The Ethical Implications of CRISPR-Cas9 Technology Bianca Amin MSB 630 Ethics in Biotechnology Research In 2015

The Ethical Implications of CRISPR-Cas9 Technology
Bianca Amin
MSB 630 Ethics in Biotechnology Research

In 2015, Chinese scientists used CRISPR technology to edit the genes of “defective” human embryos but their attempt did not produce the intended results. The Chinese scientists were a part of an explosion of new research inspired by the 2012 research publication on how the CRISPR defense system of Streptococcus pyogenes was programmable CITATION Jin12 l 1033 (1). Dr. Doudna, the scientist credited with discovering this CRISPR method, began to organize “…the scientific community to prevent this ethical line from being crossed CITATION Pol l 1033 (2).” There is a question, however, of who is to say that an “ethical line” was crossed? How is this ethical line determined? Ethics in research has a long history in the world and in this country. If we’re to avoid repeating our most heinous mistakes, then I agree that ethics must be considered when embarking on the use of CRISPR technology. We’ll review how the CRISPR system is used to edit DNA, how research ethics applies to the use of this technology, and what ethical concerns should be considered.

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The CRISPR-Cas9 system is a bacterial defense system but it can also be used to edit the DNA in our cells. Our cells and the cells of plants and animals contain DNA which houses the organism’s genome. This genome is a library of all the information needed to carry out a plant or animal’s functions. In bacterial DNA, a cluster of organized sequences was discovered to be complementary to phages, plasmids, and/or viruses that it had previously come in contact withCITATION Wat14 l 1033 (3). In between these organized sequences are conserved repeat sequences and so this cluster of sequences became known as clustered regularly interspaced short palindromic repeats or CRISPR.CITATION Wat14 l 1033 (3) If I were to assign all of the repeats an “a” and all of the sequences acquired from different phages and viruses a number, a CRISPR sequence would look something like this: …a5a4a3a2a1a… Each new acquired sequence is added in front of the existing sequences and hence a timeline exists of some of the invaders the cell came in contact with. A single RNA copy is made of the CRISPR sequences and with the help of RNAse III (a nuclease that makes “cuts” in RNA), the single RNA copy is cleaved into short segments called CRISPR RNA (crRNA). Using our example above, the crRNA segment would that look like an “a5a”. The crRNA pairs with another CRISPR RNA called tracrRNA and together they recruit proteins made from CRISPR associated sequences (Cas9 in particular). The a5a segment (sgRNA) forms a complex with the Cas9 protein and is now called the CRISPR-Cas9 complex which is able to target sequences of DNA or RNA that complements its matching genome sequence (see Figure 1). Once that recognition occurs, the CRISPR-Cas9 complex cleaves the invading DNA or RNA, making a double stranded break, which causes the invading virus or phage to lose its function when the two broken ends are cleaved together CITATION Dai16 l 1033 (4). This loss of function pathway can potentially be used to stop diseases like HIV-1, Hepatitis-B, and HPV CITATION Dai16 l 1033 (4). In genetically engineered foods, it can be used to decrease the costs of production, increase the nutritional content of foods, and produce foods that deliver therapeutic benefits for the immune system CITATION Zha16 l 1033 (5). The Chinese scientists mentioned earlier were attempting to alter a specific gene in every cell of an embryo. Because CRISPR-Cas9 is a new technology, there are some “technical pitfalls” CITATION Son16 l 1033 (6) that are still being worked out and ethical concerns are still being debated.

Ethics: a branch of philosophy that involves systematizing, defending, and recommending concepts of right and wrong conduct CITATION Wik181 l 1033 (7). Due to the sordid history of humanity, ethical concerns must be considered before embarking on this new technology to experiment on humans or for products we’ll consume for our benefit. Part of what we’ve learned from the Nuremberg Trials and the 1949 Nuremberg Code is that experiments should be “based on the results of animal experimentation” and must “not be random and unnecessary in nature CITATION Nur49 l 1033 (8).” These considerations should have been explored by the Chinese scientists, for example, prior to using human embryos for experimentation. Why didn’t the scientists first use animal germ-line cells to test their hypotheses? Were the experiments necessary? Was there an approval by an institutional review board (IRB) prior to initiating the experiment? The role of the IRB would be to provide oversight of all experiments and to protect the institution from misconduct. Since germ-line editing is not illegal in China and the experiment was not performed on humans, none of these protections would have been in place. Using CRISPR-Cas9 technology to execute germ-line experiments has exponentially propelled our progress of making designer humans a real possibility.
Current technology already allows us to select desirable embryos through IVF. Is editing an embryo’s genome just splitting hairs with IVF or is it a bridge too far? I think the latter is more likely. No one can ever really know what the consequences are for an engineered person or for their descendants. Although I’ve taken a utilitarian approach and argued in favor of choosing gender through embryo selection, I lean towards natural law when it comes to writing the genetic make-up of that child. Since humans are so prone to making mistakes, I’d rather not take the chance at trying create perfection since the risks are so great. I believe that Dr. Doudna exercised appropriate caution by imploring our “notions of responsibility to the wider world.” There are signs that her calls for caution are being taken seriously in the scientific community. In a 2016 commentary on the promise of CRISPR-Cas9 gene therapy, the authors acknowledged that “…germline manipulation is unfeasible in humans due to ethical concerns… CITATION Dai16 l 1033 (4).” Hopefully, more scientists will take this approach for the benefit of all concerned.
The use of the CRISPR-Cas9 system has also reignited the debate on the ethical implications of consuming genetically modifying organisms. CRISPR-Cas9 technology has now made genetic engineering significantly easier and cheaper, which means more GMOs will be introduced increasingly for public consumption. GMO foods are already currently in the market and consumers have been safely eating them for years CITATION Zha16 l 1033 (5). Most consumers don’t know they’ve already been beneficiaries to genetic engineering for generations. For example: botanists, farmers, and animal breeders have been manipulating the genes of plants and animals for hundreds of years using selective breeding techniques in order to produce progeny with desired traits. Cross breeding has years of proof of concept but CRISPR-Cas9 technology has not. How can we be sure that this type of genetic engineering is safe? Despite there already being widespread use of GMOs, companies have an obligation to follow the law and execute the studies needed to prove safety. The FDA has taken an additional step and has implemented new guidelines in order to keep up with the new technology. According to the FDA, “The FDA regulates GE animals under the new animal drug provisions of the Federal Food, Drug, and Cosmetic Act, because the recombinant DNA (rDNA) construct introduced into the animal meets the definition of a drugCITATION USF l 1033 (9).” Categorizing GMO/GE animals as a drug ensures food from these types of animals are held to the same standard as their non-genetically engineered counterparts. Companies are therefore legally obligated to test GMOs to prove efficacy, safety, quality, uniformity, etc. These regulations are needed to ensure companies practice non-maleficence, while also providing a benefit to society.

Despite the scientific evidence available, there are still other ethical factors to consider in this debate. The concept of justice demands that there be fair and just distribution of the benefits and opportunities that many countries have. For example, there are developing countries that could benefit from the ability to grow beans that are resistant to viral disease or sugarcane that is resistant to drought conditions. People who live in poverty conditions should benefit from the resources that GMOs can provide. Is it fair that the richest countries in the world benefit from this technology and practice mass food waste at the same time? It’s not fair and the countries with the most need should be either provided with the technology to develop their own GM foods and/or seeds that have already been modified.
There is also public argument from consumers that they have a right to know if the food they’re about to consume is genetically modified. One of the concepts of principlism is autonomy, which maintains that individuals have the right to self-determination and the right to make informed decisions. How can consumers make informed decisions without sufficient information? Consumer advocates are insisting that the food industry add clear, easy to understand labels to the products that are genetically modified. The food industry contends that genetically modified foods are no different than foods that aren’t and there’s no added benefit to labelling. The consumers’ stance is supported by the idea of informed consent. The food industry’s stance is supported by confidentiality and proprietary arguments. Although there is a stigma connected to GMOs, I favor the argument that the public has the right to know. Many people will come to realize that many of the foods they already eat are modified. There should be an education campaign to make sure people comprehend the information they’re given, dispel myths, and to encourage dialog. If the American public, government, and food industry can agree on the consumer’s right to information by implementing GMO labels, perhaps the focus can instead be concentrated on the potential benefits of GMOs and steps can be taken to mitigate the potential risks. Hiding information from the public only undermines trust and removes our right to choose.
In summary, CRISPR-Cas9 technology is an innovative scientific tool that must be used ethically. Scientists are imploring their peers to use good judgement and to consider the consequences of crossing certain ethical lines. History has taught us that ethical lines were crossed in Nuremberg when experiments were random and unnecessary. Embryo selection using IVF is certainly close to that ethical line. Many agree that although germ-line editing using CRISPR-Cas9 has become more tenable it’s also ethically unfeasible. The feasibility of CRISPR-Cas9 technology can bring justice to food insecure countries, but we also need to maintain our right to information in this country. Whatever the technology, maintaining ethical lines is necessary for a fair and just society.

Figure 1 – Mechanism of CRISPR-Cas9 gene-editing CITATION Zha16 l 1033 (5)
References
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