It took about 50 years to disprove the "Tetrnucleotide Hypothesis", which maintained that DNA consisted of four nucleotides joined together.
In a study, reported in 1934, Torbjorn Casperson filtered DNA and came to "the astonishing fact that the complexes of nucleic acids must be larger than protein molecules". Which led to three further studies.
Rudolf Signer measured the molecular weight of DNA by allowing it to flow along a narrow tube and measuring the refraction of light shone through it (flow birefringence). The way the light was bent (double refraction) seemed to indicate the presence in DNA of very long molecules oriented in the direction of the flow through the tube.
At the time, a value of 500,000 to 1 million was estimated for the molecular weight of the DNA, a number vastly higher than the weight of a "tetranucleotide".
Ultracentrifugation, made possible by the very fast centrifuges invented in Sweden, made it possible to follow the sedimentation properties of molecules in high gravitation fields (the tubes of the rapidly spinning centrifuge).
Proteins had high molecular weights, when studied in this way, with values in the 10's of thousands - true macromolecules, but DNA was even larger and in 1938 Levene and Schmidt were able to measure numbers as high as 1 million.
The numbers did not match. Different preparations of DNA gave different molecular weights (indicating that the DNA was being degraded during purification), and all of the numbers were considerably higher than the value of 1,500 for a tetranucleotide. Could it be that DNA was a polymer?
Did it matter? No one knew what DNA did, and most scientists considered it little more than a skeleton on which valuable genetic proteins were hung.