Scaling up for the Human Genome Project

1990s: Capillary sequencing

• Cost to sequence 1 million bases: £3,457
• Time to sequence a human genome: 12 years

By the mid-1990s, the Human Genome Project was in full swing.

By the mid-1990s, when the Human Genome Project was in full swing, scientists were sequencing DNA using capillary sequencers. This was much safer than previous methods and was able to process a much larger set of samples. Instead of sequencing 24 samples like the gel-based sequencing machine, capillary sequencers could manage 96 samples.

In capillary sequencing machines, DNA fragments are separated by size through a long, thin, acrylic-fibre capillary.

In capillary sequencing machines, DNA fragments are separated by size through a long, thin, acrylic-fibre capillary instead of an electrophoresis gel. A fluorescence-detecting laser, built into the machine, then shoots through the capillary fibre, making the coloured tags on the DNA bases fluoresce.

Each base terminator is labelled with a different colour: A = Green, C = Blue, G = Yellow and T = Red. The colour of the fluorescence is detected by a camera and then displayed on a computer as a graph of different coloured peaks, like this:

This would be the pattern recorded from just a small section of one of the 96 lanes in the sequencing machine, so you can imagine just how much data the machine needs to process to sequence an entire human genome!

With capillary sequencing, a single lab technician could service dozens of instruments at once.

The small diameter of the capillary allows for the use of extremely high electric fields, and consequently, very rapid separation of DNA sequencing fragments. Importantly, capillaries are also easily incorporated into an automated instrument, making them very useful during the Human Genome Project.

With capillary sequencing, a single lab technician could service dozens of instruments at once. It was no longer necessary to check each lane by eye as the DNA was contained within the capillary fibre. Both of these features helped remove a huge bottleneck from the sequencing process.

John Burton, a group leader at the Wellcome Trust Sanger Institute during the Human Genome Project, talks about how DNA sequencing technologies have changed over time to cope with increasingly large genomes, such as the human genome.