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Papers of Daniel Nathans Added to the National Library of Medicine's Profiles in Science Web Site

Daniel Nathans Photo The National Library of Medicine, a constituent institute of the National Institutes of Health, in collaboration with the Alan Mason Chesney Medical Archives of The Johns Hopkins Medical Institutions announces the release of an extensive selection from the papers of molecular biologist Daniel Nathans (1928-1999), who received the 1978 Nobel Prize in Physiology or Medicine for his innovative use of restriction enzymes in analyzing virus genomes, on the Library's Profiles in Science® Web site.

With this addition, the number of prominent researchers, public health officials, and promoters of medical research whose personal and professional records are presented on Profiles has grown to thirty. The site is at http://profiles.nlm.nih.gov.

"Dr. Nathans' work demonstrated the immense utility of restriction enzymes for genome analysis, and transformed molecular biology. Gene mapping, sequencing, cloning, and recombinant DNA technology would be inconceivable without the techniques he pioneered," said Donald A. B. Lindberg, MD, director of the National Library of Medicine.

Born and raised in Wilmington, Delaware, Nathans majored in chemistry at the University of Delaware. He went on to medical school at Washington University School of Medicine in St. Louis, planning initially to enter general practice. By the time he received his MD in 1954, however, several of his mentors had introduced him to the fascinating world of laboratory research. Nathans decided to pursue an academic medical career, combining teaching, research, and patient care. He did his internship at Columbia Presbyterian Hospital in New York, and then spent two years as a clinical research fellow at the National Cancer Institute, where he began studying protein synthesis in tumor cells. Finding himself increasingly drawn to lab research during his subsequent medical residency, he became a full-time research associate at Fritz Lipmann's laboratory at the Rockefeller Institute in 1959.

Biochemists, microbiologists, and geneticists were rapidly forging the new discipline of molecular biology during the 1950s, resolving central questions about how the genetic material DNA directs living cells to manufacture the enzymes and structural proteins they need. At the Rockefeller Institute, Nathans joined these efforts, pursuing his interest in protein synthesis in bacteria and viruses. His most important project, carried out with Norton Zinder, showed that RNA could direct the synthesis of a specific protein, and supported the emerging idea that RNA might act as a "messenger" between cellular DNA and the protein-synthesizing "machinery" of cells.

Nathans joined the faculty of the microbiology department at Johns Hopkins University in 1962, and continued investigating protein synthesis. Several years later he became interested in tumor viruses; like bacterial viruses, they promised to be excellent models of genetic mechanisms in the cells they infected. In 1969 he spent a six-month sabbatical at the Weizmann Institute in Israel, learning cell-culture techniques and getting acquainted with simian virus 40 (SV40), a small tumor virus.

While Nathans was in Israel, Hamilton Smith, a JHU colleague, wrote to him about a new enzyme he'd found in Haemophilus influenzae bacteria, which seemed to cut the DNA of other species at particular points. Nathans recognized that such an enzyme would be useful for making uniform fragments of a small virus DNA that could then be mapped, i.e., the precise molecular structure determined. Returning to JHU, he immediately set to work testing Smith's enzyme and several other known restriction enzymes on the SV40. As he hoped, the Haemophilus restriction enzyme cut the SV40 DNA into eleven specific fragments. He and his graduate student Kathleen Danna then proceeded to deduce the physical order of the fragments and to discover the point where DNA replication started.

Restriction enzymes rapidly became essential tools, stimulating a rapid expansion of discovery in molecular biology. In subsequent work, Nathans and his associates constructed physical maps of the SV40 genome, and used restriction enzymes to create mutant forms of the virus in which certain DNA segments were deleted. These mutants were reintroduced into the host cells and assessed for biological activity. In the latter part of his career, hoping to learn more about how cancerous processes began, Nathans shifted from tumor viruses to the study of cultured mouse cells, investigating the effects of substances called growth factors on cell reproduction. He and his co-workers isolated and characterized some of the first cellular genes that were activated when cells were stimulated to grow and divide.

Though widely acknowledged as a first-rate researcher, teacher, and mentor, Nathans was also an able administrator-- thoughtful, fair, deliberate, and clearheaded. (One colleague noted that Nathans had "the highest signal-to-noise ratio of anyone" he'd ever known.) He was director of the Microbiology Department at JHU from 1972 to 1982, and then served as Senior Investigator of the Howard Hughes Medical Institutes unit there from 1981 to 1999. He served on many national scientific committees, and as Interim President of JHU during 1995-96, guiding the institution through a time of difficult transitions.

Profiles in Science features correspondence, published articles, notebook excerpts, report drafts, and photographs from the Daniel Nathans Papers at the Alan Mason Chesney Medical Archives of The Johns Hopkins Medical Institutions. Visitors to the site can view, for example, excerpts from Nathans' medical school notebooks, laboratory notebooks and correspondence reflecting his early work with restriction enzymes, reports and correspondence relating to his administration of the Howard Hughes Medical Institute unit at Johns Hopkins, and letters between Nathans and Paul Berg, Maxine Singer, and Ernest Winocour.

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