A decade after the first human genome sequence was completed, it would probably be fair to say that whole genome sequencing is not yet ready for prime time. The problem is not the technology ‑ it’s the resulting vast quantity of information. For the most part, we don’t know how to interpret it or what to do with it. When it comes to helping patients, whole genome sequencing trips over the concept of actionability. When you consider a diagnostic test for a patient, the last thing you want to find in your results are “unknown unknowns.” In a research setting, “unknown unknowns” can be great. That kind of a result can lead to a dozen more experiments, all designed to wrangle that unexpected result into a theory, and then test the theory. Few physicians want to look a patient in the eye and tell them that something unusual was found in their test results, but they don’t know what it is, why it happened, or what can be done about it.
However, even as scientists carefully and methodically approach whole genome sequencing to see if it has value for patients, some patients are taking matters into their own hands, hoping that running their own personal Human Genome Project will turn up the kind of answers that their doctors can’t give them.
Lukas Wartman is patient zero of the cure by sequencing movement. Wartman was researching acute lymphoblastic leukemia when, in a deeply ironic twist of fate, he fell ill with it. Wartman’s colleagues decided to search his entire genome sequence in the hopes of finding the gene behind the cancer. Using resources at Washington University, scientist Timothy Ley and colleagues sequenced the genes of his cancer cells and healthy cells, and also ran an RNA analysis.
Miraculously, the project turned up an answer ‑ a gene normally associated with kidney cancer ‑ and there was a new drug targeting that gene malfunction. Wartman went into remission and was stable at last report a year later.
The first complete human genome sequence was completed by National Human Genome Research Institute and Celera Corp. in 2003 at a cost of over $3 billion. The technology has reached a point where it is now feasible to run multiple full genome sequences to diagnose one patient, and, perhaps spurred by Wartman’s success, a number of vendors are ramping up sequencing services for the clinical market.
Leading the pack is Illumina Inc., which rolled out a clinical individual genome sequencing service in September 2012.
Science fiction writer Jay Lake has become an early adopter of Illumina’s offering, branded TruSight IGS Rapid TAT Whole-Genome Sequencing. Diagnosed with colon cancer in 2008, Lake has run through the available treatment options, and is hoping that whole genome sequencing of his cancer will lead to a treatment to put him in remission.
With rapid turnaround service, Illumina sequencing is priced at $13,000. The analysis would be a large, additional cost. As a friend of Jay, I encouraged him to pursue sequencing, and set up a fundraiser to allow his community of friends and fans help him with the cost of sequencing, as well as the miscellaneous costs associated with long term serious illness. The response was swift and overwhelming, and the fundraiser quickly topped its goal of $20,000. Extra funds beyond the goal have allowed Lake to explore multiple analysis options, and the possibility of RNA expression analysis.
A number of other commercial vendors and academic laboratories are exploring clinical genomic sequencing services. Representatives of Science Exchange encouraged Jay to post his sequencing job where he could receive multiple bids for sequencing.
Elizabeth Iorns, a representative of Science Exchange, said many of its providers are CLIA certified, and that the group is planning to expand into clinical services in partnership with Cancer Commons, a nonprofit open science initiative working toward bringing next-generation genomics technologies to patients.
It’s not clear whether whole genome sequencing will benefit patients with cancer, or any disease, or if it will continue to be more beneficial and cost effective to screen for specific, known mutations. The success in Lukas Wartman’s case is encouraging. However, one other early adopter of sequencing technology, Steve Jobs, didn’t fare as well. In a biography published after his death, it was revealed that Jobs spent about $100,000 on sequencing for his cancer, but was not able to find the kind of target that would have cured his disease.