What is CRISPR?
Clustered regularly interspaced short palindromic repeats, also known as CRISPR, is a new gene technology arising. CRISPR is a family of DNA sequences that is currently known to be found in most archaea and many bacteria prokaryotes but is still to be discovered naturally in eukaryotic or viral DNA [1]. The development of this technology follows unsuccessful traditional gene therapies which were hoped to be able to cure types of cancer and monogenic diseases. Previous gene technology was dependent on a viral vector for delivery of therapeutic genes and could cause immunogenic toxicity and insertional oncogenesis, where genetic material is inserted into normal cells that can contribute to cancer development [2]. Alternatively, CRISPR technology can provide a more efficient solution with site-specific gene editing. However, it must be mentioned that CRISPR has its own limitations including off-target effects and DNA damage with CRISPR often triggering apoptosis over its intended use [1]. First identified in 1987 by Ishino et al in Osaka University, CRISPR’s discovery excited researchers and started the ongoing research into its biological function and its potential therapeutic uses [1]. In its natural state, CRISPR acts as the memory of the immune system by copying viral genetic information from a pathogen into its own, then encodes a complementary RNA sequence to memorise the invading pathogen. For therapeutic purposes to treat genetic disorders, CRISPR is being used alongside Cas9. Cas9 is an enzyme that allows for precise modifications by cutting DNA at specific locations [3].
Diagram of CRISPR/Cas9 technology’s mechanism [4]
Research into the combined use of CRISPR and Cas9 for specific gene editing aims to provide a therapy that could cut out faulty mutations that cause genetic diseases, then replace them with functional genes. In January 2025, NICE approved Casgevy, a CRISPR/Cas9 treatment to be given to patients suffering with severe sickle-cell disease in the UK. These patients will be the first to be prescribed CRISPR gene editing technology as a medical treatment, with widespread hopes of more to be approved in the future [5].
Is CRISPR Forever?
On the other hand, there is a growing concern regarding the potential harmful impacts that may come with gene therapy. Despite the life-changing impact that a cure could have on a person living with a genetic disorder, there are ongoing challenges regarding the complicated ethical considerations of CRISPR/Cas9 technology. The long-term consequences of CRISPR technology are still not understood and there is a concern that any modification of a person’s genome could be permanent and passed onto future generations. There is a possibility that gen technology use could affect the human gene pool and reduce prevalence of genes that are associated with genetic disorders that may have other effects. In 2019 He Jiankui alongside two collaborators were imprisoned for illegally implanting genetically modified embryos into women, from which babies were born. C-C chemokine receptor type 5 (CCR5) gene, a key gene for HIV resistance was inserted into the genome of these embryos. Despite He and his team’s argument that their work had positive intentions, their actions violated the biotechnology regulations and rules of medical ethics in China [6]. Without greater understanding of CRISPR technology’s long-term consequences on future generations, widespread access is still withheld. In the UK, the Human Fertility and Embryology Authority (HFEA) does not permit genetically edited embryos to be implanted in biological women under the Human Fertility and Embryology Act 1990 [7]. One ethical concern for a hypothetical future child with an edited genome is that their parents have consented on their behalf, yet it is the child that must endure the complications and will be required to follow through with the long-term monitoring for their own wellbeing despite not consenting themselves. Thus, the ethical principles of intervention in a person’s genome is difficult to define without knowing the safety of CRISPR for future generations.
Private Eugenics
Additionally, there is a fear that access to successful gene editing technology can redefine a socially acceptable person. Advocates concerned with rights of the disabled may argue that curative gene therapy perpetuates harmful views with the belief that disability is a problem to be solved. Procreative beneficence is an expression that describes a parental obligation to improve the genetics of their offspring [8]. The availability of treatment to cure a person of genetic disorders could increase societal pressure to access this technology. Selection of genetic traits could imply a lower value held by those with the undesired genome, increasing stigma, discrimination and marginalisation against those with genetic disorders and families who choose to not access gene technology. This raises the question of whether gene technology, including CRISPR, could encourage a future of private eugenics.
Eugenics is a theory developed by Francis Galton (1822-1911) based on the principle of manipulating the laws of genetics and inheritance to produce a perfect human race. Throughout history, prejudicial fascist states have utilised Galton’s theory to justify ethnic cleansing and murder of marginalised groups including religious minorities, LGBTQ+ individuals and those with disabilities [9]. Private eugenics refers to preventing births of undesired children to promote the birth of healthy children, which derives from individual freedom and parental choice. This is in opposition to public eugenics, which is imposed by the state and may manifest in the violation of a person’s right to reproduce or the death of undesired social and/or ethnic groups [8]. Private eugenics seems to focus more on the value of a genetic trait on a person’s life over the value of a whole life. Although good genetic traits do not equate to leading a happy, healthy life, procreative beneficence states parents will prefer to increase the odds of a favourable predisposition. However, with no objective definition of a good life, individualistic understanding could expand private eugenics’ capacity beyond medicine.
Designer Humans
With access to CRISPR technology potential, there may be an increasing clinical capability to alter their genome as they desire. The use of pre-implantation screening and gene modifying technology in medical practice could also be commodified for aesthetic purposes or alternative non-medical practices. A consumerist approach to reproduction could lead to the option of creating a “designer baby” by which parents could select an embryo based on a variety of characteristics that could be screened for, known as polygenic embryo screening [10]. The characteristics that parents desire for their future children could differ based on traits that they value but could ultimately lead to future generations with more desirable characteristics. Similarly, there is research into CRISPR’s potential applications into plastic surgery. Currently, research into CRISPR technology’s ability to aid in reconstructive approaches into plastic surgery is permitted, exploring bone formation and tissue healing amongst other therapies [11]. Integration of gene technology into plastics may expand to aesthetic purposes as research advances. Infamous self-style biohacker, Josie Zayner live streamed themselves self-injecting a homemade CRISPR treatment claimed to improve muscle enhancement. Zayner’s work was a publicity stunt and a concern to both Zayner’s safety and public safety. This raised concerns about the chances of Zayner inspiring someone to repeat these actions with no acknowledgement of risks or long-term consequences [12]. Social media influence of CRISPR in a positive light could encourage demand for CRISPR technology for aesthetic purposes.
A 2018 study by the Royal Society on 2,601 British respondents also found there is less support for gene technology’s use in aesthetics and non-medical practices than for medical needs. While 83% respondents believed that genome editing for curative treatment in otherwise incurable and life-threatening conditions would be positive, only 31% supported its use for cosmetic changes such as eye colour. 60% also opposed gene technology for enhancement of human abilities, such as intelligence [13]. As this study was conducted on a relatively small population in one time, it cannot be described as representative of the British population’s opinions on gene technology. Nevertheless, the respondents of this survey seemed cautiously optimistic about gene editing technology recognising the dangers, whilst acknowledging their hopes for a technology that could cure genetic diseases. Public opinion may persuade gene editing technology’s future to move in a particular decision, so it is important that people are aware of both the benefits and risks of gene technology.
Accessibility
However, there is also financial consideration in access to CRISPR. Private eugenics, extending beyond healthcare, may only be an option available to wealthy individuals. For example, Casgevy, the CRISPR-based therapy for sickle-cell disease, has a hefty price tag of £1.7 million per patient [14]. NICE approval of Casgevy does not grant all patients with sickle-cell disease this treatment from diagnosis but is only for a selected minority with severe symptoms that cannot be resolved through other methods [5]. As CRISPR treatment research develops and more therapies are approved, the NHS may not be in a position to support the colossal financial burden of this technology. The NICE guidelines assess cost-effectiveness of treatment via the number of quality-adjusted life years (QALYs) gained, with £20,000- 30,000 per additional QALY considered good value for money on NHS [15]. At £1.7 million, a patient must gain 85 QALYs for each QALY gained to cost £20,000. Therefore, in the UK patients may be forced to explore private companies for CRISPR therapies and could result in access only to those with cultural and financial capital. Currently, in-vitro fertilisation (IVF) treatment is in use for pre-implantation screening to select embryos without the traits of genetic disorders. Annually, it is estimated that £68 million is spent by the NHS on IVF. In the UK, a biological woman who meets the criteria can be offered three cycles of IVF on the NHS, then any cycles following are no longer NHS funded [16]. Although genetic therapies are becoming a reality, there is still a question of whether it can be widely accessible by all members of society. The financial cost of current genetic therapy by IVF and future therapies by CRISPR treatment could widen the gap between different social classes and perpetuate inequalities within society. Therefore, predicted future discrimination of those with genetic disorders will not only be surrounding the choice to not access CRISPR/Cas9 therapy, but also discrimination of those who cannot afford such expensive treatment.
In conclusion, there is hope for the future of CRISPR/Cas9’s application in medical practice. Following previous generations of unsuccessful gene editing technologies, CRISPR gene technology has appeared to shed a new light on this field. A curative treatment could be answered prayers for those affected by genetic disorders. The introduction of CRISPR technology for treatment of sickle-cell disease may pave the way to integrate CRISPR into the management of more conditions. On the other hand, the ethical considerations are too great and complicated to go ignored. Reproduction could be treated like shopping with no regard to the long-term complications and individualistic opinions of favourable genetic traits. Future generations of genetically enhanced people could perpetuate existing societal divides amongst people, increasing pressure to invest in such an expensive therapy that could lead to discrimination and marginalisation for those who do not wish to participate. Thus, without a sure understanding of CRISPR technology’s complications and regulations of genetic traits that may be edited limited to life-limiting conditions, accessibility and progression of CRISPR would be dangerous.
References
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