454 Life Sciences: Illuminating the future of genome sequencing and personalized medicine

Imagine going to the doctor with a migraine headache and knowing the next day whether your DNA is to blame. Or better yet, imagine knowing whether your DNA encodes a risk for migraines even before a headache strikes. If 454 Life Sciences' dream is realized, doctors will be able to quickly and inexpensively unlock the mysteries of patients' genomes, revealing indicators of disease susceptibility and shedding light on the potential efficacy of particular drug regimens. Due to advances in technology made by companies like 454 Life Sciences in Branford, Connecticut, personalized genomic medicine is becoming a reality and is sure to revolutionize not only your doctor's visits, but also the way society views human health and disease. Founded in 2000 with the mission of making individual human genome sequenc-ing a reality, 454 Life Sciences has proven itself a front-runner in the race toward personalizing medicine. As the story goes, 454's founder Jonathan Rothberg, PhD, was faced with a family health emergency. His newborn son was ill, and as he waited to hear news from doctors, he pondered the idea of pinpointing his child's condition by reading his genome — and, thus, his quest to provide fast, affordable genome sequencing began. The first gene sequencing technology was developed by Frederick Sanger in 1977. The innovation behind the Sanger method involved the use of dideoxynu-cleotide triphosphates to terminate elonga-tion of a DNA primer (a short fragment complementary to a single-stranded DNA template of interest). Variations of the Sanger method have contributed to almost all of our current knowledge of gene and genome sequences. However, the technique has certain limitations. In particular, large-scale projects like the sequencing of full organism genomes by the Sanger method involve the rather laborious task of creating a library of genomic fragments in bacterial plasmids, which then are sequenced and assembled. Costly reagents and time-consuming sample preparation make this approach unfeasible for use in a clinical setting , where cheap, fast, and accurate se-quencing is demanded. The Sanger method was used for the Human Genome Project and was the gold standard for decades — until 1998, when scientist Mostafa Ronaghi at Stanford University [1,2] worked out the chemistry behind the technology of pyrosequencing, the method eventually adapted by 454 Life Sciences. Pyrosequencing refers to a series of