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This review commemorates the 40th anniversary of DNA sequencing, a period in which we have already witnessed multiple technological revolutions and a growth in scale from a few kilobases to the first human genome, and now to millions of human and a myriad of other genomes. DNA sequencing has been extensively and creatively repurposed, including as a ‘counter’ for a vast range of molecular phenomena. We predict that in the long view of history, the impact of DNA sequencing will be on a par with that of the microscope. The history and future potential of DNA sequencing, including the development of the underlying technologies and the expansion of its areas of application, are reviewed. DNA sequencing at 40 This year marks the 40th anniversary of the Sanger method for DNA sequencing, the most widely used sequencing method, pioneered by Fred Sanger and his team in 1977. Jay Shendure and colleagues review the evolution of sequencing technologies since their inception, highlighting the major milestones in the development, analyses and applications of genome sequencing over the past 40 years. Despite multiple technological revolutions and growth in scale, the authors see DNA sequencing as a relatively nascent technology in the grand scheme of scientific history. They review current emerging applications and discuss the continued evolution and future of DNA sequencing from population-scale resequencing to networks of portable sensors used for real-time monitoring in environmental settings.

The first bacterial genome sequence was published 20 years ago. In this Timeline, Loman and Pallen review the first two decades of bacterial genome sequencing, discussing how advances in sequencing technologies and bioinformatics have furthered our understanding of the biology, diversity and evolution of bacteria. Twenty years ago, the publication of the first bacterial genome sequence, from Haemophilus influenzae , shook the world of bacteriology. In this Timeline, we review the first two decades of bacterial genome sequencing, which have been marked by three revolutions: whole-genome shotgun sequencing, high-throughput sequencing and single-molecule long-read sequencing. We summarize the social history of sequencing and its impact on our understanding of the biology, diversity and evolution of bacteria, while also highlighting spin-offs and translational impact in the clinic. We look forward to a 'sequencing singularity', where sequencing becomes the method of choice for as-yet unthinkable applications in bacteriology and beyond.

[...] technology development for sequencing and functional genomics - key to the success achieved thus far - must continue to be a major focus of investment by both the public and private sectors. [...] the success of personalized medicine will depend on continued accurate identification of genetic and environmental risk factors, and the ability to utilize this information in the real world to influence health behaviours and achieve better outcomes.

Human genomics comes of age To mark the tenth anniversary of the publication reporting a draft sequence of the human genome by the Human Genome Project, this issue of Nature presents three major papers about human genomics. Eric Lander, present at the birth of the Human Genome Project, looks back at what has been achieved in genomics and speculates on future prospects. Elaine Mardis discusses the DNA sequencing technologies that have catalysed the rapid genomic advances over the past ten years. And Eric Green, Mark Guyer and others from the US National Human Genome Research Institute provide a vision for the future of genomic medicine. The sequence of the human genome has dramatically accelerated biomedical research. Here I explore its impact, in the decade since its publication, on our understanding of the biological functions encoded in the genome, on the biological basis of inherited diseases and cancer, and on the evolution and history of the human species. I also discuss the road ahead in fulfilling the promise of genomics for medicine.

Genomic data will soon become a commodity; the next challenge — linking human genetic variation with physiology and disease — will be as great as the one genomicists faced a decade ago, says J. Craig Venter.

The first medical interventions were often individualized but ineffective, because doctors lacked an understanding of disease biology. As medicine became more scientific, physicians started grouping patients by disease. Now, genetic insights let doctors consider their patients' unique make-up when prescribing treatments.

After figuring out that it required Fourier transforms and computers and deep knowledge of chemistry, and had implications for medicine, I thought it was the whole package. Gail provided the world's first embryonic stem cells (called PSA-1). Some of the many applications in your lab have been gene drives in mosquitoes to eradicate malaria, to using CRISPR to eliminate 62 different porcine endogenous retrovirus genes at once toward the goal of using pig organs for human transplantation. [...]it took me years to realize I was actually more of an engineer than I was a scientist.

The scientists of today have become accustomed to the extremely rapid pace of progress in the biomedical sciences spurred on by the discovery of recombinant DNA and the advent of automated DNA sequencing and PCR, with progress usually being measured in months or years at most. What is often forgotten, however, are the many prior advances that were needed to reach our present state of knowledge. Here I illustrate this by discussing the scientific discoveries made over the course of the past century and a half that ultimately led to the recent successful development of drugs, particularly imatinib mesylate, to treat chronic myelogenous leukemia.