Milestones on Molecular Sciences

Whether in the diagnosis of diseases, the production of detergents, chemical basic materials, or foodstuffs, biotechnological processes determine modern everyday life. The advancement of knowledge made possible by the development of molecular biology has enriched the knowledge about the function of cells and of the whole organism in a revolutionary manner, and one begins to understand the complexity and diversity of the regulatory processes at the molecular level and to recognize the molecular structures involved. The following are some examples of important developmental steps.

In 1944, US American Oswald Avery hypothesized that deoxyribonucleic acids (DNA) and not proteins are the carriers of the genetic material. In 1952, this hypothesis was finally confirmed by Alfred Hershey and Martha Chase. This was the start signal for an unprecedented scientific race to elucidate the molecular structure of the DNA. In 1953, Englishman was able to decode the three-dimensional structure of the DNA, based on X-ray structure analysis of crystallized DNA performed by Rosalind Franklin and Maurice Wilkins at King's College, London, in the early 1950s. The structural model developed by Watson and Crick remains valid until today. They called this structure the DNA double helix. For their discovery, Watson and Crick received the Nobel Prize in Medicine and Physiology in 1962, together with Maurice Wilkins, who contributed to the radiographic images.

In 1955, Arthur Kornberg isolated the first DNA polymerase. For this discovery, he received the Nobel Prize in Physiology or Medicine together with Severo Ochoa in 1959. In 1958, Francis Crick formulated the "sequence hypothesis" and the "central dogma" of molecular biology. In 1959, Francois Jacob and Matthew Meselson showed that protein biosynthesis takes place on ribosomes.

The development of powerful, automated DNA sequencing methods is one of the milestones in the development of gene technology. In the years 1975 to 1977, Frederick Sanger and co-workers developed the chain termination method, and Allan Maxam and Walter Gilbert developed chemical sequencing. Sanger and Gilbert received the Nobel Prize in Chemistry in 1980 for the development of their respective sequencing methods. The chain termination method with dideoxynucleotides prevailed mainly due to its ability for automation, the quality of the sequences, and the longer sequence reads.

In 1973, selective cloning of genes became possible. In 1975, Edwin Southern developed gel transfer hybridization to detect specific DNA sequences.

In 1985, Kary B. Mullis developed the concept of the polymerase chain reaction (PCR). This method was to provide the solution to one of the most pressing biological problems of its time - the duplication of DNA. In 1982, the first recombinant drug, human insulin was approved. In 1986, the first genome sequencer came onto the market.

In 2005, new DNA sequencing techniques were introduced called "Next Generation Sequencing" (NGS) techniques. These innovative technologies have the potential to revolutionize biological and biomedical research by significantly accelerating genome analyses and by reducing their costs. The read lengths of all commercially available NGS devices are considerably shorter than those of the Sanger sequencing method. After sequencing, the pieces have to be combined to a complete genome using bioinformatics. Still, NGS has some limitations: its accuracy is less than that of the Sanger method. Moreover, the equipment for NGS is still very expensive.

Comparison of Sanger sequencing and NGS. Fig.1 Comparison of Sanger sequencing and NGS. (Park, 2016)

In 2010, a new sequencing method based on semiconductor technology was presented. In 2012, the so-called single-molecule sequencers were ready for use. Sequencing techniques based on nanostructures or nanopores make it possible to read individual nucleic acid molecules, base by base. Used massively in parallel on chips, high throughput rates can be achieved and costs saved.

The dynamic development in molecular biology research is still far from complete. Existing methods will be further refined and new procedures developed. So far, especially in biology and medicine, only the surface has been touched. We are still far away from a deeper understanding of the complex processes that take place in the body of a living being.

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Reference

  1. Park, S.T.; Kim, J. Trends in Next-Generation Sequencing and a New Era for Whole Genome Sequencing. Int Neurourol J. 2016 Nov;20(Suppl 2):S76-83.
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