Inventors of nanopore sequencing honored at Library of Congress

(Press-News.org) Two UC Santa Cruz researchers were honored on September 27 at the Library of Congress for the invention of nanopore sequencing, which became a new and revolutionary method to read DNA and RNA.

David Deamer and Mark Akeson, both emeritus professors of biomolecular engineering at the Baskin School of Engineering, received the American Association for the Advancement of Science’s (AAAS) Golden Goose Award for the invention. Their colleague and friend Daniel Branton, a Havard biologist and co-inventor of the technology, was also honored. 

The Golden Goose award is given to scientists whose federally-funded research was seemingly obscure or silly at the outset but created a deep societal impact. Each year, three groups of scientists are lauded by members of congress for their contributions to transformational research breakthroughs in a variety of science and engineering fields. 

The concept for nanopore sequencing technology, licensed to the UK-based company Oxford Nanopore Technologies, led to the creation of the MinION, the only hand-held device for genetic sequencing, priced at a fraction of the cost of other sequencers. This transformational technology allows sequencing to take place in remote and resource-poor environments and has enabled some of the most significant genomics breakthroughs of the last two decades. 

“I like to think of scientists as prospectors, and grants are the grubstakes that keep us going while we search for new knowledge,” Deamer said. “Like the rare prospector who discovers the motherlode, the discoveries emerging from basic research can sometimes change the world. The three of us have a sense of deep satisfaction that we helped to increase our understanding of how the human genome functions in health and disease.”

Nanopore’s impact

Nanopore sequencing is a unique method for achieving long reads of DNA and RNA. Long read sequencing means scientists can read longer stretches of genetic material all at once, instead of piecing together the short pieces that are achieved with traditional short read technology. Long reads are essential for whole genome sequencing efforts, such as the first complete sequence of a human genome and the first human pangenome, both efforts led by UCSC Genomics Institute researchers. 

Use of nanopore sequencing technology is widespread across the genomics field — there are currently around 73,000 research publications that cite the technology. It is being used in a large number of current wide-scale genomic studies, from mapping the spread of diseases such as Ebola and Covid-19, to understanding the genetic mechanisms that regulate cancer, to creating resources for the protection of endangered species. 

Nanopore sequencing is revolutionary because its size and portability allows sequencing to happen anywhere beyond just a typical lab setting. It can be taken to remote or resource-poor areas to do on-demand sequencing, and empower local scientists and clinicians to do DNA and RNA sequencing in their communities. The MinION has even been taken to the international space station to sequence the organisms growing there. 

“Beginning with Sanger Sequencing in 1977, DNA sequencing technology has impacted all of us,” Akeson said. “It is an honor to be a part of this legacy.” 

Inventing nanopore

Nanopore sequencing works by pulling a single strand of DNA or RNA through a tiny hole, just two nanometers wide, that is charged with an ionic current. Each of the bases of DNA (A, G, C, and T) have slightly different sizes and chemical properties, and so make a distinct change to the current as they are pulled through it. These base-specific changes are then translated to read the genetic material. 

Deamer came up with the initial concept for nanopore sequencing while at UC Davis researching nucleic acids, the material that makes up the bases of DNA and RNA. He moved to UC Santa Cruz where he began research on his new idea, recruiting Akeson and Branton as collaborators on a project that seemed impossible to many in the field. 

“When we began to work with nanopores there was extreme skepticism, which is why the Golden Goose award is recognizing nanopore sequencing,” Deamer said. “Think about it — we were proposing to pull a single molecule of DNA through a nanoscopic pore, then detect and identify each base as it zipped through. Impossible! Because it seemed so unbelievable, for ten years we were the only group working on the idea.” 

“I often tell students to be skeptical when they read research papers because exaggeration and even fraud happen in science and technology,” Akeson said. “But I also tell them that obstinate rejection of new ideas or theories is wrongheaded. Just look at the early days of CRISPR or AI to see how wrong critics can be. In the case of nanopore sequencing, our colleague Dan Branton challenged obstinate skeptics to explain what physical law prevented implementation of the technology. The usual answer was a muffled ‘There is no fundamental law – it's just too hard,’ before the critics scurried off. So we persevered – another lesson for students.”

After years of experimentation in the labs at UCSC and Harvard, the team was able to solve a myriad of biological and technological challenges to prove their idea was viable. These ideas were licensed in the form of patents to the founders of Oxford Nanopore Technologies (ONT), and in 2012 the company unveiled the MinION, the first device for nanopore sequencing.

The MinION was sold for just $1,000 at a time when competing devices were $100,000 and up. Since then, ONT has improved the speed and accuracy of the technology significantly and now offers several other more powerful devices for nanopore sequencing such as the GridION and the PromethION. The patents behind these devices are the most lucrative invention to come out of UCSC to date.

Tune in to the 2023 Golden Goose Award Ceremony via livestream on September 27 at 2:30pm PT.

END