Obituary: Professor John Szentagothai

Janos Schimert (Janos Szentagothai), anatomist and neurobiologist: born Budapest 31 October 1912; University Demonstrator in Anatomy, Budapest Medical School 1936-44; Professor of Anatomy, Pecs University 1946-63; Professor of Anatomy, Semmelweis University, Budapest 1963-77; President, Hungarian Academy of Sciences 1977-85; Emeritus Professor and Head of the Neurobiology Group, Semmelweis Medical School 1986-94; Member, Hungarian Parliament 1985-94; married 1938 Alice Biberauer (three daughters); died Budapest 8 September 1994.

JOHN SZENTAGOTHAI was one of the most creative and renowned neurobiologists of the century, a towering intellect and a great humanist.

His vision ofthe brain as a network of specific populations of nerve cells, each engaging in selective functions, like the bolts and wheels of machines, and self-

organising into modules, has provided the framework and stimulus for generations of neuroscientists. His irrepressible curiosity and enthusiasm for the beauty in the organisation of the brain never faded; no sooner would one reach his door than the question rang out, 'Now then, tell me what's new?'

He was born Janos Schimert, in Budapest in 1912, to Dr Gustav Schimert and Margit Antal, into a well-to-do medical family. With his five brothers he received a strict and privileged upbringing (he liked to boast about their Swiss nurse) which was apparent in his aristocratic manners and broad artistic and literary knowledge. At the age of 16 he received a small microscope as a Christmas present and within a few months managed to produce some hand-cut histological sections from the brain of an unfortunate mouse he caught, which he stained with the Golgi method, revealing individual nerve cells in all their beauty. As he put it, what he saw resulted in 'a love at first sight' and the 'imprinting experience' engaged him with the brain for a lifetime. Some of his later discoveries, particularly in the neocortex and cerebellum, were produced by the same Golgi method (introduced by Camillo Golgi, an Italian histologist at the end of the last century) which is used to this day for visualising nerve cells. The same method was extensively used by Ramon y Cajal, one of the greatest neuroscientists of all time.

Schimert started his medical studies at the Budapest University Medical School in 1930, and was accepted in the first year by Professor Michael von Lenhossek as a research student in the Department of Anatomy. This was a most stimulating and creative place for basic research, for Hungary wanted to show the world her intellectual powers after the great 'Carthagesque' tragedy that befell the Magyar people at the end of the First World War. As a student he described essentially correctly in his first light microscopic papers, published in German (1936- 39), the termination of vegetative peripheral nerves, 20 years before electron microscopes were invented. He applied the silver impregnation that he used for peripheral nerves to the lesioned nerves in the central nervous system, pioneering the tracing of links between pathways in the brain and spinal cord. He received his MD in 1936 and continued to teach at Budapest, becoming Associate Professor in 1942.

He changed his name from Schimert to Szentagothai (after a Magyar ancestor) as a protest against the Nazi occupation. In publications in English he signed himself John Szentagothai. The years of the Second World War were disruptive to progress, but no sooner had the dust settled in the war-ravaged country than Szentagothai was back from an American POW camp in the southern city of Pecs early in 1946 and, at the age of 34, took the Chair of Anatomy of a department whose staff had all left as a result of the war. He surrounded himself with gifted students, creating a research atmosphere where originality and discovery flourished; four of his students from the Pecs days became internationally acclaimed pioneers themselves and heads of anatomy departments in different medical schools in Hungary. Using his silver stain and ingenuity Szentagothai provided unequivocal anatomical proof for the monosynaptic bi-neuronal reflex arc of the stretch reflex. With Gyorgy Szekely he transplanted eyes and limbs of newts to reveal how nerves regenerate to innervate them and in the process recognised the principle of neuronal self-organisation. With Bela Halasz, Bela Flerko and Bela Mess he discovered how the hypothalamic area of the brain governs the secretion of hormones from the pituitary gland which in turn govern our growth, sexual physiology, and response to stress.

The kind of anatomy Szentagothai pioneered was functional indeed (later he wrote a textbook, Functional Anatomy, widely used in Hungary today). This is well illustrated by his discoveries in the extraordinary experiments he conducted on how the brain keeps the eyes steady on target while the body and the head move in three dimensions. In a series of experiments from 1946 with Andras Gomori's team he established the direct tri-neural pathway, the gyroscope of the brain, from the semicircular canals of the inner ear to the extraocular muscles that change the position of the eye (published in 1952 in a monograph in German).

In1938 he married Alice Biberauer, a women of exceptional warmth and kindness, who kept a close watch over his demanding schedule, trying to buffer the many conflicting interests draining his energy. In the later years she was a constant and cheerful companion at international meetings. Their three daughters all took up medical careers.

In 1963 he moved to the Chair of Anatomy at the Semmelweis Medical School in Budapest, where he had studied as a student 30 years earlier. Again, he created a department of world repute. In Budapest, working with Jozsef Hamori, he concentrated on the organisation of the cerebellar neuronal network and renewed a collaboration and a lifelong friendship with Sir John Eccles. Their book, published with Masao Ito from the heroic studies of the Sixties, The Cerebellum as a Neuronal Machine (1967), became a classic in the history of neuroscience. Szentagothai's recognition of the basis of lateral inhibition in the cerebellar cortex - which 'came as a flash' to him during one of his undergraduate lectures, remains a basic concept of cerebellar organisation. Also in the Sixties he discovered the principle of glomerular synapses, first in the thalamus later in the cerebellum.

Since he was a romantic visionary rather than an analytical scientist Szentagothai could generalise his findings without inhibition with an enchanting elegance. One such generalisation, the concept of the modular organisation of neural centres, can be followed through his studies in the Fifties and Sixties and was elaborated in the 1974 volume of the Neuroscience Research Programme Bulletin, published with M. A. Arbib; the copy in the Radcliffe Science Library at Oxford was read into shreds years ago. This concept, applied to the cerebral cortex, formed the theme of his Ferrier Lecture to the Royal Society in 1977. Entangling the neuronal network of the cortex, the seat of all of our conscious experience and achievements, remained his last important scientific adventure: a field, as so many others, where he leaves behind a school of thought that will continue to draw from his vision.

In the last two decades of his life, as a religious man, he grappled with the scientific and philosophical problems of the brain- mind-psyche relationship, concluding in his paper 'Too much and too soon', published in 1982 in English in Hungary: 'no speculation can remove our responsibility for our actions and behaviour'. He was deeply concerned with, and actively worked to avoid, the 'abyss of an atomic holocaust' as well as the destruction of the natural environment.

As his fame increased so did the expectations of administrative duties and he rose in the ranks of the Hungarian Academy of Sciences, being elected President in 1977 and again in 1980 until 1985. This was an arduous task requiring compromises in the interest of maintaining the academy's scientific mission, as he had to report to one of the most powerful members of the Politburo, the Deputy Prime Minister Gyorgy Aczel, a Communist ruler par excellence. In 'Too much and too soon' Szentagothai notes 'It is the ultimate joke of fate . . . that it should befall someone originating from an upper middle-class background, of unorthodox philosophy, and an utterly cynical - albeit compassionate - observer of the whole 'vanity fair' of this world to become the President of an 'Eastern-type socialist' academy. However, I try to serve my country to the best of my abilities.' As a teacher Szentagothai greatly influenced three generations of doctors and scientists, his magnetism attracting talent, and today various of his pupils lead brain research world-wide.

It is not accidental that, as measured by research publications in relation to its population or its gross domestic product, Hungary is among the first countries in the world in her impact on neuroscience research. Szentagothai's Atlas Anatomiae Corporis Humani, published with Professor Ferenc Kiss, has seen more than 82 editions and been translated into at least 13 languages including Chinese and Slovenian. He designed and drew much of the artwork for this fundamental book. He enjoyed painting and his papers are full of imaginative three-dimensional illustrations of his vision of the neuronal circuits.

In spite of his administrative duties, the many international obligations (he was equally acclaimed in the West as in the then Eastern Bloc), the lectures to the medical students (he lectured in German, French and English) that he would try to give above all other demands, his office was always open to us young scientists, who used to queue up to show our results in the hope of gaining from his criticism. And critical he was; his roaring baritone could be heard echoing in the corridors, but the discussion were infectious and his genius provided food for thought which made the place such a stimulating environment.

He liked to impress the young scientists with an image of a 'street fighter', often joking about how much he was favoured by fate by not dying of the sepsis that he got in a dissection, or at the time when as a POW in the Second World War a drunken GI pressed his loaded machine-gun to his ribs, or of the high blood pressure that he had to cope with for the last 40 years of his life, or in the heart attack that inevitably followed from the punishing schedule of administrative duties, scientific and public commitments. But he was essentially a gentle, often timid and self-doubting person, who would try to avoid conflict at all cost.

In his later years he often warned us against the 'ugly competitiveness that appeared in the field' and reminisced about the days when science was a 'gentlemanly pursuit', not a road to power and wealth. However, when the time came he stood up for his staff, friends and colleagues, irrespective of their importance. He would not hesitate to write to, phone up and harass those in power in order to help the less fortunate. On one occasion, when a young scientist needed a piece of equipment, costing dollars 1,200 and unobtainable in Hungary, he simply bought it from his publisher's royalty (equivalent to six months of his full salary) on one of his conference trips and put it on the astonished scientist's desk.

When the Soviet empire crumbled in 1989-90, Szentagothai, aged 78 and with a pacemaker that he often cursed for not allowing his heart to pump enough blood at times of high emotional involvement, again chose to do his best for his country's rebirth, serving as an MP in the colours of the governing Democratic Forum in the first democratically elected parliament. His televised parliamentary speeches, liberally spiced with Latin, Greek and literary quotations, bemused his fellow MPs and television audiences. In the turmoil of the scramble for power his voice was always a refreshing spell of humanity and caring for the future of his people.

Szentagothai lived through and influenced the turbulent history of a country that history has not favoured. He managed to maintain a creative contribution under the darkest of historic circumstances not only to his country's culture and education, but to the pool of Man's universal knowledge. In his recent witty biographical self-

portrait As a Ulysses around the Brain (1994), written as a monologue and applying James Joyce's Ulysses and Thomas Mann's Lotte in Weimar to his life, he professed that the aims of his life had been, 'to be a good neuroscientist, to remain cultural in the sense of the end of the 20th century, to remain an honourable man under the historic circumstances and above all, to remain a good Christian'. Those who knew him well bear witness to how wonderfully he succeeded in these ambitions.

(Photograph omitted)