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CRISPR: A Cautionary Tale

CRISPR

In late November 2018, the scientific community was met with a shocking announcement: a woman had given birth to the world’s first genetically-edited twins with the help of a Chinese researcher. The researcher removed the HIV-enabling gene from the twins, whose father was HIV positive.

The news was alarming for two reasons: first, the gene-editing technology at the center of the announcement, CRISPR, was still in development, and second, the births opened the door to more experimentation with the human genetic code to unknown consequences. Weeks after the births, there were still a lot of unanswered questions about what exactly happened, how healthy the newborns were and what would come next.

Reproductive Medicine Associates of New Jersey (RMANJ) third year fellow Dr. Shelby Neal is one of many in the field of assisted reproduction watching this story unfold. Here’s what she said about how we got here and where we might go.

What is CRISPR, and why is genetic-editing important?

Dr. Neal: CRISPR is a gene-editing tool that can be used to modify DNA sequences. It allows researchers to target specific mutations known to cause disease and “edit” these genes. The ability to edit genes holds promise as a method to prevent transmission of certain genetic mutations that result in disease.

What are the risks associated with CRISPR and gene-editing in general?

Dr. Neal: There is a risk that CRISPR may not be 100% effective at modifying the intended gene – it is possible that the gene may be modified in only some cells of an embryo and others may continue to grow and divide. In this situation, it is possible that the individual may still be affected by the disease. In addition, there is the risk of “off-target” effects – specifically, introduction of unintended mutations. For example, modification of the intended gene may shift the downstream genetic code, resulting in new mutations with the net effect of doing more harm than good to the embryo. Such mutations could then be passed on to subsequent generations.

The Chinese researcher removed the HIV-enabling gene from the twins, whose father was HIV positive. What are the biggest concerns regarding these first two CRISPR births?

Dr. Neal: Most scientists agree that because there is not enough data validating the safety of the technology, it was introduced prematurely. There is also concern regarding the choice of gene to be edited, with many alleging that editing of the selected gene was not medically necessary, as there are other safer and more established ways to prevent HIV transmission.

Are there any downsides to the removal of this gene?

Dr. Neal: It is quite possible that deletion of this gene may have unintended effects. The gene is thought to play other roles, including prevention of West Nile virus infection – therefore, the twins resulting from this experiment may be more susceptible to West Nile virus. It is likely that the gene has other roles as well, that are yet to be established.

When will CRISPR be ready for wide-scale use, if ever?

Dr. Neal: Far more pre-clinical investigation into the efficiency and safety of this technique will be required with transparent reporting and publication of results in peer-reviewed journals. Only once CRISPR is deemed both effective and safe could it be considered appropriate for wide-scale use, and this is a process that will take years longer.

What does this development tell you about other ART innovations that may not be ready for primetime, such as the production of human sperm and eggs from stem cells?

Dr. Neal: Although it is tempting to roll out new technology as soon as there is an indication that it may “work,” it is important to conduct the appropriate pre-clinical validation with appropriate oversight before implementing in a clinical context.

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