SMRT Sequencing — The PacBio Spirit of Past, Present, and Future

In the rapidly evolving world of DNA sequencing, the community is often focused on what’s new and what’s next. There’s not much opportunity for retrospection. But two recent articles offer an insightful look at the history of SMRT Sequencing technology, from the time it was just a gleam in the eye of some Cornell University scientists to how it works and some exciting new applications.
At Technology Networks, reporter Ruairi MacKenzie writes about the scientific beginnings of SMRT Sequencing with memories from PacBio CSO Jonas Korlach, one of the inventors of the technology.
“Korlach concluded that if only you could see DNA polymerase doing its incredible, evolution-assisted work, then you could simply let the enzyme do the heavy lifting and take notes on its performance to create a top-quality sequencing technique,” MacKenzie reports. He describes the powerful collaboration of Korlach, Watt Webb, Steven Turner, and Harold Craighead in the project that would ultimately begin the path to PacBio.
“This started off a series of experiments that aimed to create a microscope that was, in effect, a thousand times more powerful than any currently available,” the article continues. “The eventual product of a number of attempts was the zero-mode waveguide, the foundation of PacBio’s sequencing technology.”
The article also covers the various optimization experiments that ensued, such as figuring out how to create fluorescent tags that wouldn’t decrease sequencing efficiency. If you ever wondered where SMRT Sequencing got its start, this piece provides the answer.
A Wall Street Journal article covers the past 15 years of DNA sequencing, from the public/private competition to sequence the first human genome all the way to some of the most recent and compelling scientific projects being powered by SMRT Sequencing.
The article reports on potential clinical applications for long-read sequencing, such as helping to diagnose rare diseases. “Mr. Hunkapiller says PacBio’s machines can help by detecting what are called ‘structural variants,’ changes to DNA that may involve hundreds or even thousands of base pairs, making them difficult to pick up with earlier technology,” Kyle Peterson writes. “Last year a group at Stanford was able to diagnose a young man whose heart had repeatedly grown benign tumors. One of his genes on Chromosome 17 was missing 2,200 base pairs.”
The article also describes other interesting recent applications of SMRT Sequencing platforms, including the largest known genome from the tiny Mexican salamander, the 100 ants project, and bat longevity.
It’s a great time of year to reflect on the history of the technology and how scientists are applying it today, and we encourage you to check out both articles on your next coffee break.