steps of his predecessors and in 1958 he started studying Medicine (his great uncle had been a Full Professor in the Medical School at the University of Valencia and his grandfather and father were active MD's with successful practices).

At the time, an MD's training took seven years to complete and few departments or laboratories provided stimulating incentives for young students eager to pursue a career in science. Certainly, everybody had the name of one man in mind, that of the great neuroanatomist Santiago Ramón y Cajal, who was awarded the Nobel Prize in 1906. He had been a Professor in Valencia from 1883 until 1887 when he moved to Barcelona. He later established himself in Madrid (1892) where he remained until his death in 1934. From very early in his life, José was full of admiration and respect for Don Santiago, since his great uncle had been associated with Professor J. Bartual, the main disciple of Ramón y Cajal during his years in Valencia.1 Nevertheless, it is very likely that José's interest in histology and research had been directly stimulated by his father, Arturo Campos, who had initially been trained in histology and who tried to initiate a research carrier during the Second Republic. However, as for many others, he had to set aside his research due to the difficult conditions in Spain and the need to provide for his family, a decision he always regretted. This parental influence was obviously deeply imprinted in the mind of the young Valencian, who after some initial doubts on which studies to pursue, decided to register at the Medical School.

During his time in Medical School, two groups further influenced José to orient his professional life in the way he did. Although I speak of groups, this concept was almost devoid of significance in the Spanish Universities and Research organizations at the time. There were very few positions and virtually no fellowships or established funding system. Those interested in pursuing a scientific career had to approach the few people that were actually doing so individually. Thus, the two groups to which I refer were organized around Juan José Barcia-Goyanes who was Professor of Anatomy, and José María López-Piñero, Professor of History of Medicine, whose courses José and I attended in 1960–1963.

Juan José Barcia-Goyanes (1901–2003), was a very intelligent and influential person from the mainly conservative Northwestern region of Spain. He attained his full professorship in Valencia when still only 28 years old. Like many other Full Professors in Spain, he also ran a very successful clinical practice, in his case in Neurosurgery. However, when coupled with his administrative obligations as the Dean of the Medical School, he had little remaining time to dedicate to his Research, which was supported by the University and the Spanish Scientific Research Council.2 Barcia was an exceptional person, who produced a very deep impact on many of us, and especially on Campos-Ortega. In the 1950s, Barcia had brought together a multidisciplinary team that, among other research aims, applied silver impregnation techniques to the diagnosis of nervous system tumors. In this, they followed the example of Pío del Río-Hortega, the discoverer of the microglia, who had worked in Madrid in the 1930s on the histology of brain tumors. Hortega had emigrated to Argentina at the end of the Civil War where he continued working on this subject until his death in 1945. The only full-time scientist in Barcia's laboratory was Wenceslao Calvo who had spent a considerable amount of time at the W. Penfield Institute in Montreal.3 By the end of the 1950s, the group was losing momentum. After Calvo moved back to the United States, the laboratory was left in the hands of Carlos Meller, a medical student in his last year of his studies who had been attracted by the exceptional atmosphere in the laboratory. José and I were also attracted by this atmosphere and began learning some of the silver impregnation techniques under the guidance of Carlos. Despite his German origins, Carlos (Karl) Meller was also born in Valencia. Like many of us, he was very much attracted by German Science and was still under the spell of its great accomplishments before the War and the rise of Nazism. Carlos left for Germany in 1961, and we were left to our own devices and to actually control the whole laboratory. There, we spent many happy hours together discussing our many plans for the future (while I leaned towards biochemistry, José remained closer to histology). I remember discussing how to approach the problems of Neurobiology and we came up with the idea of selecting a suitable simple system. Our reasoning did not stray far from that used by Sidney Brenner when choosing to work on the nematode a few years later and, thus, in this way, we had taught ourselves the concept of a model system. Although Barcia had supported Meller in his role as a neuropathologist, we were too young and inexperienced to take over this role. Nevertheless, Barcia tolerated the time we spent and the reagents and animals we used in his laboratory, although I have always wondered how much Barcia knew of what we actually did there. However, to compensate we did help by teaching in the Department. When we later occupied official student internships in Anatomy, I took a position in Barcia's Department, while José went to the second Chair of Anatomy to occupy a similar position.

The two Departments were physically quite close, on two sides of the same wing of the building and we kept in contact (Fig. 1). At this point, I should mention our interaction with the relatively young and charismatic Professor of History of Medicine, José María López-Piñero. It was he who introduced us to a new way of analyzing science with the help of history and, for us, his course of 1962–1963 was a revelation. José María introduced us to his ideas of recovering the scientific heritage of Ramón y Cajal and the Spanish School of Histology, which was relatively inaccessible to the international community since their works were published in Spanish and French. In fact, this project was only partially completed and was superseded many years later with the English translation of Ramón y Cajal's more important books in the 1990s (Ramón y Cajal,1991, 1995, 1999). We started working on the recuperation of the contributions of the Spanish School of Histology in collaboration with the Histologist M. Luz Terrada, who happened to be López-Piñero's wife. On the occasion of the first Congress of the Spanish Society of the History of Medicine in Madrid in 1963, we published our first two papers on the origins of the Spanish School of Histology (Terrada Ferrandis et al.,1963a, b), and José María dedicated to us his book on the XVII Century Spanish Microscopist, Crisóstomo Martínez (Fig. 2). While I kept working on this project for some time, José took the lead in applying the tools of the Spanish School of Histologists and decided to follow a more practical direction of work in the Anatomy Department where he held his Internship. He started to extend the neuroanatomical work of the Spanish School using the brains of all the animals he could get hold of. These included laboratory rats, guppy fish kept in a glass bowl at home, bats caught in a small port where José spent part of his summer vacations (the animal that is used as the symbol of the town of Valencia), snakes, lizards, and small turtles, the chelonid Emys orbicularis, collected by José in Ronda (Southern Spain) where we did our military service. I remember that at the end of the second summer spent there, I brought the turtles back in my car (1964). During the journey, they escaped from the box and had to be recaptured from all the interstices of the upholstery of the car. All these animals were the subject of the experimental work that José completed during these years and that gave rise to several papers published in Spanish (Campos-Ortega,1964a, b, 1965a, b, 1967; Campos-Ortega and Ferres-Torres, 1965). These studies were those that he used to obtain his MD-PhD degree at Valencia University in 1966 (Campos-Ortega,1966).

Figure 1.

Top: The main entrance to the Valencia Medical School almost as it was in the 1960s. Bottom: J. M. López Piñero, J. A. Campos-Ortega, and J. J. Barcia-Goyanes in 1965.

Figure 2.

The Book of Crisóstomo Martínez and the dedication from J. M. López Piñero. Note that the book indicates 1964, XXV years of Peace (Spanish), as the official slogan that the regime recommended to print at that time. The dedication stood by itself, on a different page, and has been pasted in one of the front pages. Crisóstomo Martínez (1638–1694) was an anatomist and engraver born in Valencia, a contemporary of the first group of European microscopists (Malpighi, Leeuwonhoek, Swammerdam, Hooke, etc). He worked in Valencia and in Paris at the Academie de Sciences at the end of the seventeenth century. He was well known and highly respected in France and in Germany during these years. His engravings were printed and reprinted in Paris, Frankfurt, and Leipzig.

I have dwelt a little on these details because I think they faithfully reflect the scientific atmosphere in Spain at that time and how a young student like Campos-Ortega was able to take advantage of the circumstances to start his scientific career, even though they were less than favorable. Although our lives had diverged during our final years in Valencia, we were both convinced that we had to move elsewhere to pursue a serious research career under the guidance of real working scientists in each of our chosen fields. Carlos Meller had taken a position at a new Department in Göttingen where Paul Glees, a German neurophysiologist that had emigrated to the United Kingdom during the rise of the Nazism, had returned. Carlos wrote to José in 1965 asking him to come to Göttingen to take up a research assistantship similar to the one he held in the same Department.

THE GÖTTINGEN YEARS (1966–1970)

In Göttingen, under the supervision of Paul Glees, José expanded his studies into the Nervous System that he had initiated in Valencia. He moved to the study of vertebrate systems closer to humans, mostly using primates, and he concentrated on the central pathways of the visual system. Immediately, he started to publish his work in respected Journals in English (Campos-Ortega and Glees,1967a, b, c). He rapidly became aware that his immediate future would require him to become a member of the German Research System. Since a valid PhD degree was necessary to occupy the assistantship and the administrative steps to validate the Spanish PhD were inordinately slow, he decided to use some of his new results to write a new PhD Thesis, which was successfully defended in Göttingen in 1968 (Campos-Ortega,1968). During this time, he came to Madrid where I was learning enzymology at the Center of Biological Investigations. There, just a floor above me, Antonio García-Bellido and his very active research group was working on the developmental genetics of Drosophila melanogaster. Since we were both very interested in developmental biology, I am certain that I pointed out to Campos-Ortega the interesting work being carried out then by Antonio's group.

THE TÜBINGEN YEARS (1970–1973)

I am not sure how much this knowledge oriented him, however, it was clear that by the end of 1970 he had learned all he could from the scientists in Paul Glees' Laboratory. At this time, and probably due to his studies on the pathways of the visual system, Campos-Ortega was invited to participate in a multidisciplinary approach to solve problems related to vision by Valentin Braitenberg, a physiologist interested in Cybernetics and one of the Directors of the Max Plank Institute in Tübingen. They had selected the house fly Musca domestica as a model system and Campos-Ortega was invited to extend his studies on the visual system of vertebrates to this insect. Musca had been selected since the tiny size of Drosophila was not conducive to applying many of the proposed neurophysiological assays. He was joined in this task by Nicholas J. Strausfeld, and together they made significant advances in the description of the dipteran visual system (Strausfeld and Campos-Ortega,1973a, b; Campos-Ortega and Strausfeld,1973).

LATER DEVELOPMENTS

In the middle of 1973, Campos applied for a position as Professor in Freiburg where several groups were already actively working on Drosophila. He was selected for the post and again he had to glue several papers from Tübingen in a Schrift (a sort of Habilitation work) to cover the German requirements for such a post. Once in Freiburg, he immediately extended his studies to Drosophila melanogaster (Campos-Ortega,1974) and he set out to fulfill the ambitious goal of studying the development of the nervous system in the fruitfly. For this purpose, he combined a histological approach based on his previous experience with a genetic approach, influenced albeit at a distance by the work of Antonio García-Bellido's group in Madrid. In fact, Antonio García-Bellido visited him soon after he moved to Freiburg and convinced him to apply clonal analysis to the fly retina. The Madrid group, capitalizing on a gynandromorph study performed by García-Bellido in Caltech in 1969 using data initially collected by A. H. Sturtevant, had optimized the method of clonal analysis. In this way, they had discovered developmental compartments, which had tremendously important repercussions at that time. In contrast to the “Drosophilists” who tended to concentrate mostly on the cutical phenotypes of the adult, José applied these techniques to the nervous system. He was also influenced in this period by Seymour Benzer, the brilliant phage geneticist in Caltech, who at the end of the 1960s had also decided to turn to the problem of understanding how the nervous system functioned in Drosophila. Campos-Ortega also acknowledged in his initial publications on this subject the help of Peter Lawrence, based in Cambridge (UK).

Nicholas Strausfeld later moved to the EMBL (Heidelberg) where he also started working on Drosophila, and it was at this time that the Science article (Strausfeld and Campos-Ortega,1977), still focusing on Musca, was published. Independent of these events, there was a shift towards a more molecular analysis of Drosophila development, which, during the early 1970s, was driven by the group of David Hogness in the Biochemistry Department in Stanford in close association with Ed Lewis in Caltech, the last disciple of Morgan. At that time, I was working in the Department in Palo Alto and I witnessed the advances of this research program in the Departmental seminars. I could see how the progress in molecular biology and recombinant DNA technology, initially developed in the Bay Area, was being taken advantage of. Campos-Ortega eventually applied all these techniques much later in the final stage of his scientific life in Köln. To some extent, he continued to use the same approach as in his earlier days in Valencia. Although advised and helped by many of the people I have mentioned, he actually began to extend his neurohistological work by himself, first using the genetic tools devised in Madrid and then later the molecular tools developed in the United States. He certainly took advantage of the big genetic screen carried out in the latter part of the 1970s in Heidelberg by Eric Wieschaus and Christiane Nüsslein-Volhard. He had coincided with Christiane in Tübingen, in Walter Gehring's lab in Basel (a few miles away from Freiburg), and finally in Freiburg during her stay in Klaus Sander's laboratory. This connection enabled him to get the mutants he needed to describe the effects of the neurogenic genes on the nervous system during embryonic development. In this research, he was helped by a group of young scientists, such as A. Hofbauer, G. Juergens, and the late Fernando Jiménez, a molecular biologist from Madrid. Pedro Santamaría, another brilliant student of García-Bellido, was also in Freiburg in the late 1970s.

CONTACTS WITH SPAIN

I have summarized the training years of J. A. Campos-Ortega (he prematurely deceased in 2004), times that were both hard yet very interesting. Volker Hartenstein (Hartenstein,2006) describes in detail the importance of his scientific contribution using Drosophila and the zebrafish, the vertebrate system with which he returned to his origins.

Campos-Ortega married in 1965 and his first son, Arturo Campos-Lleó, was born in Valencia (1966) when he had already started to work in Göttingen. His daughter Teresa and his second son Nicolás were born and remain in Germany. One interesting question is why José decided to become German in the 1980s? Indeed, with the exception of his wife, all the family obtained German nationality then. As I have already indicated, from almost the very beginning of his career he was fully committed to become a member of the German scientific system. Not only was he grateful to the country that had provided for him and his family, but also there were practical and administrative motives associated with the benefits that his position at the University of Cologne offered him. Nevertheless, José's relationship with Spain was always intense. When in Freiburg, he was offered positions in Madrid and Bilbao but he was aware that the situation in his home country could not match that which he was enjoying in Germany and so he politely refused these offers. Once in Cologne, he was attracted to a project to found an internationally competitive research laboratory in Sevilla (Spain). The original idea was conceived by Enrique Cerdá-Olmedo, a geneticist working in Sevilla with the help of Miguel Beato, another Spaniard established in Germany (Marburg). They were soon joined by Manuel Perucho, a molecular biologist who specialized in cancer and was based in the United States (La Jolla, CA), José, and a Sevillian neurophysiologist, José López Barneo. The idea that they had in mind was to establish an institute similar to the EMBL and José's relationship with EMBO may have helped in this respect (he had been a member of the EMBO council). Initially, the idea was that the members of this team who were based outside of Spain would actually transfer at least part of their laboratories to Spain. Good progress was made, but when the building was almost finished, the project was paralyzed by administrative difficulties. This made it increasingly unlikely that the relocation of these research groups might ever take place. Recently, the original building has been assigned to house the Andalusian Center of Developmental Biology (Centro Andaluz de Biología del Desarrollo), which might have offered him a place to work happily and proudly. Indeed, it is fitting that the building where the Center is now located will now be named after him. In addition, José continued to collaborate with post-graduate courses in Andalucía and was an important member of the scientific committee of the Juan March Foundation, until recently strongly committed to research, particularly in Biology.

Finally, this article would not be complete without mentioning his proposed project to work on a History of Developmental Genetics, thereby returning to his Valencian roots. In this endeavor, he would have undoubtedly been helped by his prolific memory, and by his knowledge of those that had been involved in this field and of the scientific literature. Although not much material remains from this project, it may be sufficient to provide the necessary momentum for its continuation and completion. 3

Figure 3.

Two pictures from Göttingen. José, Paul Glees (above standing on the right in the top picture), Carlos Meller (below seated on the left in the bottom picture).

Acknowledgements

Thanks go to the CABD, the late Teruca Lleó, Arturo Campos-Lleó, María Campos-Ortega, Miguel Beato, Enrique Cerdá-Olmedo, Alberto Ferrús, Volker Hartenstein, Rainer Hertel, Alois Hofbauer, Elizabeth Knust, J. M. López Piñero, Jaime Miquel, Angela Nieto, Sigfried Roth, Eberhard Rudloff, Nick Strausfeld, the two anonymous referees selected by the editors, and all who read the draft manuscript and offered important suggestions and corrections on its initial content. Mark Sefton corrected the English. Obviously the entire responsibility of the current text is only mine.

  • 1

    Severo Ochoa, the second big Spanish name in science, had not yet received the Nobel Price (1959). He emigrated from Spain at the beginning of the Civil War and was a pupil of Juan Negrín, who was Professor of Physiology and the head of the Republican Government during most of the Civil War. In fact, he was not at the time much mentioned in the media or in educational institutions.

  • 2

    The Spanish Scientific Research Council is a scientific organization that was founded after the civil war. It combined the remains of the pre-ware Research Institutes, some of which were private and that had been confiscated by the victors. It initially provided support to groups at different Universities that were headed by Professors well connected with the Franco regime. However, it gathered more momentum in the 1960s, developing independent Institute and Centers and becoming one of the principal motors of Spanish Research Science and Development, a role which it continues to fulfill today.

  • 3

    The North American Neuropathologist's interest in the Spanish Histological School can be readily documented. It is quite likely that in Montreal, Calvo became more familiar with the methods of del Río-Hortega and the work he had done in Argentina. Wenceslao Calvo left Spain at the beginning of 1960 to go to the Brookhaven National Laboratory in the United States although later he settled in Ulm (Germany) where he retired.

Ancillary