CRISPR Gene Editing: The Promise and Peril of Designer Babies

Genome editing or Gene editing

Genome editing involves techniques that allow the modification of an organism’s DNA. Genome editing techniques enable the addition, deletion, alteration, and modification of the genetic material at a particular location in the genome.

Genome editing has emerged as a significant tool for preventing and treating diseases. It is currently used in animal models and cells to understand diseases. Scientists are using it in research and clinical trials for several diseases, including haemophilia, cystic fibrosis, and sickle cell disease. It also shows a promising potential for the treatment and prevention of conditions such as heart disease, cancer, HIV, and mental illness.

Among the various genome editing techniques explored, CRISPR-Cas9 is one of the most widely recognised. CRISPR-Cas9 stands for clustered interspaced short palindromic repeats and CRISPR-associated protein 9. CRISPR-Cas9 is known to be the most efficient, cheapest, fastest, and accurate method for genome editing. However, CRISPR’s possibility of efficient and highly targeted gene editing in single-cell embryos can bring the technology of germline editing under ethical and moral debates.

Understanding CRISPR and human germline editing

Human germline genome editing (HGGE): Germline editing involves modifying reproductive cells such as sperm, eggs, and embryos. It primarily aims to alter genetic mutations that can cause heritable diseases, potentially preventing the disease from being passed down to the next generation. It involves altering DNA in germ cells (eggs, sperm) or embryos, which might cause alterations in all cells of the individual and potentially their next generations.

CRISPR

CRISPR or “Clustered Regularly Interspaced Short Palindromic Repeats” is a natural and adaptive microbial immune system. Microorganisms such as bacteria and archaea use it for defence against bacteriophages and viruses by identifying and destroying foreign genetic material.

CRISPRS were reported for the first time in 1987, around 40% of sequenced bacteria and 90% of sequenced archae consist of CRISPRS.

Mechanism

The mechanism of CRISPR/Cas9 genome editing involves three steps: recognition, cleavage, and repair.

Recognition: A single guide RNA (sgRNA) binds to a specific DNA sequence and directs the Cas9 enzyme to it. Cas9 requires a nearby protospacer-adjacent motif (PAM) to bind efficiently.
Cleavage: Cas9’s nuclease domains (HNH and RuvC) introduce a double-strand break (DSB) in the DNA, producing blunt ends.
Repair: The cell repairs the DSB via non-homologous end joining (NHEJ), which may introduce mutations that disrupt the gene, or homology-directed repair (HDR), which enables precise modifications using a DNA template.

If genome editing occurs in germline cells, the modifications can be inherited by the next generation, leading to heritable genetic changes.

CRISPR and the concept of designer babies

CRISPR babies refer to human embryos that have undergone genetic modification using CRISPR technology. The tool allows for targeted DNA changes, mainly for correcting mutations that are associated with diseases. Although germline editing is a controversial topic, its clinical use remains restricted in many countries because of safety and ethical issues. In November 2018, Dr. He Jiankui announced the birth of twin girls whose genomes were edited using CRISPR-Cas9, aiming to confer HIV resistance, marking the first instance of germline genome editing resulting in live births, affirming predictions that germline-edited “designer babies” might become a reality soon.

While designer babies are a highly speculative concept, it implies creating babies with enhanced intelligence and physical traits involving techniques such as in vitro fertilisation (IVF) and Preimplantation Genetic Diagnosis (PGD). Although CRISPR has the potential to introduce genetic modifications, its application beyond the prevention of diseases is full of ethical controversies, speculative and complex. Currently, several technical and ethical barriers prevent the widespread use of CRISPR when it comes to non-medical enhancements.

Dr He Jiankui's CRISPR Experiment

Background

Background: Recently, the world witnessed the first instance of human germline genetic modification that resulted in live births.

Many attempts were made around human germline genetic editing, J. Huang, in the year 2015, and the team had reportedly been successful in editing human zygotes. Two years later in 2017, K. Niakan and team made genetic modifications to the human blastocysts.

However, it was in 2018 when the Chinese scientist He Jiankui claimed to have worked on the first genetically modified human babies, resulting in live births with one more pregnancy underway.

The Experiment

The experiment involved an HIV-serodiscordant couple who were informed that the experiment would make their children immune to HIV, with the medical care and fertility treatment procedures being paid by the researchers.

During the IVF procedure, sperm washing was performed, a method which significantly reduces the risk of HIV transmission, almost up to 0%. The embryos were created using sperm from male participants and eggs from their female partners. A few of the embryos were edited with the help of CRISPR, and couples were given a choice of going ahead with the unedited or edited embryos.

Dr He Jiankui primarily focused on changing the CCR5 gene with the reported intention of making white blood cells of babies unable to get HIV infection. Some suspicions have also been made about CCR5’s modification being associated with the development of brain and cognitive enhancement.

The Experimental Outcome

CRISPR modified each of the twins differently: In one of them, only one chromosome was altered, whereas in another both chromosomes were altered. Moreover, not all cells had modified CCR5 genes in both twins, which made them mosaics. As germline modifications, these genetic changes can be potentially inherited by Lulu’s and Nana’s future offspring. Additionally, it is important to note that He Jiankui’s research led to the birth of a third gene-edited child in 2019, although specific information about this baby remains unknown.

Global Response and Legal Consequences

Human gene-editing trials have already faced significant scrutiny, but the reaction to Dr. He Jiankui’s experiment was far more intense. His work sparked near-universal condemnation, with critics pointing to serious concerns such as inadequate safety protocols, flawed scientific methods, the absence of ethical oversight, and potentially undisclosed motives. As a result, legal proceedings were initiated against him. In December 2019, He Jiankui was convicted of conducting illegal medical procedures and sentenced to three years in prison.

Conclusion

Many countries have imposed strict laws, rules and even outright bans in some cases for human germline editing because of its ethical implications. While there might be a scope for research, its clinical applications face high restrictions globally.

Genome editing and CRISPR offer a highly promising potential for treating genetic diseases. Just as science is evolving, the frameworks that guide it must also evolve. So that innovation does not come at the price of ethics.