Ion Proton Sequencer ... Now that's a formidable name. And it's one that could be applied to just about any technology of the phantasmagorical sci-fi ilk. Was it that thing they used to beam Kirk, Spock, Bones and a hapless "Red Shirt" to the surface of every unknown planet? Negative. That was a transporter. Is it one of Dr. Thaddeus Venture's failed inventions from "The Venture Bros." series? Nope, you're thinking of the metasonic locator on that one.
If the Ion Proton Sequencer were a piece of fiction -- which it's not -- it would be found in the medical lab of every deep-space exploratory starship; it would study new life forms and figure out just how many trips on the transporter would reduce your DNA's double helix to something that looks like a fireman's pole. But alas, the machine is a real and revolutionary medical research device.
It was the first in a new generation of sequencers that can decode an entire human genome quickly and inexpensively. Minus the time to prepare the DNA sample, processing only takes about a day. And the company says the test costs about $1,000.
Those two factors make this machine -- and those of its competitors, like Illumina and Pacific Biosciences -- a complete game changer for medical research and treatment. Until recently, genetic decoding was still rather rare due to the prohibitive costs and time involved. It could take days or weeks just to have partial DNA sequences read. And a full decoding of a person's genome cost hundreds of thousands of dollars just a few years ago [source: NOVA].
As a result, this sort of technology was usually reserved for the lab environment. Unless doctors or researchers were dealing with an outstanding medical case with widespread health ramifications, such genetic scrutiny usually wasn't practical.
One of those outstanding cases took place in 2011, when a new strain of E. coli broke out in Germany. While investigators were busy tracking down the source, researchers were looking at the makeup of this new bacterium. They used a predecessor of the Ion Proton Sequencer called the Personal Genome Machine (PGM) Sequencer. It's made by the same company, Life Technologies, and could read long portions of the organism's genetic blueprint in hours as opposed to weeks.
Researchers were able to compare that blueprint with previously decoded E. coli and determine that they were dealing with a new variant and understand some of its traits, such as toxicity and which antibiotics it might resist. Armed with that data, doctors stood a better chance at helping patients infected with the pathogen. Ultimately, more than 4,000 people were infected, and 50 known cases were killed by it [source: World Health Organization].
So, we know genetic sequencing is powerful stuff. It's already proven that it can help stop an outbreak. Let's learn about the developments that made the Ion Proton Sequencer possible and what it could do for future medicine.
What Makes the Ion Proton Sequencer So Special?
We're going to put the name thing to rest. Ion. Proton. Sequencer. The name is basically corporate taxonomy. "Ion" comes from Ion Torrent, the name of the brand (owned by Life Technologies) that makes this device. "Proton" is the model name of this product; sort of like naming a car "Fusion" or "Tribeca," the cars don't run on nuclear power, nor are they built in a trendy Manhattan neighborhood. And "Sequencer," well, that's just what the machine is -- a sequencer. We'll call it the Proton for short.
The system was unveiled in January 2012 and got immediate attention for its bold claims of delivering $1,000 genetic sequences in a single day. Considering that the human genome had been decoded nine years earlier, potentially putting the power of human genetic information into every hospital is a giant leap forward.
The company announced that the Proton 1 chip for its new sequencer would be available by mid-2012 and capable of handling much bigger sequencing jobs than its predecessor, the Personal Genome Machine (PGM). By the end of 2012, Life Technologies said it would have the Proton II chip on the market, which could take on the entire human genome in one shot.
From the perspective of scalability, the Proton is a smash hit. The entire machine is roughly the size of a medium-sized laser printer that you might find at any office, and it costs about $150,000. That's three times as much as the PGM, but that's still a lot of earth-shattering capability for your medical dollar, considering that an MRI machine can run a few million dollars. Granted, the results offered from MRI and genetic sequencing are the proverbial apples and oranges, but they're both noninvasive procedures that can allow doctors to observe a patient's condition with life-saving detail. Considering how MRIs took off to become a tool in every hospital's standard-issue arsenal, it's likely that sequencers will become the next big must-have for any reasonably sized hospital in the next couple of years. The biggest limiting factors may prove to be finding trained personnel to run tests and interpret data, as well as receiving U.S. Food and Drug Administration approval for medical use. But we'll talk about that later.
As you can imagine, companies are lining up alongside Life Technologies to meet this demand. Days before the Proton was announced, competitor Illumina released its comparable system, the HiSeq 2500 (about $740,000 to buy new). While early speculation suggested that Illumina's system could provide cleaner reads on a single test, the Proton seems the winner in the battle of price tags [source: Herper]. In fact, now that life science companies like Life Technologies, Illumina and Pacific Biosciences have made the human genome more accessible, there will likely be an explosion of sequencers at a variety of price points competing for lab space among researchers and medical facilities.
Putting the Proton to Work
The Proton can tackle all sorts of sequencing whether it's DNA- or RNA- (ribonucleic acid) based. Life Technologies says the machine is a good fit for sequencing the following:
- Entire transcriptomes, or the transcript of the expressed genes in the genome
- Human genomes, or the complete set of genetic instructions located in a cell
- Human exomes, the areas in DNA that code for proteins
Earlier, low-resolution sequencing techniques only allowed researchers to examine small stretches of genetic data. Researchers also had to already have an idea of what they were trying to find. With this newer generation of sequencers, they're able to capture much longer stretches of data. Ready to untangle some? The two most important ingredients in this process will be the DNA strands and the sequencer's sensor-filled chip.
Before you can collect data, you have to prepare your sample, right? There are systems for that. Automated ones. For example, at the time we wrote this article, you could buy the Ion OneTouch System for $14,490 to handle sample preparation in roughly four hours for the Proton's predecessor, the Personal Genome Machine.
Now we're moving on to the chip. The Proton I semiconductor chip is filled with 165 million sensors that work a little like the ones inside a digital camera. Above the sensors are tiny wells where the sample DNA sits. The samples are blasted with nucleotides (the building blocks of nucleic acids like DNA). If a nucleotide joins up with the sample, a hydrogen ion is released, so these sensors monitor the acidity of the solution for changes. Technically speaking, this pH-based method is called Ion Semiconductor Sequencing.
The chip is where the power of the Proton machine really resides. The Proton II chip is slated to have 660 million sensors. All those sensors are kind of handy when you remember that 3.1 billion bases make up the human genome. As with digital cameras, stronger chips mean more finely detailed results and, for sequencers, longer views of the DNA strand. With every advancement in semiconductors comes another step up in resolution.
Once loaded into the Proton, the chip, with all its sensors, reads the strand of DNA while software analyzes the data for completion and accuracy, delivering the data to researchers.
According to Life Technologies, the sensor and sample prep kit come out to about $1,000 total, and the Proton is a small unit, so it's not exactly an energy hog.
In a way, the actual sequencing is the easy part. The next big area of development in software is helping researchers and doctors see and understand patterns in the genome more easily. After all, the human genome contains more than 20,000 genes [source: NOVA]. A veritable warehouse of genetic information that must be sorted in order to make any findings.
Now that we have a rough understanding of the process, let's explore the possible uses for sequencing.
How Genome Sequencing Will Benefit You
Let's start by mentioning that it's difficult to overstate the importance of genome sequencing. We've already seen it unlock a new killer bacteria. So what else can it do? Well, since DNA is the source code for all life on our planet, having the ability to read those cryptic little strands of information will help researchers and doctors understand the very foundation of diseases.
Take for instance, cancer. All day long, cells are reproducing in our bodies, using that genetic information in their DNA. Cancer occurs when some of that information is incorrectly copied over, producing cells of a different sort. Being able to read those cells helps us understand, at a much deeper level, the types of cancer a patient might be dealing with and can identify genetic predisposition for cancer. It can also help doctors pinpoint weaknesses within different cancers to create new treatments.
Genome transcription can also be used to benefit otherwise healthy patients in a preventative manner. So many health problems have their roots in our genes. For instance, some families may have tendencies toward heart disease, diabetes or even alcoholism. Using specialized software that reads patterns in gene sequences, physicians could warn patients of their vulnerable areas.
That's not to say genome sequencing can predict that a given patient will have a heart attack or become an alcoholic, but it can warn that person if he or she is at greater risk. Then, they can make informed decisions to address that risk before it becomes a medical emergency. The same might be done for everything from Alzheimer's disease to bone density problems.
It stands to reason that, one day, most people could have a map of their personal genome saved somewhere within their electronic medical file. After all, health conditions will come and go, but DNA is a lifelong blueprint. As those health conditions arise, DNA can be checked to offer doctors a deeper understanding of their patients. That's why these sequencing tools will eventually start to migrate out of labs and into hospitals clinics.
That moment hasn't arrived yet. In fact, even though it's on the market, your doctor couldn't order a reading of your genome from the Proton or any of the other next-generation systems on the market as of July 2012. Keep reading and find out why.
The Downsides of Everyman's Human Genome Sequencing
With this revolutionary technology unraveling the mysteries of our genes at such a rapid pace, it must be noted that all of Life Technologies' publicity materials for new-product launches featured the same statement buried somewhere within. They say that "these products are for research use only, and not intended for any animal or human therapeutic or diagnostic use." That's the makers' way of saying that you can use these machines to study any disease or the human genome. You just can't study a specific person's genome for the sake of helping them make decisions about their health treatment.
Since this is such a new technology, the U.S. Food and Drug Administration (FDA) must review and approve all of these next-generation sequencing machines before they're let loose on patients.
In the summer of 2011, the FDA called a panel of manufacturers and experts to discuss the questions surrounding these kinds of sequencers. While everyone agreed that they are a powerful tool, many questions have to be addressed before they will be allowed to process human genetic information for the purpose of clinical decision-making. They range from how the sample is extracted to ensure it's clean to how the software outputs and interprets its data.
With many manufacturers approaching the same problem from different angles, the FDA has determined that it needs to devise a system for validating new sequencers before they are approved for clinical use. The agency wants to give doctors assurance that the systems can guarantee a certain level of accuracy. The problem with that proposition comes with devising a standardized test for sequencers. It would be ideal if the FDA had a set of living cells that had already been sequenced and use them as the test bed. The problem is that cells will tend to mutate over time, so getting that standardized field will be difficult [source: FDA].
That being said, depending on how long it takes to be approved, the Proton might go down in medical history as the first sequencer to roughly hit the magical $1,000-per-human-genome mark, but it may already be replaced by the next round of machines before it ever has a chance to directly help patients. In the meantime, it will undoubtedly have an impact on the research community by allowing for faster, cheaper tests on everything from tumors to tree leaves.
I love bragging to my friends about the titles of my assignments for HowStuffWorks. But How the Ion Proton Sequencer works flat-out takes the blue ribbon purely on WTH factor. "You're making that up. Whatever you just said doesn't exist," was probably the best response I heard.
It's subjects like the Proton that makes writing for this site so much fun. The Proton and its peers represent a giant leap in genetic technology. The closest analogy is maybe computers in the late 1970s and '80s. As soon as they became so affordable that average families could own them, suddenly everyone started getting computers. As far as labs are concerned, the Proton is the Apple MacIntosh of genetic technology; compact, easy to use, a revolutionary presence in the market, and it packs an entire lab worth of analytics into a tiny box.
- Bio-IT World Staff. "German Teams, BGI and Life Technologies Identify Deadly European E.coli Strain." Bio-IT World. June 2, 2012. (July 18, 2012)http://www.bio-itworld.com/news/06/02/2011/German-teams-BGI-Life-Technologies-Identify-E-coli-strain.html
- Genome Web "RNA-seq Technical Guide." Oct. 30, 2009. (July 20, 2012) http://www.genomeweb.com/node/926779
- Herper, Matthew. "Biotech Firms Battle Over Same Day Genomes." Forbes. Jan. 10, 2012. (July 19, 2012). http://www.forbes.com/sites/matthewherper/2012/01/10/biotech-firms-battle-over-same-day-genomes/
- Invitrogen. "The Basics: RNA Isolation." 2012. (July 27, 2012) http://www.genomeweb.com/node/926779
- Minotta, Mauricio. "Ion Proton™ Systems Installed and Operational at the Baylor College of Medicine Human Genome Sequencing Center." April 24, 2012. (July 25, 2012) https://ir.lifetechnologies.com/releasedetail.cfm?ReleaseID=666946
- NOVA. "Cracking Your Genetic Code." PBS. March 28, 2012. (July 25, 2012) http://www.pbs.org/wgbh/nova/body/cracking-your-genetic-code.html
- Shaw, Kenna and Ralston, Amy. "Gene Expression Regulates Cell Differentiation". Nature. 2008 (July 26, 2012) http://www.nature.com/scitable/topicpage/gene-expression-regulates-cell-differentiation-931
- Stomp, Wouter. "Ion Proton DNA Sequencer Decodes a Human Genome in One Day for $1,000." Medgadget. Jan. 10, 2012. (July 18, 2012) http://medgadget.com/2012/01/ion-proton-dna-sequencer-decodes-a-human-genome-in-one-day-for-1000.html
- U.S. Food and Drug Administration (FDA). "Ultra High Throughput Sequencing for Clinical Diagnostic Applications - Approaches to Assess Analytical Validity: Report from the Public Meeting". June 23, 2011. (July 20, 2012) http://www.fda.gov/MedicalDevices/NewsEvents/WorkshopsConferences/ucm255327.htm
- World Health Organization. "Outbreaks of E. coli O104:H4 infection: update 30." July 22, 2011. (July 17, 2012) http://www.euro.who.int/en/what-we-do/health-topics/emergencies/international-health-regulations/news/news/2011/07/outbreaks-of-e.-coli-o104h4-infection-update-30