Chapter 122
Curing Rare Diseases — 11
In 2018, He Jiankui, a rogue Chinese scientist, announced, initially via YouTube videos, that twin babies had been born after he had CRISPR edited a human embryo and implanted it in the mother’s uterus. This was the first human germline editing—not just inducing a mosaic of the edits across the trillions of cells of a person’s body but enabling transmission to the next generation. It shook the science community. Days after the announcement, in a New York Times invited op-ed, I called it “a misguided, reckless use of powerful gene-altering tools to create edited human beings. We should not proceed down this road until we know far more about the consequences of what we are doing.”
Later, we learned Jiankui had actually edited thirty-one embryos, and six women were implanted. All of this was done without approval of the hospital in Guangzhou. Jiankui was imprisoned for three years for his unethical conduct and illegal medical practices and fined nearly half a million dollars.
Someday there will be a place for heritable human genome editing, but it’s still a ways off. While double-strand breaks are obligatory, worrisome large deletions, loss of chromosome segments or arms, mosaicism, and off-target edits have all been seen in lab studies of CRISPR-edited embryos. Until these potentially serious genetic defects—that will be transmissible—can be satisfactorily addressed, the trade-off for treating (and potentially curing) rare monogenic diseases isn’t acceptable.
The cost for Casgevy, the FDA-approved CRISPR genome editing for sickle cell disease, is $2.2 million; the gene therapy approach for the same disease has a list price of $3.1 million. The estimate to treat a patient with sickle cell disease using current therapies for a lifetime is about $1.7 million. But that estimate doesn’t convince payors to pick up the huge up-front cost, which for some gene therapies exceeds $4 million, the most expensive treatment in the world. There are many ideas for how the costs could be reduced or justified, and there’s an ethical obligation to provide these treatments, especially for those least likely to gain access. While much has been written, there’s no solution in sight for this chasm between a momentous medical breakthrough and profound inaccessibility. One major step is to reduce the multiple years it takes for FDA review to “create a more streamlined path for bringing much-needed CRISPR medicine tailored to patients with a one-of-a-kind genetic typo.” Collaborations between academia with industry to radically reduce the cost of manufacturing are starting to take hold. It will take time and a multipronged aggressive strategy, as the Innovative Genomics Institute published. Hopefully, in the years ahead, the barriers to getting genome editing for all who would benefit will be overcome.
Reading human genomes has become tremendously cheaper since we first learned how to do it in 2003, when it cost nearly $3 billion. We call it sequencing. The cost of a whole genome sequence is in the range of $200 in 2025, and it can be done in as little as three hours. This technology is grossly underutilized in clinical medicine. For sick newborns and babies who are critically ill without a diagnosis, a rapid-sequence identification of disease-causing mutation and a clinical management program can all be accomplished in eleven hours or less, utilizing multiple AI software packages, and have saved the lives or vital organs of hundreds of babies. The AI tools provide an exceptionally rapid and accurate means of identifying which of the millions of DNA variants may be implicated in a child’s condition and reviewing all the known medical literature and potentially useful treatments for the causative mutation.