CRISPR: Considering (What May Be) the World’s First Designer Babies

Guest post by Shannon Trujillo

On November 25th, 2018, a Chinese researcher claimed to have been the first person in the world to have successfully used the DNA-editing technique known as CRISPR-Cas9 (or just CRISPR for short) on human embryos. He reported that he used the technique on twin girls that had been born earlier that month. Dr. He Jiankui’s announcement not only sparked outrage within the scientific community, but has captured the attention of the world as a whole, too. So what exactly is CRISPR, and what are the consequences of using it?

A Brief Exploration of the Captivating Acronym Called CRISPR

For those unfazed by large and fearsome acronyms, CRISPR stands for “Clustered Regularly Interspaced Short Palindromic Repeats,” and it is the latest medical advancement garnering global attention for its potential to be used in targeted gene therapy. In short, CRISPR is designed to hone in on a particular region of the genome (such as a segment associated with a cancer) and cut out a stretch of that DNA [5]. The hope is that such a therapy will be able to prevent diseases like cancers or viral infections from being expressed, essentially by destroying the gene’s ability to replicate through breaking the DNA strand [5].

In the case of Dr. He’s experiment, he used CRISPR to edit the genes of two female embryos before they were implanted in their mother’s womb [2]. Specifically, he targeted the gene called CCR5, a protein found on the surface of white blood cells and a known binding site for the HIV virus [2]. The intention of this experiment was to confer immunity to HIV in the two girls.

Unfortunately, even though Dr. He’s research hasn’t been officially published (or peer-reviewed), the preliminary findings have been called a farce by some, and questionable by many [3]. This is due to the fact that only about half of each girl’s CCR5 genes appear to have been edited, and that those edits are actually different from a naturally occurring mutation in the region known to confer some immunity to HIV infection [3]. So now that the CRISPR seal has been (so ignominiously) broken, what’s next in the field of gene editing?

The Biological and Ethical Consequences of Using CRISPR for Gene Editing Therapy

Perhaps the paramount reason why the scientific community was outraged at Dr. He’s announcement about using CRISPR on human embryos is that he appears to have bypassed most, if not all, of the community guidelines for such research. In fact, his actions were in direct conflict with a report written by the U.S. National Academies of Sciences, Engineering and Medicine in 2017, which urged the scientific community to venture into the uncharted biological uncertainties and ethical quandaries only after ruling out all other alternatives, and ensuring that such studies be conducted with incisive oversight and transparency [3].

Regrettably, it does not appear that Dr. He adhered to any of these guidelines, since he conducted the experiment in secrecy (even going so far as to conceal it from his own academic institution) [3]. Furthermore, unlike the work of other researchers who endeavor to use CRISPR to edit mutations that actually cause diseases and that seem to have no other option for treatment, Dr. He used the gene editing therapy to prevent the (already very low) possibility of the girls acquiring the HIV virus in their lifetimes [2]. Moreover, it will be hard to elucidate the effects of the novel mutations that Dr. He introduced in the girls’ genomes, since genetics are simply not black and white. What this means is that we simply do not know if the changes made to the CCR5 gene will in fact confer any immunity to HIV for the girls, or, worse, if the changes might induce other unforeseeable consequences to their immune systems.

Beyond the issues surrounding CRISPR for medical treatment lies the more cryptic and disturbing issue of gene editing therapy for aesthetic enhancement. This notion is sometimes referred to colloquially as the “Designer Baby” movement, and elicits a potential reality that bears an eerie resemblance to Aldous Huxley’s Brave New World. In fact, a major concern in the bioethical community is that, in the wrong hands, gene editing technologies could be used to further expand the opportunity gap between the impoverished and affluent, assuming that only the latter would have access to the resources necessary to receive such treatment [1].

With that being said, it should come as no surprise that the scientific community was shocked at Dr. He’s announcement that he had independently executed the first attempt at using CRISPR treatments in human embryos, without rigorous experimental design, without peer-review, without clinical trials, and so on. This outrage is especially salient when considering the fact that his actions may have unintended ramifications beyond just those contained within the girls’ bodies. What will our CRISPR-covered future look like? A paradise of health where many cancers and debilitating disorders have been cured; or a dismal dystopia where gene editing is used to determine people’s social standing from conception. We might even consider a third reality, where CRISPR falls into suit with subjects like Lamarckism and String Theory- little more than an esoteric discipline intermittently resurrected by idiosyncratic iconoclasts.

The Uncertain Future of This Genomic Panacea

In spite of all of the excitement surrounding CRISPR and its promise for curing diseases and cancers; or more dubiously, its role in a potential designer baby crusade, there is some evidence to suggest that this treatment may not work on everyone. This has to do with the fact that researchers most often acquire CRISPR from bacteria that live on or within the human body [4].  With that being said, humans and their prokaryotic occupants do not always have the same goals “in mind”. So, as evolution would have it, the human body has a propensity to evolve defenses against potentially baleful invaders.

The concern surrounding the efficacy of CRISPR came after preliminary results from a Stanford study were published to the website bioXiv [4]. In this study, the researchers looked at the two most common versions of the Cas9 protein used in CRISPR treatment, which come from Staphylococcus aureus (which you may know sometimes causes staph infections) and Streptococcus pyogenes (which you may not know can become flesh-eating bacteria) [4]. Given the natures of these two bacteria, it should come as no surprise that our bodies have developed some defenses against such potentially unsavory strains.

The researchers first needed to determine whether or not the study participants had antibodies in their blood for the Cas9 proteins of the two strains, and they found that the majority of the participants did (79% for Staph and 65% for Strep) [4]. This suggests that such participants might not take well to CRISPR-Cas9 treatments since their bodies already have immunity built up against the very bacterial agents designed to help them.  Moreover, the team found that T cells (important cellular agents in the human immune system) of another group of participants sometimes reacted to the presence of the Cas9 proteins (46% for Staph but no response to Strep) [4]. A reaction by the T cells further suggests that such participants might already be immune to CRISPR-Cas9 treatment.

However, things need not seem so bleak. Some scientists believe that this small hiccup in the wave of CRISPR excitement should actually inspire scientists to study the promising technique even further [4]. Moreover, there may even be a number of ways to bypass the threat of an immune response to CRISPR though the use of proteins besides Cas9 [5]. In any case, most significant scientific breakthroughs take countless methodological iterations and explorations around dead-ends, so why should CRISPR be any different?

Closing Thoughts

Clearly, there are many questions as to what CRISPR is, how it may be used, and what consequences it may bring. As with most (if not all) scientific endeavors, scientists have a responsibility to ensure that their research on CRISPR is conducted thoroughly, and that their findings are peer-reviewed and transparently reported. As a consumer of all the news regarding CRISPR, and genetics more generally, one should seek reputable sources, and consider speaking with a trained professional if they have questions about what role CRISPR may play in future treatment plans.  

References & Opportunities for Further Reading

[1] Adashi, Eli Y. “The Ethics of Heritable Genome Editing.” JAMA, American Medical Association, 3 Dec. 2018, jamanetwork.com/journals/jama/fullarticle/2717816.

[2] Kolata, Gina, et al. “Chinese Scientist Claims to Use Crispr to Make First Genetically Edited Babies.” The New York Times, The New York Times, 26 Nov. 2018, www.nytimes.com/2018/11/26/health/gene-editing-babies-china.html .

[3] Yong, Ed. “The CRISPR Baby Scandal Gets Worse by the Day.” The Atlantic, Atlantic Media Company, 5 Dec. 2018, www.theatlantic.com/science/archive/2018/12/15-worrying-things-about-crispr-babies-scandal/577234/.

[4] Zhang, Sarah. “You May Already Be Immune to CRISPR.” The Atlantic, Atlantic Media Company, 9 Jan. 2018, www.theatlantic.com/science/archive/2018/01/crispr-humans-immune-system/549974/ .

[5] Zimmer, Carl. “A Crispr Conundrum: How Cells Fend Off Gene Editing.” The New York Times, The New York Times, 12 June 2018, www.nytimes.com/2018/06/12/science/crispr-cancer-gene-editing.html?action=click&module=RelatedLinks&pgtype=Article .