How do we deal with human genetic modification?

 

By: Malavan Ragulojan (c2022)

Although the future of the infamous He Jiankui has been decided in a court sentencing announced late last December, the ethical pandora’s box he unleashed has yet to be fully appreciated. In February of 2019, He Jiankui of the Southern University of Science and Technology in Shenzhen, China shocked the scientific world with claims of gene-edited babies. Made from manipulating human embryos with CRISPR-Cas9 and inserting them into a human womb, these genetically modified children purportedly did not inherit the HIV status of their HIV positive father (despite the established existence of safer alternatives to avoid this complication). Instead of a formal manuscript, He Jiankui audaciously uploaded a YouTube video detailing his work. Although proof of the experiment was never actually released, the response briefly captivated the public imagination as the idea of designer babies, Star Trek Eugenics wars, and Gattaca style genetic discrimination seemed to be just around the corner. The scientific community not only condemned the woefully premature use of CRISPR technologies, but also the unethical measures He employed in his study, including coercing patients into participating, forging ethical documents, and swapping blood samples to bypass Chinese laws regarding HIV positive research participants. Primarily as a result of his latter offense, a Chinese court sentenced He to three years of imprisonment and dealt a fine of 4 million yuan; two accomplices were given lighter sentences. It would seem He’s desire to be the pioneer of a new era in medicine has come to naught. Yet, although this man’s fate has been decided, the complexity of the issue of genetically modifying humans has only begun unravelling. 

There is no denying that in the coming years, similar cases like He Jiankui will proliferate. Part of the promise of CRISPR is its relatively low cost and ease of manipulation compared to the burdensome genetic modification technologies of the past.  An ambitious scientist willing to skirt the rules in a nation lacking the resources to regulate research could easily be the next He Jiankui. Indeed, the Russian scientist Denis Rebrikov has explicitly stated his intention to use CRISPR technologies to treat deafness (though Russian officials have attempted to quell fears of mimicry). Of course, sometimes research is clandestinely sanctioned by the state; contradictory responses from the administrators of the hospital which employed He Jiankui, in addition to the sources of funding, might suggest that elements higher up might have used the unwitting scientist as a scapegoat once the work ran afoul of the public. In a twist bordering on science fiction, the same protein He manipulated is associated with increased cognitive function in rats, leading some to suggest he may have been trying to enhance the memory of these children. Success would no doubt have intrigued Beijing. Conspiracies aside, the question remains of the implications of He’s decision for the future of genetic engineering. What was only potential has now become reality, if only a very preliminary and rudimentary one. 

That CRISPR mediated modification of humans has its benefits is an understatement. For instance, researchers at UCSF have used CRISPR to diminish transplant rejection through altering the expression of MHC class proteins on donor cells, thereby diminishing the possibility of assault by the host immune system. Duchenne Muscular Dystrophy has also been cited as a promising area for future research into genetic modification due to be the result of a single gene, making it an easier target compared to much more multifactorial diseases. As research proliferates in this ground-breaking field, more and more genetic loci will emerge as plausible targets. Previously uncurable diseases like DMD may finally be annihilated. Furthermore, genetic modification may proceed a step further into preventive care. Cancers, for instance, are fundamentally genetic. CRISPR may be employed pre-emptively to rectify problematic oncogenes and tumor suppressor genes in susceptible individuals, reducing the risk of developing such diseases. We could easily envision a future where genetic modification substantially reduces the disease burden on civilization. 

Yet, humanity is only beginning to elucidate the interactions of genes and the prolific complexity of the genome. Altering one gene could easily generate a treacherous cascade leading to unimaginable consequences that rival the original disease being targeted. Without sufficient investigation, purported cures might lead to devastating long-term consequences. However, it could also be argued that eliminating this dearth of knowledge might more be a matter of “when” as opposed to “if.” Instead, perhaps an even greater issue might not be the scientific, but the social and political. Who would have the opportunity to access these technologies is particularly poignant when one considers that germline traits will be passed down the generations. An unequal access to limited resources is one matter; a case can be argued that individuals fundamentally have the power to forge their destinies. Yet, to have a particular segment of the population be genetically altered to be permanently free from ravages like HIV or cancer and pass this down to their descendants is rather uncomfortable. Although one could argue that interbreeding would lead to the dissemination of these protections throughout society, a case could also be made that distinct genetic hierarchies could emerge, with those of altered genetic background refusing to mingle with those who have more virgin genomes. Furthermore, at what point do we draw the line? Eliminating a disease like Duchenne’s Dystrophy will eventually become the provision of immunizations to cancer. Then one could argue that myopia is also a condition that ought to be rectified genetically. Eventually, the opportunity for enhanced intelligence and beauty will readily present themselves as logical next steps. How do we want to grapple with the opportunity for human enhancement? Will individuals begin to genetically sequester themselves like in the film Gattaca, in which genetic discrimination is the norm and those without manipulation are deemed inferior?  

Despite being on the trajectory towards actualization, genetic modification has much, much farther to progress before it can even become plausible; much of the criticism directed towards He was that his efforts were far too pre-emptive given our current lack of knowledge.  However, this means a unique opportunity presents itself. A moratorium should be placed on the technologies of human genetic modification until a truly vigorous and international consensus can be achieved. I do not mean to argue either against or for the use of CRISPR in human modification. Indeed, I do not know what the right decision even is. But it is evident that unless we grapple satisfactorily with these questions, we may arrive in a predicament veering dangerously near apocalyptic science fiction. 

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