Earlier this year, the CEO of Illumina gave a presentation in which he reaffirmed his company’s intention to drive the cost of human genome sequencing down to a mere hundred dollars. This has ramifications for every branch of medicine, including rejuvenation biotechnology.
Drastically declining costs
In 2001, the year when the Human Genome Project was completed, the total cost of sequencing a full human genome was in the hundreds of millions of dollars, requiring international cooperation after a multi-year effort. Ten years later, the cost had dropped to $10,000 – four orders of magnitude – and five years after that, it dropped to the low thousands of dollars and has been declining since. Reducing this figure by yet another order of magnitude would open the door to novel experiments and therapies that were previously unfeasible.
Genomic instability and epigenetic alterations
Probably the most obvious use of genomic sequencing in the context of age-related diseases is to detect genomic instability, which is a primary hallmark of aging. As we age, our genome mutates, resulting in other hallmarks of aging along with cancer. Inexpensive genomic sequencing makes it plausible to take multiple samples from multiple cell types in a single person, analyzing the ways in which specific areas have been affected by this hallmark.
Modern genome sequencing does not merely count base pairs; it can also detect methylation of DNA, which determines whether or not that DNA actually expresses proteins. Epigenetic alterations, another primary hallmark of aging, are defined by altered methylation that turns off genes we want left on (and vice versa), and epigenetic clocks use this methylation to determine biological age. It is clear how inexpensive sequencing can allow such clocks to be analyzed more easily, and the relationships between genomic instability and epigenetic alterations can also more readily be explored.
Everything in your body, from your immune system to your reactions to specific drugs, is at least partially governed by your genes. Routine genetic sequencing makes personalized medicine much easier to achieve in a clinical setting, particularly when the relationships between specific genes and drugs are well known. Ideally, the term “family history” would quickly become irrelevant; doctors armed with your full genetic sequence, along with an index of what genes are responsible for what conditions, could tell you what sorts of conditions you are susceptible to and what sorts of treatments best suit you.
Gene therapy and cell line verification
Unfortunately, off-target alterations are a major concern for gene therapy and genetically modified cell lines. While significant strides have been made in this regard, it is still necessary to know whether or not any given cell line has sustained such unwanted mutations. A rapid, cheap, and accurate genomic sequencing solution would make the necessary checking a matter of routine.
The same would also be true for any gene therapy applied directly to a human being. While no gene therapy has yet passed clinical trials, it is not difficult to see how inexpensive genetic screening and a prescription of gene therapy can possibly go hand in hand in the future.
Accuracy and time
Obviously, for DNA sequencing to become a routine procedure, the results have to be accurate and come readily to hand. There are two metrics by which accuracy is judged: Q scores and repetitions.
Every increase of 10 in a Q score represents fewer errors by an order of magnitude. Q10 means that a full 10% of bases are incorrect; Q20 means that 1% are wrong, and Q30 means that only one in a thousand are incorrect. Illumina advertises in this PDF document that some of its main products, by and large, are Q30 or above; however, there are certain sections of DNA in which its systems fail to meet that standard.
Even getting one in a thousand base pairs wrong isn’t very good in a clinical setting, especially when the relevant tests are for genetic disorders or cancer. Therefore, genomic sequencing for clinical use is analyzed multiple times in a row, minimizing the chances of an error appearing in the final product. Illumina advertises that its DRAGEN sequencing system can process the sequencing results of an entire human genome thirty times in less than a half hour; a task that once took heavily intensive research and labor can now be completed in under a minute. In 2018, Illumina completed the full sequencing of a baby’s DNA in less than 20 hours to diagnose a genetic disease. While this was an exception, the goal is to make it a standard in time-critical settings.
Obviously, there are caveats when talking about inexpensive genome sequencing; bringing a $100 final price tag to the clinic would require it to be an entirely routine process, with fast, high-throughput machines readily available everywhere they are needed. As this requires substantial development time and investment, it is unclear when Illumina (or, potentially, one of its competitors) will get this done. However, as the cost of genomic sequencing goes down and its potential as a commonly used analysis tool goes up, it is plausible that we will see comprehensive analyses of genomic instability and epigenetic alterations regularly conducted in the near future.
Finally, while genome sequencing can verify the results of CRISPR-based and other gene therapies, this technology is for reading DNA, not writing it. If similar innovations appear that allow for accurate and inexpensive genetic modification, they will certainly revolutionize medicine as we know it.