Gene Editing: An Analysis

Context

Scientists recently for the first time succeeded in wiping out an entire population of malaria-carrying mosquitoes in the lab using a gene editing tool to programme their extinction.

What is Gene Editing?

• Genome editing is the deliberate alteration of a selected DNA sequence in a living cell. It involves editing an organism’s DNA by altering, removing or adding nucleotides to the genome.

How does genome editing work?

• It involves making cuts at specific DNA sequences with enzymes called ‘engineered nucleases’ that can make a double stranded “cut” or a single stranded “nick” in an organism’s DNA.
•  After the DNA has been cut, a modified piece of DNA similar in sequence to the site of the cut is introduced by the enzyme named DNA ligase enzyme.
• The cell uses the modified piece of DNA as the template to repair the break, filling the break with a copy of the new DNA.

About Genetic Material (DNA and RNA)

• About DNA: DNA (deoxyribonucleic acid) is the genomic material in cells that contains the genetic information used in the development and functioning of all known living organisms.
• Most of the DNA is located in the nucleus, although a small amount can be found in mitochondria (mitochondrial DNA). Within the nucleus of eukaryotic cells, DNA is organized into structures called chromosomes.
• The complete set of chromosomes in a cell makes up its genome.
• The human genome has approximately 3 billion base pairs of DNA arranged into 46 chromosomes. The information carried by DNA is held in the sequence of pieces of DNA called genes.

Difference between organisms altered using gene editing tools and genetically modified organisms (GMO):

• In GMOs, genes derived from other organisms are added to a target organism to confer the trait of interest. For example, Bt cotton contains a gene from the bacterium called Bacillus thuringiensis, which confers resistance to pink bollworms.
• Gene editing employs technologies to edit the host organism’s existing genes, making this the most precise way to elicit a genetic change. This is the key difference between a GMO and a genetically edited organism (GEO).
• A GMO contains a piece of foreign DNA while a GEO have its own DNA altered, with no addition of any foreign genes.

Genome editing systems

• There are several different types of engineered nucleases used in genome editing.
• They all contain a nuclease part to cut the DNA and a DNA-targeting part to recognise the DNA sequence they cut.
• They mainly differ in how they recognise the DNA to cut as follows:
  • RNA-based:  These contain a short sequence of RNA that binds to the target DNA to be cut.
  • Protein-based: These contain a protein that recognises and binds to the target DNA to be cut.

CRISPR-Cas9

• CRISPR-Cas9 (‘clustered regularly interspaced short palindromic repeats’) is the most common, cheap and efficient system used for genome editing.
• It is the DNA-targeting part of the system which consists of an RNA  molecule, or ‘guide’, designed to bind to specific DNA bases through complementary base-pairing.
• Cas9 stands for CRISPR-associated protein 9, and is the nuclease part that cuts the DNA.
• CRISPR-Cas9 systems can be produced relatively easily in a laboratory, or obtained in the form of commercially available kits.
• It was originally discovered in bacteria that use this system to destroy invading viruses.

Applications of Gene Editing:

• Most uses of genome editing have been in scientific research for example to investigate models of human disease.
• In a process called somatic gene editing, scientists are exploring ways to treat diseases caused by a single mutated gene such as cystic fibrosis, Huntington’s, and sickle cell disease.
• In germline gene editing sperm, eggs, and early stage embryos are altered to protect a child against inheritable diseases such as diabetes, Alzheimer’s, and forms of cancer.
• Gene therapy is an artificial method that introduces DNA into the cells of human body which is used in the replacement of genes that cause medical ill-health and destroys the problem causing genes.
• It also helps the body to fight against diseases by adding genes to the human body.
• Resurrecting extinct species: Gene editing could even be used to bring back extinct species, or at least parts of them, for example by mixing genes from extinct species back into existing ones.
• A group called The Long Now Foundation supports these scientific efforts, and hopes first to bring back the passenger pigeon and then the wooly mammoth.
• Gene drives are being developed in yeast, the fruit fly, and two mosquito species, and could be used to drive a naturally occurring, or introduced, gene for sterility through a population.

• Pest control: Since all insects have some version of doublesex so gene drive can help in developing new pest control measures.

• Control malaria outbreak: Since malaria kills more than 4 lakh people each year worldwide, according to the World Health Organization and this gene drive will be significant in controlling the malarial spread.
• Step ahead of traditional practice: Traditional approaches to control mosquitoes especially the use of insecticides is becoming less effective which gene drive can overcome.
• Agricultural breeding to create crop varieties with desirable traits like disease resistance, drought tolerance, reduced water consumption without introducing foreign DNA.
• It can be used to create transgenic animals models such as rats, mice, pigs and primates, which will decrease the time and resource consumption compared to traditional methods.

• Crops and livestock (e.g. increasing yield, introducing resistance to disease and pests, tolerance of different environmental conditions).
• Industrial biotechnology (e.g. developing ‘third generation’ biofuels and producing chemicals, materials and pharmaceuticals).
• Biomedicine (e.g. pharmaceutical development, xenotransplantation, gene and cell-based therapies, control of insect-borne diseases).

Concerns of Gene Editing:

• Commercial aspect- Gene editing might be used as a tool to make designer babies by selecting desired traits like intelligence, muscularity, eye color, height, memory etc which will create demographic disparity.
• Creation of a superior race- The gene editing can be misused by regimes e.g., soviets tried to procreate a human gorilla which will be the ultimate fighting warrior
• Tweaking with nature- Ethicists believe that reproduction is a marvel of nature and it should not be tweaked with.
• Safety Concerns: Studies have shown that edited cells can lack a cancer suppressing protein.
• Genome editing using CRISPR-Cas9 introduces unexpected off-target effects and large DNA deletions.
• Evolution is a natural phenomenon but using gene editing technology a man made phenomenon can have bitter consequences in future.
• Threat of extinction: It involves intentional modification of genetic makeup of a species which may lead to its extinction.
• Ecological risks: Manipulating and removing natural populations by gene drive may destroy food webs and shift the behaviour of diseases.
• Social risks: It can disrupt agriculture, enabling new weapons to mass extinction of species harmful to humans.
• Resistance to gene drive: There are also apprehensions that mosquitoes may develop resistance against gene drive technology like other traditional practices of malarial control.

 India’s Case:

• India with huge disease burden has no database available on Indian population with comprehensive information on the diseases common in the country.
• To address this issue, National Center for Biotechnology Information (NCBI) has presented Indian Genetic Disease Database (IGDD), an integrated and curated repository of growing number of mutation data on common genetic diseases afflicting the Indian populations.
• India’s current regulatory architecture for approving novel treatments related to gene editing is ambiguous and assigns overlapping functions to different governmental bodies.
• This framework needs to be restructured to optimize trial approval time while addressing safety requirements.
• Precision medicine, led by gene-editing research and therapies, need to be promoted through indigenous gene editing research to make such treatments available at affordable prices.
• Ease of doing research both basic and clinical stems from streamlined regulations and India now needs to balance safety and “time to approval” to ensure promotion of such research.
• The government also needs to improve infrastructure and access to funds, and spur innovation in gene editing niche to India’s pressing problems in healthcare, research etc.

Way Forward

The Nuffield Council on Bioethics has recommended following principles and measures to ensure that genome editing proceeds in ways that are ethically acceptable.

Principles

• Gene Editing must be intended to secure, and be consistent with, the welfare of the future person.
• It should not increase disadvantage, discrimination or division in society.

Measures

• The genome editing interventions should be permitted only after sufficient, broad and inclusive public debate about its use and possible implications
• The standards of clinical safety should be established clearly.

• The risks of adverse effects for individuals, groups and society should be appropriately assessed

• Gene editing, if permitted, should be strictly regulated (by the regulatory bodies in respective countries)
• It should be licensed on a case-by-case basis