An Analysis of Heritable Human Genome Editing Through the Lens of Ethics

For decades, the idea of engineered humans was one restricted to the realm of science fiction. From Mary Shelley’s 1816 novel Frankenstein to Aldous Huxley’s 1932 novel Brave New World and the 1997 science fiction thriller film Gattaca, humanity has dreamt of the intersection of science and Promethean hubris for hundreds of years. In the early 1960s, however, the fantasy of modifying the human genome pivoted from fiction to a scientific possibility with Watson and Crick’s discovery of the structure of DNA. More recently with the development of technology enabling the cutting and pasting of recombinant DNA, the field of genetic engineering has rapidly expanded. Initially misguided by remnants of the eugenics movement that had plagued America since the late nineteenth century, technical limitations proved too vast and the crusade for human improvement through genomic editing was put on hiatus.

Flashing forward to the twenty-first century, the current reality of the state of genetic engineering hit the scientific community in late 2018 when Chinese geneticist He Jiankui made international headlines with the claim that under his guidance, the first human genetically edited babies had been born. Made possible through CRISPR-Cas9 technology, for which the 2020 Chemistry Nobel-Prize was awarded to pioneering scientists Jennifer Doudna and Emmanuelle Charpentier, Jiankui modified a gene marker in the embryos of a couple diagnosed with AIDS with the intent of granting their children and future descendants a resistance to HIV. In November 2018, the embryos which Jiankui had implanted were carried to term and twin girls, Nana and Lulu, were born. Despite framing his accomplishment as a major step forward in human medical science, Jiankui’s clinical trial was almost immediately shrouded in controversy. An international community of scientists, ethicists, and medical professionals condemned him for jumping the gun on a field that is unanimously considered to be not yet cleared for human application from a moral or ethical perspective. Driven by a hunger for success and fame, it would seem Jiankui’s eagerness to achieve a major historical breakthrough and enhance his ingenuity as a scientist had blinded him to his ethical obligations as a researcher and engineer to perform sound science.

Forgoing the more sound pre-existing methods of preventing AIDS infection, such as sperm-washing and screening for healthy embryos, Jiankui designed a procedure that was neither medically necessary nor established to correct a clear genetic disorder as outlined by the Biomedical Engineering Society Code of Ethics. The gene he attempted to modify also also linked to other functions, including protection against the West Nile virus. The largely unknown effects of altering the human genome illustrate the risk undertaken by Jiankui while also highlighting the terrain yet to be covered in fully understanding the dynamics of our genetic processes. Failing to meet the guidelines that warrant grounds for a clinical trial, Jiankui misrepresented his proposal to the hospital ethics committee at Shenzhen’s HarMoniCare women and Children’s Hospital to gain approval in proceeding with his plan. Furthermore, close international scrutiny of Jiankui’s clinical trial revealed several disturbing pieces of information. Not only had his clinical trial been rushed without a proper peer review and informed ethical consent, but it remains debatable whether it was possible to even declare it a success. As it turns out, the modification of the genetic marker had only taken effect in one of the two relevant chromosomes for one of the twins. Likewise, there was some evidence of off-target edits as well as mosaics, a term used to describe when there has been enough cell division prior to the gene editing such that some of the resulting cells remained unedited. After cell division, fewer than half of the body’s cells may actually possess the modified genetic markers at birth. Apart from signaling an apparent lapse in the efficacy of the clinical trial, the evidence of mosaicism is alarming for its association with miscarriage, birth defects, developmental delay, and cancer.

Ultimately an example of failed research safety and integrity, He Jiankui’s so-called “CRISPR babies” proved to be a violation of virtually every code of ethics among engineers and medical researchers. As a result, Jiankui was put on trial by the People’s Court of Shenzhen at the end of 2019, where he pled guilty to illegal medical practice by forging ethical review documents and misleading doctors into unknowingly implanting gene-edited embryos into two women. Sentenced to three years in prison and banned for life from reproductive science, Jiankui’s actions serve as a harsh wake up call for the international community to produce a meaningful set of guidelines to direct further research and development of heritable human genome editing.

While often providing ground rules for the safe practice of genetic research, organizations such as the International Commission on the Clinical Use of Human Germline Genome Editing have been hesitant to address the ethical and moral ramifications of gene editing. Many organizations hold positions of neutrality just short of calling for bans or moratoriums, which can progressively become harder to lift. Instead, emphasis is repeatedly placed on the need for broad societal consensus, a task easier said than done. Will genetic editing widen socioeconomic class divisions? Is there a danger in lowering the diversity of the human species? If the technology were available to make healthier babies, would it be ethically wrong not to use it? With so many questions left unanswered, it is time to converse and construct a set of ethical guidelines to govern the future progression of the human race.