A recent paper was published that used clustered regularly
interspaced short palindromic repeats (CRISPR) gene-editing technology as a
treatment for Human Immunodeficiency Virus (HIV). What is CRISPR? CRISPR is
similar to the cut and paste on a computer but for genes. CRISPER is made of
two major components: a Cas9 protein that can cut DNA and a guide RNA that can
recognize a specific sequence of DNA that needs to be edited (Deshpande et al.,
2015). Once you find the sequence you want edited you take your CRISPR/Cas9
complex and cut out that unwanted sequence. From here scientist can modify,
delete or insert new DNA into the target genome sequence (Deshpande et al.,
2015).
Scientists in China took DNA in bone marrow stem cells from a
donor and edited them via CRISPER before transfusing them to the HIV positive
patient. They transfected these cells to have a mutation in their CCR5 gene.
Having a mutation in the CCR5 gene has been linked to HIV resistance (Rettner,
2019). CCR5s are proteins on the surface of white blood cells and HIV
binds with theses CCR5 coreceptor to
invade our immune cells (Wilen, 2012).
The patient was in full remission of his leukemia a month after
the bone marrow transplant. Blood test also showed that the edited cells grew
and produced blood cells in his body for 19 months. However, when the patient
stopped taking his HIV medication the virus came back. The scientists proposed
that a possible reason it didn’t fully cure the patient was because CRISPR
didn’t edited the CCR5 gene in every donor cell (Rettner, 2019).
I appreciate their efforts to advance science however; I feel
their experiment is ethically wrong on many levels. Based on non-maleficence, I
do not think that we should perform clinical trials on human subjects until we
are absolutely sure of the edited genes long-term effects. They only monitored
the patient for 19 months, which is not a sufficient amount of time to
understand the total effects. CRISPR is not perfectly precise and, as indicated
in the article, the treatment wasn’t very efficient. During the cutting and
repairing of DNA by CRISPR mistakes can be made causing abnormalities. These
abnormalities could cause cancer later on (Kosicki et al., 2018). I don’t think
it is ethical to use CRISPR gene therapy on humans until we have a better
understanding on the long-term implications.
References
Deshpande, K., Vyas, A., Balakrishnan, A., & Vyas, D.
(2015). Clustered Regularly Interspaced Short Palindromic Repeats/Cas9 Genetic
Engineering: Robotic Genetic Surgery. American journal of robotic surgery,
2(1), 49–52. doi:10.1166/ajrs.2015.1023
Kosicki,
M., Tomberg, K., & Bradley, A. (2018). Repair of double-strand breaks
induced by CRISPR-Cas9 leads to large deletions and complex rearrangements.
Nature biotechnology, 36(8), 765–771. doi:10.1038/nbt.4192
Rettner,
R. (2019) Chinese Scientists Tried to Treat HIV Using CRISPR. Retrieved from https://www.livescience.com/crispr-hiv-treatement.html
Wilen,
C. B., Tilton, J. C., & Doms, R. W. (2012). HIV: cell binding and entry.
Cold Spring Harbor perspectives in medicine, 2(8), a006866.
doi:10.1101/cshperspect.a006866
Ideally, the use of CRISPR for many mutations and infections needs more considerations for the long term implications that it has before being implemented on human subjects. However, there has been success in using CRISPR in mouse models for Duchenne Muscular Dystrophy (Nelson, et al., 2019). Duchenne Muscular Dystrophy is an x-linked recessive genetic disorder and is a good candidate for CRISPR because by using non homologous end joining (NHEJ), in vivo editing can be done to make corrections to disruptive mutations. This can be done if the exon that creates the mutation in the dystrophin protein is skipped. By passing the mutation causing DMD and restoring the expression of dystrophin without including the amino acid encoded from the excised exon.
ReplyDeleteLike with other CRISPR edits though, given that DMD aims to edit the mutation in the protein dystrophin which can then potentially "cure" patients who have the mutation, the long term effects are not known. However, since DMD is more of a straight forward mutation than HIV, given that HIV replicates almost like cancer, there is more promise in understanding long term effects that a single point mutation may have. Also, if you were a parent with a child born with DMD and you knew there was a possibility that they may be able to alter their genome to be "cured," many parents would take the non-malfeasance route and though potentially take away their child's autonomy, overall parents do not want their children to suffer and want them to have a just chance at the potential life they have ahead of them, minus the debilitating effects of DMD.
References
Nelson, C.E., Yaoying, W., Gemberling, M.P., Oliver, M.L., Waller, M.A., Bohning, J.D., Robinson-Hamm, J.N., Bulaklak, K., Castellanos Rivera, R.M., Collier, J.H., Asokan, A., Gersbach, C.A. 2019. Long-term evaluation of AAV-CRISPR genome editing for Duchenne Muscular Dystrophy. Nature Medicine. 25, 427-432. https://www.nature.com/articles/s41591-019-0344-3#Abs1
https://www.technologynetworks.com/genomics/news/one-year-later-crispr-success-in-duchenne-muscular-dystrophy-model-315586
Crispr Cas-9 has been referred to as the biggest biotechnology discovery by Quanta magazine, Vox, and many more. With any major biomedical/ biotechnical breakthrough their comes the debate of ethics, “What we ought to do?” If we can cure diseases like HIV, Cancer, Cystic Fibrosis, and many more, shouldn’t we? Coming from the Midwest, I have watched a debate of similar degree occur around me with GMOs. Our nation went through a similar debate with the emergence of nuclear power following WWII (US Department of Energy). While these technologies have had their lows, they have also had some significant roles in the betterment of our nation (Wynne 2001).
ReplyDeleteWhile I am not advocating for the unrestricted research of CRISPR Cas-9, I am advocating that we, as future health care providers and current science based graduate students, help educate on the “real risks” compared to the “perceived public risk.” Obviously, the research done by He Jiankui was unethical and as a scientific community we must not allow this unrestricted research with human subjects continue (Stein 2019). CRISPR Cas-9 is a tool and much like any tool it can be used for good and for evil. I believe that it is our responsibility to help educate and provide the general public with the tools to live a long and fruitful life. I hope that we can use CRISPR as a tool, but it is also our responsibility to “do no harm.” As the great Ben Parker stated, “With great power, comes great responsibility,” and like our fictional friend Spider-Man, we have the power and must be responsible moving forward.
Refrences
Stein, R. (2019). Chinese Scientist Says He's First To Create Genetically Modified Babies Using CRISPR. [online] Npr.org. Available at: https://www.npr.org/sections/health-shots/2018/11/26/670752865/chinese-scientist-says-hes-first-to-genetically-edit-babies.
U.S. Department of Energy Office of Nuclear Energy. (n.d.), The History of Nuclear Energy.
Science and Technology Washington, pp.1-27.
Wynne, B. (2001). Creating Public Alienation: Expert Cultures of Risk and Ethics on GMOs. Science as Culture, 10(4), pp.445-481.
Hello CalebH618,
DeleteThank you for your reply to my post. I really like what you had to say and the approach you took to say it. Thank you for giving me a different perspective on CRISPR.