Part 3 : DNA Sequence Analysis Method

Archive of Analytical Instruments that Unravel Life

Part 3
DNA Sequence Analysis Method

In 1981, the Science and Technology Agency of Japan initiated the “DNA Extraction, Synthesis, and Analysis” project, proposed by Professor Akiyoshi Wada. This project can be regarded as the beginning of industry–academia collaboration aimed at developing a high-speed automated DNA sequencer. Four companies were selected from the industrial sector to develop first-generation DNA sequencers: Mitsui Information Systems, Seiko Electronics, Fujifilm, and Toyo Soda (now Tosoh).

At that time, the Maxam–Gilbert method, which reads DNA bases using radioactive isotopes and chemical cleavage, was the mainstream approach, and polyacrylamide electrophoresis was employed. However, because this method used slab gel electrophoresis, the equipment was large and not well suited for processing a large number of samples. Nevertheless, it was adopted in space development projects, with expectations that separation performance could be improved if electrophoresis were conducted under microgravity conditions in space.

However, around the same time as the emergence of PCR, practical application of the Sanger method—developed in 1977 and based on DNA polymerase—began to attract attention. The Sanger method, which offered advantages in many respects, quickly replaced the Maxam–Gilbert method. Around this period, development shifted toward second-generation DNA sequencers, with Hitachi, Ltd. joining the original four companies to form a five-company development framework. This marked a turning point that led to significant technological advancements continuing to the present day.

Initially, capillary gel array systems began with methods involving grooves carved into slab gels. These were later followed by a revolutionary approach using capillary tubes, leading to rapid technological progress.

While the Japanese team had made progress in developing automated analysis systems, the United States—supported by vast financial resources and a wealth of innovative ideas—quickly advanced the development of DNA sequencers incorporating the Sanger method. Among them, ABI, which had achieved success with gas-phase protein sequencers, rapidly developed the world’s first automated DNA sequencer combining the Sanger method with capillary electrophoresis (product name: Prism Model 3700 DNA Analyzer). This system was launched ahead of competitors in 1987 and established a dominant position in the international market.

However, it was not widely known at the time that this instrument incorporated several technologies originally developed in Japan.