Cell-free RNA as a Fetal Timekeeper

Cancer and fetal development share a lot. This is nothing new. The 19th century pathologist John Beard noted the similarities between a tumor and a trophoblast. Building on that, Lloyd Old, a pioneer in cancer immunology said, “If you've ever seen the trophoblast invading the uterus, it invades, spreads, creates a blood supply. It also suppresses the maternal immune system. All of those are characteristics of cancer” (1). Today, tumors are being diagnosed noninvasively through the ability to find traces of circulating malignant material in blood. The same holds true for fetal development. The ability to reliably detect fetal cell-free DNA in maternal blood is changing clinical practice. I spoke with Howard Hughes Investigator and bioengineering, physics, and applied physics professor at Stanford University, Stephen Quake, who has played a central role in these innovations. Motivated to replace invasive biopsies with blood tests, Quake developed a polymorphism-independent shotgun DNA sequencing test that could detect fetal aneuploidy from maternal plasma (2). “After 10 years, this has had an enormous impact,” he says, “three million women are tested each year, and these methods have been widely adopted in the liquid biopsy space.” Quake has his sights on another challenge around childbirth—estimating gestational age and the risk for preterm delivery. “It started with the idea of following human development, and using RNA to do that,” Quake explains. In a manuscript in which he and colleagues combined high-throughput microarrays for RNA analysis with next-generation sequencing …