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04 October 2018 by Christine Stevenson

The Century of Genome Engineering

Almost since the discovery of DNA as the hereditary blueprint for life on Earth, humans have been fantasizing—and fretting—about the possibility of redrawing that blueprint to their own specifications.

Decades later, the ability to do so is finally at our fingertips, thanks to CRISPR-Cas9, the technology that has taken the world by storm with its capacity to edit the genomic content of living organisms.

Needless to say, the implications of CRISPR are nothing short of revolutionary. Every week the scientific community is made aware of an extraordinary new feat of genetic engineering made possible by the power of CRISPR, from the mice whose cataracts were cured to the identification of weak points at which to battle Zika virus to the first-ever undertaking to edit the DNA of human embryos.

With CRISPR in hand, scientists are forging full speed ahead, hardly waiting for other stakeholders to catch up. As it turns out, they may have a good reason for keeping up this momentum while they still can.

As CRISPR creeps into the spotlight, a dark cloud of controversy has begun brewing over it. CRISPR’s capacity to tinker with human embryos has been the source of a great deal of negative press around the technology, especially as more and more teams of researchers broach the touchy territory of “designer babies.”

Indeed, the prospect of engineering human embryos has captured the public’s imagination for decades. Science fiction writers and their audiences (not to mention bioethicists) have long fixated on a possible future where humans need not accept the genetic hand they are dealt when bringing a child into the world.

Today, that future no longer exists simply in our imaginations—it’s knocking at our door, threatening to bring with it a flurry of consequences, both gnarly and miraculous, that were previously confined to the realm of fiction.

Those consequences scare some people. With a growing number of research groups around the globe now experimenting with human germline editing, the word “moratorium” has graced an increasing number of lips belonging to researchers, ethicists, and laypeople alike.

In 2015, a group of leading scientists published a paper calling for such a freeze on human germline editing worldwide. However, research presses on within the CRISPR community. It seems only a matter of time before CRISPR makes the leap from its current state to use on implanted embryos that are born into the world in all of their gene-edited glory.

On the one hand, this eventuality is incredibly exciting. CRISPR carries a truly miraculous potential for the world of medicine to resolve previously intractable genetic diseases. CRISPR may someday enable cures for the most agonizing of genetic conditions before they are even able to manifest in an individual.

On the other hand, at the same time that CRISPR is moving us toward miracle cures, it is moving toward enabling what many find to be a disturbing level of control over the nonmedical minutiae of a future person’s appearance and identity.

After all, characteristics like eye color, skin color, and height all have a genetic basis (though perhaps not one that is, as of yet, fully characterized) that is just as susceptible to manipulation by CRISPR. Nonetheless, to allow characteristics like these to be hand-picked and engineered into an embryo’s reality using CRISPR would seem to represent an obvious ethical misstep.

And yet, it seems just as obvious that the use of CRISPR would be ethically permissible to correct fatal conditions that induce intense suffering, such as cystic fibrosis, Huntington’s disease, and Tay-Sachs disease. In fact, to not use CRISPR to correct the problem in these cases would seem to many an egregious ethical breach.

But what occupies the space between these two extremes—the gray area between genetic elements that are obviously medical and obviously aesthetic? Conditions and qualities that lie in this space are even trickier to size up, and the questions they pose are endless.

For example, should we be tinkering around with adverse phenotypes that are not fatal, such as mental retardation, achondroplasia, and blindness? Although such conditions may impact an individual’s quality of life, many would question whether this is enough to warrant genetic intervention.

Further, members of these disabled communities themselves have argued that to permit such intervention would amount to devaluing their identities and condoning stigma.

Would CRISPR intervention be warranted to alter MAOA gene which has been found to predispose the men who carry it to violent crime? While using CRISPR to dictate personality sounds unethical on its face, scenarios like this one show that the genetic basis for a person’s character can be harmful in very real ways.

And how about using CRISPR to correct phenylketonuria, or PKU? Individuals affected by PKU can maintain a relatively normal life as long as they consume an expensive protein-limited diet throughout childhood, without which they become severely mentally disabled. The financial burden of modern medicine’s effective but pricey solution to PKU complicates the question of whether germline correction of the disease is justified.

These few scenarios demonstrate just how complex and ethically treacherous the grey era of CRISPR germline editing can be. While the CRISPR community’s greatest source of internal turmoil today is the technology’s disputed intellectual property, it’s not hard to foresee that even weightier battles—those of the ethics of CRISPR—lie on the not-so-distant horizon.

As we tumble down the slippery slope of germline editing from scientific jackpot toward science fiction nightmare, we find that is not at all clear where one ends and the other begins. What is certain is that the technology that can make it all happen is imminent, and soon we won’t have to wonder about how these scenarios will be confronted.

For better or for worse, they’ll be playing out before our eyes.