Japan Society for the Promotion of Science

28th Recipient (2012)

Recipient

The Committee on the International Prize for Biology of Japan Society
for the Promotion of Science awards the 2012 International Prize for Biology
in the field of " Neurobiology " to
Dr. Joseph Altman, Professor Emeritus, Purdue University, USA
On Friday, September 7, 2012, the Committee on the International Prize for Biology (chaired by Dr. Takashi Sugimura, Secretary General, The Japan Academy) of Japan Society for the Promotion of Science decided to present the 28th (2012) International Prize for Biology to Dr. Joseph Altman, Professor Emeritus , USA.
The field of specialization for the 28th Prize is " Neurobiology ".
Dr. Joseph Altman

Dr. Joseph Altman

Process of Selection

The Selection Committee, established by the Committee on the International Prize for Biology and chaired by Noriyuki Satoh, Professor, Okinawa Institute of Science and Technology, distributed a total of 1,157 recommendation forms to Japanese and foreign universities, research centers, academic associations, individual researchers, and international academic organizations involved in the subject field of biology, and received a total of 55 recommendations in response. As some of these recommendations named the same individuals, the actual number of individuals recommended was 52, from 17 countries. The Selection Committee met a total of four times and very carefully reviewed all the candidates. Ultimately, the Committee decided to recommend Dr. Joseph Altman as the recipient of the 28th International Prize for Biology.

Achievements Recognized by the Award

Dr. Altman proved that neurons continue to be generated in certain areas of the adult mammalian brain. In particular, he discovered persistent neurogenesis in the dentate gyrus of the hippocampus, a center for spatial perception, memory, and learning, and he predicted that this was involved in regulation of brain functions. Dr. Altman’s discoveries were reaffirmed thirty years later and are considered to have laid the foundations for the now rapidly developing research fields of adult neurogenesis and its clinical applications.

Until the second half of the twentieth century, it was believed that there were no neuron-generating stem cells in the adult mammalian brain, and that, once constructed, neural circuits could not be repaired after injury. In the 1960s Dr. Altman showed clearly, by labeling dividing cells with radioactive tracers and performing meticulous anatomical analyses, that neural progenitor cells capable of dividing did exist in the brains of adult rats and that neurogenesis persisted in some regions, including the dentate gyrus of the hippocampus and the lateral ventricles. Further, he investigated the effects of ablating newborn neurons by X-irradiation, thereby demonstrating their importance in the expression of higher brain functions such as learning. For many years the significance of these revolutionary findings was not fully appreciated, but in the 1990s the phenomenon of adult neurogenesis was rediscovered in many mammals, including humans, and the validity of Dr. Altman’s research became clear. He has published many superb books, including atlases of brain development.

Today, the study of adult neurogenesis is seeing explosive growth, and topics such as its relationship with neuropsychiatric disorders and its physiological significance in the expression of higher brain functions are popular research subjects. Clinical applications are also anticipated in the area of regenerative therapy for brain damage and disease. Dr. Altman’s distinguished work has created a field of neuroscience and contributed greatly to its advancement.

HONORS AND AWARDS

1959              Ph.D. New York University
1960              Postdoctoral Fellow, College of Physicians and Surgeons, Columbia University
1961              Assistant Professor, New York University
1962-1968  Associate Professor, Massachusetts Institute of Technology
1968-1995  Professor, Purdue University
1995-            Professor Emeritus, Purdue University

Research Acheivements

In many tissues of living organisms, such as the bone marrow, skin, and gastrointestinal epithelium, cells continue to divide and differentiate and are constantly replaced throughout life. With regard to the brain, the father of neuroanatomy, Santiago Ramón y Cajal, established the dogma that stem cells did not exist in its tissues and that neural circuits, once constructed, would not be regenerated after injury, and this was believed implicitly for over fifty years. Dr. Altman overturned this dogma when he discovered that neural progenitor cells capable of dividing do exist in certain regions of the brains of adult mammals and demonstrated the occurrence of persistent neurogenesis.

1) The Discovery of Neurogenesis in the Dentate Gyrus of the Hippocampus
Dr. Altman was the first to report the possibility of neurogenesis in the telencephalon of adult rats, based on an autoradiographic investigation which labeled dividing cells with radioactive thymidine (Altman 1962). He then published a series of detailed analyses based largely on light microscopy, demonstrating that adult neurogenesis occurs only in a particular layer (the subgranular zone) of the dentate gyrus of the hippocampus, and that granule cells, which are interneurons, continue to be supplied after birth (Altman 1963, Altman and Das 1965, Altman 1967). To determine the physiological significance of adult neurogenesis, he next investigated the effects of selective extirpation of newborn neurons by low doses of X-irradiation and showed that behavioral abnormalities such as learning disorders occurred. In the 1960s there were limits to the precision of irradiation technology, but Dr. Altman proposed the hypothesis, extremely revolutionary for its time, that higher functions of the mammalian brain such as memory and learning can be explained not merely by adaptive changes in existing circuits but by reorganization of the circuits themselves (Altman 1967, Gazzara and Altman 1981).

These findings were ignored for many years, despite being based on very reliable data obtained with correct techniques, but in the 1990s the introduction of highly versatile technology that superseded autoradiography led to the rediscovery, in a number of laboratories, of the fact that adult neurogenesis in the dentate gyrus of the hippocampus is a universal phenomenon in mammals including humans, and it was confirmed that this had already been largely proved, in its essentials, by Dr. Altman. Subsequent research has shown that neurogenesis in the dentate gyrus of the hippocampus changes under the influence of the living environment, psychotropic drugs, and pathological stresses such as ischemia. Elucidating how it is correlated with such things as the expression of higher brain functions and neuropsychiatric disorders is one of the most important tasks in neuroscience today. Dr. Altman’s achievements have earned the greatest respect as pathbreaking research that led to the opening up of a new domain of neuroscience.

2) The Discovery of Neurogenesis in the Subventricular Zone
Today it has become clear that neurogenesis in the adult brain of rodents is localized mainly in the dentate gyrus of the hippocampus and the subventricular zone . It was Dr. Altman, again, who discovered neurogenesis in the subventricular zone along the lateral walls of the lateral ventricles. Through longitudinal quantitative analysis using autoradiography, he detected that the new neurons move long distances together until they arrive at the olfactory bulb in the rostral tip of the brain , where they differentiate into interneurons, and he named this pathway of new neurons the rostral migratory stream (Altman and Das 1966, Altman 1969). Since its discovery by Dr. Altman, the number of papers on the rostral migratory stream published in international scientific journals is approaching 500. In rodent brains, it has been shown that the subventricular zone of the lateral ventricles has the most active adult neurogenesis and plays an important role in regulating and maintaining the functions of the olfactory nerve circuits. The pathological significance of adult neurogenesis as a source of supply of neurons in injured brains has also attracted attention, and many studies are being conducted on the control mechanisms of neurogenesis and cell migration. The merits of Dr. Altman’s achievements in discovering and accurately describing the phenomenon more than thirty years before the flowering of this field of research are beyond a shadow of a doubt.

3) Neurogenesis in Rats and Humans
Dr. Altman has published many papers and anatomy books presenting detailed analyses of cell lineage and differentiation in each region of the developing brain, mainly in rats. In particular, his detailed descriptions of the behavior and fine structure of cells of all types in the formation of the cerebellar cortex, based on light and electron microscopy, are to this day frequently cited in research papers. Further, his unsurpassed developmental atlases of the rat and human brains are bestsellers consulted by many scientists. In these ways, Dr. Altman has made enormous contributions to the advancement of knowledge of the neuroanatomy of the developing brain.

The discovery of adult neurogenesis made it clear that neural circuits in the mature brain, previously believed to be fixed and unrepairable, could be rebuilt at the structural level. Many researchers are concentrating on the physiological and pathological significance of the control of neurogenesis and its failure; at the same time, the possibility is emerging of regenerative therapies for organically and functionally impaired nervous systems through the manipulation of neurogenesis, and this is currently evolving into an area of large-scale, cross-disciplinary research and development of technology. Dr. Altman’s groundbreaking work was held back and its true value long overlooked due to a doctrine that was deep-rooted and pervasive at the time, but on its rediscovery in the 1990s its importance and reliability were recognized with astonishment and he was hailed as the pioneer of this field. His distinguished achievements laid the foundations of a new field of medicine and bioscience which brings together neuroscience, stem cell biology, psychiatry, and neurology, and they have contributed greatly to its advancement.

Representative Publications

  1. Altman J. (1962) Are new neurons formed in the brains of adult mammals? Science, 135:1127-1128.
  2. Altman J. (1963) Autoradiographic investigation of cell proliferation in the brains of rats and cats. Anat Rec, 145:573-591.
  3. Altman J., and G. D. Das (1965) Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats. J Comp Neurol, 124:319-336.
  4. Altman J., and G. D. Das (1966) Autoradiographic and histological studies of postnatal neurogenesis. J Comp Neurol, 126:337-390.
  5. Altman J (1967) Postnatal growth and differentiation of the mammalian brain, with implications for a morphological theory of memory. In: Quarton GC, Melnechuck T, Schmitt FO (eds) The neurosciences, a study program, pp 723-743. Rockefeller University Press, New York
  6. Altman J (1969) Autoradiographic and histological studies of postnatal neurogenesis IV. Cell proliferation and migration in the anterior forebrain, with special reference to persisting neurogenesis in the olfactory bulb. J Comp Neurol 137:433-458
  7. Altman, J (1970) Postnatal neurogenesis and the problem of neural plasticity. In: Himwich, W. A. (ed) Developmental Neurobiology, pp 195-237. Springfield IL: Thomas.
  8. Bayer, S. A., R. L. Brunner, R. Hine and J. Altman (1973) Behavioural effects of interference with the postnatal acquisition of hippocampal granule cells. Nature, New Biol, 242:222-224.
  9. Bayer, S. A., and J. Altman (1974) Hippocampal development in the rat: Cytogenesis and morphogenesis examined with autoradiography and low-level X irradiation. J. Comp. Neurol, 158:55-80.
  10. Altman, J., and S. A. Bayer (1975) Postnatal development of the hippocampal dentate gyrus under normal and experimental conditions. In: R. L. Isaacson and K. J. Pribram (eds) The Hippocampus: A Comprehensive Treatise, Vol. 1, pp. 95-122. New York: Plenum Press.
  11. Bayer, S. A., and J. Altman (1975) Radiation induced interference with postnatal hippocampal cytogenesis in rats and its long term effects on the acquisition of neurons and glia. J. Comp. Neurol, 163:1-20.
  12. Bayer, S. A., and J. Altman (1975) The effects of X irradiation on the postnatally-forming granule cell populations in the olfactory bulb, hippocampus, and cerebellum of the rat. Exp. Neurol, 48:167-174.
  13. Gazzara R. A., and J. Altman (1981) Early postnatal X-irradiation of the hippocampus and discrimination learning in adult rats. J Comp Physiol Psychol, 95:484-495
  14. Altman, J., and S. A. Bayer. (1990) Mosaic organization of the hippocampal neuroepithelium and the multiple germinal sources of dentate granule cells. J. Comp. Neurol, 301:325 342.
  15. Altman, J., and S. A. Bayer. (1990) The prolonged sojourn of developing pyramidal cells in the intermediate zone of the hippocampus and their settling in the stratum pyramidale. J. Comp. Neurol, 301:343 364.
  16. Altman, J., and S. A. Bayer. (1990) The migration and distribution of two populations of hippocampal granule cell precursors during the perinatal and postnatal periods. J. Comp. Neurol, 301:365 381.
  17. Altman, J., and S. A. Bayer (2002) Regional differences in the stratified transitional field and the honeycomb matrix of the developing human cerebral cortex. J. Neurocytol, 31:613-32.
  18. Altman, J. (2011) The discovery of adult neurogenesis. In: T. Seki et al. (eds) Neurogenesis in the Adult Brain. Vol. 1. Berlin: Springer-Verlag.
  19. Altman, J., and S. A. Bayer (1984) Development of the Rat Spinal Cord. Adv. Anat. Embryol. Cell Biol., 85:1-168. Berlin: Springer-Verlag.
  20. Altman, J., and S. A. Bayer (1986) The Development of the Rat Hypothalamus. Adv. Anat. Embryol. Cell Biol., 100:1-178 Berlin: Springer-Verlag.
  21. Bayer, S. A., and J. Altman (1991) Neocortical Development. New York: Raven Press.
  22. Altman, J., and S. A. Bayer (1995) An Atlas of the Developing Rat Brain. Boca Raton, Florida: CRC Press.
  23. Altman, J., and S. A. Bayer (1997) Development of the Cerebellar System In Relation to Its Evolution, Structure, and Functions. Boca Raton, Florida: CRC Press.
  24. Altman, J. and S. A. Bayer (2001) Development of the Human Spinal Cord. An Interpretation Based on Experimental Studies in Animals. New York: Oxford University Press.
  25. Bayer, S. A., and J. Altman (2002-2007) Atlas of Human Central Nervous System Development, Volumes 1-5. Boca Raton, Florida: CRC Press.