Nancy Shute on NPR recently wrote,

"For more than a decade scientists have been saying that a genomic revolution will transform medicine, making it possible to scan all of a person's DNA to predict risk and customize medical care.

Well, we've got the machines. Where's the revolution?"

Researchers at Stanford University have helped explain the hold-up in their just-published report in the Journal of the American Medical Association (JAMA).

The report describes a study that sought to identify the strengths and weaknesses of the clinical application of whole genome sequencing. Twelve healthy adults were sequenced and each was found to have between two and six genetic mutations that are linked to disease. Arguably, that knowledge is a strength, but there were some clear weaknesses.

Nine of the 12 participants had their initial Illumina Inc results confirmed by a second company, Complete Genomics Inc, in order to evaluate the reproducibility of the results. It was found that

"fewer than one-third of insertion/deletion variants in inherited disease genes were confirmed by the second sequencing platform."

Additionally, it was found that

"Depending on sequencing platform, between 10% and 19% of inherited disease genes were not consistently covered at a read depth that was sufficient for a comprehensive survey of genetic variants."

Due to the inconsistency of the data, the study clinicians were unsure what to report to the participants, and often disagreed among themselves about what further action to recommend.

One participant discovered she had a mutation in the BRCA1 gene, and chose to have her ovaries removed as a preemptive measure against the greater risk of ovarian cancer that mutation confers. No other actionable results were mentioned.

The study concluded that there are major challenges to be overcome before whole genome sequencing (WGS) can be utilized in a clinical setting. It states that WGS is

"associated with incomplete coverage of inherited disease genes, low reproducibility of genetic variation with the highest potential clinical effects, and uncertainty about clinically reportable WGS findings."

The PHG Foundation also recently put out a report about the clinical use of whole genome sequencing that highlighted a number of “challenges to delivering reliable and useful results and the potential risks to patients and the health service if these challenges are not overcome.”

However, when we note the challenges of WGS becoming useful in a clinical setting, we shouldn’t automatically assume that overcoming them will lead to the most desirable outcome. While genetic testing companies and drug companies have a powerful economic incentive to market this product to new customers, it’s certainly possible that what makes sense for patients is to keep WGS for specific purposes.

The shift that WGS promises is to a focus on personalized health care based on a complete understanding of one’s genes. But it is also a shift to preventative care for diseases that may or may not ever show up. While some people will appreciate this knowledge, others may feel burdened by it. Not everyone wants to know they have a heightened risk of dying from a disease they can do nothing to prevent.

Anne Wojcicki, CEO of 23andMe, likes to make the argument that personal genomics will drive healthcare costs down, but there’s no evidence of that. The cost of the sequencing and the interpretation for the JAMA study (not including the downstream costs of clinical tests and referrals) came out to about $15,000 per participant. While this is significantly less than the costs of WGS used to be, it’s still a lot of money for very little useful information.

Donna Dickenson makes the argument in her book Me Medicine vs. We Medicine that while personalized healthcare shows potential in some cases, it can come at the cost of our commitment to public health initiatives. A comment from Geraldine Merola on the NPR article highlights the point,

"$15K each and they tested 12 subjects to find 1 mutation that may or may not lead to breast cancer... $180,000 is an awful lot of mammograms!"

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