Rewriting the Blueprint
Gene editing for improved agriculture, healthcare, and beyond.
Since the 1950s, humans have been experimenting with ways to reimagine the genomes of organisms that affect the environment and our own lives. In the past few decades, scientists have made monumental discoveries both in mechanisms that can be used in the lab, and in nature, where other organisms can help revolutionize health care, agriculture, and overall biospheric health.
Genome editing has existed for countless years--truly even before the 1950s. Gene editing is essentially the term for more efficient and precise methods of selective breeding. From mating dogs with the most favorable traits to cross-breeding key crops, gene editing has existed for ages. The main purpose of these processes is simply to create a healthier, flourishing biosphere by eradicating diseases, curing disorders, and improving food supplies.
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How these methods have been used over the decades has seen tremendous changes: from age-old cross-breeding to traditional viral-vector gene insertions to CRISPR and TALENs systems. Modern genomic discoveries can be traced back to the U.S. with genome-pioneers like Watson and Crick, but have since expanded across the globe. Advancements have not only made modifications more instantaneous--changes can occur within a generation or two, rather than waiting for decades for a gene to propagate through a population--they have also made them more precise in being able to target exact genes down to the nucleotide sequence.
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Read more to explore the history of genome editing or click here to learn about its endless possibilities
Background
1950s
1950s: Rosalind Franklin’s X-Ray technologies allowed for DNA protein studying. (BC.1)
1953: James Watson & Francis Crick discovered the double-stranded structure of DNA which they labeled as a “double-helix,” resembling a “twisted ladder” (BC.1).
1958: Arthur Kornberg synthesized DNA via in-vitro processes by isolating DNA polymerase from bacterial cells. He went on to win a Nobel Prize for his achievement. (BC.1)
1962: Osamu Shimomura isolated the green fluorescent protein (GFP) in jellyfish which was later used to test for expression of target genes in specific cells. (BC.1)
1967: DNA ligases are discovered. These are enzymes used by cells during DNA replication to link Okazaki fragments in DNA strands by phosphate and deoxyribose groups. They are also used in “sticky end” ligation for the insertion of the desired gene into a vector (BC.1, BC.2).
1960s
1968: Werner Arber hypothesized the idea that bacteria contain both “restriction”--to cut foreign genetic information as a way to combat pathogenic infection--and “modification”--to DNA from splitting--enzymes. Restriction enzymes can be used in DNA ligation to create “sticky ends” (BC.1, BC.2).
1970: Hamilton Smith of John Hopkins University School of Medicine identified the restriction enzyme Hind III in the bacteria Haemophilus influenzae Rd. (BC.1)
1971: Paul Berg developed the “cut-and-splice” method which combined DNA from two different species. The “cut-and-splice” method involves using a restriction enzyme to unravel DNA into single strands. From there, geneticists add desired nitrogenous bases to manipulate the coding and seal with ligases. (BC.1, BC.3)
1970s
1972: Recombinant DNA (rDNA) was created. rDNA is DNA comprised of genetic material from multiple organisms. (BC.1)
1975: Paul Berg organizes the Asilomar Conference for scientists to form and reach consensuses on genetic engineering ethics. Joshua Lederberg of Stanford brings light to rDNA’s potential for disease treatment. (BC.1)
1975: George Kohler and Cesar Milstein merge plasmic cancer cells with antibody-producing B cells to increase the # of cells which revolutionized immunity treatments. (BC.1)
1981: Thomas Wagner of the Ohio University uses “DNA microinjection” to transfer rabbit genes into mice to result in the first transgenic animal DNA from a foreign organism is inserted into another species’ ova (BC.1, BC.3).
1982: Genentech develops synthetic, genetically engineered insulin for diabetics which was the solution to the increased demand for the drug as it was originally harvested from animals--by 1978, 23,500 animals would have had to been used. (BC.1)
1983: Polymerase Chain Reaction is discovered by Kary Mullis PCR is a technology which allows small fragments of DNA to be amplified for more efficient analysis (ex. in gel electrophoresis) PCR can be used to target specific gene locus sites, from there these genes can be used to modify other organisms. (BC.1, BC.4)
1985: Zinc Finger Nucleases are discovered. ZFNs target specific genes are combined with the restriction enzyme Fokl to create “genomic scissors” that cause a DNA strand to undergo cleavage. The target gene(s) are broken off; the host DNA can combine with a replacement segment to achieve the desired result. This is the first instance of “backwards” genetics which allows scientists to target exact genes--infinitely more efficient than “forward” genetics which is a matter of trial and guessing (BC.1).
1988: Bt corn, genetically modified with genes from Bacillus thuringiensis, was invented to increase crop yields with resistance to the tobacco mosaic virus. (BC.1)
1980s
Click the image to find out more about PCR!
1988-2003: The Human Genome Project is funded by the US to map out the human genome in 1988. The HGP finished chromosome 22 in 1999, and the genome in 2003. The project was used to help identify/study disease causes. (BC.1)
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Simply put, genome editing is exactly as it sounds: the alteration of genetic material, specifically DNA. These changes in the basic blueprint of life act to modify the organisms to have certain traits, whether it be for plants to be more nutritious, microbes to be non-pathogenic, insects to be disease-resistant, or a certain line of humans to be free of a crippling illness.
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The challenges for this biotechnological sector lie in the sheer modernity of the technologies--many discoveries and refinements still need to be made. Imaginations of scientists are truly endless but are limited to resources and ethics. Whether it be federal regulations or social disparities, morals and ethics stand in the way of countless experiments and inventions that gene editing can give rise to.
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1990s
1993: Francisco Mojica discovers the principle of CRISPR when studying bacteria with repeating segments of DNA. (BC.1)
1994: Calgene scientists genetically modify tomatoes (The "FLVR SVR") with a reverse gene sequence of the ripening polygalacturonase enzyme, however, it is unsuccessful on the market. (BC.1)
1996: Dolly the Sheep is the first animal to be successfully cloned. (BC.1)
2000s
2001: Glivec, a gene-targeting drug for chronic myelogenous leukemia (CML) is approved by the FDA. (BC.1)
2004: The UN approves biotech-modified crops as a world hunger solution. (BC.1)
2006: Dr. Shinya Yamanaka and his team at UCSF successfully reverted mice cells to stem cells as the first-ever induced pluripotent stem cells (iPSC) (BC.1)
2011: TALENs technology is discovered which provides an easier and more efficient method of cutting portions of a genome than ZFNs as they can locate and cut a single nucleotide rather than a set of 3. Although they are much larger and can be harder to use within organisms, they are still a significant breakthrough in genomic editing. (BC.1)
2010s
2014: Kevin Esvelt suggests the possibility of gene drives to manipulate natural inheritance patterns to skew populations toward organisms with favored traits. This acts as a possibility to create malaria-resistant mosquitoes. (BC.1)
2012: Jennifer Doudna and Emmanuelle Charpentier are able to clarify the process of CRISPR as a genetic engineering tool for healthcare, agriculture, etc. (BC.1)
2015: Junjiu Huang at the Sun Yat-Sen University in Guangzhou is the first to edit a human embryo to fix a gene that caused blood disease. Viewed as unethical, his project was rejected. (BC.1)
2015: AquaBounty’s GMO salmon hits Canadian markets as the first GMO animals to be sold for human consumption. (BC.1)
2018: Vertex Pharmaceuticals & CRISPR Therapeutics were approved to use CRISPR technologies to treat B-thalassemia in humans. If successful, these treatments can also be applied to sickle cell anemia. (BC.1)
