Joseph Altman (1925–2016): A life in neurodevelopment

Joseph Altman at age 75. As a teenager in prewar Budapest, Altman spent many hours in the public library reading books about psychology, human behavior, psychoanalysis, and human brain structure. After World War II, he spent some time at the University of Heidelberg. Then his entire family immigrated to Australia, and he became a librarian at the University of New South Wales in Sydney Australia. He moved to New York with his first wife, Elizabeth Altman (an American citizen), and became a librarian in the School of Education in New York University. All this time he was continuing to read about human behavior, animal behavior, and brain structure and was looking for an opportunity to study brain and behavior on his own. Altman had the opportunity to become a neuroscientist while he was working as a tenured librarian in New York. He gave up that position and became a graduate student in psychology in the laboratory of Hans-Lukas Teuber, earning a PhD, in 1959 from New York University. That degree launched a successful career, first as a postdoctoral fellow at Columbia University, next at the Massachusetts Institute of Technology, and finally at Purdue University. From the early 1960s to 2016, he published many articles in peer-reviewed journals, books, monographs, and online free books that emphasized developmental processes in brain anatomy and function. The notes he took on animal behavior during his years as a librarian appeared in his first book (Altman, 1966). His many contributions from his own experiments are a legacy that sheds new light on the mechanisms of development at the tissue and cell level in both the central and the peripheral nervous systems. His first major discovery was that neurons are generated in adult rat and cat brains (Altman, 1962, 1963), especially in the dentate gyrus of the hippocampus (Fig. 1). This finding was nearly universally rejected by most of his colleagues, but Altman and his coworkers continued onward, adding more data to substantiate the claim (Altman and Das, 1965a; Bayer et al., 1982; Bayer, 1982). By the 1990s, other neuroscientists had confirmed that, all along, Altman and his coworkers were correct: adult neurogenesis did exist. Laboratories all over the world intensively study the phenomenon today. Altman recently received recognition for this discovery, The Prince of Asturias Award from the Crown Prince of Spain (now King Felipe) in 2011 and the International Prize for Biology from the Emperor of Japan and the Japan Society for the Promotion of Science in 2012. However, the discovery of adult neurogenesis was only the beginning. He was an enthusiastic and creative powerhouse of keen observation, well-designed experiments, and insightful interpretations. Many of his major contributions (the majority published in the Journal of Comparative Neurology) centered around an extensive study of postnatal neurogenesis in three areas of the brain, the olfactory bulb, the dentate gyrus in the hippocampus, and the cerebellar cortex (Altman and Das, 1965b, 1966). Altman was the first to describe a rostral migratory stream of stem cells and young olfactory neurons that extends from the anterior lateral ventricle all the way into the internal granular layer of the main olfactory bulb (Fig. 2; Altman, 1969b). Ten years later Rosselli-Austin and Altman (1979) showed that new microneurons are routinely generated in the adult olfactory bulb. Today, many laboratories are studying the rostral migratory stream and the stem cells inside it. Altman and his coworkers extensively studied the development of the hippocampus and its contributions to behavior. Today, these articles are often referenced and are considered classic contributions. Postnatal neurogenesis of the granule cells in the dentate gyrus was established in some overview articles (Altman and Das, 1965b, 1966, 1967) and was later quantified with progressively delayed cumulative 3H-thymidine labeling and low-level irradiation (Bayer and Altman, 1974, 1975). The Altman laboratory then sponsored an extensive analysis of neurogenesis in the entire hippocampal region (Bayer, 1980a) and its prenatal development (Bayer, 1980b). Altman revisited the hippocampus in 1990, analyzing the mosaic organization of the hippocampal neuroepithelium (Altman and Bayer, 1990a), the migration of pyramidal cells in Ammon's horn (Altman and Bayer 1990b), and the migration of dentate granule cell precursors (Altman and Bayer, 1990c). His final contribution appeared in Altman and Bayer (2014), documenting a large subgranular zone in the human hippocampus from age 1 month to 6 years. Several articles showed that, when the hippocampus was irradiated with schedules that eliminated 85% of the dentate granule cells, the animals behaved as if the entire hippocampus had been lesioned (Bayer et al., 1973; Brunner et al., 1974; Haggbloom et al., 1974; Gazzara and Altman, 1981). The irradiated animals also showed abnormalities in brain electrophysiology (Whishaw et al., 1978) and monoamine innervation (Moore et al., 1978). One of Altman's most complete contributions was a comprehensive analysis of the development of the cerebellum and the precerebellar nuclei in the brainstem. These classic articles were published between 1967 and 1987. There was a series on the normal postnatal development of the cerebellar cortex (Altman, 1969a, 1971, 1972a, 1972b, 1972c). Interspersed with these articles were many on the effects of low-level X-irradiation to eliminate all or some of the postnatal microneurons in the cerebellar cortex (Altman, 1973a, 1973b, 1976a, 1976b, 1976c; Altman and Anderson, 1969, 1972, 1973; Altman et al., 1967, 1968, 1969). Altman analyzed all of the findings and came up with one of the best explanations—backed up with experimental evidence—of cytoarchitecture in the cerebellar cortex and the planar orientation of Purkinje cell dendrites (Fig. 3; for review see Altman, 1982). Finally, there were many articles on embryonic development of the cerebellum (Altman and Bayer, 1977, 1978a, 1985a, 1985b, 1985c) and the precerebellar nuclei in the brainstem (Altman and Bayer, 1978b, 1987a, 1987b, 1987c, 1987d). During all this time, Altman also published some seminal articles on the maturation of motor behavior and the effects of interfering with cerebellar development (Wallace and Altman, 1970a, 1970b; Altman et al., 1971; Altman and Sudarshan, 1975; Altman and Bulut, 1976; Pellegrino and Altman, 1979; Gruner et al., 1980; Gruner and Altman, 1980), the effects of hypo- and hyperthyroidism (Nicholson and Altman, 1972a, 1972b, 1972c), and the effects of alcohol exposure (Bauer-Moffett and Altman, 1975), and he pioneered transplantation studies with G.D. Das (Das and Altman, 1972). Altman summarized all his findings on the cerebellum in a major book published in 1997 that is now out of print: Development of the cerebellar system in relation to its evolution, structure, and function. Throughout all of the prolific work on the olfactory bulb, hippocampus, and cerebellum, Altman continued to publish seminal articles on other topics. An extensive series appeared on the diencephalon (Wallace et al., 1969; Altman and Bayer, 1978c, 1978d, 1978e, 1979a, 1979b, 1979c, 1986, 1988a, 1988b, 1988c, 1989a, 1989b, 1989c; Bayer and Altman, 1987), the midbrain tectum (Teuber, 1960; Altman, 1961; Altman and Carpenter, 1961; Altman and Malis, 1962; Altman and Altman, 1962; Altman and Bayer, 1981b, 1981c), the brainstem (Altman and Bayer, 1980a, 1980b, 1980c, 1980d, 1981a), the spinal cord (Altman and Bayer, 1984, 2001), and the sensory ganglia (Altman and Bayer, 1982). In the late 1980s, Altman and Bayer launched a comprehensive study of neocortical development in the rat brain. The Altman laboratory was able to publish novel articles that documented the existence of specific layers in the intermediate zone visualized with 3H-thymidine autoradiography—Altman now called it the “stratified transitional field”—that are staging areas where migrating neurons pause to interact with incoming axons before continuing their migration to the cortical plate (Fig. 4; Altman and Bayer, 1990e; Bayer and Altman, 1991a, Chapter 7) and lateral migration in the embryonic neocortex (Bayer et al., 1991b). A few other articles were published (Bayer and Altman, 1990; Altman and Bayer, 1990d; Bayer, 1990a, 1990b; Bayer et al., 1991b), but the Altman lab decided to put the entire study into a book in which all the findings could be easily related to each other (Bayer and Altman, 1991a). Later, the Laboratory of Developmental Neurobiology, Inc., set up with personal finances, launched an extensive analysis of the developing human neocortex. Layers in the stratified transitional field are grossly visible in humans, and prominent regional differences exist between sensory and motor parts of the cortex (Figs. 5, 6; Altman and Bayer, 2002, 2015). On the whole though, stratification in the developing cortical intermediate zone and its importance in the mature connections of the cortex are still controversial. As with the studies on adult neurogenesis, Altman's discovery of stratification in the intermediate zone is awaiting “rediscovery” by researchers who will be more receptive in the future. Altman retired in 1995, and, because he remained as much a psychologist as a neuroscientist, he never lost interest in the relationships between mind, brain, and human behavior. Most of his time in retirement was spent writing Neural and mental evolution. origins of the human body, brain, behavior, consciousness, and culture. This free e-book summarizes his thoughts and scholarly readings of the last 70 years (download each chapter from brainmindevolution.org). He died as he was finishing the last chapter. After all, he grew up in a turbulent time and had first-hand experience of the dangers of discrimination, religious intolerance, and persecution. Adding to that rich personal history are his many years as a neuroscientist. Joseph Altman offers a unique and new perspective on the neurobiology of human nature that furthers our scientific perspective on human cultural history. Over the next few months, the last chapter of his book will be packaged and put online along with an enormous bibliography of all the scholarly articles he cites to back up his insights.