JÁNOS SZENTÁGOTHAI: AN INSPIRING AND IMAGINATIVE SCIENTIST

UNESCO and the world of science are celebrating the Centenary of János Szentágothai (d. 1994), the imaginative Hungarian neuro-anatomist, who developed a new, three- dimensional model for the functioning of brain from the 1960s. Szentágothai tutored generations of young brain researchers at Semmelweis University of Medicine in Budapest, who have a definitive influence on the field today all over the world.

Science journalist Péter Grosschmid asked Professor László Záborszky (b. 1944) of Rutgers University, Editor-in-Chief of the journal Brain Structure and Function, and external member of the Hungarian Academy of Sciences, to talk about the figure and work of Szentágothai, and the ways in which he influenced his own career.



Peter Grosschmid: Professor Záborszky, please tell us about your own studies. How did you decide at Semmelweis University to choose research instead of becoming a practising doctor?

László Záborszky: I was fortunate to be accepted as a student in 1959 at Eötvös József Grammar School, one of the best secondary schools in Budapest. I liked languages, the humanities, and for a long time I wanted to be a philologist. Eötvös was a place where many good teachers landed when they were expelled from the universities for their role in the 1956 Revolution. Natural sciences were taught on a very high level, too.
For a long time I hesitated between the career of a linguist or a doctor, but finally my father’s severe illness and premature death motivated me to attend medical school. It was a good decision as at that time the Budapest Medical School was one of the best in Europe. It had some world famous professors, including János Szentágothai, Brunó F. Straub, Ödön Kerpel-Fronius and Béla Horányi. At the beginning I focused on chemistry, my interest piqued by the lectures of Brunó F. Straub. During the first semesters I wanted to be a healing physician, but the anatomy classes of Szentágothai shifted my direction toward research. Initially anatomy was less interesting than chemistry, but by the third semester, when we covered the nervous system, I was totally absorbed by the subject.
In the third year of my university education I was admitted to the Students’ Scientific Association of the University, further confirming my decision to pursue anatomy. I finished the Medical School with distinction and there was a possibility to choose clinical work, but the Chair of the Department of Neurology suggested joining the Communist Party if I wanted to work with him. At the Department of Anatomy there was no such requirement. I was still uncertain about my decision to choose research instead of medicine, but I spent more and more time at the Department of Anatomy and that determined me to stay there.

HR: Anatomy usually is not the most popular subject among medical students, and Professor Szentágothai lectured on anatomy – although he was able to make it interesting enough to attract students even from other universities to listen. How did he attract big crowds to his lectures? How was he as a researcher and a colleague? How was his own school of followers formed around him?

LZ: As a teacher Szentágothai was a genius. He often started his lectures telling us about the scientific conference in America he just came home from the day before. He was an impressive lecturer who was able to talk enthusiastically about his subject, first and foremost about the structure of the brain.
As a researcher he wanted to visualise the three dimensional structures of the nervous system. When studying the cells with a simple microscope you see only in two dimensions, although the complexity of the structure can only be appreciated in three dimensions. He talked about the spatial structure of the brain and easily carried his listeners to a new world never seen before. It was not easy to follow his lectures; there were several of us who got lost in the sea of information, but we still enjoyed the brilliant lecturer’s artistic performance. As a real renaissance man he quoted the great authors of literature, the greatest artists, and the Bible in his lectures. Those who could follow him reached great depths. Only a few other lecturers had that ability.

He had a high prestige worldwide, especially in the USA where he was considered one of the best. He knew everything about the most recent achievements of neuroscience and was in touch with scientists in many countries. The greatest personalities of the field – Nobel Prize winners among them – visited him in Budapest to acknowledge his earlier achievements. In the sixties every scientist with valuable results in the field wanted to present them to János Szentágothai.

By the 1960s, the electron microscope offered a magnification of 10-20000x, making it possible to see the miniature connections, the synapses, between the cells of the nervous system. Szentágothai introduced a synthetic view of the brain combining extreme high magnifications to study the connections between the cells and put them into a three-dimensional view. There were no computers able to generate these images, and the ones used by the university filled several rooms or even a complete floor of the building and were too slow; their capacity was far behind that of a modern mobile phone. Nowadays we can produce seamless (continuous) magnification using computers, and the 3D image is generated automatically by software. In Szentágothai’s time you had to use your imagination, he had that great power of conceptualisation.
Although the Spanish Ramon y Cajal with his colleagues (among others Professor Mihály Lenhossék, then Chair of the Department of Anatomy in Budapest) in the early part of the 20th century laid down the foundation of the so-called neuron doctrine, stipulating that the nervous system consists of individual neurons that are only attached by the tiny synapses, this theory was attacked by the “reticularists” in the 1930s who maintained that the neurons with their long processes are in continuity. In fact, Camillo Golgi, who invented the silver-chromate impregnation showing the neurons and shared the Nobel Prize with Cajal in 1906, also thought that the nervous system was diffuse. The existence of synapses was proved only by using electron microscopy (invented in the late 1930s) in 1954. The 3D reconstruction of the system of neurons from individual cells with their synapses was Szentágothai’s achievement. He started from the spinal cord, then continued with the thalamus and the cortex. Recently almost all researchers study the cortex, and they still use Szentágothai’s inspiring and imaginative three dimensional models of neuronal circuitry. He was the first to make the structure of the nervous system imaginable and understandable for everyone. Nowadays we know that the picture is more complex but without his work it would be more difficult to understand it. At the time when molecular genetics and informatics were less developed he had to use his imagination and intuition to achieve his results that were later verified. He was able to synthetise the vast amount of information available at the time, a unique ability seldom seen in the new generation of scientists.

Professor Szentágothai supported gifted people without an agenda of his own. I was lucky because as member of the Students’ Scientific Association I had worked in the laboratory of Miklós Palkovits. With János Szentágothai I had an indirect contact, but any time when he was visited by a foreign scientist he introduced us to them. From the fourth year of the medical school I had the opportunity to meet scientists who were considered to be the gods of science.

For the microscopic investigation of nervous cells, silver compounds were used to make the cells and the connections between them visible. In the US a scientist of Swedish origin, Dr Heimer developed a method using uranyl nitrate to stabilise silver. Returning from a trip to the US, Szentágothai brought a small amount of that material in his pocket and gave it to me and a few other researchers, enabling us to try this method which was considered the most modern one that time. In 1981, Heimer invited me to work in his laboratory. Szentágothai helped his colleagues generously, he did not want to thrust himself forward, and, opposed to the still existing practice he did not want to be included among the authors of the publications of his students. He did not take advantage of being the boss, and his students and followers got ahead with his support. Several of them are now professors, heads of departments, even members of academies of sciences. Of course, he supported only people whom he thought to be talented. He never stood behind the ones with only political and other non-scientific merits. He encouraged young people, set the standards to be achieved, and when he saw the achievements of the candidates he helped them.

Although I was not among his close students, he helped when I had a promising publication. His English was very good, and he worked over the whole text sentence by sentence to make it internationally acceptable.

The morphological description of nervous cells and the detection of their connections are of no real value without the quantitative parameters. At the suggestion of János Szentágothai, we started counting the synapses. We took a certain area of the brain and tried to produce a quantitative description of the incoming and outgoing connections. It was a brand new approach using the electron microscope. That was one of the publications he rewrote sentence by sentence. For two or three weeks we worked together at least a couple of hours every day, and still he did not want to be mentioned as an author of the article. He was really selfless.

In order to establish one’s own school of followers a role model, a leading personality is needed. His progressive way of thinking attracted people like a magnet. He did not have to make efforts to recruit people, scientists interested in the theory swarmed to join him.

It was also a novelty that despite the traditions of the schools of medicine, Szentágothai also employed biologists whose theoretical knowledge was beyond that of the physicians. Not only medical students joined his team but more and more biologists chose a career in the field of neuroscience. Later when information technology became more advanced, information scientists and computer experts came to exploit the ideas of another native of Budapest, John von Neumann, to adopt information theory to provide a better understanding of the operation of the nervous system. Szentágothai himself sought contacts with mathematicians and information experts. He introduced interdisciplinarity in his institute: points of view of other branches of sciences were more and more taken into consideration. He realised that the static science of anatomy is the foundation upon which dynamic brain model could be built. He recognised how to make progress in the exploration of the most complex matter, the nervous system. The results were based on planned team-building.

The system of research financing was not simple. In the Institute there was a small research group belonging to the Hungarian Academy of Sciences which got higher grants. Those of us who were employed by the University had a tremendous teaching load, yet we had to compete with the results of those whose main job was to do research. Szentágothai himself also wrote textbooks. With more financial subsidies, probably more results could have been achieved. The new techniques required expensive equipment whose absence was compensated for by inventiveness, creative application of the existing instruments and a lot of manual work. After Szentágothai was elected President of the Academy the situation improved a bit, but his institute still lacked the full potential of a big centre of the Western World.

HRJános Szentágothai was described as a Christian believer. Was this fact known among his students? Did Christian ways of thinking surface in his teaching and research work?

LZ: Religion was not a subject of his lectures and was not discussed in his everyday life; his colleagues did not know his religious inclination. In fact while he often quoted the Bible and its stories in his lectures, these quotations were rather cultural than religious references. He had a firm scientific standing, and he was a humanist conveying Judeo-Christian values. I myself – also because of the age difference – did not belong among his closest friends, so we did not talk about these topics. His thinking was dynamic and dialectic, he was preoccupied by the relationship of the brain and the mind and the intellect, he studied the self- organisation of the nervous system, that very special matter.

HRHow was it possible to get a foreign scholarship? What was Szentágothai’s role in the procedure? Did he help his students?

LZ: It was not easy or simple. Once I asked for Szentágothai’s support when I wanted to visit a famous scientist, an anatomist at the Massachusetts Institute of Technology. He suggested that I wrote to him and in case he would be ready to receive me, I would get his support. Later when working in America with Heimer we had a regular correspondence and I asked for his help to work with one of his acquaintances at the Salk Institute, and he again advised me to make the contact myself and then he would help me. To receive his support he expected people to show sufficient initiative – you had to work hard for his support. On the other hand, his worldwide prestige was so high already in the sixties and seventies that usually a reference to the fact that you worked in his Institute was enough. At that time I already had several publications in English language journals, and people in my field knew I was working in Szentágothai’s Institute. In this field all researchers were supposed to know his name. His recommendation was an entry ticket to a lot of places and he did not risk his reputation by supporting somebody who might cause disappointment.

HRHow tolerant was the Party with the scientific relations with the West? Were there any political requirements posed on those who wanted to maintain foreign relations, travel to the West, win long-term scholarships?

ZL: At the beginning of the sixties the policy became more tolerant. I knew that even Szentágothai was not allowed to travel after 1956, but by the time I was admitted to the University there was a sort of slow thaw. I graduated in 1969, and until 1973 I was not granted a passport but afterwards I was a regular participant in congresses held abroad and received a long-term scholarship. In the Institute there was quite an influential local group of the Party which sometimes led to conflicts especially when Szentágothai was not the Head of the Institute any more. The representatives of the Party influenced appointments, and most probably I would have remained an assistant lecturer forever as I did not join the Party. But with regard to the possibilites for professional trips to the West, my generation was probably luckier than the previous one.

HRWhat was your motivation to continue your career abroad? How did you find a job in the eighties?

LZ: One of my points was the static situation in Hungary. The institutional structures were very rigid, there were no more jobs available to join the team, it was almost impossible to find a place and support to set up a new research team for a new topic; the mobility was very low. My career path in Budapest would have been to remain in the Institute where I had only a very slight chance to be independent. Those who went abroad or could join the research institute of the Hungarian Academy of Sciences (KOKI, Experimental Medical Research Institute) had a better chance for a career. Without money and an adequate laboratory I probably could have never had my own research group if I had stayed at the University. Although Szentágothai was a brilliant scientist and could help to build a career, he was not able to provide the necessary conditions. Many of us left the country and only a few returned, but many of us retained our Hungarian citizenship abroad. I requested American citizenship only when Professor György Ádám nominated me as an external member of the Academy. According to the rules only citizens of other countries with Hungarian origin doing research work abroad are eligible to the external membership of the Academy. The first time he nominated me was in 2003, and at that time I decided that I wanted to be a member of the Academy as it is the greatest honour for me, so I asked to be a citizen of the United States.

HRIn an earlier interview you mentioned that research in the life sciences is a team work. Using the World Wide Web it is possible to set up worldwide teams. Are there other former students of Szentágothai in your team? Do you have a virtual team?

LZ: I have many Hungarian students. Most of them came to me on the recommendation of my former colleagues in Hungary. Most of the Hungarian scientists who have independent funding in the US help their fellow countrymen in Hungary. They are popular here as it is well known that they are well-educated, full of ambition, and they want to achieve, perhaps even more than average Americans. This is one of the reasons I’ve wanted to keep good relationships with Hungary.

As for team building, I don’t have my own school here. In the USA it is a little more difficult to build and keep permanent teams. The country is very big, and there are several excellent universities and research institutes all over the States. The US system of research support is different from the Hungarian system. The resources needed are supposed to be raised by the researchers; I have tenure at the university, which affords a certain degree of safety, but to keep it I have to teach and raise external support for my research work. It has never been simple, and in the recent 5–10 years it has become even more difficult with the weakening economic situation of the country and because the last Republican administration did not do much to support scientific research.

Research is more or less cyclical as several years of hard work in the laboratory should follow with the publication of results (“publish or perish”). Employing new people depends on the available financial resources. Our institute is a PhD granting school where the average doctoral student spends five years completing his/her theses and then leaves. Because turnover is high, it is difficult to keep people long-term. It is possible to enrol postdoctoral scientists but sooner or later they also want to be independent and create their own research group. Considering all that, the Hungarian (European) system is more suitable for founding a school of followers.

HRApart from research cooperation do you keep in touch with your former colleagues, the members of the Szentágothai school? What do you, his student, share from his legacy with the new generations of scientists?

LZ: Péter Somogyi of Oxford University and Tamás Freund, the Director of KOKI, often visit Rutgers University, and I have spent time in Oxford. When I go to Hungary I meet my ex-colleagues, and they come to see me from Budapest, Szeged, Pécs and Debrecen.

As far as the legacy of Szentágothai is concerned, I would say his enthusiasm and his devotion to genuine science are the most influential factors. He was a romantic figure endowed with an exceptional imagination. He was convinced that science was not simply about gathering facts, and that creativity played an enormous role in interpreting these facts. He had a vision, he had the facts and he examined whether they fit together. American science is much more matter-of-fact in nature. You glean your data and you are supposed to avoid any speculation. These days we have the means to prove our theories but in the time of Professor Szentágothai imagination played a greater part. Encouraged by his example I still believe in using our creative imagination, letting our thoughts roam freely and trusting scientific speculation. I think I learned everything from him regarding methodology and attitudes towards doing research. The three-dimensional brainmodel could not have been born for a long time, were it not for his inventive ideas. My research focuses on how subcortical structures influence the function of the cerebral cortex, and I often think about what Szentágothai would have said about my data or what he had written on the subject. The charts he created for the textbooks of the1970s are still in use; I peruse them in my lectures. There are a lot of examples that I consciously or subconsciously follow.

I don’t mean to be unduly proud of myself, but one time in 1984 when I gave a lecture at the Society for Neuroscience, a renowned researcher, Ann Graybiel from MIT, remarked: “Here you have the young Szentágothai!” I am still trying in vain to prove that I deserve her prediction…

HRThe Hungarian Academy of Sciences awards Hungarian scientists living and working abroad with an external membership. What does this membership mean to you? Do you think you might have a greater influence on science in Hungary, or this title does not change anything?

LZ: The most important thing is that your work is appreciated in your homeland. The fact that the Hungarian researchers, the scientists of the Academy acknowledge my achievements gives me immense energy. I have a card signed by Sylvester E. Vizi, former President of the Hungarian Academy of Sciences saying that I’m an external member of the HAS. I carry it in my wallet at all times. I think that’s what I’m most proud of.

HRAfter two years of planning and preparation a new initiative, the Hungarian Scientific Society of New York was launched in 2010. You were elected deputy chairman. What does this “junior academy” do? How do the representatives of the different branches of science interact? The objectives of the Society include giving assistance to scientists and students who would like to do research in the US. Have Hungarian researchers availed themselves of this opportunity over the last two years? Which fields of science were represented? Does the Society receive support from Hungary? Does the Hungarian Academy treat it as a partner?

LZ: Actually, it was a series of fortunate coincidences that helped establish the Hungarian Scientific Society of New York. Two famous scientists at the Rockefeller University in New York were given honorary membership of the Hungarian Academy of Sciences. Gábor Földvári, who was Consul at that time, asked me to give a list of Hungarian scientists who should attend this official ceremony organised by Ambassador Viktor Polgár. This was what brought us together. Later, Zsófia Trombitás, Consul, suggested that the 30-plus Hungarian scientists living in New York, New Jersey and Connecticut, who didn’t really know each other on account of their different fields of research, meet from time to time. So the idea evolved spontaneously, the Consulate supported it and has provided a venue for our meetings. We set three main objectives, the first being that the Hungarian researchers meet informally. It would be nearly impossible to form groups according to subject areas of science as we work in totally different fields. There have been plans for an US-wide expansion of the Society, thus making it the most significant external body of the HAS. Our second objective is to cooperate with and support the Hungarian scientific community. The third one is to establish scholarships for talented young Hungarians. The latter is not an easy task since first we had to obtain a non-profit organisation status to become exempt from taxation. We achieved that this past spring and now we are allowed to do fundraising for the Society. We don’t have a lot of money yet, but we have just started our campaign. We are organising a conference in memory of Professor Szentágothai on 12 November. Sylvester E. Vizi and Miklós Réthelyi are invited from Hungary. Apart from them, several scientists in the US, who worked with Szentágothai at the Department of Anatomy or through the HAS will talk about their personal memories. We also got a letter from the Nobel Laureate G. Edelman who knew Szentágothai very well. It was reassuring that in his letter he wrote the following: “His efforts stand for the highest elements of Hungarian culture which, in science, combines high intelligence, historical sense and imagination in the service of the verifiable truth”. We do hope the conference will be a success; we applied for and got financial support from the Gábor Bethlen Fund. This goes to show that the attitude in Hungary has changed towards Hungarian researchers working abroad. We don’t make the officials see red any more. Every member of the Society has Hungarian ties, and now we might have a chance to make them more organised. The whole thing is still a bit loose, and we don’t have enough money to establish scholarships, but I hope that in half a year we will have a larger sum at our disposal. Our goal is to extend our scholarship programs to talented ethnic Hungarians in the Carpathian basin. This initiative has the full support of the Hungarian authorities.

The Assembly of the Hungarian Academy of Sciences includes a forum for the external members at its meetings where I spoke about the Society. The idea so captivated my fellow scientists that a Hungarian Scientific Society in Berlin has already been founded, and similar associations are expected to spring up soon in several other countries. In the US there are many Hungarian societies but without the expressed intention to do science and research. Our statute declares that only active researchers can become regular members. We, however, welcome supporting members since we badly need financial backing.

I do hope the Society will function effectively. The Consulate, led by a very talented and ambitious person, Károly Dán, has promised to help in fundraising. An excellent former student of mine, Balázs Gulyás, who lives and works in Sweden has very good ties in Hungary. We often talk, and the last time when he was here and gave a lecture at Rutgers University, we met Consul General Dán and made big plans to enhance our relations with the Hungarian scientific community concentrating mainly on young researchers.

In accordance with the statute of the Society I’m to become president and a new deputy president will be elected by the Assembly of the Society in November this year. The deputy president will replace me in two years’ time. I hope we will be able to help talented young Hungarian researchers networking with the American scientific community. I also hope that we’ll have an extended cooperation with the Academy and the Hungarian scientists working abroad.

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