Inteligencia

relating to life science in many applications since the Stone Age. If we consider the definition of biotechnology as the use of living organisms or biological processes in a productive way then biotechnology activities can be traced as early as the Stone Age with the use of enzymes, bacteria and fungi in fermentation processes, or even with the first use of agriculture through the selection and breeding of plants and animals. The technology emerged long before the scientific understanding of these living organisms. However, scientific advances due to breakthrough occurring in the 20th _{century relating to how living organisms work, have given rise to a set of new} techniques and opened new possibilities in the manipulation of living organisms. The scientific paradigm behind the development of biotechnology has been driven by the fundamental question of What is life (Morange 2003), and has been marked by the characterisation and understanding of genes (firstly through their roles and then through biochemical characterisation). This section exposes the scientific evolution behind the development of genetics.

During the 20th century, scientific advances have experienced a great leap in the explanation of hu a life th ough the u de standing of the functioning of genes. The interest in genes as an object of study arose in the late 19th _{century with attempts to understand heredity and the specific}

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characteristics of living organisms (Morange 2000). The work of Mendel on the observed heredity of plant hybridisation through inheritance of traits, from which are derived the Mendel Laws of inheritance, would later become central in genetic science. Later research from Morgan in 1910 advanced the understanding on genetics, by showing that genes were carried on chromosomes and are the basis of heredity (Fagot-Largeault et al. 2007). The subsequent research in the genetics field was oriented towards the characterisation of the chemical form of what constitute a gene (whether they were proteins or nucleic acids). In 1952, Chase and Hershey proved that genes were made of nucleic acids (DNA) (ibid.). This result was already shown by Avery in 1944, but the experiment of chase and Ensley was a much clearer demonstration of it (Morange 2007). The final and most influential scientific breakthrough was to come with the discovery of the structure of DNA. This discovery is attributed to Watson and Crick and was published in April 1953, from which they were rewarded a Nobel Prize in 1962 (Cavazzana-Calvo & Debiais 2011). However, historians have also acknowledged the role of Franklin and Wilkins who worked on the X-Ray diffraction imaging that gave a clear picture of the double helix structure of DNA. While Franklin was the one able to produce the best picture the DNA structure, the discovery was attributed to Watson and Crick because their paper was the one that was able to link the specific structure of DNA with the auto-replication characteristic of the gene.

The understanding of the structure of genes and the way they replicate had an important impact on further advances in molecular biology and biochemistry in the 1960s, to which ultimately lead to the manipulation of genes and thus living organisms in the 1970s. These most recent advances were significant in the biotechnology revolution. This revolution first started in 1973 with DNA sequencing and Recombinant DNA technology developed by Cohen and Boyer (i.e. the ability to insert a specific DNA sequence into bacteria or mammalian cells allowing the expression of the corresponding protein), followed in 1975 by the technology developed by two British researchers Milstei a d Kohle ho de eloped ell fusio , also k o as h ido a te h olog . H ido a technology intervenes in the production of monoclonal antibodies, which are used in diagnostics and cancer treatments by directing them against a specific part of a targeted protein. This technique is much more effective than the previous technology that was based on polyclonal antibodies. These advances are mainly used as vectors to distribute highly toxic drugs to clusters of cancer cells (Pisano 2006).

The other reason for such rapid advances in the study of genes is the technologies developed for sequencing them. In the 1970s Fred Sanger, Maxam and Gilbert developed a way to read sequenced genes through the codification of nucleotides, given the letters A, T, C, G

81 (respectively Adenosine, Thymidine, Cytidine, Guanosine) (Fagot-Largeault et al. 2007; Hamdouch & Depret 2001; Pisano 2006), which they were rewarded by a Nobel prize in 1980. This made the production of proteins possible and also provided the possibility to read DNA and RNA. This method, when initially developed, was extremely labour-intensive requiring manual microscopic observation. Two techniques then arrived that improved the fastidious process and sped it up significantly. The first method, called the polymerase chain reaction, was invented by Kary Mullis in 1983 and could amplify a selected fragment of DNA. Secondly, Hunkapiller and Hood in the 1980s worked on a system that could automatically read DNA, and developed the first DNA Sequencer at Applied Biosystem (the name of their company) (Pisano 2006). Since then DNA Sequencers have improved in productivity. This technology helped to considerably reduce the time needed for completing the human genome project but also supported the rapid evolution of genomics.

Following this, these discoveries led to a large scale project, the Human Genome Project, which was put in place in the 1990 and targets the identification of genes for mapping the entire human genome (Cavazzana-Calvo & Debiais 2011). After the identification and mapping of all the genes in the human genome, which officially finished in 2000 and published in 2001, the research then focused on the functions of the genes. The human genome project has created an enormous quantity of information that has now to be understood, and which will probably help in understanding links between this information and the specific functions of genes and the proteins produced by them (ibid.). The function of genes involves the understanding of how proteins are produced and the specific functions of these proteins (Pisano 2006). The study of proteins is called proteomics and looks at their structure and functions. These two tasks are quite large; while the human genome has between 25 000 to 35 000 genes, they produce between 1 and 20 million different proteins. In addition, protein sequencing is not fully automated like gene sequencing (ibid.).

These advances in genetics open the way to the emergence of many new disciplines, which includes the understanding of the expression of genes and the understanding of the proteins that genes codes for, which can come together under the umbrella of the understanding of biological systems, but also in how they interaction with their environment. The next section gives an overview of the various sciences that emerged directly from the genetics revolution.