Recipient

The Committee on the International Prize for Biology of Japan Society for the
Promotion of Science awards
the 2011 International Prize for Biology in the field of " Developmental Biology "
to
Dr. Eric Harris Davidson
Norman Chandler Professor of Cell Biology, Division of Biology
California Institute of Technology, USA.

Process of Selection

  The Selection Committee, established by the Committee on the International Prize for Biology and chaired by Masamitsu Wada, Professor of Graduate School of Science, Kyushu University, distributed a total of 1,977 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 70recommendations in response. As some of these recommendations named the same individuals, the actual number of individuals recommended was 47, from 16 countries. The Selection Committee met a total of four times and very carefully reviewed all the candidates. Ultimately, the Committee decided to recommend Dr. Eric Harris Davidson as the recipient of the 27th International Prize for Biology.

Achievements Recognized by the Award

 

  In studying the molecular mechanisms of animal development using the sea urchin, Dr. Davidson proposed “gene regulatory networks” (GRNs) as a theoretical concept and went on to prove their existence experimentally. For over 40 years, he has devoted his career to solving the key issues in developmental biology, which include the role of genes in development, how genes are turned on and off, gene expression cascades, genomic logic, and the mechanisms of development and evolution. In each of these areas, he has formulated theoretical explanations based on GRNs and successfully demonstrated their validity in the laboratory. Dr. Davidson has brought to these studies a global view of animal development which has yielded insights ahead of their time, together with an exacting and exhaustive experimental technique and an ability to rethink paradigms; this approach has led to truly exceptional research achievements.

  The developmental process—the formation of a multi-celled adult from the single-celled fertilized egg through morphogenesis and cell differentiation—is a dynamic biological phenomenon that unfolds in four dimensions. In the late 1960s, when the molecular mechanisms of development were little understood, Dr. Davidson and Dr. Roy Britten postulated in their paper “Gene regulation for higher cells: A theory” that controlled activation of genes would be needed for cells containing identical genomes to become differentiated; that what underlies the developmental process is the continuous interaction of genes resulting in control of their expression; and, moreover, that changes in these regulatory systems play a part in animal evolution. With characteristic energy, Dr. Davidson later pursued a series of experiments to verify these ideas, applying the tools of molecular biology to a model developmental system, the sea urchin embryo. He demonstrated the existence of GRNs in the sea urchin by investigating the specification of the endomesoderm and skeletogenic mesenchyme territories, and by analyzing the cis-regulatory elements that control gene expression when cells in the same territory differentiate. He also headed the project to sequence the sea urchin genome, and has succeeded in identifying the control mechanisms of gene expression on a genome-wide scale. These studies have brought about a synthesis among developmental biology, systems biology, and genomics.

  To establish the regulatory mechanisms that govern gene expression is a central task not only for developmental biologists but for scientists in fields ranging from genetics, molecular biology, cell biology, neurobiology and immunology. Today, Dr. Davidson’s concept of gene regulatory networks has been validated in every one of these fields. His research achievements, which are also informed by genomics and systems biology, have contributed greatly to the advancement of the biological sciences as a whole.

Ceremony and Commemorative Symposium

  The award ceremony was held on 28 November 2011 at the Japan Academy (7-32 Ueno Koen, Taito-ku, Tokyo). His Imperial Highness the Crown Prince representing His Majesty the Emperor attended the ceremony and the reception in honor of the award recipient. Her Majesty the Empress also participated in the reception and passed on the Emperor’s congratulations to the recipient.

  To commemorate the award to Dr. Eric Harris Davidson, the 27th International Prize for Biology Commemorative Symposium on Developmental Biology was held on 30 November and 1 December 2011 in Kyoto.

DATE OF BIRTH :	April 13, 1937
NATIONALITY :	United States of America
PRESENT POSITION :	Norman Chandler Professor of Cell Biology Division of Biology California Institute of Technology, USA

HONORS AND AWARDS

1963		PhD. Rockefeller University
1963-1965		Research Associate, Rockefeller University
1965-1971		Assistant Professor, Rockefeller University
1971-1974		Associate Professor, California Institute of Technology
1974-1981		Professor, California Institute of Technology
1981-present		Norman Chandler Professor, California Institute of Technology

Research Acheivements

  Animal development, the process by which a single-celled fertilized egg becomes a multi-celled adult through division, morphogenesis, and cell differentiation, is one of the most dynamic of all biological phenomena, and one that unfolds in four dimensions. For over 40 years, Dr. Davidson has devoted his career to solving the key issues in developmental biology, which include the role of genes in development, how genes are turned on and off, gene expression cascades, genomic logic, and the mechanisms of development and evolution. He has utilized the concept of the “gene regulatory network” (GRN) to integrate the results of this work.

1) Early Theoretical Studies
  Embryology, the search for the mechanisms of individual development in animals, emerged as a science in the mid-nineteenth century. It has been a largely experimental field, with many key discoveries being made in the laboratory. Some embryologists have also been theorists, but it is relatively rare for breakthroughs in this field to result from a marriage of theory and experiment. In 1968, at the age of 31, Dr. Davidson published the book Gene Activity in Early Development, in which he theorized that gene activation is the key mechanism underlying developmental cell differentiation and morphogenesis.

  In 1969, Dr. Davidson and Dr. Roy Britten published a paper entitled “Gene regulation for higher cells: A theory,” in which they argued that if higher cells having the same genome are to develop differentially into cells with diverse forms and functions, there would need, in principle, to be regulation of gene expression under genomic control together with interaction among the genes. The study amounted to a theoretical prediction of the molecular mechanisms of development, in an overview which took in almost all mechanisms of developmental gene regulation, including now-familiar areas such as differential gene expression in cell differentiation, the control of downstream genes by sensor, integrator, and receptor genes and the formation of gene batteries when these elements combine in large numbers. At a time when the molecular mechanisms of development were little understood, this represented a revolutionary theoretical breakthrough, and the paper gained lasting renown among geneticists and molecular biologists as well as developmental biologists.

  The theoretical discussion was also prescient in many other ways, pointing toward the importance of quantitative changes in the expression state of genes, the approach that has come to be known as systems biology, and genomic regulation of gene expression, to name but a few areas.

2) Research on Gene Regulatory Mechanisms in Sea Urchin Development
  Dr. Davidson later focused on intensive experimental research, seeking evidence of how gene expression is regulated so that animal development proceeds as programmed, both temporally and spatially.

  The sea urchin has long been used in embryology, for reasons including the ample availability of eggs at all seasons of the year and the ease of manipulation of the embryo. Taking full advantage of these features, Dr. Davidson introduced molecular biological techniques and succeeded in making the sea urchin a model system for analysis of the mechanisms of developmental gene regulation. He began by investigating cell lineage and showing that early embryonic cells become specified into three prospective territories—the ectoderm, the skeletogenic or primary mesenchyme, and the endomesoderm—which then differentiate into, respectively, the oral and aboral ectoderm, the spicules of the larval skeleton, and the mesoderm, veg1 endoderm, and endoderm. He then went on to isolate and identify cell differentiation–specific genes in each of these territories, such as the endoderm-specific gene Endo16 and the skeletogenic lineage–specific gene Sm50. He further made an in-depth analysis of the cis-regulatory elements that control expression of these genes and showed their relationship to gene regulatory factors.

  When the developmental roles of transcription factor genes and cell signaling molecule genes were established in Drosophila and other organisms, Dr. Davidson investigated how these genes control the expression and functions of differentiation genes, shedding light on their interactions as a result of his thorough work.

3) Theoretical Reformulation and Experimental Proof of Gene Regulatory Networks
  His elucidation of the regulatory mechanisms governing the expression of individual genes led Dr. Davidson to a theoretical reformulation, that is, to characterize as the essential aspect of developmental genes the fact that they act in gene cascades and networks (gene regulatory networks, or GRNs). He then authenticated this in the laboratory by analyzing the expression mechanisms of numerous genes. By around 2006, he had established that over 30 genes interact in the GRN associated with the process from skeletogenic mesenchyme specification to skeletogenic cell differentiation, and recently he found that over 40 genes are involved in the GRN associated with the process from specification to cell differentiation of the endoderm. In addition, Dr. Davidson spearheaded the sequencing of the sea urchin genome by a consortium which published its results in 2006; thanks to this genome information, research on gene regulatory mechanisms in the sea urchin is making still further progress.

  Dr. Davidson’s 2006 book The Regulatory Genome: Gene Regulatory Networks in Development and Evolution could be called a grand synthesis of his work to date. In it he makes the case, based on the evidence of many gene regulatory mechanisms, that GRNs explain the logic of development in a wide range of animal species. In a sense, the book can be seen as presenting an embryological theory complete in itself.

4) Ramifications of GRN Theory
  Dr. Davidson is also well-versed in paleontology and has done groundbreaking research on the molecular embryological mechanisms leading to animal evolution. Here, again, his work has a theoretical dimension. He suggests that each of the components that make up GRNs (such as differentiation gene batteries, plug-ins, input/output linkages, and kernels) is involved at a different stage of the evolutionary process, with changes in differentiation gene batteries acting at the species level, changes in plug-ins and input/output linkages acting at the class, order, or family level, and changes in kernels acting at or above the phylum level. Many studies are currently under way to verify these hypotheses.

  Thus, Dr. Davidson has been formulating novel theories of gene expression and its regulation since the late 1960s when the molecular mechanisms of development were as yet little understood, and he has demonstrated the validity of these theories with a very substantial body of research using the sea urchin. We owe the concept of gene regulatory networks to Dr. Davidson’s global view of animal development, which has yielded insights ahead of their time, together with his exacting and exhaustive experimental technique and his ability to rethink paradigms, an approach which has led him to truly exceptional research achievements.

  To establish the regulatory mechanisms that govern gene expression is a central task not only for developmental biologists but for scientists in fields ranging from molecular biology and cell biology to neurobiology and immunology. Today, Dr. Davidson’s concept of gene regulatory networks has been validated in every one of these fields. His research achievements, which are also informed by genomics and systems biology, have contributed greatly to the advancement of the biological sciences as a whole.

Representative Publications:

1. Davidson, E. H., Allfrey, V. G. and Mirsky, A. E. 1963. Gene expression in differentiated cells. Proc. Natl Acad. Sci. USA 49, 53-60.
2. Davidson, E. H., Haslett, G. W., Finney, R. J., Allfrey, V. G. and Mirsky, A. E. 1965. Evidence for prelocalization of cytoplasmic factors affecting gene activation in early embryogenesis. Proc. Natl Acad. Sci. USA 54, 696-704.
3. Britten, R. J. and Davidson, E. H. 1969. Gene regulation for higher cells: A theory. Science 165, 349-358.
4. Galau, G. A., Britten, R. J. and Davidson, E. H. 1974. A measurement of the sequence complexity of polysomal messenger RNA in sea urchin embryos. Cell 2, 9-21.
5. Hough, B. R., Smith, M. J., Britten, R. J. and Davidson, E. H. 1975.　Sequence complexity of heterogeneous nuclear RNA in sea urchin embryos. Cell 5, 291-299.
6. Britten, R. J. and Davidson, E. H. 1976.　Studies on nucleic acid reassociation kinetics. Empirical equations describing reassociation. Proc. Natl Acad. Sci. USA 73, 415-419.
7. Davidson, E. H., Klein, W. H. and Britten, R. J. 1977. Sequence organization in animal DNA and a speculation on hnRNA as a coordinate regulatory transcript. Dev. Biol. 55, 69-84.
8. Lee, A. S., Britten, R. J. and Davidson, E. H. 1977. Interspersion of short repetitive sequences studied in cloned sea urchin DNA fragments. Science 196, 189-192.
9. Scheller, R. H., Costantini, F. D., Kozlowski, M. R., Britten, R. J. and Davidson, E.H. 1978. Specific representation of cloned interspersed repetitive DNA sequences in sea urchin RNAs. Cell 15, 189-203.
10. Ernst, S. G., Britten, R. J. and Davidson, E. H. 1979. Distinct single-copy sequence sets in sea urchin nuclear RNAs. Proc. Natl Acad. Sci. USA 76, 2209-2212.
11. Davidson, E. H. and Britten, R. J. 1979. Regulation of gene expression: Possible role of repetitive sequences. Science 204, 1052-1059.
12. Moore, G. P., Costantini, F. D., Posakony, J. W., Davidson, E. H. and Britten, R. J. 1980. Evolutionary conservation of repetitive sequence expression in sea urchin egg RNA's. Science 208, 1046-1048.
13. Costantini, F. D., Britten, R. J. and Davidson, E. H. 1980. Message sequences and short repetitive sequences are interspersed in sea urchin egg poly(A)+ RNAs. Nature 287, 111-117.
14. Davidson, E. H. and Posakony, J. W. 1982. Repetitive sequence transcripts in development. Nature 297, 633-635.
15. Davidson, E. H., Hough-Evans, B. R. and Britten, R. J. 1982. Molecular biology of the sea urchin embryo. Science 217, 17-26.
16. Davidson, E. H., Jacobs, H. T. and Britten, R. J. 1983. Very short repetitive sequences and the coordinate induction of genes. Nature 301, 468-470.
17. Angerer, R. C. and Davidson, E. H. 1984. Molecular indices of cell lineage specification in the sea urchin embryo. Science 226, 1153-1160.
18. Flytzanis, C. N., Britten, R. J. and Davidson, E. H. 1987. Ontogenic activation of a fusion gene introduced into sea urchin eggs. Proc. Natl Acad. Sci. USA 84, 151-155.
19. Cameron, R. A., Hough-Evans, B. R., Britten, R. J. and Davidson, E. H. 1987. Lineage and fate of each blastomere of the eight-cell sea urchin embryo. Genes & Dev. 1, 75-85.
20. Katula, K. S., Hough-Evans, B. R., Britten, R. J. and Davidson, E. H. 1987. Ontogenic expression of a CyI:actin fusion gene injected into sea urchin eggs. Development 101, 437-447.
21. Calzone, F. J., Thézé, N., Thiebaud, P., Hill, R. L., Britten, R. J. and Davidson, E. H. 1988. Developmental appearance of factors that bind specifically to cis-regulatory sequences of a gene expressed in the sea urchin embryo. Genes & Dev. 2, 1074-1088.
22. Sucov, H. M., Hough-Evans, B. R., Franks, R. R., Britten, R. J. and Davidson, E. H. 1988. A regulatory domain that directs lineage-specific expression of a skeletal matrix protein gene in the sea urchin embryo. Genes & Dev. 2, 1238-1250.
23. Davidson, E. H. 1989. Lineage-specific gene expression and the regulative capacities of the sea urchin embryo: A proposed mechanism. Development 105, 421-445.
24. Davidson, E. H. 1990. How embryos work: A comparative view of diverse modes of cell fate specification. Development 108, 365-389.
25. Thiebaud, P., Goodstein, M., Calzone, F. J., Thézé, N., Britten, R. J. and Davidson, E. H. 1990. Intersecting batteries of differentially expressed genes in the sea urchin embryo. Genes & Dev. 4, 1999-2010.
26. Cameron, R. A., Fraser, S. E., Britten, R. J. and Davidson, E. H. 1991. Macromere cell fates during sea urchin development. Development 113, 1085-1092.
27. Ransick, A. and Davidson, E. H. 1993. A complete second gut induced by transplanted micromeres in the sea urchin embryo. Science 259, 1134-1138.
28. Davidson, E. H. 1994. Molecular biology of embryonic development: How far have we come in the last ten years? BioEssays 16, 603-615.
29. Davidson, E. H., Peterson, K. and Cameron, R. A. 1995. Origin of the adult bilaterian body plans: Evolution of developmental regulatory mechanisms. Science 270, 1319-1325.
30. Davidson, E. H. 1996. Biology of developmental transcription control. Proc. Natl Acad. Sci. USA 93, 9307-9308.
31. Davidson, E. H. 1997. Insights from the echinoderms. Nature 389, 679-680.
32. Yuh, C.-H., Bolouri, H. and Davidson, E. H. 1998. Genomic cis-regulatory logic: Functional analysis and computational model of a sea urchin gene control system. Science 279, 1896-1902.
33. Davidson, E. H., Cameron, R. A. and Ransick, A. 1998. Specification of cell fate in the sea urchin embryo: Summary and some proposed mechanisms. Development 125, 3269-3290.
34. Davidson, E. H. 1999. A view from the genome: Spatial control of transcription in sea urchin development. Current Opin. Genet. Dev. 9, 530-541.
35. Pasquinelli, A. E., Reinhart, B. J., Slack, F., Martindale, M. Q., Kuroda, M. I., Maller, B., Hayward, D. C., Ball, E. E., Degnan, B., Müller, P., Spring, J., Srinivasan, A., Fishman, M., Finnerty, J., Corbo, J., Levine, M., Leahy, P., Davidson, E. and Ruvkun, G. 2000. Conservation of the sequence and temporal expression of let 7 heterochronic regulatory RNA. Nature 408, 86-89.
36. Arenas-Mena, C., Cameron, R. A. and Davidson, E. H. 2000. Spatial expression of Hox cluster genes in the ontogeny of a sea urchin. Development 127, 4631-4643.
37. Davidson, E. H., Rast, J. P., Oliveri, P., Ransick, A., Calestani, C., Yuh, C.-H., Minokawa, T., Amore, G., Hinman, V., Arenas-Mena, C., Otim, O., Brown, C. T., Livi, C. B., Lee, P., Revilla, R., Rust, A. G., Pan, Z. J., Schilstra, M. J. Clarke, P. J. C., Arnone, M. I., Rowen, L., Cameron, R. A., McClay, D. R., Hood, L. and Bolouri, H. 2002. A genomic regulatory network for development. Science 295, 1669-1678.
38. Erwin, D. H. and Davidson, E. H. 2002. The last common bilaterian ancestor. Development 129, 3021-3032.
39. Istrail, S. and Davidson, E. H. 2005. Logic functions of the genomic cis-regulatory code. Proc. Natl Acad. Sci. USA 102, 4954-4959.
40. Davidson, E. H. and Erwin, D. H. 2006. Gene regulatory networks and the evolution of animal body plans. Science 311, 796-800.
41. Sea Urchin Genome Sequencing Consortium. 2006. The genome of the sea urchin Strongylocentrotus purpuratus. Science 314, 941-952.
42. Samanta, M. P., Tongprasit, W., Istrail, S., Cameron, R. A., Tu, Q., Davidson, E. H. and Stolc, V. 2006. The transcriptome of the sea urchin embryo. Science 314, 960-962.
43. Smith, J., Theodoris, C. and Davidson, E. H. 2007. A gene regulatory network subcircuit drives a dynamic pattern of gene expression. Science 318, 794-797.
44. Oliveri, P., Tu, Q. and Davidson, E. H. 2008. Global regulatory logic for specification of an embryonic cell lineage. Proc. Natl Acad. Sci. USA 105, 5955-5962.
45. Erwin, D. H. and Davidson, E. H. 2009. The evolution of hierarchical gene regulatory networks. Nature Rev. Genet. 10, 141-148.
46. Davidson, E. H. 2010. Emerging properties of animal gene regulatory networks. Nature 468, 911-920.
47. Peter, I. S. and Davidson, E. H. 2011. Evolution of gene regulatory networks controlling embryonic development. Cell 144, 970-985.
48. Peter, I. S. and Davidson, E. H. 2011. A gene regulatory network controlling the embryonic specification of endoderm. Nature 474, 635-639.