The Science Of The Next 150 Years: 50 Years in the Future
It is 2063. you walk into the doctor's office, and a nurse takes a sample of saliva, blood or a prenatal cell and applies it to a microchip the size of a letter on this page on a handheld device. Minutes later the device reads the test results. The multicolored fluorescence pattern on its display reveals the presence of DNA sequences that cause or influence any of 1,200-plus single-gene disorders. Fortunately, regulatory authorities have approved a cure for each one of these diseases: gene therapy.
Gene therapy works by using the innate biological machinery of a virus to carry healthy versions of genes into the nucleus of a cell to replace a mutation that leads to illness. It was conceived shortly after the discovery of DNA's structure in 1953, but its path to a bona fide treatment was fitful. Early attempts worked sporadically at best. In 1999 an 18-year-old died when a type of gene-carrying virus used to treat a metabolic disorder triggered a deadly immune response; the molecular payload ignited a reaction in immune cells in the patient's liver. Also that year, two infants with an inherited immune deficiency received genes, onboard retroviruses, that veered into cancer-causing genes as well as their targets—leukemia resulted.
These setbacks mired the development of gene therapy in a debate about which viruses could be used safely as a vector, the gene-bearing invader of a cell.
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After a difficult start, gene therapy began to rack up milestones. In 2012 the European Commission approved the first gene therapy for lipoprotein lipase deficiency, which impairs fat digestion.
Then, in 2014, the U.S. Food and Drug Administration approved treatments for a form of inherited blindness (Leber's congenital amaurosis), an immune deficiency (adenosine deaminase, or ADA, deficiency) and a genetic disorder affecting the brain (adrenoleukodystrophy). Though rare, the conditions were relatively easy to target.
These endorsements affirmed adeno-associated virus (AAV) as the vector of choice. Most of us already carry it in some of our cells, which means our immune systems ignore it. Retroviruses, in contrast, were retooled to self-destruct but could still cause cancer, as they had in the immunodeficient infants. And lentivirus, after winning FDA approval, failed to catch on because patients were reluctant to allow themselves to be injected with HIV, albeit in a form stripped of AIDS-related genes.
Arrival of gene therapy for hemophilia B, in 2016, proved the economic value of the technology: $30,000 for a one-time gene treatment trumped a lifetime of clotting factor injections—a bill that could tally up to an expenditure of $20 million over the course of many years.
The ability to control the immune response to the vector meant that the most imposing technical barrier had been overcome: the chemical package delivered to patients not only provided a replacement gene, it also bolstered parts of the immune reaction against cancers and infections and dampened the aspects of the response that could lead to the rejection of viral vectors.
The floodgates now opened. Because the retina is shielded from the immune system, gene therapies for about 100 forms of blindness came first. In 2019 a dozen children with the ultrarare giant axonal neuropathy became pioneers by receiving gene therapy to the spinal cord. Next on the list were spinal cord injury, amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease) and spinal muscular atrophy. Intravenous, gene-laden AAV slipped across the blood-brain barrier, thereby preventing Parkinson's and other brain diseases. No longer was it necessary to bore holes in the skull, as happened in the early part of the century.
Over time researchers came to recognize that some conditions are best treated without replacing a gene. For cystic fibrosis, drugs that could untangle a protein with a faulty structure were better because gene-treated cells in the lungs and airway do not persist. And for Duchenne muscular dystrophy, reactivating silenced genes was easier than delivering healing genes to all the muscle cells in a child's body.
The successes only left room for more. By midcentury new therapies were targeted beyond rare, single-gene disorders to embrace common conditions that reflected genetic and environmental risk factors, such as mental illnesses, diabetes and most forms of heart disease.
By 2060 the ability to use gene testing to predict a patient's future health—coupled with genetic interventions—had reached an unprecedented level of precision, with profound repercussions. With diseases stopped in their tracks, health care costs plunged as a longer-lived, physically fit population emerged.