The mid-20th century marked a period of intense investigation in biology, as researchers sought to identify the molecule responsible for heredity. By the 1940s, scientists had established that the genetic material resided within the chromosomes inside the cell nucleus. These chromosomes were known to be complex structures composed of both deoxyribonucleic acid (DNA) and protein. At the time, the overwhelming consensus within the scientific community favored protein as the molecule of inheritance.
Protein’s Vast Information Storage Potential
The sheer complexity of life, with its enormous diversity of traits and functions, suggested that the genetic molecule must possess a corresponding level of structural variability. Proteins appeared to meet this requirement perfectly, which made them the leading candidate for carrying complex genetic instructions. They are built from a large alphabet of 20 distinct amino acids, which can be arranged in nearly limitless sequences to form long polypeptide chains.
The potential for information storage in a protein molecule is immense. A protein composed of just 100 amino acids has a staggering number of possible unique sequences, far exceeding the number of genes scientists estimated were required for inheritance. This combinatorial power was viewed as the chemical structure capable of encoding the vast and intricate instructions needed to specify an organism’s entire biology.
Proteins were already recognized as the workhorses of the cell, demonstrating incredible functional diversity. They served as enzymes to catalyze biochemical reactions, acted as structural components, and functioned as signaling molecules. This known capacity for dynamic action and functional specificity strongly suggested that proteins were uniquely suited to control and direct the processes of heredity.
The Tetranucleotide Hypothesis and DNA’s Perceived Simplicity
While proteins were celebrated for their complexity, DNA was widely dismissed as the genetic material due to a fundamental misunderstanding of its chemical structure. This perception was largely shaped by the “tetranucleotide hypothesis,” a theory proposed by biochemist Phoebus Levene in the early 20th century. Levene’s work correctly identified the components of DNA—the four nitrogenous bases (Adenine, Guanine, Cytosine, and Thymine), a deoxyribose sugar, and a phosphate group—but his structural model was flawed.
The tetranucleotide hypothesis suggested that the four bases were present in equal amounts and repeated in a simple, monotonous pattern: A-T-C-G, A-T-C-G, and so on. This proposed structure implied that DNA was merely a simple polymer lacking the necessary variability to encode complex traits. Scientists reasoned that a molecule with such a uniform and repetitive structure could not possibly store the enormous and intricate information required for genetic inheritance.
DNA was relegated to the role of a simple structural scaffold within the chromosome, a kind of chemical support for the far more complex protein component. The small alphabet of just four nucleotide units, compared to the 20 amino acids in proteins, reinforced the idea that DNA was chemically too simple to account for the diversity observed in living things. This prevailing view led many researchers to overlook early experimental evidence pointing toward DNA’s true role.
Localization and Abundance of Protein in Chromosomes
Physical observations within the cell also provided compelling evidence that favored protein over DNA as the genetic material. Chromosomes, the structures known to carry genes, were found to contain roughly equal amounts of DNA and protein. The protein component included both structural histones and a variety of non-histone proteins.
Proteins were known to be metabolically dynamic, constantly being synthesized, modified, and broken down, suggesting they were the machinery of life. In contrast, DNA appeared chemically inert and stable, which researchers mistakenly interpreted as an indication of a passive, structural role.
Proteins were observed throughout the cell, fulfilling diverse and active roles in the cytoplasm as well as the nucleus. This ubiquity and functional activity made them seem like the obvious candidates for controlling the cell’s heritable traits. The close physical association of proteins with DNA in the chromosomes reinforced the belief that the protein must be the substance that transmitted genetic information.