Increased competition could benefit the genomics industry, even though research is generally difficult to convert into real-world health advances. But now, you can get your genome sequenced for just $200.
Each individual has a different arrangement of the As, Cs, Gs, and Ts—the basic building blocks that make up DNA—which make up the more than 6 billion letters that constitute the human genome. It used to require a tremendous amount of resources—money, time, and effort—to figure out the order of all those letters. Numerous researchers worked on the Human Genome Project for 13 years. $2.7 billion was the final price.
The genomics era began with that 1990 initiative, which also sparked the creation of at-home DNA tests and other innovations while assisting researchers in understanding the genetic causes of many inherited disorders and cancer. Then, scientists began sequencing more genomes, including those from bacteria, viruses, bacteria, and plants. Prior to ten years ago, sequencing a human genome cost researchers roughly $10,000. It was $1,000 a few years ago. It is roughly $600 right now.
Sequencing will soon become much more affordable. The genomics behemoth Illumina today announced the NovaSeq X series, which it claims to be its fastest and most affordable sequencing machine to date, at a business event in San Diego. The firm, which holds around 80% of the global market share for DNA sequencing, predicts that its new technique would reduce the price of each human genome to about $200 while doubling the reading speed. The more potent model will be able to sequence 20,000 genomes annually, according to Francis deSouza, CEO of Illumina; its existing machines can only accomplish roughly 7,500. The new devices will begin to be sold by Illumina today, with shipments beginning the following year.
“As we look to the next decade, we believe we’re entering the era of genomic medicine going mainstream. To do that requires the next generation of sequencers,” deSouza says. “We need price points to keep coming down to make genomic medicine and genomic tests available much more broadly.”
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Sequencing has produced genetically targeted medicines, blood tests that can spot cancer early, and long-sought diagnoses for those with uncommon disorders. The Covid-19 vaccines, which researchers began creating in January 2020 as soon as the first draft of the virus’ genome was created, can also be credited to sequencing. Technology is now crucial in research labs for a deeper knowledge of diseases and human evolution. However, it is still not widely used in medicine. That is partially due to the cost. While sequencing costs scientists about $600, the cost to patients can reach several thousand dollars due to clinical interpretation and genetic counseling, and insurance is not always an option.
Another concern is that there is not enough proof of benefits for healthy individuals to justify the expense of genome sequencing. However, in two recent studies, 12 to 15% (read below) of healthy individuals whose genomes were sequenced ended up displaying a genetic variation that demonstrated they had an increased likelihood of a treatable or preventable illness, implying that sequencing could serve as an advance notice. Presently, the test is mostly restricted to people with certain cancers or undiagnosed illnesses.
For the time being, affordable sequencing will most likely help researchers rather than patients. “We’ve been waiting for this for a long time,” says Stacey Gabriel, chief genomics officer at MIT and Harvard’s Broad Institute. “With greatly reduced costs and greatly increased speed of sequencing, we can sequence way more samples.” Although Gabriel is not linked with Illumina, the Broad Institute is an Illumina power user. Since its inception in 2004, the institute has sequenced more than 486,000 genomes using 32 of the company’s existing equipment.
According to Gabriel, researchers will be able to use the additional sequencing power in a variety of ways. One goal is to diversify genomic datasets, as the overwhelming bulk of DNA data has originated from individuals of European descent. This is a challenge for medicine since various populations may have more or less prevalent disease-causing genetic variants. “There’s really an incomplete picture and a hampered ability to translate and apply those learnings to the full population diversity in the world,” Gabriel says.
Another option is to increase the size of genetic datasets. When the Broad Institute began a project to seek for genes associated with schizophrenia in the early 2000s, researchers collected 10,000 genomes from people with the disorder, which did not yield much insights, according to Gabriel. They now have over 150,000.
Researchers have discovered numerous genes that have a significant influence on a person’s chance of developing schizophrenia by comparing those genomes to those of individuals without the disorder. Gabriel claims that by increasing the number of genomes that can be sequenced quickly and economically, more genes with a more nuanced impact on the condition will be discovered. “Once you have bigger data, the signal becomes clearer,” she says.
“This is the kind of thing that shakes up everything you’re working on,” agrees Jeremy Schmutz, a faculty investigator at HudsonAlpha Institute for Biotechnology, of new sequencing technology. “This reduction in sequencing cost allows you to scale up and do more of those large research studies.” Schmutz, who studies plants, hopes that cheaper sequencing would enable him to produce more reference genomes in order to better understand how genetics influence a plant’s physical features, or phenotype. Large genomic studies, he claims, can assist enhance agriculture by speeding up the development of certain favored crops.
To interpret DNA, Illumina’s sequencers employ a technique known as “sequencing by synthesis.” To begin, DNA strands, which are typically double-helixed, must be broken into single strands. The DNA is then cut into short fragments and dispersed on a flow cell, which is a glass surface roughly the size of a smartphone. When a flow cell is fed into the sequencer, the machine attaches fluorescent tags with different colors to each base: A, C, G, and T. Blue, for example, could represent the letter A. Each DNA fragment is duplicated one base at a time, and a matching strand of DNA is created gradually. A laser scans each letter’s base one at a time while a camera records the color coding. The technique is repeated until all fragments have been sequenced.
Illumina developed denser flow cells to boost data production and new chemical reagents to enable faster base scans in its latest devices. “The molecules in that sequencing chemistry are much stronger. They can resist heat, they can resist water, and because they’re so much tougher, we can subject them to more laser power and can scan them faster. That’s the heart of the engine that allows us to get so much more data faster and at lower costs,” says Alex Aravanis, Illumina’s chief technology officer.
Despite the fact that the price per genome is decreasing, a machine’s initial investment is still high. Illumina’s new system will cost roughly $1 million, which is comparable to the price of its current equipment. They are not yet widely used in smaller labs, hospitals, or rural areas due in large part to their expensive cost.
Another issue is that they necessitate the use of experts to operate the equipment and process the data. However, Illumina’s sequencers are totally automated and generate a report that compares each sample to a reference genome. According to Aravanis, this automation has the potential to democratize sequencing, allowing facilities without big teams of scientists and engineers to operate the machines with less resources.
There are other businesses besides Illumina that promise quicker, cheaper sequencing. Despite the fact that the San Diego-based business presently rules the industry, some of the patents defending its technology will expire this year, allowing for additional competition. A $100 genome was promised by Ultima Genomics of Newark, California, when it came out of stealth mode earlier this year. It will start selling its new sequencing machine in 2023. In the meantime, this summer saw the launch of MGI, a Chinese company, selling its sequencers in the US. Smaller, benchtop sequencing devices have also been developed by San Diego-based companies Element Biosciences and Singular Genomics that may revolutionize the industry.
The typical flow cell has been replaced by a round silicon wafer little under seven inches in diameter in Ultima’s machine design. According to Josh Lauer, the company’s chief commercial officer, the disc is less expensive to produce and has a larger surface area than a flow cell, allowing for more DNA to be read at once. Lauer claims that because the disc rotates like a record under a camera rather than moving back and forth like flow cells, it takes less reagent and speeds up imaging. “We think this will enable scientists and clinicians to do more breadth, depth and frequency of genome sequencing,” he says. “Instead of just looking at tiny parts of the genome, we want to look at the whole genome.”
Ultima’s machine is not yet readily accessible, and the business has not announced a price, though Lauer claims it will be similar to other sequencers on the market.
Increased competition could benefit the genomics industry, but research is generally difficult to convert into real-world health advances. It will most likely be some time before patients notice a direct advantage from less expensive sequencing. “We’re at the very, very beginning,” deSouza says.
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