By Harry Ostrer
Imagine this day in 2023.
You decide it is time to allow your doctor to obtain your whole genome sequence to develop a risk profile. You are 58 years old and you have been forgetting simple things. Your family is worried. Your genetic counselor asks which results you would like to learn. You choose only the results for which your doctor says something useful could be done. You find out that your Alzheimer’s disease profile confirms your fear. Your doctor immediately prescribes three drugs based on your genomic profile which will decrease the progression of symptoms. Your profile also warns of risk of pre-cancerous colon polyps and a more intensive screening procedure in put into place.
This is personalized prevention in action, the marriage of individual genetic information to evidence-based medicine. It will provide more precise diagnoses, targeted treatments, and tailored prevention strategies. This is how medical care will be provided on DNA Day 11 years from now, maybe sooner. How did we get there?
The first DNA Day in 2003 celebrated not only the discovery of the double helical, self-replicating structure of DNA some 50 years earlier, but also the complete sequencing of human genomes. Unleashing the technologies of the turn of the millennium, new efforts (International HapMap Project, the 1000 Genomes Project, and others) mapped and subsequently sequenced the genomes of people from many different groups to catalog the variation in their genomes. These variants were associated with and, in some instances, shown to cause a host of common and rare disorders. Efforts were mounted not only to diagnose diseases, but also to predict risk of future disease, responses to drug and radiation therapies and toxicities.
In 2012, the game changed with the advent of cheap, reliable sequencing that could complete an individual’s genome in a day at a cost of US $1,000. Large numbers of genomes started to be sequenced. Some were performed as clinical tests. Rather than testing the 25 genes associated with epilepsy and the 35 associated with heart disease, the whole genome was sequenced. Yet the results from only those 60 genes were reported, because that is what the doctor ordered and the patient consented. In subsequent years, the doctors would ask the labs to go back and look at the patients’ genomes for new risk factors — those for Alzheimer disease and stroke and responses to current and new therapies.
Some of the genomes were sequenced in clinical research trials to test the validity and utility of genomic sequencing for previously under-tested diseases and therapies. Some of these studies provided evidence for new diseases, previously unknown. The information derived from these clinical trials was published in medical journals and stored in online databases without any personal identifying information. This made the information available for all and enabled the lab to keep reanalyzing the sequences from the very first patients tested onward.
Not only were individuals’ genomes sequenced, but so too were the genomes of their cancers. Sequencing became a gold standard for cataloging the mutated, amplified and deleted genes that cause cancers to form, progress, spread to distant sites and respond to therapies. Indeed, these mutated genes became the targets for new therapies that were developed as magic bullets to obligate these cancers.
The results of genomic sequencing were linked to the electronic medical records that replaced paper charts as Obamacare was fully implemented in 2014 and 2015. As a result genomic sequencing became a part of everyday primary care.
Individuals asked their doctors to release their genomic sequences to them, so that they could explore their own genomes. Many people teamed up with others in a new, anonymized HIPAA-protected Genebook. This enable them to compare how much of their genomes that they shared with other members of their ethnic group. They could search for unknown relatives who shared an eighth or a sixteen of their genomes intact. They could also search for hidden ancestry with Neanderthals, Denisovans and other hominins who lived in the distant past.
All of the ethical dilemmas of the recent past have not been solved by 2023. Debates are still raging about whether to report risk of schizophrenia and other mental illnesses and likely IQ. Libertarians and genomicists wrangle in the courts about whether states could sequence the genomes of children in their newborn screening programs. This is the Era of Genomic Medicine as it reaches its maturity.
Harry Ostrer, MD is the author of Legacy: A Genetic History of the Jewish People. He is Professor of Pathology and Genetics at Albert Einstein College of Medicine and Director of Genetic and Genomic Laboratories at Montefiore Medical Center. In October 2010, he was named to the Forward 50 list of “people who have made an imprint in the past year on the ways in which American Jews view the world and relate to each other.” Read his previous blog post on “Let us now praise human population genetics.”