Perhaps one of the greatest leaps in the capabilities of the human race is nearly upon us: the ability to master our own evolution.
The possibilities and ethics of genetically engineering humans have been prevalent topics of debate in the post-genomic era. However, the discussion has been mostly theoretical until very recently. The discovery of a unique genome-editing tool called CRISPR has made waves in the scientific community for its remarkably cheap and accurate genome editing capabilities as well as in the lay world for its controversiality, as a Chinese research team recently experimented with CRISPR on non-viable human embryos. CRISPR has been shown to be incredibly accurate in many organisms, with near 100% efficiencies in editing the genome of yeast according to an article by Jacobs et al. published in Nature Communications. However, the results in humans were not especially striking, as only 28 out of 54 embryos showed successful editing. Regardless of the efficacy, the fact that the editing of human embryo genes was performed at all has struck a dissonant chord with many political and scientific groups, who fear the possible negative ramifications of exploring this taboo area of science. Many scientists have called for a moratorium for the use of CRISPR on the human germ line, and while it may be seen as a waste of a groundbreaking and possibly lifesaving genetic tool, at this point in time there is not enough consensus and trust in the scientific community to safely and ethically proceed.
The CRISPR system, which can be found in most species of bacteria and almost all species of archaea, can be most simply described as a basic type of immune system. CRISPR (clustered, regularly interspersed short palindromic repeats) provides protection from bacteriophage viruses, which infect bacteria and commandeer the host cell, turning it into a virus factory and eventually causing cell death. CRISPR’s are unique segments of bacterial and archaeal genomic DNA that bind complementary to the DNA of bacteriophages and attract the endonuclease Cas9, offering a chance to kill a phage by cutting up its DNA. What makes CRISPR such a groundbreaking tool is that the DNA sequences which Cas9 uses to find and cut foreign DNA can be manipulated by scientists. CRISPR and Cas9 offer an incredibly precise method of cutting DNA so that scientists need only add a desired segment of DNA and the cell’s own molecular machinery will (usually) insert it into the location of the cut, facilitating genetic modification. For decades it has been incredibly difficult to change DNA sequences in higher organisms due to poor specificity in cutting at the proper location, but now CRISPR offers both a cheap and effective solution.
When applied to human genetics, the CRISPR editing system promises cures for countless genetic diseases.
When applied to human genetics, the CRISPR editing system promises cures for countless genetic diseases both on the individual level and possibly the species level as well. If CRISPR were perfected, it could be theoretically possible to eradicate diseases. Patients suffering from genetic disease could have a diseased somatic allele changed into a healthy one and end their suffering. Prospective parents with a family history of genetic disease could alter a diseased gene variant in their germ cells and not only have healthy children but prevent all future generations in their family from inheriting the disease. The implications of the ease of use of CRISPR techniques for social disparities in medicine are awe inspiring: debilitating diseases with costly maintenance medications, inaccessible by low-income individuals, or that are common in the third world could be eliminated over the course of a few generations with less expense than would be required to treat them. But just as easily as one can contrive a philanthropic use for CRISPR, one can arrive at superficial applications.
The excessive and unregulated use of CRISPR for editing human genomes for non-medical reasons is a serious risk. CRISPR procedures could be produced to change eye color, hair color, intelligence, or athletic ability— applications whose market value would certainly attract attention at the expense of research into more ethical applications. What is to stop a pharmaceutical company from offering the most elite families a chance at the perfect child? As of now, nothing. Over 40 countries discourage or ban germ-line editing, but the United States is not one of them.
While CRISPR has a lot of potential in the right hands, the risk of unethical and dangerous results is magnified by the accessibility and ease of use of the technique. One of the inventors of the CRISPR technique, Jennifer Doudna, claims, “Any scientist with molecular biology skills…will be able to do this.” While it may be unfair to say that this type of profound technology should be reserved for only a handful of highly trained, dedicated individuals, there is an argument to be made that a lack of required discipline may be inappropriate when it comes to a technology that could be abused as easily as CRISPR. We cannot possibly proceed with CRISPR until we establish ground rules for how it may be used. Even once regulations are established, premature use of the technique in human subjects could mean a disastrous trial period.
While CRISPR has a lot of potential in the right hands, the risk of unethical and dangerous results is magnified by the accessibility and ease of use of the technique. … We cannot possibly proceed with CRISPR until we establish ground rules for how it may be used.
As discussed previously, what makes CRISPR so revolutionary is its precision, but when it comes to editing human somatic cells, let alone germ cells, anything less than perfection is problematic. In past gene-editing techniques for the treatment of cancers and genetic disorders, negative effects have often emerged years following treatment with no early indication.
One of the first gene-therapy human trials, described by Erica Check in Nature, was with a disease called SCID, a genetic disorder resulting in the malformation of immune B and T cells. Following insertion of a functional gene variant to replace the mutated gene responsible for the disease inside blood stem cells, nine of the 11 children treated were cured. However, in the following years, two of the patients developed leukemia as a result of the gene being placed in a detrimental region of the genome.
While CRISPR is generally more accurate than older methods when it comes to gene insertion, it is far from perfect, and erroneous insertions, however infrequent, could have consequences far more life threatening than the disease the procedure was intended to cure. These concerns are far more severe in the application of CRISPR to germline cells in contrast to somatic cells, where only the individual receiving treatment is affected. Imagine if this were done in the sperm cells of a father to prevent his children from having SCID. The genetic modifications carried in the sperm would consequently be present in every cell lineage in the child, exponentially increasing the opportunity for the development of cancer or dysfunction in any region of the child’s body. Additionally, one can conceive of transgenerational implications as any modification of the germline is passed down to subsequent generations. Even if the immediate generation is unaffected, two or more generations down the line serious complications could emerge.
It is necessary that we at least temporarily halt our progress and open up a discussion about where this technology can and should go.
With improved efficiency, the benefits of CRISPR could be great. Diseases such as Type-I diabetes, Huntington’s, Parkinson’s and countless others could not only be cured for one individual but for every future generation. However, the power and responsibility of having such technology should not be taken lightly. It is necessary that we develop restrictions for how CRISPR should be used, both to guide our research on the matter moving forward and to prevent unethical use.
Even if CRISPR is improved, we should seriously consider if it should be used for germline editing. There are many alternative options to avoid passing on genetic disease, ranging from genetic screening to adoption. Moreover, the many CRISPR-based treatments that could target somatic cells do not carry the risk of affecting countless future generations and will still be remarkably cheaper and easier than the options currently available. It is my opinion that the extensive risks and ethical concerns of the editing of human germ cells makes it a poor option no matter the effectiveness we can achieve, and based on the controversy of current research on germ cells it seems unlikely that it will be widespread within my lifetime.
Regardless of my or any other scientist’s opinion on how CRISPR should be used, it is necessary that we at least temporarily halt our progress and open up a discussion about where this technology can and should go. We need to realize what it is that we have stumbled upon: that is, something that will give our species a type of power that could define the rest of our existence. How will we choose to use it?
Check, Erika. “Gene Therapy: A Tragic Setback.” Nature 420.6912 (2002): 116-18. Web.
Jacobs, Jake Z., Keith M. Ciccaglione, Vincent Tournier, and Mikel Zaratiegui. “Implementation of the
CRISPR-Cas9 System in Fission Yeast.” Nature Communications Nat Comms 5 (2014): 5344. Web.
Lanpier, Edward. “Don’t Edit the Human Germ Line.” Nature.com. Nature Publishing Group, 12 Mar 2015. Web. 13 Oct. 2015
Regalado, Antonio. “Engineering the Perfect Baby.” Review. MIT Technology Review May-June 2015: 26-33. Print.