In the Princeton Journal for Bioethics’ 2nd sponsored event, Professor Shirley Tilghman, faculty member of the molecular biology department and president emerita of the university, delivered a brief overview and fielded questions from students on the topic of CRISPR, a rapidly developing biomedical technology with serious therapeutic and ethical implications. Tilghman herself remarked at the beginning of the talk that the level of controversy surrounding the further development and application of CRISPR has not been seen in her discipline since the emergence of recombinant DNA (the first instance of artificially engineered genetic material) in the late 1970s.
“The level of controversy surrounding… CRISPR has not been seen… since the emergence of recombinant DNA in the late 1970s.”
The CRISPR technology—an acronym for Clustered Regularly Interspaced Short Palindromic Repeats—is derived from an immunological response mechanism by bacteria to viruses. The bacterium can essentially steal a small fragment of DNA from a virus that has previously attacked it, which is then transcribed into a spacer that is inserted into the CRISPR array in the bacteria’s own DNA. The bacteria can then employ this viral DNA to guide Cas9 enzymes to latch onto viruses with matching genetic material and slice open their DNA, preventing the virus from replicating and thus neutralizing its threat.
CRISPR’s potential as a tool for genetic editing and engineering was first demonstrated by a group of researchers led by Jennifer Doudna of Cal Berkeley in 2012. “Once we understood [Cas9] as a programmable DNA-cutting enzyme,” Doudna recalled, “[we realized] oh my gosh, this could be a tool.”1 By harnessing the guide RNA and DNA-cutting mechanism in bacteria, scientists can now alter the genetic sequencing of other organisms by deleting undesirable base-pairs and even potentially replacing them with the “correct” sequence of base pairs with donor DNA.
In the three years since CRISPR’s discovery, the pace of development for this technology and the extent of its implications for the biomedical field as a whole have been, in Tilghman’s view, unprecedented. Though scientists have still achieved only a preliminary level of understanding of the underlying mechanisms and potential uses of CRISPR, it has already been employed for extensive commercial application. A NY Times article from November 26th titled, “Open Season is Seen in Gene Editing of Animals,” highlighted the use of CRISPR in breeding hornless cows and hogs resistant to swine flu.2 Moreover, Professor Tilghman singled out the potential for the technology to address concerns over genetically modified organisms (GMOs), which are denigrated by critics as possessing “foreign DNA.” CRISPR could be used to improve the yield and nutritional value of crops through genetic modification, while still ensuring that the DNA in the altered species is entirely endemic, thus reconciling the opposing sides of the GMO debate.
The potential use for CRISPR to genetically engineer human beings has been a flashpoint for controversy. One can only imagine the potential medical applications for CRISPR; researchers at Stanford have already demonstrated how CRISPR can be used to make human T-cells resistant to HIV infection and a British infant with severe leukemia has been successfully treated with a regimen centered on the use of CRISPR technology.
CRISPR has raised serious concerns about the ethics of genetic engineering, manifesting in the popular media’s frequent allusions to future “designer babies.” These concerns exploded earlier in the year when reports of Chinese researchers using CRISPR on human embryos became public (despite the facts that the embryos used were triploid and thus unviable and that the results from the experiment revealed the limits of our current understanding of the technology). Though Tilghman was quick to counter that such narratives are undoubtedly premature—our understanding of CRISPR is nowhere near advanced enough to mold “designer babies,” even if we wanted to—the ethical implications of this incredibly potent technology are indeed unsettling.
In her discussion of the key ethical issues involving using CRISPR on humans, Tilghman framed the two central dimensions of the debate as determining the morality of the use of CRISPR in somatic vs. germline contexts and as therapy vs. genetic enhancement. The somatic-germline debate—whether CRISPR should be used only to treat individual patients (restricting use to somatic cells) or if genetic alteration can also occur in germ cells so as to affect following generations—has largely been decided in the medical community, which is in favor of somatic use and prohibits germline engineering. Distinguishing between purely therapeutic measures and genetic enhancement (the former of which is widely deemed permissible), on the other hand, is a bit more difficult and represents the central ethical quandary confronting the researchers and moral philosophers.
Though stressing that these concerns must ultimately be addressed in a concerted and delicate fashion, Tilghman noted that the execution of gene therapy is incredibly difficult and that genetic enhancement of human beings is entirely out of the question at the moment, due to both the limitations of current use of CRISPR and our larger ignorance of the complex interactions between genes. Limited gene editing using CRISPR, however, is relatively easy, precise, and versatile. Ultimately, in the immediate future, it will be up to policy makers—whose track record in the US on such issues is quite lacking—to provide a legal framework for further research into the use of CRISPR to maximize the medical and commercial potential of this genetic breakthrough while remaining within stringent standards of ethical practice. Achieving such a task will be incredibly difficult, and Tilghman articulated that it is imperative to proceed forward delicately and deliberately in the further development of CRISPR so that we can successfully fulfill its incredible promise: to improve dramatically the welfare of our entire human society.
- Zimmer, C. (2015, February). Breakthrough DNA Editor Borne of Bacteria. Quanta Magazine. Retrieved from https://www.quantamagazine.org/20150206-crispr-dna-editor-bacteria/.
- Harmon, A. (2015, November). Open Season Is Seen in Gene Editing of Animals. NYTimes. Retrieved from http://www.nytimes.com/2015/11/27/us/2015-11-27-us-animal-gene-editing.html.