In 1996, President Clinton offered a promissory vision for human genetics when he said: “I think it won't be too many years before parents will be able to go home from the hospital with their newborn babies with a genetic map in their hands that will tell them, here's what your child's future will likely be like.”

The rapid evolution of genetic sequencing technologies has advanced that vision. In October 2006, the cost of sequencing an entire human genome was $10.4 million; by 2014 the cost had decreased a thousand fold. The term next generation sequencing (NGS) describes a variety of laboratory methods that allow efficient determination of the precise order of nucleotides in a DNA sequence. The papers in this issue of the Journal of Law, Medicine & Ethics focus on “clinical NGS,” which refers to rapid DNA sequencing using second-, third- and fourth-generation sequencing technologies to perform genome-wide sequencing of multiple genes or alleles for clinical prognostic, diagnostic, and therapeutic purposes.

Since the first draft of the human genome was published in 2001, DNA sequencing technology has advanced at a remarkable pace. Launched in 1990, the Human Genome Project sought to sequence all three billion base pairs of the haploid human genome, an endeavor that took more than a decade and cost nearly three billion dollars. The subsequent development of so-called “next generation” sequencing (NGS) methods has raised the possibility that real-time, affordable genome sequencing will soon be widely available. Currently, NGS methods can be used to sequence up to 60 billion base pairs per day. Whole-genome sequencing costs an estimated $5,000-10,000, with that number predicted to fall to $1000 in the near future.

In the past few years, the availability of high-throughput NGS methods has led to a proliferation of potential and actual clinical applications for NGS. NGS therefore has the potential to usher in the long-awaited era of personalized medicine.

Clinical next generation sequencing (NGS) is a term that refers to a variety of technologies that permit rapid sequencing of large numbers of DNA segments, up to and including entire genomes. As an approach that is playing an increasingly important role in obtaining genetic information from patients, it may be viewed by public and private payers either positively, as an enabler of the promised benefits of personalized medicine, or as “the perfect storm” resulting from the confluence of high market demand, an uproven technology, and an unprepared delivery system. A number of recent studies have noted that coverage and reimbursement will be critical for clinical integration of NGS, yet the evidentiary pathway for payer decision-making is unclear. Although there are multiple reasons for this uncertain reimbursement environment, the situation stems in large part from a long-standing lack of alignment between the information needs of regulators and post-regulatory decision-makers such as payers.

Whether, and to what degree, do patents granted on human genes cast a shadow of uncertainty over genomics and its applications? Will owners of patents on individual genes or clusters of genes sue those performing whole-genome analyses on human samples for patent infringement? These are related questions that have haunted molecular diagnostics companies and services, coloring scientific, clinical, and business decisions. Can the profusion of whole-genome analysis methods proceed without fear of patent infringement liability?

Whole-genome sequencing (WGS) is proceeding apace. Academic centers have been performing whole-genome and -exome sequencing (WES) in research for at least five years, and academic clinical laboratories with national reach have been doing sequencing for clinical applications for almost as long. Companies have also been offering WGS and WES as a clinical service for a few years now. So far as we know, no one has been sued for infringement of “gene patents” for performing WGS.

The genetic testing industry is in a period of potentially major structural change driven by several factors. These include weaker patent protections after Association for Molecular Pathology v. Myriad Genetics (the “Myriad decision”) and Mayo Collaborative Services v. Prometheus Laboratories, Inc.; a continuing shift from single-gene tests to genome-scale sequencing; and a set of February 2014 amendments to the Clinical Laboratory Improvement Amendments of 1988 (CLIA) regulations and the Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule. This article explores the nature of these changes and why they strain existing regulatory frameworks for protecting patients, research subjects, and other consumers who receive genetic testing.

Oversight of genetic testing has, at least to date, had two major thrusts: (1) privacy and ethical protections and (2) traditional consumer health and safety regulations. Examples of the first are the Genetic Information Nondiscrimination Act and the HIPAA Privacy Rule, which after 2013 amendments expressly protects genetic privacy as well as other medical privacy.