“While sequencing costs continue to decline, healthcare costs are going up,” says Dr. Eric Topol. “Wouldn’t it be great if we could use genetic information to help find treatment that’s right for each individual?”
Dr. Topol, director of the Scripps Translational Science Institute, envisions a day when the combination of wireless technology and medicine will be common practice, providing individualized information about a person’s health. Topol was voted the Most Influential Physician Executive by Modern Healthcare magazine in 2012 and continues to push the field from what he calls “old medicine” to “new medicine.”
“Today, we practice population medicine,” he says. “We require mass screenings; we prescribe statins to everyone for heart disease. But average is over. In the future, we will be practicing medicine at the individual level.” Topol advocates the use of genetic information for individualized medicine “from pre-womb to tomb,” arguing that the genome has a place in healthcare during every stage of life.
From Family Planning to Birth
“The percentage of serious recessive alleles is very high in our population,” Topol says, citing cystic fibrosis and Fragile X syndrome as examples. “When you’re planning to have a baby, wouldn’t you want to know if your future child is at risk?” Although several fetal sequencing tests (such as the verifi® prenatal test) are available today, they have not yet become routine. Recent advances in noninvasive prenatal testing are making prenatal screening more widely adopted as an alternative to invasive methods, but it still has a long way to come. Newborn screening is also making great strides, with sequencing enabling rapid diagnosis of newborns in a clinically relevant timeframe that was never before possible. Once a distant goal, widespread newborn genome sequencing is becoming a real possibility in the present day.
Diagnosing and Monitoring Disease
Sequencing has been increasingly used to find the causes of rare or undiagnosed diseases. The story of Lilly Grossman demonstrates how the family finally found an answer for Lilly’s undiagnosed disease through a study called IDIOM (Idiopathic Diseases of Man), led by Topol and his daughter Sarah. Lilly experienced severe tremors since the age of one-and-a-half years, and was misdiagnosed with a spectrum of disorders including cerebral palsy, glutaric aciduria, and mitochondrial disease before finding an answer through sequencing. By performing whole-genome and whole-exome trio sequencing studies, the IDIOM team identified mutations in ADCY5 and DOCK3 that were responsible for Lilly’s disease. A recent study in the New England Journal of Medicine discusses the use of sequencing for disease diagnosis, and Topol comments that molecular diagnosis rates will continue to grow along with developments in sequencing technology and its implementation.
In addition to personal health information, infectious disease surveillance is also undergoing a revolution. With sequencing technology, investigators can sequence a pathogen to track an epidemic to its source and control outbreaks. Researchers and epidemiologists around the world are using next-generation sequencing to track viral diseases such as influenza, as well as bacterial outbreaks such as tuberculosis, Escherichia coli, Staphylococcus aureus, and more.
Cancer, Aging, and a Dose of Prevention
A significant proportion of genomic research has focused on cancer. Projects like The Cancer Genome Atlas and the TCGA Pan-Cancer Analysis project are compiling sequence data for germline and somatic mutations from cancer patients, aiding navigation of different cancer pathways. Ultimately, this research could help physicians prescribe treatments that are appropriate to each patient’s genetic information. Even as tumor sequencing studies become more common, non-coding RNA, single-cell sequencing, and cell-free DNA represent future areas of exploration for cancer genomics.
Data sharing among patients has been one of the most exciting developments during this age of genomic information. Topol advocates for open, online medical resources to bridge the digital and DNA worlds. He also notes that pharmacogenomics is gaining traction in the medical practice, and soon we may live in a world where patients undergo requisite tests for genetic markers that indicate potential response, rejection, or side effects before a drug is prescribed.
Topol also argues that genetic information can be used for disease prevention. Today, we can predict certain diseases—for example, macular degeneration— at a young age, and with this information individuals at risk can take action to reduce their chances of developing the disease. The problem, Topol states, is that many of the genes associated with various diseases can have thousands of variants. The challenge lies in distinguishing functional from nonfunctional variants. The rise of single-cell sequencing provides another opportunity to obtain genetic information relevant to health. If we could detect genomic signals from individual cells in real time, one could potentially monitor their personal health from home, without a physician. During his appearance on The Colbert Report, Topol described a nanosensor that detects signals in the blood indicating a heart attack and sends a warning to the wearer. Genomic technology may also help to uncover the mechanisms of healthy aging, suggesting that the power of the genome can inform individual health throughout one’s entire life. As advances in sequencing technology enable single cell or even cell-free DNA analysis, the potential implications for human health continue to grow.