The dawn of DNA sequencing

1970s: Gel-based systems

No methods existed to read the genetic code, even in the simplest of genomes, so Fred was a real pioneer.

DNA sequencing began in 1977 with the development of the ‘Chain Termination Method’. This was developed by Fred Sanger and his team” at the Medical Research Council Laboratory of Molecular Biology in Cambridge, UK. Before this, no methods existed to read the genetic code, even in the simplest of genomes, so Fred was a real pioneer.

Fred Sanger based his DNA sequencing method, also known as the ‘Sanger Method’, on the natural process of DNA replication, where new strands of DNA are synthesised using an existing strand as a template. During the replication many new radioactively-labelled DNA strands are created and using ‘terminator’ bases each strand can be replicated at different lengths.

Electrophoresis helps to separate DNA fragments according to size.

The process also involved a technique called electrophoresis, which is still widely used today. This technique helps to separate DNA fragments according to size. DNA fragments are loaded into a gel and then an electrical current is passed through it. This pulls the DNA through the gel with small fragments moving further along the gel than larger fragments. An X-ray image of the gel, called an autoradiogram, can then be made to visualise the sequence of DNA.

Interpreting the results

In the early days, scientists had to read the sequence of DNA letters by hand.

In the early days, scientists had to read the sequence of DNA bases (A, C, G and T) off the autoradiogram by hand. Each base was in a separate lane and the autoradiogram was read from the bottom up (lowest base first to highest base last). The data was then manually entered into a computer.

As you can imagine, this was a long process. About 12 hours was required for the electrophoresis, another 12 hours for the autoradiogram to be developed and many hours to read the sequence!

The technique Fred developed is the foundation for the DNA sequencing technologies still used today.

Nonetheless, this technique set the ball rolling for modern DNA sequencing techniques and made way for many new discoveries. Fred Sanger and his team” were the first scientists to sequence a whole genome using this method. This genome was just over 5,000 bases long and from a virus called phiX174 that infects bacteria.

After this success, Sanger’s team” went on to sequence other genomes including the DNA from human mitochondria (the energy powerhouses of our cells). The technique Fred developed is the foundation for the DNA sequencing technologies still used today and has shaped genomics, the study of genomes.