Nanopore Sequencing & the Problem With Patents

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Picture Credit: DNA | Public Domain Pictures

In 2003, researchers from all over the world achieved one of the greatest scientific endeavors of their time: identifying and mapping out the entire human genome. With over 20,000 genes analyzed, the scientific community reaped the benefits of the age of genomics, where scientists could identify the thousands of nucleotide base pairs involved with specific genetic diseases like Huntington’s and pinpoint the mutations that underlie different forms of cancer.

But now, a device from Oxford Nanopore Technologies could bring the same power of DNA sequencing from the laboratory into the palm of your hand. It’s called the MinION and it can sequence the DNA of any given sample in a matter of hours.

For decades, conventional DNA sequencing was widely regarded as a tedious, time-consuming process. In order to identify the genome of a particular sample, a researcher would have to create numerous identical copies of the DNA molecules, break each of those copies into tiny pieces for the machine to read, sequence each fragment individually and finally reassemble those pieces together again. It’s the equivalent to reading a book by shredding it to read each word separately and then taping the pages back together again. In addition, this cumbersome process involved expensive machines the size of refrigerators and took days or weeks to run.

Due to these practical limitations, many researchers have to rely on the products and services of large corporations to obtain the DNA sequence of their samples. Today, the one that currently dominates the sequencing market is Illumina, Inc., a corporate giant worth billions of dollars. At the moment, Illumina provides machines for almost every large sequencing center in the world and now has an almost complete monopoly in the industry. However, Oxford Nanopore Technologies intends to bring down this powerful behemoth with a revolutionary new way of reading DNA called nanopore sequencing, which identifies the nucleotide base pairs directly without breaking apart the DNA molecule.

The idea is rather brilliant. A nanopore is simply a very tiny hole, about 2.5 nanometers wide. Nanopore sequencing relies on the use of an incredibly thin synthetic membrane with numerous nanopores as well as nanopore sensors. When the membrane is submerged in liquid by itself and a current is ran through, a steady electrical pattern is measured as ions pass through the tiny holes.

These patterns change once a DNA sample is placed on the membrane. When the electrical current pulls a DNA molecule through a nanopore, the nucleotide bases block the pore and stop some of the ions from passing by. This blockage alters the current that the sensor is reading and ultimately causes the electrical pattern to dip. What makes this method so effective is that each nucleotide base of DNA blocks the pore in different ways and generates a unique and identifiable change in the current. In other words, one can identify the DNA sequence by simply reading the various spikes in the electrical pattern.

In addition to its speed, easy usage and portability, the MinION also boasts a 99.99 percent accuracy based on a performance of 90 percent without any false positives. Not only that, Oxford Nanopore Technologies set the price of their new, revolutionary sequencing gadget to a mere $1,000. When the MinION was first revealed to the world in 2012, one scientist tweeted: “I felt a great disturbance in the force, as if a million Illumina investors cried out in pain.”

The idea of genetically identifying any organic substance at any place and time has enormous implications. A DNA sequencer like MinION could not only be used in a lab but also in the field with little to no difficulties. During the Ebola outbreak in 2015, microbiologist Nick Loman used his newly-bought MinION to track the progress of the epidemic in real time while other scientists had to wait weeks for the results of their analysis to arrive.

For something as time-sensitive as a deadly epidemic, nanopore sequencing could save tens of thousands of lives. Not only that, Oxford Nanopore aims to make their product available to everyone everywhere. From NASA astronauts in space to high school students, the company envisions a future where DNA sequencing devices can become like telescopes, a formerly expensive scientific instrument that is now available to the everyday consumer.

Unsurprisingly, Illumina is trying everything in its power to stop MinION’s momentum. Last February, the sequencing industry monopolist filed several lawsuits against Oxford Nanopore Technologies claiming that the British company committed patent infringement by using bacteria-derived pores known as Mycobacterium smegmatis porin (Msp) to create their synthetic membrane.

At the moment, Illumina holds the patents for any system that use these Msp. Oxford Nanopore responded almost immediately, accusing the corporate giant of acting on unsubstantiated speculation to prevent the MinION from ever reaching the market all so that Illumina can maintain its monopoly.

This move by Illumina illustrates just one of numerous legal issues that stand in the way of scientific progress. The scientific community is often plagued by patent aggregators, people or companies who enforce patent rights to make a profit or keep such patents away from those who may pose a threat against them. Despite not using their patents for research or manufacturing purposes, these entities prey on smaller companies to force them out of business. Never having proven their ability to produce their own nanopore sequencer, Illumina could very well be yet another patent aggregator trying to neutralize the incoming threat to their business.

Even if the MinION does not contain Msp pores, Illumina could still utilize the doctrine of equivalents. This aspect of patent law claims that Oxford Nanopore Technologies could still be liable for patent infringement as long as the product in question performs the same function as the patented invention in the same way. Originally created to cover the difficulty in describing the invention exactly, the doctrine can now be used to back companies like Oxford Nanopore into a corner.

Depending on the outcome of this legal battle, the entire course of scientific progress can be altered. With such great scientific advancements at risk due to capitalistic greed, it’s time to take another look at our patent system to prevent other innovations from becoming similarly obstructed. Overhauling the patent system is essential to taking money and special interests out of scientific research and thereby crafting an atmosphere more conducive to intellectual cohabitation and progress.

According to phylogenomics researcher Joe Parker, nanopore sequencing can bring about a second age of genomics. If that future can never come to fruition, then the same bleak stasis will certainly sabotage other shining opportunities for society as well.

Originally published on May 4, 2016, in The Miscellany NewsNanopore sequencing research should be encouraged

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