The National Library of Medicine, a constituent institute of the National Institutes of Health, announces the release of an extensive selection from the papers of Sol Spiegelman (1914-1983), a pioneering molecular biologist whose discoveries helped reveal the mechanisms of gene action and laid the foundations of recombinant DNA technology, on the Library's Profiles in Science website.

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 23. The site is at http://profiles.nlm.nih.gov.

"Sol Spiegelman was an extraordinarily creative scientist; his achievements include the first test-tube synthesis of an infective virus RNA and the development of RNA-DNA hybridization, an essential technique in molecular biology," said Donald A. B. Lindberg, M.D., director of the National Library of Medicine.

Born and raised in New York City, Spiegelman pursued his early scientific studies at City College. Summer work at hospital research labs sparked his interest in bacterial mutations. His Ph.D. research — begun at Columbia University, and finished in 1944 at Washington University in St. Louis — verified earlier observations that bacteria could sometimes adapt to the presence of novel nutrient substances by producing the enzymes necessary to digest them, without undergoing a genetic mutation. He later showed that genes for making various enzymes could be turned off and on by the presence of different nutrients. This technique, enzyme induction, became a powerful tool for understanding how the genetic information encoded in DNA is transcribed to produce enzymes that help direct cellular life processes.

During the 1950s, Spiegelman shifted his focus to the strange biological situation of a class of phages — viruses that infect bacteria. These viruses have RNA, not DNA, as their genetic material. Over the next decade Spiegelman determined how RNA viruses exploit cellular information to survive and replicate in a host cell dominated by DNA, finding that each phage produced a specific replicating enzyme to allow reproduction of its own viral RNA. By 1965, he was able to synthesize a biologically active viral RNA.

Spiegelman is perhaps best known for developing the formidable technique of DNA-RNA hybridization. This technique takes advantage of the fact that the four nitrogenous bases of DNA always pair up in the same way: adenine with thymine (or uracil in the case of RNA), and cytosine with guanine. If a given length of double-stranded DNA is "unzipped" into its single strands, and then exposed to a strand of RNA whose sequence of bases is complementary to it, the RNA will bond to one of the strands of the DNA. Such hybridization will occur only between genetic sequences that are nearly identical, allowing researchers to connect up related sequences of DNA and RNA, and even to identify DNA sequences that constitute individual genes.

Molecular hybridization has been an essential tool for studying the organization of the genome and has made possible recombinant DNA technology. Spiegelman received the 1975 Lasker Award for basic medical research in recognition of both this work and his synthesis of viral RNA.

In 1969, Spiegelman decided to shift his research focus to cancer, a subject that had hovered in the background of his research since his undergraduate days. He explored whether RNA tumor viruses–which had been shown to cause certain animal cancers — had a role in human cancers. He did find significant similarities between the RNA in some animal tumor viruses and in several human tumor types. Although later researchers found that few human cancers are directly caused by viruses, Spiegelman’s work greatly expanded scientific understanding of how they worked at the molecular level.

Profiles in Science features correspondence, published articles, and photographs from the Sol Spiegelman Papers at the National Library of Medicine. Visitors to the site can view, for example, letters exchanged between Spiegelman and Joshua Lederberg, Francis Crick, Jacques Monod, Seymour Cohen, Tracy Sonneborn, and other pioneers in genetics and molecular biology.

Located in Bethesda, Maryland, the National Library of Medicine is the world's largest library of the health sciences. For more information, visit the website at http://www.nlm.nih.gov/.

The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.