Looking back to the future: From the development of the gene concept to toxicogenomics

Abstract

Initial progress in the science of ‘genetics’ in the first half of the 20^th century was mainly driven by studies utilizing mutations and consequent changes in phenotype. The structural and functional nature of the gene was far from being understood. That state of understanding started changing from the 1940s. In the following decades, with the discovery of the double helix followed by the discoveries on gene structure and expression, there was a period when the structural and functional aspects of the gene could be conceived in terms of one entity, the cistron. However, the discovery of intervening sequences caused this unified concept to fall apart, making the gene concept a subject of philosophical debate again. Meanwhile, over time, technological progress in molecular biology had the field forge ahead rapidly, ultimately leading to the sequencing of the human genome and genomes of other species, and giving birth to the science of genomics. Developments in genomics have given rise to certain applied sub-disciplines like pharmacogenomics and toxicogenomics. While the full potential of pharmaco- and toxicogenomics is yet to be harnessed, they nevertheless have had an impact in drug development and safety assessment, such that the future promise of genomics seems achievable. At present, it is a good opportunity to revisit the path from the development of the initial gene concept and the philosophical debate surrounding the meaning of the term ‘gene’ to the current state of understanding of genes and genomes and their role in health and disease.

Keywords::

• Gene
• gene concept
• cistron
• genome
• toxicogenomics
• pharmacogenomics
• microarray
• sequencing

Acknowledgement

The opinions expressed in this article are the author’s personal opinions and do not reflect those of FDA, DHHS, or the Federal Government

Declaration of interest: The author reports no conflicts of interest. The author alone is responsible for the content and writing of the paper.