In 2018, Chinese scientist He Jiankui announced the birth of twin girls, and another girl on the way, whose genomes he had edited to reduce their likelihood of contracting human immunodeficiency virus (HIV). His reasoning for modifying their genomes was that the three girls’ fathers have HIV, and he wanted to make sure the girls did not also contract the virus. Individuals can only contract HIV through contact with specific bodily fluids from someone with HIV, including breastmilk and blood, but the potential of contracting the disease is reduced when CCR5 is inhibited by mutations. When the girls were embryos, he used a technique called CRISPR to genetically modify the girls’ CCR5 gene, preventing HIV from entering their cells. The genetically modified gene has the potential to be passed on to the girls’ potential offspring. His announcement sparked both national and international condemnation, with many ethicists arguing that he acted irresponsibly.
Three years prior to He Jiankui’s announcement, the National Academies of Science, the UK Royal Society, and Chinese Academy of Sciences had held the first International Summit on Human Gene Editing to determine how the international science community should proceed with the advent and popularization of CRISPR. The major takeaways of the Summit, illustrated in the final statement, included an emphasis on continued research on human gene editing with the caveat that genetically modified embryos should not yet be implanted for pregnancy. They also stated that the clinical use of CRISPR in somatic cells (i.e., body cells) should follow existing regulatory frameworks for gene therapy, with additional moral and ethical considerations for germline cells (i.e., sex cells). The international bodies stated that there should be more research on risk-benefit analysis and an emphasis on achieving broad social consensus before undertaking germline genetic engineering, but ultimately concluded that individual countries should regulate themselves. China banned gene editing on human embryos for clinical use based on these recommendations.
It was at the Second International Summit on Human Genome Editing in November 2018, hosted by the National Academy of Science, National Academy of Medicine, Royal Society, and Academy of Sciences of Hong Kong, that He made his announcement about the newborn girls. Taking this new information into account, the concluding statement from this second conference promoted the prompt reporting of clinical uses of germline editing and the need for an ongoing international forum. At the end of 2019, He went to trial for violating Chinese law. The Shenzhen court found him guilty of forging ethical review documents and misleading doctors into implanting the genetically modified embryos into two women, and sentenced him to three years in prison.
There should be... an emphasis on achieving broad social consensus before undertaking germline genetic engineering
Human gene editing has been becoming increasingly possible since the discovery of gene therapy techniques in the 1980s. Now that gene editing technologies have become cheaper, faster, and more accurate, governments are being forced to collaborate with scientists and ethicists to determine the best approach to regulate this transformative technology.
The history of human genome editing has not been terribly long. Although genes and heritability have been known and understood since the late-1880s when Gregor Mendel experimented on plants, it was not until the 1950’s that scientists started really understanding the human genome.
In 1952, Rosalind Franklin, James Watson, and Francis Crick discovered the double-helix structure of deoxyribonucleic acid (DNA). This gave further insight into how DNA is replicated and passed from parent to offspring and the fact that small mutations acquired during this process could lead to disease.
In the 1980’s, scientists first attempted to reduce the effects of these mutated DNA sequences using gene therapy. Instead of repairing mutated DNA sequences, which requires breaking DNA, early gene therapy focused on giving a functional copy of a gene to patients with a mutated gene. The Human Genome Project, which took place from 1990-2003, was an international effort to sequence the entire human genome. This project successfully identified 99% of the gene-containing regions (exons) of DNA with 99.99% accuracy and identified more than 3 million single nucleotide polymorphisms (SNPs), which are genetic variations, giving further insight into genetic mutations and diseases.
Scientists started cloning and genetically engineering animals before doing anything to humans. Two prime examples of the developing technology were the birth of Dolly the Sheep, a sheep that was the result of cloning, in 1997 and the commercialization of GloFish in 2003. Dolly was the first recognized cloned animal and was able to successfully give birth to six lambs. Although she did not have any abnormal health issues, her telomeres were smaller than those of normal sheep her age. Telomeres are repeated DNA sequences at the ends of chromosomes that progressively get smaller as the chromosomes are replicated during cell division. They are commonly referred to as an animal’s “molecular clock.” Dolly eventually developed tumors and was euthanized in 2003 to avoid suffering.
GloFish, which were modified so that they would glow in a variety of colors, are unique in that they were one of the first genetically modified organisms with the potential to pass their genetically engineered DNA to subsequent generations. This is the crux of the debate with respect to germline editing, every change made to germline cells has the potential to be passed to offspring. This is in direct contrast to genetically modifying an organism’s somatic cells, which typically cannot be passed on. There were fears that pet owners would release these transgenic fish into the wild, affecting native fish species, but the general consensus within the scientific community was that their ability to glow would act more as an “Eat Me” sign than as a competitive advantage.
In the 2000s, scientists improved techniques that create double-stranded breaks in DNA, allowing them to insert or delete desired genetic sequences. A number of gene editing techniques continued to develop, but were overshadowed in 2012 when Drs. Jennifer Doudna and Emmanuelle Charpentier at the University of California, Berkeley developed the CRISPR-Cas9 system. This new system offered a way to accurately, effectively, and efficiently insert or remove DNA sequences from chromosomes. This technology revolutionized the genetic engineering world, and now companies are capitalizing on the technology by offering DIY At Home CRISPR kits that allow consumers to change the DNA in bacteria; though at least one person has tried to use this technology on themselves.
Current laws "severely restrict public funding efforts to clone human beings."
National Bioethics Advisory Commission
The United States has passed minimal legislation regarding cloning and human gene editing. With respect to cloning, there is no legislation banning cloning on humans; still, human cloning is effectively illegal. The government distinguishes between reproductive and therapeutic cloning of human embryos, and in 1997, the National Bioethics Advisory Commission produced a report titled Cloning Human Beings. This report reflects the committee’s thoughts on the restrictions on human cloning, highlighting that public law “severely restrict[s] public funding efforts to clone human beings.” Although there are no outright bans, the federal government uses financial restrictions to prevent human cloning in federally funded research. This means that the federal government does not provide grants or funding for research involving human cloning. Privately funded research could still use cloned human embryos, but any additional research on those cloned products would be ineligible for federal funding. For all federally funded research involving cloning, including the common practice of nonhuman animal cloning, the Food and Drug Association (FDA) is the governmental agency in charge. When in doubt, though, the FDA consults the Recombinant DNA Advisory Committee.
Human gene editing, which is a much newer phenomenon than human cloning, is also neither outright banned nor allowed. In 2016, a rider provision on human gene editing was included in the Consolidated Appropriations Act. Section 749 of the act states, “None of the funds made available by this Act may be used…in research in which a human embryo is intentionally created or modified to include a heritable genetic modification.” The rider, which was set to expire after three years, was supposed to enable support for biomedical research in an ethical and scientific way. In 2019, it was renewed, but congress members were concerned about the rider stifling research on interventions to prevent inheritable diseases. The funding restriction does not outlaw human gene editing for somatic cells, and still permits the research, development, and use of gene therapies.
When the Consolidated Appropriations Act of 2016 passed, Glenn Cohen, a Harvard law and bioethics professor, and Eli Adashi, a biologist at Brown University, expressed concerns that the bill would cause the US to lose its competitive edge with other nations and stall research on methods to prevent genetic diseases, like mitochondrial replacement therapy. Congress members had similar concerns with the renewal of the rider in 2019, saying that it might stifle progress for people with mitochondrial disorders who want to avoid passing on the disorder to their children. In 2016, the House Appropriations Committee tried to drop the banning provision for this exact reason.
After the 2016 law was passed, the PEW Research Institute released public polling data showing that most Americans were wary about gene edited babies. Some of the most outspoken critics have been disability rights activists, who argue against gene editing, saying that it will promote social inequalities, increase ableism (the view that disabilities are abnormal rather than natural human diversity), and exacerbate discrimination toward those with disabilities. There are concerns that the excitement around CRISPR and gene editing is derived from a eugenic mindset with the intention to have a society without disability.
There are concerns about [gene editing] exacerbating social inequalities
Scientists and nonscientists alike believe that the advent and usage of CRISPR will lead to designer babies, that is, babies that have been genetically modified to express traits their parents want and avoid traits their parents do not want. To create a designer baby, parents would need to not only pay for the CRISPR technology, which has gotten progressively cheaper in recent years, but also pay for in vitro fertilization, which is expensive and inaccessible to many families. Along with fears of ableism and further discrimination against folks with disabilities, there are concerns about exacerbating social inequalities.
It is important to incorporate a variety of voices in the ethical and moral debate surrounding human gene editing. Hearing from disability rights activists, social justice activists, geneticists, sociologists, and other relevant stakeholders will allow for a nuanced debate as to how to properly proceed with this technology.
The SciPol Takeaway
Due to the uncertainty and debate surrounding the sociological effects of germline editing, the government should continue its current course of action. It has used soft power through financial means to regulate germline editing and, in the absence of a clear consensus among stakeholders, this approach will continue to be sufficient for regulating this technology.
Assistant Editor for Health @ SciPol.org
Any future policies will need to adequately distinguish between somatic and germline editing and undergo a thorough analysis of the possible impacts on individuals with disabilities, minorities, and people who are socioeconomically disadvantaged. Without proper regulation of germline editing, there could be catastrophic effects on those who’s parents did not decide, or were economically unable, to genetically engineer away certain disadvantageous traits. Additionally, because the United States has a different cultural and socioeconomic landscape than other countries, lawmakers should be wary of following the international consensus for guidelines regarding germline editing. The United States is 9th in the world for income inequality, with only Turkey, Chile, Mexico, Brazil, Costa Rica, India, China, and South Africa having greater disparities. This should prompt US lawmakers to assess human gene editing policies within the context of preventing further inequality. Countries without these drastic disparities might not have to consider the individual economic impacts of human gene editing, which underscores the importance of tailoring US human gene editing policy to unique concerns in the US.
Somatic cell gene editing has been proven to help people who have access to the technology. These types of gene edits are not passed onto the next generation and, although there is still potential for harm, there should be less hesitancy by policymakers to expand research in this area. Additionally, human genome research should continue so that it can be implemented and used in the safest way possible when society is ready for all versions of this technology.