The Ethics of Gene Manipulation
The concept of gene editing (adding, disrupting or changing the sequence of a specific gene) has been a staple of science fantasy for several decades. From Aldous Huxley’s Brave New World to the 1997 film Gattaca*, the ability to manipulate an embryo’s genes has carried dangerous implications. Yet this technology continuously entertains the human mind, challenging science and research to go where it never has before. Gene editing, and more specifically human gene editing, is taking center stage in the research world as its realization becomes ever closer.
Though many techniques for gene editing have been explored, none have been more effective or flexible than the CRISPR-Cas9 complex. CRISPR, or clustered regularly interspaced short palindromic repeats, are short sequences of RNA used to match a DNA sequence of interest. The CRISPR region can bind to unique sequences of RNA (tracrRNA). The tracrRNA can be any sequence, even one not found in the genome of the organism.
CRISPR is only a small portion of a larger strand of RNA known as crRNA. crRNA includes a variable region that can be manipulated to bind to other sequences in the DNA. The crRNA is bound to Cas9, an enzyme that can cut DNA.
So how does this complex work? First, the tracrRNA is attached to the CRISPR region of the crRNA (two methods are depicted in the figure below). Then, this crRNA:tracrRNA complex binds to Cas9. The variable region on the crRNA acts as a guide, searching the DNA for a matching sequence. Once identified, the crRNA binds to that DNA strand, inducing Cas9 to cut the DNA. In repairing the cut, the replacement RNA will be used as a template for the insertion of the replacement sequence in the genome. The CRISPR-Cas9 complex offers the potential of inducing precise mutations into the genome without altering other parts of the genome.
Since its first application in 2013, scientists have used the CRISPR-Cas9 complex to edit the genome of other species. From bacteria and plant cells, the CRISPR-Cas9 complex has been used to edit genes and thereby the genomes of a variety of organisms. A groundbreaking application of CRISPR was achieved at MIT when Daniel Anderson’s team successfully edited the genome of living adult mice, curing them of a rare genetic liver disorder. CRISPR-Cas9 presents the opportunity to cure genetic diseases from birth. Experiments have been conducted with animal embryos, and more recently, human adult cells.
This technology is powerful, but does it cross ethical boundaries? When is the line drawn between innovation and danger?
On April 22, 2015, Nature published an article regarding a Chinese research team’s efforts to genetically modify human embryos. Though unsuccessful, the attempt is an exploration into uncharted territory. If such research continues, will there be a day where embryos can be genetically modified to not only be free of genetic disease, but also to have specific traits? The endeavor has raised questions about the ethics and dangers of such research. A month and a half before the article’s publication, Nature published an article authored by notable figures in the research of gene-editing technology. It warned against editing of the human genome: “Heritable human genetic modifications pose serious risks, and the therapeutic benefits are tenuous.” Their concerns included the exploitation of such research for non-therapeutic purposes, evoking a Gattaca-like world harboring shadows of the Holocaust.
Advocators of gene editing believe a world like Gattaca could never be realized; the understanding of the roles of specific genes is so limited that even though we would know how to edit, we would not know what to edit. Furthermore, CRISPR-Cas9 techniques are still being adjusted to be more precise and will not make it to clinical trials until at least a few years from now.
Nonetheless, scientists from both sides of the debate agree that the effects of embryonic genome editing are unknown and future research (if conducted) should proceed with caution. As of now, the ideal vision for CRISPR-Cas9 would be its application in treating, and possible curing, genetic disorders and reducing the risk of cancer and other diseases. However, it is too well known that good intentions are not enough; no scientist considers what inventions their research might fuel — Einstein did not have the atomic bomb in mind when he was carrying out his work on matter and energy. We cannot know exactly what consequences gene-editing research will have and for what it will be employed. The question is — are we willing to find out?
*Gattaca is a 1997 science fiction film directed by Andrew Niccol, starring Ethan Hawke, Jude Law and Uma Thurman. It presents a future society governed by eugenics in which human embryos are genetically manipulated to ensure that children are at minimum risk for genetic disorders and possess the best heritable traits of their parents. More information can be found here: http://www.sonypictures.com/movies/gattaca/