Discovering DNA encodes heredity and prions are infectious proteins

Annu Rev Genet. 2006:40:25-45. doi: 10.1146/annurev.genet.40.121505.133522.

Abstract

The resemblance between the discoveries that DNA is the basis of heredity and that prions are infectious proteins is remarkable. Though four decades separated these two discoveries, the biochemical methodologies and scientific philosophies that were employed are surprisingly similar. In both cases, bioassays available at the time that the projects were initiated proved to be inadequate to support purification studies. Improved bioassays allowed the transforming principle (TP) to be purified from pneumococci and prions from scrapie-infected hamster brains. Publications describing TP as composed of DNA prompted some scientists to contend that undetected proteins must contaminate TP enriched fractions. The simplicity of DNA was thought to prevent it from encoding genetic information. By the time prions were discovered, the genomes of all infectious pathogens including viruses, bacteria, fungi and parasites had been shown to be comprised of nucleic acids and so an antithetical refrain became widely echoed: DNA or RNA molecules must be hiding among the proteins of prions. Finding the unexpected and being asked to demonstrate unequivocally the absence of a possible contaminant represent uncanny parallels between the discoveries that DNA encodes the genotype and that prions are infectious proteins.

Publication types

  • Historical Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Assay
  • Cricetinae
  • DNA / history*
  • DNA / metabolism
  • Heredity*
  • History, 20th Century
  • Humans
  • Mice
  • Models, Biological
  • Molecular Biology / history*
  • Prions / genetics
  • Prions / history*
  • Prions / pathogenicity
  • Scrapie / metabolism
  • Transformation, Genetic*

Substances

  • Prions
  • DNA