Friday, September 29, 2017

CRISPR: a case for revision



            It started out as kids; along for the ride as our patents watched science fiction thrillers. The writers and directors would look into the future and ‘wow’ audiences with what they thought it would hold. Star Trek gave us teleportation, Back to the Future gave us time travel, Blade Runner let us look into a world of replicants (artificial intelligence), and many more. What all of these movies had in common though are dreams. As adults now, we have watched some of those dreams materialize, and we’ve watched others merely fade away.

            Accurate and precise gene editing was once one of those dreams. CRISPR was once one of those dreams! Now it is anything but that, and as with every great discovery there is excitement, but there are also many ethical questions that accompany the use of such a tool.

            Clustered Regularly Interspaced Short Palindromic Repeats, more commonly known as CRISPR or CRISPR-Cas9, (once part of a E. Coli defense system) are RNA-guided engineered nucleases. That’s a lot to take in from one definition so I will try to explain it a little better. CRISPR is composed of two subunits: the first subunit is the Cas9 nuclease, which acts like scissors to cut the DNA, and second subunit is a small RNA molecule that can precisely and accurately direct Cas9 to where it is supposed to cut the DNA. Once cut, the new DNA or gene can be incorporated by the repair enzymes. Scientist were able to take advantage of what was originally a defensive mechanism and turn it into an offensive mechanism. (1)

            Wait! Haven’t scientist been able to edit genes for quite some time? The answer is yes, but to a large extent we’ve used applications that are inferior to CRISPR (since its discovery). Targeting the genome before CRISPR was mainly done through engineering DNA nucleases. Two examples of this would be (the oldest and most studied) Zinc Finger Nucleases (ZFNs), and Transcription Activation-Like Effector Nucleases (TALENs). Although both ZFNs and TALENs have been essential for research, their shortcomings for gene therapeutics are made aware by the advantages of CRISPR. ZFNs and TALENs can be expensive, they can be very hard to make, they can be toxic, and they often times (ZFN more so that TALEN) have poor targeting. (2)

            Ben Parker once said, “With great power comes great responsibility” and that is very true in the world of science whenever a new tool like CRISPR is discovered.

            The ability to edit a genome is amazing! It’s exciting, and above all else it has the real power to effect lives. Diseases like malaria, that shake entire continents could be eradicated. HIV, Huntington’s Disease, and any other genetic disease could be a thing of the past. Isn’t that everyone’s goal when choosing a career in healthcare? To help patients, or develop ways to help patients?

            The power to effect change at all is intoxicating, but can sometimes be detrimental. When looking at CRISPR, the ethical questions raised by it are not different from the same ones raised about gene editing/therapy. Most of the ethical problems associated with CRISPR are from a misuse of the tool, but some are purely associated to using the tool at all.
            The first question that comes to mind is for me is the regulation of CRISPR not only in terms of when to use it, but also how it is consumed. I hate to bring up the past, but in a way CRISPR can be seen as a form of positive eugenics. Especially if strict regulations are not placed on it. Theoretically parents in the future could pick and choose how their babies would be edited, leading to “designer” babies. If CRISPR isn’t available to all, or can only be used by those with the resources then that could lead to selective advantages for some (this is all highly hypothetical though). It will take a lot of work from organizations around the world to not only work together for uniform regulation, but to also enforce these regulations across borders. (3)

Also, are the benefits of CRISPR worth the risk? Anytime you work with editing the genome there is a chance that you don’t get your desired effect. There are off-target effects that can be deleterious too if CRISPR is used. If you can cure one disease, but that cure leads to other problems is it worth it? (4)

All of that aside, CRISPR was, is, and will continue to be a discovery for the ages. The very fact that we can have these conversations now is amazing. Elon Musk recently said in an interview with Neil deGrasse Tyson on StarTalk Radio that there were five things he thought would change the future of humanity. They are the internet, sustainable energy, space exploration, artificial intelligence, and rewriting human genetics. All of those are honorable quest, but as future healthcare professionals rewriting the human genome is right up our alley and CRISPR just might be the tool that helps us reach that goal. (5)

             
          


Citations:
1.     Ledford H. CRISPR: gene editing is just the beginning. Nature. 531, 156-159. 10 March 2016.
2.     Mestrovic T. How Does CRISPR Compare to Other Gene-Editing Techniques? News Medical Life Sciences. 13 January 2016.
3.     Mulvilhill J. et al. Ethical issues of CRISPR technology and gene editing through the lens of solidarity. British Medical Bulletin, Volume 122, Issue 1, 1 June 2017, Pages 17-29.
4.     Rodriguez E (2016). Ethical Issues in Genome Editing using Crispr/Cas9 System. J Clin Res Bioeth 7:266. doi:10.4172/2155-9627.1000266
5.     Zimmer C. Breakthrough DNA editing born of bacteria. Quanta Magazine 2015. https://www.quantamagazine.org/20150206-crispr-dna-editor-bacteria/
6.     Welsh J. 5 things Elon Musk believed would change the future of humanity in 1995. Science. Business Insider. 6 April 2015.

 By Christopher Adams, Master's of Medical Science Student, University of Kentucky
           


8 comments:

  1. Really interesting post, I like that you brought up the ethical implications of this kind of work. There is definitely a lot to consider with this kind of research. It is a risky business working with the human genome.

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  2. Very interesting and controversial topic circulating in the science world today! In one article released by MIT, the author cited the U.S. intelligence community as calling CRISPR a "potential weapon of mass destruction.” I'm curious to see how these gene editing methods can be seen as a destructive offensive move rather than a constructive offensive move. I am also curious to hear what evolutionary biologists think about gene editing to eradicate problems commonly found within our genome. I'd like to see what these biologists would have to say, or what studies could possibly provide insight into, about how this form of man-induced artificial selection could compare with natural selection itself.

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  3. CRISPR has been a controversial topic in past few years specially in the ethical terms that it can be used to make baby with superpower (kind of!). Although I agree that its potentials for unethical uses are possible, with proper regulation that can be avoided. Its like We have tons of nuclear weapons that can be used to destroy the whole planet multiple times, but that doesn't happens very often right?

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  4. You are raising some important and necessary questions about the use of CRISPR. I do believe that this new tool needs to be heavily regulated. As you mentioned CRISPR provides the mean to edit the human genome and who knows how that could impact the world. On one hand it is amazing to have a tool researchers can use to create cell and animal models that can accelerate research into diseases such as cancer or mental illness. However we have to acknowledge those who will use CRISPR for reasons other than improving the world's quality of life. New policies on the use of CRISPR should be implemented to prevent scientists from misusing such tool.

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  5. CRISPR has been one of the most efficient forms of gene editing. But, as stated it has become subject to ethical controversy. It has been said changing a gene to be resistant to a particular disease would genetically modify who a person becomes. It is my opinion that it can be properly regulated and pose as an effective way to end fatal diseases.

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  6. I'm very curious to see where this entire field goes. As students we constantly hear about CRISPR, but I feel as if the general public is still unaware, and how they may respond to such a product? I think gene editing could be extremely beneficial in people whose diseases are advanced and difficult to treat, so I'm interested to see all the future advancements and restrictions placed on this form of gene editing.

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  7. I think this a very interesting topic you choose, you raised very important questions in regards to the use of CRISPR. I am curious what types of regulations are in place now or what types of regulations are they considering for this gene editing tool. I am also curious how it would be used to cure certain diseases. However, I do think CRISPR will be a very helpful tool in the future if properly regulated and available to everyone.

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  8. To manipulate the human genome to better the lives of patients is an astonishing discovery and something that would have been impossible to think about by early scientists. The advances made in the field of genetics and micro biology have led to incredible discovers and I can not wait for more !!

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