Recent discovery of a new, efficient method to alter the genome of any organism has raised widespread concern, both within the scientific community and within the general public, that the genetic makeup of humans should not be permanently altered under any circumstances. Yet there are many ethical applications of this technology to human disease, including some that make permanent changes in the human genome.
From a scientific perspective, genome editing using the CRISPR/Cas9 system - an abbreviation for the cumbersome scientific name, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-Associated protein 9 - is an exciting new approach. In the past, efficient techniques for altering genes only worked in specific organisms or cell types, such as bacteria. Techniques that could be applied to other organisms were imprecise, time consuming and expensive, making widespread practical applications of these technologies unlikely.
CRISPR has dramatically changed the equation because it allows for precise alterations to be made to multiple genes simultaneously, enabling scientists to rapidly modify the genetic makeup of any living species.
Genome editing is already proving to be a powerful tool for understanding the basic functions of genes. In the future, this technology could also be used uncontroversially to eliminate disease-causing mutations and restore natural function in the body tissues of human patients. With sufficient testing to ensure that such corrections have not introduced any unintended alterations to the genome, CRISPR-mediated “gene-therapy” could bring relief to many individuals with debilitating or even fatal genetic conditions. For example, sickle cell anemia is caused by a mutation in the human gene for hemoglobin. If bone-marrow cells from an adult patient were restored to the natural state by gene editing and then re-engrafted, the patient would be permanently cured.
In contrast, genome editing could also be used for more controversial purposes: to create new or hybrid species of organisms and to introduce desirable genetic traits to an existing organism. Such “genetically modified organisms” (GMOs) are not new, but CRISPR greatly increases the ease and efficiency of such modifications, and expands the range of organisms that could be genetically enhanced—including humans.
And therein lies the controversy.
Making permanent, heritable alterations to the human genome, or “germ-line modifications,” is a grave and irrevocable step. And it is a direction that has already been initiated. A Chinese group recently published experiments using CRISPR-mediated gene editing in human zygotes. The embryos used for this study were genetically abnormal, and therefore were rejected for infertility treatment, but the work proved that CRISPR editing works in human zygotes.
In response to the Chinese study, the International Society for Stem Cell Research (ISSCR) called for “a moratorium on attempts at human clinical germline genome editing while extensive scientific analysis of the potential risks is conducted, along with broad public discussion of the societal and ethical implications.” Yet how reasonable is this moratorium? In particular, is it possible to determine accurately the “potential risks” of genome editing?
It is important to distinguish between three potential applications of CRISPR technology to human germline genome editing: restoring natural function, enhancing function, and introducing novel function. All of these applications carry two types of risk: first, the risk associated with failure of the technique itself (i.e. did the procedure actually produce the intended alteration, and not introduce any “off-target” changes to the genome?); and second, the long-term risks to the individual and the species. The overall risk of any proposed manipulation differs, depending on what kind of manipulation is being considered.
In situations where a genetic mutation causes serious or fatal disease, replacing a defective gene with a healthy copy of that gene merely restores natural function. For example, if a child inherits a defective copy of an essential gene from one parent, replacing that defective copy with the natural copy from the other parent would involve no risk to the child beyond the risks associated with the editing technique itself. And using existing technology, the safety of the procedure could be determined with sufficient accuracy to ensure that the intended alteration, and no other, had indeed been produced.
Importantly, the long-term consequences of having a normal copy of the gene have been tested by millions of humans over many thousands of years. A germline modification of this type that was made in a human zygote would still carry the ethical concerns raised by in vitro fertilization procedures and manipulation of human embryos, but it would not raise concerns regarding the long-term consequences of altering the human genome.
Experimental manipulation of embryonic humans is likely to be an insurmountable ethical concern, but in the case of restoring natural function, it is largely unrelated to genome editing. Importantly, if the correction did not involve manipulation of embryos - if the defect was corrected in germ cells, for example - such a manipulation would not be ethically problematic and there would be no deleterious long-term consequences for the individuals produced from such “corrected” gametes.
In contrast, the long-term consequences of manipulations that either enhance function or provide novel function cannot be predicted. Evolution works by introducing alterations and then subjecting them to the test of time. If, after many hundreds of generations, the alteration persists, it is either neutral or beneficial. If it kills or weakens the individual, both the alteration and the individual possessing it are less likely to persist. Importantly, such deleterious effects often do not show up until the individual is an adult. And if the negative effects are subtle, it may take thousands of individuals with the same alteration before those effects are reliably detected. To initiate such a long-term, multi-generational experiment on humans is profoundly unethical.
There is nothing inherently wrong with genetic engineering. Humans have amplified some genetic traits and eliminated others for centuries by selectively breeding animals and plants with desirable characteristics. The CRISPR/Cas9 system has merely given us an enormously more efficient way of accomplishing the same goals. Genome editing has the potential to be a powerful and beneficent tool for eliminating disease-causing genetic mutations or mitigating their effects. It would be unethical to arbitrarily restrict such beneficent applications of this technology.
Yet if genome editing is used as a eugenic tool to produce “superior” human beings, it raises serious ethical concerns that society cannot afford to leave in the hands of scientists alone. Responsible citizens need to look beyond the technical safety of the procedure and engage the difficult question of whether the future of the human species is something to be left in the hands of scientists with the power to edit the human genome.