In this episode, part 2 of the discovery of DNA, we come to understand how DNA was first isolated and demonstrated to be the molecule responsible for heritable traits. In the early to mid-19th century, biologists assumed that heritable traits were transmitted by proteins in cells.
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In this episode, part 2 of the discovery of DNA, we come to understand how DNA was first isolated and demonstrated to be the molecule responsible for heritable traits. In the early to mid-19th century, biologists assumed that heritable traits were transmitted by proteins in cells. Scientists at the time were isolating and purifying a large number of proteins from cells. Because of the wide variety of proteins being found, it seemed only natural that heritable information was being passed down from generation to generation through information embedded in proteins.
However, physician and biologist Johann Friedrich Miescher wasn’t convinced. Miescher studied the composition of pus from used bandages that were full of white blood cells, or leukocytes. Yeah, gross stuff, but in the 19th century it was not uncommon for physicians and chemists to study bodily fluids to figure out what they are composed of. In any case, unlike red blood cells which do not contain a nucleus nor DNA, white blood cells are nucleated and therefore do contain DNA. In 1869, Miescher isolated and identified a substance he called ‘nuclein’ because he believed it had come from the nucleus of white blood cells.
A few years later, in 1881, Albrecht Kossel identified nuclein as composed of nucleic acids and gave it its present chemical name, deoxyribonucleic acid or DNA. He also isolated the five nucleotide bases that are the building blocks of DNA and RNA: adenine (A), cytosine (C), guanine (G), thymine (T) and uracil (U). He was the first biologist to do a systematic study of cell division.
A year later in 1882 he discovered mitosis. He also observed that during mitosis, chromosomes doubled in number prior to cells separating into two daughter cells. This bolstered the argument that DNA, in the form of chromosomes, was the molecule responsible for trait inheritance.
However, chromosomes are only visible as distinct objects during a short time during the process of cell division. Most of the time nuclear DNA can’t be seen in the form of chromosomes but rather as a tangled mess of filaments like a pile of spaghetti. Walther Flemming, an anatomist from Germany, observed this fibrous material within the nucleus of cells. He named this material ‘chromatin’.
Flemming appeared to have no knowledge of Gregor Mendel’s work, and so didn’t make the connection between chromosomes and heritable traits.
The chromosome theory of inheritance was developed independently by Theodor Boveri and Walter Sutton. Boveri studied sea urchins and observed that without the full number of chromosomes in the sea urchin egg, it wouldn’t develop normally. This was a clue that chromosomes were necessary for inheriting information from parent to offspring. Walter Sutton studied grasshopper procreation, and observed that both the female eggs and male sperm contained matched pairs of chromosomes after undergoing a cellular process in reproduction called meiosis. He connected the dots and suggested that chromosomes might be the molecules responsible for the inheritance patterns Gregor Mendel had discovered.
Sir Archibald Edward Garrod finally associated Mendel’s laws of inheritance with a human disease. He published the first findings about recessive inheritance of human disease in 1902. Garrod led the way for understanding genetic disorders as producing errors in the chemical pathways in the body. Today many of these are known as inborn errors of metabolism.
More major breakthroughs in our understanding of DNA came in the 1940s. As is usually the case in science, there were many researchers involved, but I will touch on the highlights for the sake of keeping this brief. Microbiologist Oswald Avery was working on pneumococcus bacteria. The bacteria come in two forms, the R and the S versions. The R version is harmless but the S version causes disease. It was already known at the time that if you killed a colony of the S version and added the R version, the R version would transform into the disease-producing S version. This meant that something, presumably a chemical, could be transferred from the S version of bacteria to transform the R version from harmless to disease-causing. Avery treated the S version of bacteria with enzymes that destroyed proteins, but still transformed the R version into the S version. However, when he treated the bacteria with an enzyme that destroyed DNA, the transformation did not take place. This was essentially solid proof that DNA was the substance responsible for giving bacteria molecular information. By extension, this also meant that DNA was very likely the molecular responsible for heritable traits.
Between 1944 and 1950, Erwin Chargaff studies the composition of DNA in different species of living organisms. He found that the amount of the nucleic acids adenine, thymine, cytosine, and guanine were different in different species, but the ratio of adenine to thymine and cytosine and guanine, were always one-to-one. In other words, the proportion of A to T was always identical, as was the proportion of C to G. This was an important clue in determining that actual structure of DNA and how it encodes hereditary information.
All of the history discussed so far culminated in one of the most important, and dramatic, discoveries in scientific history. That will be discussed in the next episode.