Genetic disorders are among the most difficult for doctors to treat. Not only do they cause a lot suffering, but they also cost numerous lives. A cure for heritable diseases would therefore fulfill a long-pursued dream. Fortunately, it is now possible to conceive of a world in which this is a reality. On August 2nd, a group of scientists announced that they had managed to consistently repair a genetic defect in human embryos for the first time, thanks to a process called CRISPR/Cas9.
CRISPR/Cas9 is a powerful system that can change how DNA is expressed in the cells of living organisms, including humans. Scientists first became aware of CRISPR’s existence by studying the immune system of bacteria. They noticed that bacteria had something resembling a genetic “memory”, meaning that the bacteria could store and then recall part of the genetic code of previous viruses that had infected it. Once the bacterium had spotted a potential threat, the CaS9 protein would compare the virus’s RNA with the genetic information from the previous infection. If the Cas9 protein found a match, then it would attempt to pacify the virus by cutting its genes into smaller pieces. In 2007, scientists revealed that they could isolate the CRISPR/Cas9 system and use it on any organism. Once injected into a living cell, CRISPR could identify and cut out parts of a desired genetic sequence. Scientists also discovered how to substitute one genetic sequence for another.
This new study represents a significant leap in the use of CRISPR/Cas9. The researchers behind the study managed to correct a heart condition called hypertrophic cardiomyopathy (HCM for short) — a disease in which part of the heart is abnormally enlarged due to thickened muscles. Many people with HCM exhibit few symptoms and may not realize they carry the disease until sudden cardiac arrest occurs, which is a particular vulnerability in young athletes. Doctors cannot normally prevent the transmission of the faulty gene across generations, but if the condition is caught in time, it can be successfully managed with medication or surgery.
The study, which was carried out by a team of scientists from Portland, Oregon, targeted a gene called MYBPC3. The scientists combined the eggs from 12 healthy women with the sperm from a male volunteer who carried the genetic defect in MYBPC3. Before the sperm was injected into the egg, the male’s germ line — essentially, the set of heritable genes that is passed from parent to offspring — was edited by CRISPR to remove the defective genetic sequence. The offspring therefore inherited one healthy line from the mother and one edited line from the father. As the embryo divided, the cells began to spontaneously repair themselves by substituting the missing sequence from the father’s germ line for the mother’s healthy MYBPC3 gene. Approximately 72 percent of the cells carried this corrected sequence.
Despite the success of the study, it only has limited clinical use. The study involved a very complex process in which the defective gene first had to be correctly diagnosed, and then a viable embryo had to be conceived through in vitro fertilization. It’s difficult to replicate this in a normal setting. Gene editing also raises profound questions about the ethics and desirability of tampering with human genetics. From a purely technical perspective, gene editing represents an enormous undertaking. Some diseases or traits are not caused by a single gene. Instead, they’re spread across hundreds of different genes. Editing the human genome on a mass scale like this could have complex tradeoffs and unintended consequences for both individuals and society. Many of these consequences may not be apparent for decades to come. The standard for safety and efficacy needs to be set very high before gene editing starts to become common practice.