Recipient

The Committee on the International Prize for Biologyof Japan Society for the
Promotion of Science awards
the 2007 International Prize for Biology in the field of "Genetics"
to
Dr. David Swenson Hogness
Munzer Professor of Developmental Biology and Biochemistry,
Emeritus, Stanford University School of Medicine, U.S.A.

Process of Selection

 The Selection Committee, established by the Committee on the International Prize for Biology and chaired by Motonori Hoshi, Professor, The Open University of Japan, distributed a total of 1,818 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 61 recommendations in response. As some of these recommendations named the same individuals, the actual number of individuals recommended was 44, from 15 countries. The Selection Committee met a total of four times and very carefully reviewed all the candidates. Ultimately, the Committee decided to recommend Dr. David Swenson Hogness as the recipient of the 23rd International Prize for Biology. This year’s award is conferred based on the results of the Selection Committee’s deliberations.

Achievements Recognized by the Award

Dr. Hogness was born in 1925. He studied chemistry and biology at California Institute of Technology, obtaining his doctorate in 1952. After doing genetic research using bacteria at Jacques Monod’s laboratory at the Institut Pasteur, Paris, he joined the faculty of Washington University; in 1959, he was appointed Assistant Professor of Biochemistry in the School of Medicine, Stanford University. While holding various chairs at Stanford University, he has dedicated his career to studying gene structure and function and the regulatory mechanisms of gene expression in higher eukaryotes. His numerous breakthroughs, including the techniques he developed for genome analysis, have been fundamental to our current understanding of genes. Among his many contributions, he found the TATA box which plays an important role in regulating gene expression: his analysis of Drosophila genes led to the discovery that the genes of higher eukaryotes consist of sequences of two kinds: exons, which code information for protein synthesis, and introns, which do not carry protein-encoding information; he established that the expression of many genes is controlled by regulatory regions or cis-elements located on the same strand; and he demonstrated that genes play key roles in animal morphogenesis, so that the absence of a certain gene’s function results in a developmental abnormality. These findings extended the frontiers of genetics, molecular biology, and molecular developmental biology; indeed, they laid the foundations for an entire field, which we know today as genomics.

Dr. Hogness has been elected a member of the National Academy of Science (U.S.A.), an honorary member of the Japanese Biochemical Society, and an associate member of the European Molecular Biology Organization (EMBO), among other honors. He has also received many awards, including the Genetics Society of America Medal; Germany’s Humboldt Research Award; the Darwin Prize of the University of Edinburgh; and the Thomas Hunt Morgan Medal of the Genetics Society of America.

Further, Dr. Hogness’s laboratory has nurtured the careers of many younger researchers, such as Dr. Jeremy Nathans, who is known for his work with red and green opsins, or photoreceptive proteins, in mammals. These many contributions, which have benefited other areas of genetic science in addition to his own field of research, make Dr. Hogness a worthy recipient of the International Prize for Biology.

Ceremony and Symposium

The award ceremony was convened on Monday, November 19, 2007, at the Japan Academy (7-32 Ueno Koen, Taito-ku, Tokyo). Their Majesties the Emperor and Empress attended the ceremony and a party in honor of the award recipient. To commemorate the award to Dr. David Swenson Hogness, the 23rd International Prize for Biology Commemorative Symposium on Genetics took place on November 21 and 22, 2007, at the Shiran Kaikan Conference Hall, Kyoto University.
At the symposium, Dr. Hogness and his colleagues at the forefront of genetic research, both in Japan and overseas, lectured on their latest findings.

DATE OF BIRTH :	November 17, 1925
CITIZENSHIP :	United States of America
POSITION :	Munzer Professor of Developmental Biology and Biochemistry, Emeritus, Stanford University of Medicine, U. S. A.

HONORS AND AWARDS

1977		Ricketts Award, University of Chicago
1984		Genetics Society of America Medal
1988		Newcomb Cleveland Prize
1995		Humboldt Research Award
1995		Darwin Prize, University of Edinburgh
1997		March of Dimes Prize in Developmental Biology
2002		Lifetime Achievement Award (Society of Developmental Biology, U.S.A.)
2003		Thomas Hunt Morgan Medal (Genetics Society of America)

Research Acheivements

1) By 1973, Dr. Hogness had succeeded in producing "libraries" of genomic DNA of the fruit fly Drosophila melanogaster, the first such libraries for a higher eukaryote. Using these libraries to map genomic DNA sequences, he determined that, in the genomes of higher eukaryotes, some sequences exist as single copies while others are repeated. The former discovery led to single-copy sequences being identified as genes, while the discovery of repetitive sequences led to the identification of transposable elements.

Next, utilizing these libraries in clonal-hybridization, Dr. Hogness succeeded in isolating and analyzing histone and rDNA genes in Drosophila, the first time that this had been achieved for genes of a multicellular organism. His analysis of the 5'-upstream region in histone genes resulted in the discovery of a highly conserved sequence immediately upstream of the transcription initiation site. This sequence, now known as the TATA box, plays an important role in regulating gene expression. This work provided the key to understanding the basis of gene expression in higher eukaryotes. Further, his analysis of rDNA gene led to the discovery that, whereas in the prokaryotes there is a direct, one-to-one coupling between the mRNA produced by transcription and its translation into protein, higher eukaryotic genes are interrupted by sequences known as introns.

2) Dr. Hogness also provided the first proof of the essential role of genes in animal morphogenesis. In Drosophila, he focused on the Ultrabithorax (Ubx) mutant, in which the rear thoracic segment duplicates the middle segment and a second set of wings develops, and succeeded in identifying the gene responsible by developing the method known today as "positional cloning" or "chromosome walking." By mapping the Ubx gene that he had isolated and identified in this way, he showed that these dynamic morphological changes are caused by a mutation in a single protein-encoding gene, rather than several, as had been previously thought, and thus demonstrated the importance of the role of individual genes in morphogenesis. He then went on to show that this mutation involves a change, not in the gene itself, but in the region that regulates its expression; specifically, he revealed that expression of this gene is regulated by two large cis-regulatory elements located in the 5'-upstream region.

This seminal work paved the way for what is known today as "functional genomics," the field that studies how genes and their regulatory regions are arranged on the chromosomes and the factors that lead to gene mutations, among other questions. The methods that Dr. Hogness developed and applied in mapping the Ubx gene have since made it possible to identify and elucidate the genes responsible for seven other homeotic mutations in Drosophila.

3) Dr. Hogness also recognized that, if we are to understand morphogenesis at a molecular level, it is important to know the timing of gene regulatory mechanisms. Accordingly, he studied how the hormone ecdysone acts to regulate metamorphosis in Drosophila. He found that secreted ecdysone first binds to a nuclear receptor to form a complex, which then activates the primary response genes involved in metamorphosis by acting as a transcription factor and regulating the transcription of the target genes; these primary response genes, in turn, encode transcription factors that activate the secondary response genes, the "working" genes of metamorphosis. These discoveries, which showed a series of genes functioning in a cascade, laid the foundations of our current knowledge of the molecular mechanisms of gene expression and regulation in biological development.

Representative Publications:

1. Hogness, D.S., Cohn, M., and Monod, J. (1955). Studies on the induced synthesis of b-galactosidase in Escherichia coli: the kinetics and mechanism of sulfur incorporation. Biochim. Biophys. Acta l6, 99-ll6.
2. Kaiser, A.D. and Hogness, D.S. (l960). The transformation of Escherichia coli with deoxyribonucleic acid isolated from bacteriophage ldg. J. Mol. Biol. 2, 392-4l5.
3. Hogness, D.S., Doerfler, W., Egan, J.B., and Black, L. (1966). The position and orientation of genes in l and ldg DNA. Cold Spring Harbor Symp. Quant. Biol. 3l, l29-l38.
4. Wensink, P.C., Finnegan, D.J., Donelson, J.E., and Hogness, D.S. (1974). A system for mapping DNA sequences in the chromosomes of Drosophila melanogaster. Cell 3, 3l5-325.
5. Glover, D.M., White, R.L., Finnegan, D.J. and Hogness, D.S. (1975). Characterization of six cloned DNAs from Drosophila melanogaster, including one that contains the genes for rRNA. Cell 5, l49-l57.
6. Grunstein, M. and Hogness, D.S. (1l975). Colony hybridization: a method for the isolation of cloned DNAs that contain a specific gene. Proc. Nat. Acad. Sci. USA 72, 396l-3956.
7. Glover, D.M. and Hogness, D.S. (1977). A novel arrangement of the l8S and 28S sequences in a repeating unit of Drosophila melanogaster. Cell l0, l67-l76.
8. White, R.L. and Hogness, D.S. (1977). R-loop mapping of the l8S and 28S sequences in the long and short repeating units of Drosophila melanogaster rDNA. Cell l0, l77-l92.
9. Young, M.W. and Hogness, D.S. (1977). A new approach for identifying and mapping structural genes in Drosophila melanogaster. In: Eucaryotic Genetics System: ICN-UCLA Symposia on Molecular and Cellular Biology, Vol. 8, pp. 3l5-33l, Academic Press, New York (eds. G. Wilcox, J. Abelson and C. F. Fox).
10. Finnegan, D.J., Rubin, G.M., Young, M.W., and Hogness, D.S. (1978). Repeated gene families in Drosophila melanogaster. Cold Spring Harb. Symp. Quant. Biol. 42, l053-l063.
11. Muskavitch, M.A.T. and Hogness, D.S. (1980). Molecular Analysis of a Gene in a Developmentally Regulated Puff of Drosophila melanogaster. Proc. Natl. Acad. Sci. USA, 77, 7362-7366.
12. Bender, W., Spierer, P. and Hogness, D. S. (1983). Chromosomal walking and jumping to isolate DNA from the Ace and rosy Loci and the Bithorax Complex in Drosophila melanogaster. J. Mol. Biol., (1983) 168, 17-33.
13. Spierer, P., Spierer, A., Bender, W. and Hogness, D.S. (1983). Molecular mapping of genetic and chromomeric units in Drosophila melanogaster. J. Mol. Biol., (1983) 168, 35-50.
14. Bender, W., Akam, M., Karch, F., Beachy, P.A., Peifer, M., Spierer, P., Lewis, E.B. and Hogness, D.S. Molecular Genetics of the Bithorax Complex in Drosophila melanogaster (1983). Science, 221, 23-29.
15. Nathans, J. and Hogness, D.S. (1984). Isolation, sequence analysis and intron-exon arrangement of the gene encoding bovine rhodopsin. Cell, 34, 807-814.
16. Beachy, P.A., Helfand, S.L. and Hogness, D.S. (1985). Segmental distribution of bithorax complex proteins during Drosophila development. Nature, 313, 545-551.
17. Nathans, J., Thomas, D. and Hogness, D.S. (1986). Molecular genetics of human color vision: the genes encoding blue, green, and red pigments. Science 232, 193-202.
18. Beachy, P.A., Krasnow, M.A., Gavis, E.R. and Hogness, D.S. (1988). An Ultrabithorax protein binds sequences near its own and the Antennapedia P1 promoters. Cell 55, 1069-1081.
19. Seagraves, W.A. and Hogness, D.S. (1990). The E75 ecdysone-inducible gene responsible for the 75B early puff in Drosophila encodes two new members of the steroid receptor superfamily. Genes & Develop. 4, 204-219.
20. Koelle, M.R., Talbot, W.S., Segraves, W.A., Bender, M.T., Cherbas, P. and Hogness, D.S. (1991). A Drosophila Ecdysone Receptor, EcR, is a New Member of the Steroid Receptor Superfamily, Cell 67, 59-77.
21. Gibson, G. and Hogness, D.S. (1996) Effect of polymorphism in the Drosophila regulatory gene Ultrabithorax on homeotic stability. Science 271, 200-203.
22. White, K.P., Hurban, P., Watanabe, T., and Hogness, D.S. (1997). Coordination of Drosophila Metamorphosis by Two Ecdysone-induced Nuclear Receptors. Science, 276, 114-117.
23. Arbeitman, M., Hogness, D.S. (2000). Molecular Chaperones Activate the Drosophila Ecdysone Receptor, an RXR. Heterodimer. Cell 101, 67-77