A recent paper published in the journal Cell revealed the cautionary finding that unwanted changes are introduced after modifying genes in human embryos with CRISPR/Cas9. The study, led by Dr Dietrich Egli, assistant professor of developmental cell biology at Columbia University Vagelos College of Physicians and Surgeons, tested the effects of CRISPR-based genome editing on embryos carrying a mutation in a gene called EYS (eyes shut homolog) which could lead to hereditary blindness. It shows that applying this potent approach to repair a blindness-causing gene in the formation of an early embryo discards the whole chromosome, or a considerable portion of it, and that the loss of the chromosome is widespread.
CRISPR-based genome editing has revolutionised molecular life sciences. It allows scientists to perform accurate modifications in the genomes of living tissues and may lead to new medical therapies such as innovative cancer treatments and curing hereditary illnesses. In October 2020, CRISPR discoverers (Professors Emmanuelle Charpentier of Max Planck Institute for Infection Biology, Germany, and Jennifer Doudna of University of California, Berkeley) were jointly awarded the Nobel Prize in chemistry.
However, like most innovative techniques, there are currently technical challenges. For example, it is possible to produce so-called off-target effects, where edits are performed in the wrong area. Researchers are still unsure as to how this might affect patients. Another concern is mosaicism, where some cells carry the edit but others do not. Such changes performed to sperm, egg and embryos can be passed to subsequent generations. In the second international summit on human genome editing, there was broad agreement among the experts in attendance that these risks are high.
Despite these serious concerns, in December 2018, Dr He Jiankui shocked the world by announcing that the first babies had been born with altered genomes (see BioNews 978). His work has attracted a backlash from the international scientific community and various governments. Dr He has been sentenced to three years in jail and fined for performing 'illegal medical practices'.
The new research indicates that CRISPR genome editing is currently not ready for clinical application to correct mutations in this early phase of human development. These findings should deter premature clinical use of genome editing on embryos. Thus, using CRISPR to edit the genomes of embryos is a far-off reality.
Due to the serious ethical concerns, the US government does not allow the use of federal funds to perform research on human embryos. The experiment was sponsored by private funding (the New York Stem Cell Foundation and the Russell Berrie Foundation programme). In Australia, section 15 of the Prohibition of Human Cloning for Reproduction Act 2002 prohibits a person from altering the genome of a human embryo in such a manner that the change is heritable by its descendants and the person intended this to be so. The penalty for this offence is imprisonment for 15 years.
We need to guide responsible and ethical research to achieve safe and effective use. In November 2020, the members of the International Society for Stem Cell Research (ISSCR) task force were charged with revising the 2016 ISSCR Guidelines (the Guidelines for Stem Cell Research and Clinical Translation). The ISSCR is the largest stem cell organisation in the world. As a contribution to the developing and controversial stem cell field, this organisation has developed guidelines that address the global diversity of ethical, legal, ethical, cultural and political perspectives related to stem cell research and its translation to clinical application. The guidelines underscore widely shared principles that call for rigour, oversight and transparency. Strict adherence to these principles assures that such cutting-edge research is being conducted with integrity and that innovative medical treatments are evidence-based. Recent advances in this field include innovations in genome editing, organoids and chimeras. Responding to these various developments in science, the updates will encompass a broader and more expansive scope of research and clinical endeavour, imposing rigour on every stage of the study, addressing the cost of regenerative medicine products and stressing the need for precise and effective public communication.
The persuasive ISSCR Guidelines have been adopted by some scientists, clinicians and institutions around the world. While mere guidelines do not supersede local laws, they could inform the interpretation as well as the development of local laws and provide guidance for research practices not covered by the law. As these guidelines will be updated soon, it is important that they do not encourage the clinical application of the CRISPR approach on genome-editing human embryos for the time being.