Allan Maxam and Walter Gilbert describe a novel method for sequencing DNA using chemical cleavage. The technique involves breaking DNA molecules at specific bases (adenine, guanine, cytosine, or thymine) with chemical reagents, producing radioactive fragments that can be resolved by polyacrylamide gel electrophoresis. The method is based on reactions that preferentially cleave at guanines, adenines, and cytosines, with hydrazine specifically cleaving at thymine and cytosine. The sensitivity of the technique allows for the sequencing of at least 100 bases from the labeled end of the DNA molecule. The authors detail the specific chemistry of the reactions, including the use of dimethyl sulfate and hydrazine, and provide a step-by-step protocol for labeling, cleavage, and gel electrophoresis. They also discuss the advantages of the method, such as its ease of control and the ability to distinguish between different bases, and highlight its applications in sequencing double-stranded and single-stranded DNA.Allan Maxam and Walter Gilbert describe a novel method for sequencing DNA using chemical cleavage. The technique involves breaking DNA molecules at specific bases (adenine, guanine, cytosine, or thymine) with chemical reagents, producing radioactive fragments that can be resolved by polyacrylamide gel electrophoresis. The method is based on reactions that preferentially cleave at guanines, adenines, and cytosines, with hydrazine specifically cleaving at thymine and cytosine. The sensitivity of the technique allows for the sequencing of at least 100 bases from the labeled end of the DNA molecule. The authors detail the specific chemistry of the reactions, including the use of dimethyl sulfate and hydrazine, and provide a step-by-step protocol for labeling, cleavage, and gel electrophoresis. They also discuss the advantages of the method, such as its ease of control and the ability to distinguish between different bases, and highlight its applications in sequencing double-stranded and single-stranded DNA.