Introduction

Every year billions of dollars are invested in research worldwide to find solutions for deadly diseases like cancer, AIDS, TB etc. Much research is now focused on DNA and everyone is trying to understand what is happening within DNA at the molecular level. Whenever I ask my students within a molecular biology class, “Who discovered DNA?” many of my students give a very quick response “Watson and Crick”. It reminds me of a statement made by L. Pray that “Many people believe that American biologist James Watson and English physicist Francis Crick discovered DNA in the 1950s”1. Then a few students respond, “No sir” Watson and Crick uncovered the structure of DNA. But still it remains a question to my students: who discovered DNA? When there is no answer, I start explaining history of DNA discovery. I remind them about Friedrich Miescher who isolated DNA for the first time in 1869 and how Watson and Crick deciphered the structure of DNA in 1953. It took almost 85 years to discover the molecular details of DNA structure. Friedrich Miescher was a brilliant scientist but he suffered when his findings were not published immediately and his boss published his results after repeating his experiments on his own. It took almost two years to get his results published. Even Miescher had the opinion that the new substance (“nuclein”) could be thought of as genetic material but various established theories stopped his journey. Many scientists at that time were of the opinion that some proteins could be genetic material and they were busy finding novel proteins which could act as genetic material. Friedrich Miescher died in 1895 without getting credit for his discovery2. Later in 1919, the “Tetra nucleotide hypothesis” proposed by Levene become an obstacle in DNA structure discovery as he proposed DNA as an inert molecule having four nucleotides repeatedly arranged. Levene was also a brilliant scientist and had published more than 700 papers and many scientists followed his opinions3,4. In the coming years scientists were not interested in doing work on DNA until 1928 when Griffith gave some evidence that it is not the proteins which acts as a genetic material5. His experimental findings were worked out further in 1944 by Avery et al. and they clearly demonstrated that it is DNA which acts as a transforming agent but still they faced opposition. Still, many scientists were slow to accept this clear proof that DNA, not protein, is the genetic molecule6,7. From 1950 onwards Chargaff used to meet and discuss with scientists that he had different results showing that DNA cannot be an inert molecule thus clearly rejecting the “Tetra nucleotide hypothesis”. But his views were not given much importance (http://www.dnai.org)8. In 1952, Hershey and Chase did a classical experiment which proved without doubt that DNA is genetic material9. It created interest in others to solve out molecular details of DNA. In 1953 Linus Pauling (one of the famous Nobel laureates) proposed a triple helical model of DNA in which they proposed phosphate groups are inside while nitrogenous bases are outside10. Really Pauling’s authority in science might have become another obstacle in the discovery of the correct DNA model, if Watson and Crick had not realized that phosphate groups cannot be inside, as this would destabilize DNA due to high negative charge. Watson, Crick and Wilkinson proposed the double helical structure of DNA based on work done by Rosalin Franklin11–13. Linus Pauling himself visited Watson and Crick and was convinced about their proposed model (https://paulingblog.wordpress.com/2009/04/30/the-watson-and-crick-structure-of-dna/). Watson, Crick and Wilkinson received the Nobel Prize in 1963 for solving the structure of DNA. Yes, truly their findings have changed molecular biology research worldwide. Many scientists started developing new molecular techniques and the fundamentals of biology are based on it. In 1973 E.M. Southern developed the Southern hybridization technique to detect DNA14 and later in 1977, northern hybridization was developed by Alwine et al. to detect levels of RNA15. In 1983, Dr Kary Mulis developed PCR (Polymerase Chain Reaction) for DNA amplification, which is also based on antiparallel complementary hybridization of DNA and for this he was awarded Nobel Prize in 199316. In 1973, Boyer, Cohen and Chang developed cloning techniques which has allowed the production of recombinant protein and a whole new science of recombinant DNA technology has been developed based on this17. On the basis of Watson and Crick model of DNA and using Sanger DNA sequencing chemistry, scientists throughout the world invested billions of dollars and developed the Human Genome Project18,19. Today efforts are being taken to sequence the genome of each organism. On the basis of homologous DNA sequence, gene knockout technology was developed and many scientists have tried to characterize functions of various proteins and DNA elements on the basis of gene knockouts20–22. Capecchi, Evans and Smithies, were awarded the Nobel Prize for developing gene knockout technology in 2007. In 1998, siRNA technology was developed by Andrew Z. Fire and Craig C. Mello for which they were awarded Nobel Prize in 200623 and Microarray technology was developed by Pat Brown which provides powerful tools for global characterization of gene expression24. Yes, truly whole molecular biology has flourished with much new information and technologies in last 60 years based on the Watson and Crick model of DNA and it will not be possible for me to write about all techniques.