This post is a part of our Bioethics in the News series
By Jennifer Carter-Johnson, PhD, JD
The excitement and potential of CRISPR to treat severe genetic conditions by editing disease-causing DNA has taken an unexpected hit. A recent Wall Street Journal article highlighted the unexpected results from a CRISPR study in which attempts to edit a human gene responsible for blindness resulted in the loss of the entire chromosome from the cells in the embryos. These results echo another study conducted in human cell lines published earlier in 2019.
CRISPR is a targeted gene editing process that allows scientists to direct genetic modifications with far more precision than prior procedures. CRISPR has been touted as a gigantic leap in the ability to modify DNA by creating or repairing pinpoint DNA mutations without affecting other areas of the chromosome on which the gene resides. The recent study indicates that the technique might not be as straightforward in humans – and thus neither will be its use to fight disease.
CRISPR Technology – Promise and Problems
The value in CRISPR mediated genetic modification can be seen in a wide variety of biotechnology products, such as genetically modified crops and new biologics. But perhaps the most exciting and most controversial potential for CRISPR can be found in the desire to modify embryonic genomes to remove genetic abnormalities for which we currently have no cure.
This promise of embryonic gene editing is appealing not only because it would remove the condition from the child born from the gene-edited embryo, but also because the offspring of that child would also be free of the condition. CRISPR gene editing – because it is done at the embryonic stage – creates germline mutations that are passed to future generations. In a therapeutic use of CRISPR, those mutations would be cures for often untreatable diseases.
However, it is this very promise that raises many of the problems with CRISPR embryonic gene editing. Much debate has surrounded embryonic gene editing. Until this recent news, there were fears that CRISPR may make gene editing too easy. The technological development of CRISPR in embryonic gene editing is moving at a breakneck pace as scientists around the world are working on procedures. Biohackers work in their garages and livestream the use of CRISPR to edit their own genomes.
Many are debating which genes should be targeted and how fast the research into actual trials should proceed. Most agree that severe diseases would be the best place to start, but should the technology be deployed for cosmetic benefits such as eye color, or diseases for which a treatment exists? The dangers of CRISPR editing are unclear, and there has been an informal moratorium on the use of the technology to create children. Despite that, there has been at least one rogue scientist who has created genetically modified embryos and brought them to full term birth.
International Policy on Human Gene Editing
The scientific research is not occurring in a vacuum. Each country decides how CRISPR can be used in its medical system – both when the technique is safe enough and on which diseases it should be used.
An international commission recently pronounced that the technology is not ready for clinic implementation because scientists don’t understand the full safety issues surrounding its use in human embryos. The commission described some of the potential clinical uses in the future and outlined a basic safety protocol for approval.
One of the creators of CRISPR, Jennifer Doudna, has also spoken out against applying CRISPR too hastily to embryonic gene editing.
Based on the recent studies showing loss of chromosomes, the international commission and other scientists are correct to call for a moratorium on clinical embryonic gene editing.
CRISPR – The Path Forward
The setback in CRISPR gene editing does not mean that the technology and research should be discarded. The potential to change lives is too great; however, the dangers of use with our current understanding are even greater. So how do we move forward with CRISPR in embryonic gene editing? The answer must include balance – in research strategies and in voices.
While the technology is not ready for clinical use, and we have not yet determined which uses would be appropriate if it were available, the science should not stand still. The research surrounding CRISPR gene editing will yield insights into human biology that we cannot predict. For example, the loss of chromosome length in human embryonic cells undergoing CRISPR treatment seems to be different than the response of other species of embryonic cells. And debates about the appropriate use of the technology will allow us to discover more about ourselves as humans.
As we debate the best way to develop and deploy CRISPR technology, we should look to a variety of stakeholders. Scientists have a solid track record in understanding when recombinant DNA technology has potentially hazardous implications. In the 1970s, the Asilomar Conference allowed scientists to put together research guidelines that allowed the technology to be developed without harming public health. In fact, the international scientific consensus not to use the technology such as described above indicates that scientists are beginning that work. Such a moratorium on clinical uses gives us time to understand how to deploy the technology in the safest manner.
Additionally, there is a role for the voices of the patients whose lives could be changed by the technology. Patients may not be in the best place to judge when the technology should be deemed safe enough to deploy, but they certainly will have input about which mutations cause hardships that merit the risk of germline editing. Many of these patients already work with scientists on potential treatments for their diseases. CRISPR discussions may open another avenue for many.
Finally, there is a role for legal regulation of the use of CRISPR. Governments should listen to the voices of scientists and potential patients in drafting these regulations. But as shown by the example of at least one rogue scientist, there needs to be teeth to the moratorium on CRISPR clinical use at this time. CRISPR and its use in human gene editing raise complicated issues and hold great promise as a powerful tool to defeat genetic diseases. The development of those technologies will not be straightforward or without risk and will require more basic science research to achieve clinical efficacy. But with proper planning, we may learn more about ourselves as humans on the path to a cure.
Jennifer Carter-Johnson, PhD, JD, is Associate Dean for Academic Affairs and Associate Professor of Law in the Michigan State University College of Law. Dr. Carter-Johnson is a member of the Michigan State Bar. She is registered to practice before the U.S. Patent and Trademark Office.
Join the discussion! Your comments and responses to this commentary are welcomed. The author will respond to all comments made by Tuesday, December 15, 2020. With your participation, we hope to create discussions rich with insights from diverse perspectives.
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More Bioethics in the News from Dr. Carter-Johnson: Biohacking: How a DIY Approach to Biology Can Shape Our Future; Web of Interests Surrounding Medicines Makes Patient Access Increasingly Difficult; Humanity in the Age of Genetic Modification; Defining The Spectrum of “Normal”: What is a Disease?; Dawn of False Hope: Spread of “Right To Try” Laws across the U.S.
References
- Marcus AD. Crispr Gene Editing Can Lead to Big Mistakes in Human Embryos. The Wall Street Journal. Oct. 29, 2020. https://www.wsj.com/articles/crispr-gene-editing-can-lead-to-big-mistakes-in-human-embryos-11603983608.
- Cullot G, Boutin J, Toutain J, et al. CRISPR-Cas9 genome editing induces megabase-scale chromosomal truncations. Nature Communications 10, 1136 (2019). https://doi.org/10.1038/s41467-019-09006-2.
- Zuccaro MV, Xu J, Mitchell C, et al. Allele-Specific Chromosome Removal after Cas9 Cleavage in Human Embryos. Cell, Oct. 29, 2020. https://doi.org/10.1016/j.cell.2020.10.025.
- Zayner J. [Video] DIY Human CRISPR. Facebook, 2017. https://www.facebook.com/josiah.zayner/videos/10102950199937847/. Accessed November 25, 2020.
- Wen P, Marcus AD. Chinese Scientist Who Gene-Edited Babies Is Sent to Prison. The Wall Street Journal. Dec. 30, 2019. https://www.wsj.com/articles/chinese-scientist-who-gene-edited-babies-is-sent-to-prison-11577703233?mod=article_inline.
- Global Gene Editing Regulation Tracker and Index. Genetic Literacy Project. https://crispr-gene-editing-regs-tracker.geneticliteracyproject.org/.
- National Academy of Medicine, National Academy of Sciences, and the Royal Society. 2020. Heritable Human Genome Editing. Washington, DC: The National Academies Press. https://doi.org/10.17226/25665.
- Berg P. Asilomar 1975: DNA modification secured. Nature 455, 290-291 (2008). https://doi.org/10.1038/455290a.
MSU Bioethics 
Dr. Carter-Johnson, thank you for the information on CRISPR and gene editing. I was unaware of the advancements that scientists have made in this area. With gene editing scientists are making some risky choices, especially in humans. Since human embryos appear to not be a primary study, the effects it may have on humans is not even available. I can understand trying to eliminate some unwanted characteristics such as blindness as you mentioned, but what about other characteristic that some people use to define themselves as unique? How do we decide we are desired characteristics, and which are undesired? One thing everyone seems to agree on is the need for more research and legal oversite to even begin to think of moving forward with CRISPR and human gene editing.
Cassandra, I think you have hit upon one of the biggest issues with gene editing embryos – what should be edited? I like to think of the question more broadly as well. What is a disease?
We all might agree that treating a debilitating disease should be a goal. But maybe not. What about deafness? Many in the deaf community see deafness as part of their culture – not as a disease. Similarly, autistic people often speak about being embraced for who they are rather than finding a “cure”.
But culture and personality aren’t the only issues. The gene for sickle cell anemia carries resistance to malaria. Do other genetic variations increase risk of some diseases but protect from others?
Dr. Carter-Johnson, thank you for taking the time to write this blogpost. I find myself slightly speechless after having read this article. CRISPR and gene editing is something I really have no prior knowledge on, nor was aware of the current work towards them. Though you describe the study on these topics to be focused more heavily in other areas, and not on human embryos, the thoughts of what could come with that are immeasurable. The idea of being able to modify an embryo is quite amazing, but also brings to surface some red flags for me. Do you think that if one day these sort of modifications are possible, that all diversity we currently see will be wiped out? Again, I know this is a far out thought, but I can’t help but think about this. Thank you for this blogpost, very interesting read!
-Kalli Feldpausch
Hi Kali, I think that gene editing could be be a threat to at least some diversity. We have seen in agriculture – where genetically modifying crops has been a huge driver of industry for 30 plus years now- the growth of monoculture or single variety cultivation with a reduction in the types of genetic variety that have traditionally developed in response to local conditions such as drought, late frosts, etc.
It is not unreasonable to think that parents who choose gene editing for embryos might, if given the option, choose to correct disease mutations AND edit for height, intellect, athleticism, or any other number of socially desirable traits that could lead to less diversity overall.
Since we don’t know what challenges we will face in the future – such as pandemics – we don’t know which genetic mutations might be protective in the long run.
Also, my apologies for leaving an “L” out of your name. I try to type faster than I really can sometimes!
Dr. Carter-Johnson,
Thank you for your blog entry. I find the science behind CRISPR to be fascinating, although I do not have a deep knowledge of this area. Your entry provided a peek into this progressive science and it is exciting to consider the benefits of this. I can certainly see the ramifications of not having legal oversight to CRISPR. While the possibility of alleviating conditions for the future, has there been push back in continued progression with CRISPR?
Again, thank you for your post!
Alexandra Kruger
Alexandra, yes, there has certainly been pushback. Scientists themselves have warned about moving too fast with the technology. Luckily, internationally, most governments are working together (or at least on parallel tracks) to slow down the clinical implementations of CRISPR in human embryos. Additionally, there are many who push back against using embryos in any research.
There has been much less pushback about using CRISPR in treatments for adults. Those treatments do not impact the germline so are not passed on to offspring and thus are less risky in many ways. I think we are getting close to having some real breakthroughs in treatments based on CRISPR research.
Dr. Carter-Johnson,
I appreciate the time you took to discuss the concept of CRISPR. I remember hearing about it in passing, but finding out more through your entry has certainly been eye-opening. I believe that it can be a powerful, yet helpful tool, if used appropriately. There have been many trials and tribulations when dealing with genetic modifications and early detection, especially when the fetus is still in its developmental cycle. I think that the use of CRISPR technology has a positive future, however there needs to be far more testing and certainty of targeting the necessary genes before human trials can even be considered. There was also a point that you touched on that I felt was crucial to consider: while most can agree that CRISPR technology can be used to target severe diseases, there are those that would want to use it to modify genetic makeup purely for cosmetic reasons. In a culture that is struggling, but fighting, for individuality and body-positivity, it seems that this kind of manipulation would divert from this movement. Nonetheless, I believe that there can be a significant amount of good that comes from this technology and I hope to see the progress in my lifetime.
Thank you!
Elizabeth, Yes, the celebration of diversity that is gaining ground today could be jeopardized by an rampant use of CRISPR gene editing if prospective parents are allowed to chase the “popular” trends. Additionally, since such usage is likely to be limited to those with the resources to pay for it, unpopular traits could become associated with the poor or lower classes, making some traits even more of a stigma.
There is so much good that can be done, but we do need to be mindful of the potential pitfalls.
Dr. Carter-Johnson,
Thank you for your thorough and understandable explanation of CRISPR – it made a complex concept much easier to grasp! While the advancements in CRISPR technology are fascinating, and very promising for human use and the cure of previously incurable diseases; I completely agree with you that there is more research to be done and more understanding to be gained. I also agree with your suggestion for the need of some sort of regulation when it comes to the use of this technology. Furthermore, I would wonder what would qualify as “worthy” of CRISPR intervention, and for which diseases would CRISPR be deemed necessary? Would this then be covered by someone’s insurance? Advancements in science are always exciting, and bring to the surface many questions and curiosities. I look forward to learning more about this groundbreaking technology.
Thanks again,
Mackenzie
Mackenzie,
Two great questions. I addressed the question of what is a disease in my response to Cassandra, but even if we could agree on that, a “worthy” disease is the next step because the research will be expense.
Insurance coverage for CRISPR is a huge issue. To use CRISPR on embryos, conception requires the use of assisted reproductive technologies (ART) – which cost $$$. Insurance companies cover ART differently depending on the policy and the need. Layering gene editing of the embryo on top of the already costly procedures would make insurance companies run the numbers to decide whether coverage would be financially worth it. Like the cost of many medical procedures, this will impact the poor and working class more heavily than other areas of society.
Dr. Carter-Johnson,
I really enjoyed reading your article. I found the topic very interesting as I am not familiar with CRISPR. Your article on the topic has really opened my eyes to the subject and the potential positive outcomes that could come from it. I appreciated your explanation of what CRISPR is because it helped me understand the concept more. If CRISPR is proven to be effective and safe, I think that the idea could be extremely beneficial to future parents. You mentioned how there has been some debate on which genes should be targeted. Do you think that in the future CRISPR should be allowed to be done in order to change eye color or be used for other cosmetic benefits? Personally, I think that idea is interesting to think about; however, I think eye color and other cosmetic changes should be considered last. I think that first the use of CRISPR should be focused on fixing conditions that cause severe diseases that are not treatable. Overall, I think that the concept is really interesting and I think it would be beneficial for many children in the future.
Thank you,
Hannah Dennis
Cosmetic changes are a huge point of debate. Obviously, curing disease should come first. But as the technology develops it may be easy to make multiple changes at once. I spoke to concerns about genetic diversity in some of the comment above. But the idea of killing cosmetic diversity would also be problematic as well. It could be a signal of financial means that only people with lots of money can have purple eyes. Such a signal would allow for further social stratification as only the rich could afford certain types of augmentations.
Dr. Carter-Johnson,
Thank you for your informed and thoughtful post regarding the use of CRISPR. As some others have mentioned in the comments, I have heard snippets about this intervention previously, but I appreciated diving deeper with this blog post. In reading this, it is clear that there are some ethical dilemmas with CRISPR utilization, and I am curious to continue to read about future developments.
I agree with you that “the science should not stand still.” With any scientific breakthrough, thorough research and clinical trials must be completed prior to formal implementation. I am wondering if you could speak more to your statement that continued research on the efficacy of CRISPR will lead to us learning more about ourselves?
Also, I did not previously know that countries can set their own standards regarding when/how CRISPR can be used… it also sounds like there is an international commission. Is this task force’s purpose simply to collaborate regarding research findings or are they making decisions for widespread implementation guidelines?
Thank you again for your insightful analysis of this topic. Very interesting to read and think about!
Best,
Kerri
Hi Kerri,
As we learn more about how CRISPR work in human cells as opposed to animal models, we will learn more about how human cells actually work. For example. the process has been tested and used in many animal models to do date. But one of the first tries in human embryos reveal major problems with the technique. Those problems indicate that there are likely some major difference in DNA repair for human embryos than in the cells and animals we have been studying. We will need to learn more about embryonic development in order to create working clinical treatments.
Internationally, each country sets its own laws. While there are some treaties where multiple countries agree to be bound by the same sets of laws, each country implements those treaties on their own. So a task force would collect data, determine issues and even produce proposed laws or policy guidance. But it would be up to each country to pass the laws to implement all or part of the proposal as it chose.
Dr. Carter-Johnson,
Thank you for sharing this information with us all. I have never had the opportunity to dive deeper into CRISPR gene editing. As a current social work graduate student here at MSU, I have not had the privilege to expand my knowledge within this field. I can say that this information was completely informational and worthy of exploring in my field as a soon to be a medical social worker. You discussed several concerns as to how and why this is a bioethical dilemma and how this can be both a positive in negative if further researched.
I was able to learn that CRISPR is a targeted gene-editing process and that this is such a huge advancement in science. This type of technology has such a value in biotechnology products (crops, biologics, etc.) and can be necessary for improving life itself in the near future. Embryonic editing is also a great advancement of what we have not necessarily thought of prior to this. This is such a large promise around embryonic gene editing though and with that, you have allowed me to critically think about what this means for us all. Some questions that you began to explore were which genes should be targeted and how fast is too fast to be using CRISPR? There are many unclear dangers around this use of technology even though it is incredibly interesting. I also loved that you talked about knowing when is it safe, and what should be targeted first to use this for clinical use of CRISPR as these were big concerns of mine as well.
As we all know, there are potential hazardous implications that come with this technology. We have to be able to use this in the safest manner even though we do not necessarily know what that means yet. Patients’ lives are going to be at the forefront of this issue and we have to take into consideration what the patient’s role will be. CRISPR discussions may have a role in navigating what laws, regulations, and roles will be played upon who will use it for human gene editing. After reading this blog, it is clear that there will always be a risk but with proper planning and understanding of these risks, we may have a better opportunity to regulating and maintaining further research with CRISPR.
Thank you so much for sharing your knowledge and understanding with us about this topic. I am very grateful for your insight and am looking forward to reading and seeing more information about this topic soon.
Best,
Ravyn A. Rooney
Ravyn, Yes, the risk v. reward calculations will be so important. Risks will include both risks to the patient and risks to society- especially as we gauge the impact of “cosmetic” or other genetic manipulations not directed a serious immediate diseases. For a great movie that explores those potential issues – see Gattaca.
Dr. Carter-Johnson,
Thank you for your insight on the topic of CRISPR, explaining the potential dangers with the technology as well as the need for further research. I recall hearing about CRISPR in my human biology courses in my undergraduate studies and always found it to be an interesting concept, but I do have my concerns. One of my worries is that CRISPR will eventually be used to “perfect” the human race. If we genetically modify human embryos to create the “perfect” human being, we will significantly lack in diversity.
I understand that CRISPR can be beneficial to help eliminate unfavorable birth defects or medical conditions with no cure, but as others have mentioned, it seems like it would be hard to draw the line when it comes to what conditions should be eliminated and what conditions should not. If CRISPR is used to eliminate many of these conditions, it may also target those who actually live with those conditions and make them feel like society thinks everyone is better off without them or they feel that they are less than.
I can see CRISPR as an amazing asset in the future, but we still have a long way to go when it comes to making sure that the technology will be used in the most beneficial ways without causing more harm than good.
Thank you again for your thoughtful blog post.
-Kaitlin Schutz
Kaitlin,
This sentence from your comment struck me: If CRISPR is used to eliminate many of these conditions, it may also target those who actually live with those conditions and make them feel like society thinks everyone is better off without them or they feel that they are less than.” I think it is so on point!
I just mentioned the movie Gattaca above but I think it also bears recommending here to your point. In that movie, embryonic engineering creates an entire underclass of people who did not receive the tech.
That scenario is extreme but is in some ways already happening. Take Down’s Syndrome as an example. In the US, close to 70% of people who receive genetic counseling that the fetus contains genetic abnormalities that lead to Down’s syndrome choose to abort. In Iceland, that number is close to 100% with only about 2 people born with the disorder each year. The impact on education and medical access as fewer people are trained to deal with people with Down’s Syndrome should be emphasized. But, as you note, the practice also potentially speaks to how society views people with the condition.