In lieu of an interview transcript, I have decided to summarize the interviews I conducted. All the ideas summarized below are Dr. Lunshof’s responses to my interview questions.
Dr. Jeantine Lunshof is a philosopher and ethicist working in Dr. George Church’s lab at Harvard Medical School. Her role as an ethicist in the Church lab is to work alongside the scientists as a collaborator, listening and learning from what they present.
Regarding the ethical concerns that arise regarding genome editing, Dr. Lunshof stated that it is dependent on one’s background, be it their cultural background or religious background. Some people may hold religious or cultural beliefs in which they think that we should not intervene in the DNA, the building blocks of life. Dr. Lunshof did state that she does not share this view but she is aware that there are people in society, in this country or elsewhere, where they will completely reject genome editing.
When talking about genome editing, there is both somatic and germline. In order to get a better understanding of each, I asked Dr. Lunshof about the concerns associated with each technique. With germline there is the concern of inheritance. In this case, you would be making an edit in the germ cells of the person which will affect both the person and their offspring. This does however depend on the species and for how long the edit will last. The idea with germline editing is that you are editing the embryo to have a certain trait or the lack of a specific disease. Because you are making the edit in the germ cells, all the cells in the child will be edited, it is not clear, however, if this is indefinitely the case. Experiments have shown that it does not seem to go on forever; there is a fading out. This is the case in genetically modified organisms (GMOs). The genes reshuffle and the wild type restores itself. Such a finding is very important because by proving that the edit will not be passed down indefinitely, we must rethink our ethical arguments. With the execution of all these experiments, uncertainty is also an issue. Scientists may not know what the result of an experiment should be. But Dr. Lunshof did however mention that it is important not to be hasty with drawing conclusions; we must first look at what is occurring.
In terms of the potential to cure diseases using genome editing, you would want the edit to stay within the genome as the generations proceed. Once again there is the uncertainty since you would have two genomes making up the embryo; one from the mother and the other from the father. There may be other factors in the genome that trigger a variant of such a disease or may cause instability. The problem in humans is that we have very long generation times so we can not be certain of the outcomes.
On the other hand, somatic cell editing would not be inherited. Dr. Lunshof mentioned that there are an increasing amount of somatic interventions that are getting approval and there are many in trial. It is important to mention that CRISPR is not the only method of genome editing. There is also Zinc Finger Nucleases and TALENs. In gene therapy, there are applications that are more suitable for some therapies than others.
To get a better understanding of these three genome editing technologies, I then asked Dr. Lunshof if there were more ethical questions surrounding CRISPR compared to Zinc Finger Nucleases and TALENs. One thing that Dr. Lunshof stated that is important to note is that “when you look at the ethical principles, then it is of course nonsense to make a difference between if you say editing genes, gene therapy, somatic gene therapy.” You must ask the question of whether it is morally justifiable to distinguish between these technologies. The one thing to note, however, is that one of the biggest advantages associated with CRISPR is that it is very precise compared with the other technologies.
Another application of CRISPR is gene drives. A gene drive is a mechanism for preferential inheritance of a particular DNA sequence. When asked about whether there are more concerns surrounding gene drives compared to other technologies, Dr. Lunshof responded that it is very much based on a personal value system as well as to what degree one takes an anthropocentric position. She also believes that ecological interventions using gene drives are far more risky and difficult in a normative sense compared to somatic and germline editing, since the genome editing in humans is the individual’s decision. With an ecological intervention, the effects are very widespread, and even unstoppable to a degree. Over time, there may be a “ripple effect” and no one will want to take responsibility for the disaster. Additionally, with ecological interventions, the effects are not going to stay within national borders, running into regulatory issues.
Dr. Lunshof also believes that it is important for everyone to be involved in the discussion of genome editing. For gene drives, it is important for those in the region being affected to participate in the discussion of the topic before it is implemented since gene drives are localized.
Dr. Lushof also described one of the newest technologies that is being developed called daisy drives. Daisy drives are constructs in which the spreading of the gene drive is limited over time as well as a set number of generations and areas. Some of the criteria Dr. Lunshof believes must be implemented for a morally acceptable application of these technologies include: localization, time sensitive, as well as reversibility.
An interesting characteristic of gene drives is that they are reversible. Because gene drives are sexually transmitted, this technology only works in sexually reproducing animals. In order to introduce the gene drive, you need a founding family.after releasing the altered species into the wild, you can potentially reverse its effects by engineering a founding family that has the reverse gene, and once these newly engineered organisms are released, they will overpower the earlier changes you had made. Dr. Lushof also mentioned that it is very important for scientists to be open about their research and share their new discoveries with the public. It is important for the public to be informed about such topics.
Another thought-provoking topic Dr. Lunshof mentioned was base editing. Many scientists agree that base editing will most likely going to be successful in making changes to the human germline rather than technologies such as CRISPR/Cas9.