The article discusses the sequencing of the human genome and its significance. It highlights the 20th anniversary of sequencing the first genome from a living species and the 15th anniversary of the White House announcement of the first draft of the human genome sequence. The authors mention their 2001 publication of the human genome sequence and their recent study on a completely synthetic genome, which proved that DNA is the software of life. The human genome sequence, consisting of 6 billion letters, requires philosophical and scientific scrutiny. It contains the instructions for building and maintaining the human body. Since the initial publication in 2001, understanding of the genome has begun to emerge. The authors' first human genome sequence article was a significant milestone, as the whole-genome shotgun (WGS) strategy was considered radical and unproven. They used WGS to sequence the first genome, *Hemophilus influenzae*, and then applied it to other genomes. The WGS strategy was faster, cheaper, and produced higher-quality sequences than other methods. In contrast, the federal Human Genome Project used a clone-by-clone approach. At Celera, they used 350 capillary DNA sequencing machines to generate 25 million sequence reads over 9 months for about $100 million. They also developed efficient computational algorithms for genome assembly. The human genome contains only about 1% protein-coding DNA, making it challenging to identify coding regions. Expressed sequence tags and other complementary DNA sequences showed that alternative splicing is common in human genes, leading to diverse protein variants. Non-protein-coding RNAs also play important roles in gene regulation. Every human is unique, with differences that matter for traits and disease risks. Sequencing a mixture of 5 people revealed a nonrandom distribution of genetic variants, suggesting variation in mutation rates and selection across the genome. The WGS method has been so successful that over 99% of sequenced genomes have used it. Today, the method is efficient and cost-effective, proving its long-term value. The article is dedicated to two colleagues who contributed to the first human genome sequencing.The article discusses the sequencing of the human genome and its significance. It highlights the 20th anniversary of sequencing the first genome from a living species and the 15th anniversary of the White House announcement of the first draft of the human genome sequence. The authors mention their 2001 publication of the human genome sequence and their recent study on a completely synthetic genome, which proved that DNA is the software of life. The human genome sequence, consisting of 6 billion letters, requires philosophical and scientific scrutiny. It contains the instructions for building and maintaining the human body. Since the initial publication in 2001, understanding of the genome has begun to emerge. The authors' first human genome sequence article was a significant milestone, as the whole-genome shotgun (WGS) strategy was considered radical and unproven. They used WGS to sequence the first genome, *Hemophilus influenzae*, and then applied it to other genomes. The WGS strategy was faster, cheaper, and produced higher-quality sequences than other methods. In contrast, the federal Human Genome Project used a clone-by-clone approach. At Celera, they used 350 capillary DNA sequencing machines to generate 25 million sequence reads over 9 months for about $100 million. They also developed efficient computational algorithms for genome assembly. The human genome contains only about 1% protein-coding DNA, making it challenging to identify coding regions. Expressed sequence tags and other complementary DNA sequences showed that alternative splicing is common in human genes, leading to diverse protein variants. Non-protein-coding RNAs also play important roles in gene regulation. Every human is unique, with differences that matter for traits and disease risks. Sequencing a mixture of 5 people revealed a nonrandom distribution of genetic variants, suggesting variation in mutation rates and selection across the genome. The WGS method has been so successful that over 99% of sequenced genomes have used it. Today, the method is efficient and cost-effective, proving its long-term value. The article is dedicated to two colleagues who contributed to the first human genome sequencing.