Tuesday, October 6, 2015

Should the New CRISPR Technique be Approved for Use?

Picture by: Duncan Hull
Recently geneticists have come up with a new piece of bioengineering technology known as CRISPR. CRISPR is an acronym for clustered regularly interspaced short palindromic repeats and has the ability to edit genes in a quick and efficient way that has yet to be seen so far in the genetic engineering field. There has been a lot of hype built up by the new CRISPR method. James Wilson, a medical geneticist at UPenn says, “It’s just really spectacular” (Ledford). This technology has already been used to engineer genomes of over twelve species (Oye). It is still in its newer stages of development and has the potential to alter the DNA of species beyond the usual mice and fruit flies that are chosen for experimentation (Ledford). Though CRISPR has such great potential, it is still in its developmental stages, which means it also has the potential to be very dangerous. The use of the CRISPR-Cas9 method should be indefinitely halted until the time comes where the scientific community can trust that it is not dangerous for human beings or ecosystems.

CRISPR uses a Cas9 enzyme and a protein to cut DNA at the specific base code it is programmed for. By description, CRISPR is the messiah of the genetic engineering field. It far surpasses the previous methods of genome editing in cost, efficiency, and precision. It costs roughly $30 to buy the RNA fragment that makes this technique successful which is notably less than all other of the other genetic engineering methods that have been used so far (Ledford). An article written for the Proceedings of the National Academy of Sciences states that CRISPR, “offers simplicity, flexibility, and precision in gene targeting,” that requires little training (Webber). The CRISPR technology is certainly exciting and it is understandable that the genetic engineering field is being turned upside down by it.

Malaria bacteria
Picture by: NIAID
This technology has the potential to do great things. Two of these include eradicating malaria bacteria from mosquito-vectors and removing invasive species that are currently damaging ecosystems. Malaria kills 650,000 people per year and this count does not include the many other diseases transmitted through insect vectors (Esvelt). If the gene drive is successful, CRISPR could be a part of removing diseases that have inflicted immense suffering on human beings (Esvelt). Invasive species have become a huge ecological and economic problem for many nations around the world. In the United States, invasive species account for $42 billion in damages (Esvelt).

Yes, there is a great, currently untapped, potential with this new technology, but it is also flawed. Many scientists are of the opinion that CRISPR still has a long way to go before it can be ready for effective, safe use. James Haber, a microbiologist at Brandeis University says, “These enzymes will cut in places, other than the places you have designed them to cut, and that has a lot of implications” (Ledford). Accidentally damaging a nontarget gene has the potential to damage the entire species. This altering of genes is very powerful and should be handled prudently.

One of the big dangers of cutting the wrong gene is creating cancerous cells. Keith Young from the Massachusetts General Hospital in Boston describes mutation frequencies when these accidental, off-target cuts are made in DNA strands. They range from 0.1 to 60 percent mutation frequency. Even lower mutation frequencies can create catastrophic outcomes for individuals and later populations through gene drives, the movement of altered genetic material throughout generations. CRISPR is said to be very precise, but precise is not enough when the possibility of cancer is on the table. (Ledford)

If this CRISPR method has the ability to remove disease and alter entire genomes, even possibly create malignant, cancerous cells, it may also have the ability to be used as a weapon. Human beings have dreamed up new forms of biological warfare since 600 BC and have continued to use it throughout all of history(Riedel). If mosquitos can be made to no longer carry the dreaded malaria bacteria, other insects can be altered to carry more fearsome diseases as well.

In the recent past, policymakers have considered moving toward regulating the CRISPR method, but at the time it was not something that was believed to be urgent. Less than one year later the CRISPR technology has spread throughout the genetics community and policymakers are a step behind. (“Driving Test”)

In the past, unregulated scientific solutions have spelled disaster. The birth of the modern FDA stems from the past catastrophe of thalidomide babies (“Thalidomide”). Though thalidomide is a drug and CRISPR alters genes, the CRISPR technology would be considered a toxin or a veterinary medicine in terms of how it is regulated (Oye). Thalidomide is a drug that was administered to pregnant women to help them sleep, but the aftermath of using this drug was child deformity. Children were being born with shrunken or absent appendages (“Thalidomide”). If this drug had been thoroughly tested and officially regulated it would not have been able to damage the lives of so many people worldwide.

Children with deformities caused Thalidomide taken by their mothers during pregnancy
Picture by: Luciana Christante

Unfortunately, the FDA-that was so changed by the thalidomide babies of the 1950s and 1960s-has not been doing a good job fulfilling its duties. Recently the FDA has been working either too fast or too slow (“FDA vulnerability revealed”). Certain cases are being pushed forward because of political agenda while other, more important ones sit on the backburner. The FDA was recently pressured into approving a drug that helps increase a woman’s libido. This drug had very little effect at all in trials and had quite the list of risks accompanying it, nonetheless the women supporters coerced the FDA into approving a drug that has, “a poorly understood reaction with alcohol.” (“FDA vulnerability revealed”) If a national organization responds this way to the arm-twisting of a group of protestors, they are not to be trusted with the regulation of something as important as changing the DNA of entire species. If proper regulation is not a method that can be trusted to keep CRISPR in check, it should not be pursued any further.

The Proceedings of the National Academy of Sciences published their opinion that, “without a regulatory framework that provides a mechanism to work with these issues with clarity and transparency for the CRISPR-Cas9 gene drive, this putative silver bullet technology could become a global conservation threat” (Webber). Author Kenneth Oye and his peers write,

“For emerging technologies that affect the global commons, concepts and applications
should be published in advance of construction, testing, and release. This lead time
enables public discussion of environmental and security concerns, research into areas of
uncertainty, and development and testing of safety features. It allows adaptation of
regulations and conventions in light of emerging information on benefits, risks, and
policy gaps. Most important, lead time will allow for broadly inclusive and well-informed
public discussion to determine if, when, and how gene drives should be used” (Oye). The scientific community believes that it is important to fully understand this new CRISPR technique before it should be allowed for use. Uncertain technology should not be unchecked by regulation.

Picture by: Gian Luigi Perrella
Heidi Ledford, author of “CRISPR-the disruptor,” argues that while it may not be fully understood at this point, CRISPR is an amazing, new technology that will break barriers in the genetic field. Ledford cites ideas from multiple authors to illustrate her thoughts on CRISPR (Ledford). She quotes Micky Eubanks who says, “...when you give it more thought and weigh it against the environmental changes that we have already made and continue to make, it would be a drop in the ocean” (Ledford). Something that allows human beings to bring about the eradication of species is not something to be considered ‘a drop in the ocean’ as Eubanks calls it. One of these environmental changes she alludes to is climate change, which is not a positive environmental alteration that should be used as a reason to continue messing up the planet. Drops in the ocean have ripple effects and until it can be determined that the outcome of this technology will be a positive one, it is unsafe to move forward with it. Ledford herself says, “This issue is not black and white” (Ledford). While what she says is true, there is a clear cut solution to it and that is to halt the application of the CRISPR technology.

The CRISPR-Cas9 technology does have some potentially amazing benefits and it is an incredible scientific feat. That being said it is too early to say that it will be able to rid insect vectors of disease and safely alter genes the way that many scientists believe it will. It is an impressive technology but it is not proven to be safe and at this point in its development CRISPR is certainly not ready to be used outside of anything but a contained laboratory. If it is never proven to be safe, it should never be used in nature or in human beings.


References

“Driving Test: ‘Gene drive’ techniques have the potential to alter whole populations. Regulators
must catch up.” Nature 524.7563. 4 Aug. 2015. Print.

Esvelt, Kevin M., Andrea L. Smidler, Flaminia Catteruccia, and George M. Church. “Concerning
RNA-guided gene drives for the alteration of wild populations.” eLife. 17 Jul. 2014. Print.

"FDA vulnerability revealed." Nature 524.7566. Nature Publishing Group, 26 Aug. 2015. Web.
03 Oct. 2015.
Ledford, Heidi. “CRISPR, the disruptor.” Nature 522.7554. 3 Jul. 2015. Print.

Oye, Kenneth A., et al. “Regulating Gene Drives.” Science 345.6197 (8 Aug. 2014): 626-628.
Print.

Riedel, Stefan. “Biological warfare and bioterrorism: a historical review.” NCBI 17(4). Oct.
2004. Print.

"Thalidomide." Science Museum. Brought to Life: Exploring the History of Medicine. N.p., n.d.
Web. 03 Oct. 2015.

Webber, Bruce L, Raghu, S., and Edwards, Owain R. “Opinion: Is CRISPR-based gene drive a
biocontrol silver bullet or global conservation threat?” PNAS 112.34. N.d. Print.




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