The discovery of DNA was a slow process, one that occurred over the course of almost a hundred years. During that time many different scientists were responsible for contributing to its overall meaning, scientists that included biologists, chemists, and physicists. It was never a problem worked solely on by biologists, and it took a whole cast of characters in order to finally get to the model of DNA that we know of today.
Early Organic Chemistry Work
Friedrich August Kekule was one of the first scientists to put forth the idea of carbon atoms being able to link to each other. Kekule found that carbon (which is a component of all organic molecules) is especially important because it can bond to four different chemicals or atoms at the same time. He managed to uncover this truth by using, what we would consider, to be very rudimentary chemistry techniques. His main tool was to use chemical reactions in order to distill down his theory about carbon. This novel idea led to further discoveries that individual elements could be attached to each other in different shapes and patterns. Through this insight into one of the most important of the elements of the periodic table, scientists began to unravel the idea of the macromolecule.
The macromolecule theory was founded on the ideas of Emil Fischer, that the molecules being seen by researchers were actually just parts torn off from the whole organism. He attempted to prove his hypothesis by breaking down the different molecules or “residues” of a polypeptide (a smaller form of what he considered a macromolecule). He concluded that there were thirty different residues, which made up this smaller portion.
This conclusion ended up disproving the idea of the body as a macromolecule. If looked at mathematically, the different ways that those 30 residues could be utilized would leave almost no room for any more within the body. In the end, the theory of the macromolecule for the whole body was proven incorrect. Which allowed an opening for a young Swiss doctor studying cells, to step onto the DNA stage.
Friedrich Miescherand Nuclein
Our next act in the story of DNA begins with pus. Friedrich Miescher was a Swiss doctor who was interested in what was called, at the time (1868), physiological chemistry. We now think of it as the study of biochemistry. Miescher was interested in leukocytes, or white blood cells, and one of the best ways to get them was from the pus found on surgical bandages. He developed a method of washing the leukocytes from the bandages and then separating the nucleus of the cell from its other components. He was interested in looking at what made up the inside of the nucleus, expected proteins and lipids.
What he found was a large structure that was very hard to dissolve, and would reconstitute itself in certain conditions. He concluded that this was not one of the proteins, but a completely different molecule entirely. He called this molecule nuclein, as it was found in the nucleus of the cell.
Miescher determined that nuclein contained organically linked phosphorus, which at the time, was in and of itself a large discovery. He determined almost the exact ratio of phosphorus to the other elements in the nuclein, which included carbon, hydrogen, nitrogen, and oxygen. He also theorized that it was a multi-basic acid, believing it to have at least three or four bases. We now know this to be a very close theory to what was later found to be true by Phoebus Levene.
Phoebus Levene And Edwin Chargaff
At the time that Phoebus Levene was working, scientists were attempting to figure out the linkage of nuclein, or as it became called, nucleic acid. In his long career Levene discovered many important facts about DNA and RNA. One of the most important, and one that eventually helped Watson and Crick, was that nucleic acid was made up of three components, a phosphate-sugar-base, connection. It was some time before Levene’s work was fully understood in the context of DNA. Edwin Chargaff would utilize Levene’s work, and expand upon it further.
Chargaff was interested in examining the DNA from different species. He found that while Levene had suggested that nucleic acids remained in the same sequence, his research showed the exact opposite. Each species had a different amount of nucleotides in its DNA. He also found that certain nucleotodes seemed to exist in the same ratio as another nucleotide. Adenine was usually similar to the amount of Thymine. Guanine was usually similar to the amount of Cytosine. These relationships would later become known as “Chargaff’s Rules”.
Watson, Crick, Wilkins & Franklin
By the 1950’s the rush was on to discover the structure of DNA. There were two main competing laboratories, both using very different methods to elucidate the complex structure. Maurice Wilkins and Rosalind Franklin were working at King’s College and were using X-ray diffraction in order to study DNA’s structure. James Watson and Francis Crick were at Cambridge University and were using a modeling approach to the DNA question.
What occurred next remains a bit of a controversy in scientific circles. Watson and Crick were very close to finding the structure of DNA. But they were missing a piece of evidence that they just could not seem to find. Rosalind Franklin had a picture of DNA, entitled Picture 51 that showed an interesting arrangement of molecules. Wilkins, in a slightly imprudent maneuver, showed the picture to Watson and Crick without Franklin’s permission.
The picture revealed what the two had been edging towards. DNA was a double helix, with a sugar-phosphate backbone, with the bases (adenine, thymine, guanine, and cytosine) facing inward. Each of the strands of the double helix ran opposite to each other, allowing for the strands to bond between the matching bases, in the same ratio as Edwin Chargaff had predicted. All four published papers on DNA in the same edition of the scientific journal Nature, detailing their findings on the structure of DNA.
James Watson, Francis Crick, and Maurice Wilkins were given the Noble Prize for their work. Rosalind Franklin had already passed away from cancer at that time, and the award cannot be given posthumously. While Watson and Crick rightly get most of the acknowledgment for figuring out the structure of DNA. Franklin and Wilkins were indispensable in helping to add to their knowledge in order to lead them to their famous discovery.
- Ralf Dahm, Hum Genet (2008) 122:565-581