Wednesday, November 15, 2017

Modifying the Genome: What is Genetic Engineering?










What is Genetic Engineering?

The genome is our genetic code and is made of all the DNA that determines how our bodies are put together and maintained (learn more about genomes). The genome is like an instruction manual for an organism, and the DNA is like the script from beginning to end. If you were able to change the DNA script in an organism's genome, then you would be able to alter that organism's characteristics or function.

Genetic engineering or genetic modification "is the process of altering the DNA in an organism's genome. . . Genetic engineering is used by scientists to enhance or modify the characteristics of an individual organism."[1]

Technically speaking, humans have been modifying the genomes of organisms for thousands of years through methods like selective breeding.[2] In selective breeding, if a desirable characteristic appears in a plant or animal, a farmer can try to breed animals or select and plant seeds with the desired trait to try and grow that trait among their herds or crops. If the farmer keeps mating organisms with the desired trait, the number of organisms with the desired trait will grow, eventually creating whole new varieties of crops or herds.[2]

Evolution of corn [4]
Corn as we know it today—with its rows of bright yellow, juicy kernels—is the result of selective breeding. Archaeologists have traced corn's ancestry to teosinte, a tough type of grass that bears little resemblance to corn.[3] When these plants would produce new, desirable characteristics through a mutation (like larger plants or tastier kernels) farmers would choose seeds from the preferred plants to try and produce crops with the same desired traits. This artificial evolution of crops over thousands of years is what eventually lead to a type of corn that is incredibly different from how it used to be.

But when we hear "genetic engineering," or "genetically modified organisms," or "genome editing," we generally don't think of thousands of years of selective breeding. What separates these methods from selective breeding?

The World Health Organization defines a genetically modified organism or GMO as "organisms (i.e. plants, animals or microorganisms) in which the genetic material (DNA) has been altered in a way that does not occur naturally by mating and/or natural recombination."[5]

These genetic engineering methods can involve "changing one base pair [a single "rung" on DNA's ladder-shape], deleting a whole region of DNA, or introducing an additional copy of a gene. It may also mean extracting DNA from another organism's genome and combining it with the DNA of that individual.[1] There are different techniques for genetically modifying organisms. Some are older technologies dating back to the 1970s, and some are new, cutting-edge techniques.[7]

A Few Examples of Genetic Engineering Methods. . .


Agrobacterium
Agrobacterium is a bacteria that infects plants. When it infects a plant, it inserts and integrates some of its own DNA into the DNA of the host plant's cells.[2][7] In the early 1980s, scientists developed Agrobacterium strains without the disease-causing genes that remained able to "infect" the plant and transfer DNA.[2] By replacing the disease-causing DNA with other DNA, scientists could use Agrobacterium to deliver DNA of their choosing into the plant to become part of its own DNA.
Gene editing methods in plants [6]

The "gene gun"

Scientists in 1987 discovered that DNA could be delivered to plant cells by "shooting" seeds or plant tissue with gold or tungsten micro-particles coated in the desired DNA.[2][7] The DNA, after injection, would integrate with the plant's DNA.

These methods of genetic engineering introduce DNA to an organism and allow it to integrate with the organism's DNA. When DNA is added or changed, a new trait may then develop in an organism. Other methods target and edit specific pieces of DNA. These methods are referred to as genome or gene editing, and are defined as "the use of biotechnological techniques to make changes to specific DNA sequences in the genome of a living organism."[8[Italics added.]

Zinc Finger Nucleases (ZFNs)
ZFNs are a type of genome editing technology referred to as engineered nucleases.[9][10] Engineered nucleases have two parts: a part that targets and binds to a specific part of the DNA, and a nuclease (enzymepart to "cut" the DNA.[10] The "binding" part of ZFNs are "zinc finger" proteins. ZFNs were effectively developed in 2005 and are a method of targeting and cutting a specific piece of DNA in the genome.[9] The "cutting" part of the ZFN is a FokI enzyme, and the cut occurs when the two FokI come together across the DNA strand.[11]
Image credit: Genome Research Limited [10]

Transcription activator-like effector nucleases (TALENs)
TALENs are also a type of engineered nucleases, effectively developed in 2010.[9] The binding part of TALENs are proteins called "transcription activator-like effectors" that come from bacteria that infect plants.[10] The cutting part of TALENs, like ZFNs, are a FokI nuclease and cut DNA in an identical manner.[11]

Image Credit: Genome Research Limited [10]
TALENs are able to be engineered to bind to the correct part of DNA more easily than ZFNs.[10] However, TALENs still don't always bring about the desired change, and the nucleases can be difficult to make.[10]

Engineered nucleases produce a "double strand" break in the DNA. The cell will repair the DNA strand either by rejoining the broken ends (deleting the DNA section that was cut from the sequence), or by deleting and then inserting a new piece of DNA to fill the gap (adding a DNA section, usually chosen by the scientist, to the sequence).[10][11]

CRISPR-Cas9
"CRISPR" stands for "clustered regularly interspaced short palindromic repeats" and is a type of immune system found in bacteria that protects them against viruses.[12] Cas9 is a protein (Cas9 stands for "CRISPR-associated protein 9) and cuts invasive viral DNA into pieces to protect the cell.[12]

In 2012 it was discovered that this system could be used as a genome editing technology.[12] CRISPR consists of an RNA molecule that is able to seek out DNA with a matching sequence. (RNA is a single-stranded molecule that is almost identical to DNA.)[13] It is able to search through all DNA in the cell and bind to the specific DNA bases that match its own sequence.[11][12] Cas9 is the part of the system that then cuts the DNA targeted by the RNA molecule.[11][12]

This system is "programmable," and scientists discovered that they could program CRISPR-Cas9 to "seek out" and then "cut" specific pieces of DNA that they wanted to target.

CRISPR-Cas9 is regarded as a groundbreaking genome editing technology, because prior methods were considered either too inefficient or too difficult for scientists to frequently use them in their laboratories.[12] CRISPR-Cas9 is currently considered the most inexpensive and efficient method of genome editing today.[11]



Results of Genetic Engineering

There are many crops grown today that have been genetically modified to have certain traits. According to the World Health Organization, the vast majority of genetically modified crops are modified to have one of three traits: "resistance to insect damage; resistance to viral infections; and tolerance towards certain herbicides."[5] Some crops include genetically modified corn, soybeans, cotton, alfalfa, and canola.[14]

There are fewer examples of genetically modified animals that are on the market. For human consumption, a variety of genetically modified salmon was approved for sale in the United States (2015) and in Canada (2016) (but has yet to officially reach the market in the U.S.).[15] As pets, a zebra fish genetically modified to glow in the dark was permitted for sale in the United States in 2003.[16] For laboratory experiments, many genetically modified rats and mice are used within labs around the world.[16]

There are even fewer examples of human genetic engineering that seek to make permanent, inheritable changes to a human genome. The first-ever genome editing experiment to alter a human embryo took place in China in 2015.[17] Most experiments that have used genome editing techniques on human DNA performed the experiments on early embryos, which were later destroyed after the experiment ended.[17] Genome editing on human DNA is tightly regulated around the world, and is even criminalized in some countries. The United Nations has even called for a world-wide moratorium on editing human DNA until ethical and safety issues can be resolved.[18]


Public Attitudes towards GMOs

Genetically modified organisms continue to provoke concerns from people around the world. Some people believe genetically modified crops are not safe for human consumption, or are less healthy than "natural" foods. Some people believe that releasing genetically modified organisms into the environment could harm ecosystems. Some also claim that the potential to genetically modify animals or humans violates nature and could have serious implications for the future of the human race and society as we know it.

On the opposing side, many argue that most applications of genome editing are safe, can benefit humanity and the environment, and can be prudently implemented to have a positive impact on the future. The questions created here are worth exploring, and I hope to touch on some of them in later blog posts!

 Have anything to add? Additional sources, helpful and relevant resources, and professional insights are welcome! Share in the comments below.


SOURCES

[1] yourgenome. (c2017). What is Genetic Engineering? yourgenome. [Online]. [Accessed 15 November 2017]. Available from: https://www.yourgenome.org/facts/what-is-genetic-engineering.

[2] National Research Council (US) Committee on Identifying and Assessing Unintended Effects of Genetically Engineered Foods on Human Health. (2004). Methods and Mechanisms for Genetic Manipulation of Plants, Animals, and Microorganisms. In: Safety of Genetically Engineered Foods: Approaches to Assessing Unintended Health Effects. Washington (DC): National Academies Press (US).  Available from: https://www.ncbi.nlm.nih.gov/books/NBK215771/

[3] Carroll, SB. (2010). Tracking the Ancestry of Corn back 9,000 Years. The New York Times. [Online]. May 24. [Accessed 02 November 2017]. Available from: http://www.nytimes.com/2010/05/25/science/25creature.html.

[4] Photo credit: © Robert S. Peabody Museum of Archaeology, Phillips Academy, Andover, Massachusetts. All Rights Reserved. {Accessed 02 November 2017]. Available from: http://learn.genetics.utah.edu/content/selection/corn/.

[5] World Health Organization. (2014). Frequently Asked Questions on Genetically Modified Foods. [Online]. [Accessed 02 November 2017]. Available from: http://www.who.int/foodsafety/areas_work/food-technology/faq-genetically-modified-food/en/.

[6] Powell, C. (2015). How to Make a GMO. Harvard University: The Graduate School of Arts and Sciences. [Online]. Available from: http://sitn.hms.harvard.edu/flash/2015/how-to-make-a-gmo/.

[7] Nuffield Council on Bioethics. (1999). The Scientific Basis of Genetic Modification. In: Genetically Modified Crops: The Ethical and Social Issues, pp. 22-23. [Online]. [Accessed 02 November 2017]. Available from: http://nuffieldbioethics.org/report/gm-crops-2/chapter-downloads/.

[8] Merriam Webster. [Online]. s.v. Gene Editing. [Accessed 02 November 2017]. Available from: https://www.merriam-webster.com/dictionary/gene%2Bediting.

[9] Nuffield Council on Bioethics. (2016). Genome Editing. In: Genome Editing: An Ethical Review. London: Nuffield Council on Bioethics, p. 8. [Online]. [Accessed 02 November 2017]. Available from: http://nuffieldbioethics.org/wp-content/uploads/Genome-editing-an-ethical-review.pdf.

[10] Nature Video. (2011). Method of the Year 2011: Gene-editing Nucleases. [Online]. [Accessed 02 November 2017]. Available from: https://www.youtube.com/watch?v=zDkUFzZoQAs.

[11] yourgenome. (c2017). What is Genome Editing? yourgenome. [Online]. [Accessed 02 November 2017]. Available from: http://www.yourgenome.org/facts/what-is-genome-editing.

[12] Doudna, J. 2015. How CRISPR Lets Us Edit Our DNA. TEDGlobal, September 2015, London. [Online]. [Accessed 02 November 2017]. Available from: https://www.ted.com/talks/jennifer_doudna_we_can_now_edit_our_dna_but_let_s_do_it_wisely#t-48530.

[13] Nature Education. (c2014). Ribonucleic Acid/RNA. Scitable. [Online]. [Accessed 02 November 2017]. Available from: https://www.nature.com/scitable/definition/ribonucleic-acid-rna-45.

[14] Johnson, D. and O'Connor, S. (2015). These Charts Show Every Genetically Modified Food People Already Eat in the U.S. Time. [Online]. [Accessed 03 November 2017]. Available from: http://time.com/3840073/gmo-food-charts/.

[15] Gallegos, J. (2017). GMO Salmon Caught in U.S. Regulatory Net, but Canadians have Eaten 5 Tons. Washington Post. [Online]. [Accessed 03 November 2017]. Available from: https://www.washingtonpost.com/news/speaking-of-science/wp/2017/08/04/gmo-salmon-caught-in-u-s-regulatory-net-but-canadians-have-eaten-5-tons/?utm_term=.c42f83a8c469.

[16] U.S. Food and Drug Administration. (2015). Consumer Q&A. U.S. Food and Drug Administration. [Online] [Accessed 03 November 2017]. Available from: https://www.fda.gov/AnimalVeterinary/DevelopmentApprovalProcess/GeneticEngineering/GeneticallyEngineeredAnimals/ucm113672.htm.

[17] Spicer, C. (2017). US Lab May Have Edited Human Embryos for First Time. BioNews. [Online]. [Accessed 15 November, 2017]. Available from: http://www.bionews.org.uk/page_866686.asp.

[18] International Bioethics Committee. (2015). Report of the IBC on Updating Its Reflection on the Human Genome and Human Rights. UNESCO. [Online]. [Accessed 15 November, 2017]. Available from: http://unesdoc.unesco.org/images/0023/002332/233258E.pdf .

No comments:

Post a Comment