Introduction

The main protagonist in this tale is Ladislav Kováč (LK; Fig. 1), who is not only a world-class biochemist, but also one of the last polyhistors. Thus it would seem logical that this chapter would be written by him. Needless to say, he would have done it brilliantly, just as the 18th-century polymath Thomas Young did for Encyclopedia Britannica (Robinson 2023). In contrast to Young though, LK does not have an ambition to highlight his achievements. So, as we think this chapter is essential for a special issue on cognitive biology, we felt obliged to try to write this “prelude.” However, we opted for a little trick. To make the text as close as possible to LK’s style, we decided to employ a nonconventional format. We have divided the era predating cognitive biology into defined periods, but instead of describing them by ourselves, we filled them with LK’s own words. As a template we employed an interview of LK with a newspaper produced in his native village, where he succinctly described his path from Slovak mountains to cognitive biology (hence the title). Where appropriate, we included citations from other—almost exclusively Slovak—sources that are difficult to access for the audience of this journal. LK’s responses were edited for clarity and are interspersed with short comments and relevant references providing a broader context for those readers who are not as familiar with the corresponding research topics or the sociopolitical circumstances (Fig. 2). We believe that such a hybrid form might be not only more entertaining than a conventional review article, but it may provide a complex and more accurate picture about the motivations that eventually resulted in the birth of cognitive biology.

Fig. 1
figure 1

Wisdom of youth versus wisdom of old age. LK: “The wisdom of life is like a coin with two sides: one is the wisdom of youth and the other is the wisdom of old age. The wisdom of old age is the wisdom of experience. Rather passive than active. But life sustains and drives the wisdom of youth: dreams, plans, enthusiasm, belief in ideals. … The wisdom of old age, the feeling that life had meaning and was fulfilled, must be lived through the wisdom of youth. … The true wisdom of old age is not selfish, it also includes respect for the wisdom of the young and a calm empathetic sharing of their desires and joys” (Kováč 2018b). Left picture: second half of the 1930s; photographer unknown. Right picture: 2005; photographer: Jordan Kolarov (Department of Biochemistry, Comenius University Bratislava)

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Fig. 2
figure 2

A timeline of events leading to the birth of cognitive biology. See text for more details. The timeline spans nearly a century of scientific progress that is discussed by LK as follows: “It was in the logic of the development of science that the twentieth century was the romantic phase of science (as if we have forgotten that it was the ‘bloodiest century’). In the twenty-first century, the nature and mission of science is changing. Complexity itself becomes the subject of science's interest. However, the contradiction between the natural character of the savannah and the environment of the artificial world is growing strongly. And it is only in the logic of the growth of knowledge that science is pushed out of the cultural scene by simplified technoscience. It superimposes on the complexities of the world of the human individual and society a simplified artificial world, in which ‘rational’ material artifacts (however ‘miraculous’ they may be, e.g., new DNA sequencers or communication technology) come into ever-greater conflict with the complexity of social dynamics. Living in conditions of uncertainty and unpredictability causes individual and social stress and accelerates the disintegration of metaconceptual foundations, as well as the disintegration of democracy” (Kováč 2018a)

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You are Wrong, Mr. Teacher; I Will Become the Next Štefánik!

LK was born in 1932 in a small village, Závažná Poruba (formerly Zavážna Poruba; a nuance appreciated only by native Slovaks), in a part of Slovakia called the Liptov region. The village lies at the foot of the Low Tatras, a picturesque mountain range separated from its better-known cousin, the High Tatras, by the iconic Slovak river Váh. Here is what LK had to say (in 2004) about his childhood to Dušan Migaľa, the editor-in-chief of the village’s newspaper, Porubské noviny:

Question (Q): “Every person has a curriculum vitae. Can you tell me about your CV after high school graduation in Liptovský Mikuláš?”

LK: “If you allow me, I would not like to start my curriculum vitae with my graduation. Curriculum means ‘running’ in Latin. We run through our life from birth to death. However, it is not running at a steady speed; as we age it constantly slows down. Its graphical representation could look like a logarithmic curve: if we run 100 km in the first decade of life, in the second it is only 50, 25 in the third, 12 and a half in the fourth decade, and so on. It is easy to deduce that in the eighth decade of life we are just dragging our feet: in 10 years we are unable to walk even 1 km. If, on the other hand, we extrapolate the curve to the beginning, in the first days and weeks after birth we run at an astronomical speed: the beginnings of life would have to be measured in light years. In fact, we should count the beginning not from birth, but from conception. This speed also determines our biological time. In terms of biological time, we spend in the mother's body, as embryos, 99% of its entire life. Paradoxically, as the running of life slows down with age, we subjectively feel that time is speeding up—time flies very quickly for an old person. But that's precisely why, with such a slow drag through life, there are quite a few new experiences within a year.

I emphasize this because the first years of life after birth, even perhaps the first minutes and hours, but also the weeks and months before birth, are the most important for a person's life. It is when the permanent form of a human being is produced. If I were to use an analogy according to which a person is assembled like a computer from individual parts, then during the first period the hardware is formed. When the computer’s hardware is constructed, only then the software is installed—but we know very well that the characteristics of the computer, its performance, its memory capacity, etc., are primarily determined by hardware, not software.”

Q: “What are your recollections of your early childhood?”

LK: “Artists suspected a long time ago that a person is shaped by childhood. My schoolmate from Závažná Poruba, the poet Milan Rúfus, expresses this repeatedly in his poems and essays. At the beginning of the twentieth century, the psychiatrist Sigmund Freud based his entire teaching, psychoanalysis, on this assumption. Today, this view has a firm scientific basis: the construction of the human brain, i.e., the creation of its hardware, continues long after birth, with the first experiences deciding which structures are permanently formed and which are not. These structures are the basis of all future behavior. The ethologist Konrad Lorenz called this deposition of basic forms of behavior into the animal brain imprinting. There are sensitive periods in human development, we call them critical periods, when imprinting occurs. It seems that two critical periods are particularly important: the first are the initial months and years, or perhaps rather even the first minutes, after birth—that's when the emotional skeleton of a person is built. What is created during this period will remain for life. Someone becomes rude, insensitive, dissatisfied, envious, full of complexes of inferiority, someone acquires the ability to enjoy even small everyday things, being able to empathize with the feelings of others. Similarly, during this period children are imprinted with ambitions to succeed and win, a sense of fair play or tendencies to lie and cheat. Of course, hereditary dispositions are also important, but I do not want to talk about them now. The second important critical period is around puberty—in it, symbolic values are permanently embedded in the human brain, for example worldview, patriotism, basic ideas about the meaning of one's life. I think that it is easy to deduce from these findings how important, even decisive in a person's life, there are two social institutions that mainly determine what is imprinted on a child and an adolescent—family and school.”

Q: “Tell me about your family.”

LK: “My childhood was probably strongly influenced by my maternal grandparents, with whom we lived in a joint household. My grandfather was Ján Broska, curator and parish clerk in Závažná Poruba. He became a legend when the military authorities wanted to tear down the bell from the tower during World War I (cannons were cast from the bells at the time). He was willing to let himself to be shot, but he did not allow the bell to be removed. A man of strict life principles, a prototype of the Lutheran Puritan. When he milked the cow at dawn, he could be heard chanting to himself in the barn, ‘The sun is already rising, praise the Lord, right from the morning, because he was your protection, my little soul.’ Sunday lunch the family started with prayer; and every night before going to bed he read religious texts from the ancient book The Well of Life. He knew the world: like many others of his generation, he participated in building Budapest as a bricklayer. When I went with him as a boy to mow the grass on the nearby meadows, along the way he recited to me geographical knowledge that he had to learn in the grammar school: 'From the town of Ružomberok we are approaching the town of Liptovský Svätý Mikuláš, recognized by the smoking chimneys of the tanneries…’ I didn't like mowing, I was terribly bored. Up to today, the smell of dried hay does not intoxicate me, but makes me feel uncomfortable. The sweetest thing was the obligatory afternoon nap in the shade under the trees, after we had eaten halušky [gnocchi-like Slovak dish] and drank sour milk, which grandma brought to the meadows for lunch.

“Grandmother, petite, with crooked legs, was a person of immense kindness and goodness. When I was going to school, she would sometimes, somewhat secretly, cook one hard-boiled egg in the morning, and she never forgot to add that if you eat one egg, it's the same as eating half a kilo of meat. Chickens ran around the yard in abundance, but eggs were scarce; she used to take them twice a week, together with milk and cream, to her customers in Liptovský Mikuláš. She was able to complete the journey [about 5 km] in half an hour. She would not sit down the entire day. Tired, she fell asleep in the evening at the kitchen table reading over The Well of Life, which always outraged the grandfather: such disrespect for the Scriptures, to read and sleep at the same time! They shared a simple narrow bed in the kitchen. She also died in it, with my grandfather by her side until the last minute. He himself passed away in a way that still fills me with respect. Well, more like amazement. Shortly after her death, he fell ill in the middle of the summer with a banal cold. Surely, he would have been easily able to get out of it, as he always did. But he said to himself that his life is over and that it was necessary to end it. He got out of bed, went to the barn to say goodbye to the cow and the lambs, stroked them, blessed them. Then he lay down, and in two days he was dead.”

Q: “What about your father?”

LK: “My father was an extraordinary person. He was born in one of the few local peasant households where the family also had horses. He was raised, along with his younger brothers, by a strict stepmother. They lived in a single room. The mother served simple meals, the boys sitting around at the table, wooden spoons in hand, and competed to be the first to fill their bellies. At the age of twelve, he already went carrying wood from a nearby valley. It was a difficult and dangerous job even for adults. We elders still remember the old men who were limping because they had been injured in the forest. My father was a good student, so he entered a prestigious school in Liptovský Mikuláš. He was probably the first of the villagers to study there (in Hungarian) for the whole three years. However, he did not escape the fate of his contemporaries: he worked as a bricklayer in Budapest for one or two summers.

“With such a poor education, the ambitious boy was able to take a mason's course in Bratislava after World War I, learned to draw building plans and began with the local masons and carpenters to build family houses around the region. There are still many existing houses whose plans he drew and managed their construction—all for free—such as the evangelical church and the cultural center in Závažná Poruba.

“But he also liked this job. He rebuilt his father-in-law's house and made a ‘merchandise shop’ for his wife. Even that did not satisfy him. This is what his working day looked like in the peak years of his life: at five o'clock in the morning, he boarded a passenger train and rode to Poprad [city in the Spiš region of Slovakia]. There he worked as a roadmaster at the district office—he designed and managed the construction of roads in Spiš. Even now, most of the asphalt roads in Spiš have their first foundation from his time. After finishing his eight-hour shift in Poprad, he returned home. He helped my mother in the store, and here and there, although rarely, he went with me and my grandfather to mow. On Sundays, he sat at the table at home and drew up plans for family houses with precise strokes—he also continued to perform his work as a master bricklayer. Even that was not enough: after the mobilization of the Czechoslovak army against the Germans in 1938, he also became the mayor of the village. He gave up the position, not because it was too much for him, but from a wisdom that might be called statesmanlike, as soon as the Germans started the war with the Soviet Union. Who knows how he would have ended up with his nature. His uncle, Peter Niňaj, then took over the position of mayor. The man who risked his life many times during the Slovak National Uprising [a semi-military revolt organized by the Slovak resistance movement during World War II] and after it, saved many villagers and was responsible for the fact that none of the Jews who were hiding in the local cellars and slaughterhouses were betrayed to the Germans. He probably also prevented the Germans from burning down the village as happened to Smrečany, the village from the opposite side of the river Váh.”

Q: “Let’s move on to your school years.”

LK: “The three years of grammar school in Závažná Poruba had no less influence on my formation than my family. The legendary teacher Alžbeta Jašková, who was selflessly helped by her sister, ‘Miss’ as she was called by the locals, taught me to read and write, but probably also instilled in me the basics of decent behavior and morals. For educational reasons, she sometimes gave us ‘kicks’: she lightly hit the tips of our fingers a few times with a hazelnut mallet, which we, the boys, helped her to make with great pleasure. The mindset of the village, its ‘ideology’ in the days of my youth, was represented by three main components: piety, patriotism, and social feeling (Communists and Social Democrats had a political majority in the village during the First Czechoslovak Republic). Part of piety was also the respect for teachers and especially for priests. Those of us who studied well and were more ambitious naturally imagined that they would become priests. In the eyes of the village, and of course us children, the priests represented the pinnacle of education and wisdom. After all, the first high school graduate from the village, Ján Agnet, went to study theology. When he, as the first local college graduate, was ordained a priest, it was probably the biggest celebration that the villagers had experienced. Patriotism, on the other hand, manifested itself in respect for written texts, for literature in general. If not to be a priest, then to be a writer and a poet—these were the goals of our youth. With boys a few years older, Milan Rúfus and my cousin Dušan Kováč, we created a three-member ‘Rázus cultural association’ [Martin Rázus was a Slovak poet, dramatist, writer, politician, and Lutheran priest]. Its mission was to cultivate literature. My grandfather, of course, was already looking forward to what kind of priest I would become. My father, a technical talent, maybe even a technical genius, would have wanted me to be something else: a world-famous architect—that is probably how he once dreamed of himself. However, as a six- or seven-year-old still with the idea of a priest's career, when I was nine, I saw myself rather in the position of the new Martin Rázus. And then, one day in May, something radically changed. We had a celebration at school in memory of Milan Rastislav Štefánik, a famous Slovak astronomer [and politician]. Patriotic songs were sung, poems were recited, and teacher Ján Vaško gave a ceremonial speech. At the end of the speech, he said the words that may have become decisive in my life: ‘Štefánik was a great scientist. None of you will ever be like him.’

“I still remember that dramatic moment. No matter what, lightning struck somewhere inside me and there was a loud thunder. Something protested in my spirit: ‘You are wrong, teacher. I will become the second Slovak Štefánik.’

“It was childishly naive, but beautiful. Well, I did not become the second Štefánik—I grew up into what became an unfavorable period. But something permanently changed in me then. I guess there is no better example of imprinting than this episode of my life.”

The First University

According to LK, as highlighted in his lecture summarizing his career (Kováč 2018a), he graduated from two universities, the first—though metaphorical—taking place during the final months of World War II. Here is its description:

LK: “The end of World War II played a decisive role in my formation. At the beginning of 1945, German troops fortified themselves near Liptovský Mikuláš, and for the whole two months the front line was not moving. We had to leave our village that was only a few hundred meters from the front line. The village was destroyed in the fierce fighting. An artillery shell fell through the roof of my parents' house on a bookshelf with an extensive library, collected by my uncle on the modest salary of a village teacher. When the front finally moved, I was in charge of the salvation of the collection from the scattered and torn books. Then, as a 13-year-old boy, I graduated from my first university. Dostoyevsky, Tolstoy, Alexander Dumas; the first Slovak History of Philosophy by Štefan Osuský, Conversations with T.G. Masaryk by Karel Čapek, and even Marx's Capital in thin red notebooks; dozens of years of the Czech magazine Výběr, which the Slovak teacher did not stop taking even during the Protectorate; the German weekly newspaper Signal; Czech and Slovak daily newspapers, collected over two decades.

“The final decision about my life path was probably made at the high school in Liptovský Mikuláš. It was a good school, whose foundations were laid by devoted Czech professors. One of them, Oldřich Nuska, was our class teacher from the first to the eighth grade. He taught us history and geography. Like other professors, he entered the class in a ceremonial civilian suit (the same one for the whole eight years), but he took us—ten- or eleven-year-old kids—as his partners. And then, one fine autumn morning, at the beginning of the fourth grade, the day began in a different way. We had our first chemistry class. A gentleman in a white coat entered the classroom, uttered only a few words, placed a bowl of water on the table, and opened a dark bottle that he had brought with him. With tweezers, he took out a piece of a strange gray substance from the bottle and threw it into the water. There was an explosion and flames coming out of the water. Above them stood this teacher as a magician. ‘This is chemistry; it is aimed at exploring the secrets of the world,’ he said. In that short moment this Czech professor, Jan Šafránek, hooked me definitively to chemistry.

“Chemistry became my life’s destiny. Even when it served me to investigate the chemical foundations of life—in the form of biochemistry—and today, when I ask myself more complex questions about human nature, about the dynamics of society, about the nature of politics, about the technique of education, about human happiness. The basis of my approach to interpreting the world is still biology, and below that, at the very bottom, chemistry.”

The Second University

Q: “Science has become your destiny. Please describe the area of your research.”

LK: “In order to be a scientist, of course, you must first get an appropriate education. I was very lucky with the school and the teachers. I was originally drawn to philosophy; I felt an unbearable need to understand humanity's place and mission in the universe, to understand the dramatic times in which we lived, to understand the motives that compel us to live and act. But in the end, I chose to study chemistry and biology. As a high school student, unlike many of my classmates, I did not possess a miniature chemistry laboratory; I didn't even collect butterflies and beetles. At that time, I chose the study of natural sciences due to a kind of stubborn negation of the opinion of existentialists, whom I eagerly read at the time, that natural science knowledge is irrelevant to the understanding of a human being and its destiny. It seemed to me that, on the contrary, natural science knowledge, step by step, could make it possible to understand and answer basic questions about human nature. Today I do not even know why, but after graduation I applied to study not in Bratislava or Košice, like other classmates, but in Prague. It was one of the best decisions of my life. At that time the top Czech scientists were teaching at the Faculty of Natural Sciences of Charles University. For example, I was taught physical chemistry by a man who is still the only Czechoslovak scientist who received the Nobel Prize for science, Jaroslav Heyrovský. My main supervisor was Arnošt Kleinzeller. As a medic, he escaped from the Germans, before World War II broke out, to England and there he graduated in biochemistry under the guidance of the best biochemists in the world. One of them, Hans Krebs, was awarded the Nobel Prize for discovery of the tricarboxylic acid cycle. In one of his autobiographical essays, Krebs made a kind of family tree, from which it was clear that his teachers were also Nobel Prize winners. It could be deduced from this that in the future Nobel prizes will also be awarded to his students.

“Although he did not make it to the Nobel Prize, Kleinzeller made several fundamental discoveries as a young man in England. He has substantially contributed to the discovery of the tricarboxylic acids cycle. Together with Joseph and Dorothy Needham, he described the principal biochemical mechanism of muscle contraction. He also initiated studies on the intermediary metabolism of lipids. After the war, he returned to Prague. At that time Czechoslovak biochemistry was just emerging as a discipline. Its early protagonists were persisting, admirable in their amateurish enthusiasm, but still only self-taught. By training and thinking, they remained organic chemists. At the Faculty of Natural Sciences, in the toilets, urine did not flow into the sewers, but was collected in special collectors: it served nascent biochemists as a source for separating chemical substances by paper chromatography. In the Academy of Sciences, the organic synthesis of peptides and nucleotides, as well as an ambitious project of protein sequencing—also using paper chromatography—were underway. The isolation of plant alkaloids and terpenes, successfully carried out by workers in academia and universities, was also considered biochemistry.

“In contrast, at the time of his return to Prague, Kleinzeller was already a mature scientist and a talented teacher. He transferred from England to Prague not only knowledge of modern biochemical techniques, but especially British biochemical thinking: questioning of traditional views and a search for alternatives; uncompromising criticality, accepted as part of an exciting intellectual game; raising fundamental questions, with an overlap from science to philosophy. Kleinzeller came to Prague as a trained biochemist, he represented continuity with the main tradition of European biochemistry and began to create his own biochemistry school. However, in Prague he fell into a small local circle full of animosity and envy. During the political trials in the 1950s he had to leave the Czech Technical University. He was eventually accepted at Charles University but was offered only an inferior position. He had to struggle for survival, often with scarce means, and he no longer had much time or energy for research. But the few of us who became his students managed to get passionate about science and he taught us first-class English biochemical thinking. So, I can say without exaggeration that I had two Nobel Prize winners as teachers, Heyrovský and Krebs.”

Q: “What was your first scientific project?”

LK: “At the time I was an undergraduate student, Kleinzeller was pursuing the following research problem: yeasts were cultivated in media containing a particular amino acid and the preliminary data seemed to support the conclusion that the cells' proteins were enriched in this particular amino acid. That would be of an enormous practical significance: the nutritional value of standard yeast cultures is relatively low due to a low content of lysine and methionine. As fresh undergraduate students we were to continue in this research direction and my role was to show that cultivation of yeasts on sulphur-containing amino acids will yield their higher content of the cellular proteins. Kleinzeller not only had the ability to ignite his students but at the same time to make them skeptical about what he was teaching. And we doubted that the amino acid composition of proteins could be changed by such simple means. In Czechoslovakia, Lysenkoism was at its peak and the experiment would go in line with this dogmatic concept. However, we were discovering biochemical genetics, the Nature article of Watson and Crick on the structure of deoxyribonucleic acid was just published; the heroic era of biochemistry culminating with the elucidation of the genetic code just started. Whoever was reading the scientific literature must have known by then that the amino acid composition of cellular proteins could be changed only via changing the corresponding genes. But the term gene was prohibited and Kleinzeller himself, in the frog-and-mouse battles, attacked his opponents by accusing them of believing in genes.

“But he let his students believe in genes. We told him that the results on changing the amino acid composition of yeast cellular proteins that he published with his graduate student are not reliable. He was able to take criticism. I remember an early evening walk through the streets of Prague's Albertov [university quarter] during which we talked about that. The conversation turned to discussion about the ethics of scientific work, about the normative value of scientific truth. He tried to explain to me that in addition to the absolute criteria, there are additional aspects: the struggle for prestige, for status, an unequal competition with people who are not interested in scientific work at all, who are interested in status, secured warm places…. He was, one could say, harsh even to himself: he admitted that, measured by the standards of his teachers, Krebs and the Needhams, it was necessary under unfavorable circumstances to resort to methods which they would most certainly condemn. These conversations, which were later repeated several times and even once culminated in a private seminar dedicated to the ethics of scientific work, were, in my opinion, of decisive importance for my formation. They stand at the beginning of my belief that there is only one science, only one criterion, only one scientific ethics. That there are no compromises in the question of scientific truth, in all its aspects, just as in the question of the value and meaning of scientific work.

“After two months of preparation for the undergraduate thesis, I informed my supervisor that I did not believe in the proposed goal and suggested to him that—as long as we wish to stay with the topic of sulphur amino acids in yeast—we should study the mechanism of their biosynthesis. Nothing was known about this mechanism at the time. It was a youthfully naive proposal: a scientific problem for a decade and not for a thesis that lasted six months. However, Kleinzeller was understanding and agreed.

“My undergraduate thesis had all the signs of inexperience. But it was also very ambitious: the discussion included a proposal for a mechanism for how sulphur-containing amino acids are synthesized in microorganisms. Kleinzeller suggested to us, the undergraduates, to write manuscripts and publish the results in Chemical Letters. Fascinated by science, we were eager for scientific glory. We wrote the papers and delivered them to the publisher…. In the meantime, insecurity began to gnaw at us. The results were obtained hastily; some experiments were not even repeated. The second classmate—Arnošt Kotyk—who also submitted the work for publication, was experiencing similar doubts. Two months later we retracted the papers. Kleinzeller was angry; he somehow reconciled with me, but from that moment he completely broke up with the other colleague. It wasn't until three years later, when I was already working at the university in Bratislava, that I returned to the problem. I reproduced the results, performed additional experiments; Kotyk in Prague repeated the measurements with radioactive sulphur. The work was published in Nature (Kleinzeller et al. 1959). It can be said that—although based on indirect experimental evidence—it was the first explicit formulation of the mechanism according to which inorganic sulphate is first attached to an organic nitrogenous compound and only then transformed into cysteine. … That's how I have entered the scientific world.”

Bratislava’s World-Class School of Bioenergetics

Although biochemistry was firmly established as a scientific discipline at the beginning of the 20th century, there was no biochemical research in Slovakia until the mid-1960s. This changed after the appointment of LK at the Faculty of Natural Sciences of Comenius University Bratislava after his graduation from Charles University in Prague (1954, MSc) and the Czechoslovak Academy of Sciences in Prague (1957, PhD). After a few years in a biochemical section of the Department of Organic and Analytical Chemistry and since 1966 as the head of an independent Department of Biochemistry, LK attracted a group of young enthusiasts and established a school that within a few years revealed important secrets of cellular bioenergetics. Here is the period recollected from the interview with Dušan Migaľa, LK’s 2018 lecture, and the report written after the dissolution of the Department of Biochemistry (Kováč 1972, 2004, 2018a):

Q: “Is it true that you were a candidate for the Nobel Prize?”

LK: “Before I answer the question, I have to recapitulate what happened after I finished my studies at Charles University. I completed my doctoral studies in Prague—at that time it was called postgraduate studies—partly at the university, partly at the Czechoslovak Academy of Sciences. During my studies of an enigmatic succinate dehydrogenase activity in plants, I encountered one of the most exciting moments of my life. For the first time I experienced a unique intense feeling, the moment when a human takes in nature's secret thanks to one's intellect. After pipetting my enzyme preparation into the Warburg tubes, I excitedly watched as the oxygen was gradually consumed, proving my assumption to be correct. My work was soon published (Kováč 1957a, b, 1958a, b). It was a great satisfaction for me, in terms of the criteria I had set for myself as an undergraduate student, that an authoritative monograph on plant physiology cited my work as genuinely the first case of purification of this enzyme (Wolf 1960). Later I tried to show that what I found in the case of plant succinate dehydrogenase is also true for a yeast enzyme. Excited, I prepared a paper for Chemical Letters, which was—timewise—my first publication (Kováč 1957c). However, it soon became evident that my conclusions about the yeast enzyme were incorrect. So, in spite of my earlier resolutions, the main result of my first publication was wrong. A closer inspection of the yeast enzyme has shown that in yeast there are two succinate dehydrogenases: one canonical and one with very peculiar properties. This observation was also published (Kováč 1958c, d) and together with the first papers it was the basis of my dissertation.

“Kleinzeller was my supervisor, but at the time our encounters were only sporadic. The modest environment at the Department of Animal Physiology of Charles University became decisive for my scientific and personal development. The room I was sitting in wasn't quite a laboratory. One visitor commented with huge disappointment on the workplace. When it got dark, huge Periplaneta americana cockroaches, which were the research subject of my colleagues at the time, were moving on the floor, on the tables, on the beakers. However, the intellectual environment that existed there at that time was unique. Kubišta, Čerkasov, Novotný, Blažka—four people with whom it was possible to constantly talk about scientific problems, with whom it was possible to share enthusiasm for new discoveries described in the literature; thoughtful, cultured people, indeed philosophers. Moreover, dozens of other intelligent biologists; a stimulating atmosphere; bright and hardworking students. It was Cambridge in miniature.

“After three years I finished my dissertation. Kleinzeller urged me to stay working with him in Prague. However, my Slovak patriotism imprinted during my childhood prevailed. I decided to initiate biochemical research in Slovakia, at Comenius University Bratislava. Literally from scratch—back then, in the second half of the 50s of the last century, there was no biochemistry in Slovakia. Again, I was extremely lucky: I quickly managed to raise my students into dedicated, passionate, and hardworking collaborators. It didn't even take ten years for us to become a world-renowned workplace. No longer did we learn from the world, but the world wanted to learn from us—I was invited as a visiting professor at universities in France, Germany, and the United States of America. However, when I returned from a long visit in the USA in 1970, Russians had already occupied Czechoslovakia and political cleansings had just begun. In October 1970 the Department of Biochemistry was abolished 'due to a very bad personal situation.' In February 1971, I was dismissed from the university on the grounds that, 'after the reorganization of the department you had become redundant, and the university had no possibility of employing you.' In June 1971, I was hired as a researcher at the Biochemical Institute of Comenius University only to be dismissed a month later on the grounds that, 'you do not meet the requirements placed on you and therefore you do not have the prerequisites to work at this institution.' Most of my young colleagues had to leave with me, thus the workplace was completely destroyed. I was able to get a job as an ordinary chemist in the psychiatric hospital in Pezinok, a small town near Bratislava. But there, instead of scientific research, my job became examining the blood and urine of mentally ill patients. It was when I was commuting from Bratislava to Pezinok every day, marred by severe, often almost suicidal, depressions from a wasted life, when the news spread throughout Czechoslovakia and neighboring countries that several important scientific groups from around the world proposed our group for the Nobel Prize. Apparently, they did not know that the group did not exist anymore. Objectively, I think that at that time our work had not yet reached the Nobel Prize level, so we probably would not have received it then, but it seems to me almost certain that we would have worked on it, if there had not been stupid, senseless, absurd dismissal of the members of our department thus making it impossible for us to continue our work.”

Q: “What was the essence of your discoveries?”

LK: “Maybe it will sound a little immodest, but it seems to me that our story should be part of the books on the history of science. Not for its political absurdity, but as proof of how crucial originality is in science. The scientist wants to be successful, especially in the eyes of his colleagues, with whom he actually plays a game full of tension. S/he wants to win the game. But that's why such a game is played according to accepted standard rules—it concerns the generally interesting and most promising topics. At that time, such a topic was the question of how energy is transformed in living organisms. It was known that in each of our cells we have something like miniature power plants—we call them mitochondria—in which the energy from the food we consume is transformed into forms that allow us to move, do work, and even think. It was not known how the transformation of cellular energy takes place. This is what I wanted to discover, in parallel with other scientists elsewhere in the world. If I had had the expensive equipment and expensive chemicals they had, I would probably have done the same thing as them. However, there was neither money nor equipment at the University in Bratislava at that time. Necessity forced me to look for original ways, to choose a path that no one had taken. For a negligible amount of money I bought several batches of baker's yeast at the local food store, and that was enough for a week of experiments. Yeasts, unicellular creatures, similarly to human cells contain mitochondria. In addition, yeasts have one advantage: they can be used not only for chemical experiments, but also for genetic analysis. And that's what we did then: we combined biochemical and genetic approaches in the study of cellular ‘power plants.’ We were at least ten years ahead of the world. The study of cellular bioenergetics by means of biochemical genetics was soon entertained by other leading laboratories, and soon the Nobel Prizes literally started pouring out of this type of research—gene manipulation, genetic engineering, biotechnology were born. When I was allowed to return to the university after the fall of Communism, it was possible to directly follow up on what we had started doing 20 years ago. It was still interesting and even after such a long time the problems were still relevant—except that the 20 lost years could not be caught up. The world was not waiting for us. We were good at mitochondrial biochemistry and genetics, but not the best anymore.”

Q: “Explain the reasons for the dissolution of your group.”

LK: “The political committees in 1970 could not accuse me of any ‘hostile’ political activity. I was not in the Communist Party and I was not involved in any illegal organizations. And so it was officially justified that I was expelled for my ‘subversive’ opinions. That I allegedly corrupted young people, instilling in them a ‘bourgeois’ view of the world. Since I returned home from the US, although most people did not return then and many rather tried to escape abroad from our normalization cage, rumors also spread that I had returned from America to be an American spy. At the same time, I must say, my American colleagues warned me before my departure from the USA. They offered me favorable positions at leading American universities. But I wanted to prove to them, as I once did when I preferred Bratislava to Prague, that even here, in materially and spiritually much more modest conditions, we can be competitive. I probably even confidently thought: if I've already done it once, why shouldn't I do it a second time?! The members of the committee made me responsible even for young colleagues, some of whom were party members at the time and were expelled from it after the vetting—they say I messed them up. There was probably only one piece of truth in that: these young people did not bow before the vetting commission and label the Russian invasion as ‘brotherly help,’ as all those who went through the party purges had to do at that time. My young colleagues understood it as aggression and occupation and said so. If they hadn't done that, they would probably have been ashamed in front of me. Indeed, I not only taught, but also required my colleagues and students to be non-tactical and always speak openly what they thought.

“However, the real reason for the breakdown of our group at the beginning of normalization was simpler. Envy. The political purges of the 1970s gave an opportunity to poor, incompetent, envious people to destroy what they could not reach. And also to eliminate those who threatened them. In the case of the dissolution of our department, politics was only a pretext. Of course, I have never made a secret of the fact that only the best experts, strong personalities, people with high morals, in whom students see their role models, belong to universities. Even today, these views of mine, still publicly declared, worry and irritate many, even today they see in them my threat, even today they scream that I would also instill these views in my students—except, fortunately, today there are no more party committees that could repeat what they did to us decades ago. This is a great advantage, but also the viability of democracy.”

The results obtained by LK’s group between 1958 and 1970, without any exaggeration, were at the cutting edge of the biochemical research of that era. They were recognized by leading figures in the field, as demonstrated not only by the unusual number of citations, but by the co-authorship of papers with such great minds as Efraim Racker, Benno Hess, Gottfried Schatz, or Piotr P. Slonimski. Many studies became classics and are cited 50 years after their publication. The Department of Biochemistry in Bratislava was not only highly successful, but also a happy workplace (Fig. 3). To summarize the most important output of this early, highly productive, successful, yet abruptly terminated, period, let’s cite an excerpt from LK’s report entitled Biochemical Genetics of Oxidative Phosphorylation, written nearly 10 years after his dismissal from the university (Kováč 1978):

Fig. 3
figure 3

Heyday of Slovak biochemistry. Under modest conditions, a group of young enthusiasts started to produce world-class scientific outputs. The pictures were taken by an unknown photographer, late 1960s. From left: Miloslav Greksák, Jana Irmlerová, Ladislav Kováč, Kazimír Kollár, Eva Böhmerová, Štefan Kužela, Helena Fečíková, Július Šubík, Yvetta Gbelská, and Jordan Kolarov

Full size image

LK: “The aim of the work was to contribute to the elucidation of oxidative phosphorylation. The research was accomplished in a 17-year period, and it deals with five basic themes:

  1. 1.

    Studies on succinate dehydrogenase. A simple method for the determination of succinate dehydrogenase was elaborated. The method was applied in a procedure for partial purification of plant succinate dehydrogenase. Succinate dehydrogenase and fumarate reductase activities of higher plants were assigned to a single enzyme. On the other hand, in yeast Saccharomyces cerevisiae two different enzymes were characterized: one, a ‘classical’ succinate dehydrogenase similar to animal and plant enzyme and a fumarate reductase resembling a similar enzyme found in anaerobic microorganisms. On the basis of data on distribution of the two enzymes in yeast growing under different conditions and in respiration-deficient mutants a hypothesis was advanced ascribing a role for fumarate reductase in anaerobic cells (Kováč 1958a, b, c, 1960; Kováč and Motýlová 1962).

  2. 2.

    Effect of uncouplers of oxidative phosphorylation on energy-requiring processes in anaerobic cells. It was found that uncouplers inhibited induced enzyme synthesis in Escherichia coli and yeast under anaerobic conditions and also in respiration-deficient mutants lacking respiratory enzymes. A conclusion was reached that uncouplers interfered not only with the mitochondrial membrane but also with other cellular membranes. This lent support to the chemiosmotic theory of oxidative phosphorylation (e.g., Kováč and Istenesová 1964; Kováč and Kužela 1966; Galleotti et al. 1968; Kováč et al. 1968a, 1970a).

  3. 3.

    Biogenesis of mitochondrial components. A relationship between lipid composition and respiratory enzymes synthesis was elucidated. It was concluded that synthesis of mitochondrial components is a process of coordinated successive synthetic steps (Kováč et al. 1967a, b, 1969).

  4. 4.

    Properties of mitochondria of yeast Saccharomyces cerevisiae. A procedure for the isolation of yeast mitochondria from protoplasts was worked out. It was shown that yeast mitochondria were similar to animal mitochondria. Properties of mitochondria isolated from various yeast mutants were examined. Mitochondria from a pleiotropic yeast mutant carrying deletions in mitochondrial DNA were found to be deficient in reactions of oxidative phosphorylation lacking a membrane component conferring oligomycin sensitivity to the mitochondrial ATPase. Oxidative phosphorylation was found to be intact in single-gene mutants lacking only one respiratory chain component. A mutant with lesion in terminal steps of oxidative phosphorylation was studied and the lesion was located in the translocation of adenine nucleotides across the inner mitochondrial membrane. By these studies a new approach to the mitochondrial energy coupling was worked out, combining genetic and biochemical principles and methods (Kováč and Hrušovská 1968; Kováč and Weissová 1968; Kováč et al. 1968b, 1970b, 1972; Kováčová et al. 1968; Kormančíková et al. 1969; Kováč 1969; Šubík et al. 1970, 1972a; Kolarov et al. 1972a, b; Schatz and Kováč 1974). For a comprehensive review describing the utility of mutants in the study of mitochondrial energy conversion see Kováč (1974).

  5. 5.

    A role of mitochondria in control of cell growth and multiplication. By employing mutants carrying specific lesions in mitochondria and also wild-type yeast inhibited in various steps of the mitochondrial energy-coupling process a conclusion was reached that intramitochondrial ATP is obligatorily needed in eukaryotic cells for continuous cell growth and division (Šubík et al. 1972b, 1974; Kováč et al. 1977, 1978).”

The “case study” illustrating far-reaching impacts of the results obtained by Kováč and colleagues is the story of the so-called op1 mutant. Originally isolated by Tadeusz Lachowicz in the Piotr Slonimski laboratory in Gif-sur-Yvette, France, it exhibited a peculiar phenotype: though the cells exhibited normal respiration, they were unable to grow on nonfermentative carbon sources (Kováč et al. 1967a, b). Moreover, they were unable to tolerate a loss of mitochondrial DNA (Kováčová et al. 1968). In hindsight, one must appreciate the visionary character of this pioneering paper. For example, based on biochemical characterization of the mutant, but without any direct evidence, the authors explicitly mention a “possibility would be a lesion in the last step of the mitochondrial phosphorylation system, that is, in the adenine nucleotide translocation through the membrane” (Kováč et al. 1967a, b). Exploring this and other alternatives took several more years. The importance of this research question is exemplified by the invitation letter sent by Efraim Racker to the rector of Comenius University: “It has been made the most interesting discovery of a new mutant which apparently cannot catalyze oxidative phosphorylation. With the aid of our various protein fractions, it may be possible to determine the site of this metabolic defect. It may be the first time that such a genetic lesion in energy metabolism could be clearly defined.” The year spent at Cornell University in the Racker laboratory did not yield the solution of the enigma. On the other hand, LK made a series of experiments demonstrating the validity of the Mitchell’s chemiosmotic theory for mitochondrial membranes of yeasts (Kováč et al. 1972) and contributed to Racker’s conversion from a strong Mitchell’s opponent to one of its strongest defenders, who provided one of the most decisive experimental supports for chemiosmosis (Racker and Stoekenius 1974).

The grand finale for the op1 mutant took place in Bratislava. Development of the procedure of isolation of pure and functional mitochondria enabled initiation of a series of ingenious experiments that resulted in the identification of the malfunctioning component. Indeed, it turned out to be a translocator of adenine nucleotides (ADP/ATP translocator) that enables an antiport of ADP and ATP across the inner mitochondrial membrane. Unfortunately, many papers on this fascinating topic were published after the members of LK’s group were already scattered at institutes around and near Bratislava.

Years in Academic Exile: Opening New Venues

After his dismissal from the university, LK was entrapped in a catch-22 situation: the regime persecuted those without formal employment, yet for people like LK it was nearly impossible to find a position. The psychiatric hospital in Pezinok served as a refuge for half a decade (1970–1976). Although a depressing period, LK was not a mere clinical biochemist. He persuaded a director to allow him to perform real research. He carried out a series of introspection experiments aimed at understanding evolution of affective evaluation of external stimuli (Kováč 1977, 1982; Kováč and Varečka 1978). In parallel, similar to using yeasts to investigate cellular energetics, he employed a simple model organism, the fruit fly Drosophila melanogaster, to investigate its behavior (Kováč et al. 1978, 1979). Although he did not have time to pursue further experimental studies on this subject, it again demonstrated his vision and gut feelings for an important problem and a simple yet powerful experimental strategy to tackle it. As he later testified, the stay in Pezinok was one of the catalysts for the development of cognitive biology.

In the late 1970s, LK was offered a position at the Institute of Animal Physiology of the Slovak Academy of Sciences in Ivanka pri Dunaji—still a substantial distance for everyday commuting, but much closer to Bratislava than Pezinok. More importantly, LK was able to reunite with some members of his former team and return to some unfinished experiments. Some of the projects were aimed at a continuation of the earlier studies, such as membrane biogenesis (Kováč et al. 1980), selective effect of ionophores on mitochondrial membranes (Kováč and Poliachová 1981; Kováč and Varečka 1981; Kováč et al. 1982a, b, c), or essentiality of intramitochondrial ATP for cell viability (Gbelská et al. 1983). At the same time, he initiated new lines of research. For example, he and colleagues developed and optimized novel methods for delivery of DNA into yeast cells by means of analysis of the factors influencing the interaction of DNA with plasma membrane (Brzobohatý and Kováč 1985, 1986a, b; Kováč et al. 1987). It was in Ivanka pri Dunaji where one of the first successful restorations of respiratory capacity was achieved by a transfer of isolated mitochondria into respiratory-deficient cells (Sulo et al. 1989; Osuský et al. 1997), a proof-of-concept experiment substantiating the possibility of intra- and interspecific transfer of mitochondria later applied in primates (Kenyon and Moraes 1997). When the regime somewhat weakened, LK was allowed to travel abroad. In one of his trips he returned to the Slonimski lab that—once again—was puzzled by a strange mutant whose phenotype did not make sense. To make a long story short, LK found that the “mutant” was in fact a contaminant yeast species. For some reason (gut feeling again?) he did not terminate the “project” in an autoclave but investigated the cells of this species (now known as Candida parapsilosis) in more detail. Surprisingly, he found that it contained a linear mitochondrial genome (Kováč et al. 1984). At that time it was not only surprising (most eukaryotes were then known to possess mitochondrial DNA with a circular map), but also initiated an original (and still ongoing) research program related to the question of maintenance of telomeres not only in mitochondria, but also in the nuclei of eukaryotic cells (Nosek et al. 1998; Tomáška et al. 2009).

The Birth of Cognitive Biology

Some of us could witness these studies coming out from the LK’s lab as his students during the 1980s. LK was still persona non grata at the university, but his wife, Vlasta Kováčová, was a teacher at the Department of Genetics, so she “smuggled” us in to the institute in Ivanka. In addition to participating in experiments, we experienced vivid informal discussions organized by LK on various subjects, some very far from biochemistry or genetics. The institute was an oasis of free thinking and critical exchange of ideas. It was then when we received reprints of the first reports on cognitive biology (Kováč 1986, 1987). This was three years before the collapse of Communism in Eastern Europe. The events associated with the transition to democracy in Czechoslovakia in November 1989 fully absorbed LK. For a few months he served as a minister for education, science, and sport and then as an ambassador at UNESCO. This period as well as the 30 years that followed after he finally returned to the university, would be worthy of a separate chapter as it was rich in events and original thoughts materialized in dozens of original papers, books, and essays. The other articles in this issue of Biological Theory on cognitive biology highlight one of the routes of LK’s work. To briefly summarize these directions, we will take a shortcut and finish this prelude with LK’s response to the following question from the 2004 interview:

Q: “What is the current focus of your research?”

LK: “Today, my young colleagues are successfully continuing the work that we started in the early 1970s. Biochemical genetics, or, as it is more commonly called today, the molecular biology of mitochondria, is successfully developing in our country. They do it much better than I could at my current age. But this is an opportunity for me to try again, now not so much under the pressure of necessity but on the basis of life experiences, for new originality, for research in areas in which others do not explore, for breaking new paths. Using my experience not only in biochemistry and genetics (1954–1970); but also in psychiatry, which I learned in the psychiatric hospital in Pezinok (1970–1976); and ethology (behavioral science), which I got to know a little during my employment at the Institute of Animal Physiology of the Slovak Academy of Sciences in Ivanka pri Dunaji (1977–1989) and thoroughly during my stay at the Austrian institute of ethology named after Konrad Lorenz (1997–1999), incidentally also a Nobel Prize winner. But also, with the use of experience from politics—on one hand from the painful lesson that I just described (1970), and on the other hand, and especially, from my direct professional participation in politics (1989–1990) and diplomacy (1990–1992). The scientific fields we are developing can be called biopolitics, biopedagogy, biosociology—and their common denominator is a discipline that was born here in Slovakia and which I have no doubt that my successors will develop into a form that the world will admire: cognitive biology.

“The main lesson learned not by me, but by my entire generation that has lived its life in the dramatic period of the second half of the twentieth century, is perhaps this: Individual humans are weak creatures, not beasts, but rather timid, frightened animals, whose fear pushes them into highly solidary social groups. We are hyperemotional—of all animals we are the most sensitive to pain and the most driven by pleasure. We are mythophiles—we need to have a clear, comprehensible, and complete interpretation of the world. We tend to accept only our own interpretation, to believe in our truth as the only one, and to hate those who profess other truths. When, with all this limitation and weakness, we become part of modern institutions, we are terribly dangerous. Actually, it is not us, human individuals, but these institutions that are dangerous. That was the case of the Communist Party, whose anonymous decisions so heavily, unfairly, and irrationally affected the life path of many of us. But this is also the case today with the institutions behind the war in Iraq, behind the suicide attacks in Palestine, behind all those who enforce their only truth with blood and sword. But also, such institutions as the global market and modern science. We cannot even predict where they will take us in the coming years. That is why I am convinced that the main task of science today should be the investigation of human behavior and social dynamics.”

Concluding Remarks

In the 1960s, life sciences in general and biochemistry in particular were still at the “romantic” stage (Tomáška 2011). The scientific community was small and connected via personal ties, the textbooks were relatively thin and up-to-date, and reading just a handful of journals on a weekly basis was sufficient to have a nearly complete overview of the state of the art of an entire discipline. The field was ripe for major discoveries that were primarily driven by original ideas and were not necessarily dependent on the latest technology. The story of Ladislav Kováč repeatedly demonstrates this principle, cognitive biology being the most recent example. We should enjoy this romantic period of the field and take full advantage of its nascent nature.