In lieu of an interview transcript, I have decided to summarize the interviews I conducted. All the ideas summarized below are Dr. Church’s responses to my interview questions.
Dr. George Church is a Professor of Genetics at Harvard Medical School and Professor of Health Sciences and Technology at Harvard and the Massachusetts Institute of Technology (MIT). During my interview with Dr. Church, we talked about CRISPR and his thoughts about this emerging technology.
I began my interview with Dr. Church asking about what he thinks the general public should know about genome editing using CRISPR/Cas9, in order to allay any misgivings they may have about the technology. Dr. Church responded that it is important to stimulate conversation about what we can do to prevent bad outcomes. Some of the things we could do to prevent these bad outcomes is making sure to have good regulatory agencies in place. In the case of CRISPR, there is the Food and Drug Administration, the United States Department of Agriculture as well as the United States Environmental Protection Agency.
Dr. Church also brought up that the types of questions that arise surrounding CRISPR include those surrounding human rights, stigma, equality, discrimination as well as safety and efficacy. These concerns are not unique to CRISPR and are the same as any other therapeutic. CRISPR is not fundamentally different.
When thinking about such a ground-breaking technology the question of regulation also arises. Dr. Church believes that CRISPR should absolutely be regulated, especially since it affects the human body.
One of the major concerns with this technology is germline editing. CRISPR can be used to alter gene in ways that can be passed down to future generations. When asked about whether scientists should be allowed edit the human genome, Dr. Church stated that he believes it is not any better to make random mutations than to make directed mutations. For example, chemotherapy, induces random mutations into our germline. Regarding the topic of abortion. Dr. Church stated that if an alternative, such as CRISPR was available, to prevent the child from inheriting a genetic disease, people would most likely use it. If both parents are carriers of a serious genetic disease, then they have a good chance of having their children affected by this disease. If CRISPR is used to t edit the father’s sperm, however, then no embryos are at risk, thus reducing the number of pregnancy terminations. It could be a win-win that both conservatives and liberals could embrace.
Because of the great potential of CRISPR technology, the question arises of what it should be applied to and which applications should be prioritized. Dr. Church believes infectious diseases for which drugs and vaccines do not work are suitable targets for such a technology. This includes HIV, to provide an alternative to drugs and vaccines which are mostly failing and resistance is occurring quickly. Dr. Church noted that rare genetic diseases may not be the most suitable targets because a lot of rare genetic diseases can be handled by genetic counseling and it seems that is more cost effective and possibly more effective to target other diseases instead.
Yet another use proposed by Dr. Church was using CRISPR for transplantation. Pigs can be engineered to be organ donors and this could benefit people because it could be more reproducible and maybe of even higher quality than looking for someone who is a compatible organ donor and, has died under the right circumstances and happens to be able to get the organs in time before they become necrotic.
But how would scientists be able to cure a disease if they do not know what causes the disease? To this question, Dr. Church said that there are cases where we can develop therapies without knowing the cause. In the case of smallpox, for example, scientists did not know anything about viruses and not much about bacteria nor about how the immune system worked. Nevertheless, scientists were able to figure out that they could inoculate using cowpox. Additionally, there are instances where multiple things cause a disease but one thing cures it.
CRISPR was not the first gene editing tool to be discovered. Before CRISPR there was Zinc Finger Nucleases (ZFNs) and Transcription activator-like effector nucleases (TALENs). I thus asked Dr. Church how these other technologies differ from CRISPR and why CRISPR is seen to be special compared with these other technologies. Dr. Church responded that he actually thinks that CRISPR is not that special. He stated, “It’s a little bit easier for academics to prototype, but that doesn’t make any difference to the pharmaceutical industry.” What does differ about CRISPR though is that it is a little more efficient than ZFNs and TALENs. Dr. Church also mentioned that gene editing is not the only way of doing gene therapy. The main way of doing gene therapy, in fact, is additive, where you are adding something that is missing. CRISPR on the other hand is mainly subtractive. Dr. Church mentioned that, for the most part, editing with CRISPR, ZNFs and and TALENs, “is mostly imprecise editing, it’s subtraction, it’s eliminating genetic function.” As a result, Dr. Church believes that there are going to be technologies in the future that are going to be better than CRISPR, where you can edit multiple genes and do so precisely.
With the development of such gene editing technologies, there also come concerns. Some of these concerns include off-target effects and mosaicism. Dr. Church stated that he thinks that both off-target effects and mosaicism are small problems and off-target effects being less so. “If they are properly designed and tested, the CRISPR off-target rate is less than the spontaneous mutation rate.” For CRISPR, you can empirically determine where it goes.
In terms of mosaicism, when you wanted to correct a gene, you would take the cells out, insert the gene editing mechanism, put them back into the body and maybe only half of the cells you inserted the CRISPR in were correct, and then the other half would be killed by the virus. Essentially, the cells that got the therapy would survive and the ones that did not would die. Another way you can address mosaicism, which is less common therapeutically, is that if you are working with stem cells, you can purify the stem cells which have obtained the correct therapy and then you can put that pure population of cells into the person. The third way is that you leave everything like it is; there’s no selection in the body or the lab. My final question to Dr. Church was regarding what CRISPR does not do. Dr. Church stated that he believes CRISPR is not great at precise editing or multiple edits at once and CRISPR is also not good at delivery. CRISPR is not a delivery mechanism and thus needs something else to deliver it to the right place efficiently.