The DNA helix at 50
Authors: Inder M. Verma
Journal: Molecular Therapy (2003)

The eternal thing in man, that heeds no call to die.—Thomas Hardy April of this year marks the 50th anniversary of the DNA helix, perhaps the most recognizable icon in biology. Although George Mandel proposed the “inheritance factors"— a mechanism for passing on traits from one generation to the next—in 1865, it was nearly another 80 years before Oswald Avery and colleagues showed that DNA could transfer genetic traits between bacteria. The publication proposing the DNA double helix did not initially attract much attention in the scientific community. According to Robert Colby, a science historian writing in Nature earlier this year, of the 20 articles on DNA published in Nature in 1953, a mere seven mentioned the double helix. It is perhaps surprising today to find that such a seminal paper received such a lukewarm reception. Of course, scientists naturally react with skepticism to anything truly new. In fact, a big problem at the time was imagining how the two entwined chains could unwind without getting tangled. Moreover, in the early 1950s, protein chemists were predominant in the biological sciences, and the DNA helix itself did nothing to explain how proteins were synthesized. Arthur Kornberg, who discovered DNA polymerase, said that “the significance of the DNA helix did not intrude into my work until 1956.” The subsequent rapid discovery of mRNA, in vitro protein synthesis and the central dogma of “DNA-RNA-protein” cemented the importance of the DNA helix. As James Watson recently observed, “the molecule is so beautiful and its glory was reflected on Francis [Crick] and me.” In the ensuing 50 years, biology has undergone an explosion of knowledge and has become an applied science in addition to a descriptive one. We now know in reasonable detail how cells proliferate, differentiate and die during development. Perhaps the greatest strides have been made in human genetics. We have determined the complete nucleotide sequence not only of humans, but also of mice and other model organisms, agriculturally relevant species, and large numbers of pathogenic microbes. Forward and backward genetics has allowed the identification of genes involved in a vast number of inherited and acquired diseases. Use of single nucleotide polymorphisms combined with family histories of diseases will soon allow the scientific community to identify and isolate genes involved in more complex genetic diseases like schizophrenia, depression, asthma and cancer. Identification of genes involved in the pathogenesis of disease offers to the practitioners of gene therapy the potential for genetic intervention to either correct a disorder or slow down its progression. The ability of gene chip analysis to identify signature genes in human tumors or other diseases is a nascent diagnostic tool that may lead to a better prediction of the prognosis—and hence predict more effective treatments. The application of the knowledge inherent in DNA has begun to have a strong impact on society at large. Just a few months ago, the death sentences of hundreds of prisoners were commuted due to new information derived from DNA fingerprinting technology. As we have seen with the controversy over cloning technology, certain religious and moral beliefs have left society ill-prepared to take full advantage of the novel breakthroughs, or to anticipate the resulting ethical and social consequences. The cloning technology used to generate Dolly has rocked the scientific, religious, and political communities, leading to a whole set of new and controversial rules and regulations. True, the structure of DNA helix alone could not have been responsible for the tremendous changes that we have observed in the last 50 years in biology, but it was definitively the primer.