Intended for healthcare professionals

Medical Milestones

Discovery of structure of DNA: the best is yet to come

BMJ 2007; 334 doi: (Published 04 January 2007) Cite this as: BMJ 2007;334:s9
  1. John Burn, medical director and head of institute
  1. 1Institute of Human Genetics, Centre for Life, Newcastle upon Tyne NE1 3BZ

    Watson and Crick's discovery of the structure of DNA has opened up a world of possibilities in new treatments

    If the competition to determine the 15 greatest medical milestones was judged on the basis of international recognition, then DNA, the ultimate in three letter acronyms, would easily win the prize. Indeed, as the greatest scientific discovery of the past millennium, the elucidation of the structure of DNA would rank very highly, if not first. Surely, then, a competition that focuses on 166 years of medicine would be a pushover—or perhaps not. For the effects of the discovery of the structure of DNA have yet to reachw their peak. Once they have, the case for DNA will be unanswerably strong.

    It is appropriate that I declare an interest. My interest in becoming a clinical geneticist was sparked by the excitement of having the code of DNA explained to my sixth form biology class by a visiting scientist. A similarly revelatory moment occurred much later when I took my daughter, who was killing time between her university interviews at Cambridge in 1994, to see the tiny brass plaque “celebrating” the 1953 discovery of the double helix in what is now a bike shed. As we marvelled at this manifestation of typical British understatement, our conversation turned to the imminent impact of the human genome project and, the next day, to a proposal that led to the successful effort to create the millennium landmark Centre for Life in Newcastle, which brings the wonders of DNA to visitors as well as being a centre for teaching, research, and genetic medicine.

    Our biggest research project

    It is easy, in retrospect, to regard that 1953 discovery by our centre's patrons, Jim Watson and the late Francis Crick, as but a minor step along the road from Gregor Mendel's discovery of the principles of single gene inheritance in 1866 and Archibald Garrod's recognition in 1923 that alkaptonuria followed the same principles of genetic transmission. Geneticists were able to make great advances before the discovery of the double helix, not least Karl Landsteiner's recognition of blood groups in 1909; but as late as 1952 leaders in research had no idea how genes worked. It was Watson and Crick's recognition, at a stroke, of the digital basis of genetic information and the mechanism of inheritance that opened the floodgates to further discoveries. The most dramatic evidence of that flood of research is the human genome project, humanity's biggest research endeavour, which has permitted ever more rapid progress in linking variants in the sequences of genes to thousands of genetic disorders.

    Gene testing for everyone

    Genetic disorders are collectively a major health problem in the developed world, but even in these countries many doctors are liable to think DNA means “Did Not Attend.” Technology has not yet caught up with our aspirations, and sequencing is slow and expensive. However, this is changing as “array” technology and “lab on a chip” devices begin to allow low cost, high throughput genetic testing. Meanwhile, large scale projects such as UK Biobank will permit prospective studies that will link genetic predisposition to outcome in common diseases. Already we are seeing breakthroughs in common diseases such as eczema and inflammatory bowel disease. Mutations in the gene coding for filaggrin, a protein that binds to keratin in skin cells, and in the CARD15 gene sequence are responsible, respectively, for a significant proportion of predisposition to these diseases and affect up to one in 10 people in each case. More importantly, such discoveries expose the relevant pathogenic pathways. New interventions that focus on epidermal permeability in eczema and on recognition in the gut of bacterial cell walls in inflammatory bowel disease are likely to be more important than direct testing of patients for DNA variation in the underlying genes.

    Practising clinicians will probably remain unconvinced: all these promising developments sound like “jam tomorrow.” Yet it is too easy to miss the significance of such developments in many fields. After severe acute respiratory syndrome hit the headlines around the world, no one expressed surprise when the nature of the infectious agent was published in a matter of weeks, a critical step that depended completely on the ability to analyse DNA. Virology and bacteriology have now embraced analytical techniques that are based on DNA testing with an enthusiasm equivalent to that seen in forensic science. In most developed countries every newborn baby is screened for the genetic condition phenylketonuria, and all surgical patients have their blood group analysed—more examples of how genetic science can reach the whole population without being recognised as “genetics.”

    Leaping into the future

    But the best is yet to come. Human factor VIII, used in the treatment of haemophilia, and human insulin will be followed by any number of human gene products whose manufacture will have its origins in that first report of the double helix. From hepatitis B vaccine to trastuzumab (Herceptin), an understanding of DNA permeates all sorts of developments in treatment. When the first patients are treated with a new stem cell treatment, few will note that treatment's critical dependence on our ability to unravel the genetics of early human development and to manipulate the genetic control of tissue differentiation.

    Zhou Enlai, first premier of the People's Republic of China, is reported to have said, when asked to give his opinion of the French revolution, that “it is too soon to say.” Some might make a similar argument in the case of DNA. Such scepticism will risk ridicule in years to come. The evidence already before us is dramatic, but it is nothing compared with the tsunami to come.


    • Publication of this online supplement is made possible by an educational grant from AstraZeneca

    • Competing interests: None declared.