Decades of MRC research into the human genome has led to the development of technologies such as DNA sequencing, fingerprinting and chips that have had a huge impact on medical research and medicine. Today, the industry based on genomics, including gene-based services, diagnostics and potential new drugs, is worth around £3.5 billion per year.
Professor James Watson and Dr Francis Crick, working in the MRC’s unit at the Cavendish Laboratory in Cambridge, famously described the structure of DNA in the scientific journal Nature in April 19531.The work owed a substantial debt to Dr Rosalind Franklin and Professor Maurice Wilkins at the MRC Biophysics Unit at King’s College London.
The discovery transformed scientists’ understanding of human diseases and treatments and triggered the development of new DNA technologies with enormous economic and health benefits. Professors Watson and Wilkins and Dr Crick won the 1962 Nobel Prize in Physiology or Medicine for this work; Dr Franklin had died four years previously.
The code of life
Determining the structure of DNA laid the foundation for a genetic revolution that went on to establish in the 1960s that three-letter DNA ‘codons’ formed the basis of instructions for building proteins. In the 1970s, MRC scientist Dr Frederick Sanger’s DNA sequencing technique2 and other methods to manipulate and analyse DNA gave scientists the basic toolkit to begin exploring the DNA blueprint. Dr Sanger won two Nobel Prizes for this and further work on the structure of proteins.
Building on this work, in 1998 UK and US researchers including the MRC Laboratory of Molecular Biology’s Dr Sydney Brenner and Sir John Sulston finished sequencing the C. elegans genome – the first complete sequence of a multicellular organism3. Their work provided the techniques for a vast international project that culminated in 2003 with a team of researchers, including MRC scientists, establishing the DNA sequence of the entire human genome.
DNA and forensic science
DNA fingerprinting technology was invented in 1984 by MRC-funded scientist Sir Alec Jeffreys at the University of Leicester4. His invention has helped to push forward the fields of genetics and genomics and has led to research into genetic markers of human diseases. The technique has also revolutionised forensic science, matched donors to patients in need of lifesaving organ transplants, and provided an infallible method of paternity testing. And it has helped to establish family relationships in immigration cases, determined human origins and patterns of migration, and helped save endangered animal species.
The technique built on work by MRC-funded scientist Sir Edwin Southern, who invented a novel method for analysing DNA called Southern blotting. Sir Alec exploited Southern blotting to develop a way to distinguish all humans – except for identical twins – from each other. He discovered that each person’s DNA had a distinct and unique pattern of repeat areas called microsatellites. Unrelated humans have different numbers of microsatellite repeats at particular sites on their DNA. DNA fingerprinting can detect the number of repeats in several different locations, making it possible to establish a match that is exceptionally unlikely to arise by coincidence. The patterns in an individual’s genetic fingerprint are a hybrid of patterns from their parents’ DNA.
In the UK in 2005, the UK Forensic Science Service (FSS) used DNA fingerprinting techniques to match 40,000 samples from crime scenes to people’s records on the National DNA Database, including 165 homicides, 100 attempted murders and 570 rapes. Also, the FSS has developed what they describe as a world-leading DNA expert system enabling automatic analysis and interpretation of DNA profiles. The system is now being made available to the international forensic community including the USA, Canada, Europe, Australia and New Zealand, resulting in an important economic spin-off for the UK from the technology.
Genes on chips
Sir Edwin, in his laboratory at Oxford University, went on to further develop Southern blotting, culminating in the invention of today’s DNA chip, or microarray, technology. He invented a technique for attaching ordered arrangements of thousands of DNA molecules to the surface of a chip the size of a thumb nail. These chips allow scientists to compare the sequence or expression of genes in different tissues or individuals, enabling diagnosis of disease and potentially enabling choice of treatment based on genetic make-up. DNA chip technology is also used in drug discovery to identify potential drug targets, and can be used to study changes in gene expression in response to drug treatment. The global market for DNA chips reached almost £1.6 billion in 2005.
1. Watson & Crick (1953). Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid. Nature, 171, 737.
2. Sanger & Coulson (1975). A rapid method for determining sequences in DNA by primed synthesis with DNA polymerase. J Mol Biol, 94, 441.
3. C. elegans Sequencing Consortium (1998). Genome sequence of the nematode C. elegans: a platform for investigating biology. Science, 282, 2012.
4. Gill et al. (1985). Forensic application of DNA ‘fingerprints’. Nature, 318, 577.
MRC, July 2006