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CRISPR-Cas9, A Programmable Nuclease - Is It Medicine or Poison?

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  • Registration Date : 2015-10-06

In the future, with the highly developed genetic engineering techniques available, human beings will tend to select parents’ superior characters and pass them on to their offsprings. What happened in the SF movie “Gattaca” is coming true before our very eyes. This movie covers the world’s dyian future, where people are born not through natural pregnancy but only through artificial insemination. This controversial topic has taken center stage since the “Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs).” This programmable nuclease was first discovered by a Korean research team in 2013.
CRISPRs are used to arbitrarily modify plant or animal genomes as well as the human genome. Thus, CRISPRs are expected to be used to develop a cure for intractable diseases. However, there are also some concerns over its possible destruction of ecosystems and the ethical issue of the prospect of “designer babies.” With this, will CRISPRs, the programmable nuclease, act as a medicine or poison to human beings?






A Panacea for the World
To someone, CRISPRs have a meaning similar to a panacea, which can cure all machine in the world. In particular, life scientists well known as a relaxed posture say that CRISPRs “seem set to win the Nobel Prize” even referring to them as a “revolution.” The main question is “Why?”



● Revival of Extinct Animals

CRISPRs can be used to bring back extinct animals that disappeared thousands of years ago. Trials to revive mammoths have been in vain so far, and this is because of the damaged DNA. Professor George Church and his research team at Harvard Medical School announced that their mammoth revival process includes the insertion of the genetic characters of the mammoth, including a covering of long hair that makes it possible to survive in polar regions, into the DNA of current elephant skin cells. Their gene-editing technique is to make an induced pluripotent stem cell, or an iPSC, from the somatic cell of an elephant, and to insert mammoth genes into it.


● New Genetically Modified Organisms
Controversy over the harmful effects of genetically modified organisms (GMOs) is still ongoing. Most genetically modified organisms are made by artificially inserting transgenes into plants using a soil bacterium, “Agrobacterium.” Resulting in the insertion of hundreds of or thousands of transgenes, this process poses a safety issue. Jin-soo Kim, the director of the Center for Genome Engineering of IBS, has recently succeeded in plant transformation with the Cas9 RNA-guided engineered nuclease targeting a specific nucleotide sequence (within 10 sequences). This method can minimize the side effects of GMOs.


● Generating a Genetically Modified Mouse
It took one year or so to generate a genetically modified mouse before the advent of the CRISP mechanisms. This is because the existing genetically modified mice were made through a highly complicated process: modifying genes at the level of an embryonic stem cell and inserting the modified embryonic stem cell into the blastocyst before transplantation and verification. On the other hand, a mouse with a new character can simply be generated by inserting the Cas9 RNA-guided engineered nuclease into a fertilized egg. It takes six months to generate a genetically modified mouse.


● Extracorporeal Therapy to Fight AIDS and Cancer
Diseases can be treated in a manner that collects immunocytes from a patient whose genes are modified before being injected into the patient again. For instance, HIV attacks CD4 T-cells found on the surface of immune cells. If the zinc-finger nuclease is used to cause a genetic mutation in the gene encoding the CCR5 protein, the channel through which HIV invades, this generates resistance to HIV. A phase II clinical trial for this treatment is ongoing. CRISPRs can inactivate the CCR5 in a more complex manner. With this, CAR T-Cell immunotherapy is currently being developed. This therapy is to edit the immunological genome to recognize specific cancer cells before inserting the edited genome to attack cancer cells.




A Poison Threatening the Future of Society
CRISPRs cleave desired DNA like how scissors paper if a special enzyme is inserted into a cell. Despite this function, some are worried about this CRISPRs-based technique because of how it performs surgery as if editing the DNA of human beings, animals, and plants. Do you agree that CRISPRs will lead to a dyian society?


Anxiety and Concern about CRISPRs
Despite many advantages, the programmable nuclease CRISPRs have recently been in the middle of the controversy in terms of bioethics. This was triggered when it was revealed that Chinese researchers attempted to edit the genes of human eggs and embryos, not animal embryos or human adult cells. 
Dr. Junjiu Huang and his team at Shanghai University of Engineering Science announced the result of editing the genome of fertilized human egg using CRISPRs in April 2015. Also, they said they were waiting for the approval of Chinese authorities’ for research intended to genetically manipulate discarded human embryos. This team was reported to have manipulated an embryo that would develop into a living monkey using the gene editing technique. According to the analysis of the academic circle, this technique can be applied to human beings.

Many express their concerns on these experiments. Although the Chinese government prohibits embryonic genes from being edited, it fails to strictly control all gene editing activities. This triggers concerns on issues such as unauthorized stem cell therapy.
Of course, it is impossible to make a monster in a lab as seen in SF movies for now. We do not yet have the ability to modify the genome of a higher organism including human beings. Creating a Hulk, for example, can be compared to changing a car into a Transformer.



Golden Time to Begin Discussions

Benefits given by civilization and scientific development can serve as a double-edged sword to society and the Earth in general. Human beings have had many developments ranging from nuclear energy or biochemical weapons even to artificial intelligence for the purpose of improving the quality of life. However, the developed techniques can be a poison that may lead us to self-destruction, depending on the users and how these techniques are used. This also applies to CRISPRs. The destiny of our descendants completely depends on how discerning we will be in the use of the techniques.
CRISPR systems are being developed at a very fast pace; however, fortunately, we still have some time to hold discussions on the issues related to CRISPRs. The future of human beings and CRISPRs may be determined by how we will make use of this remaining time. The social consensus on how to use this formidable power has to come first. Globally noted researchers, including Dr. Jennifer Doudna, who discovered CRISPRs, had issued a statement intended to restrain from editing the human genome before the Chinese research team announced their lab results.
Knowing all these, wow about Korea? In the country, the genetic manipulation of human reproductive cells is banned pursuant to the Bioethics and Safety Act. However, public interest on this issue is imperceptible. The time to begin a discussion to prevent the thoughtless utilization of CRISPRs has come.