DNA: How It Was Established As the Carrier of Genetic Information?
In the early 1980’s there was much debate occurring between scientists on which macromolecule in the cells carried genetic information. Many scientists during that day argued that proteins were the place where genetic information was stored and not DNA, merely because DNA was too simple; it had only 4 bases, while proteins had 20 different structures. However, through three very famous experiments, this theory was proven wrong and the debate was settled, and DNA was confirmed to be the genetic carrier.
The first of these experiments was performed by Frederick Griffiths in 1928. His experiment focused on the fact that genetic information could be transferred between organisms through transformation. His experiment consisted of lab mice, a rough-avirulent strain of Streptococcus pneumoniae, and a smooth-virulent strain of Streptococcus pneumoniae. In his first trial, Griffiths injected the mouse with living smooth stain and noted that the mouse died. He then injected a second mouse with living rough strain and found that the mouse lived. Next, he injected a third mouse with heat-killed smooth strain and observed that the mouse lived. Finally, he injected a fourth mouse with heat-killed smooth and living rough strain and saw that the mouse died. From this he could establish that there was something that was causing the living rough strain to transform into the virulent smooth strain. He called this unknown material the “transforming principal”.
In 1944, sixteen years after Griffiths completed and published his experiment, scientists Oswald Avery, Colin Munro MacLeod, and Maclyn McCarty performed an experiment based on Griffiths results. They were curious to find out what the “transforming principal” was. The first step in the Avery, McCarthy and MacLeod Experiment was to purify the DNA and proteins from the Streptococcus pneumoniae. In order to do this, they had to kill the bacteria with heat and extracting the water-soluble products. Then the protein was separated from the DNA using chloroform and was hydrolyzed with an enzyme. And the DNA was precipitated using alcohol fractionation. Once they had the protein and DNA purified their next question was which one transforms the avirulent bacteria into the virulent bacteria. When they inject the injected extracted protein into the bacteria, the mouse lived because the smooth strain was unable to transform the rough strain. When they injected the DNA into the bacteria and injected the mouse, the mouse died because the DNA transformed the rough strain into the virulent smooth strain. Their conclusion was that DNA was indeed the “transforming principal” in Griffiths’ experiment. However people still were not fully convinced. Some scientists argued that Avery, McCarthy, and MacLeod could have a contaminant in their experiment and argued that it could have been the transforming factor, not the DNA.
The argument finally came to a rest with an experiment performed by Alfred Hershey, and Martha Chase in 1952. They used bacteriophages that contained a DNA molecule surrounded by a protein coat. When the phages were introduced to the bacteria, they attach to the outside of the cell and inject their DNA into the bacterial cell. The protein coating however, is left on the outside of the cell. In the first part of the Hershey Chase experiment, the phages were grown in a medium containing radioactively labeled S35 amino acids. The DNA was not labeled. The S35 phage were then introduced to the bacteria and permitted to infect the cell, causing the radioactive protein coat to persist outside of the cell. When synthesis of new phages occurred within the cell, the protein coating was not labeled with radioactive material. They then blended the bacterial solution to detach the outer radioactive protein shells. When tested, they observed that the new phages did not have the radioactive protein coating. In the second part of the experiment, the phages were grown in a medium containing radioactively labeled P32 DNA. The protein was not labeled. Again the phages were permitted to attach and inject their DNA into bacterial cells. Once synthesis of new phages could occur inside the bacteria, the solution was again blended and the protein coats detached from the outside of the infected bacterial cells. When tested, they found that the new phages did have radioactive labeled DNA. Their conclusion confirmed that DNA was indeed the carrier of genetic information.
These three vital experiments shaped how scientists viewed the inheritance of genetic material and stirred a curiosity in scientists to understand how inheritance worked. Watson and Crick’s model of DNA followed shortly after the Hershey Chase experiment, and gave insight into the structure of DNA and how genes could be passed on throughout generations. From there, experiments on different models of how DNA was copied were debated. Many more experiments on DNA replication and inheritance have followed and will continue to do so, thanks to these brilliant scientists.