 DNA is considered the molecule of life, and is now easily identified as a double helix. However, figuring out its structure and how DNA works was not an easy task. And just a little over 60 years ago, it was still a complete mystery. Then in 1953 came Watson and Crick, who, with the help from colleagues Rosalind Franklin and Morris Wilkins, discovered how the 6 billion base pairs that make up our genetic material are stored in a cell. The DNA was actually a helix made of two strands. This DNA was passed on from generation to generation as a double helix. Specific DNA bases, which we call A adenine, T thymine, G guanine, and C cytosine are found on both strands and pair with each other in a conserved way. A pairs with T and G pairs with C. Our DNA is made up of these four bases in a variety of different orders that code for all of life. This is an amazing fact. These four bases are the sole building blocks for our 6 billion bases genetic code, which defines our identity as humans and as individuals, our height, hair color, disease, susceptibility, and much, much more. Discovering the structure of DNA was a very important first step to understanding how this seemingly simple molecule controls all of life. However, one important question lingered. When a cell divides, the daughter cell will have the same DNA sequence as the parental cell. So how does this happen? How does one cell produce a second cell with the same exact DNA sequence? In other words, how does DNA replicate? This is a fundamental question that is the basis of life. We all come from a single cell that will produce an entire organism with trillions of cells that all have the exact same DNA sequence. And we are able to have children that share our DNA because their eggs and sperm carry our DNA sequence. Understanding how DNA replicates and how all of our cells can carry the same DNA sequence is the basis for understanding development, inheritance, heritability, and life. In 1953, the question lingered. How does DNA replicate? There were a few theories, three actually. One of them was conservative replication, where a DNA molecule would get copied and make a second new red DNA molecule. The second was dispersive, where the DNA molecule would be cut at various parts, each of which would get copied here in red and reattached to produce two DNA molecules. And the third was semi-conservative, where two DNA strands would separate and each one would serve as a template to copy a second red strand, thus producing two DNA molecules. But which one was it? Many scientists did not believe that two DNA strands could separate because of how strong a DNA molecule is, so they were skeptical of the semi-conservative model. The only way to solve this was to create an experiment. So tell the new DNA strand from the old one. So two scientists, Matthew Miselson and Franklin Stahl, had an idea to design an experiment that would be known as the most beautiful experiment in biology. Their findings are published in their article titled The Replication of DNA in E. Coli, published in May 1958 in the Proceedings of National Academy of Sciences. These scientists used bacteria to answer the question of DNA replication, since it could be easily grown in the laboratory. They grew the cells in the presence of a specific type of nitrogen, which is found in DNA that would make all of the DNA very heavy. They used centrifugation, which can separate things according to their weight. Initially, all of the DNA in the cell was heavy, and was at the bottom of the tube, since it was grown in heavy nitrogen. Then they started growing these cells in the presence of light nitrogen, so all of the DNA made in subsequent cell divisions would be lighter. For one cell division, the DNA was half as heavy, so half of the DNA molecule contained heavy nitrogen and the other half didn't. This is not in line with the conservative DNA replication model, which would predict that one molecule would be all light and the other all heavy. However, this is in line with the semi-conservative or the dispersive model. After two cell divisions, the DNA molecule was now either half heavy and half light or entirely light. So this is now not in line with the dispersive model, which would predict that the DNA after two cell divisions would contain a mixture of heavy and light DNA. Instead, this experiment agrees with the semi-conservative DNA replication model. Every cell gets one old DNA strand and one new one. By discovering that two strands of DNA can separate and provide the template for the production of two new strands, Misselson and Stahl revolutionized genetics. Scientists were very skeptical that this was even possible, but Misselson and Stahl proved it with a beautifully designed experiment. They also went on to show that heating DNA can cause the DNA strands to separate. This simple concept is the basis for an important technique we frequently use in the laboratory called polymerase chain reaction, which is used in genetic testing, forensics, and paternity tests. Misselson and Stahl identified the fundamental process by which our DNA gets passed on from cell to cell. This is the basis for inheritance and an essential part of our development from a single cell to a complete organism that maintains the same DNA sequence in all of its cells. This exciting finding opened up many new doors and research avenues. Because DNA is the command center of the cell, we could now study how DNA gives orders for the cell to follow. What controls the ability of DNA to make protein? How does one cell know it's a heart cell and another cell know it's a liver cell if they all have the same DNA? Now, DNA wasn't just a static double helix. It was a molecule that was animated. It could make more of itself. It could instruct a cell to behave a certain way. All of the secrets of biology were ready to be answered. Today we understand many of these questions. We know that the process of DNA replication is very complex, with many proteins coming together to make this happen, as well as proofreading and repair mechanisms to make sure that DNA is properly copied. We can even produce a heart cell from a skin cell. We know what controls cell division and how we can stop or accelerate it. We know what sorts of things can cause mutations or changes in the DNA sequence and how that influences cell behavior, such as in cancer. It's amazing now to look back at this very fundamental finding that DNA replicates in a semi-conservative manner and see how it has revolutionized biology and our appreciation for DNA. This video has been provided to you by Eureka Science and iBiology, bringing the world's best biology to you.