Thirty-seven years after Watson, Crick, and Franklin solved the double helix in 1953, biology was ready for a much bigger question: what exactly is written in the human genome? In the late 1980s the U.S. Department of Energy and the National Institutes of Health set an ambitious target — to read, letter by letter, the roughly 3 billion base pairs (A, T, G, C) spread across the 23 chromosomes of a human cell. The project officially began on 1 October 1990, with a 15-year timetable and a 3 billion dollar budget. It was led first by James Watson and then by Francis Collins; 20 major institutes from the United States, the United Kingdom (the Sanger Centre), France, Germany, Japan, and China divided the work.

In 1998 came an earthquake. An iconoclastic scientist named Craig Venter founded a private company, Celera Genomics, and announced that with a faster "shotgun" sequencing technique he would finish the same job in three years for a tenth of the cost — and intended to patent the results. The race between the public consortium and Celera became one of the most intense rivalries in modern science. On 26 June 2000, at the White House, President Bill Clinton stood Francis Collins and Craig Venter side by side and announced the joint completion of a draft genome: "Today we are learning the language in which God created life." The full sequence was completed on 14 April 2003 — the 50th anniversary of the publication of the DNA structure. The result was a surprise: the human genome contained not 100,000 but only about 20,000 protein-coding genes — fewer than a banana plant.

The real legacy was less the sequence itself than the wave that followed it. In 2001 sequencing a single human genome cost 100 million dollars; by 2014 the figure was 1,000 dollars, and by 2022 it had fallen below 100 dollars — a price drop five times faster than Moore's Law. Genome sequencing turned tumour profiling in cancer treatment, prenatal diagnosis, identification of rare diseases, and ancestry tests (23andMe, AncestryDNA) into mass-market services. During the pandemic the genome of SARS-CoV-2 was released to the world on 11 January 2020 — weeks after the virus emerged from Wuhan — and the first mRNA vaccines were in production within 11 months; such speed was only possible because this infrastructure existed.

But illumination also brought shadows. Fears that genetic information would be used by insurers or employers to discriminate led to the 2008 Genetic Information Nondiscrimination Act (GINA) in the United States. Companies like 23andMe gathered the DNA of millions into private databases; in 2018 the Golden State Killer was caught after 40 years through a relative's genealogy test — but the same databases also meant a new capacity for surveillance. In 2018 the Chinese scientist He Jiankui announced the birth of the first CRISPR-edited human embryos as twin girls, provoking international outrage and a prison sentence. The Human Genome Project drew the map of 21st-century biology; which directions to take across that map is still being argued.