Unnatural Base Pair Report

In this report, Zhang Y, et al., explored the idea of expanding the genetic alphabet although it has only ever consisted of four natural bases. The four natural bases generally base pair to form A-T and C-G; however, the authors created an organism that consists of those in addition to another base pair: X-Y. Considering the fact that X and Y do not typically occur in nature, the authors actually ended up creating a semisynthetic organism (SSO) that has an unnatural base pair (UBP) and may be able to create new life.

The numerous past failed efforts in creating a suitable UBP contributed to the progression of the authors creating a SSO. In the past, the authors grew Escherichia coli with compatible unnatural nucleoside triphosphates, dNaM and d5SICS, which are essential in replicating UBPs. They implemented a nucleoside triphosphate transporter (NTT2) to allow the E. coli to import the UBPs, ensuring they would be present
in the replicated DNA. Unfortunately, the SSO did not grow well because of the expression of NTT2; therefore, even under controlled conditions it was unable to retain the UBP information.

Although this was a drawback, the authors created an optimized transporter system that possessed a lower toxicity. They recreated their base Y so that it could be replicated more efficiently and also store increased UBP information. While this was better than before, it still needed work. It was necessary to find a way to maintain bacterial life and have it pass on their synthetic DNA: X and Y bases. This caused the authors to investigate the CRISPR-associated (Cas) system, precisely Cas9, because of its potential to immunize the cell. The CRISPR-Cas9 was able to get rid of DNA not containing the new X and Y bases. This ensured that only the correctly grown cells were being incorporated into the bacterial DNA. It was found that plasmids containing Cas9 were better able to retain UBPs. Zhang Y, et al., allowed us to see that CRISPR-Cas9 can serve to efficiently stabilize the SSO which shows growth while being able to store an increased amount of information. The results demonstrate that SSOs possess benefits that natural organisms do not.

This just goes to show how the future of science has no boundaries. This is still a new technology in its infancy, meaning that there is an unlimited amount of possibilities as to where this could take us. As of now it is being used to store new information into organisms; however, I believe in the future it may be implemented in combating diseases by creating new proteins to make synthetic amino acids. Essentially, this would allow us to treat diseases that we, until now, consider to be terminal. Additionally, considering that E. coli is a simple organism I wonder how this technology will work in more complex organisms such as eukaryotes. The idea of new bases being applied to various animals and humans sounds both exciting and scary.

I found this study to be extremely fascinating. Ever since I took my first biology course, I have always been told that there are four natural base pairs, and that is it –nothing more and nothing less. However, this paper changes everything. It shows that life as we have always known it is changing by introducing the idea of creating some sort of alien-life.

While understanding that this technology possesses great potential for expanding the world of genetics, I still have numerous concerns.
Considering it is still an up and coming technology, I find it worrisome that nothing like this has ever been done before. In one way or another scientists are basically playing with nature and acting as “God.” How do we know this new alien-life is not going to have significant consequences? For example, I wonder how the expansion of the genetic code effects our environment and other organisms. It is possible that one of the organisms can get loose and cause more harm than good. When we discussed GMOs an experiment demonstrated that one organism getting loose had the potential to reduce the population size to zero, resulting in an ecological disaster. I am afraid that this genetic expansion might have the same negative impacts. Does that mean that there will be more regulation to prevent things such disasters like that from happening? These are questions that I believe only time and more experimentation will
tell.

The most apparent challenge with this study seems that it has taken a lot of work to get them authors to where there are and there is not much for the authors to compare their work to. This had to have been pretty costly for the authors.

I liked that the authors implemented various figures that better allowed readers to understand the complicated process. Although I have a science background, I am not too familiar with this technology; therefore, the graphs allowed me to better visualize how the different transporters played a role in the UBPs. I would have liked for the authors to have talked more about future implications and where they predict the direction of this technology.

All in all, it is clear that the expansion of the genetic alphabet brings not only technology but curiosity to what could come. The addition of the X and Y bases definitely proves to me that science is advancing, rapidly. I am interested in seeing what the focus of future studies will be in regards to UBPs and SSOs. I believe there is still a lot of work that still needs to be done for us to better understand this technology; however, I am excited to see where this technology will take us.