We are all born individuals with a genome; a three billion letter DNA code that interacts with the environment to make us who we are. We have flaws, and sometimes disease, but we are all human. The editing of our genomes, the essence of our humanity, is both a controversial and thrilling prospect. Genetically-engineered humans are a common feature of sci-fi novels and movies, but with the discovery of the gene-editing tool CRISPR, modifying human genomes has become feasible. With this ground-breaking technology comes many ethical implications. Many scientists agree to proceed with caution in its use, and call for a need to have ethical discussions before using it for certain purposes. The co-inventor of CRISPR gene editing technology, Jennifer Doudna, has repeatedly called for a “global conversation about CRISPR technology to consider the ethical and societal implications” of its use.
CRISPR gene editing is currently in early stages of being trialled in adult humans to treat diseases that are the result of mutations in a single gene, such as cystic fibrosis. It also has the potential to be used to advance cancer therapeutics. New immunotherapy can be developed using CRISPR to modify T-cells to locate and kill cancer cells. However, while genome modifications are ethically acceptable in consenting adults, there are very strict guidelines for experimenting with human embryos. Scientists who work in genetics make an important distinction between editing adult cells and editing germline cells such as those in sperm, an egg, or embryo. Legislation to prohibit or restrict germline editing has been introduced in many countries including Australia, Belgium, Brazil, Canada, France, Germany, Israel, the Netherlands, and the United Kingdom.
Alcino Silva, a neurobiologist whose lab uncovered the new role for CCR5 in brain function commented that “those mutations will likely have an impact on cognitive function in the twins” whether that was He’s intention or not.
In November 2018, global experts gathered in the University of Hong Kong for the Second International Summit on Human Genome Editing to discuss the science, application, ethics, and governance of human genome editing. The summit was embroiled in controversy as Chinese scientist He Jiankui spoke at the summit on his claim to have created the world’s first genetically modified babies. The organisers of the summit condemned He’s announcement, describing the claim that human embryos had been edited and implanted as “unexpected and deeply disturbing” and as failing to “conform with international norms”.
According to scientist He, the twin girls, known under the pseudonyms Lulu and Nana, the world’s first genome edited babies, were born “normal and healthy” in November 2018. His claims that he genetically modified them to be resistant to HIV sparked controversy and shock in both the scientific community and general public around the globe.
“However the use of this technology opens the gateway to creating “designer babies”: babies specifically designed for superficial, desirable traits such as eye colour.”
Documents posted on China’s clinical-trial registry show that He attempted to mimic a trait already found in some members of the population: resistance to HIV. Individuals with a protein called CCR5 do not contract HIV, the virus that causes AIDS. In homozygous carriers of the CCR5 genetic mutation, the CCR5 protein is altered so that the virus is unable to bind to the receptor and thus cannot enter the white blood cells which it normally infects. He’s researchers purportedly used the editing tool CRISPR, which relies on the Cas9 enzyme to cut DNA, in order to disable the normal CCR5 gene in the pair of fertilised eggs. Studies are underway to target the same CCR5 gene in adults with HIV, but this is the first time anything like this has been carried out in embryos. The Organising Committee of the Second International Summit on Human Genome Editing described He’s procedure as “irresponsible” and with flaws including “an inadequate medical indication, a poorly designed study protocol, a failure to meet ethical standards for protecting the welfare of research subjects, and a lack of transparency in the development, review, and conduct of the clinical procedures”.
The issue with disabling specific genes is that many genes have more than one function. The gene He changed in the twins, CCR5, allows HIV to enter cells. This is fairly well-established in adults, but its implications in embryos are unknown. New research from the University of California and published in the journal Cell suggests that the deletion of CCR5, the same alteration introduced in the girls, improves the brain’s ability to form new connections and memories, as well as its ability to recover after a stroke. But what does this mean for the Lulu and Nana? Alcino Silva, a neurobiologist whose lab uncovered the new role for CCR5 in brain function commented that “those mutations will likely have an impact on cognitive function in the twins,” whether that was He’s intention or not. Even more shocking than the possibility of unintended side effects is that at the time of He’s announcement in November 2018, the trial results had not been verified through independent genome testing or published in a peer review journal.
“There are also concerns that when targeting a gene, there may be unintentional edits to the genome in other locations that could cause irreversible and unpredictable side effects that may not be apparent until later in life.”
Germline gene-editing in embryos, such as what He Jiankui claims to have done, could potentially be used to prevent disabling genetic diseases in the future. 6% of children born every year are born with a serious birth defect of genetic origin. There is a strong argument to be made that using CRISPR to eliminate life-threatening conditions would be a good thing for humanity. One such disease is Huntington’s, a neurodegenerative disease caused by a single inherited genetic mutation which can be screened for by genome sequencing. If a scientist can prevent inherited disease flow between parents and offspring, conditions such as cystic fibrosis could be eliminated as they arise.
However, the use of this technology opens the gateway to creating “designer babies”: babies specifically designed for superficial, desirable traits such as eye colour. This may exacerbate inequalities of access to medical procedures as well as discrimination, leading to a new era of “genetic inequality”. Thus, the births of these twin girls represents a significant and controversial leap in genetic modification and scientific ethics.
Francis Collins, director of the National Institutes of Health argues that there “remain strong arguments against engaging” in genome editing. Many people share his concerns that “altering the germline in a way that affects the next generation without their consent” presents a serious ethical issue. Collins also addresses the “serious and unquantifiable safety issues” associated with genome editing. Some of those issues are that genes do not work in isolation, so targeting one gene may have knock-on effects on other genes. There are also concerns that when targeting a gene, there may be unintentional edits to the genome in other locations that could cause irreversible and unpredictable side effects that may not be apparent until later in life. Many scientists have confirmed that although CRISPR has great potential, it currently is not safe or precise enough to be used to edit the genome of human embryos. According to a paper published in Nature Biotechnology in July 2018, the gene-editing tool can cause disruptions and deletions in DNA near the intended target in the genome.
The World Health Organisation (WHO) issued a statement in response to He’s trial. Margaret Hamburg, co-chair of the WHO committee and former head of the Food and Drug Administration in the US, said: “The committee agrees it is irresponsible at this time for anyone to proceed with clinical applications of human germline genome editing.” In the wake of He’s controversial experiment, WHO established a committee of 18 researchers and bioethicists to develop an international framework to govern the use of gene-editing technologies in human. The committee advised that there is an “urgent need” to create a transparent global library of all experiments involving human genome editing.
Xu Nanping, a vice-minister in the Ministry of Science and Technology in China, said He’s “shocking and unacceptable” experiment “violated China’s relevant laws and regulations” as well as “the ethical bottom line that the academic community adheres to”. The Chinese state media described He as acting for “fame and fortune” rather than for the benefit of his patients. The authorities also believe He forged both ethical review documents and blood tests to circumvent a ban on assisted reproduction for HIV-positive patients, state media reported.
Since his announcement, the Chinese government has launched an investigation into He’s work and he has been confined to a state owned apartment in Shenzhen under armed guard since December awaiting sanctions. He’s controversial experiments have propelled the scientific community from their place of careful ethical consideration to a reality where there are people alive who have been embryonically genome-edited. The full repercussions of this rapid, unchecked advance remain to be revealed, but now, more than ever, conversations on what kind of gene-editing is ethical must happen.