Genome editing

Genome editing, which is also called gene editing, is a group of processes and technologies that allow scientists to change genes and DNA inside living organisms. Scientists use gene editing to add, remove, or change genes and parts of genes. They have developed several ways to do this and use gene editing in many applications. Medical research is one of the most important and widely publicized applications for gene editing, but scientists have also used gene editing in research dealing with plants, food, and animals. Gene editing is controversial, and scientists who take part in it have ethical questions to consider. For example, scientists will one day have the ability to create embryos with certain genetic traits, such as a specific eye color and a low risk of disease. Although some of these aspects are seen as positive developments, the possibility exists that wealthy and well-connected people will be able to create offspring with genetic traits that most people consider to be superior while less wealthy people will continue to naturally pass on genetic information to their offspring.

Background

A gene is the basic unit of heredity. Genes are made up of deoxyribonucleic acid (DNA) and are similar to the blueprints of the body. Genes are arranged on chromosomes. Not all organisms have the same number of genes. Humans have approximately twenty-thousand genes that serve as the blueprints for the human body. The majority of these twenty-thousand genes are the same in all humans, but less than 1 percent differ. This small number of genes creates genetic differences among humans. Alleles are various forms of the same genes, and the differences between alleles are caused by minor changes in the DNA on the gene. Alleles can create distinctive physical features and personality traits.

Scientists learned about genes, DNA, and inheritance in the early 1900s. By the 1950s, they had the idea to change some genes to prevent or cure diseases. Scientists continued to conduct research and testing to develop genetic editing techniques that could be used in the future. In the 1980s, scientists conducted some of the first successful tests using genetic testing. In 1985, they discovered the first process that allowed them to conduct highly targeted gene editing. The process used zinc finger nucleases (ZFNs). Between the 1980s and 2010s, scientists developed two other main methods for gene editing.

Overview

As soon as scientists understood genes, DNA, and heritability, they were able to foresee a time when humans would be able to edit individual genes to cure diseases or choose favorable traits in embryos. They also saw the potential for curing genetic diseases in people and other organisms who were already born. Scientists began to search for processes that would allow them to add, remove, or alter specific genes. They found that they needed techniques to break the double-helix strands of DNA in the exact locations where they wanted to change the genetic information. Since organisms have so many genes and so much DNA, finding processes that were precise enough to make accurate and effective changes was difficult. Since the 1980s, scientists have developed three main processes to edit genes.

The first precise gene-editing process scientists developed used zinc finger nucleases (ZFNs). ZFNs are proteins that can target and cut specific sections of DNA so that scientists can alter those sections. The ZFNs have two domains. One domain binds to the DNA. The other domain cleaves the DNA. When the two domains work together, they act similar to a pair of scissors. They target a section of DNA and cut it. Once the DNA is cut, scientists can add, delete, or alter it. ZFNs were commonly used to alter genes in plants. ZFNs have also been used to alter DNA in zebrafish, rats, and other organisms. ZFNs do not always alter the correct DNA sequence, making the process somewhat unreliable. Nevertheless, scientists have developed ZFN technology that can perform highly specific actions that may help treat human illnesses.

Scientists next discovered transcription activator-like effector nucleases (TALENs), which helped them perform gene editing. TALENs use a transcription activator-like effector to bind to DNA. Scientists pair the TALENs with a DNA cleavage domain to cut the DNA strands. Once the DNA strands are cut, the TALENs can be used to target specific DNA sequences and are often more accurate in targeting these sequences than ZFNs. Scientists are also conducting numerous experiments with TALENS, including trying to correct gene mutations that cause diseases in humans.

CRISPR-Cas9, or simply CRISPR, is another technology that scientists use in gene editing that was developed in the early 2000s. Scientists discovered CRISPR-Cas9 from sections of repeating DNA that occur in bacteria. The repeated sections were of particular interest because it is rare for parts of bacteria genomes to repeat. American scientist Jennifer Doudna realized that the repeating sections must benefit the bacteria in some way. Through further research, Doudna and others realized that the repeated sections of DNA matched the DNA sequences of viruses. Scientists knew that bacteria are often killed by viruses, so they surmised that the virus DNA must be a defense mechanism against viruses. Scientists then learned that a bacterium most likely picked up the virus DNA after destroying a particular virus, cutting up its DNA, and then absorbing some of the cut-up virus DNA into its own DNA right into the sections where the repetitions occur. The bacteria use the virus DNA in the future to more effectively defeat the same type of virus in the future. The bacteria use the Cas9 enzyme (or a similar enzyme) to cut the virus’s DNA. The scientists studying these repeated sections of DNA realized that they could use these repeats as a gene-editing tool.

The scientists learned to use the Cas9 enzyme to cut DNA in other types of organisms. When scientists cut the DNA, they could add, delete, or alter genes at the location of the cut. The scientists just replace the repeated DNA sections with customized sections of DNA. Then, the Cas9 enzyme will target those very specific sections. The CRISPR-Cas9 technology has greatly advanced the science of gene editing. It is generally cheaper and easier to use than TALENs and ZFNs. By the 2020s, CRISPR had become the most popular and most-studied gene-editing technology. Although the technology is popular, it also has some drawbacks. The Cas9 enzyme is large, making it difficult to deliver to cells. Scientists also worry that CRISPR mutations could have unforeseen consequences in future generations of organisms.

Many scientists, doctors, and ethicists have considered the possible consequences and ethics of gene editing. Adding, deleting, and altering genes in living organisms could have various unforeseen consequences, and some genetic changes could affect the offspring of the organisms that were first altered by gene editing. Ethical discussions about gene editing usually begin by differentiating germline and somatic gene editing. Somatic gene editing affects only the genes inside the organism being treated or experimented on. For example, a person receiving gene therapy treatments for an illness will have genetic changes made to cells inside the body, but those changes would not change the DNA in the cells of any of the person’s offspring. Germline genetic engineering refers to scientists making changes that will affect the future offspring of the organism being changed. Germline changes affect all cells inside an organism, including eggs and sperm. Since eggs and sperm will pass on their DNA to future offspring, germline editing will create changes in all future generations that come from the organism that was treated or experimented on. Somatic and germline gene editing have different possible implications, so scientists and ethicists often differentiate between the two types of gene editing when they discuss the ethics of gene editing.

Scientists also consider the possible benefits and drawbacks that gene editing can have. Since the 1950s, scientists have understood that gene editing could help alleviate certain types of diseases and the suffering they can cause. Gene editing could also help humans create more nutritional foods and animals with fewer physical health problems. Yet, gene editing, particularly germline editing, could also have drawbacks and unforeseen consequences, particularly when applied to human beings and passed down to future generations. Gene editing could be used to create human embryos with qualities that make them more likely to have power and influence. For example, embryos could be designed to be strong, fast, and intelligent. People with money could use this science to engineer offspring that are more likely to be powerful and successful in society. This could create a rigid class system in which people who can afford genetic engineering will maintain most of the power.

Many scientists and ethicists believe that the science driving gene editing is developing more quickly than an understanding of the ethical implications of the technology. In 2018, a Chinese scientist announced that he had edited the genes of two human embryos, and they had been brought to term and born. This caused a major disturbance in the field of gene editing, as the embryos had received germline editing, which meant that all their cells (including any sperm or eggs) were changed by the editing. Many scientists, including those involved in gene editing, called for a moratorium on germline editing in human embryos. The scientist who made the announcement was removed from his job because he violated the ethical norms held by most geneticists around the world.

Despite the ethical concerns of gene editing, it has the potential for changing many aspects of life. One of the most important fields that will benefit from gene editing is medicine. Scientists use gene-editing technology to understand the etiology of certain diseases. They have also used it to understand what methods would be most helpful for treating certain diseases. Scientists have used gene therapy, which is somewhat different than gene editing, to treat disease. In gene therapy, doctors insert healthy genes into a person who already has mutated genes that are causing a health problem. The mutated genes stay inside the person along with the healthy genes. The healthy genes can help the body react in different ways, which is what makes gene therapy effective. Scientists are also experimenting with gene-editing technology to treat and cure many types of diseases caused by genes.

Gene drives are another possible, though controversial, application of gene editing. Some scientists hope to use gene drives to eradicate populations of pest animals. Many scientists have suggested using gene drives to kill mosquitoes, which spread illnesses that kill millions of people every year. To create gene drives, scientists introduce genes that stop females of a species from laying eggs. Over time, the gene that prevents females from producing offspring will pass throughout the population. Eventually, the species will be unable to reproduce and will die out. Although this solution would greatly reduce disease and death in human populations, the technology is very controversial. Gene drives are germline changes that spread from parent to offspring. Some scientists worry that unleashing such changes to organisms in the wild could have unforeseen consequences. Other scientists worry about the ethics of eradicating entire populations of animals.

Gene editing has many other possible applications. People could genetically alter pets, such as certain dog breeds, to eliminate physical or health problems. People could also genetically alter algae or other organisms to create more potent biofuels, which could help reduce human reliance on fossil fuels. Scientists have experimented with altering the genes of plants and animals that humans use for food to make them more nutritious, and many consumers already purchase and eat genetically modified plants and animals known as genetically modified organisms (GMOs). Scientists could also someday alter the genes of foods, such as peanuts, that many people are allergic to. Scientists could remove the proteins that cause allergies, making the foods safe for all people to eat. Furthermore, scientists could use gene editing to revive species of plants and animals that have long ago gone extinct. Scientists could alter the genes of species alive today to make them into species from the past. Although all these applications of gene editing are possible, many are controversial and still unobtainable through the gene-editing technology currently available.

Developments in the field of genome editing continued throughout the twenty-first century, as did considerations of the ethical implications. CRISPR-Cas12 and CRISPR-Cas13 were the newest variants of the CRISPR-Cas technologies, and they could target DNA and RNA specifically. Novel editing technologies and delivery methods were also developed. However, as genome editing technology expanded, so did discussions of the ethical implications of genome editing in public discourse. As new possibilities become available, new regulations are needed to address the limitations to be put in place. 

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