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The CRISPR controversy: is it a GENE-ious phenomenon or catastrophic disaster?

There's no denying that the 21st century is a unique time period in our lifetime where genetic engineering has taken on a whole new meaning.

The name 'He Jiankui' was one that few had heard of—that was until a global news frenzy erupted and struck last week where the young Chinese researcher and associate professor at Southern University of Science and Technology in Shenzhen had made his first step into fame by claiming that he had made the first genetically engineered set of twin babies (Nana and Lulu) utilising CRISPR technology. Since the announcement, many people from the scientific community have stated their opinions regarding the scientific experiment—NIH Director, Francis Collins, stated that the experiment was "profoundly disturbing", and Julian Savulescu, a bioethicist, called Mr. Jiankui's work a "monstrosity". Southern University of Science and Technology has denounced Mr. Jiankui's work and a statement was issued calling the experiment a “serious violation of academic ethics and standards."

It is important to note that Mr. Jiankui's work has not been peer-reviewed and following the outcry regarding the bioethics, safety, and lack of self-regulation surrounding this experiment, the work has now been stopped.

So what exactly is a CRISPR baby?

The basis of the experiment is to produce designer babies by manipulating genetics. CRISPR-Cas9 is an acronym that stands for Clustered Regularly Interspaced Short Palindromic Repeats, it involves using a set of DNA sequences that specifically target and modify components of DNA strands. Mr. Jiankui's implemented this technology in an effort to provide a treatment option for protection against the HIV virus.

According to the Chinese researcher, his experiment commenced with the intent of enlisting seven couples—where each couple had one HIV positive male and one HIV negative female—who were in the process of going through in vitro fertilisation and had used this as a guise of developing an AIDS vaccine. The experiment involved modifying embryos in an attempt to incorporate a natural resistance to the HIV virus that is encoded in the genomes involved. This was done by utilising CRISPR to deactivate a single gene called CCR5 in the seven embryos. Six of these embryos were then implanted into their corresponding mothers.

CCR5 is a gene that the HIV virus is able to utilise as an entry point to infiltrate and attack human cells. The goal is essentially to lock the virus out and this can be approached in a plethora of mechanisms for e.g. deactivating the CCR5 and introducing immune cells of HIV patient back into the body. One area of contention regarding this experiment revolves around the topic of need. Paula Cannon, from the University of Southern California, has eluded to the fact that the genetic modification technique employed in this experiment seemed unreasonable and unnecessary as a treatment option for HIV. If HIV treatment was under-developed—or if there were absolutely no clinical treatment options for those suffering from HIV—then the narrative may have turned out to be rather different than to what it is now. However, antiviral drugs are readily available for HIV sufferers and are used as a prophylactic measure to help keep symptoms at bay to allow the individual to carry on living a normal and healthy life. The use of genetic editing for HIV treatment has been seen as unnecessary.

Dr. Paula Cannon, a Distinguished Professor in the Department of Molecular Microbiology & Immunology at the University of Southern California’s Keck School of Medicine, asked “was this a reasonable thing to do? I would say emphatically no. The idea that being born HIV-susceptible, which is what the vast majority of humans are, is somehow a disease state that requires the extraordinary intervention of gene editing blows my mind. I feel like he’s appropriating this potentially valuable therapy as a shortcut to doing something in the sphere of gene editing. He’s either very naive or very cynical.”

The ethics of this experiment are being called into question.

This experiment has been seen as a concerning example of what may be developed in the future. The safety parameters regarding such experiments have been scrutinised as it appears that the level of precision that is needed to safely perform such experiments haven't been verified for use in human embryos. It has been reported that Mr. Jianku had also deliberately kept this experiment secret and the laboratory web page chronicling the details have allegedly disappeared.

Mr. Jianku, a Stanford trained associate professor at the Southern University of Science and Technology in Shenzhen China, had published a paper in the CRISPR journal where he outlines the various ethical principles regarding this sector of genetic manipulation in the scientific community. Interestingly enough, a lot of the ethical principles stated were then violated upon the genetic modification of baby Luna and baby Nana.

CRISPR is not new to the scientific community. In fact, CRISPR has been used in an attempt to treat cancers and various diseases such as malaria and early-onset Alzheimers. The root of the uproar that arose last week concerns the issue of using embryos to perform such genetic modifications.

When genetically modifying an embryo, it doesn't just affect the cells that you are trying to change, every single cell belonging to that embryo will experience that genetic modification.

The cells of the twins eggs will be transformed, meaning that as these infants grow and develop, these changes will be experienced by their offspring and succeeding generations. This type of scientific work involves close monitoring and evaluation to follow-up any unexpected consequences and effects of such genetic editing techniques. For example, understanding and analysing whether the CCR5 was edited properly, any off-target effects that may be experienced as a result and the effects of aging on the newly edited CRISPR genes. Essentially the curiosity surrounding this experiment lies in the details—many of which are yet to be known.

What consequences may result from this experiment?
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Here are the pros and cons of using CRISPR/Cas9 in human embryos. We could cure genetic disorders before the baby is even born! This could possibly reduce the use of other expensive technologies and is an extremely accurate method! Although this technology has the potential for amazing things, there are some ethical issues to consider. Human embryos obviously can’t give their consent on this treatment. It is possible for them to grow up and decide they don’t agree with gene therapy as treatment. Also, if genes can be altered to treat genetic disorders who’s to say we can’t also decide what our babies will look like? Or what if we find a gene linked to intelligence or athleticism, can we ethically use gene therapy to enhance those genes? Another thing we want to consider is the cost of technology and the availability for all people to use no matter their social standing. What do you think: do the pros outweigh the cons? #crisprcas9 #genetics #science #humans #embryos #traits #geneticdisorder #genetherapy #DNA #crisprbaby #ethics #prosandcons #biology

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Only time will tell us what the possible impending consequences of CRISPR technology could be—especially when it comes to analysing applications of this technology to in-vitro fertilisation. Incidentally, this is not the first time CCR5 genes have been employed in genetic research studies. It has been shown that suppressing the CCR5 gene can possibly lead to an increased risk of contracting other illnesses. Two published studies regarding CCR5 have shown that there are scenarios were some cells will show a poor response to genetic modifications and have an increased risk of developing cancer.

CRISPR technology is one that has not yet been peer-reviewed or analysed to a sufficient level so that the benefit to risk ratio can be established and where the clinical efficacy and safety parameters can be clearly outlined. This, along with the ethical and moral parameters, are factors that are fueling the uproar from the scientific community. Some have called this experiment audacious while others have stated that Mr. Jiankui's work may be an innovative, pioneering start to the future implementation of CRISPR technology—I think it's safe to say that this case embodies an important landmark in the world of genetics.