The CRISPR Era: A Promising Future with Dark Implications

crispr-8-3-18

By: Ben Cashdollar

In November 2018, a Chinese researcher claimed that he created the world’s first genetically edited babies, a pair of twin girls who are purportedly immune to the Human Immunodeficiency Virus (HIV). The scientist, He Jiankui, “feel[s] proud” of this accomplishment, a stark contrast to the highly critical reaction of the scientific community at-large. While the scientific accuracy of Jiankui’s claims remains in dispute, this story is an undisputed harbinger of a new era, one where human-kind can wield scientific understanding to alter with impunity the genetic code of any living organism. This newfound ability raises several pressing ethical concerns, and underscores that our society is woefully unprepared to address the challenges created in the age of genetic editing.

What is Gene Editing?

The importance of DNA as a vehicle for genetic inheritance wasn’t understood until the 1940s; less than 100 years later, scientists today possess the ability to identify the traits individuals have inherited by way of genetic testing. Moreover, recent genetic editing techniques provide scientists and medical professional an unprecedented degree control over what traits an individual inherits. Put differently, if genetic testing is thought of as taking a test with the answer key in hand, then genetic editing is akin to writing that test and the answer key yourself. Genetic testing allows you to understand how your DNA affects you, genetic editing allows you to control what DNA is present to being with. (For more WJLTA content Ben has written on genetic testing, see here.)

While scientists have been able to effectuate genetic editing for decades, the discovery of the CRISPR-Cas9 system (referred to as simply “CRISPR”) was a breakthrough because of its editing precision. In a nutshell, CRISPR allows for the cutting of DNA at specific locations. These cuts can be used to remove, add, or alter genetic material, effectively allowing scientists to re-write the genome.

The Potential Good of Genetic Editing

In a medical context, the potential beneficial applications of CRISPR are only limited by the constraints of the human genome; any genetic disease can plausibly be cured by removing the associated DNA sequences from an individual’s genome. The value of this endeavor cannot be overstated. Given time, cancer, inherited heart disease, and any number of other genetic disorders could be eradicated.

Another potential use aims to combat the current organ donor crisis by using CRISPR to modify pig organs so that they are compatible for transplantation in humans. It is current practice to replace failing human heart valves with their porcine equivalent, but CRISPR could allow for the transplantation of an entire pig heart into a human suffering from heart failure.

CRISPR’s application is not limited to medicine; it is also being used to revolutionize the agriculture industry. Genetic editing can be used to create plants that produce higher crop yields, are more nutritious, are disease-resistant, are impervious to droughts or pests, or that can better-endure extreme weather conditions.

The Potential Bad of Genetic Editing

CRISPR is precise, but it is not perfect. Still present is the concern that a CRISPR-based therapeutic edits or alterations could have unforeseen “off-target effects.” Any CRISPR-based drug would be engineering to operate at a specific “target” DNA sequence within a “target” gene. However, it is also possible that this “target” DNA sequence is shared by multiple different genes. Recognizing this target DNA sequence, despite being “off-target” in regard to the underlying gene, a CRISPR drug would edit these “off-target” genes, in addition to the target sequence. The off-target effects that result vary in severity based on the gene edited; regardless, this is not a desirable outcome, and is of even greater concern in the context of “germline” genome editing, where any change is passed on to future generations.

Performed at a sperm, ovum, or embryo level, germline edits are incorporated into every cell of an individual’s being, fundamentally changing their genome forever. This contrasts with somatic gene editing, where the changes made are neither body-wide nor heritable. Both methods can be used to achieve the same ends but operate with drastically different scope: somatic editing makes localized changes to a part of the body, whereas germline editing changes the body.

While curing heritable diseases or solving world hunger are undeniably noble purposes, genetic editing, especially germline genetic editing, can also be used to pursue less humanitarian ends. Eugenics, the science of improving a human population by controlled breeding to increase the occurrence of desirable heritable characteristics, is an unsavory reality in the post-CRISPR world. While the aforementioned genetic disease eradication is a form of beneficial eugenics, an individual’s genes are responsible for much more than their health.

The occurrence of a “desirable heritable characteristic” is determined by genetics. For example, a number of physical traits related to an individual’s appearance, muscle strength, and intelligence are all influenced by genetics. Knowledge of these specific genes, combined with the power of CRISPR to make germline genetic edits, would inevitably lead to the creation of “designer babies” that are genetically predisposed to be superior to their non-edited counterparts. Today’s society is already divided by a number of social, political, and economic factors; the existence of genetically-superior individuals would further compound existing issues and exaggerate everyday disparities.

Moving Forward

Our laws presume that “all men are created equal,” but a future where genetic editing is the norm forces us to question that presumption. The inherent danger of CRISPR is the potential for a single individual to effectuate enormous change – the birth of the “CRISPR twins” is a prime example. Without regulation, oversight, and enforcement on an international scale, such haphazard practices could become the norm in the future.

Moreover, germline genomic editing techniques create concerns regarding informed consent, the requirement that physicians provide their patients information about potential procedures and available alternatives so that the patient can make an informed opinion regarding their course of treatment. This requirement becomes quite complicated in a world where substantial genetic modification can be performed prior to birth, and raises questions regarding the amount of control parents should be afforded over their child’s genome.

In the US, germline editing is not per se illegal. The National Institute of Health (NIH), the biggest funder of research in the country, does not fund germline genome editing research. To be clear, this is not an outright prohibition on germline editing research, but merely a prohibition on using NIH funds to finance germline editing research. Current US legislation similarly only prohibits the use of federal funds to finance germline editing experiments. Internationally, a number of countries have laws restricting germline genetic editing, but the scope of these restrictions is highly variable.

CRISPR is still an evolving technology, and as the underlying science advances so too must our collective understanding of its ethically and socially permissible uses. Proper application of this technology has the potential to revolutionize the healthcare and agriculture industries, but along with that potential comes the risk of misuse and exploitation for personal gain. This is a discussion that must parallel the development of the technology itself, as CRISPR’s theoretical and practical limitations will directly affect the expansiveness of any attendant regulation. Undoubtedly, the fate of CRISPR will be shaped by present-day conversations and experiences. These issues extend beyond national boundaries. Our response must be of similar scope. It is our responsibility to ensure that we consider all potential ramifications of this remarkable technology, as CRISPR’s fate will directly impact humanity’s future.

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