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March 24 - April 10, 2019
The potential utility of therapeutic gene editing goes far beyond simply reverting mutated genes back to their healthy states. Some scientists are employing CRISPR in human cells to block viral infections, just like this molecular defense system naturally evolved to do in bacteria.
And in another landmark effort, the first human life was saved by gene editing in combination with another emerging breakthrough in medicine: cancer immunotherapy, in which the body’s own immune system is trained to hunt down and kill cancerous cells.
The fact that gene editing might be able to reverse the course of a disease—permanently—by targeting its underlying genetic cause is thrilling enough.
CRISPR offers the greatest hope to treat monogenic genetic diseases—those caused by a single mutated gene.
By the end of 2015, no fewer than four independent laboratories delivered CRISPR to fully grown mice suffering from muscular dystrophy and showed that the ravages of the disease could be reversed.
Cancer is caused by DNA mutations, some of which are inherited and some of which are acquired over the course of one’s life.
The question, I was beginning to realize, was not if gene editing would be used to alter DNA in human germ cells but rather when, and how. It was also becoming clear to me that, if I wanted to have a say in when and how CRISPR would be used to change the genetic makeup of future humans, I would first have to understand exactly how much of a break from previous scientific accomplishments germline editing would be.
After all, if a human life could be created in a petri dish, the same type of sterile environment where gene-editing technologies were being developed, it was conceivable that the two methods would someday converge. Research aimed at circumventing infertility had inadvertently refined a procedure that would become integral to future discussions of germline manipulation.
Over the last few decades of the twentieth century, scientists had devised more and more ingenious ways of engineering animal genomes, from cloning to virus-based gene addition to the earliest uses of precision gene editing.
But the ability to generate multiple embryos in the laboratory using multiple eggs and sperm changed all that. Instead of implanting random embryos into the mother, IVF doctors could first analyze the DNA of candidate embryos to make sure they were selecting ones with the healthiest genomes—a practice that’s come to be known as preimplantation genetic diagnosis, or PGD.
After all, if prenatal testing indicates that a fetus suffers from damaging genetic defects, there are typically only two options: proceed with the pregnancy or terminate it. Unsurprisingly, given the controversy surrounding selective abortion, the use of this sort of testing has been the source of vigorous debate.
In this way, I fell into a common trap; scientists, like anyone else, feel most comfortable when surrounded by others like themselves, people who speak the same language and worry about the same issues, big and small.
The ability to refashion the human genome was a truly incredible power, one that could be devastating if it fell into the wrong hands. The thought frightened me even more because, by this point, CRISPR had been widely disseminated to users around the globe. Tens of thousands of CRISPR-related tools had already been shipped to dozens of countries, and the knowledge and protocols needed to create designer mutations in mammals—at least in mice and monkeys—had been described in great detail in numerous published articles.
Every person experiences roughly one million mutations throughout the body per second, and in a rapidly proliferating organ like the intestinal epithelium, nearly every single letter of the genome will have been
mutated at least once in at least one cell by the time an individual turns sixty.
And if we look over our shoulders at the course of evolution that has led to this moment, we’ll see that it’s littered with organisms that certainly didn’t benefit from the mutational chaos that underpins evolution. It turns out nature is less an engineer than a tinkerer, and a fairly sloppy one at that. Its carelessness can seem like outright cruelty for those people unlucky enough to inherit genetic mutations that turned out to be suboptimal.
In my mind the distinction between natural and unnatural is a false dichotomy, and if it prevents us from alleviating human suffering, it’s also a dangerous one.
My views on the ethics of germline editing continue to evolve—but as they do, I find myself returning time and again to the issue of choice. Above all else, we must respect people’s freedom to choose their own genetic destiny and strive for healthier, happier lives. If people are given this freedom of choice, they will do with it what they personally think is right—whatever that may be.
