On 2 October 2020, we lost a great neuroscientist, Gerta Vrbová, who not only shared her original ideas and the scientific validation of many of them, but also her personal experience of the Holocaust and its aftermath in Czechoslovakia. She will be remembered by physiologists and neuroscientists for her role in recognizing and proving the key role of neuromuscular activity in the development of the neuromuscular system and in the control of skeletal muscle properties throughout life. Further, she applied her findings to the understanding of neuromuscular disorders. She died in London at the age of 93, having lived a life in which she always saw the glass as half full and not half empty. We mourn her loss. Gerta Sidonová, the surviving child of two, was born in Trnava, Slovakia on the 28 November 1926. After the German takeover of Czechoslovakia, Gerta's formal education ended as she and her fellow Jewish students were barred from the schools they were attending. In 1942 she and her parents escaped the first deportations to concentration camps by walking to Hungary where they stayed safe with relatives until 1944 when they returned to Czechoslovakia. Upon her return and subsequent detention, she escaped from the Gestapo, losing both parents, walked back to Hungary and, finally, returned to her country in 1945. Despite these hardships, Gerta completed her school education in 3 months and was one of ∼4000 students to receive admission to the medical school at the newly opened Charles University in Prague. Only a small proportion graduated in 1950, amongst them Gerta. Navigating through difficult times formed the backdrop for Gerta's original thinking and ideas that characterized her scientific career. In November 1949, Gerta married Dr Rudolf Vrba, a survivor of the Holocaust and one of only five to have escaped from Auschwitz. This was 6 months after her fascination with the nervous system led her to the entrance of the Institute for Brain Research on the campus of Charles University. Opening a door to a laboratory, she was welcomed by Dr Ernest Gutmann, himself a Czech survivor of the Holocaust, who would foster and collaborate with her over the next 8 years. Professor Gutmann's interest in denervated and reinnervated muscle dated back to his war-time research in England. His research was carried out, in part, with J. Z. Young at University College London in the Anatomy Department, which Gerta would later join as a reader in 1976. Gutmann and Gerta performed many experiments in a laboratory at the Physiological Department of the Biological Institute of the Academy of Sciences in Prague. With little equipment besides a balance to weigh muscles, along with an oven, these experiments were the foundation of her continued work on denervated muscle and muscle properties when she arrived in London and later, in 1967, when she established her own laboratory in the Physiology Department at the University of Birmingham. En route to England to marry Dr Sidney Hilton in London, Gerta spent a year in the laboratory of Professor Fritz Buchthal in Copenhagen. Her journey there along with her two young children, Helena and Zuza, involved crossing the mountains to escape from Czechoslovakia en route to Poland and from there to Copenhagen by plane. Using the original electrophysiological recording techniques of Buchthal, Gerta noted the different patterns of activity of motor units in slow- and fast-twitch muscles and thereby derived her original idea that it was these patterns that determined muscle properties. Once in London, she was successful in obtaining a research grant from the Medical Research Council with which she initiated her studies at Kings College London on the role of neuromuscular activity in controlling skeletal muscle properties. She continued with these ground-breaking studies in Birmingham when Hilton accepted the position of Chairman of the Department of Physiology. Skeletal muscles differ in their colour with both the blood supply as well as their content of both myoglobin and mitochondria being higher and lower in ‘red’ and ‘white’ muscles, respectively. She noted that the speed of their contractions was well matched to the firing patterns of their motoneurons, with the ‘red’ muscles slow-contracting and generating tetanic contractions at low frequencies and the ‘white’ muscles fast-contracting, generating tetanic forces at higher frequencies (Vrbová, 1963). Using an implanted electrical stimulator designed and constructed by Stanley Salmons in the Anatomy Department, Gerta demonstrated that the contractile speed of the fast ‘white’ muscle was transformed to that of slow ‘red’ muscle by imposing the slow firing pattern (Salmons & Vrbová, 1969). These critical experiments, along with later collaborative experiments with Professor Dirk Pette in Konstanz, her Czech colleague Olga Hudlicka, and graduate students including Maggie Brown and Mary Cotter, established that the pattern of neuromuscular activity determines the biochemical, anatomical and physiological properties of skeletal muscles (Cotter et al. 1973; Pette et al. 1973, 1976; Brown et al. 1976; Hudlicka et al. 1977; Kwong and Vrbová, 1981; reviewed by Pette & Vrbová, 1985, 1992, 2017). Rosemary Jones and Tessa Gordon were to be her first graduate students in her laboratory in the Physiology Department. Gerta had rejected the view that trophic substances regulated muscle properties and her research work demonstrated that neural activity regulated these properties. Likewise, Gerta argued against the published view that denervation hypersensitivity of muscles to acetylcholine results from the loss of trophic substance(s) from the motor nerve, demonstrating that it is the loss of neuromuscular activity that accounts for the development and persistence of the hypersensitivity (Jones & Vrbová, 1975). In line with these arguments for neuromuscular activity controlling the restriction of acetylcholine receptors to the endplate zone, a result confirmed by many later studies, Gerta used the same argument to account for the single and multiple endplates on fast-twitch muscles and slow-tonic muscles, respectively, in the chick: the greater and lesser quantal contents of the nerves contacting the developing fast and slow muscles depolarize the membranes to evoke action potentials or not, respectively. As a result, fast-twitch muscles sustain only one neuromuscular junction whilst slow-twitch and tonic muscles have multiple endplates which are separated by the distance of the decay of the neurally induced membrane depolarization (Gordon et al. 1976). In 1976, Gerta moved to London with her two younger children, Caroline and Peter, accepting the position as Reader in the Department of Anatomy and Developmental Neurobiology at University College London. She continued work initiated in Birmingham on the development of muscle properties (Gordon et al. 1974, 1977a,b; Gordon & Vrbová, 1975a,b) but her main foci were (1) the basis for the critical period of the susceptibility of immature motoneurons to cell death prior to the maturation of synaptic transmission between the nerves and their muscle fibres, (2) the role of activity in establishing the pattern of muscle innervation during neonatal development, and (3) the feasibility of inserting embryonic ventral spinal cord into adult lumbar spinal cord to populate the cord after neonatal motoneuronal depletion and, in turn, to reinnervate denervated muscle. These animal studies were conducted with her students, postdoctoral fellows and research associates. These included Maggie Lowrie, Angela Connold, Linda Greensmith, Roberto Naverrete, Antal Nógrádi, Uma Shahani and Katarzyna Sieradzan. Her association with neurologists, Victor Dubowitz in London, Milan Dimitrijević in Belgrade and Irena Hausmanova-Petruzewicz in Warsaw, built on her own medical background translating experimental data into potential treatments for childhood genetic diseases of muscular dystrophy and spinal muscular atrophy (Luthert et al. 1980; Scott et al. 1986; Lenman et al. 1989; Vrbová, Hausmanowa-Petrusewicz & Vrbová, 2005; Vrbová & Sławińska, 2018). Gerta's interest in childhood diseases spurred her research into the developmental maturation of the neuromuscular system and the critical period of motoneurone survival in the first days of life in rats when nerve injury results in death of the neonatal motoneurons (Krisnan et al. 1985). Gerta's experimental approach was to use pharmacological means to reduce the activity of injured neonatal motoneurons to promote their premature maturation (Mentis et al. 1993; Greensmith & Vrbová, 1996). This approach demonstrated the reliance for survival of the neuromuscular system on the normal course of maturation of electrophysiological, biochemical and anatomical properties concomitant with the progressive increase in daily activity (Vrbová et al. 1985; Naverrete & Vrbová, 1993). This was noted in observations of neonatal rats raising their bodies and beginning to walk as the activation of their hindlimbs increased progressively. The anatomical properties included the establishment of the normal innervation of several muscle fibres by one motoneuron, replacing the neonatal polyneuronal innervation in which several motoneurons innervate each muscle fibre (O'Brian et al. 1978, 1980; Duxson & Vrbová, 1985; Connold et al. 1986). These studies inspired Gerta and Katarzyna Sieradzan to insert the ventral horn of embryonic spinal cord or the motoneurons themselves into the adult spinal cord in which motoneurons had been depleted by neonatal nerve injury. Results revealed that neonatal motoneurons extended axons and successfully reinnervated denervated muscles. The success of Gerta's scientific career is reflected by more than 270 scientific papers that she published over a 70-year period and by her inspiration and mentorship. Gerta's overall view was that activity is a crucial element of the working of excitable cells including neurons and muscles. This view had obvious practical applications that include the use of electrical stimulators in rehabilitation medicine to activate paralysed muscles and, in turn, restore limb movements. Many of her students, postdoctoral fellows, visiting scientists and collaborating scientists now have independent and successful research careers, making major contributions to the fields of peripheral nerve injury and motoneuron diseases of amyotrophic lateral sclerosis and spinal muscular atrophy (Gordon in Canada, Greensmith in London), Parkinson's, Huntington's and Pompe diseases, and epilepsy (Sieradzan in Bristol), multiple sclerosis (Jones in Bristol) and ventral root avulsion (Nógrádi in Szeged), and in the field of locomotion (Sławińska in Warsaw). Gerta's collaborator Dirk Pette in Germany published extensively on the plasticity of the molecular properties of skeletal muscle in response to electrical stimulation. Her colleague and the co-author of this obituary, Ugo Carraro in Italy, demonstrated that direct electrical stimulation modified the properties of denervated muscles (Carraro, 2021). Ugo met Gerta in 1980 during her visit to Professor Aloisi where he was his last young fellow. He shared his findings that hemi-diaphragms with a mixture of fibre types expressed only fast-type myosin light chains after long-term denervation (Carraro et al. 1979), a finding in agreement with Gerta's findings of slow-twitch muscles becoming fast-contracting when deprived of their continuous activity (Vrbová 1963; Salmons & Vrbová, 1969). Ugo maintained his contact with Gerta, Gerta attending his regular meetings of PaduaMuscleDays and always contributing to discussions of the translational research for skeletal muscle biology, including rehabilitation. Gerta's medical background always informed her work and her approach to scientific questions. Her characteristic approach to neuroscientific discovery was one of quick assimilation of knowledge from scientific talks at seminars and meetings and from informal contact with fellow and visiting scientists. She had the ability to see the relevance of scientific work to medical applications, she read the literature extensively, and she developed original experimental designs to test novel hypotheses. Her thoughts and questions were always penetrating and insightful, such that her contributions at meetings were sought by many. Her interactions with students and colleagues were inspiring at both scientific and personal levels, and she remained in contact with them over many years. Tessa Gordon and Gerta remained in regular mail, phone and personal contact after Tessa left for the University of Alberta in Canada and Gerta moved to University College London in 1976. They exchanged scientific ideas and data whilst retaining their mutual interest in their families and the books that they both enjoyed. Gerta travelled to Alberta and Tessa to London, sharing their lives and interests to the end of Gerta's life. Gerta, on a holiday in Wales in July 2015 with Rosemary, her husband, David, and Tessa, reminisced over her love of the Gower coast, which she visited over many years. Gerta was a sensitive, intellectual, well-read and well-rounded person who loved and was loved by her children, friends, trainees and colleagues. Her scientific and personal contributions will be remembered and followed for many years to come. We have her published scientific papers and reviews to continue her work. On a personal level, we have her experiences of the Holocaust and the Second World War, which she set down in her two books authored in her eighties. Her first book, Trust and Deceit, provides an account of her personal tribulations of returning to the antisemitism of her hometown of Trnava, her delight in coming to Prague, her medical studies, life with her first husband, Rudolf Vrba, and her discovery and love of research in Professor Gutmann's laboratory. In addition, she describes her enthusiasm in joining the Communist Party followed by ensuing disillusionment with the communist regime as she witnessed many intellectuals, including several of her professors, being murdered or sent to work in uranium mines. None. Both authors have read and approved the final version of this manuscript and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All persons designated as authors qualify for authorship, and all those who qualify for authorship are listed. None.