Genes are made of protein because proteins are complex enough to carry hereditary information, while DNA is only a structural scaffold.

Proteins looked like the obvious hereditary material. They were chemically diverse and structurally complicated, while DNA seemed monotonous—a polymer built from only four nucleotides. For many geneticists, protein simply looked more capable of encoding biological complexity.

Avery, MacLeod, and McCarty tested the question through bacterial transformation. They purified the material that could transfer a heritable trait between strains of Streptococcus pneumoniae and then selectively destroyed different molecular classes.

Destroying protein did not eliminate the transforming activity. Destroying DNA did.

The 1944 result was pivotal but not instantly accepted. Some researchers worried about contamination or remained convinced that proteins were the more plausible information carrier. Later bacteriophage experiments and the elucidation of DNA structure made the case overwhelming.

DNA is now recognized as the hereditary material of cellular organisms and many viruses, with sequence information stored in its nucleotides.

Some viruses use RNA genomes instead, so heredity is not universally restricted to DNA. The historical reversal concerns the protein-versus-DNA question in cellular genetics.