Discovering DNA: Friedrich Miescher and the early years of nucleic acid research.

Center for Brain Research, Medical University of Vienna, Spitalgasse 4, 1090, Vienna, Austria,
Human Genetics (Impact Factor: 4.63). 02/2008; 122(6):565-81. DOI:10.1007/s00439-007-0433-0
Source: PubMed

ABSTRACT In the winter of 1868/9 the young Swiss doctor Friedrich Miescher, working in the laboratory of Felix Hoppe-Seyler at the University of Tübingen, performed experiments on the chemical composition of leukocytes that lead to the discovery of DNA. In his experiments, Miescher noticed a precipitate of an unknown substance, which he characterised further. Its properties during the isolation procedure and its resistance to protease digestion indicated that the novel substance was not a protein or lipid. Analyses of its elementary composition revealed that, unlike proteins, it contained large amounts of phosphorous and, as Miescher confirmed later, lacked sulphur. Miescher recognised that he had discovered a novel molecule. Since he had isolated it from the cells' nuclei he named it nuclein, a name preserved in today's designation deoxyribonucleic acid. In subsequent work Miescher showed that nuclein was a characteristic component of all nuclei and hypothesised that it would prove to be inextricably linked to the function of this organelle. He suggested that its abundance in tissues might be related to their physiological status with increases in "nuclear substances" preceding cell division. Miescher even speculated that it might have a role in the transmission of hereditary traits, but subsequently rejected the idea. This article reviews the events and circumstances leading to Miescher's discovery of DNA and places them within their historic context. It also tries to elucidate why it was Miescher who discovered DNA and why his name is not universally associated with this molecule today.

0 0
1 Bookmark
  • [show abstract] [hide abstract]
    ABSTRACT: Nuc 'em: A variety of nucleic acids can be catalytically alkylated with rhodium-carbenoids generated from diazo compounds in aqueous buffer through an NH insertion process (see scheme; MES=2-(N-morpholino)ethanesulfonic acid). The method specifically targets unpaired bases such as those present in single strands, turn regions, and overhangs while leaving double-stranded sequences untouched.
    Angewandte Chemie International Edition 10/2012; · 13.73 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: Spatially structured microfluidic channels in a state far from thermal equilibrium have been developed to address three fundamental problems in modern (bio-)analytics: the usually fixed separation criterion (e.g. a gel density is not changeable on the fly), the usually unknown polarizability properties of samples for dielectrophoretic manipulation and the requirement of a specifically designed chiral selector for chiral separation. 1) Typical biotechnological separation techniques like filters, chromatography, or gel electrophoresis have a fixed implemented separation criterion, e.g. defined by pore size, affinity of the steady phase, or gel density. To overcome this limit, the aim of the first project is the development and functional characterization of a microfluidic ratchet device with a dynamically changeable separation criterion. Depending on the applied voltage scheme, an arbitrarily selectable sub-group of the available species in the analyte solution is forced to migrate into opposite direction than the remaining species. Changing the voltage scheme will immediately switch the separation criterion. The device is based on a sophisticated interplay between electrophoresis and dielectrophoresis and operates with any charged and polarizable material in solution such as e.g. micro- and nanoparticles, cells, or biomolecules. 2) Many microfluidic systems rely on dielectrophoresis to immobilize, manipulate, or sort a somehow polarizable sample. However, the actual polarizability value usually remains unknown and appropriate electric fields to trigger dielectrophoresis are found via trial and error. The second project uses dielectrophoretic traps in a tilted potential implemented in a microfluidic channel to automatically quantify single molecule (here DNA) polarizabilities via fluorescence video microscopy. The approach is tested by reproducing a well-known scaling law between the buffer solution’s ionic strength and the polarizability for two different DNA types. In a second experiment the influence of the required fluorescence staining on the polarizability is investigated. Besides the pure quantification of polarizability in basic research, this system could be used to automatically tune dielectrophoretic traps in a final product to broaden its range of possible analyte classes. 3) When chiral molecules are about to be separated after synthesis, a chromatography setup is used which typically requires chiral selection or derivatization agents. Usually these chemicals have to be redeveloped for every new analyte. The third project’s aim is the implementation of a generic and continuously operating principle to separate chiral molecules in microfluidic channels without the need for any chiral selection or derivatization agent. Two conceptually different microfluidic approaches with excellent sorting performance were developed and experimentally evaluated. Following Curie’s principle, both approaches rely on microfluidic structures that somehow break the symmetry in the channel in every relevant dimension. Injected model enantiomers are demonstrated to split up according to their chirality and to accumulate near opposite channel walls.
    01/2013, Degree: Dr. rer. nat., Supervisor: Dario Anselmetti
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: There have been a wide variety of approaches for handling the pieces of DNA as the "unplugged" tools for digital information storage and processing, including a series of studies applied to the security-related area, such as DNA-based digital barcodes, water marks and cryptography. In the present article, novel designs of artificial genes as the media for storing the digitally compressed data for images are proposed for bio-computing purpose while natural genes principally encode for proteins. Furthermore, the proposed system allows cryptographical application of DNA through biochemically editable designs with capacity for steganographical numeric data embedment. As a model case of image-coding DNA technique application, numerically and biochemically combined protocols are employed for ciphering the given "passwords" and/or secret numbers using DNA sequences. The "passwords" of interest were decomposed into single letters and translated into the font image coded on the separate DNA chains with both the coding regions in which the images are encoded based on the novel run-length encoding rule, and the non-coding regions designed for biochemical editing and the remodeling processes revealing the hidden orientation of letters composing the original "passwords." The latter processes require the molecular biological tools for digestion and ligation of the fragmented DNA molecules targeting at the polymerase chain reaction-engineered termini of the chains. Lastly, additional protocols for steganographical overwriting of the numeric data of interests over the image-coding DNA are also discussed.
    Communicative & integrative biology 03/2013; 6(2):e23478.

Full-text (2 Sources)

Available from
Mar 6, 2013