Long-read sequencing and long-range PCR genotyping showed that cellular repair of CRISPR-Cas9 induced double-stranded (DS) breaks often led to large deletions and rearrangements.The problem with these methods is that only looking near the target leads researchers to miss variation and underestimate the damage. Furthermore, hardly any labs conduct full genome sequencing of cells modified using CRISPR, instead using PCR to search for large deletions. Investigation of the genetic changes has been limited to locations either very close to or very far from the target sequence. Prior to these new studies, no one had looked at the impact of CRISPR-Cas9 mediated genome editing on downstream genes. Each of these papers examined the extent to which CRISPR-Cas9 genome editing led to on- and off-target damage by varying the generally accepted protocols to check for these errors. Others evaluated the researcher’s work and provided recommendations that refined the methods.Īfter years of optimistic research and the advent of the first clinical trials related to CRISPR-Cas9, a cluster of publications ( Nature Medicine – Brief Communication, Nature Medicine – Letters and Nature Biotechnology – Letters) in the last month have led the scientific community to seriously question the reliability of CRISPR-Cas9 technology for the first time. (Check out these past blog articles about CRISPR if you want to learn more about the basics of CRISPR.) This prompted an explosion in CRISPR-Cas9 research, demonstrating that the technology had wide-ranging and potentially revolutionary research and therapeutic applications. Initially, a few scientists published some papers identifying CRISPR-Cas9 as an efficient and reliable way to perform gene-editing. If you have been following CRISPR-Cas9 in the literature over the past few years, the process of consensus building has been observable in real-time. Moreover, while basic science education is quite effective at instilling in students the process of the scientific method, what seems to get neglected is how the work of one lab to test one hypothesis fits into the larger concept of a theory formed by consensus. Unfortunately, the people that communicate science (scientists, doctors, reporters, writers, educators, etc.) don’t always do a very good job communicating this nuance. What this person should conclude, however, is that science is working exactly how it should and this immediate conflict will get resolved over time as more scientists try to answer the same question. The non-scientist who learns about both studies concludes that since the studies are in conflict, there must be something wrong with the scientists or the process, and thus completely disregard the value of either study. The next month, another study will be published that finds an increased risk of cancer in individuals who eat a lot of chocolate. Typically, the way this plays out is a study will claim a certain food-let’s say chocolate-is associated with a lower cancer risk, so people conclude they should eat more chocolate. I am reminded of this dilemma every time new research about nutrition is picked up by popular media. It is also the part of scientific inquiry that so often leads the public to misunderstand and mistrust scientific findings. Building consensus is the time-consuming process that includes peer review, publication and replication of results. While this process is integral to doing science, what gives scientific findings credibility and value is consensus from the scientific community. As I listened to a TED talk about the subject, I was reminded that for the general public the foundation of science is the scientific method-the linear process of making an observation, asking a question, forming an hypothesis, making a prediction and testing the hypothesis. Scientific inquiry is a process that is revered as much as it is misunderstood.
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