Exp Brain Res (1992) 88:463-465

Experimental Brain Research �9 Springer-Verlag 1992

Otto Detlev Creutzfeldt, 1927-1992

On January 23, 1992, a few months before his 65th birth- day, Otto Detlev Creutzfeldt died, knowing that he had an uncurable disease. He bad served as the editor-in- chief of this journal for more than 20 years and has been its guiding spirit.

Otto Creutzfeldt was born on April 1, 1927, in Berlin, as the son of the great neurologist, Hans-Gerhard Creutzfeldt, whose name has become associated with the Jacob-Creutzfeldt disease. After receiving his school edu- cation at the Humanistic Gymnasium, in 1945 Otto Creutzfeldt started to study theology, history and philos- ophy at the universities of Kiel and Tfibingen, subjects which continued to fascinate him throughout his life and which provide a key to understanding his motiva- tions and aspirations. Otto Creutzfeldt was a humanist in the true sense of the word, passionately searching for ways to penetrate the mysteries of life and, above all, the conditio humana. In 1948 he decided not to con- tinue his studies of the humanities, but to enter the facul- ties of medicine at the universities of Kiel, Heidelberg, and finally Freiburg, where he obtained his MD in 1953. Maybe he succumbed to the attraction of a discipline that promises a holistic approach to the understanding of human beings, allowing for the coexistence of rigor- ous rednctionism and intuitive comprehension.

Between 1953 and 1959 Otto Creutzfeldt was an assis- tant and trainee in various medical disciplines : physiolo-

gy with Prof. Hoffmann in Freiburg, psychiatry with Prof. Miiller in Bern, and neurophysiology and neurolo- gy with Prof. Jung, again in Freiburg. At the end of these Lehr- und Wanderjahre, Otto Creutzfeldt was a fully trained neurologist, familiar with neurological and psychiatric diseases, domains where the specific limita- tions and dangers of human existence are particularly clearly exposed. In addition, he was already a member of the scientific community as author of a number of important papers in the field of electrophysiology. The years with Richard Jung, the eminent neurologist and pioneer of single neuron recordings in mammalian brains, were decisive for Creutzfeldt's future orientation. Richard Jung's main interest was to relate electrophysio- logical events in the brain to behavior, to clinical phe- nomena such as motor disorders and epilepsy, to mental states such as sleep, wakefulness and attention and, above all, to perception. Jung insisted that it is the search for such relations that matters, not the analysis of the neuronal substrate per se. Two congenial minds had found one another: Richard Jung and Otto Creutzfeldt formed a close and wonderful friendship until Richard Jung died in 1986.

During his stay in Freiburg, Otto Creutzfeldt laid the foundations upon which he built the admirable range of his interests and the fields of research to which he would later make so many seminal contributions. He

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adapted the single-unit recording technique - at that time still a daring and highly sophisticated endeavor - and applied it to the most complex structure there is, the cerebral cortex, a structure that subsequently never ceased to exert a deep fascination for him and became his major scientific challenge. Otto Creutzfeldt studied neuronal activity during epileptic seizures, described changes in firing patterns associated with changes in arousal, and investigated responses in somatosensory and visual cortex to sensory stimulation. He also pro- duced seminal papers on the interactions at the level of single cortical neurons of unspecific modulatory affer- ents from central core structures and specific sensory inputs. He was one of the first to emphasize the impor- tant influence of central states on sensory responses and to point out that inhibition plays an important role in sculpting the response properties of neurons in the cen- tral nervous system. O.I. Grfisser, K. Lehmann, H. Kornhuber and G. Baumgartner are among the col- leagues who witnessed Otto Creutzfeldt's years in Frei- burg and have remained his friends since then. The spirit of these years, which were not only decisive for individ- ual careers but also for the development of basic and clinical neurophysiology in Germany, can be appreciated by reading the obituaries which Otto Creutzfeldt wrote in this journal in 1986 for Richard Jung and then in 1991 for his close friend, Gfinther Baumgartner.

Otto Creutzfeldt understood his scientific efforts as an integral part of his life. His priorities were therefore the same for both domains. He was driven by genuine curiosity and strove for harmony, esthetic solutions and synthesis. He had a fine mastery of the flute, and one of his greatest pleasures was to join his friends, and in the last few years also his children, to play chamber music, preferably by composers of the Renaissance and Baroque periods. Competition and priority did not fig- ure in his vocabulary other than as attributes of fair sportsmanship. This is why his colleagues, coauthors, and later his pupils, were always at ease with him, grew beside him and, if time allowed, became his friends. Otto Creutzfeldt was strict and categorical when consistency, logical stringency and validation of results were at stake, but he was inexhaustibly generous and flexible when it came to personal matters, curricular worries, or the very private problems of those for whom he had assumed responsibility. Those who had the privilege of getting close to him know about his touching inability to say " n o " if a " y e s " was going to relieve someone's grief even if there were good reasons at an impersonal or political level for remaining firm.

Like most German post-doctorates who wished to begin an independent scientific career at the time, Otto Creutzfeldt went abroad. He worked for two years as a research anatomist at U C L A Medical School before moving to the Max-Planck-Institute for Psychiatry in Munich where he was to stay for nearly 10 years from 1962 to 1971. These were decisive years both for this institute and for all of us who had the chance to share part of the Munich era with him. In 1963, he obtained his degree in clinical neurophysiology from the Universi- ty of Munich, and in 1965 he was nominated scientific member and consultant neurologist of the Max-Planck

Society, and in 1968 head of the Department of Neuro- physiology at the MPI for Psychiatry. He was now in a position to formulate and realize his scientific concepts with great freedom, to create a permissive environment for cross-fertilization between basic and clinical re- search, and to form his own school of pupils. The then revolutionary intracellular recordings from neurons in the central nervous system were pioneered in Creutz- feldt's department. These were seminal studies on the relation between postsynaptic potentials in cortical neu- rons and EEG activity, on synaptic interactions between specific and non-specific thalamic inputs in the motor and the visual cortex, on synaptic transmission in the lateral geniculate nucleus and visual cortex, and on the role of postsynaptic inhibition in the formation of visual receptive fields. The names of l l .D. Lux, A.C. Nacimien- to, J.M. Fuster, S. Watanabe, M. Konichi, J. McIllwain, M. Ito and U. Kuhnt will remain associated with these pioneering studies and illustrate the then unusual inter- national breadth of Creutzfeldt's laboratory. It is still highly rewarding to consult these now classical papers, especially since there has been a renaissance of intracel- lular studies in vivo during the last few decades. How- ever, these investigations, which at the time were still extremely demanding, were only one, albeit important, facet of Creutzfeldt's approach. In parallel, he initiated a systematic search for neurophysiological correlates of visual perception, starting with a detailed analysis of receptive field properties in all visual centers known at that time and extending these studies to recordings from awake animals. H. Noda, H. Scheich, A. Herz, M. Stra- schill, B. Sakmann, R. Freeman, and H. W/issle were among the many colleagues and students who figured repeatedly as authors of papers in this field of visual neurophysiology. Despite these numerous, extremely successful and rewarding advances in basic research, however, Otto Creutzfeldt had not forgotten what Ri- chard Jung had imprinted in all of his pupils, that basic and clinical research should and can go hand in hand. The conditions in Munich were ideal because the clinic was under the same roof as the Department of Basic Research. Creutzfeldt thus developed a research unit for clinical neurophysiology, thereby allowing for optimal exchange of concepts and techniques between clinicians and neurobiologists. This proved to be an exceptionally fertile marriage, and the offspring were a respectable number of important studies on the applicability of com- puter-based analyses of EEG patterns. These approaches also prepared the ground for the development of algo- rithms to locate the dipoles responsible for evoked po- tentials, work that was pursued after Creutzfeldt left the institute in 1971.

The time period in Munich is already sufficiently re- mote to be seen as a historical epoch. However, it was extraordinarily influential and stands for an unmistak- able synthesis of fundamental and clinical research in the field of neurophysiology. It saw the initiation to neu- roscience of an impressive number of pupils who now have more than a dozen chairs in German universities and Max-Planck-Institutes. Creutzfeldt formed a school with a profound and lasting impact on German neuro- science.

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Despite, or perhaps even because of, this splendid career, Otto Creutzfeldt, then 44 years old, accepted the challenge to move to G6ttingen and create a new De- partment of Neurobiology in the newly founded Max- Planck-Institute for Biophysical Chemistry. Creutzfeldt followed the call of Manfred Eigen, the eminent biophys- icist, who then was famous not only for his measure- ments of ultrafast chemical reactions, but also for his theories on the molecular processes at the transition from matter to life. Here was an institute devoted to the analysis of elementary mechanisms at a level which, as far as living structures were concerned, was maximally distant from the level of complexity of higher nervous systems. The question of why Otto Creutzfeldt opted for this new challenge is intimately related to the ques- tion of why he had chosen to devote his life to the explo- ration of higher-order brains. Answers to these questions are bound to remain fragmentary, but Otto Creutzfeldt's oeuvre, especially where it goes beyond the publication of data in specialized journals, his famous monograph on the" cortex cerebri," an impressive collection of book chapters, and his conferences with interdisciplinary audi- ences are revealing. There is a passionate interest in philo- sophical problems associated with the subdivision of the world into levels of inanimate matter, living organ- isms, and mental phenomena. Thoroughly acquainted with the history of philosophical and theological con- cepts, endowed with rich clinical experience about the close relationship between the mental processes and neu- ronal substrates, and finally with his "hands-on" knowl- edge about brain mechanisms, he was in the rare position of being able to treat the mind-body problem competent- ly at both levels. The more he knew, the more he felt attracted and fascinated by the question of to what ex- tent the mental phenomena, perception of quality, con- sciousness, and emotions could be considered as emer- gent properties of an immensely complex aggregation of matter. A variant of this question poses also itself at the transition from inanimate to living structures; in both cases a continuous increase in the complexity of aggregated matter appears to support the emergence of new qualities. Here, then, is perhaps one of the moti- vations for Creutzfeld's move to G6ttingen, a vision of continuity, a longing for synthesis, a fascinating ability to understand the abstract, which allowed him to view together what seemed far apart to others.

The conditions in G6ttingen permitted substantial ex- pansion of the department, and Creutzfeldt used this opportunity to develop a permissive environment for a broad range of activities. Work in the acoustic and soma- tosensory system complemented the continuing studies of the visual system, the latter focusing more and more on mechanisms of color coding in the primate lateral geniculate and on principles of cortical organization.

Particularly revealing for Creutzfeldt's ability to sense quality and to grant freedom for individual development is the fact that it was in his department that B. Sakmann and E. Neher performed the experiments in the early 1980s which were honoured with the Nobel Prize for Medicine in 1991.

Despite his many responsibilities as head of a large department, as acting director for the entire institute for two terms, as editor in chief of Experimental Brain Research, as author of multiple contributions to the dis- cussion on ~ animal rights," Otto Creutzfeldt continued to have his own laboratory and to perform experiments. He had to collect the data himself to satisfy his curiosity. This is also why he chose to spend a sabbatical with the neurosurgeon, G. Ojemann, in Seattle and to realize his dream of recording from neurons in the cerebral cortex of humans and to establish direct relationships between cellular responses and cognitive behavior. This collaboration led to an impressive series of papers, the last of which are still in press.

It is touching to read through the last titles of his impressive publication list, which altogether comprises more than 200 experimental reports and more than 20 major philosophical contributions on the mind-matter problem and the ethical implications of the neuro- sciences. One realizes Otto Creutzfeldt's fidelity to the projects that he developed as a young scientist: his work with patients; intracellular studies in the cortex in vivo, this time with the whole-cell patch technique; single-unit studies in awake monkeys in search for a correlation between single-unit activity and perception; his last book, edited together with Sir John Eccles, The principles of design and operation of the brain. This book summa- rizes the material presented at a symposium at the Ponti- ficia Academia Scientiarium, to which Otto Creutzfeldt was nominated for membership in 1990.

Otto Creutzfeldt has been taken away too early and too abruptly. Throughout his life he generously and without hesitation gave of the most precious goods he could share, his time: time to listen, time to discuss, time to help, and time to take over yet another obliga- tion. In the years to come he would have had the chance to use some of this time for himself, to look back on his rich life, to enjoy the recognition of his achievements, the careers of his pupils, and the friends all over the world who were waiting for him and, above all, he was longing to find more time for his wonderful family, his wife Mary, his son Benjamin, and the three daughters Corinna, Ruth and Claire, who lost a loving, warm- hearted husband and father. The scientific community lost a pioneer of modern neurophysiology and many of us a dear friend.

W. Singer, Frankfurt/M.