The birth of molecular biology

Following classical genetics, it was a perpetual process of numerous discoveries made in the first half of the 20th century that molded the science. Among others, some of them were the invention of X-ray crystallography (Tony Broad), electron microscope, identification of amino acids, the sequencing of protein Insulin, followed by automatic amino acid analyzers in the late 1950s, the discovery of the structure of DNA, the solving of three-dimensional structures of proteins myoglobin and hemoglobin, and deciphering the genetic code.

The unveiling of the complexities of life required a convergence of research within many disciplines, chemistry, physics, genetics, engineering, and mathematics. Consequently, Warren Weaver, an American mathematician, recognized early on that biology was going through notable changes and coined the term 'molecular biology' already in 1938.

The discovery of restriction enzymes or endonucleases, proteins that cut DNA at specific sites, gave scientists tools that paved the way for genetic engineering. The chain of discoveries began in the early 1950s experiments showing some bacteria strains being able to resist or restrict virus infection; hence, the term restriction enzyme.

Werner Arber conducted subsequent investigations in the 1960s with bacteriophages and bacteria. The results of these experiments inspired him to propose a hypothesis that some bacterial strains contain enzymes recognizing viral DNA and cutting it to pieces; thus, rendering the virus nonfunctional. These enzymes left bacterial DNA unaffected for the reason that they only cut at the DNA positions containing a specific nucleotide sequence that was not present in the bacterial genome, and if they were, DNA would protect itself via some other mechanism. Soon after, Arber together with Stuart Linn isolated an enzyme that provided resistance to viral infection for E. coli and an enzyme adding methyl groups to bacterial DNA, protecting it from degradation. Furthermore, they found that the restriction enzyme cut only unmethylated DNA.

In 1970, Hamilton Smith isolated restriction enzyme from Haemophilus influenzae bacteria and demonstrated that the enzyme cuts virus DNA at specific positions consisting of six nucleotides and left the bacterial DNA intact.

Perhaps Daniel Nathans had a vision when he together with Kathleen Danna^(*) later used a combination of restriction enzymes to cut Simian virus (SV40) genome into thousands of fragments of varying lengths. The determined lengths of these fragments combined with the knowledge of the unique base pair sequences at which each restriction enzyme cut, it was possible to construct a physical map of the Simian virus. Recognizing the power of this 'restriction enzyme digest' method, numerous scientists used it to assemble physical maps of a copious number of other genomes.

Werner Arber, Hamilton Smith, and Hamilton Smith shared the Nobel Prize in Physiology or Medicine in 1978 "for the discovery of restriction enzymes and their application to problems of molecular genetics."^(*)